SCHOLAR/TRAINEE ABSTRACTS
Best Practices
P1
A MODEL TO IMPROVE PREDICTION OF NEGATIVE ORAL FOOD CHALLENGES
Beigelman A 1, Schechtman KB1, Strunk RC1, Garbutt JM1, Jaenicke MW1, Stein JS1, Bacharier LB1
1Washington University School of Medicine, St. Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: Clinical guidelines recommend that children with food‐specific‐IgE (FSIgE) #2 kUa/L to milk, egg or peanut (or #5 kUa/L to peanut without a history of previous reaction) are appropriate candidates for oral food challenge (OFC) to investigate tolerance to these foods. This recommendation is based on research showing that these FSIgE cutoffs are associated with approximately 50% likelihoods of negative OFC. Objective: To develop a statistical model that improves the prediction of negative OFC compared to the current criteria using FSIgE cutoffs value alone. METHODS/STUDY POPULATION: We collected demographics, severity of previous reaction, history of atopic diseases, total IgE and FSIgE values, and skin tests results on children who underwent OFCs based on the recommended FSIgE cutoffs. We developed separate logistic regression models for each food for the prediction of negative OFC. RESULTS/ANTICIPATED RESULTS: 444 OFC met our inclusion criteria. The proportions of negative OFCs were 58%, 42%, and 63% to milk, egg and peanut respectively. Statistically significant predictors for negative challenges in the regression models included: lower FSIgE levels (all foods), higher total IgE (milk), consumption of baked egg products (egg), and non‐Caucasian race (egg and peanut). Using these factors allowed for identification of children with the highest likelihoods of negative OFCs. DISCUSSION/SIGNIFICANCE OF IMPACT: OFCs conducted based upon the currently recommended FSIgE values resulted in negative OFC to milk, egg and peanut in 42–63% of the time. Our models identified combinations of prediction factors that increased the rate of negative OFC, and thus can be utilized for selection of optimal OFC candidates.
P2
APPROACHES TO MEETING THE NIH RCR TRAINING REQUIREMENT IN CLINICAL AND TRANSLATIONAL RESEARCH
Steneck NH 1, Anderson L1
1University of Michigan, Ann Arbor, MI, USA
OBJECTIVES/SPECIFIC AIMS: To review and assess different approaches to meeting the NIH RCR training requirement in clinical and translational research. METHODS/STUDY POPULATION: Survey of Websites, personal interviews, and test interventions with K scholars. RESULTS/ANTICIPATED RESULTS: By presentation time, we will have completed the Website review and interviews as well as conducted and evaluated training programs on five test sites (University of Michigan, University of Pittsburgh, Duke, University of North Carolina and Oregon Health and Science University). Our anticipated findings are that (1) RCR training for K scholar varies considerably and (2) is poorly assessed. We are not sure if we will be able to demonstrate whether one of the approaches we are testing will prove more effective than others. DISCUSSION/SIGNIFICANCE OF IMPACT: K scholars are in the unique position of transitioning from mentee to mentor. The report from this project will provide information on the special needs this position creates for RCR training and advice on how to meet these needs. In improving RCR training for the immediate next generation of mentors, we hope to have a major impact on efforts to promote integrity in clinical and translational research.
P3
CAN CAPNOGRAPHY IMPROVE PEDIATRIC SEDATION SAFETY IN THE EMERGENCY DEPARTMENT?
Langhan M 1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Capnography is not used routinely during sedation. The addition of capnography has been shown to reduce oxygen desaturations in controlled settings such as the operating room. The pediatric emergency department (PED) is a chaotic environment that changes rapidly and in which providers are often caring for multiple patients simultaneously. Aim 1a: To determine if the addition of capnography to standard monitoring during moderate sedation will increase the frequency of staff interventions in response to apnea and hypoventilation, such as verbal commands, patient stimulation, and repositioning, in order to improve ventilation. Aim 1b: To determine whether the addition of capnography will lead to a decrease in oxygen desaturations (<95%). METHODS/STUDY POPULATION: This is a randomized controlled trial of children age 1–20 years who receive IV medication to induce moderate sedation. All staff will receive focused training on capnography. Subjects will undergo both standard monitoring and capnography, but be randomized as to whether the staff responsible for sedation will see the capnography readings. The primary outcomes will be staff interventions for hypoventilation, such as airway repositioning, verbal commands or stimulation of the patient, and oxygen desaturations. RESULTS/ANTICIPATED RESULTS: We hypothesize that the addition of capnography during moderate sedation will improve recognition of hypoventilation and apnea. This will lead to increased staff interventions to improve ventilation which will lead to a reduction in oxygen desaturations. DISCUSSION/SIGNIFICANCE OF IMPACT: Capnography may be shown to increase patient safety by providing staff with a way to continuously and noninvasively monitor ventilatory status, providing faster recognition of hypoventilation, and allow interventions to occur prior to oxygen desaturations, hypercarbia, and further respiratory compromise.
P4
CLINICAL TRANSLATION OF DIABETES SCREENING AND PREVENTION: BASELINE DATA AND METHODOLOGY TO BRIDGE THE GAP
Aroda VR 1, Janas J2, St Clair C1, Shara N1, Evans N3, Blackman M3, Ratner R1, Basch P4
1MedStar Health Research Institute, Hyattsville, MD, USA; 2Clinical Content Consultants, Concord, NH, USA; 3Washington DC VAMC, Washington, DC, USA; 4MedStar Health, Columbia, MD, USA
OBJECTIVES/SPECIFIC AIMS: Type 2 diabetes mellitus (T2DM) is a growing clinical epidemic. There is evidence that T2DM can be prevented or delayed, but this requires appropriate identification of the at‐risk population, estimated to be 35% in U.S. adults > = 20 years of age. We aim to evaluate patterns of care in diabetes screening and prevention in a large healthcare system, and propose a methodology to overcome current barriers in identification of individuals at high risk of diabetes. METHODS/STUDY POPULATION: We queried the electronic health record database of a large healthcare system of 296,564 active patients aged 20 years or older. RESULTS/ANTICIPATED RESULTS: We found that only 3.1% (n = 9040) carried a clinical diagnosis of prediabetes, as ascertained by ICD 9 codes for prediabetes or impaired fasting glucose or impaired glucose tolerance. In comparison, the laboratory based prevalence of prediabetes based on HbA1c or fasting plasma glucose was about 4.7%. Only 0.02% of those with a clinical diagnosis of prediabetes had a diagnosis code listed for dietary or exercise counseling. For patients with prediabetes at highest risk of developing T2DM (HbA1c 6.0–6.4%), 8.0% received treatment with metformin. DISCUSSION/SIGNIFICANCE OF IMPACT: There remains a gap in the healthcare setting in the implementation of current guidelines for identification and treatment of individuals at risk for diabetes, with limited screening of individuals at increased risk and inadequate diagnoses of those with laboratory values consistent with prediabetes. We propose the use of clinical decision support systems to facilitate the appropriate identification of individuals with prediabetes in the healthcare setting.
P5
EFFECT OF A CHAIR‐SIDE DIAGNOSTIC FOR HbA1c ON ENROLLMENT YIELD IN THE DIABETES AND PERIODONTAL THERAPY TRIAL (DPTT)
Grewal S 1, Sayasith C1, Tenzler R1, Hughes J1, Roth A1, Urbankova A1, Gelato MC2, Engebretson S3, Paquette D1
1School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA; 2School of Medicine, Stony Brook University, Stony Brook, NY, USA; 3College of Dentistry, New York University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: To assess the use of rapid chair‐side HbA1c test in diabetic subjects. A chair side HbA1c analysis may help to determine those most likely to be eligible, and improve baseline‐scheduling efficiency. METHODS/STUDY POPULATION: Blood samples obtained from eligible research participants for DPTT were sent to the core laboratory as well as analyzed at chair‐side at clinic site. Subject demographic and behavioral factors such as age, gender, education, employment status, smoking and overall dental health were also collected. RESULTS/ANTICIPATED RESULTS: From April to December 2011, 100 study subjects were screened for HbA1c. Mean of HbA1c analysis from core laboratory was 7.4% and for the chair‐side analysis was 7.5% respectively. Appropriate statistical tests are being performed to analyze these results and the effect of other factors on the enrollment yields. DISCUSSION/SIGNIFICANCE OF IMPACT: Outcome and success of a clinic trial depends on the recruitment, enrollment and retention of clinic trial participants. The DPTT is a multicenter clinic trial to evaluate the effect of mechanical periodontal therapy on glycemic control as measured by glycosylated hemoglobin A1c (HbA1c). For enrollment, subjects must have type 2 diabetes, moderate to severe periodontal disease and HbA1c values ≥7% and <9%. HbA1c analysis is performed at a core laboratory and may take up to two days for results. Meanwhile, a rapid chair‐side HbA1c test is performed on subjects. The present data suggest that the chair‐side test for HbA1c is an effective screening diagnostic used for the identification of diabetic subjects with elevated HbA1c, which may lead to scheduling efficiency.
P6
FACILITATORS OF DAILY ACTIVITY PARTICIPATION OF HISPANIC ELDERLY MEN LIVING ALONE
Orellano EM 1, Rosario M1, Colón Z1, Acevedo S1
1Medical Sciences Campus University of Puerto Rico, San Juan, Puerto Rico
OBJECTIVES/SPECIFIC AIMS: This study explored the strategies and facilitators of daily life activities participation of Hispanic men who live alone. METHODS/STUDY POPULATION: Twenty Hispanic live‐alone men 70 years and older were included. A concurrent nested mixed method design was used. The quantitative phase consisted of the administration of a tool to measure participation restrictions. The qualitative phase consisted of in‐depth interviews with a phenomenological approach with a subsample of twelve participants of the quantitative phase to facilitate interpretation of the results. Data analysis included descriptive statistics and thematic content analysis using the Stevick‐Colaizzi‐Keen method. RESULTS/ANTICIPATED RESULTS: Informants described maintaining participation in daily life activities through a set of occupational competence strategies (including social interaction strategies, lifestyle choices, and occupational adaptations) to promote physical and mental health and wellbeing. These strategies seem directly modified through personal facilitators, which included keeping active in fulfilling occupations, maintaining a positive state of mind, perceived self‐efficacy, and use of humor. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that daily participation of older men who live alone result from a complex interaction between occupational competence strategies and personal facilitators. Since participation in daily life activities is a significant prerequisite and goal for healthy living, these results can be used to design appropriate preventive or rehabilitative public health interventions for older adults that are culturally relevant and sensitive to gender differences to reduce existent health disparities. Reseach supported by Grant # R25RR017589 from the National Center for Research Resources, National Institutes of Health at the University of Puerto Rico, Medical Sciences Campus.
P7
IMPACT OF SECONDARY PREVENTION THERAPIES ON MORTALITY AFTER A FIRST ISCHEMIC STROKE IN PUERTO RICO
Rojas ME 1, Pericchi LR2, Zevallos JC3
1School of Pharmacy, University of Puerto Rico, San Juan, Puerto Rico; 2Department of Mathematics, University of Puerto Rico, San Juan, Puerto Rico; 3Medicine and Public Health, University of Puerto Rico, San Juan, Puerto Rico
OBJECTIVES/SPECIFIC AIMS: The aim of this study is to evaluate the association between the prescription of secondary prevention therapies and mortality during hospitalization and after discharge, at 30 days, six months and one year in patients discharged with a first ischemic stroke. METHODS/STUDY POPULATION: Data collection will be obtained retrospectively from the PR cardiovascular disease surveillance study electronic database, which contains information from the medical charts of 2,701 hospitalized patients with a first ischemic stroke (ICD‐9 codes 434.00 to 438.00) from 14 medical centers in PR during 2007 and 2009. The hypothesis that acute stroke patients receiving secondary prevention therapies have fewer complications and better survival rates than those not receiving this evidence‐based approach will be tested using Kaplan‐Meier and Cox estimators. RESULTS/ANTICIPATED RESULTS: Preliminary results will be presented DISCUSSION/SIGNIFICANCE OF IMPACT: In 2005, stroke was responsible for 143,579 deaths in the United States. In Puerto Rico (PR) stroke caused 1,204 deaths in the same year and has been the leading cause of severe, long‐term disability for several decades. The risk of a recurrent stroke is highest during the first 6 months after the first episode. Since the early 2000s, the American Heart and the American Stroke Associations have developed evidence‐based stroke secondary prevention guidelines, which consist of the prescription of antiplatelets, anticoagulants, antihypertensives, lipid‐lowering agents and lifestyle modifications before hospital discharge. However, results from a 2007 acute stroke study at the University of PR Carolina Hospital showed that less than 40% of patients were prescribed secondary prevention therapies.
P8
IMPLEMENTATION AND OUTCOME ANALYSIS OF AN INSTITUTIONAL PEDIATRIC ACUTE HEMATOGENOUS OSTEOMYELITIS (AHO) DIAGNOSIS AND MANAGEMENT PATHWAY
Parikh K 1, Hoffner W1, Hyun D1
1Children’s National Medical Center, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: (1) To evaluate AHO pathway implementation by comparing pre‐ and postimplementation cohorts, specifically blood culture and MRI utilization, and time to obtain MRI. (2) To compare clinical outcomes, specifically length of hospital stay and rate of pathogen identification, between the pre‐ and post‐implementation cohorts. METHODS/STUDY POPULATION: Retrospective cohort study reviewing patient charts with principal discharge diagnosis of osteomyelitis from prepathway (January 1, 2005 to March 31, 2008) and postpathway implementation (April 1, 2008 to October 31, 2010) periods. RESULTS/ANTICIPATED RESULTS: 46 charts were reviewed, 22 patients in the preimplementation cohort and 24 patients in postimplementation cohort. Demographic factors between the two cohorts were similar, including age, sex, and severity level. In the postimplementation cohort, 96% of patients had blood cultures and 96% had a MRI study for diagnosis, compared to 77% and 73%, respectively, in the preimplementation cohort. A clinically significant decrease in time to obtain MRI was noted from 48 hrs in the preimplementation cohort to 20 hrs in the postimplementation cohort. However, mean length of stay was 6.5 days in both cohorts. Pathogen identification was not improved in the postimplementation cohort (58% post‐implementation versus 73% preimplementation). DISCUSSION/SIGNIFICANCE OF IMPACT: Implementation of a AHO pathway at our institution has been successful, with an increased rate of blood cultures and MRI for diagnosis, and a decreased time to obtaining MRI. However, improved clinical outcomes such as shortened LOS and increased pathogen identification were not demonstrable in this small study. A larger study is needed to fully evaluate the impact of pathway implementation.
P9
INTERPROFESSIONAL STRATEGIES TO REDUCE THE RISK OF EARLY CHILDHOOD CARIES
Hallas D 1, Fernandez J2, Lim L2, Catapano P3,2
1New York University, New York, NY, USA; 2New York University College of Denistry, New York, NY, USA; 3New York University & Bellevue Hospital, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: To implement an interdisciplinary culturally sensitive oral health educational program for parents of newborns on the postpartum unit. METHODS/STUDY POPULATION: A prospective randomized controlled pretest, posttest experimental design was used to assess the effectiveness of an oral health education intervention for parents of newborns while on the postpartum unit. Ninety seven mothers and infants were enrolled. Each mother in the treatment and control group took the same pretest (instrument #1) prior to randomization. Twelve months later each mother took a posttest during the infant’s first oral health examination. Instrument #2 was the Caries Risk Assessment and instrument #3 was the clinical oral health examination at the 12 month‐old visit. RESULTS/ANTICIPATED RESULTS: Differences in the changes in the pretest and posttest scores will be determined by split‐plot analysis of covariance (ANOVA). Mean scores on the caries risk assessment will be compared using the t‐test. Findings from the oral health examinations from each infant in the treatment and control group will be assessed using the following scoring: no cavities = 0; white spots = 1; and cavitation = 2 (per tooth). Differences between the intervention group and the control group will be assessed by computing the chi‐square statistic for the 2 × 3 cross tabulation table. All findings from the study including statistical analysis will be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: An oral health educational program provided to mothers during the immediate post partum period has the potential to reduce the incidence of ECC in their infants.
P10
PREDICTORS OF VON WILLEBRAND DISEASE IN CHILDREN
Sidonio RF 1, Ragni M2
1Vanderbilt University, Nashville, TN, USA; 2Hemophilia Center of Western Pennsylvania, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: Bleeding and bruising are common symptoms for which children are referred to a pediatric hematologist. Although bleeding scores have been validated to quantify bleeding risk in adults, there are no similar definitive data in children. The aim was to describe presenting bleeding symptoms in children and evaluate if these bleeding symptoms were predictive of von Willebrand disease (VWD) or low von Willebrand factor (VWF). METHODS/STUDY POPULATION: We performed a retrospective chart review of consecutive pediatric patients referred for perceived bleeding symptoms to the coagulation clinic at The Children’s Hospital of Pittsburgh of UPMC. All underwent a uniform bleeding symptom inventory and hemostatic testing. Single and multiple variable logistic regression models were created to predict either VWD, low VWF, or nonspecific defective platelet aggregation, using the predictor variables of family bleeding history, mucocutaneous bleeding, cutaneous bleeding, and surgical bleeding, based on The International Society on Thrombosis and Hemostasis (ISTH) bleeding definitions. RESULTS/ANTICIPATED RESULTS: Of 298 pediatric patients evaluated, 8% had VWD and 34% had low VWF. Further, 16% had a nonspecific platelet aggregation disorder, 41% had normal hemostatic testing, and 1% had factor VIII or IX deficiency. In single and multiple variable logistic regression analysis, neither a personal or family bleeding history at presentation, nor the presence of two or more bleeding symptoms were predictive of VWD, low VWF, or nonspecific defective platelet aggregation. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that qualitative assessment of bleeding symptoms alone is not useful in children.
P11
STATEWIDE OUTCOMES OF PATIENTS UNDERGOING INTERHOSPITAL MEDICAL TRANSPORT
Reimer A 1,2, Schiltz N3
1Case Western Reserve University, Cleveland, OH, USA; 2Cleveland Clinic, Cleveland, OH, USA; 3Case Western Reserve University, Cleveland, OH, USA
OBJECTIVES/SPECIFIC AIMS: To compare clinical outcomes and healthcare services utilization between persons transferred between hospitals via medical transport and those that are not transferred through comparing total bed days and charges incurred. METHODS/STUDY POPULATION: Data from the California State Inpatient Database, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, will be used to assess for differences between patients that were transferred between acute care hospitals with patients that were not transferred. Descriptive statistics, significance testing and regression will be performed to potentially identify predictors and describe transferred patients’ clinical outcomes. RESULTS/ANTICIPATED RESULTS: We anticipate significant differences in patient outcomes with the transported patients exhibiting increased morbidity as compared to nontransferred patients, experiencing longer lengths of stay, incurring more charges, and experiencing higher mortality rates. DISCUSSION/SIGNIFICANCE OF IMPACT: Previous studies have reported increased mortality rates for patients that are transferred from one hospital to another for higher levels of care. This study will provide additional understanding of patient outcomes on a statewide level, moving beyond individual hospital or study results, and may provide support of a more global phenomenon of increased patient mortality. This project is a work in progress.
P12
VALIDATION OF GENEXPERT SA NASAL COMPLETE OFF LABEL USE FOR MRSA INGUINAL COLONIZATION IN CUTANEOUS ABSCESS PATIENTS
May L 1, Dissen E1, McCann C1, Jordan J1
1George Washington University, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Methicillin resistant Staphylococcus aureus (MRSA) carriage is associated with risk of cutaneous abscesses and rapid detection in the emergency department (ED) is an important infection control strategy. The FDA‐cleared Cepheid GeneXpert SA Nasal Complete (NC) is approved for detection of S. aureus in nares specimens; the RT‐PCR targets spa, mecA, and SCCmec with a turnaround time of ~1 hour. Objectives: (1) Validated the use of the GeneXpert NC for inguinal colonization (2) Examined the proportion of ED patients with cutaneous abscesses who displayed nares or inguinal colonization with MRSA (3) Assessed pathogen concordance between wound and colonization. METHODS/STUDY POPULATION: Ongoing prospective observational study of adults ≥18 y with cutaneous abscesses receiving an incision and drainage in an urban ED. Bilateral nares and inguinal swabs were obtained. Culture and GeneXpert testing performed using the GeneXpert MRSA/SA SSTI assay for the wound specimen and the GeneXpert SA NC for the nares and inguinal specimens. Culture was done by direct plating on chrome agar, if not present TSB broth enrichment performed. RESULTS/ANTICIPATED RESULTS: Of the 82 subjects enrolled 21 were colonized with MRSA; of those 100% inguinal and 67% nares. Subjects had 69% MRSA wound and nares concordance and 90% wound and inguinal concordance. GeneXpert compared to culture had 79% sensitivity, 97% specificity, and 92% negative predictive value. DISCUSSION/SIGNIFICANCE OF IMPACT: Off label use of the NC assay for inguinal colonization was validated as a rapid and accurate screening test and could prevent unnecessary isolation for admitted patients. Inguinal MRSA colonization was more common that in the nares; 33% of colonized subjects would have been missed with nares testing alone. Multiple testing sites should be conidered for MRSA screening.
CLINICAL EPIDEMIOLOGY
P13
ACCURACY OF ICD‐9 CODES TO IDENTIFY PEDIATRIC COMMUNITY ACQUIRED PNEUMONIA (CAP)
Williams D 1, Hall M2, Myers A3, Queen M3, Wiggleton C1, McClain L1, Auger K4, Jerardi K4, Shah S4, Tieder J5
1Vanderbilt University, Nashville, TN, USA; 2Child Health Corporation of America, Kansas City, MO, USA; 3Mercy Children’s Hospital, Kansas City, MO, USA; 4Cincinnati Children’s Hospital, Cincinnati, OH, USA; 5Seattle Children’s Hospital, Seattle, WA, USA
OBJECTIVES/SPECIFIC AIMS: To assess the accuracy of ICD‐9 coding algorithms for identifying pediatric CAP hospitalizations. METHODS/STUDY POPULATION: We included data from 5 children’s hospitals that contribute to the Pediatric Health Information System. All hospitalizations for children 60d‐18y with an ICD‐9 discharge code for pneumonia (primary or any secondary) in 2010 were selected (N = 6804). Those with a concomitant ICD‐9 coded diagnosis that excluded CAP (e.g. cystic fibrosis) were removed (N = 1,865). We randomly selected 20% of the remaining discharges for chart review. Those with a clear alternative diagnosis or a condition that precluded CAP were considered non‐CAP. All remaining discharges had evidence of acute respiratory illness plus a provider diagnosis of pneumonia and were classified as CAP. Positive predictive values (PPV) and relative sensitivities of 6 ICD‐9 coding algorithms were compared. RESULTS/ANTICIPATED RESULTS: Of 1,032 charts reviewed, 695 (67%) were classified as CAP. Including only those with a primary diagnosis of pneumonia improved PPV (80%) but only identified 72% of those with CAP. Similarly, including those with a primary diagnosis of pneumonia or those with a primary diagnosis of a pneumonia related complication plus a secondary diagnosis of pneumonia improved PPV (79%) and identified 74% of those with CAP. Finally, excluding those with chronic comorbid conditions improved PPV for all 3 algorithms (81–88%) but only identified 65–90% of those with CAP. DISCUSSION/SIGNIFICANCE OF IMPACT: Administrative data is useful for studying CAP. However, careful selection of ICD‐9 codes is critical to ensure valid study conclusions.
P14
ADIPOSITY TRACKING AND ITS HERITABILITY IN CHILD AND ADOLESCENT TWINS IN RURAL CHINA
Arguelles LM 1, Xu X2, Wang X3
1Northwestern University the Feinberg School of Medicine, Department of Preventive Medicine, Chicago, IL, USA; 2University of Illinois at Chicago School of Public Health, Center for Population Genetics, Chicago, IL, USA; 3Johns Hopkins University, School of Public Health, Baltimore, MD, USA
OBJECTIVES/SPECIFIC AIMS: Examine adiposity tracking and estimate its heritability in a large prospective cohort of prepubertal and pubertal child and adolescent twins in rural China. METHODS/STUDY POPULATION: This report included 1,317 child and adolescent twins from Anqing, China. Twins were aged 6 to 18 years at baseline and had completed follow‐up at 6 years. Anthropometric measures included body mass index (BMI), waist circumference (WC), total body fat (TBF), percent body fat (%BF), trunk fat (TRF), and percent trunk fat (%TRF). Adiposity measures were obtained by dual‐energy x‐ray absorptiometry (DEXA). Locally weighted nonparametric smoothing function (SAS LOESS, SAS Institute, Cary, NC, USA) were used to describe (1) “tracking” of adiposity measurements from baseline to 6‐year follow‐up, and (2) gender differences in the growth of adiposity measurements across age. Structural equation modeling was used to estimate the heritability of tracking using the software Mx. RESULTS/ANTICIPATED RESULTS: All anthropometric measures, except%TRF, tracked from baseline to follow‐up in both genders. The genetic correlation of BMI = 0.60(0.46–0.72); TBF = 0.43(0.29–0.55); %TBF = 0.37(0.23–0.50); WC = 0.35(0.11–0.56); TR = 0.41(0.27–0.54); and%TR = 0.33(0.07–0.59). DISCUSSION/SIGNIFICANCE OF IMPACT: The tracking of adiposity measures in this pediatric population underscores the importance of closely monitoring individuals with high BMI or adiposity over time; those in the low and medium tertile should also be monitored for their upward “mobility.” The weak genetic correlations in adiposity tracking suggests that environmental changes can influence adiposity depots.
P15
AGGRESSIVE EVENT MEASUREMENT: COMPARING DIFFERENCES IN EVENT RATES
Iennaco JD 1, Fennie KP3, Bowers L4, Dixon J1, Whittemore R1, Busch SH2, Scahill L1
1Yale University School of Nursing, New Haven, CT, USA; 2Yale University School of Public Health, New Haven, CT, USA; 3Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA; 4Institute of Psychiatry, Kings College London, London, United Kingdom
OBJECTIVES/SPECIFIC AIMS: Aggressive event rates were measured in an acute inpatient psychiatric setting to determine the differences between three methods of counting worker exposure to patient verbal and physical aggression. METHODS/STUDY POPULATION: Measures included standard restraint reports, questionnaires, and handheld event counters. Data was collected on two adult inpatient psychiatric units. Clinical workers completed questionnaires (PCC‐SR, SOAS‐R) over a six week period and carried hand held counters to count aggressive events over two week periods on each unit. RESULTS/ANTICIPATED RESULTS: Preliminary results indicate that change of shift questionnaire use identifies from 3.6 to 30 times the number of events per unit, however worker specific rates of exposure are not identified. Handheld counters provide worker specific rates of verbal aggressive event exposures 27 times greater than that from restraint records. Counters identify rates of worker exposure to physical aggression up to 5.6 times greater than restraint record rates. DISCUSSION/SIGNIFICANCE OF IMPACT: Use of restraint rates and questionnaires undercount aggressive events and worker aggression exposure. Differences in event rates represent events not resulting in patient seclusion or restraint, offering information on event resolution that otherwise is not counted. Improved accuracy of aggression measurement has implications for quality improvement, occupational health and patient intervention to reduce aggressive events.
P16
APO E4 AND LIPOPROTEIN‐ASSOCIATED PHOSPHOLIPASE A2 SYNERGISTICALLY INCREASE CARDIOVASCULAR RISK
Erdembileg A 1, Gungor Z2, Byambaa E1, Zhang W1, Kim K1, Berglund L1
1University of California, Davis, Davis, CA, USA; 2University of Istanbul, Istanbul, Turkey
OBJECTIVES/SPECIFIC AIMS: Genetic factors and inflammation contribute to cardiovascular risk, but little is known to what extent these act together. Thus, genetic variation of the apolipoprotein E (apoE) locus impacts lipoprotein metabolism and apo E4 has been implicated as conveying increased risk for coronary artery disease (CAD). ApoE has also been implicated as contributing to other chronic disease conditions as well as modulating immune response and inflammatory properties. We hypothesized that the presence of apo E4 is associated with an increased inflammatory burden in subjects with CAD as compared to subjects without CAD. METHODS/STUDY POPULATION: ApoE genotypes, systemic (C‐reactive protein [CRP], fibrinogen, serum amyloid‐A [SAA]) and vascular inflammatory markers (lipoprotein‐associated phospholipase A2 [Lp‐PLA2] and pentraxin‐3 [PTX‐3]) were assessed in 528 subjects, 321 Caucasians and 207 African Americans, undergoing coronary angiography. RESULTS/ANTICIPATED RESULTS: For both ethnic groups, Lp‐PLA2 index, an integrated measure of Lp‐PLA2 mass and activity, increased significantly and stepwise across apoE isoforms (p = 0.009 and p = 0.026 for African Americans and Caucasians respectively). No differences were found for other inflammatory markers tested (CRP, fibrinogen, SAA and PTX‐3). For the top cardiovascular score tertile, apo E4 carriers had a significantly higher level of Lp‐PLA2 index in both ethnic groups (p = 0.020 and p = 0.010, respectively). DISCUSSION/SIGNIFICANCE OF IMPACT: The presence of the apo E4 isoform was associated with a higher level of Lp‐PLA2 index, a marker of vascular inflammation. Our results suggest that genetic variation at the apoE locus may impact cardiovascular disease risk through enhanced vascular inflammation.
P17
ASD PREVALENCE STUDIES: STEPPING STONES TO UNDERSTANDING GEX IN DEVELOPMENTAL PSYCHOPATHOLOGY
Kim Y 1
1Yale University School of Medicine, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Identifying the etiology of ASD is challenging due to methodological shortcoming including phenotypic heterogeneity and the use of mainly clinical samples that may reflect biased selection. Using total population approach in a two‐stage prevalence study, we will (1) Examine a comprehensive prevalence of ASD; (2) Describe entire distribution of ASD phenotype including clinical and non‐clinical populations; and (3) Establish an epidemiologically‐ascertained population‐based cohort of ASD to examine the roles of GEX in the risks for ASD. METHODS/STUDY POPULATION: Target Population (N = 55,266) included all 7–12 year‐old children attending elementary schools in Goyang City, South Korea, between years 2005 and 2006. 1st Screening Stage (N = 23,337) was performed with Parent/teacher Autism Spectrum Screening Questionnaires. In 2nd stage, Confirmative Diagnoses (N = 286) were made by clinical best estimate diagnoses utilizing ADOS, ADI‐R and cognitive tests. RESULTS/ANTICIPATED RESULTS: ASD prevalence estimate was 2.64% (clinical sample 0.8%, comparable; 1.8% prevalence in the nonclinical sample.) The majority of children in the clinical sample had autistic disorder with more severe symptoms, male:female = 5:1, and mean IQ 75. For the nonclinical sample, most children were diagnosed with other types of ASD with lesser severity, male:female = 2.5:1, and mean IQ 98. DISCUSSION/SIGNIFICANCE OF IMPACT: Comprehensive ASD phenotype represents less male dominance and average IQ without seeking clinical services. Etiological research requires unbiased, population‐based, epidemiologically ascertained study subjects. For the future study, we will: (1) develop an independent community sample with dimensional phenotype measures (N = 10,000); (2) acquire blood markers for ASD biological markers; and (3) conduct whole genome genotyping to examine the roles of GEX in the risks for ASD.
P18
ASSESSING DRINKING PATTERNS UTILIZING COMPUTERIZED ALCOHOL SCREENING AND BRIEF INTERVENTION (CASI) IN THE EMERGENCY DEPARTMENT SPANISH‐SPEAKING POPULATION
Lotfipour S 1, Hoonpongsimanont W1, Roumani S1, Cisneros V1, Chakravarthy B1, Anderson C1, Dykzeul B1, Moreno F1, Sumrell C1, Vaca F2
1UC Irvine Medical Center, Irvine, CA, USA; 2Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Spanish‐speaking patients are being screened for alcohol use in the Emergency Department (ED) using a computerized alcohol screening and brief intervention (CASI) program. CASI utilizes the Alcohol Disorders Identification Test (AUDIT) for screening, compares daily and weekly drinking to National Institute on Alcohol Abuse and Alcoholism (NIAAA) thresholds for safe drinking, and provides a brief intervention as necessary. The aim is to assess drinking patterns of Spanish‐speaking patients using a bilingual CASI tablet in the ED. METHODS/STUDY POPULATION: Data from 1,816 Spanish‐speaking ED patients who took CASI was analyzed using descriptive statistics, the chi‐square test for independence, and the Kruskal‐Wallis rank‐sum test for comparisons using quantitative variables. RESULTS/ANTICIPATED RESULTS: Overall, 15% of Spanish‐speaking patients were at‐risk drinkers (defined as exceeding the NIAAA thresholds with an AUDIT #19), and 5% had an AUDIT score consistent with alcohol dependency (≥20). A higher percentage of Spanish‐speaking males than females were at‐risk drinkers or dependent. Spanish speaking males exhibited higher frequency of drinking days per week and higher number of drinks per day compared to females. Nondrinking behavior increased in older patients and at‐risk drinkers decreased. Males and females were ready to change their behavior after intervention, 61% and 67% respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: CASI found significant at‐risk and dependent drinking behavior in Spanish‐speaking ED patients. The majority of patients were ready to change their drinking behavior. More alcohol screening and brief intervention should be tested and become readily accessible for Spanish‐speaking patients.
P19
ASSOCIATION BETWEEN VITAMIN D ANALOGUES AND CALCIFIC UREMIC ARTERIOLOPATHY—A MATCHED CASE CONTROL STUDY
Nigwekar S 1
1Massachusetts General Hospital, Boston, MA, USA
OBJECTIVES/SPECIFIC AIMS: Calcific uremic arteriolopathy (CUA), a disorder of skin and subcutaneous tissue, is characterized by arteriolar medial calcification, endovascular fibrosis and thrombosis leading to septal panniculitis. It affects 4% of maintenance hemodialysis patients and is associated with significant mortality (60–80% at 1‐year) and morbidity. Recent reports suggest that its incidence is on the rise; however, reasons for this are not clear. Vitamin D analogues (VDAs) are commonly used in dialysis patients to manage secondary hyperparathyroidism. Experimental studies have shown that VDAs induce vascular and soft tissue calcification and can lead to CUA. However, whether their use is associated with CUA has not been studied in humans. This study will test the hypothesis that VDAs are associated with increase in the odds of CUA in maintenance hemodialysis patients. METHODS/STUDY POPULATION: This matched case control study included cases of skin biopsy confirmed CUA diagnosed between 2006 and 2011 at the participating institutes. Controls were patients on maintenance hemodialysis without CUA and were matched to cases for dialysis vintage. Relevant data were abstracted from hospital and outpatient dialysis records. RESULTS/ANTICIPATED RESULTS: There were 35 cases of CUA. Mean age of the cases was 61 years (±3 years) and 40% were males. Mean age of the controls was 62 years (±3 years) and 42% were males. Further results will be presented at the conference. DISCUSSION/SIGNIFICANCE OF IMPACT: If VDAs are found to be significantly associated with CUA then clinicians would need to be cautious in selecting patients to be treated with VDAs and avoid VDAs in patients who are at high risk for CUA. Establishing this association will also enable clinicians to maintain high index of suspicion for CUA when a dialysis patient on VDAs presents with painful skin lesions.
P20
ASSOCIATION OF AKI WITH MORTALITY AND COMPLICATIONS IN HOSPITALIZED PATIENTS WITH CIRRHOSIS
Belcher JM 1, Garcia‐Tsao G1, Sanyal AJ2, Ansari N3, Parikh CR1
1Yale University, New Haven, CT, USA; 2Virginia Commonwealth University, Richmond, VA, USA; 3Jacobi Medical Center, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: Acute kidney injury (AKI) is a common and devastating complication in patients with cirrhosis. However, the definitions of AKI employed in studies involving patients with cirrhosis have not been standardized, lack sensitivity and are often limited to narrow clinical settings. We conducted a multicenter, prospective observational cohort study of patients with cirrhosis and AKI, utilizing the modern acute kidney injury network (AKIN) definition, to assess for the association between AKI severity and progression and in‐hospital mortality. METHODS/STUDY POPULATION: n/a. RESULTS/ANTICIPATED RESULTS: A total of 192 patients were enrolled. Fifty (26%) patients died during their hospitalization. The severity of AKI worsened following the initial fulfillment of AKIN criteria in 85 (44%) of patients. Worsening of AKI was significantly more common among nonsurvivors, 80%, than among survivors, 32%, (p < 0.0001). A strong stepwise association was noted between both degree of progression and peak AKIN stage and mortality. For patients with peak stages of 2 and 3, those who progressed to that degree had higher mortality than those presented with that level of dysfunction but did not progress. Nonsurvivors ultimately experienced significantly more severe AKI, with 84% reaching stage 3 versus 38% of survivors, (p < 0.0001). On multivariate logistic regression, progression of AKI was independently associated with mortality, OR 3.8 (95% CI 1.3–11.1). DISCUSSION/SIGNIFICANCE OF IMPACT: AKI, as defined by AKIN criteria, in patients with cirrhosis is frequently progressive and severe and is independently associated with mortality in a stage‐dependent fashion. Methods for earlier diagnosis of AKI and prediction of progression may result in improved outcomes by facilitating targeted and timely treatment of AKI.
P21
BASELINE VITAMIN D DEFICIENCY IS NOT ASSOCIATED WITH POOR CLINICAL OUTCOMES IN OSTEOARTICULAR INFECTIONS
Marschall J 1, Lewis J1, Warren DK1, Babcock H1, Fraser VJ1
1Washington University School of Medicine, Saint Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: The role of vitamin D in osteoarticular infections is unclear. We hypothesized that vitamin D deficiency is associated with lower likelihood of treatment success. METHODS/STUDY POPULATION: We conducted a retrospective cohort study of patients (pts) seen by the WU bone and joint ID consult service that had a vitamin D level drawn at baseline. Successful treatment was determined at early and late follow‐up after completing IV antibiotics. Vitamin D baseline levels were correlated with treatment success. RESULTS/ANTICIPATED RESULTS: We included 159 pts with bone and/or joint infections and baseline vitamin D levels seen in 2009/2010. Mean age was 56 years (SD ±16); patients were predominantly male (84; 53%) and white (117; 74%). As part of the inpatient management, vitamin D deficiency was identified and treated. The median vitamin D level was 20 ng/mL (5–112); 121 (76%) pts had levels <30 and were deficient. Risk factors for vitamin deficiency included seasonality [84 (82%) deficient in fall/winter vs. 37 (65%) in spring/summer (p = 0.02)]. Overall, treatment success was 90% (113/125) at early and 88% (104/119) at late follow‐up. Vitamin D baseline levels were similar in those with or without successful clinical outcomes, both at early [21 ng/mL (5–112) vs. 21 (9–42); p = 0.8] and late follow‐up [22 (5–112) vs. 17 (6–32); p = 0.08]. Follow‐up levels were only obtained in 40 (25%) pts, with a median level of 31 ng/mL (8–91); 17/40 (43%) were still deficient at that point. DISCUSSION/SIGNIFICANCE OF IMPACT: To our knowledge this is the first report on vitamin D deficiency and its impact on outcomes of osteoarticular infections. Vitamin D deficiency was frequent in this cohort. With vitamin D supplementation, there was no difference in treatment success whether patients had baseline vitamin D deficiency or not.
P22
BEHAVIORAL FACTORS ASSOCIATED WITH OBESITY IN 2‐ TO 3‐YEAR‐OLD CHILDREN
Lowry KW 1,2, Jedraszko A1, DeCator D1, Egan M1, Fital K1, Carroll D1, Lavigne J1,2
1Children’s Memorial Hospital, Chicago, IL, USA; 2Northwestern University, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: To determine how parent, child, and home factors influence child weight in early childhood. METHODS/STUDY POPULATION: Parent‐child dyads of 2‐ to 3‐year‐old children participated in an extensive home‐based assessment. Data collection included the Child Feeding Questionnaire, the Children’s Eating Behavior Questionnaire, selected subscales of the Home Environment Scale, parent and child Food Frequency Questionnaires, and a videotaped and coded mealtime interaction. RESULTS/ANTICIPATED RESULTS: One hundred five diverse families (59% minority) participated in the project representing 40 Chicago Community Areas. Child and parent rates of overweight and obesity were consistent with state averages (child overweight = 15%, child obesity 10%, maternal overweight = 25%, maternal obesity = 39%) and maternal BMI was positively associated with child weight percentile (r = 0.25, p < 0.01). Individual regression equations, controlling for maternal weight, were used to determine the impact of child, parent, and household factors and indicated that more restriction (B = 9.67, SE = 3.52, p < 0.01), less pressure to eat (B =−7.74, SE = 2.52, p < 0.01), faster child eating/less satiety responsiveness (B =−14.05, SE = 5.73, p = 0.02), and higher access to high‐sugar/high‐fat foods (B = 6.54, SE = 2.96, p = 0.03) were associated with higher child weight percentile. Combining these factors into a single multivariate regression model with 4 steps (maternal BMI, parent, child, home factors) accounted for 27% of the variance in child weight percentile at this age. DISCUSSION/SIGNIFICANCE OF IMPACT: Five potentially modifiable, parent, child, and household factors had a significant impact on child weight early in development. An intervention to target these factors may have a significant impact on pediatric obesity.
P23
BLOOD ARSENIC CONCENTRATIONS OF JAMAICAN CHILDREN WITH AND WITHOUT AUTISM SPECTRUM DISORDERS
Rahbar MH 1, Samms‐Vaughan M2, Ardjomand‐Hessabi M1, Loveland KA1, Dickerson AS1, Chen Z1, Bressler J1, Shakespeare‐Pellington S2, Grove ML1, Bloom K1, Wirth J3, Pearson DA1, Boerwinkle E1
1The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; 2The University of the West Indies (UWI), Mona Campus, Kingston, Jamaica; 3Michigan State University, East Lansing, MI, USA
OBJECTIVES/SPECIFIC AIMS: To compare the mean total blood arsenic concentrations in children with and without autism spectrum disorders (ASD) in Jamaica. METHODS/STUDY POPULATION: Based on data collected during 2009–11 from 65 ASD cases (2–8 years) and their age‐, and sex‐matched controls, we used General Linear Models to test whether there is an association between blood arsenic concentrations and ASD as well as sources of drinking water, and consumption of seafood and vegetables in Jamaican children. RESULTS/ANTICIPATED RESULTS: After controlling for frequency of vegetables, fruits, and seafood consumption in a multivariable model, we did not find a significant association (C = 0.3807) between blood arsenic concentrations and ASD. However, regardless of the ASD status, children with higher levels of seafood consumption had a significantly (p = 0.0168) higher blood arsenic concentration than did those who reported a lower level of seafood consumption. Moreover, children who did not report piped water as their source of drinking water had a higher (p = 0.0118) geometric mean blood arsenic concentration compared to those with piped water. Furthermore, children who ate certain types of vegetables, particularly root vegetables, had significantly higher geometric mean blood arsenic concentrations compared to those who did not consume these vegetables (all p < 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Based on our findings we recommend that Jamaicans assess arsenic in various sources, such as water and food, particularly seafood and vegetables, as this could potentially reduce the risk of diseases associated with exposure to arsenic.
P24
BONE MINERAL DENSITY AND VITAMIN D STATUS IN AFRICAN AMERICAN CHILDREN WITH FOREARM FRACTURES
Ryan L 1, Teach S1, Brandoli C1, Singer S1, Wood R1, Freishtat R1, Wright J1, Tosi L1, Chamberlain J1
1Children’s National Medical Center, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Among adults and healthy Caucasian children, bone health deficiencies contribute to forearm fracture risk. Although African American (AA) children may be at higher risk for bone health deficits, the relationship between forearm fracture risk and bone health has not been investigated in this population. Our objective is to determine if AA children with forearm fractures have decreased bone mineral density (BMD) and an increased prevalence of vitamin D insufficiency (serum 25‐hydroxy vitamin D level < 20 ng/mL) compared to fracture‐free controls. METHODS/STUDY POPULATION: This case–control study included cases (AA children, ages 5–9 years, with forearm fracture) and AA fracture‐free controls. Evaluation included measurement of BMD, serum 25‐hydroxy vitamin D level, body mass index and diet, including calcium intake. Bivariable and multivariable analyses were used to test the association of bone health indices with fracture status, while controlling for confounding variables. RESULTS/ANTICIPATED RESULTS: The final sample included 78 cases and 74 controls. Cases had significantly lower total body z‐scores for BMD [adj OR 0.6 (0.4–0.9)] and were significantly more likely to be vitamin D insufficient [adj OR 3.1 (1.1–8.7)] in comparison to controls. There were no significant differences between cases and controls in mean age, gender, parental education level, season of enrollment, sun exposure, mean dietary calcium nutrient density or mean dietary vitamin D intake. DISCUSSION/SIGNIFICANCE OF IMPACT: These data support an association between risk for forearm fracture in AA children and lower BMD and vitamin D insufficiency. Because suboptimal bone health in childhood also negatively impacts adult bone health, early identification of at‐risk children with forearm fractures may allow early intervention with short and long term benefits.
P25
CARDIAC SCREENING OF HIGH SCHOOL ATHLETES FOR RISK OF SUDDEN DEATH: A COMMUNITY MULTIDISCIPLINARY APPROACH
Klamerus M 2,1, Zack PM1,2, Madala M1, Shah I1, Bakr O1
1Ingham Cardiovascular Group, Okemos, MI, USA; 2Michigan State University, East Lansing, MI, USA
OBJECTIVES/SPECIFIC AIMS: Sudden death during high school athletic participation is a rare but tragic event that can occasionally be predicted by abnormalities on screening electrocardiography (ECG). The European Society of Cardiology and International Olympic Committee recommend that young athletes receive ECG prior to sports participation. The American Heart Association does not currently recommend ECG, but does not oppose community volunteer‐based athlete screening programs. METHODS/STUDY POPULATION: We instituted a free screening program for local high school athletes administered by cardiologists, mid‐level medical providers, exercise physiologists, nursing personnel, medical assistants and cardiac technologists. The program included a comprehensive questionnaire, focused cardiac examination and ECG. Limited echocardiography was performed when indicated by cardiac examination or ECG abnormalities. RESULTS/ANTICIPATED RESULTS: During the initial three screening sessions, 138 students participated. The findings were normal in 135 students, with 3 students (2.2%) found to have abnormal results. Identified abnormalities included ECG and echocardiography evidence of severe pulmonary hypertension, prolonged QT interval on ECG and marked systemic hypertension. Students found to have abnormalities were advised not to participate in competitive sports pending additional evaluation and treatment. DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that a volunteer community wide multidisciplinary approach to preparticipation cardiac screening of high school athletes is feasible. Further investigation is needed to confirm our observed frequency of abnormal findings during screening and to assess the impact of wider implementation of volunteer screening programs on the incidence of sudden death during high school athletic participation.
P26
CARDIOVASCULAR DISEASE RISK IN ADOLESCENTS WITH CONGENITAL ADRENAL HYPERPLASIA
Kim M 1, Ryabets‐Leinhard A1, Gilsanz V1, Geffner M1
1Children’s Hospital Los Angeles, Los Angeles, CA, USA
OBJECTIVES/SPECIFIC AIMS: Aims are to characterize cardiovascular disease (CVD) risk factors [metabolic syndrome components, inflammatory markers, intima‐media thickness (IMT)] and to describe the relationship between hyperandrogenism, and adiposity and insulin sensitivity, in teens with CAH. We hypothesize that they have increased intrahepatic fat (IF), visceral fat (VF), and IMT, in part due to androgen excess. METHODS/STUDY POPULATION: Using a matched case–control design we have recruited 18 cases and 10 controls of a projected 40 per group. CT was used to quantify VF, subcutaneous fat (SF), and IF; DXA, BIA and anthropometric measures for body composition; IMT for subclinical atherosclerosis; and fasting lipids, insulin, glucose, androgens, inflammatory markers, and blood pressure were evaluated. RESULTS/ANTICIPATED RESULTS: Compared to controls matched for sex, age, ethnicity and BMI, teens with CAH (>11 y, 61% female, 60% overweight/obese) had significantly increased VF (19.9 ± 18.8 cm2 vs. 30.7 ± 23.0; p < 0.02). Among cases, there was no sex difference with respect to IMT or IF. SHBG correlated negatively with abdominal fat on CT (r =−0.51; p < 0.05) and trunk fat on DXA (r =−0.59; p < 0.02), while androstenedione correlated with L‐sided IMT (r = 0.50; p < 0.05). VF (r = 0.52; p < 0.05) and SF (r = 0.57; 0.59; p < 0.05) correlated positively with insulin and HOMA. DXA showed a positive association between HOMA and upper body fat (arms, trunk; r = 0.51;0.55; p < 0.05) and leptin (arms, trunk, legs; r = 0.85; 0.85; 0.87; p < 0.001). DISCUSSION/SIGNIFICANCE OF IMPACT: There could be a relationship between hyperandrogenism, and abdominal fat and IMT in teens with CAH. A lack of sex difference noted, and a possible role of elevated circulating androgens could suggest that females with CAH exhibit a cardiovascular phenotype more similar to their male counterparts, in part due to androgen excess or a lack of protective effect from estrogen.
P27
CHARACTERISTICS OF METHICILLIN‐RESISTANT AND METHICILLIN‐SUSCEPTIBLE S. AUREUS STRAINS FROM PATIENTS WITH COMMUNITY‐ACQUIRED PURULENT SKIN AND SOFT TISSUE INFECTIONS IN WASHINGTON, DC
May L 1, McCann C1, Dissen E1, Kan H2, Diallo A2, Jordan J1
1George Washington University, Washington, DC, USA; 2DC Department of Health, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: S. aureus is responsible for >50% of all Emergency Department (ED)skin and soft tissue infections (SSTI). Many community acquired strains have unique resistance traits and/or virulence factors. It is important that healthcare providers understand the characteristics of these infections within their local communities to provide appropriate treatment. We describe (1) clinical and demographic characteristics of an urban population presenting with SSTI and (2) molecular typing of S. aureus isolates. METHODS/STUDY POPULATION: Consenting subjects (≥18 y) who presented to an urban ED with purulent SSTI and received incision and drainage were enrolled in this ongoing, IRB approved study. A wound swab was sent to the clinical laboratory for culture and antimicrobial susceptibility testing. S. aureus isolates were further characterized by S. aureus Protein A (spa) sequence typing, PCR for methicillin resistance genes (SCCmec and mecA) and Panton‐Valentine Leukocidin (PVL) toxin gene (LukF‐PV and LukS‐PV). RESULTS/ANTICIPATED RESULTS: 72 subjects have been enrolled, of which 50% are male, 80.5% are black and 30.5% have significant comorbidities (diabetes, HIV, IDU). S. aureus was isolated from 54% pf subjects, of which 72% were MRSA and 28% were MSSA. Spa type t008 was responsible for 50% of S. aureus infections. PVL toxin gene was present in 100% of MRSA and 55% of MSSA isolates; no difference in 48 h outcome between PVL(+) or PVL(−) infections was observed. DISCUSSION/SIGNIFICANCE OF IMPACT: This study revealed data similar to previous findings in a DC population. Healthcare workers should be aware of these strain characteristics to provide appropriate treatment. Ongoing surveillance of community acquired S. aureus is important to detect emerging strains.
P28
CHLAMYDIA AND GONORRHEA INCIDENCE AMONG BLACK AND WHITE HIV NEGATIVE MSM IN ATLANTA, GA
Kelley CF 1, Rosenberg ES1, O’Hara B1, del Rio C1, Sullivan PS1
1Emory University, Atlanta, GA, USA
OBJECTIVES/SPECIFIC AIMS: Differences in sexually transmitted infections (STI) between HIV negative black and white men who have sex with men (MSM) likely contribute to disparities in HIV incidence. We report data on urethral and rectal C. trachomatis (CT) and N. gonorrhoeae (GC) incidence from a cohort of black and white HIV negative MSM. METHODS/STUDY POPULATION: The Emory InvolveMENt study is an ongoing longitudinal cohort of black and white MSM aged 18–40 years in Atlanta designed to evaluate factors that contribute to disparities in STI and HIV incidence. Participants are recruited from community‐based venues and tested for urethral and rectal CT and GC by NAAT at 3–6 month intervals. Incidence rates were calculated per 100 person‐years (PY) with exact Poisson 95% confidence intervals (CI) and compared for black and white MSM with exact binomial tests. RESULTS/ANTICIPATED RESULTS: Enrollment through September 2011 included 333 HIV negative MSM (40% black, 60% white) contributing 120.1 years of person‐time. A total of 12 participants had incident CT (6 black and 6 white MSM) for an incidence rate of 11.3 per 100 PY (95% CI 4.1, 24.6) for black MSM and 9.5 per 100 PY (3.5, 20.7) for white MSM (p for rate difference = 0.99). Seven GC infections were diagnosed among black MSM, rate 12.8 per 100 PY (5.2, 26.5), and 0 among white MSM, rate 0 per 100 PY (0, 5.7) (p for rate difference = 0.008). All GC and 50% of CT cases occurred among black MSM <25 years of age. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest high incidences of urethral and rectal CT among HIV negative black and white MSM and significantly higher GC incidence among HIV negative black MSM in Atlanta. Young black MSM appear to be at highest risk of incident GC infection. Differences in susceptibility to STI, sexual practices, and sexual networks deserve further investigation particularly as they relate to HIV acquisition.
P29
CLINICAL CHARACTERISTICS OF RESPIRATORY INFECTION IN ADULTS WITH ENTEROVIRUS 68 (EV68)
Kraft CS 1, Jacob JT1, Sears MH1, Burd EM1, Caliendo AM1, Hill CE1, Nix W2, Oberste M2
1Emory University, Atlanta, GA, USA; 2Centers for Disease Control and Prevention, Atlanta, GA, USA
OBJECTIVES/SPECIFIC AIMS: EV68 was initially isolated in 1962 from children with a respiratory illness, and prior to 2003,12 clinical samples have been isolated and characterized. After determination of the presence of EV68 in our patient population, we wanted to determine the clinical characteristics in adults as compared to patients with other serotypes/species of human rhinovirus (HRV). METHODS/STUDY POPULATION: Sixty‐eight primary samples that were positive for rhinovirus were sequenced to target the region spanning the VP4 gene and 59 terminus of the VP2 gene. Generation of neighbor‐joining trees demonstrated a phylogeny consistent with EV68. Comparison between the patients with EV68 and the HRV species was performed using Fisher’s exact test. RESULTS/ANTICIPATED RESULTS: Six patients had EV68 and 62 patients had HRV (species A, B or C). The median age of patients with EV68 was 42.5 years (40.0 years for HRV). Fever was present in 5 out of 6 patients in the EV68 group and in 33 of the HRV group (p = NS). There were 6 patients with HIV in the HRV group (p = NS) and 22 patients in the HRV group had abnormal chest x‐rays (p = NS). Two patients (66%) in the EV68 group were immunocompromised, compared with 27 (43%) in the HRV group (p = NS). Three patients were admitted to the hospital in the EV68 group and 38 patients in the HRV group (p = NS). Length of stay was 3.7 days (±1.2) for the EV68 group and 7.5 days (±7.7) for the HRV group. There were no deaths in the patients with EV68 and 5 deaths in the HRV group (p = NS). DISCUSSION/SIGNIFICANCE OF IMPACT: Adult patients with EV68 have similar clinical characteristics to individuals with HRV.
P30
CLINICAL CHARACTERISTICS, DEMOGRAPHICS AND OUTCOMES OF NEONATES WITH FETOMATERNAL HEMORRHAGE, 1993–2008
Stroustrup A 1, Trasande L2
1Mount Sinai School of Medicine, New York, NY, USA; 2New York University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: To determine clinical characteristics, demographics, and short‐term outcomes of neonates diagnosed with fetomaternal hemorrhage (FMH). METHODS/STUDY POPULATION: We analyzed a multiyear dataset concatenated from the 1993–2008 Nationwide Inpatient Sample, a statistically representative sample of hospital care in the United States. Singleton births diagnosed with FMH were identified by ICD‐9 code 762.3. Descriptive, univariate, and multivariable regression analyses were performed to determine the national annual incidence of FMH over time as well as demographics and clinical characteristics of neonates with FMH. RESULTS/ANTICIPATED RESULTS: Fetomaternal hemorrhage was identified in 12,116 singleton births. Newborns with FMH required high intensity of care: 26.3% received mechanical ventilation, 22.4% received blood product transfusion, and 27.8% underwent central line placement. Preterm birth (OR 3.7), placental abruption (OR 9.8) and umbilical cord anomaly (OR 11.4) were risk factors for FMH. Higher patient income was associated with increased likelihood of FMH diagnosis (OR 1.2), and whites were more likely to be diagnosed than ethnic minorities (OR 1.9). There was reduced frequency of diagnosis in the Southern United States (OR 0.8 versus the Northeastern United States). DISCUSSION/SIGNIFICANCE OF IMPACT: Diagnosis of FMH is associated with significant morbidity as well as regional, socioeconomic, and racial disparity. Further study is needed to distinguish between diagnostic coding bias and true epidemiology of the disease. This is the first report of socioeconomic and racial/ethnic disparities in FMH, which may represent disparities in detection that require national attention.
P31
COMMUNICATION AND COPING IN MOTHERS OF ADOLESCENTS WITH TYPE1 DIABETES
Jaser SS 1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: The aim of this multimethod, prospective study is to identify risk and protective factors for adolescents with type 1 diabetes (T1D). METHODS/STUDY POPULATION: Adolescents age 10–16 with T1D and their mothers completed measures of coping, depression, and anxiety, and participated in a brief videotaped discussion about diabetes stress. Videos were coded for specific parenting behaviors. Glycosylated hemoglobin data were obtained from medical records. RESULTS/ANTICIPATED RESULTS: Results from the ongoing study identified adaptive coping strategies for mothers dealing with diabetes‐related stress. Specifically, primary control coping strategies (e.g., problem solving) and secondary control coping strategies (e.g., acceptance) were related to fewer symptoms of maternal depression (r =−0.36, −0.39, both p < 0.005) and anxiety (r =−0.47, −.41, both p < 0.001). In contrast, disengagement coping strategies (e.g., avoidance) were related to greater symptoms of maternal depression (r = .34, p = 0.003) and anxiety (r = .41, p = < 0.001). Further, observed parenting behaviors were found to predict adolescent outcomes. Higher levels of observed intrusive parenting (e.g., interrupting) were related to greater of depressive symptoms in adolescents (r = .51, p = 0.001) at baseline, and predicted poorer glycemic control (r = .38, p = 0.028) 6 months later. On the other hand, expressions of positive reinforcement (e.g., “you’ve been so good about checking your blood sugar before meals”) predicted better glycemic control 6 months later (r = .37, p = 0.032). DISCUSSION/SIGNIFICANCE OF IMPACT: The relationship between maternal communication and coping behaviors and adolescent outcomes supports the need for an intervention for mothers of adolescents with T1D. The next step is to develop and test a cognitive behavioral intervention for distressed mothers aimed at improving communication and coping.
P32
COMPARATIVE EFFECTIVENESS OF AMPICILLIN AND THIRD GENERATION CEPHALOSPORINS FOR PEDIATRIC PATIENTS HOSPITALIZED WITH COMMUNITY‐ACQUIRED PNEUMONIA
Leyenaar J 1, Shieh M2, Pekow PS2, Lindenauer PK2
1Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA; 2Center for Quality of Care Research, Baystate Medical Center, Springfield, MA, USA
OBJECTIVES/SPECIFIC AIMS: Community‐acquired pneumonia (CAP) is a leading cause of pediatric hospitalization in the United States. Despite substantial disease burden and healthcare costs, little is known about the impact of the choice of antibiotic on outcomes in the management of CAP in hospitalized children. Our research aims to compare the effectiveness of parenteral ampicillin and third generation cephalosporins in the treatment of community acquired pneumonia in hospitalized children. METHODS/STUDY POPULATION: We are conducting a retrospective cohort study of previously well children who were hospitalized with CAP at 400 US hospitals that participate in the Perspective comparative database. Unadjusted associations between antibiotic treatment arm and patient and hospital characteristics will be assessed. A propensity score model will be constructed to control for observable patient and hospital characteristics. Negative binomial regression will be used to test for associations between antibiotic treatment regimen and length of stay, with adjustment for propensity score and other covariates. We will also compare outcomes in a sample of patients matched on propensity for treatment with third generation cephalosporins yet who received ampicillin. To minimize the risk of residual selection bias we will take advantage of variation in care across hospitals to conduct an instrumental variable analysis using the ampicillin prescribing rate as the instrument. RESULTS/ANTICIPATED RESULTS: Forthcoming. DISCUSSION/SIGNIFICANCE OF IMPACT: Should equivalence of these antibiotic regimens be found, decisions regarding antibiotic choice may be made in light of treatment costs and convenience as well as antibiotic stewardship.
P33
CORRELATES OF STI HISTORY AMONG LOW‐INCOME HISPANIC, BLACK, AND WHITE WOMEN AGED 16 TO 24 YEARS
Lugo JM 1, DeMaria AL1, Berenson AB1
1University of Texas Medical Branch, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: To describe sexually transmitted infection (STI) history and the extent to which it was related to demographic characteristics and sexual and reproductive history among low‐income Hispanic, black, and white women. METHODS/STUDY POPULATION: Data were collected from 1,155 low‐income women aged 16 to 24 years who were seeking family planning services at one of four publicly funded reproductive health clinics in the Texas Gulf Coast region. A self‐report paper‐and‐pencil instrument (Spanish or English) was utilized. Additional objective data was collected from clinical medical records. Data were analyzed using descriptive statistics and logistic regression analyses. All procedures and protocols were approved by the Institutional Review Board of the University of Texas Medical Branch. Informed consent was received from each participant and participants were reimbursed ≥20. RESULTS/ANTICIPATED RESULTS: The mean age of participants was 19.89 years (SD = 2.40; range = 16 to 24). Of the 1,155 participants, 643 (55.6%) were 16–19 years old and 512 (44.3%) were 20–24 years old. Overall, 54.2% (n = 626) self‐identified as Hispanic, 18.6% (n = 215) as black, and 24.8% (n = 287) as white. Over one‐quarter of participants (27.1%; n = 313) had ever been diagnosed with a STI. Having had a STI was associated with being Hispanic or black, underweight or normal weight, a tobacco user, using a condom during last vaginal intercourse, having had one or more pregnancies, and having multiple vaginal intercourse partners. DISCUSSION/SIGNIFICANCE OF IMPACT: STIs are extremely common among women of varying demographics. As the number of women diagnosed with sexuality‐related infections and diseases remains steady, it is important for clinicians to familiarize themselves with those individuals at risk so they can appropriately advise these individuals on safe sexual and reproductive health measures.
P34
EARLY CHILDHOOD PHYSICAL ACTIVITY: DIFFERENCES BETWEEN BOYS AND GIRLS AND TRACKING OVER FIVE YEARS
Edwards NM 1, Khoury PR1, Kalkwarf HJ1, Claytor RP2, Daniels SR3
1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 2Miami University, Oxford, OH, USA; 3University of Colorado School of Medicine, Aurora, CO, USA
OBJECTIVES/SPECIFIC AIMS: To determine whether relative high physical activity (PA) levels at 3 years of age are sustained in subsequent years during early childhood and to examine for sex differences. METHODS/STUDY POPULATION: In this prospective observational study, objective measures of PA (accelerometer) were collected every 4 months beginning at 3 years of age until 7 years of age. PA for each year of age (e.g., 3.0–3.99 y) was calculated as mean daily vector magnitudes per minute averaged across valid days (≥1). Spearman rank correlation coefficients between PA at age 3 y and ages 4–7 y were calculated. Participants were categorized into gender‐specific PA tertiles at each age. Differences in PA throughout the study between sexes and between the High PA tertile and Middle/Low PA tertile at age 3 y were tested using t‐tests. RESULTS/ANTICIPATED RESULTS: A total of 342 children had accelerometry data available for analysis at age 3. At age 3, PA was 613 ± 201 vpm (mean ± SD) in boys and 564 ± 199 vpm in girls; boys’ PA remained higher at each age (p < 0.01). PA at age 3 y was significantly correlated with PA levels at ages 4 through 7 y (0.16–0.37, p < 0.015). Participants in the highest tertile of PA at age 3 y were approximately twice as likely to remain in the highest tertile in subsequent years compared with those not in the highest tertile at age 3 (50% vs. 26%; p < 0.001). DISCUSSION/SIGNIFICANCE OF IMPACT: Boys are more active than girls at ages 3 through 7 y. Children who are relatively more physically active at age 3 y have a significantly greater likelihood of maintaining higher PA levels from age 4 to 7 y than their peers, highlighting the importance of establishing healthy PA levels early in life.
P35
EFFECT OF CARDIOVASCULAR DISEASE (CVD) RISK FACTORS ON BLOOD PRESSURE (BP) IN CHILDREN
Redwine KM 1, Brown W1, Binz T1, Swearingen C1
1University of Arkansas for Medical Sciences, Dept of Pediatrics, Little Rock, AR, USA
OBJECTIVES/SPECIFIC AIMS: To examine the effects of CVD risk factors on BP in children. METHODS/STUDY POPULATION: BP screening is ongoing in 6th graders in the Little Rock Public Schools. Demographics, height and weight are collected. Body mass index is calculated and obesity status determined by CDC criteria. Four BP measurements are taken after 5 min of rest using an Omron 705‐CP monitor. A mean of all 4 BPs was used for this analysis. Parents report the child’s health history (hx) including hypertension (HTN) in a first degree relative and presence of a household smoker. Subjects complete a shortened 2009 Middle School Youth Risk Behavior Survey. Differences in BP between risk factor groups were determined using t‐tests with linear regression models used to evaluate their additive effects on BP. RESULTS/ANTICIPATED RESULTS: 582 students (11.9 ± 0.46 yrs) have completed the study. 233 (39%) are male. 376 (62%) are African American, 134 (23%) non‐Hispanic white, and 57 (9%) Hispanic white. BP levels are higher among African Americans (SBP 109.8 ± 10.59 vs. 105.6 ± 8.98 p < 0.001; DBP 65.8 ± 8.80 vs. 62.6 ± 7.77 p < 0.001), with worsening CDC obesity level (SBP 1.5.2 ± 9.69 vs. 110.1 ± 8.84 vs. 113.0 ± 9.97 p < 0.001; DBP 62.9 ± 8.47 vs. 65.0 ± 8.69 vs. 67.76 ± 7.74 p < 0.001), among those with a family hx of HTN (SBP 111.2 ± 10.59 vs. 106.6 ± 9.65 p < 0.001; DBP 66.8 ± 8.68 vs. 63.4 ± 8.28 p < 0.001), and among those with a house‐hold smoker (SBP 110.2 ± 10.57 vs. 107.4 ± 9.98 p < 0.01; DBP 65.9 ± 8.87 vs. 64.0 ± 8.41 p < 0.05). In a multivariate model including age, race, gender, family hx of HTN, CDC obesity catergories, physical activity levels, and screen time, these risk factors maintained their significant effect on BP. DISCUSSION/SIGNIFICANCE OF IMPACT: Multiple CVD risk factors affect BP in children. While obesity is a well‐established modifiable risk factor for HTN in children, exposure to second‐hand smoke may also raise BP at this age.
P36
ENVIRONMENTAL PESTICIDES AND ALLERGIES IN THE US: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2005–2006
Jerschow E 1, McGinn AP2, De Vos GS2, Jariwala S1, Vernon N1, Rosenstreich D1
1Montefiore Medical Center, Bronx, NY, USA; 2Albert Einstein College of Medicine, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: We sought to test the association between exposure to environmental pesticides as a group of chlorophenols, and allergic sensitization measured by allergen‐specific serum IgE levels, in a US nationally representative sample of 2,353 persons 6 years of age and older in the National Health and Nutrition Examination Survey 2005–2006. METHODS/STUDY POPULATION: Exposure to chlorophenols was defined as urine levels of their metabolites at the 75th percentile and above. Association of the exposure to chlorophenols with food and environmental allergies was assessed in logistic regression models after adjustment for sample weights and potential confounders. RESULTS/ANTICIPATED RESULTS: Food allergies were more common in those with exposure to one or more chlorophenol metabolites. After multivariate adjustment, chlorophenol levels at the 75th percentile and above were associated with the presence of food allergy (OR 1.7, CI (1.3; 2.3), p = 0.002). There was no significant association between chlorophenol exposure and environmental allergies. Conclusions: High urine levels of chlorophenols are associated with the presence of food allergies. DISCUSSION/SIGNIFICANCE OF IMPACT: Previous research supports a possible link between westernized life style and allergic conditions. The westernized life style is associated with a reduced exposure to the rich microbial milieu of the soil and increased exposure to environmental pollutants, including pesticides. Pesticides may affect human health either by toxicity through ingestion or indirectly by decreased microbial contact. Finding a positive association in this cross‐sectional study could prompt further investigation of the effects of pollution on allergic diseases and asthma.
P37
FACTORS THAT CONTRIBUTE TO INSOMNIA IN YOUNG ADULTS OF AFRICAN DESCENT EXPOSED TO TRAUMA
Hall Brown T 1, Mellman TA1
1Howard University College of Medicine, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Insomnia (difficulty initiating and maintaining sleep) has been linked to compromised quality of life and predicts psychiatric morbidity. More recently it has also been linked to adverse health outcomes such as obesity, hypertension, and early mortality. Exposure to severe trauma and posttraumatic Stress Disorder (PTSD) has been associated with similar deleterious outcomes and features sleep disturbances, specifically insomnia and nightmares. African Americans residing in the inner city disproportionately report short sleep and trauma exposure. This study examined factors that contribute to insomnia in young adult minorities with high rates of trauma exposure. METHODS/STUDY POPULATION: We administered questionnaires to 400 healthy volunteers of African descent between the ages of 18 and 34. The study measures assessed sleep habits, insomnia severity, trauma exposure, PTSD severity, and sleep‐related vigilance (feeling on guard when falling asleep). RESULTS/ANTICIPATED RESULTS: Fifty‐four percent of the sample endorsed having at least sub‐threshold insomnia and 30% reported sleeping <6 hours. Seventy‐five percent experienced at least one type of trauma with 36% having probable PTSD. Regression analyses showed that fear of sleep was the strongest independent predictor of insomnia contributing 29% of the variance even after accounting for age, gender, short sleep duration, environmental stressors, and trauma severity. DISCUSSION/SIGNIFICANCE OF IMPACT: Addressing sleep vigilance in individuals exposed to trauma may lead to healthier sleep habits that will diminish the risk of adverse health outcomes in this population.
P38
FEAR OF INJURY WITH PHYSICAL ACTIVITY IS GREATER IN ADULTS WITH DIABETES THAN IN ADULTS WITHOUT DIABETES
Huebschmann A 1, Crane LA2, Belansky ES2, Scarbro S2, Marshall JA2, Regensteiner JG1
1University of Colorado School of Medicine, Aurora, CO, USA; 2Colorado School of Public Health, Aurora, CO, USA
OBJECTIVES/SPECIFIC AIMS: Physical activity is a cornerstone of treatment for diabetes, yet people with diabetes perform less moderate and vigorous physical activity (MVPA) than people without diabetes. In contrast, whether differences in walking activity exist has been understudied. Diabetes‐specific barriers to physical activity are one possible explanation for lower MVPA in diabetes. We hypothesized that people with diabetes would perform less walking and combined MVPA and would be less likely to anticipate increasing physical activity if barriers were theoretically absent, compared with people without diabetes. METHODS/STUDY POPULATION: We surveyed 1,848 randomly selected rural Colorado adult residents by telephone from 2002 to 2004. Respondents reported weekly walking and MVPA duration and their likelihood of increasing physical activity if each of seven barriers was theoretically absent. RESULTS/ANTICIPATED RESULTS: People with diabetes (n = 129) had lower odds of walking and MVPA than people without diabetes (walking: adjusted odds ratio 0.62 [95% CI 0.40–0.95]; MVPA: adjusted odds ratio 0.60 [0.36–0.99]; ≥10 vs. <10 min/week, adjusted for age, sex, BMI, and ethnicity). Respondents with diabetes reported fear of injury as a barrier to physical activity more often than respondents without diabetes (56 vs. 39%; p = 0.0002), although this relationship was attenuated after adjusting for age and BMI (adjusted odds ratio 1.36 [0.93–1.99]). DISCUSSION/SIGNIFICANCE OF IMPACT: Although walking is a preferred form of activity in diabetes, people with diabetes walk less than people without diabetes. Reducing fear of injury may potentially increase physical activity for people with diabetes, particularly in older and more overweight individuals.
P39
FEASIBILITY OF PORTABLE MONITOR FOR DIAGNOSIS OF OBSTRUCTIVE SLEEP APNEA (OSA) IN VULNERABLE POPULATIONS
Nickerson J 1, Krieger A2, Horowitz C1
1Mount Sinai School of Medicine, New York, CA, USA; 2Weill Cornell Medical College, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Despite high prevalence of risk factors, minorities are underdiagnosed for OSA, partly due to decreased access to costly studies. Treatment for OSA may improve glucose levels, rendering its diagnosis vital among prediabetics. Portable OSA monitoring devices may improve access to diagnosis, yet no data exist on vulnerable populations. We aimed to determine the feasibility of portable OSA diagnosis in a prediabetic, minority population. METHODS/STUDY POPULATION: We recruited a convenience sample of adult, overweight, prediabetic minorities. All participants wore ApneaLinkPlus portable monitor overnight and engaged in open‐ended interviews about their experience. Those with AHI >15/hour received auto‐CPAP machines. We analyzed interview transcripts and calculated means and standard deviations for continuous variables, proportions for categorical variables and group comparisons using chi‐square and student’s t‐test in SPSS v17. RESULTS/ANTICIPATED RESULTS: We tested 52 prediabetic, overweight adults. Demographics were: 64% Latino, 31% Black, 13.5% male, and 50% with income <≥15,000/year. Portable OSA diagnosis was feasible in this population: 100% monitors returned, no participants required in‐lab testing, participants found monitors comfortable and convenient (87% recommend test). We found 48% with OSA (>5 AHI/hour); 13% mod/sev OSA (>15 AHI/hour) requiring CPAP; 35% mild OSA requiring lifestyle counseling. Epworth Scale did not predict OSA (p = 0.506). Interviews showed that despite minor discomfort, most recommend increased OSA testing in their community. They also were concerned about progression to diabetes, and thought weight loss could improve OSA symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Portable OSA monitors represent a feasible method to increasing OSA diagnosis in high‐prevalence minority populations.
P40
GENETIC VARIATIONS OF INTERLEUKIN 28B IN RS12979860 AND RS8099917 ALLELES OF CHRONIC HEPATITIS C VIRUS INFECTED PATIENTS IN PUERTO RICO
Miranda EI 1, Morales L1, Pérez CM1, Rodríguez Medina J1, Torres E1
1University of Puerto Rico, San Juan, Puerto Rico
OBJECTIVES/SPECIFIC AIMS: Determine the prevalence of interleukin‐28B (IL28B) single nucleotide polymorphisms (SNPs) genotyping among Chronic Hepatitis C Virus (HCV) infected patients in Puerto Rico (PR). Correlate the IL28B SNPs genotype with the liver histology of HCV‐infected patients in PR. METHODS/STUDY POPULATION: Since 2002 a total of 250 patients have been recruited from the UPR Medical Sciences Clinics. Demographic and medical data was obtained and blood samples were drawn from each patient. Frequency distributions were generated to describe the demographic, clinical and biochemical characteristics of patients with Hepatitis C. Analytical methods include, DNA sequencing, capillary electrophoresis and single‐strand conformation polymorphism. RESULTS/ANTICIPATED RESULTS: Pending. It is anticipated that PR patients will be significantly different from other Hispanic populations. DISCUSSION/SIGNIFICANCE OF IMPACT: HCV infection is one of the leading etiologies of chronic liver disease, hepatocellular carcinoma and liver transplantation. The prevalence of HCV is about 3% worldwide. In PR, an overall prevalence of 2.3% was estimated among the adult population. Several genome‐wide association studies from different parts of the world indicated that SNPs near the IL28B gene (rs8099917 and rs12979860), which is located on chromosome 19 and encodes IFN λ‐3, are highly associated with spontaneous or treatment‐induced viral clearance in HCV patients. The high prevalence of HCV in PR predicts a significant burden of disease. Since Puerto Ricans are not genetically similar as Hispanics in the US, we are proposing to obtain the genetic variations near IL28b gene with the purpose of gathering information and statistics about the disease, which would serve for further studies that could benefit the population in general.
P41
HERITABILITY OF PROPOSED DSM‐5 AUTISM SYMPTOM DOMAINS IN A LARGE, CLINICALLY ASCERTAINED SAMPLE
Frazier T 1, Thompson L2, Law P3, Eng C1, Youngstrom E4, Morris N2
1Cleveland Clinic, Cleveland, OH, USA; 2Case Western Reserve University, Cleveland, OH, USA; 3Kennedy Krieger Institute, Baltimore, OH, USA; 4University of North Carolina at Chapel Hill, Chapel Hill, OH, USA
OBJECTIVES/SPECIFIC AIMS: The present study estimated extreme group heritability, individual differences heritability, and shared environmental effects on proposed DSM‐5 autism symptoms. METHODS/STUDY POPULATION: Twin data were obtained from the Interactive Autism Network (IAN; ASD‐affected twin pairs N = 369). Caregivers reported autism symptoms using the Social Responsiveness Scale (SRS) and/or the Social Communication Questionnaire (SCQ). Basic and augmented DeFries‐Fulker regression models were computed in extreme groups using SCQ and SRS total scores and domain scores reflecting social communication/interaction (SCI) and restricted/repetitive behavior (RRB) symptoms. RESULTS/ANTICIPATED RESULTS: Extreme group heritability (hg2) was very large (smallest β= .92, SE = .15, p < 0.001) and consistent across total, SCI, and RRB scores. Shared environment (c2) and individual differences heritability (h2) were not significant when extreme scores were examined (c2 largest β= .54, SE = .82, p > 0.10; h2 largest β= .52, SE = .48, p > 0.10). Bivariate (cross‐construct) heritability analyses—where twin pairs are selected for a high score on one symptom domain and group heritability is calculated for the second domain—indicated substantial genetic correlations for extreme SCI and RRB scores (smallest β= .81, SE = .15, p < 0.001). DISCUSSION/SIGNIFICANCE OF IMPACT: The present results indicate strong heritability and minimal environmental influences on the autism phenotype. These findings should be considered preliminary and will require confirmation with more extensive modeling. If confirmed, results support a strong investment in genomic research and suggest that genetic influences are likely to be pleiotropic, simultaneously driving SCI and RRB symptoms.
P42
INSULIN RESISTANCE AND CEREBROSPINAL FLUID BIOMARKERS IN PUERTO RICANS WITH EARLY ALZHEIMER'S DISEASE
Sepulveda V 1, Vega I3, Carrion J4, Jimenez I1, Arnold S2, Wojna V1
1University of Puerto Rico School of Medicine, SJ, Puerto Rico; 2University of Pennsylvania School of Medicine, Philadelphia, PA, USA; 3University of Puerto Rico Department of Biology, SJ, Puerto Rico; 4University of Puerto Rico School of Public Health, SJ, Puerto Rico
OBJECTIVES/SPECIFIC AIMS: Insulin Resistance (IR) plays a role in the pathophysiology of Alzheimer’s Disease (AD).Insulin regulates the amyloid precursor protein and its derivative βamyloid (Aβ1–42), a neuropathological hallmark of AD. CSF tau and βamyloid are potential biomarkers of AD. A link between IR and the amyloid pathway may exist in the pathogenesis of AD. We propose to study the association between CSF Aβ1–42, total and ptau and plasma IR in Puerto Ricans with early AD. METHODS/STUDY POPULATION: Puerto Ricans diagnosed with early AD based on the NIH and AD Association criteria will be recruited from outpatents clinics. Aβ1–42, total and ptau will be assay in CSF using ELISA. Blood glucose tests will be performed to determine IR (OGTT, FBS, fasting insulin). Homeostatic model assessment (HOMA) will be calculated using FBS and fasting insulin. Association between demographics and clinical characteristics with CSF markers and IR will be determined. RESULTS/ANTICIPATED RESULTS: This study will advance our knowledge on the role of IR in the development of AD. It will provide further data that CSF tau, βamyloid and IR are linked and that in combination can be used as biomarkers for early detection of AD. DISCUSSION/SIGNIFICANCE OF IMPACT: Around 25% of patients with IR will develop diabetes which is currently a risk factor for AD. The prevalence of diabetes is higher in Puerto Ricans compared with non‐Hispanic whites. This study is timely, given that IR associated conditions such as diabetes has reached epidemic proportions in the Puerto Rican population. The prevalence of such chronic conditions, in combination with a rapidly ageing population, may result in an increase in the prevalence of AD.
P43
INVESTIGATING A SEXUAL NETWORK OF BLACK MEN WHO HAVE SEX WITH MEN IN NORTH CAROLINA: IMPLICATIONS FOR HIV TRANSMISSION AND PREVENTION
Hurt CB 1, Beagle S1,2, Leone P1,2, Sugarbaker A1, Pike E1, Kuruc J1, Foust E2, Eron J1, Cohen M1, Hightow‐Weidman LB1
1UNC Chapel Hill, Chapel Hill, NC, USA; 2NC Dept of Health & Human Services, Raleigh, NC, USA
OBJECTIVES/SPECIFIC AIMS: Investigate a sexual network of young, black MSM; characterize the risk environment in which these men acquire HIV; and assess prevention needs. METHODS/STUDY POPULATION: We used network mapping alongside descriptive and bivariate statistics to characterize network members and sexual dyads. RESULTS/ANTICIPATED RESULTS: The network included 398 individuals and 419 sexual relationships. Three‐quarters were black (n = 299), 94% were MSM. Median age at first network appearance was 26 (range, 16–56) and decreased over time (p < 0.01). HIV prevalence in the network was at least 30% (n = 117); serostatus was unknown for 47% of the network, either because they were untraceable (n = 150) or refused HIV testing (n = 39). Incident sexually transmitted infections were noted in 25 HIV‐infected network members following HIV diagnosis (21%; 22 syphilis, 3 gonorrhea), after a median of 1.91 years (IQR, 1.08–2.85); all were MSM. Eighty‐two serodiscordant relationships were observed; 20% involved clients with acute HIV infection. Approximately 40% of dyads involved clients with chronic HIV (n = 167), reflecting ongoing sexual activity following diagnosis. In multivariable models, having a one‐time sexual encounter increased the risk of untraceable partners (RR 4.51, 95%CI, 2.27,8.97), while being acutely HIV infected at diagnosis reduced it (RR 0.27, 95%CI, 0.08,0.89). DISCUSSION/SIGNIFICANCE OF IMPACT: HIV prevalence in this sexual network rivals that of sub‐Saharan Africa, reflecting dramatically increased chances of acquiring HIV from the moment individuals join the network. Prevention efforts for this population must consider the effect of sexual networks on HIV risk, and find ways to leverage network structure to reduce transmission.
P44
LIFESTYLE BARRIERS TO DIABETES MANAGEMENT IN URBAN LATINO YOUNG ADULTS
Pyatak B 1, Weigensberg MJ2, Clark FA1
1Div. of Occupational Science and Occupational Therapy, USC, Los Angeles, CA, USA; 2Dept. of Pedatrics, Keck School of Medicine, USC, Los Angeles, CA, USA
OBJECTIVES/SPECIFIC AIMS: Young adults (YAs) with type 1 or type 2 diabetes (T1D/T2D) are at high risk for poor health outcomes. Reasons for this in low‐SES Latino YAs may include lifestyle barriers to diabetes self‐management (DSM) adherence. Study aims: (1) To characterize lifestyle barriers to DSM adherence among low‐SES Latino YAs age 18–30 with T1D or T2D. (2) To examine differences in barriers in T1D versus T2D. METHODS/STUDY POPULATION: Participants, as part of two clinical studies, were recruited from diabetes or primary care clinics and completed semi‐structured interviews on their lifestyles and DSM adherence. In Study 1, a convenience sample of 20 YAs with T1D were interviewed upon enrollment in a diabetes clinic. In Study 2, 10 purposively sampled YAs with T2D each completed a series of interviews until data saturation was achieved. Chart reviews were conducted to verify diagnoses and medical histories. Interviews were audiotaped and transcribed for narrative thematic analysis using N*Vivo software. Rigor was achieved through member checking, peer review of themes, and an audit trail of analytic memos. RESULTS/ANTICIPATED RESULTS: Preliminary analyses found that barriers to DSM included logistical challenges in accessing care; view of DSM as incompatible with life goals or activities; lack of health literacy and self‐advocacy skills; and lack of social support. YAs with T2D, versus T1D, had more shame and responsibility, a more fatalistic view of diabetes, and perceived diabetes as less severe. DISCUSSION/SIGNIFICANCE OF IMPACT: This study identified lifestyle areas to address in an intervention for DSM adherence. Behavioral and contextual barriers were similar in YAs with T1D and T2D, but differences in attitude and motivation for DSM will need to be accounted for in an intervention aimed at both groups.
P45
MODERATE‐COMPLICATED METHICILLIN‐RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) SKIN AND SOFT TISSUE INFECTIONS (SSTIS) IN 10 PRIMARY CARE CLINICS: A STARNET STUDY
Frei CR 1,2, Labreche MJ1,2, Forcade NA1,2, Parchman ML3, Du LC4, Nyren NR4, Trevino LB4, Pena J4, Mann MW4, Munoz A4, Trevino SB4, Wickes BL2, Mortensen EM2,3, Jorgensen JH2, Pollock BH2
1UT Austin, Austin, TX, USA; 2UT Health Science Center, San Antonio, TX, USA; 3VERDICT, South Texas Veterans Health Care System, San Antonio, TX, USA; 4South Texas Ambulatory Research Network (STARNet), San Antonio, TX, USA
OBJECTIVES/SPECIFIC AIMS: To determine the proportion of patients admitted to primary care clinics who have moderate‐complicated MRSA SSTIs. METHODS/STUDY POPULATION: Clinicians from 10 primary care clinics in a regional PBRN collected clinical data and skin cultures from 72 patients with MRSA SSTIs. U.S. Food and Drug Administration criteria were used to classify SSTIs as moderate‐complicated (diabetes mellitus or lesions ≥ 5 cm in diameter) or mild‐uncomplicated infections. Contingency table analysis was used to compare patient and treatment characteristics between the two groups. RESULTS/ANTICIPATED RESULTS: Half the patients were male (50%) and most were Hispanic (75%). Two‐thirds (67%) had moderate‐complicated SSTIs. Diabetes was present in 46% of the patients with moderate‐complicated SSTIs; 81% had a lesion ≥ 5 cm and 27% had both diabetes and a lesion ≥ 5 cm. Incision and drainage (I&D) plus antibiotics were used for treatment in 63% of patients with moderate‐complicated and 67% with mild‐uncomplicated infections (p = 0.7, chi‐square); 27% and 29% received antibiotics without I&D (p = 0.9); 8% and 4% received I&D only (p = 0.5); 2% and 0% went for surgery (p = 0.3). Trimethoprim‐sulfamethoxazole (TMP‐SMX) was prescribed to 95% of the moderate‐complicated and 87% of the mild‐uncomplicated patients (p = 0.3); 17% and 13% received TMP‐SMX in combination with other antibiotics (p = 0.7). DISCUSSION/SIGNIFICANCE OF IMPACT: Moderate‐complicated SSTIs are common in the primary care setting. I&D plus antibiotics are underutilized in these patients.
P46
NEUROTICISM AND AGGRESSION IN TREATMENT‐SEEKING ALCOHOLICS WITH COMORBID POSTTRAUMATIC STRESS DISORDER (PTSD)
Sells JR 1, Schwandt ML1, Kwako LE1, Hommer DW1, Heilig M1, George DT1, Ramchandani VA1
1Laboratory of Clinical and Translational Studies, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Bethesda, MD, USA
OBJECTIVES/SPECIFIC AIMS: Our previous studies demonstrated differences in personality, specifically neurotic traits, in a sample of treatment‐seeking alcoholics with comorbid PTSD. The purpose of our current analysis is to extend the characterization of our sample regarding facets of neuroticism and aggression. METHODS/STUDY POPULATION: The sample was 411 treatment‐seeking alcoholics (300 male) undergoing detoxification and inpatient treatment in the NIAAA treatment research program at the NIH Clinical Center. The sample included 79 (19.2%) patients with comorbid PTSD assessed using Structured Clinical Interview for DSM‐IV‐TR diagnoses. Neuroticism was assessed using NEO Personality Inventory. Aggression was assessed using Buss‐Perry Aggression Questionnaire. RESULTS/ANTICIPATED RESULTS: There was a high prevalence of neuroticism in this sample of patients with PTSD with significant correlation on several facets including: anxiety (p = 0.016), angry hostility (p = 0.002), depression (p < 0.001), self‐consciousness (p = 0.003), and vulnerability (p = 0.003). Patients with PTSD showed higher verbal aggression (p = 0.016) and hostility (p < 0.001) than patients without PTSD. Physical aggression was associated with PTSD only in males (p = 0.053). DISCUSSION/SIGNIFICANCE OF IMPACT: There was a high prevalence of neurotic traits and aggression in this sample of alcoholics with comorbid PTSD, which is consistent with the clinical phenotype of this population. These findings substantiate the heterogeneity of alcoholism and the need for specialized treatment.
P47
OSTEOPOROSIS AMONG HIV‐INFECTED INDIVIDUALS IN CHINA
Hsieh E 1, Fraenkel L1, Insogna K1, Bradley EH2, Li TS3
1Yale School of Medicine, New Haven, CT, USA; 2Yale School of Public Health, New Haven, CT, USA; 3Peking Union Medical College Hospital, Beijing, China
OBJECTIVES/SPECIFIC AIMS: (1) Compare the course trajectory of bone turnover markers (BTM) in a cohort of Chinese patients with HIV following initiation of antiretroviral therapy (ART) over a one‐year period in two ART regimens and a third crossover group. (2) Measure the association between risk factors for osteoporosis (OP) and bone turnover in this cohort. (3) Measure health beliefs regarding OP and OP prevention measures in this cohort. METHODS/STUDY POPULATION: This study involves secondary data analysis of BTM in stored serologic samples collected at six time points over one‐year from a multicenter randomized controlled trial comparing two ART regimens and a crossover group (n = 355). Associations between time varying risk factors and BTM will be examined. A cross‐sectional survey using previously validated scales will measure health beliefs regarding OP and OP prevention measures. RESULTS/ANTICIPATED RESULTS: (1) Bone turnover will increase in the first six months of ART initiation, stabilize over the following six months, and bone formation will lag behind bone resorption. The length of time to stabilization of BTM in the crossover group will be prolonged compared with the other two groups. (2) Risk factors such as low BMI, smoking, and lipodystrophy will be associated with increased bone turnover. (3) Knowledge regarding OP will be limited and subjects will perceive barriers to prevention. DISCUSSION/SIGNIFICANCE OF IMPACT: Countries in economic transition such as China have borne a disproportionate increase in the rate of OP and associated fracture. Patients with HIV are a subgroup at higher risk for bone loss both due to HIV itself as well as ART‐associated increases in bone turnover. No studies have measured this phenomenon in China, nor attempted to assess health beliefs and attitudes towards OP prevention in this population.
P48
OVERWEIGHT, OBESITY, AND INTENTIONAL WEIGHT LOSS IN CHRONIC KIDNEY DISEASE
Navaneethan SD 1, Kirwan JP1, Arrigain S1, Schreiber MJ1, Sehgal AR2, Schold JD1
1Cleveland Clinic, Cleveland, OH, USA; 2MetroHealth Medical Center, Cleveland, OH, USA
OBJECTIVES/SPECIFIC AIMS: Obesity and chronic kidney disease (CKD) have emerged as major public health problems. We aimed to examine: (1) lifestyle and behavioral factors, (2) factors related to pursuing weight loss, and (3) weight loss modalities pursued by CKD and non‐CKD individuals who are overweight and obese. METHODS/STUDY POPULATION: Cross‐sectional analysis of 10,971 overweight and obese adult participants in the National Health and Nutrition Examination Surveys conducted between 1999–2006. We examined the differences in lifestyle and behavioral factors between CKD and non‐CKD participants and factors associated with pursuing weight loss using survey regression models. RESULTS/ANTICIPATED RESULTS: The total daily energy intake of the CKD population was lower than the non‐CKD group (1987 kcal/day vs. 2063 kcal/day, p = 0.02) even after adjusting for relevant covariates. However, the percentage of energy derived from protein was similar between the groups. Sixty‐six percent of the CKD population did not meet the minimum recommended leisure time physical activity goals compared to 57% among non‐CKD (p < 0.001). Fifty percent of CKD participants pursued weight loss (vs. 55% of non‐CKD individuals, p = 0.01). Among participants pursuing weight loss, modalities including dietary interventions utilized by CKD and non‐CKD participants were similar. Eight percent of CKD participants used medications to promote weight loss. DISCUSSION/SIGNIFICANCE OF IMPACT: Lifestyle and behavioral factors related to obesity and weight loss are similar between overweight and obese CKD and non‐CKD participants. A significant proportion of the CKD population use weight loss modalities that may be harmful. Future clinical trials evaluating the efficacy and optimal modalities to treat obesity in the CKD population are warranted.
P49
PATTERNS OF COMORBID CHRONIC DISEASES AND GERIATRIC CONDITIONS ASSOCIATED WITH GREATER SEVERITY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
Chang SS 1, Gill TM1
1Yale School of Medicine, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Extrapulmonary diseases commonly occur throughout all stages of COPD, complicating its management and prognosis, especially as COPD worsens. Geriatric conditions, which confer high risk of adverse health outcomes, add to the complexity of effectively managing COPD in older adults. Identifying patterns of comorbid chronic diseases and geriatric conditions which are associated with greater COPD severity in older adults will provide insight into enhanced approaches to optimize outcomes. METHODS/STUDY POPULATION: Data were from the Cardiovascular Health Study, a cohort of adults aged 65–80 who completed baseline spirometry (N = 3583). COPD was defined by spirometric criteria for airflow limitation, using the lambda‐mu‐sigma (LMS) method, an approach which accounts for age‐related changes in lung function. We performed ordinal logistic regression to evaluate the relationships between patterns of comorbidities and COPD severity, staged according to LMS‐derived spirometric z‐scores (mild, moderate, and severe). Models were adjusted for age, gender, education, smoking, and other coexisting conditions. RESULTS/ANTICIPATED RESULTS: Of the participants with COPD (13.8%), comorbid hypertension (HTN) and arthritis (28.0%), diabetes mellitus (DM) and HTN (15.4%), and HTN and polypharmacy (11.1%) were among the most frequent comorbidity patterns. Those who had comorbid HTN and arthritis (adjusted OR = 1.56, 95%CI = 1.03–2.36), DM and HTN (1.69, 1.01–2.82), and HTN and polypharmacy (1.93, 1.05–3.56) were more likely than individuals without these respective comorbidities to have greater COPD severity. DISCUSSION/SIGNIFICANCE OF IMPACT: Specific patterns of comorbid chronic diseases and geriatric conditions are associated with worsening COPD. These findings could inform the design of interventions to improve outcomes in older adults with COPD.
P50
POOR ASTHMA CONTROL IN OLDER ADULTS IS LINKED TO CHRONIC EXPOSURE TO TRAFFIC POLLUTANTS AND OBESITY
Epstein T 1,2, Ryan P3,1, Bernstein C4, Levin L1, Bernstein J1,4, Villareal M1, LeMasters G1, Bernstein D1
1University of Cincinnati, Cincinnati, OH, USA; 2Cincinnati VA, Cincinnati, OH, USA; 3Cincinnati Children’s, Cincinnati, OH, USA; 4Bernstein Clinical Research, Cincinnati, OH, USA
OBJECTIVES/SPECIFIC AIMS: Environmental and host predictors of asthma control in asthmatics > age 65 are poorly understood. We examined the effects of residential exposure to traffic exhaust, as measured by elemental carbon attributable to traffic (ECAT), and other environmental and host predictors on asthma control in older adults. METHODS/STUDY POPULATION: Asthmatics > age 65 from allergy and pulmonary clinics in Cincinnati completed the validated asthma control questionnaire (ACQ), pulmonary function testing, and skin prick testing (SPT) to 10 aeroallergens. Subjects had physicians’ diagnosed asthma and reversibility in FEV1 or a positive methacholine test; those with COPD were excluded. A land‐use regression model was applied to estimate ECAT using current residential addresses. Regression models were used to compare independent variables (including ECAT, BMI, demographics) with 6 (asthma symptoms) and 7‐item (includes FEV1) ACQ scores. RESULTS/ANTICIPATED RESULTS: One hundred four asthmatics participated. In the adjusted model, residential exposure to ECAT > 0.39 μg/m3 was significantly associated with poorer asthma control based on 6‐ and 7‐item ACQ scores (adjusted β= 2.85 [0.58, 5.12]; p = 0.02). There was a significant association between higher BMI and poorer asthma control (adjusted β= 1.15 [0.53, 1.76]; p < 0.001). Atopics (SPT+) had significantly better asthma control than nonatopics (adjusted β=−0.39 [−0.67, −0.11]; p < 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first study demonstrating that chronic residential exposure to traffic pollutants significantly worsens asthma control in older adults. Obesity and nonatopic status also significantly worsen asthma control in this population.
P51
POTENTIAL MEDIATORS OF SEASON OF BIRTH'S EFFECTS ON FOOD ALLERGY
Keet C 1, Matsui EC1, Wood RA1
1Johns Hopkins School of Medicine, Baltimore, MD, USA
OBJECTIVES/SPECIFIC AIMS: To determine (1) whether fall birth increases risk of food allergy among the general US population and (2) what factors may interact with or mediate the relationship. METHODS/STUDY POPULATION: Three study populations were used; 5,862 children from the National Health and Nutrition Examination Survey III (NHANES III), 1,677 well characterized food allergic children from the Johns Hopkins Pediatric Allergy Clinic (JH), and the 1,114,701 births in Maryland from 1990–2005. For NHANES, food allergy was defined by self‐report of an acute reaction to a food, and for JH, milk, egg and peanut allergy were defined as in previously published reports. Logistic regression was used to compare fall or non–fall birth (1) between food allergic and nonallergic subjects in NHANES, and (2) between JH food allergic subjects and the general Maryland population. NHANES data were adjusted for ethnicity, age, income and sex. For NHANES, stratification by ethnicity (Caucasian vs. non‐Caucasian) was examined. For JH, interactions between season and eczema were examined. RESULTS/ANTICIPATED RESULTS: Fall birth was more common among food allergic subjects in both the NHANES population (OR: 1.91, 95% CI: 1.31–2.77) and the JH/Maryland population (OR: 1.29, 95%CI: 1.16–1.43). Ethnicity interacted with season of birth (OR 2.34, 95% CI 1.43–3.82 for Caucasians, OR 1.19, 95% CI 0.77–1.86 for non‐Caucasians, p = 0.04 for interaction). Fall birth was only a risk factor for food allergy among those with a history of eczema (OR 1.39, 95% CI 1.23–1.57, compared to OR 1.01, 95% CI 0.82–1.24 among those without eczema, p = 0.01 for interaction). DISCUSSION/SIGNIFICANCE OF IMPACT: Fall birth is a significant risk factor for food allergy, and interacts with both ethnicity and season, supporting the role of vitamin D in seasonal effects, and suggesting that the effects of season may be related to variation in skin barrier.
P52
PREVALENCE OF DIAGNOSED AND SURVEY‐ASSESSED FIBROMYALGIA IN OLMSTED COUNTY
Vincent A 1, Whipple MO1, Hawkins ES1, Lahr BD1, St. Sauver J1
1Mayo Clinic, Rochester, MN, USA
OBJECTIVES/SPECIFIC AIMS: Our primary objective was to estimate the prevalence of fibromyalgia (FM) in Olmsted County. Specifically, we sought to estimate prevalence of diagnosed FM through medical record review and in a community sample using a validated FM survey tool. This allowed us to estimate FM prevalence and assess differences between the two methods. METHODS/STUDY POPULATION: We used the Rochester Epidemiology Project (REP) diagnostic index to retrieve a list of Olmsted County residents age 21 and older with HICDA code 07893213 or equivalent ICD‐9 code 729.1 between 1/1/2005 and 12/31/2009. We then reviewed medical records to estimate the number of patients diagnosed with FM by a healthcare provider. To estimate FM in the community sample, we mailed the FM survey tool to an age‐ and sex‐stratified random sample of 3000 free living adults from Olmsted County. RESULTS/ANTICIPATED RESULTS: We identified and reviewed medical records of 3,164 patients. Of these, 1115 patients had been diagnosed with FM by a healthcare provider. The estimated prevalence of diagnosed FM in Olmsted County was 1.13% (95% CI, 1.07%–1.20%). Eight hundred thirty of the stratified random sample of 3,000 Olmsted County residents responded to the survey. Of these, 44 (5.30%) met survey criteria for FM. Based on this sample, the age‐ and gender‐adjusted prevalence of FM using the survey tool was estimated to be 6.36% (95% CI, 4.28%–8.44%). Despite similarities in age, participants who met survey criteria for FM in the random community survey differed from those with diagnosed FM; a higher proportion were male (32% vs. 6%, p < .001) and had lower symptom severity scores (p = 0.011). DISCUSSION/SIGNIFICANCE OF IMPACT: Prevalence of diagnosed FM in Olmsted County is 1.13% and prevalence of FM in Olmsted County by survey method is 6.36%. Our study suggests that FM may be underdiagnosed, particularly in men.
P53
PREVALENCE OF SHINGLES AND ASSOCIATION WITH PTSD and DEPRESSION AMONG HIV INFECTED WOMEN IN RWANDA
Sinayobye J 1, Hoover DR2, Shi Q3, Cohen M4, Mutimura E5, Cohen HW1, Anastos K1
1Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA; 2Rutgers University, New Brunswick, NJ, USA; 3New York Medical College, Valhalla, NY, USA; 4Cook County Medical Center, Chicago, IL, USA; 5Women’s Equity in Access to Care and Treatment (WE‐ACTx), Kigali, Rwanda
OBJECTIVES/SPECIFIC AIMS: we examined the prevalence of self‐reported shingles in the last 6 months and its association with PTSD, depression, and severity of HIV disease in HIV infected and uninfected Rwandan women. METHODS/STUDY POPULATION: This cross‐sectional analysis was conducted in the Rwanda Women’s Interassociation Study and Assessment (RWISA). The outcome of interest was self‐reported shingles in the past 6 months. The exposures were PTSD and Depressive symptoms, defined using the HTQ and CES‐D respectively. Forward stepwise selection logistic regression built multivariate predictive models of shingles. RESULTS/ANTICIPATED RESULTS: Overall prevalence of shingles in the past 6 months was 9.7% (n = 91). Shingles was significantly more prevalent in the HIV infected than uninfected women (p < 0.001) and among infected women was strongly associated with lower immunologic status (CD4 count) (p < 0.001). In multivariate analysis, having HIV infection with CD4 < 200 cells/μl (aOR) = 17.7; 95% CI 4.1–77.1) and CD4 = 200–350 cells/μl (aOR = 13.4; 95% CI 3.1–58.4) were independently associated with reported shingles in the past 6 months. PTSD was borderline associated with shingles (aOR = 1.56; 95% CI 0.96–2.65; p value 0.09) whereas depressive symptoms were not DISCUSSION/SIGNIFICANCE OF IMPACT: PTSD was borderline significantly associated with shingles. However, the association with depressive symptoms was much weaker and perhaps mediated by confounding with poor health status. Our data confirmed previous findings of a strong relationship of shingles with greater immunosuppression in women with HIV infection.
P54
PROGNOSTIC IMPLICATION OF ELEVATED CARDIAC TROPONIN I LEVELS AT ED PRESENTATION
Korley FK 1, Shah SH1, Chang TT1, Hill PM1
1Johns Hopkins University, Baltimore, MD, USA
OBJECTIVES/SPECIFIC AIMS: Determine the association between cardiac troponin I (cTnI) concentration at ED presentation and all‐cause mortality. METHODS/STUDY POPULATION: Retrospective study of patients presenting to an urban academic ED from May 2008 to February 2010, who were evaluated for MI. The assay has a 10% coefficient of variation at 0.06 ng/ml, and only values equal to or greater than this concentration are reported by our lab (positive cTnI). cTnI at presentation was categorized into: <0.06 ng/ml, 0.06–0.08 ng/ml, 0.09–0.49 ng/ml, and >0.50 ng/ml. All‐cause mortality during the year after index ED visit was ascertained by reviewing patient electronic medical records and the Social Security Death Index. Cox proportional hazards and logistic regression models were used to determine the association between cTnI at presentation and all‐cause mortality. RESULTS/ANTICIPATED RESULTS: Of 5,191 eligible patients, 989 (19%) had at least one positive cTnI and were included in our analysis. 241 (24.4%) of the cTnI positive patients died during the year after their ED visit. Compared to patients with a negative initial cTnI on presentation, those with a positive cTnI on presentation had a higher hazard ratio of death (1.72 [1.02–2.87] for the 0.06–0.08 ng/ml category; 1.77 [1.08–2.91] for the 0.09–0.49 ng/ml category; and 1.71 [0.93–3.16] for the >0.50 ng/ml category). However, after adjusting for age, mean arterial pressure and glomerular filtration rate (GFR), this difference was no longer statistically significant. Age and low mean arterial pressure at presentation and low GFR are associated with death within 1 year. DISCUSSION/SIGNIFICANCE OF IMPACT: The 1 year mortality rate for patients with a positive cTnI is high, however, the hazard ratio for death for patients with a high cTnI value at presentation is similar to that for patients with a low cTnI value at presentation.
P55
PUBIC HAIR REMOVAL AND GROOMING BEHAVIORS AMONG LOW‐INCOME HISPANIC, BLACK, AND WHITE WOMEN AGED 16 TO 40 YEARS
DeMaria AL 1, Berenson AB1
1University of Texas Medical Branch, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: To describe pubic hair removal and grooming behaviors (shaving, waxing, trimming or dyeing) and the extent to which grooming was related to demographic characteristics and sexual behavior among low‐income Hispanic, black, and white women of varying ages. METHODS/STUDY POPULATION: Data for the current study were collected via an anonymous, self‐administered cross‐sectional written survey from 2,270 women aged 16 to 40 years. Participants were recruited from one of three publicly funded reproductive health clinics in the Texas Gulf Coast region between July 2010 and August 2011. All procedures and protocols were approved by the Institutional Review Board of the University of Texas Medical Branch. Informed consent was received from each participant. Those who participated were reimbursed ≥5 for their time. RESULTS/ANTICIPATED RESULTS: The mean age of participants was 26.3 years (SD = 6.27; range = 16 to 40). Participants reported a variety of pubic hair removal and grooming behaviors, with about one‐half (49.7%; n = 1,128) of women being current groomers. Grooming was associated with being white, a younger age, being under or normal weight, having a yearly household income > ≥30,000, higher education. DISCUSSION/SIGNIFICANCE OF IMPACT: Pubic hair grooming is extremely common among women of varying demographics. It is important for clinicians to familiarize themselves with pubic hair grooming behaviors so they can appropriately address health implications (e.g., epidermal abrasion, razor burn, ingrown hairs, folliculitis, vulvitis, etc.) and advise patients on safe practices.
P56
RESETTING THE BAR: FREQUENCY OF SEVERE HYPOGLYCEMIA (SH) AND DIABETIC KETOACIDOSIS (DKA) AMONG CHILDREN WITH TYPE 1 DIABETES (T1D) IN THE T1D EXCHANGE REGISTRY
Cengiz E 1, Wolfsdorf J2, Miller K3
1Yale University School of Medicine, New Haven, CT, USA; 2Children’s Hospital Boston, Boston, MA, USA; 3Jaeb Center for Health Research, Tampa, FL, USA
OBJECTIVES/SPECIFIC AIMS: DKA and SH are the major life threatening complications of diabetes, and yet only a few multicenter studies have investigated the frequency of these important complications in pediatric patients. The T1D Exchange Clinic Registry currently includes approximately 60 adult and pediatric centers in the U.S and has over 8,000 participants with T1D. The aim of this study was to investigate the rate of DKA and SH in pediatric T1D Exchange participants. METHODS/STUDY POPULATION: Data obtained from 4,120 participants (age <18 years, T1D for ≥ 1 yr, 48% female, 82% non‐Hispanic white, mean ± SD age 11.9 ± 3.6 years, T1D duration 5.2 ± 3.5 yrs, HbA1c 8.4%± 1.5%) were analyzed. Frequencies of DKA and SH (defined as any of the following: seizure or coma, glucagon injection, emergency medical team called and treated while hypoglycemic) in the 12 months prior to enrollment were obtained from clinic records. RESULTS/ANTICIPATED RESULTS: In the prior 12 months, DKA occurred in 5.7% (21% with >1 event) and SH in 4.7% (27% with >1 event) of participants. The incidence rates were 7.8% and 6.6% per 100 person‐yrs, respectively. The 14–17 yo age group had more episodes of DKA (p < 0.001) and the <5 yo age group had more episodes of hypoglycemia (p = 0.05) compared with other age groups. The proportion of participants with both a DKA and SH event was 1%, 1%, and 2% in the 1–5, 6–12, and 13–17 yo groups, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: DKA and SH remain major challenges for youth with T1D. Identifying high risk groups and developing interventions targeted at these groups are needed to reduce the burden of these complications.
P57
RISK FACTORS FOR NEURODEVELOPMENTAL OUTCOMES OF INFANTS WITH TWIN‐TWIN TRANSFUSION SYNDROME (TTTS)
Vanderbilt D 1,2, Schrager S1, Seri I1,2, Chmait R2
1CHLA, Los Angeles, CA, USA; 2Keck School of Medicine, Los Angeles, CA, USA
OBJECTIVES/SPECIFIC AIMS: This study describes risk factors associated with neurodevelopmental outcomes of infants with TTTS at 24 months. METHODS/STUDY POPULATION: A retrospective cohort study of infants who underwent fetoscopic selective laser photocoagulation for TTTS was performed at a single fetal‐medicine university center in Los Angeles. Neurodevelopment at 24 months (±6 weeks) was assessed using the Battelle Developmental Inventory (BDI) total standardized score. Based on previous literature, higher Quintero stage, later gestational age at surgery, lower gestational age at birth, and lower birth weight (from a clinical database) were hypothesized to be associated with lower/worse BDI scores. Other covariates included current weight, head circumference, sex, ethnicity, corrected age, and other demographic factors. Multilevel linear regression models using Mplus were used to evaluate risk factors for BDI. RESULTS/ANTICIPATED RESULTS: Preliminary data from 1 years of recruitment are presented. To date, 71 children (30 twin pairs and 11 singletons) from 41 families were assessed. 38 (54%) were male; 34 (48%) were donors; 30 (42%) were Latino and 28 (39%) were White; and 11 (26%) of mothers had high school degree or less. Average BDI score was within normal levels (102.1 SD = 12.4) and none of the children were in the developmental delay range of #70. Lower birth weight (β= 0.52, p < 0.001); higher current weight (β=−0.40, p < 0.05) and lower head circumference (β= 0.40, p < 0.01) were associated with worse outcome. DISCUSSION/SIGNIFICANCE OF IMPACT: While this cohort of TTTS infants showed developmental quotients in the average range, birth weight, current weight and lower head circumference emerged as determinants of neurodevelopmental outcome. These results may have direct translational implications for early clinical and psychosocial interventions of these infants.
P58
SEROTONIN TRANSPORTER GENE FUNCTIONAL POLYMORPHISMS AND SUSCEPTIBILITY TO BIPOLAR DISORDER: AN UPDATED META‐ANALYSIS OF ASSOCIATION STUDIES
Fan J 1
1Case Western Reserve University, Cleveland, OH, USA
OBJECTIVES/SPECIFIC AIMS: In view of the conflicting results concerning the association between bipolar disorder and the two common SLC6A4 gene polymorphisms, the promoter insertion/deletion (5‐HTTLPR) and the intron 2 variable number tandem repeat (STin2 VNTR) polymorphisms, we pooled results of all published original association studies to determine the overall strength of putative association between the two SLC6A4 gene polymorphisms and bipolar disorder. METHODS/STUDY POPULATION: MEDLINE and Web of Science databases were searched through August 2010. Meta‐analysis was conducted using the DerSimonian‐Laird random‐effects model. The method described previously by Lohmueller et al. (2003) was utilized to calculate the combined effect size from both case‐control and family‐based association studies. RESULTS/ANTICIPATED RESULTS: For the 5‐HTTLPR polymorphism: meta‐analysis showed no statistically significant evidence for association between the Short allele and bipolar disorder (pooled odds ratio (OR) = 1.05, 95% Confidence Interval (CI) = 0.99–1.11, p = 0.075). For the STin2 VNTR polymorphism: meta‐analysis showed no statistically significant evidence for association between the STin2.12 allele and bipolar disorder (pooled OR = 1.07, 95% CI = 0.97–1.17, p = 0.17). For both 5‐HTTLPR and STin2 VNTR polymorphisms, the pooled ORs were not excessively affected by the inclusion of any single study. No significant evidence for small‐study effects within each group of studies was observed. DISCUSSION/SIGNIFICANCE OF IMPACT: In contrast to previous studies, an updated meta‐analysis including more recently published association studies suggests that neither the 5‐HTTLPR polymorphism nor the STin2 VNTR polymorphism is likely a risk factor for bipolar disorder susceptibility.
P59
THE ASSOCIATION BETWEEN PHYSICAL FUNCTION, NEUROCOGNITION, AND SYMPTOMS IN OLDER ADULTS WITH SCHIZOPHRENIA
Leutwyler H 1, Hubbard E1, Shin S1, Miller B1, Jeste D2, Vinogradov S1
1UCSF, San Francisco, CA, USA; 2UCSD, San Diego, CA, USA
OBJECTIVES/SPECIFIC AIMS: Older adults with schizophrenia exhibit poorer physical function compared to the general population. Some contributing factors are known, including lower socioeconomic status, adverse effects of medication, smoking, sedentary habits, and healthcare disparities. However, the associations linking neurocognitive performance, psychiatric symptoms, and physical function have not been adequately explored. METHODS/STUDY POPULATION: In this ongoing cross‐sectional study in 50 older adults with schizophrenia, participants are assessed on neurocognitive function (MATRICS Consensus Cognitive Battery), symptoms (Positive and Negative Syndrome Scale), and physical function (SF‐12 physical function sub score and the Timed Get Up and Go Test). Pearson’s bivariate correlations (two‐tailed) are used to test the following hypotheses: (1) More severe schizophrenia symptoms will be associated to poorer physical function. (2) More severe neurocognitive deficits will be associated to poorer physical function. RESULTS/ANTICIPATED RESULTS: To date, 26 participants have completed the study. Preliminary analyses revealed that poorer self rated physical function (SF‐12) was associated with higher severity of symptoms (PANSS Total score, r =−.49, p = 0.01). Worse physical function as measured by the Timed Get Up and Go Test was significantly associated with more severe negative symptoms (r = .38. p = 0.06). Better SF‐12 scores were associated with higher scores on the category fluency test(r = .48, p = 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest that more severe schizophrenia symptoms and more severe neurocognitive deficits negatively impact physical function. These data may help to inform the design of interventions that can promote physical function in older adults with schizophrenia.
P60
THE IMPACT OF COGNITIVE IMPAIRMENT ON MORTALITY IN OLDER ADULTS WITH HEART FAILURE
Gure TR 1, Blaum CS1,2, Ha J1, Hummel SL1, Min LC1,2, Cigolle CT1,2, Galecki A1, Langa KM1,2
1University of Michigan, Ann Arbor, MI, USA; 2VA Health Care System, Ann Arbor, MI, USA
OBJECTIVES/SPECIFIC AIMS: Background: Cognitive impairment (CI) is highly prevalent in older adults with heart failure (HF), yet our understanding of the impact of CI on mortality in this population is limited. We aimed to estimate the risk of death over 4 yrs of follow‐up in older adults with HF, stratified by cognitive function. METHODS/STUDY POPULATION: Methods: We used the 2004 wave of the Health and Retirement Study (HRS) linked to Medicare claims. A HF case‐finding algorithm identified HRS respondents with highest likelihood of a HF diagnosis (“HF patients”). CI was assessed using previously published HRS population‐based screening measures. Death was identified using the HRS data verified by National Death Index. We tested the relationship between cognitive function and mortality in HF patients using unweighted Kaplan‐Meier survival curves and Cox proportional hazard models. RESULTS/ANTICIPATED RESULTS: Results: Of 707 HF patients identified, 286 (42%) died over the 4 yr‐period. Survival of older HF patients was significantly influenced by their cognitive status (p < 0.001, log rank test). HF subjects with moderate/severe CI compared to those with HF who have normal cognition have significantly higher risk of death in the 4‐year time period after controlling for sociodemographics, comorbidity burden, and the time‐varying effect of cognitive performance (HRR: 2.48; 95% CI: 1.73–3.35). DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: In older adults with HF, CI is associated with a higher risk of death than normal cognitive function. Potential mechanisms, such as interference with optimal self‐management, are important clinical questions to consider in future research.
P61
THYROID CANCER DETECTION BASED ON TUMOR SIZE
Valderrabano R 2,1, Hunter R2,1, Haymart M3
1University of Puerto Rico School of Health Professions, San Juan, Puerto Rico; 2Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico; 3University of Michigan Medical School, Ann Arbor, MI, USA
OBJECTIVES/SPECIFIC AIMS: Establish a data base of fine needle aspiration (FNA) of thyroid nodules done under sonographic guidance. Establish characteristics of thyroid nodules that are positive, indeterminate and negative for malignancy. METHODS/STUDY POPULATION: A database will be created from the medical records of over 500 patients who underwent sonographically guided FNAs performed by two pathologists at several practice locations within the island of Puerto Rico. The patient demographic characteristics such as age and gender and clinicopathological characteristics of the thyroid nodules such as size, location, multifocality, number of biopsies and sonographic characteristics, will be described. These data will be compared to the results of FNA for these patients. FNA results will be categorized as insufficient sample, negative for malignancy, positive for malignancy or indeterminate. RESULTS/ANTICIPATED RESULTS: Ultrasound‐guided FNA biopsy of thyroid nodules will provide a reliable diagnosis of thyroid carcinoma. Rates of diagnosis of carcinoma will be similar in nodules over 1 cm and under 1 cm but over 0.5 cm. Rates of biopsies which yield insufficient samples will increase with decreasing nodule size. DISCUSSION/SIGNIFICANCE OF IMPACT: The incidence of differentiated thyroid cancer has increased more than six fold in the past 7 years. Thyroid nodules suspicious for malignancy are submitted to FNA, the results of which are critical for therapeutic decision making. FNA for nodules less than 1 cm is not currently recommended except in high risk patients, nevertheless the rate of thyroid malignancy does not seem to be lower in small nodules. Even though modern alternatives to palpation guided FNA may improve sampling, the value of performing biopsies on small nodules is still under debate.
CLINICAL TRIAL
P62
A BROAD CORTICAL RESERVE ACCELERATES RESPONSE TO COGNITIVE ENHANCEMENT THERAPY IN EARLY COURSE SCHIZOPHRENIA
Eack SM 1, Wojtalik JA1, Prasad KM1, Francis AN2, Bhojraj TS2, Cho RY1, Greenwald DP1, Hogarty SS1, Keshavan MS2,1
1University of Pittsburgh, Pittsburgh, PA, USA; 2Harvard Medical School, Boston, MA, USA
OBJECTIVES/SPECIFIC AIMS: Cognitive rehabilitation has emerged as an effective method for improving cognition in many individuals with schizophrenia. Biological markers could offer key insights into understanding heterogeneity of clinical response to these interventions. This study investigated the effects of pretreatment neurobiologic reserves on response to Cognitive Enhancement Therapy (CET) in early course schizophrenia. METHODS/STUDY POPULATION: Outpatients in the early course of schizophrenia or schizoaffective disorder were randomly assigned to CET (n = 29) or an Enriched Supportive Therapy control (n = 21) and treated for two years. Structural neuroimaging data were collected prior to treatment and moderator analyses were conducted to examine the impact of greater pretreatment cortical surface area and gray matter volume on differential neurocognitive and social‐cognitive response to CET. RESULTS/ANTICIPATED RESULTS: Greater whole brain cortical surface area and gray matter volume prior to initiating treatment significantly moderated the effects of CET on social cognition, but not neurocognition. Patients with a greater neurobiologic reserve demonstrated a rapid social‐cognitive response to CET in the first year of treatment (d = .64), whereas patients with less neurobiologic reserve improved little in the first year (d = .09), but achieved a comparable social‐cognitive response (d = .45) by the second year of treatment. DISCUSSION/SIGNIFICANCE OF IMPACT: A broad cortical surface area and gray matter reserve is associated with an accelerated social‐cognitive response to CET in early schizophrenia. The benefits of cognitive rehabilitation are still apparent after a longer duration of treatment in those with less initial neurobiologic resources.
P63
ACE INHIBITOR USE BY OLDER ADULTS IS ASSOCIATED WITH IMPROVED FUNCTIONAL RESPONSES TO EXERCISE
Buford TW 1, Manini TM1, Hsu F2, Cesari M3, Anton SD1, Nayfield S1, Stafford RS4, Church TS5, Pahor M1, Carter CS1
1University of Florida College of Medicine, Gainesville, FL, FL, USA; 2Wake Forest School of Medicine, Winston‐Salem, NC, USA; 3Université de Toulouse, Toulouse, France; 4Stanford University Medical School, Stanford, CA, USA; 5Pennington Biomedical Research Center, Baton Rouge, LA, USA
OBJECTIVES/SPECIFIC AIMS: To assess the association of ACE inhibitor (ACEi) use with exercise‐derived improvements in physical function among physically‐limited older adults. METHODS/STUDY POPULATION: Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE‐P) study. LIFE‐P investigated the effects of 12‐months of either structured physical activity or health education to promote successful aging. Four hundred twenty‐four adults aged 70–89 years at risk for physical disablility participated. This analysis compared change in outcome measures at 6‐ and 12‐months among participants who (1) did not use antihypertensive (AHT) drugs, (2) used ACEi, and (3) used AHT drugs excluding ACEi. Primary outcome measures were change in performance on a battery of short‐duration mobility tasks (SPPB) and walking speed during a 400 meter test. RESULTS/ANTICIPATED RESULTS: PA improved the adjusted SPPB score among ACEi users (p < 0.001) and users of other AHT drugs (p = 0.005) but not among AHT nonusers (p = 0.911). Adjusted SPPB changes at 12 months were 0.95 points among ACEi users, 0.77 points among users of other AHT drugs, and −0.08 points among AHT nonusers. PA improved the adjusted walking speed of ACEi users (p < 0.001) but did not improve walking speed among the other two groups across study visits. At 12 months adjusted changes were 0.06 m/sec among ACEi users, 0.05 m/sec among AHT nonusers, and 0.02 m/sec among users of other AHT drugs. DISCUSSION/SIGNIFICANCE OF IMPACT: Among older adults at risk for disability, exercise‐derived improvements in physical function were greatest among ACEi users.
P64
ASSESSING THE CULTURAL COMPETENCY AND DISEASE AWARENESS OF INPATIENT AND OUTPATIENT ONCOLOGY NURSES PROVIDING CARE FOR PATIENTS DIAGNOSED WITH ADULT T‐CELL LEUKEMIA/LYMPHOMA (ATLL)
Cortese M 1, Cunningham R2, Godbold J1, Gabrilove J1
1Mount Sinai School of Medicine, New York, NY, USA; 2University of Pennsylvania, Philadelphia, PA, USA
OBJECTIVES/SPECIFIC AIMS: (1) To assess the cultural competency and disease awareness of inpatient and outpatient oncology nurses at Mount Sinai Medical Center who provide care for patients diagnosed with ATLL. (2) To assess if nurses who have graduated from a nursing baccalaureate program in the past 10 years have more cultural competence than those nurses who have graduated more than 10 years ago. METHODS/STUDY POPULATION: A descriptive design was utilized. Oncology nurses from Mount Sinai Medical Center and ONS Tri‐State area chapters were enrolled. One survey assessed knowledge regarding Japanese and Caribbean culture; and another survey assessed disease awareness regarding HTLV‐1 and ATLL. The target sample was 126 nurses. Using nQuery Advisor version 6.0 statistical analysis software, it was determined that 126 subjects will provide a margin of error of 0.165 for a 95% confidence interval about the mean score in the total group. For the secondary objective, the sample size was based on a 2 sided t‐test with a significance level of 5%, a power of 95% and a correlation coefficient 0.10. RESULTS/ANTICIPATED RESULTS: The results of this study showed that 73 out of 129 nurses scored less than 50% of the questions correctly on the ATLL disease knowledge survey, 20 out of 129 nurses scored less than 50% of the questions correctly on the Japanese cultural awareness survey, and 25 out of 129 nurses scored less than 50% of the questions correctly. DISCUSSION/SIGNIFICANCE OF IMPACT: Cultural competence in the part of nursing has shown better patient care outcomes. These results show that nurses need further education regarding ATLL, Haitian and Japanese culture. A second study is currently in progress to address this need and incorporate the patient’s perception.
P65
CUE‐INDUCED MOTIVATION FOR REWARD IN PARKINSON'S PATIENTS: POTENTIAL ASSOCIATION WITH IMPULSIVE/COMPULSIVE BEHAVIORS
Taylor J 1, Aldridge W1, Persad C1, Patil PG1, Chou KL1
1University of Michigan, Ann Arbor, MI, USA
OBJECTIVES/SPECIFIC AIMS: Some Parkinson’s patients develop impulsive/compulsive behaviors when treated with dopamine replacement therapy. Basic science studies suggest that dopamine receptor stimulation amplifies the ability of reward‐related cues to trigger reward‐seeking behavior. We have begun to investigate whether Parkinson’s patients with impulsive/compulsive behaviors are strongly motivated by environmental stimuli associated with reward. METHODS/STUDY POPULATION: We are using a human version of the Pavlovian Instrumental Transfer (PIT) task to measure cue‐induced motivation for reward in Parkinson’s patients. Participants first learn to work for quarters by squeezing a handgrip device. Then they learn that one audiovisual conditioned stimulus (CS+) predicts quarters, while a control stimulus (CS−) did not. In the transfer phase, we measure the motivational value of the reward‐associated cue was by comparing the number of handgrips made in response to the CS+ compared to the CS−. We hypothesized that the difference between the CS+ responses and the CS− responses would positively correlate with the severity of impulsive/compulsive behavior. RESULTS/ANTICIPATED RESULTS: Contrary to our hypothesis, we have not found a significant relationship between impulsive/compulsive behavior severity and motivation triggered by the CS+ compared to the CS− (R2 =−.38, ns) in the transfer portion of the task thus far (n = 10). Interestingly, however, the QUIP‐RS scores positively correlate with the number of responses to the CS+ (R2 =−.70, p < 0.05) and to the CS− (R2 =−.80, p < 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: This may indicate that those who suffer from impulsive/compulsive behavior may not have the ability to discriminate between the motivational value of cues prior to initiating an instrumental response for reward.
P66
DELAYED INSULIN SECRETORY RESPONSES BECOME MORE PROMINENT WITH LONGER DURATION OF TYPE 1 DIABETES (T1D)
Sherr J 1, Rink L1, Wurtz A1, Herold K1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Previous reports have characterized insulin secretion rates (ISR) with nondiabetic (ND) controls having early secretion profiles (@<45 minutes) after ingestion of a mixed meal test (MMT). Subjects with T1D followed for 2 yrs after diagnosis showed that delayed responders had a slower decline in total ISR; however, ISR has not been assessed in subjects with longer disease duration. METHODS/STUDY POPULATION: Data derived from MMT were analyzed in (1) 20 subjects with T1D < 1 yr duration, (2) 13 subjects with T1D 2–5 yrs, (3) 21 subjects with T1D >5 yrs, (4) 38 ND controls. Only subjects with detectable C‐peptide were analyzed (100% T1D < 1 yr, 85% T1D 2–5 yrs, 57% T1D >5 yrs). Chronobiological Series Analyzer (CSA) was used to calculate ISR by deconvolution of C‐peptide using a 2‐compartment model for hormone clearance. Parameters used included the subject’s age, sex, height, and diabetes status. Total ISR area under the curve (AUC) and time of peak insulin secretion was calculated. RESULTS/ANTICIPATED RESULTS: Mean Total ISR AUC was 48,870 pmol for the ND controls. There was a decline in total ISR AUC with duration of T1D [mean total ISR AUC for T1D < 1 yr 33,485 pmol; 16,166 for T1D 2–5 yrs; 9,669 pmols for T1D > 5 yrs] (p < 0.0001 for all vs. ND). A higher proportion of delayed responders was seen with increasing duration of T1D (p < 0.001). DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that there is an increase in delayed insulin secretory responses in individuals with longer duration T1D. We hypothesize that those with early patterns of insulin secretion had faster loss of insulin production. Prospective follow‐up after diagnosis will help to confirm if delayed responders are more likely to maintain endogenous insulin secretion. Characterization of these individuals and their inclusion in immunomodulatory trials would be warranted.
P67
DETERMINANTS OF THE 6‐MINUTE WALK TEST IN OLDER ADULTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION
Silva J 1, Shaffer J1, Teruya S1, Maurer M1
1Columbia University Medical Center, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: The 6‐minute walk test (6MWT) is a common used measurement to assess functional status and exercise capacity in patients with systolic heart failure for which the causes of exercise intolerance have been identified. We examined the relationship between 6MWT and cardiac and noncardiac comorbidities in older adults with heart failure with preserved ejection fraction (HFPEF). METHODS/STUDY POPULATION: We analyzed prospective data from an ongoing clinical trial (NCT00286182) of older patients with HFPEF evaluating their exercise capacity with the 6MWT. Clinical, laboratory, depression score, pain index and quality of life data were collected. The relationships were correlated by Pearson’s coefficient and multivariate regression analysis (p < 0.05). RESULTS/ANTICIPATED RESULTS: 56 older patients with HFPEF (68% female; mean age 77 ± 11 years; EF 58 ± 9%, NYHA Class 2.7 ± 0.6, BNP 430 ± 366 pg/ml) were analyzed. No training effect was noted during measurement of the walking distance and repeated 6MWT was reproducible (r = 0.90, p < 0.0001). Height and weight did not significantly influence 6MWT. 6MWT was strongly associated with quality of life indicators as assessed by the Kansas City Cardiomyopathy Questionnaire (r = 0.48, p = 0.0002), Minnesota Living with Heart Failure Questionnaire (r =−0.43, p < 0.002) and Geriatric Depression Score (r =−0.27, p < 0.05). Multivariate regression analysis indicated that advanced age, higher BNP and more pain on the WOMAC index were identified as independent predictors of poor 6MWT performance (p < 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: 6MWT is reproducible in older adults with HFPEF and both cardiovascular and non‐cardiovascular factors are determinants of performance in this population. These data have potential impacts on the use of this measure in clinical trials when evaluating exercise capacity in older adults with HFPEF.
P68
DETERMINATION OF HEMODYNAMIC PARAMETERS DURING 6‐MINUTE WALK TEST IN PULMONARY HYPERTENSION
Tonelli A 1, Arelli V1, Ramos J1, McCarthy K1, Pichurko B1, Dweik R1
1Cleveland Clinic, Cleveland, OH, USA
OBJECTIVES/SPECIFIC AIMS: To determine the cardiac output and stroke volume response during 6‐minute walk test in patients with pulmonary hypertension (PH). METHODS/STUDY POPULATION: We included patients with PH confirmed by right heart catheterization. We determined heart rate (HR), cardiac output (CO), cardiac index (CI) and stroke volume (SV) during the 6‐minute walk test using a new generation portable impedance cardiography device (Physioflow enduro, Manatec Biomedical) with real time wireless monitoring. RESULTS/ANTICIPATED RESULTS: Eighteen patients participated in the study. Mean (SD) age was 51.4 (16) years, 61% female. Pulmonary arterial hypertension was present in 78% of the patients; the rest had chronic thromboembolic PH or PH associated with parenchymal lung disease. Pulmonary vascular resistance was 11 (9) Wood Units. Six‐minute walk test results included a distance walk of 378 (117) meters or 67 (19)% of predicted. Stroke volume increased from 54 (18) mL at rest to 80 (23) mL with activity. CO increased from 4.3 (1.1) L/min at rest to 9 (2.3) L/min with activity. The CI increased from 2.3 (0.7) L/min/m2 at rest to 4.8 (1.5) L/min/m2 during the test. All the comparisons at rest versus activity were statistically significant (p < 0.001). The CO slope (from baseline to maximal CO) was 0.72 (0.42) L/min. Distance walked in meters and percentage of predicted was associated with the slope of CO increase (R = 0.49, p = 0.039). Distance walked was significantly and directly associated with CO, CI and SV difference between activity and rest (R from 0.5–0.58). DISCUSSION/SIGNIFICANCE OF IMPACT: Real time wireless impedance cardiography based on pure signal morphology analysis allows the noninvasive determination of hemodynamic parameters in PH patients during six‐minute walk test. SV, CO and CI increase with activity in direct relation with the distance walked.
P69
EFFECT OF ENDURANCE EXERCISE ON NONALCOHOLIC FATTY LIVER DISEASE
Sullivan S 1, Kirk EP2, Mittendorfer B1, Patterson BW1, Klein S1
1Washington University School of Medicine, St. Louis, MO, USA; 2Southern Illinois Univeristy – Edwardsville, Edwardsville, IL, USA
OBJECTIVES/SPECIFIC AIMS: Nonalcoholic fatty liver disease (NAFLD) affects 33% of US adults. Lifestyle modification has been recommended as a treatment; however the independent effects of exercise on NAFLD are not well understood. The aims of this study were to determine the effect of moderate intensity exercise training on intrahepatic triglyceride content and hepatic lipoprotein kinetics in weight stable obese persons with NAFLD. METHODS/STUDY POPULATION: Obese persons with intrahepatic triglyceride content >10% on magnetic resonance spectroscopy were eligible for this study and were randomly assigned to a control group or an exercise group (30–60 min, 5 days/week, VO2 max 45–55%) for 16 weeks. Magnetic resonance spectroscopy, dual‐energy‐x‐ray absorptiometry, peak aerobic capacity test, and hepatic lipoprotein studies were performed at baseline and postintervention. RESULTS/ANTICIPATED RESULTS: Six control subjects (BMI 40.0 ± 5.4 kg/m2, age 47.5 ± 7.5 years) and 12 exercise subjects (BMI 37.1 ± 4.0 kg/m2, age 48.6 ± 7.5 years) completed the study. Intrahepatic triglyceride content decreased in the exercise group compared to the control group (−10.27 ± 16%, p = 0.044). No changes were seen in hepatic lipoprotein plasma concentrations or kinetics. Plasma alanine transaminase concentration decreased in the exercise group compared to the control group (−12.8 ± 19%, p = 0.02), and correlated with change in intrahepatic triglyceride content (R2 = 0.596, p < 0.001). DISCUSSION/SIGNIFICANCE OF IMPACT: Moderate intensity endurance exercise training without weight loss results in small but beneficial effects on intrahepatic triglyceride content and plasma alanine trasnaminase concentration, but does not affect hepatic lipoprotein kinetics in obese persons with NAFLD.
P70
EVALUATION OF INTRAVENOUS (IV) ETHANOL SELF‐ADMINISTRATION IN HEAVY DRINKERS
Vatsalya V 1, Coe MA1, Cooke ME1, Issa J1, Barlett S2, Hommer DW1, Heilig M1, Ramchandani VA1
1NIAAA, Bethesda, MD, USA; 2Gallo Clinic and Research Center, Emeryville, CA, USA
OBJECTIVES/SPECIFIC AIMS: Considerable clinical and experimental evidence in humans and animal models links nicotine use with heavy consumption and severity of alcohol problems. This study aims to evaluate IV ethanol self‐administration behavior in smoking and nonsmoking heavy drinkers. METHODS/STUDY POPULATION: 37 male and female, smoking and nonsmoking, heavy drinkers, aged 21–58 years, underwent a baseline Computer‐Assisted Self‐infusion of Ethanol (CASE) session as part of a medication study. The session consisted of an initial 25‐min priming phase followed by a 125‐min ad lib phase, where subjects could press a button for short standardized ethanol infusions. Self‐administration measures included peak breath alcohol level (BrTH), average BrTH (AvgBrTH) and number of button presses. Alcohol use disorder identification test (AUDIT) score was used to index hazardous and harmful alcohol use. RESULTS/ANTICIPATED RESULTS: There was a significant correlation among self‐administration measures in this sample. MANOVA analysis indicated a significant effect of AUDIT score on self‐administration measures. There was no effect of sex or smoking history; however there was a trend for association of peak BrTH with the Fagerström measure of smoking dependence and breath carbon monoxide (BrCOC) levels in smokers. AvgBrTH showed significant association with (AUDIT as a covariate) BrCOC. Drinking history measures were not significantly associated with self‐administration measures. DISCUSSION/SIGNIFICANCE OF IMPACT: Heavy drinkers demonstrated robust IV ethanol self‐administration that was associated with hazardous and harmful alcohol use. There were no differences in self‐administration measures between smokers and nonsmokers in this sample.
P71
INCREASED DETECTION OF ALCOHOL CONSUMPTION AND AT‐RISK DRINKING WITH COMPUTERIZED ALCOHOL SCREENING AND BRIEF INTERVENTION (CASI) IN AN EMERGENCY DEPARTMENT POPULATION
Lotfipour S 1, Howard J1, Roumani S1, Hoonpongsimanont W1, Chakravarthy B1, Anderson C1, Cisneros V1, Dykzeul B1, Moreno F1, Sumrell C1, Vaca F2
1UC Irvine Medical Center, Irvine, CA, USA; 2Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: A comparison of a brief person‐to‐person Medical Screening Examination (MSE) to Computerized Alcohol Screening and Intervention (CASI) for emergency department (ED) patients that consume alcohol, and those that are at‐risk for alcohol related disease was conducted. METHODS/STUDY POPULATION: Single‐institution, retrospective review of CASI/MSE database in the ED setting from January 2008 through December 2009. Inclusion in the study included age > 18, and completion of both the MSE and CASI. We analyzed of the CASI/MSE database for alcohol use by comparing age, gender, primary language (English, Spanish), and Alcohol Use Disorders Identification Test (AUDIT) scores. RESULTS/ANTICIPATED RESULTS: Complete MSE and CASI data were available for 5,835 patients. Overall, CASI showed an increase in detection of alcohol consumption and at‐risk drinking over MSE across all ages, gender, and primary language. MSE found 75% nondrinkers, 22% drinkers not at risk, and 2.5% at‐risk drinkers. CASI found 56% nondrinkers, 33% drinkers not at risk, and 11.5% at‐risk drinkers. CASI found 9.6% of patients had AUDIT > 8. Finally, for 389 patients under the age of 21, MSE found 79% nondrinkers, 19% drinkers not at risk, and 2% drinkers at risk, while CASI found was 51% nondrinkers, 33% drinkers not at risk, and 16% drinkers at risk, with 13% of patients had AUDIT scores ≥8. DISCUSSION/SIGNIFICANCE OF IMPACT: CASI displays increased detection of alcohol consumption compared with MSE across all ages, gender, and primary language of English and Spanish. A significant number of patients with at‐risk consumption were discovered by CASI and received intervention, including underage drinkers.
P72
REDUCTION OF HYPERTROPHIC SCARS BY PROPRANOLOL
Finnerty CC 1, Hegde SD1, Hawkins H1, El‐Ayadi A1, He J1, Rodriguez NA1, Prasai A1, Bergmann J1, Porro LJ1, Herndon DN1
1The University of Texas Medical Branch / Shriners Hospitals for Children, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: Hypertrophic scarring (HS) occurs in severely burned patients. These scars are inflammatory, pruritic, and impair mobility and function. We have shown that propranolol, a nonselective β‐blocker, decreases postburn HS. Here we examined histological sections to identify differences between HS from control or propranolol treated patients. METHODS/STUDY POPULATION: 20 patients were enrolled in the study. 10 patients received placebo (Control: C) and 10 received 4 mg/Kg/day propranolol (P) for 1 year postburn. The demographics were similar. HS biopsies were taken 18 months postburn. Six observers, blinded to treatment, scored H&E stained sections using a novel scoring system devised by our group. The criteria assessed included dermal inflammation, percent nodularity, vascularity, loss of rete ridges, collagen fiber size, collagen fiber orientation, blood vessel location, presence of cysts, and epidermal thickness, each scored from 0 (normal skin) to 4 (very abnormal). Scores for each group were tabulated and significance set at p < 0.05. RESULTS/ANTICIPATED RESULTS: HS from patients treated with p had significant reductions (p < 0.05) in scar vascularity (P:1.23 ± 0.07, C:2.15 ± 0.04), perivascular inflammation (P:1.1 ± 0.11, C:1.8 ± 0.11) and dermal inflammation (P:0.94 ± 0.009, C:1.80 ± 0.11). DISCUSSION/SIGNIFICANCE OF IMPACT: The mechanism by which propranolol reduces post‐burn HS is unknown; these results indicate that angiogenesis and inflammation may be reduced by propranolol treatment. Future studies will focus on elucidating the impact of propranolol during wound healing.
P73
SAFETY, TOLERABILITY, AND EFFICACY OF THE DIETARY SUPPLEMENT COENZYME Q10 IN HEMODIALYSIS PATIENTS
Yeung C 1, Claessens AJ1, Linke LJ2, Clark C2, Ikizler T3, Shen D1, Himmelfarb J2
1University of Washington, Seattle, WA, USA; 2University of Washington (Kidney Research Institute), Seattle, WA, USA; 3Vanderbilt University, Nashville, TN, USA
OBJECTIVES/SPECIFIC AIMS: Administration of coenzyme Q10 (CoQ10) has been shown to improve mitochondrial coupling of respiration to oxidative phosphorylation, improve oxidative stress, and may be associated with clinical cardiovascular benefits in diverse patient populations. Our objective was to evaluate the pharmacokinetics, safety tolerability and efficacy of CoQ10 administration in the hemodialysis population. METHODS/STUDY POPULATION: We performed a multiple ascending dose study in 20 hemodialysis patients. CoQ10 supplement (Vitaline) was successively administered at doses of 300 mg, 600 mg, 1200 mg, and 1800 mg for 14 days each. Safety and tolerability were assessed. Plasma CoQ10 concentrations were measured by LC/MS. Plasma F2‐isoprostane concentration was measured by GC/MS to assess systemic oxidative stress. RESULTS/ANTICIPATED RESULTS: Fifteen of 20 subjects (75%) completed the entire sequence. CoQ10 supplementation was generally well tolerated and no severe adverse events were attributed to CoQ10. All laboratory values were within normal limits. CoQ10 was not significantly removed from circulation by hemodialysis. Mean Plasma F2‐isoprostane concentration decreased following the 1200 and 1800 mg CoQ10 administration. DISCUSSION/SIGNIFICANCE OF IMPACT: CoQ10 up to 1800 mg daily was shown to be safe and well tolerated in most subjects. The observed decrease in plasma levels of F2‐isoprostanes suggests that CoQ10 is a promising antioxidant in dialysis patients. A double‐blinded, randomized, placebo‐controlled pilot study to assess the efficacy of CoQ10 in hemodialysis patients is warranted.
P74
SCHOOL‐BASED HEALTH CENTER INTERVENTION IMPROVES BODY MASS INDEX IN OVERWEIGHT AND OBESE ADOLESCENTS
Kong AS 1, Sussman AL1, Yahne C1, Skipper B1, Burge MR1, Davis S1
1University of New Mexico Health Sciences Center, Albuquerque, NM, USA
OBJECTIVES/SPECIFIC AIMS: To determine the feasibility of a school‐based health center (SBHC) weight management program, the Adolescents Committed to Improvement of Nutrition and Physical Activity (ACTION) study was undertaken. ACTION was based on patient centered motivational interviewing principles and was created using a community based participatory approach. METHODS/STUDY POPULATION: Two urban New Mexico SBHCs were randomized to deliver either ACTION or standard care. ACTION consisted of eight clinical visits with overweight and obese adolescents to modify behavior toward healthy eating and physical activity. An educational nutrition and physical activity DVD for students and a clinician toolkit were created and used during clinical visits. Standard care consisted of one visit with the SBHC provider who reviewed the students’ risks for metabolic syndrome and prescribed recommendations for healthy weight. Sixty nondiabetic overweight or obese adolescents were enrolled. Measures included BMI percentile, waist circumference, insulin resistance by homeostasis model assessment (HOMA‐IR), blood pressure, triglycerides and HDL‐C levels. Pre‐ to post‐ changes for participants were compared between groups. RESULTS/ANTICIPATED RESULTS: Fifty‐one students (mean age 15 years, 62% female, 75% Hispanic) completed pre‐ and post‐ measures. ACTION students (n = 28) had improvements in BMI percentile (p = 0.04) and waist circumference (p = 0.04) as compared with students in the standard care group (n = 23). No differences were found between the two groups in the following measures: blood pressure, HOMA‐IR, triglycerides and HDL‐C. DISCUSSION/SIGNIFICANCE OF IMPACT: A SBHC weight management program was not only feasible but produced promising outcomes in BMI percentile and waist circumference.
P75
TARGETED DEPRESSION EDUCATION INCREASES MOTHERS’ MENTAL HEALTHCARE SEEKING
Fernandez y Garcia E 1, Joseph J1, Hinton L1, Kravitz RL1
1University of California Davis, Sacramento, CA, USA
OBJECTIVES/SPECIFIC AIMS: Pediatric visits provide a unique opportunity to intervene in maternal depression. We sought to develop and pilot a pediatric office‐based, targeted intervention to motivate mothers with depressive symptoms to seek further care. METHODS/STUDY POPULATION: Messages normalizing symptoms in the context of parenting yet linking care to child health (from previous research) were delivered in the office by verbal script and a pamphlet (including a menu of care resources), followed in 2 days by a brief telephone motivational interview. The control intervention included: scripted verbal depression education (excluding targeted and behavior change messages), JAMA Depression Patient Page, resource menu, and telephone demographic survey. Of 1,475 potentially eligible English‐speaking parents presenting to the pediatric office (April–October 2011), 128 were mothers with a positive PHQ‐2 screener not currently under care of a MH professional; 104 consented to participate and were randomized. A research assistant blinded to intervention allocation administered the interventions. Any self‐reported depression care seeking attempt (primary outcome), was assessed at 2 weeks via telephone. RESULTS/ANTICIPATED RESULTS: Primary outcome data were available for 42 intervention and 43 control mothers. Groups differed significantly overall (p = 0.023 Fisher’s Exact test, STATA 10) in the proportions seeking mental health professionals (33% intervention; 12% control), other medical professionals or clergy (24%; 35%), Internet Websites only (17%; 7%), and none (26%; 47%). DISCUSSION/SIGNIFICANCE OF IMPACT: This novel intervention uses parent‐targeting to encourage mothers with depressive symptoms in pediatric settings to seek care. The results demonstrate a successful attempt to use the pediatric context to intervene in maternal depression and encourage scaling to a larger effectiveness trial.
P76
TEST‐RETEST RELIABILITY OF INTRAVENOUS ALCOHOL SELF‐ADMINISTRATION IN SOCIAL DRINKERS USING A PROGRESSIVE RATIO PARADIGM
Stangl BL 1, Zametkin M1, Vatsalya V1, Ramchandani VA1
1NIH/NIAAA, Bethesda, MD, USA
OBJECTIVES/SPECIFIC AIMS: The objective was to develop and characterize intravenous (IV) alcohol self‐administration in healthy social drinkers using a progressive‐ratio (PR) paradigm. METHODS/STUDY POPULATION: Healthy social drinkers (N = 12) underwent two identical self‐administration sessions that consisted of a 25‐min priming phase where subjects were prompted to push a button to receive individually standardized alcohol infusions, followed by a 125‐min “progressive ratio” (PR) phase where subjects had to push the button an increasing number of times for each subsequent infusion. Self‐administration measures included number of button presses (NBP), peak (PEAK) and average (AVG) Breath Alcohol Concentration (BrAC), and time to peak BrAC (TP). Subjective measures included the Drug Effects Questionnaire (DEQ), Alcohol Urge Questionnaire (AUQ) and Alcohol Effects Questionnaire (AEFQ). RESULTS/ANTICIPATED RESULTS: Results indicated a high degree of correlation between sessions for all self‐administration measures (all correlation coefficients >.81, p < 0.002). There was also a high degree of correlation between measures within each session (NBP vs. PEAK: R2 = 0.82, p < 0.001, NBP vs. ABPR: R2 = 0.79, p < 0.001), indicating a high level of internal consistency. The AUQ total score following priming was predictive of AVG, NBP and PEAK and the difference in urge score from baseline to after priming was predictive of AVG and PEAK. DISCUSSION/SIGNIFICANCE OF IMPACT: IV alcohol self‐administration measures demonstrated substantial test‐retest reliability and internal consistency between measures. Measures of alcohol urges were predictive of alcohol self‐administration. Results demonstrate the sensitivity of the PR paradigm to the motivational properties of alcohol intake behavior.
P77
THE EFFICACY OF MINDFULNESS‐BASED STRETCHING AND BREATHING EXERCISE AS A COMPLEMENTARY THERAPY FOR POSTTRAUMATIC STRESS DISORDER: A PROSPECTIVE RANDOMIZED STUDY
Kim S 1,2, Schneider S1, Kravitz L1, Mermier C1, Burge MR2,3
1Dept of Health, Exercise & Sports Sciences, University of New Mexico, Albuquerque, NM, USA; 2Clinical & Translational Science Center, University of New Mexico, Albuquerque, NM, USA; 3Dept of Internal Medicine, University of New Mexico, Albuquerque, NM, USA
OBJECTIVES/SPECIFIC AIMS: Nurses are known to experience high levels of work‐related stress. The purpose of this study is to explore the relationships between changes in biomarkers (cortisol, ACTH and DHEAS) and posttraumatic stress disorder (PTSD) symptom severity resulting from nurses with high levels of stress participating in an 8‐week program of mindfulness‐based stretching and breathing exercise. METHODS/STUDY POPULATION: Thirty‐three nurses recruited from the University of New Mexico hospital underwent an 8‐week exercise intervention for this randomized, crossover clinical trial. Participants were screened with the PTSD Checklist Civilian version (PCL‐C). Participants were randomly assigned to either the wait‐list control group or the exercise group. Cortisol, ACTH, DHEAS and PTSD symptom severity were measured at weeks 0, 4, 8, 12, and 16. RESULTS/ANTICIPATED RESULTS: The study is currently underway. We anticipate that there will be a negative relationship between changes in cortisol concentrations and PTSD symptom severity, as well as a positive relationship between changes in cortisol and ACTH levels and between the ratio of cortisol/DHEA and symptom severity. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will provide a better understanding of the relationship between changes in PTSD symptom severity and biomarker levels as a result of the exercise intervention. This contribution is likely to be significant because it will advance knowledge about the physiological regulation anomalies of the autonomic nervous system associated with PTSD and increase our understanding of how exercise affects PTSD symptomology.
P78
THE FATTY ACID TRANSLOCASA GENE, CD36, AND LINGUAL LIPASE INFLUENCE ORAL SENSITIVITY TO FAT IN OBESE SUBJECTS
Pepino MY 1, Love‐Gregory L1, Klein S1, Abumrad NA1
1Washington University, St Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: The precise orosensory inputs engaged for dietary lipids detection in people are not known. We evaluated whether a common SNP (rs1761667) in the CD36 gene that reduces CD36 expression and the addition of orlistat, a lipase inhibitor, to reduce fatty acids (FA) release from triacylglycerols (TG), the main component of dietary fats, would attenuate fat orosensory sensitivity in humans. METHODS/STUDY POPULATION: Twenty‐one obese subjects with different rs1761667 genotypes (6 AA, 7 AG and 8 GG) were studied on two occasions in which oleic acid and triolein orosensory detection thresholds were measured using emulsions prepared with and without orlistat. RESULTS/ANTICIPATED RESULTS: Subjects homozygous for the G‐allele had 8 fold lower oral detection thresholds for oleic acid and triolein than subjects homozygous for the A allele, which associates with lower CD36 expression (p = 0.03). Thresholds for heterozygous subjects were intermediate. Addition of orlistat increased detection thresholds to triolein (log threshold =−0.3 ± 0.2 vs. 0.3 ± 0.1; p < 0.001) but not oleic acid (log threshold =−1.0 ± 0.2 vs. −0.8 ± 0.2; p > 0.2) DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first experimental evidence for a role of CD36 in fat gustatory perception in humans. The CD36 SNP tested is common which suggests that it might contribute to individual differences in fat perception. The data also support involvement of lingual lipase and are consistent with the concept that FA and not TG is the sensed stimulus.
P79
TOWARD DETECTION OF CLINICALLY MEANINGFUL CHANGE IN THE SEVERITY OF TOURETTE SYNDROME: A SIGNAL DETECTION ANALYSIS AND MIXTURE MODEL OF THE YALE GLOBAL TIC SEVERITY SCALE
Jeon S 1, Scahill L1
1Yale University School of Nursing, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: To demonstrate statistical strategies of classifying positive treatment response based on dimensional measure (Yale Global Tic Severity Scale [YGTSS]) and a categorical measure (Clinical Global Impression‐Improvement [CGI‐I]). METHODS/STUDY POPULATION: Two hundred forty‐eight subjects with Tourette syndrome or Chronic Tic Disorder participated in one of two identical clinical trials. Subjects (177 males, 71 females) were randomly assigned to behavioral intervention or supportive therapy for 10 weeks. Tic severity (YGTSS Total Tic score) was rated at baseline, Weeks 5 and 10 by a blinded clinician. At Weeks 5 and 10, the blinded clinician also rated the CGI‐I (Positive Response = score of 2 or 1). We examined the association between the reduction in the YGTSS and scores of 2 or 1 on the CGI‐I. Then, using signal detection analysis (SDA), we maximized agreement with the CGI‐I classifications and cutoffs of YGTSS reduction. A mixture model method was implemented to classify Dimensional Response based on the YGTSS. RESULTS/ANTICIPATED RESULTS: Subjects with milder tics were more likely to show a Positive Response at Week 5. This trend was not evident at Week 10. The odds ratio (OR) of Positive Response for behavioral intervention at Week 5 was 2.65 (95% CI = 1.18, 5.98) and 5.65 (95% CI = 2.97, 10.74) at Week 10. The SDA approach showed optimal cutoffs of 30% and 25% reduction on the YGTSS total for Positive Response at Week 5 and 10, respectively. Differ with CGI‐I, the mixture model provided consistent ORs of Dimensional Response over time. Consistent mean reduction of YGTSS was observed between Positive and Dimensional Response. DISCUSSION/SIGNIFICANCE OF IMPACT: The findings suggest that the CGI‐I successfully reflects the dimensional measure and the alternative classifications also need to be implemented for additional information.
P80
TRASTUZUMAB ALTERS HEART RATE VARABILITY
Geisberg C 1, Paranjape SY1, Diedrich A1, Sawyer DB1, Lenihan D1, Raj SR1
1Vanderbilt, Nashville, TN, USA
OBJECTIVES/SPECIFIC AIMS: Heart rate variability (HRV) is a noninvasive measure of autonomic tone. HRV is high in health, but reduced in heart failure patients, suggesting autonomic imbalance, which is associated with poor prognosis. Decreased HRV is a sensitive indicator of anthracycline cardiotoxicity. The effects of trastuzumab (TSZ; HER2+ antagonist), a modern breast cancer (BCA) chemotherapy, on autonomic balance is unknown. Neuregulin (NRG) is a ligand for the HER2+ receptor that can increase parasympathetic (PNS) tone in animal models. Thus TSZ might be expected to decrease PNS tone, and shift to increased sympathetic (SNS) tone. METHODS/STUDY POPULATION: In this pilot study, 9 HER2+ BCA patients receiving TSZ were enrolled. Supine plasma catecholamines, and 10 min. continuous ECG were obtained at baseline, and 3 mo. into TSZ treatment. HRV was measured using a Fourier transform with low frequency (LF) and high frequency (HF) power, defined a 0.04–0.15 Hz and 0.15–0.4 Hz respectively, and normalized to total power (no units). HF HRV is a marker of PNS and LF HRV has inputs from both the SNS and PNS. Data were analyzed with paired t‐tests (mean ± SEM). RESULTS/ANTICIPATED RESULTS: Compared to baseline, TSZ therapy resulted in a relative increase in HF power (27 ± 5 vs. 34 ± 4; p = 0.043) and a trend to decreased LF power (69 ± 6 vs. 61 ± 5; p = 0.058). There was a concomitant trend to a decrease with TSZ in norepinephrine (303 ± 43 vs. 264 ± 23 pg/ml; p = 0.5) and epinephrine (31 ± 9 vs. 22 ± 8 pg/ml; p = 0.068). DISCUSSION/SIGNIFICANCE OF IMPACT: The pilot study demonstrates a relative shift to increased PNS tone in BCA patients receiving the NRG/ErbB2 (HER2+) antagonist TSZ. There are no increases in markers of SNS tone, as are often seen with anthracyclines. While these changes are generally favorable in patients with cardiomyopathy, there are not yet data that show that HRV and catecholamines will predict cardiac dysfunction over the course of the 5‐year study.
P81
UNIPOLAR VERSUS BIPOLAR HEMOSTASIS IN TOTAL KNEE ARTHROPLASTY: A PROSPECTIVE RANDOMIZED TRIAL
Lovy A 1, Plymale M1, Capogna B1, Adler M1, Hirsh D1, Kim S1
1Albert Einstein College of Medicine, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: Patients undergoing total knee arthroplasty (TKA) often require blood transfusions due to the significant amount of intraoperative and postoperative blood loss associated with the procedure. Several strategies exist to reduce the amount of blood loss associated with TKA, including the use of a bipolar sealer. Our hypothesis was that use of bipolar sealer compared to standard unipolar electrocautery would not reduce blood loss or transfusion requirements associated with TKA. METHODS/STUDY POPULATION: We randomized 113 consecutive patients undergoing primary unilateral total knee arthroplasty into either unipolar or bipolar hemostasis treatment groups. A strict intraoperative coagulation protocol was followed by each of the three surgeons in order to ensure standardization. RESULTS/ANTICIPATED RESULTS: The mean postoperative drain output in the unipolar group was 776.5 ml compared to 778.7 ml, and was not statistically significant (p = 0.97). There were no statistically significant differences in postoperative day one through three hemoglobin (p = 0.2–0.6) or hematocrit (p = 0.17–0.46) values. The transfusion requirement in the unipolar group was 36% and 40% in the bipolar group (p = 0.67). DISCUSSION/SIGNIFICANCE OF IMPACT: The use of a bipolar sealer compared to standard unipolar electrocauterization showed no significant difference in postoperative drain output, postoperative hemoglobin and hematocrit values, or transfusion requirements.
P82
VIDEO CAPSULE ENDOSCOPY (VCE) IN THE EMERGENCY DEPARTMENT: A NOVEL APPROACH TO DIAGNOSING ACUTE UPPER GASTROINTESTINAL HEMORRHAGE (AUGIH)
Meltzer AC 1, Patel G1, Smith M1, Shah P1, Fleischer D2
1GWU, Washington, DC, USA; 2Mayo Clinic, Scottsdale, AZ, USA
OBJECTIVES/SPECIFIC AIMS: Our objectives were to demonstrate (1) ED patient tolerance for VCE, (2) the agreement of VCE interpretation between ED and GI physicians, and (3) the ability of VCE to detect active bleeding compared to subsequent upper endoscopy (EGD) or patient follow‐up. METHODS/STUDY POPULATION: This study was conducted over a 6‐month period at an urban academic ED. Investigators performed VCE (Pillcam Eso2, Given Imaging) on subjects identified to have suspected AUGIH (melena, hematemesis or coffee‐ground emesis within past 24 hours). Following the VCE, subjects completed a short survey regarding procedure tolerance. Approximately 30 minutes of video were recorded per subject and reviewed by 4 blinded physicians (2 ED physicians with training in reading VCE studies but no formal endoscopic training and 2 GI physicians with VCE experience.) Subjects were followed for clinical outcomes and EGD results. RESULTS/ANTICIPATED RESULTS: Twenty‐five subjects (mean age 52 years old, 13 female) were enrolled.No subjects suffered any complications related to the VCE. Compared to the GI physicians’ interpretation, each of the two ED physicians demonstrated good agreement regarding the presence of fresh blood (κ= 0.83 and κ= 0.90). The presence or absence of fresh blood on VCE showed a sensitivity of 83%, specificity of 84%, PPV of 0.63 and NPV of 0.94 compared to the gold standard of active bleeding on EGD within 24 hours (20 subjects) or patient follow‐up (5 subjects). DISCUSSION/SIGNIFICANCE OF IMPACT: VCE was well tolerated in ED patients with suspected AUGIH and ED physicians with VCE training were able to interpret the presence of fresh blood with good agreement with experienced GI physicians’ interpretation and EGD. Future prospective multicenter studies will allow ED physicians and GI physicians to further collaborate in the care of AUGIH.
ETHICS
P83
ASSOCIATION BETWEEN PHYSICIANS’ BELIEFS AND WHETHER THE OPTION OF COMFORT CARE IS OFFERED FOR PATIENTS WITH ADVANCED CRITICAL ILLNESS
Schenker Y 1, Tiver GA1, Hong S1, White DB1
1University of Pittsburgh, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: To assess how comfort care is presented to surrogates of critically ill patients and whether physicians’ beliefs are associated with whether comfort care is presented as an option. METHODS/STUDY POPULATION: Mixed‐methods study of audio‐recorded physician‐family conferences in 5 ICUs at two hospitals. 169 family members and 54 physicians participated in 72 conferences about treatment decisions for patients at high risk of death. Transcripts of audio‐recorded conferences were coded to identify whether physicians offered comfort care as an alternative to life sustaining treatment. Physicians completed a questionnaire indicating the strength of their belief that life support should be withdrawn. We used hierarchical logistic regression to assess the association between physician beliefs and the presentation of comfort care. RESULTS/ANTICIPATED RESULTS: The inpatient mortality rate was 72%. Using a broad definition of comfort‐oriented treatment, comfort care was presented as an option in 56% [95% CI, 44%‐67%] of conferences. In clustered multivariate models adjusting for APACHE II score and number of days in the ICU, the only independent predictor of offering comfort care as an option was the strength of the physician’s belief that life support should be foregone (OR 1.38 [1.14–1.66], p = 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Among patients with advanced critical illness, the possibility of comfort‐oriented treatment was not explicitly offered in nearly half of clinician‐family conferences. The more strongly physicians believed that life support should be continued, the less likely they were to offer comfort care.
P84
ETHICAL PROTECTIONS IN COMMUNITY‐ENGAGED RESEARCH: A NATIONALLY IMPLEMENTABLE, LOCALLY DELIVERABLE TRAINING PROGRAM
Solomon S 1, Piechowski‐Whitney P2
1Saint Louis University, Saint Louis, MO, USA; 2University of Michigan, Ann Arbor, MI, USA
OBJECTIVES/SPECIFIC AIMS: (1) Adapt workshop materials from a local pilot workshop into a nationally implementable, locally deliverable training; (2) Develop and implement webinars to train participating program facilitators to conduct the workshops; (3) Assess the effectiveness of the workshop materials, the facilitator webinar and the workshops conducted by the facilitators METHODS/STUDY POPULATION: Step 1: Workshop. Format each component of the workshop into form amenable to online facilitator training and face‐to‐face learning. Step 2: Training. Create electronic training materials, face‐to‐face webinars, and instructional videos to train workshop facilitators at each of 13 collaborating CTSA sites. Step 3: Assessment. (1) comprehension of the basic elements of and process to ensure human participants protections in research; (2) the relative effectiveness of different workshop presentation formats; (3) the effectiveness of the train‐the‐facilitator webinars RESULTS/ANTICIPATED RESULTS: Evidence‐based materials and a strategic plan for making available a nationally implementable, locally deliverable human research participants training workshop for community‐based researchers, collaborators and staff. DISCUSSION/SIGNIFICANCE OF IMPACT: (1) Readily available materials and a way to train workshop facilitators should make it easier for institutions to engage and qualify community members for participation in research, thereby expediting the review process. (2) The national approach to training proposed in this project will make collaboration easier by providing a way to establish a consistent approach to training. (3) By focusing on a workshop format, this project introduces a novel approach to blended learning. The Web will be used to share teaching materials, but most of the training takes place through face‐to‐face workshops.
P85
MEDICAL HEALTHCARE ETHICS IN VULNERABLE POPULATIONS (MEDIC): CLINICAL RESEARCH THROUGH THE PATIENT'S EYES
Libin AV 1, Schladen MM1, Pascalev A3, Otado JA3, Baigis J2, Fitzgerald KT2, Zimmet SG2, Nunlee‐Bland G3, Verbalis JG2
1MedStar Health Research Institute, Washington, DC, USA; 2Georgetown University, Washington, DC, USA; 3Howard University, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Aim 1. Explore the ethical aspects of participation in clinical research conducted to develop medical interventions for vulnerable populations with chronic health conditions as typified by chronic hyponatremia and diabetes. Aim 2. Explore group differences in ethical decision making via a scale developed from Aim 1 findings. Aim 3. Translate the results of Aims 1 and 2 to educational materials to enhance consumer, clinician, and researcher understanding of ethical decision‐making around medical research involving patients with chronic illness. METHODS/STUDY POPULATION: Mixed methods. Qualitative Arm (Aim 1): Focus groups and key informant interviews conducted with 40 patients with chronic hyponatremia or diabetes and their healthcare providers. Quantitative Arm (Aim 2): Cross‐sectional design, testing of group differences in 100 patients and providers. Knowledge Translation Arm (Aim 3): User‐centered design and test of materials via the GHUCCTS Website. RESULTS/ANTICIPATED RESULTS: Decision making patterns displayed by persons with chronic illness will differ according to demographics as well as morbidity. Patterns in patient versus provider groups will differ along the dimensions of decisional autonomy, respect for privacy, and perception of risk‐benefit. DISCUSSION/SIGNIFICANCE OF IMPACT: Targeting characteristics of decision making that devolve from lived experiences of chronic illness will improve understanding of the implications of chronic disease research and increase the quality of informed consent.
P86
RESEARCH ETHICS CONSULTATION SERVICE IN THE INSTITUTE FOR TRANSLATIONAL SCIENCES: OUTCOMES FOR ONE YEAR
Farroni JS 1, McKinney E1,2, Carter MA1,2
1Institute for Translational Sciences, University of Texas Medical Branch at Galveston, Galveston, TX, USA; 2Institute for Medical Humanities, University of Texas Medical Branch at Galveston, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: The Research Ethics Consultation Service (RECS) provides expertise and advise on translational ethics, promotes interdisciplinary teamwork, supports protocol and consent form development and assists to streamline IRB review. The RECS expands beyond the traditional consultation model to a more preemptive approach. Three formal mechanisms have been adopted within the RECS where ethics expertise is sought to address and/or proactively identify ethical issues: (1) formal consultation requests, (2) representation on the Scientific Review Committee (SRC), evaluating scientific merit in addition to identifying and exploring ethical concerns that come to light during protocol reviews, (3) ethics review of Multidisciplinary Translational Team (MTT) ethical standards, team science attributes and alignment with the Institutional strategic plan. METHODS/STUDY POPULATION: A twelve month assessment was conducted on these services provided by the RECS. RESULTS/ANTICIPATED RESULTS: There was a total of 45 consults: 18 SRC protocols, 10 MTT applications and 17 formal consultations. Of the 17 formal consultations, 12 (70.6%) presented multiple issues (29 total issues). The most common issues included inadequate informed consent forms (47.1%), insufficient specimen collection/use (29.4%), concerns regarding subject vulnerability (17.6%) and confidentiality/privacy (17.6%). DISCUSSION/SIGNIFICANCE OF IMPACT: These results are guiding the development of best practices and educational opportunities to address gaps in core competencies. The overall impact of these functions by the RECS is to seek resolution of ethical issues, promote integrity and foster trust throughout the translational research enterprise.
HEALTH SERVICES RESEARCH
P87
ASSESSING ORGANIZATIONAL CAPACITY FOR ACHIEVING EHR MEANINGFUL USE
Shea CM 1, Malone R2, Weinberger M1, Weiner B1, Reiter K1, Thornhill J2, Lord J2, Nguyen N1
1University of North Carolina‐Chapel Hill, Chapel Hill, NC, USA; 2UNC Health Care System, Chapel Hill, NC, USA
OBJECTIVES/SPECIFIC AIMS: Achieving stage 1 of Meaningful Use (MU) of electronic health records (EHR) requires eligible professionals to satisfy 26 requirements. To be successful, healthcare systems will need appropriate organizational capacity, including resources (e.g., people, technology) and structures/processes (e.g., work groups, workflows). This study focused on organizational capacity for achieving MU within an academic medical center. The aims were to (1) develop and implement a tool for assessing capacity and (2) provide analysis to inform MU change efforts. METHODS/STUDY POPULATION: Using a structured interview guide to provide standardized responses about MU‐related human resources, work processes, and IT resources, we conducted interviews with medical directors, nurse managers, and clinic managers in 46 outpatient clinical service areas within UNC Health Care System. RESULTS/ANTICIPATED RESULTS: Preliminary results suggest that most clinical service areas have necessary human resources (e.g., physician and nurse champions). However, most service areas lack either standard processes for at least one core MU requirement and/or tools/metrics for tracking compliance with existing standards. The most common barriers to MU achievement identified by clinic leadership are inadequate functionality of the EHR, developing workflow changes, overcoming resistance to change, and handling increased workloads due to MU requirements. DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding current organizational capacity for achieving MU is a step toward effective implementation. This study provides a method and tool for doing so that can be adapted to other organizational contexts and innovations aimed at changing behavior and transforming the delivery system. Preliminary results highlight the importance of standardization in achieving such aims.
P88
ASSOCIATION BETWEEN ANTICIPATORY GRIEF AND SOCIAL PROBLEM SOLVING AMONG CAREGIVERS
Fowler NR 1, Hansen A2, Garand L3
1University of Pittsburgh, Pittsburgh, PA, USA; 2Carnegie Mellon University, Pittsburgh, PA, USA; 3University of Pittsburgh‐Nursing, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: Caregivers of adults with cognitive impairment (CI) must solve problems and participate in shared decision making for medical decisions. Little is known about the role of anticipatory grief on caregivers’ ability to solve problems and participate in medical decisions. This study examines the association between anticipatory grief and social problem solving abilities of caregivers for older adults CI. METHODS/STUDY POPULATION: Retrospective analysis of baseline measures from a caregiver self‐management intervention clinical trial. Included 73 caregivers of patients with either MCI or dementia from the University of Pittsburgh Alzheimer’s Disease Research Center. Primary outcome measure was social problem‐solving ability using the Social Problem‐Solving Inventory‐Revised: Short (SPSI‐R:S). Primary independent variable was anticipatory grief using the Anticipatory Grief Scale (AGS). The regression model collapsed AGS scores into tertiles. Covariables included two personality traits (openness to experience and conscientiousness), household income, patient diagnosis, and caregiver role. RESULTS/ANTICIPATED RESULTS: Mean age of caregivers was 64.9 years and 78.1% were female. 75.3% were spouses, 79.5% had some college and 46.5% reported an annual household income of ≥≥60,000. They endorsed a mean standardized SPSI‐R:S score of 110.2 (9.8) and a mean AGS score of 70.1 (14.8). The multivariable model indicates those who had AGS scores in the lowest teritle had significantly higher social problem solving abilities scores (p < 0.05) compared to those with AGS scores in the highest tertile. DISCUSSION/SIGNIFICANCE OF IMPACT: Anticipatory grief may impact problem solving and decision‐making abilities. It may be appropriate to develop decision aids for caregivers that explicitly address these emotions.
P89
COGNITIVE IMPAIRMENT AND MEDICARE UTILIZATION NEAR THE END OF LIFE
Nicholas LH 1, Langa K1, Iwashyna TJ1, Weir D1
1University of Michigan, Ann Arbor, MI, USA
OBJECTIVES/SPECIFIC AIMS: Although cognitive impairment may hinder patients’ abilities to assess treatment options at the end of life, little is known about end‐of‐life care for cognitively impaired older adults. METHODS/STUDY POPULATION: We used survey data from the Health and Retirement Study linked to Medicare claims for 3,302 respondents who died between 1998 and 2007. Discharge abstracts are used to assess receipt of life‐sustaining treatments, in‐hospital death and intensive care unit (ICU) stays. Multivariate logistic regressions compared treatment cognitively impaired and unimpaired decedents. RESULTS/ANTICIPATED RESULTS: Twenty‐nine percent of Medicare decedents were borderline impaired and 30% were cognitively impaired. Cognitively impaired and unimpaired decedents were equally likely to be hospitalized in the last six months of life. Forty percent of decedents with borderline or full cognitive impairment had written advance directives in place. Compared to unimpaired decedents, cognitively impaired patients were less likely to receive life‐sustaining interventions (OR = 0.68, 95% CI [0.57,0.81]); equally likely to die in the hospital (OR = 0.98, 95% CI [0.82,1.16]), and less likely to have an ICU stay (OR = 0.82, 95% CI [0.67,0.99]). DISCUSSION/SIGNIFICANCE OF IMPACT: The majority of elderly decedents reach the end of life without documented treatment preferences or surrogate decision‐maker and possible incapacity for informed consent. Cognitively impaired patients face similar odds of receiving many aggressive treatments near the end of life. Physician discussions earlier in life are potentially helpful to create awareness, facilitate decision making while unimpaired.
P90
COLLABORATION TURNS EHR INTO CER
Allison GM 1,3, Guglioti J3, Palchuck MB2, Aggarwal N2, Paulus JK3
1Tufts Medical Center, Boston, MA, USA; 2Recombinant Data Corp, Newton, MA, USA; 3Tufts CTSI, Boston, MA, USA
OBJECTIVES/SPECIFIC AIMS: Research on medical care best practices is urgently needed. However, appropriately detailed manual chart abstraction is prohibitive. One solution is a multidisciplinary collaboration using EHRs. Our group has demonstrated use of a Data Warehouse (DW) to facilitate the study of OutPatient IV Antibiotic Therapy (OPAT) in a tertiary care academic hospital where approximately 400 patients per year are discharged home with intravenous antibiotics. Aims 1. Computer‐aided “seeding” of OPAT research database. Aim 2. Verify accuracy of automatic data population METHODS/STUDY POPULATION: OPAT database was created (REDCap Software,Vanderbilt University). Precise query definitions were mapped to unique variable names. A Kettle (Pentaho Data Integration “Kettle” Project, http://kettle.pentaho.com/) ETL job was created to extract, normalize and load data from DW into the database. Tufts Medical Center IRB approved this project. RESULTS/ANTICIPATED RESULTS: 46 fields and 3372 discrete facts were populated from DW into 73 individual patient database records. Statistical analysis comparing automatic versus usual database construction will use kappa for categorical variables and the intraclass correlation coefficient for continuous variables. DISCUSSION/SIGNIFICANCE OF IMPACT: The multidisciplinary approach and intrastructure we have demonstrated can facilitate comparative effectiveness research with existing clinical data allowing faster, cheaper and more detailed clinical studies. Funding This project was supported by grant number UL1 RR025752 from the National Center for Research Resources (NCRR) and grant number KM1 CA156726 from the National Cancer Institute (NCI). The content is solely the responsibility of the authors and does not necessarily represent the official views of NCRR or NCI.
P91
COMPARATIVE EFFECTIVENESS OF USING COMMUNITY HEALTH WORKERS FOR LTC SYSTEM NAVIGATION COMPARED TO STANDARD PRACTICE
Felix HC 1, Stewart K1, Mays G2, Cottoms N3, Olson M3
1UAMS, Little Rock, AR, USA; 2University of Kentucky, Lexington, KY, USA; 3TCRHN, Helena, AR, USA
OBJECTIVES/SPECIFIC AIMS: A significant portion of Medicaid expenditures go for long‐term care (LTC) services and ways to lower those costs are sought, including offering more home and community‐based services (HCBS). However, the complexity of HCBS delivery systems may limit access for those at greatest risk of nursing home entry and the availability of HCBS may increase usage by those who would not have otherwise used LTC services, thereby increasing cost. We report results of a comparative effectiveness study that examined use of Community Health Workers (CHWs) to identify Medicaid beneficiaries with unmet LTC needs and link them to needed HCBS compared to standard practice (no outreach / agency‐based enrollment). METHODS/STUDY POPULATION: The cost savings to the Arkansas Medicaid program was estimated using a quasi‐experimental design in which 919 participants were observed 1 year prior to their participation and up to 3 years after participation, and compared to a similar group of 944 Medicaid residents residing in similar nonintervention counties in the state. Propensity score matching was used to ensure a close match between the participant group and the comparison group on preparticipation measures of demographics, case mix, and service use. Multivariate difference‐in‐difference estimation was used to estimate program effects. RESULTS/ANTICIPATED RESULTS: Analysis found a 23.8% reduction in annual Medicaid spending per participant over the 3‐year demonstration (p < 0.01) producing a ≥2.6 million savings for the Arkansas Medicaid program. The return on ≥1 investment was ≥2.92. DISCUSSION/SIGNIFICANCE OF IMPACT: Results suggest CHWs may a better targeting and navigation mechanism for the LTC delivery system compared to standard practice and can help lower costs. Further research is needed to confirm results over time.
P92
COMPARISON OF A DECISION RULE VERSUS USUAL CARE TO RISK STRATIFY CHILDREN FOR ABDOMINAL INJURY AFTER TRAUMA: A COST‐EFFECTIVENESS ANALYSIS
Nishijima DK 1, Clark J1, Melnikow J1, Yang Z1, Mumma B1, Kuppermann N1, Holmes J1
1UC Davis School of Medicine, Sacramento, CA, USA
OBJECTIVES/SPECIFIC AIMS: A decision rule was developed to identify pediatric patients with blunt abdominal trauma (BAT) who are at very low risk for an intra‐abdominal injury that would require intervention (IAI). The objective of this study was to model the cost‐effectiveness of the decision rule compared to usual care for pediatric patients with BAT. We hypothesize that implementation of the decision rule will project lower CT utilization and cost. METHODS/STUDY POPULATION: We constructed a cost‐effectiveness analysis model comparing implementation of the decision rule versus usual care in pediatric patients with BAT. Analyses were performed from the societal perspective. Probabilities were derived from a multisite cohort study of children with BAT; costs were estimated based on study coordinating site costs. Outcome measures include missed IAI, number of abdominal CT scans, total costs, and incremental cost‐effectiveness ratios. Sensitivity analyses were conducted varying imputed probabilities, costs, and scenarios. RESULTS/ANTICIPATED RESULTS: Using a hypothetical cohort of 100,000 pediatric patients with BAT, the base‐case analysis projected that the implementation of the decision rule would result in 50 additional missed IAI, a total cost savings of 6.2 million dollars, and 9,922 fewer abdominal CT scans compared to usual care. The usual care strategy would cost 124,000 and require 47 additional abdominal CT scans to prevent missing one additional IAI. Findings were robust under multiple sensitivity analyses. DISCUSSION/SIGNIFICANCE OF IMPACT: Compared to usual care, implementation of the clinical decision rule in the evaluation of pediatric patients with BAT would reduce healthcare costs and radiation exposure with low risk of adverse outcomes.
P93
CULTURAL AND LINGUISTIC ENHANCEMENT OF SURVEY INSTRUMENTS THROUGH COMMUNITY‐BASED PARTICIPATORY RESEARCH
Formea CM 1, Mohamed AA3, Hassan A2, Osman A2, Weis JA3, Sia IG4, Wieland ML4
1Department of Pharmacy, Mayo Clinic, Rochester, MN, USA; 2Somali Community Resettlement Services, Rochester, MN, USA; 3Center for Translational Science Activities, Mayo Clinic, Rochester, MN, USA; 4Department of Medicine, Mayo Clinic, Rochester, MN, USA
OBJECTIVES/SPECIFIC AIMS: To describe lessons learned from a process of English to Somali translation of a diabetes survey through a community‐based participatory research (CBPR) approach. METHODS/STUDY POPULATION: Through the infrastructure of an experienced CBPR partnership, the survey was translated through the 3‐step World Health Organization process of forward translation, group deliberation, and back translation. Forward translation was conducted by a professional Somali translator. Group deliberation was conducted through 12 hours of meetings between 3 Somali community partners and 1 academic. Notes taken by the academic partner were inductively organized and analyzed for meaning to elucidate generalizable themes highlighting benefits and limitations of the participatory meetings on the final survey instrument and its eventual implementation. RESULTS/ANTICIPATED RESULTS: The survey underwent significant cultural and linguistic revisions to approximate the meaning of the original survey. The group deliberation process addressed themes of cultural and religious practices, the role of family, generational gaps, gender gaps, illiteracy, and distrust of the medical community. Participatory group deliberation improved the survey product and prevented “fatal” cultural and linguistic flaws in the survey that were not achieved through the initial traditional translation. DISCUSSION/SIGNIFICANCE OF IMPACT: Survey translation through a CBPR approach magnified the process of group deliberation about survey meaning towards improved cultural and linguistic relevance. This approach is likely to enhance community acceptance of the survey instrument during the implementation phase.
P94
ENHANCING DRUG INTERACTION ALERTS WITH CONTEXTUAL LABORATORY DATA
Duke J 1,2
1Indiana University, Indianapolis, IN, USA; 2Regenstrief Institute, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: Adherence to computerized drug‐drug interaction (DDI) alerts is remarkably low (49%– 96% are overridden). A major cause is that physicians do not perceive these warnings as relevant to the individual patient. We conducted a randomized trial to determine whether the incorporation of patient‐specific laboratory data would improve DDI alert adherence. METHODS/STUDY POPULATION: We randomized 1,100 outpatient physicians to either control or intervention groups. For a 6 month period (Mar.–Sept. 2011), intervention physicians received enhanced alerts for any DDIs associated with hyperkalemia, rhabdomyolysis, or increased risk of bleeding. These alerts included the most recent laboratory results relevant to each condition (e.g., potassium for hyperkalemia, CK for rhabdomyolysis). Control physicians received routine alerts with no laboratory data. For each alert, we recorded whether the physician overrode or accepted the alert and the laboratory values shown to the physician. Labs were defined as worrisome for K>5.0, Cr > 1.4, CK >200, INR > 3, Hct < 33, and Plt<120. RESULTS/ANTICIPATED RESULTS: There were 3,270 alerts triggered for 146 physicians in the intervention group and 2,929 alerts triggered for 148 physicians in the control group. The override rate was significantly lower in the intervention group (93.9% vs. 95.5%, p = 0.003). In the intervention group, there was no significant difference between alerts containing worrisome labs and those containing normal labs (94.3% vs. 93.9%, p = 0.72). The intervention decreased overriding significantly in rhabdomyolysis alerts (92.6% vs. 95.5%) and bleeding alerts (93.5% vs. 94.8%) but not hyperkalemia (95.5% vs. 95.7%). DISCUSSION/SIGNIFICANCE OF IMPACT: We have demonstrated a small improvement in adherence to DDI alerts through incorporation of relevant patient‐specific laboratory data. Surprisingly, display of more worrisome values did not increase rates of alert adherence.
P95
EXAMINING MENTAL HEALTH HOSPITALIZATIONS FOR ASIAN AMERICAN AND PACIFIC ISLANDER (AAPI) YOUTH IN CALIFORNIA
Javier JR 1, Liu TR2, Saynina O3, Huffman LC3, Wise PH3
1Southern California Clinical and Translational Science Institute, Children’s Hospital Los Angeles, USC Keck School of Medicine, Department of Pediatrics, Division of General Pediatrics, Los Angeles, CA, USA; 2Western University of Health Sciences, Pomona, CA, USA; 3Stanford University School of Medicine, Center for Health Policy, Primary Care and Outcomes Research, Department of Pediatrics, Palo Alto, CA, USA
OBJECTIVES/SPECIFIC AIMS: To describe the primary mental health diagnoses of AAPI youth hospitalized for a mental health condition and to compare the probability of hospitalization across race/ethnicity. METHODS/STUDY POPULATION: We used California’s Office of Statewide Health Planning and Development discharge database to perform a retrospective population cross‐sectional study of 225,105 pediatric (ages 5–17) psychiatric hospitalizations in California between 1999 and 2007. We used logistic regression to assess associations between hospitalization for a mental health condition and race/ethnicity. RESULTS/ANTICIPATED RESULTS: For all race/ethnicities, the mental health condition most frequently associated with hospitalization was a depressive disorder (21%). For AAPIs, the next most common diagnoses were psychoses (16.7%), bipolar disorder (9.9%), stress disorder (7.8%), disruptive disorder (6.5%), other mental health condition (3.0%), drug and alcohol disorders (2.9%), anxiety disorders (2.3%), and developmental disorders (1.2%). Compared to non‐Hispanic white children, AAPI, Black, Hispanic, and Other ethnicity children are less likely to be hospitalized for a mental health condition (AORs ranging from 0.39–0.80). DISCUSSION/SIGNIFICANCE OF IMPACT: Depressive disorders represent the largest proportion of psychiatric hospitalizations across race/ethnic groups, including AAPI youth. These findings suggest a need to develop programs that provide prevention and early detection of depression for all ethnicities.
P96
FAITH‐BASED VIEWS OF DEPRESSION IN RURAL ARKANSAS
Bryant K 1, Greer‐Williams N1, Hartwig M1
1University of Arkansas for Medical Sciences, Little Rock, AR, USA
OBJECTIVES/SPECIFIC AIMS: The aim of the study was to describe how predominantly African American rural churches distinguish effective means to recognize and cope with depressive symptoms. METHODS/STUDY POPULATION: The study followed the principles of Community Based Participatory Research. The participants were recruited by a community leader in the Arkansas Delta. The participants included a group of pastors, a group of persons interested in health and a group of men who have experienced symptoms of depression. The primary data source were focus groups. Qualitative analyses were completed by three experienced researchers. RESULTS/ANTICIPATED RESULTS: A total of five focus groups were completed over a three‐ month period. In addition, two individual interviews were conducted. A convenience sample of 24 persons participated in focus groups and interviews, including nine pastors. The preliminary findings include three themes related to barriers. The first barrier was related to the lack of knowledge about depression in the community. The second, stigma was related to persons not understanding depression, therefore labeling those with it as “crazy” or being inhabited by a spirit. The final barrier was trust and confidentiality, being in a small community; participants felt that if they shared their personal information about what they were going through that it would not be held in confidence. DISCUSSION/SIGNIFICANCE OF IMPACT: Though the analyses are not complete, the preliminary results suggest that persons in rural and remote areas require additional information about depression and its symptoms. Persons in rural communities also deal with greater societal stigma for seeking mental health services, with a primary concern of confidentiality and privacy. Therefore, programs are needed to educate the community about depression and to provide innovative treatment options which may include the faith community.
P97
FAR‐REACHING EFFECTS OF CLOSURES ON PATIENTS IN NEIGHBORING COMMUNITIES: EFFECTS OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Hsia R 1, Srebotnjak T2, Maselli J1
1UCSF School of Medicine, San Francisco, CA, USA; 2Ecologic Institute, San Mateo, CA, USA
OBJECTIVES/SPECIFIC AIMS: Between 1990–2009, the number of nonrural Emergency Departments (EDs) dropped by 27%. Negative health outcomes have been documented in patients who experience ED closure directly. We seek to determine if patients who experience ED closure indirectly—those with a closure in their vicinity but do not need to travel farther—have higher AMI inpatient mortality rates than patients without closures. METHODS/STUDY POPULATION: We performed a retrospective study using all admissions from non–federal hospitals in California for acute myocardial infarction (AMI) between 1999–2008. We compared inpatient mortality from AMI for patients who lived in a community within 2.5 miles or 5 miles of a closure but did not travel farther to the nearest ED with those who did not have a closure. We used patient‐level data from the California Office of Statewide Health and Planning Development (OSHPD) database patient discharge data, and locations of patient residence and hospitals were geo‐coded to determine any changes in distance to the nearest ED. We applied a generalized linear mixed effects model framework to estimate a patient’s likelihood to die in the hospital of AMI as a function of being affected by a neighborhood closure event. RESULTS/ANTICIPATED RESULTS: Between 1998–2008, there were 352,064 patients with AMI and 29 ED closures in California. Of the AMI patients, 5868 (1.7%) experienced an ED closure within a 2.5‐mile radius and had 15% higher odds (OR 1.15, 95% CI 1.04, 1.96) of mortality compared with those who did not. Results of the 5‐mile radii analyses were similar (OR 1.13, 95% CI 1.03, 1.23). DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest that patients indirectly experiencing ED closure face poor health outcomes. These results should be considered in closure and regionalization decisions.
P98
HIV‐RELATED STIGMA AS A MEDIATOR OF THE RELATION BETWEEN MULTIPLE‐MINORITY STATUS AND MENTAL HEALTH BURDEN IN AN AGING HIV‐POSITIVE POPULATION
Storholm ED 1, Halkitis PN1
1NYU, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Using Minority Stress Theory as a guiding paradigm, we sought to document the mental health burdens of a diverse group of men and women ages 50 and over living with HIV with regard to depression, loneliness, and diminished psychological well‐being. Specifically, we aimed to examine whether multiple‐minority status and HIV‐related stigma explained these mental health burdens. METHODS/STUDY POPULATION: Cross‐sectional analyses of 904 diverse men and women ages 50 and over living with HIV in New York City were conducted to examine the lived experiences and needs of aging HIV‐positive individuals. RESULTS/ANTICIPATED RESULTS: Mediation modeling demonstrated that the effects of minority stressors on mental health burden were mediated by HIV‐related stigma. The mediation was significant for the overall sample and for the male subsample. DISCUSSION/SIGNIFICANCE OF IMPACT: Results suggest that in order to fully address the mental health burdens experienced by aging HIV‐positive individuals, we must continue to address mental health burdens directly, and at the same time, look beyond the psychiatric symptoms to address the structural inequities faced by individuals based on their multiple‐minority status.
P99
NOVEL TRANSLATIONAL APPROACH TO HIV MEDICATION MANAGEMENT UTILIZING TASK SHIFTING AND HEALTHCARE INFORMATICS
Morse GD 2, Gavi S1, Sayidine F2, Mudzviti T1, Hakim J1, Maponga CC1, Difrancesco R2
1University of Zimbabwe, Harare, Zimbabwe; 2University at Buffalo, Buffalo, NY, USA
OBJECTIVES/SPECIFIC AIMS: Managing HIV/AIDS with combination antiretroviral therapy (cART) poses complex challenges for resource limited settings where high disease prevalence and shortages of health workers coexist. Public health institutions in Zimbabwe have used information technology to retain patient visit records; though, the data has not been translated for improving long term care for patients with chronic illnesses. The research aims are: 1) Compare outcomes of evidence‐based methods that utilize task shifting with an electronic medical record (EMR), to the standard of care for cART, 2) Determine the factors that contribute to successful medication management algorithms in a community support group setting. METHODS/STUDY POPULATION: Customized EMR algorithms to generate composite drug complexity scores based on the weighting of dosage form, pill burden, dosing schedule, administration instructions, potential side effects, and clinically significant drug interactions allow for patients to be stratified based on risk for suboptimal treatment outcomes and provide clinical decision support for medication management. Furthermore, expanding the pool of health personnel through task shifting to include pharmacists, medication technicians, and community health workers yields greater efficiency in the utilization of health workers. RESULTS/ANTICIPATED RESULTS: A combined effort of task shifting among healthcare providers along with EMR imparts a novel strategy to improve provision of ARV medications and maximize cost savings in government supported programs. DISCUSSION/SIGNIFICANCE OF IMPACT: This effort is in collaboration with the UZ School of Medicine, the Ministry of Health and the Medicines Control Authority to develop comprehensive data in support of national guidelines and policy implementation for HIV/AIDS treatment.
P100
PERCEPTIONS OF DEPRESSION AMONG DIVERSE AFRICAN AMERICAN WOMEN
Holden K 1, Bradford D1, Babalola D1
1Morehouse School of Medicine, Atlanta, GA, USA
OBJECTIVES/SPECIFIC AIMS: Depression is one of the most prevalent mental health problems in the United States that is associated with considerable impairment in functioning. The purpose of this study was to ascertain diverse African American women’s (AAW) perceptions about contributors, risk factors, and perceived need for treatment for depression. METHODS/STUDY POPULATION: This cross‐sectional qualitative study included a convenience sample of 63 adult AAW recruited from an urban community (n = 15), a community based primary healthcare center (n = 23), and a small private academic institution (n = 25). Three mental health and wellness empowerment sessions were held for each of the three cohorts of women where they participated in focus groups. RESULTS/ANTICIPATED RESULTS: Analysis of data indicated several distinctive themes from cohort; however, among the total sample it was suggested that depression is experienced uniquely by ethnically diverse women; and they indicated the following issues as significant considerations for understanding depression as it relates to AAW: chronic stress; health problems; economic problems; problems within personal relationships; overwhelming caregiver responsibilities; societal pressure to succeed; racism and sexism within society; self‐doubt/poor self‐acceptance and satisfaction; and poor personal spiritual/religious foundation. Stigma, inadequate education about mental illness, and poor insurance coverage were identified as barriers to help‐seeking for mental healthcare. DISCUSSION/SIGNIFICANCE OF IMPACT: It is imperative that researchers, clinicians, and public health professionals carefully examine influences on depression and models of care from holistic, culturally responsive, and contextual perspectives.
P101
POPULATION‐BASED COMPARATIVE EFFECTIVENESS OF TRANSURETHRAL RESECTION OF THE PROSTATE AND LASER THERAPIES FOR BENIGN PROSTATIC HYPERPLASIA
Strope SA 1, Yang L1, Nepple KG1, Andriole GL1, Owens PL1
1Washington University, Saint Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: As the American population ages, benign prostatic hyperplasia (BPH) and its associated lower urinary tract symptoms (LUTS) have become increasingly important causes of chronic morbidity. We assessed the comparative effectiveness of two common forms of surgical therapy, transurethral resection of the prostate (TURP) and laser therapies for BPH. METHODS/STUDY POPULATION: Using patient level discharge data and revisit files from the Agency for Healthcare Research and Quality, we evaluated a cohort of patients who underwent TURP or laser therapy for BPH in 2005 in California. Short‐term outcomes (in‐hospital complications, length of stay, 30‐day readmission, 30‐day repeat surgery, 30‐day emergency room visits) were compared between the therapies through regression analysis. Long‐term retreatment (defined as absence of secondary procedures for BPH or complications of therapy) was assessed with survival analysis. Analyses were adjusted for medical comorbidity, race, age, and insurance status. RESULTS/ANTICIPATED RESULTS: From 11,645 discharges, mean length of stay was shorter for laser patients versus TURP [0.70 versus 2.03 days respectively, (p < 0.0001)]. Thirty‐day revisits occurred in 16% of laser patients and 17.7% of TURP patients (p = 0.0338). Retreatment rates at 4 years were 8.3% for TURP and 12.8% for laser (p < 0.0001). After adjustment, TURP patients were 37% less likely to require repeat therapy than laser patients (HR 0.64; p < 0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: Laser procedures and TURP both provide effective management of BPH/LUTS. Laser procedures are associated with less need for hospitalization then TURP, but appear to involve a tradeoff in long‐term efficacy.
P102
PRISONER REENTRY: A STUDY OF HEALTH BEHAVIORS AND ACCESS TO CARE AMONG MEN WITH CRIMINAL JUSTICE AND SUBSTANCE USE BACKGROUNDS
Valera P 1
1Albert Einstein College of Medicine, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: To describe the health needs of ethnic minority men who have extensive criminal justice and substance histories. METHODS/STUDY POPULATION: Thirty participants were sampled and met the following eligibility criteria: (1) be male, (2) ages 35–65 years old, (3) reside in the Bronx, (4) report prior criminal justice status or persistent misdemeanors within the past 5 years, (5) never been diagnosed with cancer, (6) report substance abuse history, (7) provide informed consent, and (8) agree to the interview being audio‐taped. RESULTS/ANTICIPATED RESULTS: Participants were predominately black and Latino, with the mean age of 43 years old. The participants’ involvement with the criminal justice system varied, however, all participant attended programs to address substance use problems upon release. The health statuses of the participants were poor. Majority of the men were diagnosed with an infectious disease (e.g., Hepatitis C, HIV), and /or a chronic condition (e.g., asthma, hypertension, high blood pressure, addiction). DISCUSSION/SIGNIFICANCE OF IMPACT: There is a need for health policies to improve the screening, assessment and treatment programs for men involved in community‐based corrections. This includes a better tracking system and linkages between healthcare providers and social service agencies especially for men with special healthcare needs. Results highlight the need to develop chronic care management program for this population with the goals of improving quality and health outcomes and saving cost.
P103
RECEPTIVENESS TO INTEGRATING FAMILY PLANNING SERVICES INTO HIV CARE AMONG HIV‐INFECTED PATIENTS IN NYANZA PROVINCE, KENYA
Newmann S 1, Cohen CR1, Onono M2, Blat C1, Steinfeld R1, Bukusi EA2, Shade SB1, Grossman D3
1UCSF, San Francisco, CA, USA; 2KEMRI, Nairobi, Kenya; 3Ibis Reproductive Health, Oakland, CA, USA
OBJECTIVES/SPECIFIC AIMS: To assess receptiveness to integrating family planning (FP) into HIV care services among HIV‐infected people enrolled in HIV care in Nyanza Province, Kenya METHODS/STUDY POPULATION: Individual surveys were conducted among patients enrolled at 18 HIV care clinics in Nyanza Province, Kenya. Data analyzed using logistic regression and the generalized estimating equation. RESULTS/ANTICIPATED RESULTS: Only 26% of women (n = 489) and 16% of men (n = 487) reported they or their partners were currently using a more effective method of contraception (MEC): hormonal, intrauterine, or permanent. The majority of participants not using MEC preferred to cease or delay childbearing for at least two years (women: 74%, men: 70%). Most participants (women: 89%, men: 98%) said they would have liked their HIV provider to discuss contraception during their visit. Among people not using MEC, most women (71%) and men (68%) felt they or their partners would be more likely to use contraception if it were available in the HIV clinic. Multivariable analysis found receptivity to FP/HIV service integration to be correlated, among women, with (adjusted OR, 95% CI): age > 35 years (0.25, 0.11–0.43); owning a cell phone (0.47, 0.29–0.77); having a partner (2.32, 1.16–4.76); not using FP (2.55, 1.25–5.24); infertility (0.12, 0.04–0.41); and making FP decisions with her partner (2.91, 1.39–6.09); and, among men, with age > 35 years (2.82, 1.30–6.10) and not taking ARV’s (3.70, 1.56–8.81). DISCUSSION/SIGNIFICANCE OF IMPACT: Integration of family planning into HIV care and treatment appears acceptable to and might decrease the high unmet need for contraception among HIV‐infected individuals in western Kenya, leading to decreased unintended pregnancy among HIV‐infected women in this and similar contexts.
P104
RELATIONSHIP BETWEEN THE CNTNAP2 GENE VARIANT AND COGNITIVE AND BEHAVIORAL FLEXIBILITY IN CHILDREN WITH AUTISM SPECTRUM DISORDERS
Kenworthy L 1, Sharber AC1, Strang J1, Abrams DN1, Devaney JM2, Yerys B3
1Children’s National Medical Center, Center for Autism Spectrum Disorders, Rockville, MD, USA; 2Children’s National Medical Center, Center for Genetic Medicine Research, Washington, DC, USA; 3Childrens Hospital of Philadelphia, Center for Autism Research, Philadelphia, PA, USA
OBJECTIVES/SPECIFIC AIMS: Examine the relationship between the SNP in the CNTNAP2 gene (rs2710102) and RRBI characteristics assessed by BRIEF, Flexibility Questionnaire, and Repetitive Behavior Scale‐Revised (compulsive domain). METHODS/STUDY POPULATION: We examined 45 children with ASD (80% male; M age = 10.06 years (SD = 1.80); M IQ = 107.40 (SD = 19.94)). Diagnosis was confirmed with ADI‐R and ADOS. Children were also assessed using BRIEF, FQ, and RBS‐R. Saliva samples for the CNTNAP2 gene and parent‐rated phenotypic measures were used. Spearman’s rho correlation, univariate ANOVA, and Cohen’s d explored the relationship of CNTNAP2 ASD risk allele presence and RRBI behaviors. RESULTS/ANTICIPATED RESULTS: Significant Spearman’s rho correlation between increasing risk alleles and difficulties on the Shift scale (rho(N = 45) = 0.31, p < 0.05) were found. The homozygous nonrisk allele group had the lowest means across 3 flexibility measures, the heterozygote had higher scores, and the homozygous high risk allele group had the highest scores. Homozygous groups had medium‐to‐large effects for differences in flexibility measures (Cohen’s d: 0.46–0.99), and preliminary ANOVAs yielded marginal findings for BRIEF. DISCUSSION/SIGNIFICANCE OF IMPACT: We find preliminary evidence of association between CNTNAP2 genetic variation and scores on continuous measures of cognitive and behavioral flexibility, supporting the hypothesis that the risk allele for a SNP in the CNTNAP2 gene may relate to higher parent ratings of RRBI behaviors. Further research between RRBI symptoms and this CNTNAP2 SNP is warranted.
P105
RELATIONSHIP OF SELF–BLOOD PRESSURE MONITORING, MEDICATION ADHERENCE, AND BLOOD PRESURE CONTROL AMONG MUNICIPAL WORKERS WITH HYPERTENSION
Breaux‐Shropshire TL 1,2, Brown KC2
1University of Alabama, Birmingham, AL, USA; 2University of Alabama at Birmingham School of Nursing, Birmingham, AL, USA
OBJECTIVES/SPECIFIC AIMS: Uncontrolled blood pressure (BP) remains a major public health issue. Medication adherence is a key factor in BP management; however, adherence behavior is not clearly understood and the most significant factor or factors that contribute to the problem of poor medication adherence and BP control are unknown. The purpose of this study was to determine the relationship among self–blood pressure monitoring, medication adherence, self‐efficacy, stage of change, and BP control among municipal safety workers with access to health insurance. METHODS/STUDY POPULATION: A convenience sample of 149 hypertensive workers completed self‐administered questionnaires. RESULTS/ANTICIPATED RESULTS: The participants were primarily well educated, middle aged (M = 47, SD = 8.4), African American, male municipal employees in the public safety department of a large southeastern US city. The majority of the study participants were in the maintenance stage of change (88.5%), reported good medication adherence (70%) and confidence of adherence to their antihypertensive medication (70.6%), used self–blood pressure monitoring (70%), and demonstrated controlled BP (75.70%). Stage of change was a significant independent predictor of self–blood pressure monitoring but not blood pressure control. There was a strong relationship between medication adherence and medication adherence self efficacy (r = .549, p < .05). DISCUSSION/SIGNIFICANCE OF IMPACT: The study findings suggest that the self‐blood pressure monitoring and BP control rate in the current study may be attribute to the fact that the study’s participants are in the maintenance stage of change, have access to insurance, and participate in a workplace wellness program, which includes an annual health screen.
P106
SOURCES OF VARIATION IN HOSPITAL INFECTION RATES IN WOMEN FOLLOWING CHILDBIRTH
Goff SL 1, Norwitz ER2, Avrunin JS1, Pekow PS1, Lindenauer PK1
1Baystate Medical Center/Tufts University School of Medicine, Springfield, MA, USA; 2Tufts University School of Medicine, Boston, MA, USA
OBJECTIVES/SPECIFIC AIMS: Infections associated with childbirth are a major source of maternal morbidity and hospital costs in the U.S. Identifying potential sources of variation in risk‐adjusted infection rates is an important first step toward reducing childbirth‐associated morbidity for women. METHODS/STUDY POPULATION: We conducted a retrospective cohort study using Perspective, a national inpatient data set. Hospitals with more than 100 deliveries between January 1, 2008 and December 31, 2009 were included; inter‐hospital transfers and nonviable fetuses were excluded. Hierarchical generalized linear models were used to estimate risk‐adjusted hospital infection rates. We then examined the association of selected clinical practices (e.g., amnio‐infusion) and organizational characteristics (e.g., teaching status) with risk‐adjusted infection rates. RESULTS/ANTICIPATED RESULTS: 1,001,189 deliveries at 355 hospitals met inclusion criteria. The overall mean risk‐adjusted infection rate was 4.4% (SD 1.9%, range 1.1–10.8%). Positive correlations were found between infection and use of forceps, vacuum, amnio‐infusion, internal version, and cervical dilation (all p < 0.05); episiotomy showed a negative correlation (p < .05). Higher risk‐adjusted infection rates were found for hospitals in western compared to southern region hospitals (5.2% vs. 4.0%), larger (> 400 beds) compared to smaller (<200 beds) hospitals (4.8% vs. 4.1%), and teaching compared to nonteaching hospitals (4.8% vs. 4.3%). DISCUSSION/SIGNIFICANCE OF IMPACT: Rate of maternal infection related to childbirth varies among hospitals and is associated with specific clinical practices and organizational characteristics, suggesting opportunities for intervention to prevent these infections.
P107
STATE‐MANDATED HOSPITAL INFECTION REPORTING IS NOT ASSOCIATED WITH DECREASED PEDIATRIC HEALTHCARE ASSOCIATED INFECTIONS
Rinke ML 1, Bundy DG1, Abdullah F1, Colantuoni E2, Zhang Y2, Miller MR1
1Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
OBJECTIVES/SPECIFIC AIMS: To determine if United States regions with higher rates of state mandated public healthcare associated infection reporting have lower rates of “selected infections due to medical care” as defined by the Agency for Healthcare Research and Quality’s Pediatric Quality Indicator 12 tool (PDI12). METHODS/STUDY POPULATION: Utilizing the Kids’ Inpatient Databases for 1997–2009, rates of PDI12 were calculated and compared within four national regions: Northeast (100% public reporting), Midwest (33% public reporting), South (62% public reporting) and West (38% public reporting). Logistic regressions were performed adjusting for variables suggesting higher regional acuity and higher risk of PDI12. RESULTS/ANTICIPATED RESULTS: There were 13,945,243 discharges in the databases, with national rates of PDI12 per 1,000 eligible discharges of: 1997: 2.3, 2000: 2.5, 2003: 2.7, 2006: 2.7 and 2009: 1.3. Using weighted adjusted models, the odds ratio for PDI12 rates comparing 2009 to 1997–2006 in the Northeast region was 0.33 (95% CI: 0.26, 0.42), in the Midwest region was 0.19 (95% CI: 0.13, 0.28), in the South region was 0.14 (95% CI: 0.10, 0.20) and in the West region was 0.28 (95% CI: 0.22, 0.35). The odds ratios in both the Midwest and the South were significantly lower than the Northeast (Midwest compared to Northeast p = 0.019, South compared to Northeast p < 0.0001). All sensitivity analyses demonstrated similar conclusions. DISCUSSION/SIGNIFICANCE OF IMPACT: Higher regional rates of public healthcare associated infection reporting are not associated with lower rates of PDI12 utilizing multiple models. Public reporting may not be robust enough to affect PDI12 rates or children may be inadequately targeted in these reporting efforts.
P108
SUPPORT SERVICE USE AMONG DISTRESSED FAMILY CAREGIVERS OF LUNG CANCER PATIENTS
Mosher CE 1, Ostroff J2
1Indiana University‐Purdue University Indianapolis, Indianapolis, IN, USA; 2Memorial Sloan‐Kettering Cancer Center, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Psychological distress affects up to 50% of family caregivers of cancer patients. Lung cancer may increase caregivers’ risk of distress more than other cancers because of its high physical symptom burden and smoking‐related stigma. Although family caregivers of cancer patients have been found to underuse support services, little is known about service use among family caregivers of lung cancer patients. In this study, we investigated the prevalence of mental health and integrative medicine service use (e.g., yoga) and its predictors among distressed family caregivers of lung cancer patients. METHODS/STUDY POPULATION: Primary family caregivers of lung cancer patients (n = 83, 74% female, 82% Caucasian, mean age 55 years) with clinically elevated symptoms of anxiety or depression were recruited from two cancer centers within 3 to 12 weeks of the patient’s new visit to the thoracic oncology clinic. The majority (63%) were caregivers for patients with advanced disease. Surveys were completed at baseline and 3 months later. RESULTS/ANTICIPATED RESULTS: Of the 74 distressed caregivers who completed the study, 22% used mental health services and 32% used integrative medicine services during the study period. Higher levels of anxiety (r = .24, p < 0.05) and the patient’s receipt of chemotherapy (χ2(1, N = 74) = 9.39, p < .01) predicted caregivers’ mental health service use. Higher levels of anxiety (r = .24, p < 0.05), greater education (r = .38, p < 0.01), and being unmarried (χ2(1, N = 72) = 7.79, p < 0.01) predicted integrative medicine service use. Level of depressive symptoms and other demographic (e.g., age, gender) and medical variables did not predict mental health or integrative medicine service use. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings suggest that distressed caregivers underuse support services and that anxiety is associated with greater support seeking.
P109
TEXT MESSAGING AMONG RESIDENT AND FACULTY SURGEONS: PREVALENCE, PURPOSE, AND PATIENT CARE
Shah DR 1, Galante JM1, Bold RJ1, Canter RJ1, Martinez SR1
1University of California Davis, Sacramento, CA, USA
OBJECTIVES/SPECIFIC AIMS: We aimed to determine the prevalence and purpose of texting among resident and attending surgeons and to identify factors associated with patient care–related texting. METHODS/STUDY POPULATION: Surgery residents and attending staff at our university medical center were asked to complete an email survey. The prevalence, frequency, purpose, and concerns about text messaging were examined by gender, age, academic rank or postgraduate year (PGY) level, and specialty or current clinical rotation. Descriptive and bivariate analyses were used as appropriate. RESULTS/ANTICIPATED RESULTS: Overall, 73(65%) surveyed physicians responded, including 45 resident (66%) and 28 attending staff surgeons (62%). Of responding attending staff, 65% texted residents, while 44% of residents texted attending staff. Of attending staff whom texted, most texted residents (83%) and other attending staff (60%) about patient care. Of residents who texted, 80% texted attending staff about patient care. Attending staff (48%) and residents (54%) most frequently communicated with other attending staff using a page followed by a telephone conversation. For routine patient care issues, however, both attending staff (42%) and residents (49%) most commonly reported that they preferred text messaging. On bivariate analysis, older age was associated with decreased odds of texting residents (OR 0.85, 95%CI:0.75–0.93), but not texting attending staff. Gender, academic rank or PGY level, specialty, or current clinical location were not significant predictors of texting residents or attending staff. DISCUSSION/SIGNIFICANCE OF IMPACT: As texting increases in prevalence among physicians, data such as these will facilitate the development of guidelines for the appropriate use of patient care–related texting. Data relating resident and attending texting to patient care outcomes are needed.
P110
THE EXPERIENCE OF PRIMARY CARE CLINICIANS WHO USE A TELEPHONE CONSULTATION SERVICE FOR HIV MANAGEMENT ASSISTANCE
Waldura J 1, Neff S1, Goldschmidt RH1
1UCSF, San Francisco, CA, USA
OBJECTIVES/SPECIFIC AIMS: Telemedicine holds promise as an efficient way to connect primary care clinicians with specialists. In the USA federally funded HIV telephone consultation service (HIV Warmline) offers live, direct access to HIV specialists for clinical consultation. The impact of HIV Warmline “teleconsultation” on primary care clinicians’ self‐perceived ability to care for HIV has not been studied. We sought to determine if primary care clinicians who used the HIV Warmline felt more capable of managing HIV independently in their own practices. METHODS/STUDY POPULATION: We conducted an online survey targeting primary care physicians and nonphysician providers (N = 191, 59% response rate) who used the HIV Warmline for teleconsultation between 1/2008 and 3/2010. Participants were asked to compare the HIV Warmline to other methods of obtaining HIV clinical support, and then rated its impact on confidence in their HIV skills and referral patterns. RESULTS/ANTICIPATED RESULTS: Respondents found the Warmline to be quicker (65%), more applicable (70%) and more trustworthy (57.0%) than other sources of HIV information; 90% had improved confidence about caring for HIV, 67% stated it changed the way they managed HIV, and 74% were able to avoid referring patients to specialists. All valued the availability of live, free consultation. DISCUSSION/SIGNIFICANCE OF IMPACT: Primary care clinicians who used the HIV Warmline experienced increased confidence in their HIV care and expressed less need to refer patients to outside consultants. This study suggests that teleconsultation may be a powerful tool to assist primary care clinicians in delivering more comprehensive HIV care. The direct impact of teleconsultation on actual referral rates, quality of patient care and clinical outcomes needs to be studied.
P111
THE RELATIONSHIPS OF NURSING HOME RESIDENT QUALITY OF LIFE AND FAMILY SATISFACTION AT A FACILITY LEVEL IN MINNESOTA
Shippee T 1, Kane RL1, Kane RA1
1University of Minnesota, Minneapolis, MN, USA
OBJECTIVES/SPECIFIC AIMS: This study measures family members’ satisfaction with nursing home care for residents in Minnesota. For the past five years, Minnesota has used an innovative measure of residents’ quality of life (QOL), which has been published in an online report card. In 2010, the state also implemented a measure of family satisfaction with residents’ care to be integrated into the report card. Aim 1: To calculate facility‐level scores for family members’ satisfaction with resident care. Aim 2: To examine the association between family scores and residents’ reports of their QOL. METHODS/STUDY POPULATION: Family members’ satisfaction with residents’ care was assessed via a mail survey distributed to a sample of family members in all 376 nursing homes in Minnesota in 2010. A total of 16,792 surveys (60% response rate) were received. Factor analysis was used to identify key domains for family satisfaction. Data from the 2010 family satisfaction survey were regressed against resident QOL measures. RESULTS/ANTICIPATED RESULTS: (1) Three distinct domains were identified for family member satisfaction; “general,”“facility,” and “food.” (2) Family satisfaction scores were positively skewed, with low variation across facilities. (3) Family satisfaction had a weak association with resident QOL across different domains. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings point to the multifactorial nature of family satisfaction measures which could lead to the development of different profiles for a given facility. Low concordance between family and resident satisfaction raises concerns about the use of proxies for nursing home resident surveys. Findings could be used to develop multipronged interventions for facilities to improve their performance according to family member’s evaluations.
P112
TRANSLATING GENOMIC RESEARCH FINDINGS INTO IMPROVED HEALTH
Arar N 1, Delgado E1, Winkler P1, Guerrero M1
1UTHSCSA, San Antonio, TX, USA
OBJECTIVES/SPECIFIC AIMS: Comprehensive familial risk assessment represents a critical step towards the implementation of personalized medicine and will complement current/future genetic testings. The main objective of this project is to assess consumers’ (1) experience and satisfaction in using the Surgeon General’s (SG) online FHH tool, and (2) identify facilitators and barriers to using FHH information. METHODS/STUDY POPULATION: Research staff worked with the Translation Advisory Board members in five different Counties in South TX to recruit subjects and identify a convenient location to conduct this study at each county. Mixed‐methods using qualitative and quantitative approaches were employed in this study. A total of 75 community members were invited to enter their FHH information using the online SG‐FHH tool, complete the study’s satisfaction survey. RESULTS/ANTICIPATED RESULTS: Participants’ average age was 44.52 (range: 19–72). Most of participants (85%) said that they have access to a computer with Internet and 90% reported that they know how to use a computer, while 10% indicated that they are unable to use a computer. More than two‐thirds of the participants felt that items on the SG FHH tool were easy to understand and felt that FHH categories were relevant to their family’s health. All participants viewed the SG‐FHH tool as useful and indicated that they would likely recommend the tool to others. Some barriers reported to using the SG‐FHH tool were lack of computer skills, knowledge of family health history and concerns about privacy and confidentiality. DISCUSSION/SIGNIFICANCE OF IMPACT: This study provided information on the performance and functionality of an inexpensive and widely accessible method for FHH collection. Our findings highlighted several opportunities and challenges of utilizing FHH information as a clinical and genomic tool in the community.
P113
VARIABILITY AND EFFICIENCY OF ICU UTILIZATION IN PATIENTS WITH TRAUMATIC INTRACRANIAL HEMORRHAGE
Nishijima DK 1, Newgard CD2, Staudenmayer KL3, Slattery DE4, Haukoos JS5, Gee C6, White NJ7, Maxim P8, Hsia RY8, Melnikow JE1, Holmes JF1
1UC Davis, Sacramento, CA, USA; 2OHSU, Portland, OR, USA; 3Stanford, Palo Alto, CA, USA; 4Univ of Nevada, Las Vegas, NV, USA; 5Denver Health, Denver, CO, USA; 6Univ of Utah, Salt Lake City, UT, USA; 7Univ of Washington, Seattle, WA, USA; 8UCSF, San Francisco, CA, USA
OBJECTIVES/SPECIFIC AIMS: Patients with any degree of traumatic intracranial hemorrhage (tICH) are frequently admitted to the ICU for observation although many never require critical care interventions (CCI). Across a consortium of trauma centers we examined: (1) the variability of ICU utilization and (2) the proportion of adult patients with tICH admitted to the ICU who never received a CCI during hospitalization. METHODS/STUDY POPULATION: A structured, retrospective cohort study of adult patients with tICH was conducted within a consortium of eight trauma centers in the Western US from 2005 to 2010. ICU utilization was determined for patients with a normal mental status and an injury severity score [ISS] <16. CCI was defined as intubation, neurosurgery, blood transfusion, vasopressor use, invasive monitoring, or cardiac arrest. Variability between sites in ICU utilization and ICU patients not receiving a CCI was compared using descriptive statistics. RESULTS/ANTICIPATED RESULTS: Of 16,633 adult patients with tICH (mean age 48 years; ±21 years), 3,826 (23%) had a normal mental status and an ISS<16. There was substantial variability in ICU utilization across centers (range 29–99%). Overall, 57% of adult patients with tICH admitted to the ICU did not receive a CCI during hospitalization (range 48–68%). DISCUSSION/SIGNIFICANCE OF IMPACT: Across a consortium of trauma centers, there was wide variability in ICU utilization within a similar cohort of patients with tICH. Moreover, a large proportion of patients with tICH admitted to the ICU never required a CCI, indicating the potential to improve ICU utilization for tICH.
P114
VARIATION IN PEDIATRIC HEALTHCARE UTILIZATION BY MEDICAL COMPLEXITY
Kuo D 1, Melguizo M1, Robbins J1, Casey P1, Nick T1
1University of Arkansas for Medical Sciences, Little Rock, AR, USA
OBJECTIVES/SPECIFIC AIMS: Profile the variation in pediatric healthcare utilization by medical complexity. METHODS/STUDY POPULATION: Cross‐sectional study of the 2008 Medical Expenditure Panel Survey (MEPS), a national population sample describing healthcare use. The 2008 Full‐Year Consolidated Data Set contains data reported from encounters in calendar year 2008. Medical complexity was defined by a higher number of positive items from the five question Children with Special Health Care Needs (CSHCN) Screener tool. Children with medical complexity (CMC) were defined by ≥4 positive screener items; less‐complex CMC were defined by 1 positive screener item. Outcomes included the number of inpatient, outpatient, and emergency room (ER) visits. ICD‐9 codes were grouped by Clinical Classifications Software. To test for differences in the effect of CSHCN on demographic and outcome variables, chi‐square tests and linear regression were performed using complex sample survey procedures in SAS 9.2. RESULTS/ANTICIPATED RESULTS: Of 9,139 children #17 years in the 2008 MEPS, 1,541 were CSHCN; 842 met 1 criterion, 335 met 2, 194 met 3, and 170 met 4–5 criteria to be classified as CMC. Older age, male gender, white/non‐hispanic race/ethnicity, and public insurance were all associated with higher medical complexity (all p < 0.001). CMC had a mean of 12.8 outpatient, 0.13, and 0.33 ER visits/child; less‐complex CSHCN had 4.0 outpatient, 0.04 inpatient, and 0.20 ER visits/child (all p < 0.05). The most common reasons for non‐CSHCN and less‐complex CSHCN outpatient visits were acute upper respiratory infections and viral illnesses, while the top three groups for CMC visits were for mental health, led by attention‐deficit/conduct/disruptive behavior. DISCUSSION/SIGNIFICANCE OF IMPACT: Healthcare reform models for CMC should account for mental health conditions that may be driving high numbers of outpatient encounters.
METHODOLOGY
P115
HOUSEHOLD AIR POLLUTION AND ANTHROPOMETRIC GROWTH OF GUATEMALAN CHILDREN
Thompson LM 1
1University of California, San Francisco, San Francisco, CA, USA
OBJECTIVES/SPECIFIC AIMS: We explore whether children differentially exposed to air pollution in early childhood have decreased anthropometric growth. METHODS/STUDY POPULATION: The RESPIRE intervention trial was conducted in rural Guatemalan between 2002 and 2004. The primary aim of the study was to examine the impact of an introduced wood‐fired chimney stove on pneumonia incidence in children <18 months. The present study examined anthropometric growth of these children. The 2006 WHO Growth Reference standards were used to determine stunting (height‐for‐age z‐scores), wasting (weight‐for‐age z‐scores) and underweight (weight‐for‐height z‐scores). Random intercept, random slope mixed models were used to evaluate the primary predictor of interest (child‐averaged personal exposures to carbon monoxide) and other factors that contribute to undernutrition were evaluated. RESULTS/ANTICIPATED RESULTS: Maximum likelihood estimates for wasting, stunting and underweight represent the continuous change in median z‐scores. Only wasting showed a weak statistical association (p = 0.11) with log‐transformed carbon monoxide. Significant predictors of wasting (p < 0.05) were: infant age; maternal body mass index < 18.5; maternal age; economic support; season; steam bath use; and pneumonia or diarrhea in last 2 weeks. Stunting and underweight were statistically associated (p < 0.05) with male gender; infant age; maternal height; season and diarrhea (p = .0001). DISCUSSION/SIGNIFICANCE OF IMPACT: We did not find a relationship between child anthropometric measures and HAP. This may reflect the short time under observation. HAZ, WAZ and WHZ scores were reduced if mothers were of short stature or low body mass index, indicating the intergenerational cycle of maternal poor nutrition and infant growth. Season of measurement was related to all outcomes, and may serve as a proxy for food availability.
P116
A SMART TEXTILE SHIRT FOR LOW‐COST HIGH‐THROUGHPUT SLEEP APNEA SCREENING
Bianchi MT 1, Lipoma T2, Darling C2
1Massachusetts General Hospital, Boston, MA, USA; 2Nyx Devices, Boston, MA, USA
OBJECTIVES/SPECIFIC AIMS: Sleep apnea is a reversible cause of morbidity and mortality. Although sleep apnea is prevalent in the adult population, particularly those with comorbid medical and neurological disease, epidemiological studies suggest that a large portion of affected individuals remain undiagnosed. The weak association with subjective sleepiness, the failure to triage cases not fitting the traditional (i.e., Pickwickian) presentation, and the poor performance of screening tools contribute to this problem. We developed a smart‐textile shirt to meet the important clinical need for reliable population‐based screening for occult sleep apnea. METHODS/STUDY POPULATION: Adults with or without sleep apnea were analyzed. The Partners IRB approved this study. We have a patent pending on the shirt. This study was supported by the Center for Integration of Medicine and Innovative Technology. RESULTS/ANTICIPATED RESULTS: The capacitance sensors correlated strongly with respiratory effort from the chest and abdomen. We developed a respiratory event detection algorithm from PSG data of patients with absent, mild, moderate, or severe sleep apnea (10–20 in each group). Respiratory event counts from the algorithm showed high correlation (>0.7 r‐values with PSG‐scoring. The sensitivity for any sleep apnea (cutoff index of >5 events per hour) was nearly 100%, and specificity was over 75%. DISCUSSION/SIGNIFICANCE OF IMPACT: The smart shirt is a promising apnea screening tool. Larger validations with principled parameter optimization are underway to determine the utility of this novel device in large‐scale screening.
P117
ASSESSING STAKEHOLDER PREFERENCES WITH THE STANDARD GAMBLE
Sheldrick RC 1,2, Leslie LK1,2, Parsons SK1,2, Rodday AM3, Wong JB1,3
1Tufts University School of Medicine, Boston, MA, USA; 2Floating Hospital for Children, Tufts Medical Center, Boston, MA, USA; 3Institute of Clinical Research & Health Policy Studies, Tufts Medical Center, Boston, MA, USA
OBJECTIVES/SPECIFIC AIMS: To assess stakeholders’ preferences for medical outcomes, the standard gamble elicits the value or “utility” of a health condition relative to perfect health and immediate death. Alternatively, the “chaining” method employs a risk of immediate worse health. Our goal was to compare physicians’ responses to these two standard gambles. METHODS/STUDY POPULATION: We mailed surveys to 291 physicians who were randomly assigned to complete standard gambles with chaining or without. Each respondent rated descriptions of mild, moderate, and severe ADHD. Based on previous studies, we hypothesized that chained gambles would yield higher utilities. We tested for differences using the Somers’ D test. RESULTS/ANTICIPATED RESULTS: One hundred twenty‐seven physicians (44%) completed the survey. Experimental conditions did not differ on demographic variables, and participants in both conditions rated the more severe ADHD health states with lower utility scores (p < 0.001). Among demographic variables, years‐in‐practice was positively associated with utility (p = 0.01). Controlling for this variable, participants randomly assigned to complete chained standard gambles reported higher utilities for moderate (p = 0.03) and severe ADHD (p = 0.04). DISCUSSION/SIGNIFICANCE OF IMPACT: Comparative effectiveness studies are central to the process of translating research into practice. To compare the effectiveness of disparate interventions, assessments of stakeholders’ preferences are used to estimate quality‐adjusted life‐years, which are a standard metric for evaluating and comparing otherwise disparate interventions. Our results suggest that such estimates are sensitive to methodology, in particular to how the standard gamble is administered.
P118
CAN CHOICE OF FUNCTIONAL STATUS MEASURE INFLUENCE EVIDENCE FOR CLINICAL PRACTICE?
Van Cleave JH 1, Egleston BL2, Bourbonniere M3, Cardone L4, McCorkle R5
1New York University, New York, NY, USA; 2Fox Chase Cancer Center, Philadelphia, PA, USA; 3Thomas Jefferson University Hospital, Philadelphia, PA, USA; 4Mount Sinai Medical Center, New York, NY, USA; 5Yale School of Nursing, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: We explored whether two functional status measures, SF‐12 Physical Component Summary Score (SF‐12 PCS) and Enforced Social Dependency Scale (ESDS), generate similar data in older women following gynecological cancer surgery. METHODS/STUDY POPULATION: Study participants were women ages 65 and over (n = 49). Data were collected at baseline (postoperative period) then 3 and 6 months. Both SF‐12 PCS and ESDS were converted to standardized norm‐based scoring. We then fit multiple linear regression models using generalized estimating equations (GEE) to compare the two measures. A slope coefficient (β) equal to one would provide evidence of perfect agreement. RESULTS/ANTICIPATED RESULTS: Study participants’ mean age was 72.5. A majority of patients were white (93.9%) and primarily treated with surgery and chemotherapy (63.3%). Using GEE, we demonstrated that the relationship between the two measures was less than 1.0, signaling less than perfect agreement (Beta = 0.16, 95% CI 0.06 to 0.26, p = 0.002). Multiple linear regression analysis by data collection time showed a nonsignificant and negative relationship at baseline which became significantly positive at 3 and 6 months (Baseline: Beta =−0.09, 95% CI −0.33 to 0.14, p = 0.429; 3 Months: 0.28, 95% CI 0.14 to 0.41, p < 0.001; 6 Months: 0.48, 95% CI 0.29 to 0.66, p < 0.001). DISCUSSION/SIGNIFICANCE OF IMPACT: The findings suggest that differing functional status measures have the potential to generate dissimilar data among older women undergoing gynecological cancer surgery. Thus, researchers’ choice of functional status measure may influence the evidence guiding clinical practice in this population.
P119
CLINICAL IMPLICATIONS OF PULSE RATE ON PERCEPTION OF SWALLOWING COMPONENTS FROM THE MBSIMP
Bonilha H 1, Blair J1, Carnes B1, Martin‐Harris B1
1Medical University of South Carolina, Charleston, SC, USA
OBJECTIVES/SPECIFIC AIMS: Modified barium swallow studies (MBSS) at 30 pulses per second (pps) are believed to allow for greater accuracy in assessment of swallowing function compared to lower pulse rates; however it exposes patients to increased radiation. Thus, it is necessary to verify and quantify the improvement gained from the higher pulse rates to determine the risk/benefit ratio. We previously found a difference in diagnostic indicators between 15 and 30 pps MBSSs. This study explored differences in treatment plan and prognosis based on 15 and 30 pps MBSSs. METHODS/STUDY POPULATION: Ten MBSSs, from five patients at both 15 and 30 pps, were previously scored on MBSS measurements (MBSImP©) on 17 physiologic components on individual swallow scores, Overall Impression (OI) scores and Penetration Aspiration Scale (PAS) scores. Five speech‐language pathologists (SLPs) determined compensatory strategies, diet change, and treatment modality based on the scores from the ten MBSSs. RESULTS/ANTICIPATED RESULTS: At least one SLP determined a different treatment plan (compensatory strategies, exercises, diet modification) or prognosis for all of the five patients when decisions were made based on 15 pps versus 30 pps. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings demonstrate the potential for clinically significant differences in not only diagnostic indicators, but also treatment planning and prognosis when pulse rates are reduced to minimize radiation exposure. Future larger sample size studies should address the clinical importance of the differences, evaluate the threshold of frame rate needed to reliably and accurately score MBSS, and determine the relevance of these findings to patient quality of life.
P120
COMPARISON OF MODELED AND NONMODELED CLEARANCES FOR EFAVIRENZ (EFV)
Venuto C 1,2, Ma Q2, DiFrancesco R2, Hochreiter J2, Morse GD2
1University of Rochester, Rochester, NY, USA; 2University at Buffalo, Buffalo, NY, USA
OBJECTIVES/SPECIFIC AIMS: Summary of pharmacokinetic (PK) data in large clinical trials often employs population pharmacokinetic (PopPK) modeling. Although PopPK methods are powerful, they are time‐intensive. For drugs, like EFV, that display a relatively “flat” PK profile (i.e., slowly absorbed and eliminated), it may be possible to apply a less laborious noncompartmental (NC) PK approach. We sought to compare the PopPK and NC approaches for evaluating EFV clearance (CL). METHODS/STUDY POPULATION: PK data came from the AIDS Clinical Trial Group Study 5202, which randomized 929 HIV‐infected patients treated with once‐daily EFV. The study design was limited to sparse sampling and aimed to collect 3 plasma concentration samples per patient. Models to estimate mean CL were constructed based on steady‐state samples. NC analysis for CL was calculated by dividing the dose of EFV by the product of the dosing interval and the steady‐state plasma EFV concentration for time points between 4 and 26 hours post‐dose. RESULTS/ANTICIPATED RESULTS: For the PopPK model, a total of 2153 concentrations from 802 subjects were analyzed. In the NC CL calculation, there were 1940 concentrations from 783 subjects. The overall estimated mean (%SEM) CL values of EFV were 11.2 L/h (1.8%) and 12.9 L/h (26%) for the PopPK and NC approaches, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Prior pharmacokinetic studies have shown estimated mean EFV CL values to range between 8.8 (6.98%) and 11.7 (4.3%) L/h. Although both approaches to the 5202 data provided estimates of mean CL values on the higher end of the scale, the two analyses do not appear to be interchangeable. As indicated by the smaller percent standard error of the mean, the PopPK approach provided a more precise estimate of the mean EFV CL compared to the NC approach.
P121
CORRELATION BETWEEN “SELF‐PERCEIVED” VERSUS “QUIZ‐BASED” CANCER SCREENING AND TREATMENT KNOWLEDGE
Bazargan M 1, Jones L1, Smith J1, Vargas R2, Forge N1, Wright A1, Yazdanshenas H1, Maxwell A2
1Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA; 2University of California, Los Angeles, Los Angeles, CA, USA
OBJECTIVES/SPECIFIC AIMS: Enhancing public awareness of early detection and treatment of cancer can be effective in reducing its morbidity and mortality. An important step in this direction is to determine how much people really do know about cancer detection and treatment. This study aims to examine the correlation between “self‐perceived” knowledge of cancer prevention and treatment versus “quiz‐based” items. METHODS/STUDY POPULATION: Data was collected from 180 community individuals who participated in a full day cancer prevention and screening promotion conference in LA county, on July 2011. The study questionnaire included 34 “true/false” quiz‐based knowledge items, and 12 “self‐perceived” cancer knowledge items, and other personal and sociodemographic measures. The study protocol was approved by the CDU IRB. RESULTS/ANTICIPATED RESULTS:“Self‐perceived” cancer knowledge was correlated with age, primary language, education, body mass index, insurance, self‐report health, access to medical care, having a regular physician, ever discussing risk of cancer with a doctor, chance of survival if cancer was detected, obtaining mammography (for women), and FOB, PAS (for men) in the past 2 years (p = 0.05). Correlates of ‘quiz‐based’ cancer knowledge include: education, self‐report health, chance of survival if cancer detected, mammography and PAS (p = 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data shows that self‐perceived knowledge items were stronger predictors of cancer screening prevention and treatment than the quiz‐based items in this sample of community individuals. Our findings suggest what people say they know about cancer screening and treatment is a better predictor of their cancer preventive behaviors than predesigned quiz based items.
P122
DELUSIONAL THINKING IN NONCLINICAL SUBJECTS IS ASSOCIATED WITH REDUCED LATERAL TEMPORAL CORTEX ACTIVITY
Brent B 1, Coombs G2, Keshavan M1, Seidman L1, Moran J3, Holt D4
1Beth Israel Deaconess Medical Center, Boston, MA, USA; 2Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; 3Massachusetts Institute of Technology, Cambridge, MA, USA; 4Massachusetts General Hospital, Boston, MA, USA
OBJECTIVES/SPECIFIC AIMS: Delusional thinking, which characterizes psychotic disorders, is also seen in nonclinical populations, and its neurobiological basis is poorly understood. Abnormalities within brain systems supporting social cognition, including the default network may increase delusional vulnerability. We examined this hypothesis by testing associations between subclinical delusions and activity and functional connectivity of default network regions. METHODS/STUDY POPULATION: Twenty‐two subjects without clinical diagnoses underwent fMRI scanning while judging if trait adjectives described themselves, a close other, or were emotionally positive or negative. A resting‐state scan was collected. Responses during social versus nonsocial tasks and functional connectivity of the activated network were measured. Correlations with delusional thinking (Peters Delusions Inventory) were calculated. RESULTS/ANTICIPATED RESULTS: Delusions were inversely correlated with left lateral temporal cortex (LTC) response during social reflection (SR). Functional connectivity between the LTC region showing this association and the left medial prefrontal cortex (MPFC) was inversely correlated with delusional thinking. The strength of left LTC‐MPFC functional connectivity predicted the left LTC activation during SR. DISCUSSION/SIGNIFICANCE OF IMPACT: Abnormalities within neural circuitry mediating social cognition may contribute to delusional beliefs. If replicated in future, longitudinal studies of clinical or genetic risk individuals, these findings may foster the earlier detection and treatment of persons at risk for psychotic disorders and help reduce the morbidity and mortality associated with psychosis.
P123
DIGITALLY STAINED CONFOCAL MOSAIC MICROSCOPY (DSCMM) PROVIDES RAPID PATHOLOGY
Gareau D 1,3, Jacques SL3, Bar A3, Nehal K2, Rajadhyaksha M2
1The Rockefeller University, New York, NY, USA; 2Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Oregon Health & Science University, Portland, OR, USA
OBJECTIVES/SPECIFIC AIMS: We aim to evaluate DSCMM as a potential alternative to hematoxylin and eosin‐stained histopathology for residual tumor screening in cancer excision margins. Replacement of frozen histopathology in Mohs surgery could save 400 M/yr in the United States. METHODS/STUDY POPULATION: 250 patients undergoing Mohs surgery for basal (BCC) or squamous cell carcinoma (SCC) were consented under the institutions IRB‐approved protocols and enrolled in this study. Discarded tissue was collected and imaged with a prototype confocal microscope which visualized cells by optical sectioning. RESULTS/ANTICIPATED RESULTS: Confocal mosaics appeared similar to correlating gold standard histopathology. Overall sensitivity/Specificity was 96.6%/89.2% for BCC and 100%/94% for SCC. DISCUSSION/SIGNIFICANCE OF IMPACT: A critical engineering task for translating medical devices from the bench to the bedside is user conformability. DSCMM is not only safe and effective, but it represents a conditioned stimulus that triggers a comfortable recognition of morphology. Histological staining of pathological cancer margins is commonly viewed with hematoxylin‐ and eosin‐stained sections, but DSCMM is ten times faster, ten times cheaper, and appears similar. Optical and computational developments have eliminated the need to retrain the medical community, but there are subtle differences between this new technology and the gold standard H&E. After the ongoing final refinement stages, DSCMM may provide a rapid alternative to intra‐operative histopathology for staged surgical cancer excision margin pathology evaluation.
P124
DOSE‐FINDING FOR A BEHAVIORAL INTERVENTION: MOVING BEYOND THE “BENCH‐TO‐BEDSIDE” PARADIGM IN TRANSLATIONAL SCIENCE
Shaffer JA 1, Maurer MS1, Lee S1, Clemow L1, Schwartz JE1, Davidson KW1
1Columbia University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Prevailing definitions of translational science emphasize its use of research that progresses “from bench‐to‐bedside.” We demonstrate an alternate, interdisciplinary model of translational science in which dose‐finding methodology from clinical oncology is applied to optimize a behavioral intervention for patients with stable heart failure, depression, and poor quality of life (QoL). METHODS/STUDY POPULATION: Thirty participants, assigned to 10 cohorts of 3 participants each, will receive varying doses (2–10 sessions) of Problem‐Solving Therapy (PST) using adaptive dose‐finding methodology. “Efficacy” will be defined as a 10‐point increase in QoL in 75% of participants, and “toxicity” will be defined as a 10% worsening of either depression or QoL scores in 15% of participants. The optimal dose of PST identified with this design will be used to plan a comparative effectiveness randomized controlled trial. Planning for this trial involved a multidisciplinary team of biostatisticians, cardiologists, and social scientists, and utilized the resources of a Clinical and Translational Science Award (CTSA). RESULTS/ANTICIPATED RESULTS: During 3 weeks of screening, 12 potentially eligible participants have been approached. Of those approached, 11 consented for screening, 8 were excluded for lack of depression, 1 was excluded for not having impaired QoL, 1 was excluded for recent cardiac decompensation, and 1 was enrolled and has completed 2 PST treatment sessions. DISCUSSION/SIGNIFICANCE OF IMPACT: The application of dose‐finding methodology, which was originally designed for clinical oncology and pharmaceutical trials, to behavioral cardiology represents a novel reconceptualization of what is meant by translational science. This project demonstrates how the resources of a CTSA can be embraced to expand the paradigm of translational science.
P125
DRINKING BEHAVIOR AND READINESS TO CHANGE IN A TRAUMA POPULATION AND FEASIBILITY OF COMPUTERIZED ALCOHOL SCREENING AND BRIEF INTERVENTION (CASI)
Lofipour S 1, Hoonpongsimanont W1, Cisneros V1, Roumani S1, Chakravarthy B1, Anderson C1, Barrios C1
1UC Irvine School of Medicine, Irvine, CA, USA
OBJECTIVES/SPECIFIC AIMS: To assess drinking patterns in trauma patients using the Alcohol Use Disorder Identification Test (AUDIT), examine self‐reported readiness‐to‐change scores after brief intervention, and to evaluate the feasibility of Computerized Alcohol Screening and brief Intervention (CASI) in a trauma population. METHODS/STUDY POPULATION: A retrospective study was conducted in a tertiary care university hospital, level I trauma center. CASI was administered to trauma patients, aged 18 and over using a bilingual computerized tablet. The data was analyzed by comparing demographic groups using the chi‐square test for independence and descriptive statistics. RESULTS/ANTICIPATED RESULTS: Out of 1,145 trauma patients enrolled, 286 (25%) drank more than recommended (AUDIT score greater than 8) and 92 (4%) were dependent. Spanish speaking males compared to English speaking males drank a higher than recommended percentage and were dependent. Half of patients who drank more than recommended rated themselves eight or higher on a 10‐point readiness‐to‐change scale. Readiness‐to‐change score revealed no significant difference (p > 0.05) among age, gender, and language. Trauma patients found CASI easy (92%) and a comfort in use (87%). Median length of implementation time ranged from 3 to 9 minutes. DISCUSSION/SIGNIFICANCE OF IMPACT: CASI was able to identify and provide personalized feedback to trauma patients who drank. Half of trauma patients were ready to change their drinking behavior after CASI administration. Bilingual CASI improved alcohol screening and feasibility by reducing the language barrier and administrative time. Limitations included a convenience sample and other language considerations. CASI should be readily available in more trauma populations.
P126
FGF‐BP1 PATHWAYS CONTROL AFTER INDUCTION OF A CONDITIONAL TRANSGENE IN A MOUSE MODEL: INFORMATION DERIVED FROM mRNA EXPRESSION PATTERN ANALYSIS
Deslattes Mays A 1, Tassi E1, Wellstein A1
1Georgetown University, Gaithersburg, MD, USA
OBJECTIVES/SPECIFIC AIMS: Distinct expression patterns are evident when data, properly normalized, are filtered by time points. Using a study on FGFBP1 activation, phenotypically observed pathways are recapitulated from solely the gene expression information and gene of known and unknown function not previously in these pathways are placed based upon correlative analysis. METHODS/STUDY POPULATION: Five cDNA Affymetrix arrays were run on kidneys of FGF‐BP1 transgenic mice. Two arrays were run for animals under doxycyclin diet with the transgene switched off, one array was run with induction of the FGF‐BP1 transgene for 24 hours, one array was run with induction of the FGF‐BP1 transgene for 336 hours, representing a chronic induction of the transgene. RESULTS/ANTICIPATED RESULTS: Distinct expression patterns are obtained by biclustering at the specific time points. The patterns of expression, thus filtered, represent a specific and distinctive communication patterns. These communication patterns represent the activated and suppressed genes and pathways at those distinct time points. Studying these genes, in this order, and with this pattern, allows the exploration of the signal transduction and activation pathway in response to the activation of the FGFBP1 transgene. DISCUSSION/SIGNIFICANCE OF IMPACT: Systems biology approaches explores context, place and function of genes, uses gene expression patterns obtained from genome‐wide microarray studies or RNA Sequencing studies, places genes in canonical pathways and uses correlative analysis to place the remainder of the genes. Being able to use these gene expression technologies allows exploration of the dynamic nature of remodeling events of stressed organisms. Interestingly, the transgene expression improved cell motility, angiogenesis and wound healing in the transgenic mouse model.
P127
IDENTIFICATION OF ESOPHAGEAL MICROBIOTA IN ESOPHAGITIS
Fillon SA 1, Kelly CJ1, Harris JK1, Schroeder S1, Wagner BD1, Fang R1, Moore W1, Yeckes A1, Stevens M1, Robertson C2, Pace N2, Ackerman SJ3, Furuta GT1
1University of Colorado Denver, Aurora, CO, USA; 2University of Colorado Boulder, Boulder, CO, USA; 3University of Illinois Chicago, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Esophagitis is characterized by upper intestinal symptoms in association with chronic inflammation. The two most common forms of esophagitis are related to acid injury, gastroesophageal reflux disease (GERD) and allergy, eosinophilic esophagitis (EoE). The etiology of these diseases is unknown, but recent data implicates microbial triggering. The Enterotest utilizes a swallowed capsule containing a nylon string, a capture device used to detect intestinal parasites. The aim of this study was to identify the esophageal microbiome in patients with esophagitis using the Enterotest “Esophageal String Test” (EST). We hypothesized that the EST can measure esophageal microbiota similar to mucosal biopsies, and that alterations in microbial populations are present in esophagitis. METHODS/STUDY POPULATION: Nasal swab, oral and esophageal string samples and mucosal biopsies were collected from children with EoE (n = 36), GERD (n = 8) and normal controls (n = 25). Microbiome was determined by 16S rDNA amplification and 454 pyrosequencing. RESULTS/ANTICIPATED RESULTS: Many of the medians of the % sequences are different between normal and diagnoses of esophagitis e.g., Streptococcus median abundance in Normal is 35.6, in EoE 37.5 and in GERD 27.4. A different microbiome was observed in the nose and the oral cavity as compared to the esophagus. DISCUSSION/SIGNIFICANCE OF IMPACT: Streptococcus was decreased on the esophageal string from children with GERD. The minimally invasive string technology of the EST can be used to capture the microbiome in esophageal inflammatory diseases and is comparable to mucosal biopsy.
P128
IS A SHORTER ATRIOVENTRICULAR SEPTAL LENGTH AN INTERMEDIATE PHENOTYPE IN THE SPECTRUM OF NONSYNDROMIC ATRIOVENTRICULAR SEPTAL DEFECTS?
Patel SS 1, Mahoney LT1, Burns TL1
1Univ of Iowa, Iowa City, IA, USA
OBJECTIVES/SPECIFIC AIMS: Atrioventricular septal defects (AVSD) account for 7% of all congenital cardiovascular malformations. The atrioventricular septum (AVS) is the portion of the septal tissue that separates the right atrium from the left ventricle; deficiency of the AVS contributes to the AVSD phenotype. A case‐control study was performed to identify whether an intermediate phenotype consisting of a shortened AVS existed in relatives of children with an AVSD. METHODS/STUDY POPULATION: The AVS length (AVSL) was measured in echocardiograms of clinically unaffected parents and siblings from families that were identified through a child with a nonsyndromic AVSD and in families with no history of congenital heart disease. RESULTS/ANTICIPATED RESULTS: No significant differences were seen between case and control families in terms of gender, age, weight, or height. The AVSL was significantly shorter in case parents when compared to control parents. Similar findings were noted within the sibling groups. There was significant evidence for two component distributions in the case parent, case sibling, and control sibling groups after standardizing the AVSL for age and BSA (asAVSL). Heritability of asAVSL was 0.82 and 0.71 in nonsyndromic and control families, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Evidence for two component distributions from the analysis of asAVSL for case parents and case siblings suggests the presence of an intermediate phenotype for nonsyndromic AVSD. The high heritability in the control families suggests that there may be polygenic involvement in the determination of AVSL. Broadening the definition of AVSD to include those with a shortened AVSL may increase the power of genetic association and mapping studies to identify susceptibility genes for AVSD.
P129
MULTIPLE PROPENSITY SCORES TO ASSESS THE EFFECT OF STATIN USE WITHIN 24 HOURS OF ADMISSION FOR ACUTE MYOCARDIAL INFRACTION ON IN‐HOSPITAL AND 30 DAYS MORTALITY
Hadar N 1, Dahabreh IJ1, Goldberg RJ2
1Tufts Medical Center, Boston, MA, USA; 2Department of Medicine, UMass, Worcester, MA, USA
OBJECTIVES/SPECIFIC AIMS: To determine the effect of early statin use within 24 hours of admission for Acute Myocardial Infarction (AMI) on in‐hospital and 30 days mortality. METHODS/STUDY POPULATION: The study population consist of metropolitan Worcester, MA residents hospitalized with validated AMI at 11 community medical centers during 2005 and 2007. We will apply generalization of the propensity score (PS) method, for assign the effect of early statin in patient with AMI in four treatment groups based on the time that the statin was administrated to the patients. Patients would be classified as: (1) yes/yes if they had been receiving a statin before the index hospitalization and if the patient received a statin within 24 hours of admission; (2) no/yes if they had not been receiving statin therapy before the index hospitalization and if they were started on statin therapy within 24 hours of hospital admission; (3) yes/no if patients were previously on statin therapy but were not prescribed statin therapy within 24 hours of admission; (4) no/no if they had never been receiving a statin before the index hospitalization and if the patient did not received a statin within 24 hours of admission. RESULTS/ANTICIPATED RESULTS: Analysis not conducted yet. DISCUSSION/SIGNIFICANCE OF IMPACT: Techniques based on the PS have long been used for causal inference in observational studies for reducing bias. Until recently, the PS method has been mostly used for 2 treatment settings. In many cases, however, we interested in the comparison of more than 2 treatments. Several years ago, two possible extensions to standard PS for ordinal and categorical treatments respectively were suggested. In this project, we aim to apply this contemporary method for exploring this important clinical question.
P130
NORTHWESTERN UNIVERSITY FAMOUS FACES TEST: PERFORMANCE AND NEUROANATOMIC CORRELATES IN PRIMARY PROGRESSIVE APHASIA
Rogalski EJ 1, Gefen T1, Wieneke C1, Weintraub S1, Mesulam M1
1Northwestern University, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Remembering the names of famous individuals is often impaired in older adults with dementia. As more information emerges about dementia, patients are being diagnosed earlier in the course of the illness, often below the typical cutoff age of 65 years, experiencing what is known as “early onset dementia”(e.g., primary progressive aphasia (PPA), early onset Alzheimer’s disease). Though there are several tests available for assessing knowledge of famous faces none were designed recently and therefore their stimuli may be inappropriate for individuals under age 70. To fill this need, we developed the Northwestern University Famous Faces Test (NUFFACE), a series of 20 photographs of famous individuals who reached their height of fame in current years, rendering the stimuli more culturally relevant and age‐appropriate for younger patient populations. METHODS/STUDY POPULATION: Our initial investigation of the NUFFACE test was conducted in a group of 30 patients with PPA, and 27 healthy controls of a similar age. We also examined associations between performance on the NUFFACE test and measures of cortical thickness to better understand the neurobiology of naming versus knowing a famous face. RESULTS/ANTICIPATED RESULTS: Control subjects performed at ceiling 95.5% on average, suggesting the stimuli were age‐appropriate. As expected, PPA patients performed worse than controls. Facial recognition impairments in the PPA group were associated with bilateral temporal atrophy while anatomic correlations with naming impairments were restricted to the left anterior temporal lobe, which demonstrate an anatomic dissociation for naming versus knowing faces. DISCUSSION/SIGNIFICANCE OF IMPACT: Results suggest that the NUFFACE test is a valid measure of famous face identification for the current generation of individuals aged 40–70.
P131
OPTIMIZED SELECTION OF SAMPLES FOR WHOLE GENOME SEQUENCING STUDIES OF UNRELATED SUBJECTS
Edwards TL 1, Li C2
1Vanderbilt University, Nashville, TN, USA; 2Vanderbilt University Department of Biostatistics, Nashville, TN, USA
OBJECTIVES/SPECIFIC AIMS: Sequencing studies using whole‐genome or exome scans are still more expensive than genome wide association studies (GWAS) on a per‐subject basis. As a result, subsets of subjects from a larger study are often selected for sequencing. METHODS/STUDY POPULATION: To perform an agnostic investigation of the entire genome, subjects may be selected that capture founder genomes, and avoid redundant information from regions that were inherited identical by descent (IBD) from a common ancestor. We present SampleSeq2 (SS2) a greedy algorithm that can select a subset of optimally unrelated subjects, estimate the number of founder chromosomes, GT, or select the minimum number of subjects with a target GT. RESULTS/ANTICIPATED RESULTS: We evaluated SS2 compared to a random draw by simulation and using the Amish study of Successful Aging. Comparing the known value of GT from simulation to the estimate of GT, the estimate was close to the true value of GT, and SS2 increased GT relative to a random draw across a range of sample sizes. There were 4995 subjects in the full Amish pedigree with 827 in the aging study. We compared SS2 with random selection for K subjects (K = 50, 100). For K = 50, average GT was 41.5 using SS2 and 29.7 for random selection. On average, SS2 resulted in 39% more founder genomes. For K = 100 the average GT was 60.6 for SS2 and 39.9 for random selection, 52% more founder genomes. We also note that the size of the region inherited IBD among cases is 20% smaller on average using SS2, decreasing the scope and cost of subsequent investigations. DISCUSSION/SIGNIFICANCE OF IMPACT: This increase in founder chromosomes improves the power of association tests, mitigates the effects of cryptic relatedness, increases the total yield of alleles from sequencing, and minimizes the average size of regions shared IBD around disease alleles in cases.
P132
POWERFUL MULTILOCUS TESTS OF GENETIC ASSOCIATION IN THE PRESENCE OF CONFOUNDING EFFECTS AMONG MARKERS
Wang T 1
1Albert Einstein College of Medicine, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: Genome‐wide association studies (GWAS) have emerged as a prevailing approach for identifying loci associated with common human diseases. As compelling as these associations are, the findings of GWAS explain only a small proportion of the heritability for most common diseases. One reason for this may be that associations are masked by the confounding effects among SNP markers and hence not able to be detected. To overcome the bias, it is necessary to detect associations of multiple correlated SNP markers simultaneously. However, the conventional multi‐locus tests could be very inefficient when multiple SNP markers are in strong linkage disequilibrium because of the large number of degrees of freedom involved in the test statistics. METHODS/STUDY POPULATION: A new score test based on the penalized likelihood function are proposed to balance the efficiency and bias for testing assocaitions of multiple SNP markers. Under this approach, the standard regression‐type global score statistic and the variance‐component score statistic are two specific cases of the proposed penalize likelihood score statistics. The properties of the new score test are evaluated by an extensive simulation study. Finally, this new test is applied to the GWAS data of breast cancer for identifying new loci. RESULTS/ANTICIPATED RESULTS: Our results suggest the proposed test can maintain good control of Type I error rate, and attain higher power than the conventional score test owing to the reduced number of degrees of freedom and the score test based on the variance‐component model in the presence of confounding effects among SNP markers. DISCUSSION/SIGNIFICANCE OF IMPACT: The new analytic tool has the potential to facilitate the research of mapping genes of complex diseases/traits.
P133
RANKING OF MEDICAL SCHOOLS: HOW ROBUST ARE THE FINDINGS?
Hurtado Rua SM 1, Mazumdar M1
1Weill Cornell Medical College, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Medical schools have been ranked by news organizations and researchers using a variety of metrics summarized by a composite index. A composite index is an aggregation of school performance measurements (such as average MCAT and GPA,% of minorities, etc.). Its construction can be as simple as computing a weighted average or somewhat more complex as a regression based index. However, little attention has been paid to the methodological issues underlying the definition and construction of these indices. Implication of changing indices to ranks ignoring the variability is also rarely discussed. Our objective is to investigate the sensitivity of the composite indices to their construction and to estimate confidence intervals (CI) of the ranks. METHODS/STUDY POPULATION: A statistical simulation was conducted to evaluate the performance of different methodologies underlying construction of the composite indices, their transformation to the ranks and related CI [frequentist intervals and Bayesian high posterior density (HPD) intervals] RESULTS/ANTICIPATED RESULTS: EARLY RESULTS: We have found that the values of the composite index and theirs associated ranks are sensitive to random variation and the aggregation methodology used. DISCUSSION/SIGNIFICANCE OF IMPACT: Care is warranted when interpreting ranks of medical schools. We demonstrate the sensitivity of composite indices and ranks and propose that ranks should always report with a measure of sampling variability (standard deviation, CI or HPD). This work will help with use of improved methodology in the field of school ranking.
P134
TARGETED CAPTURE AND DEEP SEQUENCING OF mRNA 39 ENDS
Lin L 1, Wan J1, Raikwar NS1, Thomas CP1, Xing Y1
1University of Iowa, Iowa City, IA, USA
OBJECTIVES/SPECIFIC AIMS: Investigate alternative 39 end usage and polyadenylation of the human placental transcriptome under normoxic and hypoxic conditions. METHODS/STUDY POPULATION: Primary human trophoblast cultures and JEG3 cells, a choriocarcinoma cell line that has features of both cytotrophoblasts and extravillous trophoblasts, were treated under normoxic (20% O2) or hypoxic (2% O2) conditions for 48 hours. Total RNAs are extracted and subjected to an efficient multiplexing protocol for targeted capture and deep sequencing of mRNA 39 ends based on Illumina high‐throughput sequencing platforms. RESULTS/ANTICIPATED RESULTS: Our data indicate that placental hypoxia induces a striking alteration in the global pattern of mRNA polyadenylation, affecting downstream genes important for human parturition and labor. DISCUSSION/SIGNIFICANCE OF IMPACT: Alternative 39 end usage and polyadenylation is a prevalent mechanism for generating transcript and protein diversity in higher eukaryotes. Changes in 39 terminal exon splicing and alternative polyadenylation can profoundly affect the resulting mRNA and protein isoforms and also induce changes in microRNA targeting and mRNA stability. Important prior work has revealed widespread changes in 39 end usage and polyadenylation in development and disease. As placental hypoxia is strongly implicated in pregnancy‐related disorders such as preeclampsia, our study also provides novel insights into the posttranscriptional gene regulatory network underlying normal and pathological pregnancies.
OUTCOMES RESEARCH
P135
PREDICTORS OF PROGRESSION OF RIGHT HEART FAILURE
Prendergast HM 1, Dudley S2
1University of Illinois, Chicago, IL, USA; 2University of Illinois‐Cardiology, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Significant health disparities in diastolic heart failure have been reported. We hypothesize that in ethnic minority patients who have disease progression, there will be greater associations with BMI, uncontrolled hypertension, and age as compared to other ethnic groups and that ethnic minority patients will have earlier progression of disease at younger ages. Aim 1: Determine whether diastolic dysfunction risk factors are weighted differently in a predominately African American population as compared to other racial ethnic groups in an academic setting versus a longitudinal community cohort study. Aim 2: Develop a validation cohort identified from Aim 1 and longitudinally follow this cohort for time‐dependent changes in diastolic function. Aim 3 will examine the role of psychosocial factors/stress on diastolic dysfunction progression in the validation longitudinal cohort. METHODS/STUDY POPULATION: This study is a cross‐sectional analysis of patients with diastolic dysfunction on outpatient echocardiograms performed at an academic teaching institution along with a subanalysis of patients with diastolic dysfunction on cardiac MRI from a longitudinal community cohort study. RESULTS/ANTICIPATED RESULTS: At the completion of this project, it is our expectation that we will identify early predictors of diastolic dysfunction in ethnic minorities as well as other high‐risk patient groups. DISCUSSION/SIGNIFICANCE OF IMPACT: This proposed research is innovative as it is among the first to evaluate the time‐dependent longitudinal changes and progression from diastolic dysfunction to diastolic heart failure in a predominately ethnic minority population with higher rates of hypertension and obesity. The information obtained from the proposed study will be hypothesis generating for future research studies and an intervention trial.
P136
SYMPTOMS OF DEPRESSION IN SURVIVORS OF SEVERE SEPSIS
Davydow D 1, Hough C1, Langa K2, Iwashyna TJ2
1University of Washington, Seattle, WA, USA; 2University of Michigan, Ann Arbor, MI, USA
OBJECTIVES/SPECIFIC AIMS: To examine if incident severe sepsis is associated with increased risk of subsequent depressive symptoms and to assess which patient characteristics are associated with increased risk of depressive symptoms. METHODS/STUDY POPULATION: Design: Prospective longitudinal cohort study. Setting: Population‐based cohort of older U.S. adults interviewed as part of the Health and Retirement Study (1998–2006). Participants: Four hundred thirty‐nine patients who survived 471 hospitalizations for severe sepsis and completed at least one follow‐up interview. Measurements: Depressive symptoms were assessed with a modified version of the Center for Epidemiologic Studies Depression Scale. Severe sepsis was identified using a validated algorithm in Medicare claims. RESULTS/ANTICIPATED RESULTS: The point prevalence of substantial depressive symptoms was 28% at a median of 1.2 years before sepsis, and remained 28% at a median of 0.9 years after sepsis. Neither incident severe sepsis [Relative Risk (RR) 1.00, 95%Confidence Interval (95%CI) (0.73, 1.34)] nor severe sepsis‐related clinical characteristics were significantly associated with subsequent depressive symptoms. These results were robust to potential threats from missing data or alternative outcome definitions. After adjustment, presepsis substantial depressive symptoms [RR 2.20, 95%CI (1.66, 2.90)] and worse postsepsis functional impairment [RR 1.08 per new limitation, 95%CI (1.03, 1.13)] were independently associated with substantial depressive symptoms following sepsis. DISCUSSION/SIGNIFICANCE OF IMPACT: The prevalence of substantial depressive symptoms in severe sepsis survivors is high, but is not increased relative to their presepsis levels. Identifying this large subset of severe sepsis survivors at increased risk for major depression, and beginning interventions prior to hospital discharge, may improve outcomes.
P137
A COMPARISON OF CHEMOTHERAPY, MATCHED RELATED DONOR, AND MATCHED UNRELATED DONOR HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) FOR CHILDHOOD ACUTE MYELOID LEUKEMIA (AML) WITH POOR RISK CYTOGENETICS
Kelly MJ 1, Horan JT2, Alonzo TA3, Eapen M4, Parsons SK1, Woods WG2
1The Floating Hospital for Children, Boston, MA, USA; 2Emory University, Atlanta, GA, USA; 3Children’s Oncology Group, Arcadia, CA, USA; 4Center for International Bone Marrow Transplant Research, Milwaukee, WI, USA
OBJECTIVES/SPECIFIC AIMS: The primary objective of the study is to determine the optimal treatment in pediatric AML with poor risk cytogenetics. We aim to compare the 5‐year overall survival and 5‐year event free survival among children and young adults with poor risk AML treated with either chemotherapy alone, matched related door HSCT, or matched unrelated donor HSCT in first remission (CR1). METHODS/STUDY POPULATION: A retrospective cohort study is in progress including children who have been treated with chemotherapy or HSCT in CR1 for poor risk AML from 1989–2005. Patients have been drawn from five consecutive Children’s Oncology Group trials and from the Center for International Bone Marrow Transplant Research registry. Poor risk disease is defined by the following cytogenetic abnormalities: monosomy 7, monosomy 5, deletions of 5q, abnormalities of 3q, t(6;9), abnormal 12p, high risk MLL rearranged AML, or complex karyotype. RESULTS/ANTICIPATED RESULTS: The data set includes 149 patients treated with chemotherapy alone and 149 patients treated with either matched related or unrelated donor HSCT. Survival analysis is in progress. DISCUSSION/SIGNIFICANCE OF IMPACT: Previous analyses of poor risk AML patients have been limited by their small sample size and it is currently unknown whether this subgroup benefits from HSCT in CR1. We hypothesize that poor risk patients may not benefit from HSCT in CR1. If this hypothesis is true, the current recommendation to transplant all poor risk patients in CR1 may need to be reconsidered.
P138
A PROTOTYPE HEAD‐MOTION MONITORING SYSTEM FOR IN‐HOME VESTIBULAR REHABILITATION THERAPY
Bhatti P 1, Herdman SJ2, Datta Roy S1, Hall CD3, Tusa RJ2
1Georgia Institute of Technology, Atlanta, GA, USA; 2Emory University, Atlanta, GA, USA; 3James H. Quillen VA Medical Center University, Mountain Home, TN, USA
OBJECTIVES/SPECIFIC AIMS: This work reports the use of a head‐motion monitoring system (HAMMS) to record patient head movements while completing in‐home vestibular rehabilitation therapy exercises. The main aim is to assess the adherence of patients completing in‐home exercise. We hypothesize that patients over‐report exercise completion and that the HAMMS will improve adherence. METHODS/STUDY POPULATION: We focus on critical gaze stabilization exercises for patients with unilateral or bilateral vestibular hypofunction: adaptation and substitution exercises. A prototype head‐worn system capable of capturing and storing human head rotation in both the yaw and pitch planes has been developed to monitor patients while completing these exercises. Head rotations were measured with a dual‐axis gyroscope (±500‐degrees/sec max.) and stored. RESULTS/ANTICIPATED RESULTS: A 52 year‐old male with a resection of a left acoustic neuroma (unilateral vestibular loss) wore the HAMMS during all in‐home exercises. He was instructed to perform the gaze stabilization exercises four times daily. Using the stored record, a total weekly exercise time of (118 minutes) was computed and compared with an expected exercise time (140 minutes). For adaptation exercises, 75–100 sec were observed (60 sec expected). For substitution exercises, 100–140 sec were observed (120 sec expected). No (expected) rest periods were noted between each exercise. DISCUSSION/SIGNIFICANCE OF IMPACT: We have prototyped a compact system that can be used to monitor head motion in patients performing vestibular rehabilitation exercises at home. We demonstrated the capability to capture the exercise motion “signature” of a patient. The HAMMS has the potential to improve clinical outcomes and reduce treatment duration.
P139
AGE‐RELATED MELANOMA‐SPECIFIC SURVIVAL DISPARITIES IN PATIENTS WITH SENTINEL LYMPH NODE METASTASIS
Martinez SR 1, Shah DR1, Yang AD1, Maverakis E1
1University of California, Sacramento, CA, USA
OBJECTIVES/SPECIFIC AIMS: Our goal was to assess if elderly patients with SLN metastases have poorer rates of melanoma‐specific survival relative to their younger counterparts. METHODS/STUDY POPULATION: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent SLN biopsy for intermediate thickness cutaneous melanoma (Breslow thickness 0.75 to 4.00 mm) from 2004 to 2008 and were found to have SLN metastasis. Multivariate Cox proportional hazards models assessed the influence of patient, tumor, and treatment‐specific factors on melanoma‐specific survival. RESULTS/ANTICIPATED RESULTS: Entry criteria were met by 849 patients. On multivariate analysis of the entire patient cohort, patients in the three oldest age groups had an increased risk of melanoma‐specific mortality: age 60 to 69 (HR 2.28, CI 1.07–4.88), age 70 to 79 (HR 2.90, CI 1.32–6.39), and age ≥ 80 years (HR 3.50, CI 1.45–8.45). Additional factors associated an increased risk of melanoma‐specific death included T3 tumors (HR 3.58, CI 1.08–11.86), head and neck primary site (HR 2.27, CI 1.32–3.90), and primary tumor ulceration (HR 1.55, CI 1.01–2.37). Receipt of CLND did not predict improved melanoma‐specific survival. Among patients who did not undergo CLND (n = 244), increased melanoma‐specific mortality was predicted by patient age 70 to 79 years (HR 6.36, CI 1.17–34.69), head and neck primary site (HR 5.02, CI 1.87–13.471), and lentigo maligna histology (HR 63.56, CI 4.80–841.49). Among patients who received a CLND (n = 605), increased melanoma‐specific mortality was predicted by age ≥ 80 years (HR 3.26, CI 1.08–9.85) and primary tumor ulceration (HR 1.83, CI 1.10–3.04). DISCUSSION/SIGNIFICANCE OF IMPACT: Elderly patients with SLN metastasis have poorer melanoma‐specific survival than their younger counterparts. The reason for this disparity is not related to use or avoidance of CLND.
P140
ASSESSMENT OF PORCINE AORTIC TISSUE AS A BIOLOGIC VASCULAR GRAFT MATERIAL
Ostdiek AM 1,2, Altschul L1, Grant S1
1Department of Biological Engineering, University of Missouri, Columbia, MO, USA; 2Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA
OBJECTIVES/SPECIFIC AIMS: Cardiovascular disease is the leading cause of mortality in the United States. Arterial replacement has become a common treatment for this disease, however there is a lack of readily available, easily stored, functional small‐diameter vascular grafts. Our research involves the development of a vascular scaffold consisting of gold nanoparticles conjugated to decellularized porcine aortic tissue. METHODS/STUDY POPULATION: Porcine aortas were collected from freshly euthanized animals and underwent a decellularization protocol. Twenty nanometer gold nanoparticles (AuNP) at a concentration 4 times the stock solution (AuNP‐4x) were crosslinked to the aortic scaffolds using an EDC/NHS solution. A DAPI staining protocol was used to assess the effectiveness of the decellularization protocol. A WST‐1 assay was used to test the biocompatibility of the scaffolds after 3 days in L‐292 culture. RESULTS/ANTICIPATED RESULTS: The results showed no evidence of residual DNA in the decellularized tissue using the DAPI stain. The WST‐1 assay comparing decellularized, crosslinked, and AuNP‐4x showed no statistical differences (p > 0.05) between the groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These results demonstrated that porcine aortic tissue can be thoroughly decellularized using our current protocol and is biocompatible. The attachment of AuNPs does not adversely affect cell viability. Further tests will examine the amount of cell proliferation that occurs on the scaffolds, as well as examining the mechanical properties.
P141
BARRIERS TO PHYSICAL ACTIVITY IN SCHOOLCHILDREN WITH ASTHMA: A PARENT PERSPECTIVE
Reznik M 1, Bauman LJ1
1Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: To identify barriers to PA in inner‐city schoolchildren with asthma. METHODS/STUDY POPULATION: Qualitative semistructured interviews with parents of inner‐city minority children with asthma from 10 Bronx, NY elementary schools. Sampling continued until theoretical saturation was reached. Interviews were recorded, transcribed and independently coded for common themes. Emerging themes were discussed and agreed upon by both investigators. RESULTS/ANTICIPATED RESULTS: 23 parental interviews were completed (21 mothers, 2 fathers). Barriers to PA were identified at all levels of the Socioecologic Model (community, school, family and child). Several dominant themes emerged from the data. The most commonly mentioned barrier to PA was living in an unsafe neighborhood involving drugs, violence, and shoot outs (N = 21). Although all parents mentioned having an available park in their neighborhood, most preferred to travel to a distant park out of the borough or the city due to the safety concerns. The second most commonly mentioned barrier was financial burden and the lack of free or affordable after‐school physical activity programs (N = 15). Other commonly identified barriers were: parental worry about occurrence of asthma attacks with PA (N = 15); their child’s preference for sedentary behaviors that involve TV and video games (N = 11); infrequent or complete lack of physical education classes in schools (N = 10); lack of trust in the ability of school personnel to manage acute asthma (N = 10); their child’s lack of symptom awareness and not knowing their limit during exercise (N = 8); and child’s PA incompetency (N = 5). DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate a complex multilevel set of barriers to PA. Single‐solution approaches to enhance PA in children with asthma are likely to have only limited impact on this pervasive problem.
P142
CHEST CT SCAN FINDINGS AND IMPLICATIONS FOR LUNG CANCER SCREENING IN HIV INFECTED PATIENTS
Sigel KM 1, Wisnivesky J1, Brown S2, Joon K2, Maria R3, Akgun K4, Shahrir S5, David R6, Crothers K5
1Mount Sinai School of Medicine, New York, NY, USA; 2Bronx VAMC, Bronx, NY, USA; 3Michael Debakey VAMC, Houston, TX, USA; 4Yale School of Medicine, New Haven, CT, USA; 5University of Washington School of Medicine, Seatle, WA, USA; 6Atlanta VAMC, Atlanta, GA, USA
OBJECTIVES/SPECIFIC AIMS: Increased risk of lung cancer among HIV infected compared to uninfected persons suggests that HIV infected persons, especially smokers, may benefit from targeted screening interventions. High prevalence of baseline imaging findings may alter the risk/benefit profile of screening in this group. We used chest CT scans from a cohort of HIV infected and uninfected outpatients to compare the prevalence of incidental abnormalities by HIV status. METHODS/STUDY POPULATION: Subjects were 145 HIV infected and 125 uninfected Veterans enrolled in the prospective multicenter EXHALE Study between 2009–2010. Participants’ baseline CT scans were interpreted by site radiologists. The prevalence of abnormal findings was compared by HIV status. Charts of subjects from a single site were also reviewed for subsequent evaluation and diagnoses based on the study CTs (N = 104). RESULTS/ANTICIPATED RESULTS: The largely male, ethnically diverse cohort included over 80% current or former smokers. Pulmonary nodules were the most common incidental abnormality, and were found in similar proportions in HIV infected and uninfected subjects (49% vs. 46%; p = 0.7). Follow‐up was recommended in similar numbers for HIV infected and uninfected subjects (23% vs. 29%; p = 0.3). The proportion of patients with new pulmonary diagnoses as a result of these CT scans were similar between groups (10% vs. 10%; p = 0.9). DISCUSSION/SIGNIFICANCE OF IMPACT: HIV infected patients did not have higher rates of incidental pulmonary nodules on chest CT in this cohort. These data suggest similar incidence of positive screening scans among HIV‐infected compared to HIV‐uninfected persons.
P143
CLEFT PALATE REPAIR: FACTORS IMPACTING QUALITY
Nguyen C 1, Curtin C2, Khosla R2, Hernandez‐Boussard T3, Davies S4, Bhattacharya J4
1Stanford University School of Medicine, Menlo Park, CA, USA; 2Division of Plastic Surgery, Stanford University School of Medicine, Stanford, CA, USA; 3Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA; 4Center for Health Policy/Primary Care Outcomes Research, Stanford University, Stanford, CA, USA
OBJECTIVES/SPECIFIC AIMS: (1) Compare cleft palate outcomes between hospital types (2) Recognize clinical and economic consequences due to extended hospital stay (3) Assess volume and hospital factors impacting surgical outcomes METHODS/STUDY POPULATION: We utilized data from the Healthcare Cost and Utilization Project (HCUP) Kids Inpatient Database (KID) from 1997, 2000, 2003, and 2006. Cohort was identified using the ICD‐9‐CM procedure code for cleft palate repair (27.62). We examined patient and hospital characteristics. We divided the hospitals into Pediatric Hospitals (PH), General Hospitals, and Non‐accredited Children’s Hospital (NAPH). Quality measures were mean length of stay (LOS) and complications. We performed logistic regression with our dependent variable being longer average hospital stay: LOS > 2 days. RESULTS/ANTICIPATED RESULTS: We found 14,153 patients. Mean LOS 2 days (SD 0.04), mortality rate 0.01%, and transfusion rate 0.3%. Less than 3% of children experienced a complication during their hospital stay. Complication rates quadrupled in patients with LOS > 2 days. Mean total charges for cleft palate repair was 13,873 overall, but increased to 27,514 with LOS > 2 days. Both General Hospitals and NAPH had 4.3 times the odds of LOS > 2 days than PH. Children with comorbidities had 2.7 times the odds of LOS>2 days than children without comorbidities. DISCUSSION/SIGNIFICANCE OF IMPACT: Cleft palate surgery is safe with low rates of perioperative mortality and morbidity. Hospital factors appear to play a role in the quality of care with PH having the shortest LOS, fewest patients with LOS > 2, and quickest discharge for patients requiring LOS > 2.
P144
CONFLICTING MEDICATION INFORMATION IS ASSOCIATED WITH WORSE MEDICATION ADHERENCE
Carpenter D 1, Blalock S1, DeVellis R1
1University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
OBJECTIVES/SPECIFIC AIMS: This abstract describes whether arthritis patients are exposed to conflicting medication information, which is defined as contradictory medication information from two or more sources. This abstract also documents sources of conflicting information and the association between conflicting information and medication adherence. METHODS/STUDY POPULATION: Data were collected from 328 arthritis patients as part of the Information Networks for Osteoarthritis Resources and Medications Study. Using an online survey, patients reported how often they had received conflicting information about 12 medication topics and sources of conflicting information. Patients also used a Visual Analog Scale to report medication adherence. We ran a linear regression model in SPSS to determine if conflicting information was associated with medication adherence when controlling for various demographic/clinical variables. RESULTS/ANTICIPATED RESULTS: A majority of patients (80.1%) received conflicting medication information and were most likely to receive conflicting information about side effects and proper dosage. Two doctors (27.4%), media sources (21.6%), and the Internet (20.7%) were the most common sources of conflicting information. The regression model revealed that more information source use (B = .22 p < 0.01), lower perceived medication regimen complexity (B =−.17, p < 0.05), and less conflicting information (B =−.13, p < 0.05) were associated with better medication adherence. DISCUSSION/SIGNIFICANCE OF IMPACT: Conflicting medication information is problematic for arthritis patients because it is associated with worse medication adherence. Patients may be especially distressed by conflicting information received from trusted sources, like healthcare providers. Interventions designed to help patients reconcile conflicting information from multiple sources may be warranted.
P145
DOES THE PIPERACILLIN MIC FOR PSEUDOMONAS AERUGINOSA INFLUENCE CLINICAL OUTCOMES OF CHILDREN WITH PSEUDOMONAL BACTEREMIA?
Tamma P 1, Turnbull AE2, Milstone AM1, Carroll KC1, Cosgrove SE1
1Johns Hopkins Medical Institutions, Baltimore, MD, USA; 2Johns Hopkins School of Public Health, Baltimore, MD, USA
OBJECTIVES/SPECIFIC AIMS: The Clinical and Laboratory Standards Institute (CLSI) recently elected to adjust the previous piperacillin susceptibility breakpoint of #64 μg/ml against Pseudomonas aeruginosa to #16 μg/ml, based largely on pharmacokinetic‐pharmacodynamic (PK‐PD) modeling studies. Data on whether PK‐PD modeling correlate with clinical outcomes in children are needed before resorting to broader classes of antibiotics to treat P. aeruginosa. METHODS/STUDY POPULATION: We performed a retrospective cohort study of children with P. aeruginosa bacteremia between 2000–2010 who were prescribed piperacillin. Baseline characteristics and clinical outcomes of children with piperacillin minimum inhibitory concentrations (MICs) #16 μg/ml and 32 to 64 μg/ml were compared. The primary outcome was 30‐day mortality. RESULTS/ANTICIPATED RESULTS: There were 170 children with P. aeruginosa bacteremia receiving piperacillin therapy who met inclusion criteria. One‐hundred twenty four (78%) children had piperacillin MICs #16 μg/ml and 46 (28%) children had piperacillin MICs 32 to 64 μg/ml. There was no significant difference in baseline characteristics between the 2 groups. Thirty‐day mortality was 9% and 24% in children with a piperacillin MIC of #16 μg/ml and 32 to 64 μg/ml, respectively. Using multivariable logistic regression, children with elevated MICs had an increased odds of mortality compared to children with lower MICs (odds ratio, 3.18; 95% CI 1.26–8.04). DISCUSSION/SIGNIFICANCE OF IMPACT: Our finding that elevated piperacillin MICs predict mortality in children supports the recent CLSI recommendation to lower the breakpoint of piperacillin against P. aeruginosa to #16 μg/ml. Alternate therapeutic choices should be considered when piperacillin MICs against P. aeruginosa are ≥32 μg/ml.
P146
EFFICACY OF NUTRITION INFORMATION AT THE POINT OF SELECTION
Lipscomb ER 1, Eicher‐Miller H2, McCrory M2
1Indiana University SOM, Indianapolis, IN, USA; 2Purdue, W. Lafayette, IN, USA
OBJECTIVES/SPECIFIC AIMS: The intent of the menu labeling provision in the Patient Protection and Affordable Care Act of 2010 is to help people make healthier dietary choices by requiring nutrition information, e.g., total calories, for standard menu items on menus and menu boards. Thus, the study objective is to determine if provision of nutrition information at POS influences food sales and intake. METHODS/STUDY POPULATION: A quantitative systematic literature review is in process. The following databases have been culled: ABI/Inform; Business Source Premier; CINAHL, EconLit; EMBASE; OVID, ProQuest, ProQuest Central; PsychInfo; SCI; Wiley Online Library, CENTRAL, CDSR, The Cochrane Library, and Cochrane Methodology Register. A total of 387 titles were identified, including 2 via hand search. A total of 210 titles were discarded; 177 abstracts were retained and 89 have been screened by two reviewers. Currently, 39 abstracts have been discarded based on inapt study design and outcomes; opposing assessments are under review by an arbitrator. The remaining 25 articles are under review by the first two reviewers. Eligibility criteria include RCTs, quasi‐randomized trials, nonrandomized studies, and interrupted time series that measure food sales and/or food intake in settings such as restaurants, cafeterias, and similar sites. There are no exclusions based on study participant characteristics. RESULTS/ANTICIPATED RESULTS: For articles now under review, settings include: cafeteria (12); restaurant (8); laboratory (4); and other (1). Outcomes include: food sales (11); food intake (6); food choice (4); and other (4). Participants include: parent‐child dyad (1); adults (20); adolescents (1); and children (3). DISCUSSION/SIGNIFICANCE OF IMPACT: In absence of decisive efficacy of menu labels, further research will be crucial to understand how people process and utilize nutrition data so that current policies can be revised.
P147
EXECUTIVE FUNCTION, ADHERENCE, AND TRANSITION READINESS IN EMERGING ADULTS WITH TYPE 1 DIABETES
Monaghan M 1, McCormick King M1, Younge T1, Cogen FR1, Streisand R1
1Children’s National Medical Center, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Type 1 diabetes (T1D) management involves daily adherence to a demanding medical regimen. Barriers to adherence include forgetting and poor planning, suggesting executive functions (EF; i.e., skills related to memory, attention, and problem solving) play a key role in optimal disease management. In emerging adults, EF are not yet fully developed but likely crucial for greater autonomy in T1D management and successful transition to adult medical care. This study explored relationships among EF, T1D self‐care, and transition readiness. METHODS/STUDY POPULATION: Preliminary baseline data were collected from 25 participants (M = 18.2 ± .35 years; 60% female; 88% Caucasian) in an ongoing longitudinal study of neurocognitive predictors of health outcomes in late adolescents with T1D. Adolescents and a parent completed questionnaires assessing EF, T1D adherence, and transition readiness. Average number of blood glucose (BG) checks/day and A1c were taken from medical chart review. RESULTS/ANTICIPATED RESULTS: Correlations revealed a significant relationship between parent‐reported EF domains and adherence (Global Executive Composite (GEC): r =−.57, p < 0.01), as well as number of BG checks per day (GEC r =−.44, p = 0.03). Adolescent report of EF skills of planning/organization skills was significantly related to A1c (r = .53, p < 0.01). No significant relationships were detected between EF and transition readiness. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results suggest greater EF skills are associated with better T1D self‐care, including adherence and objective markers of T1D care. Readiness for transition was not associated with EF, although more sophisticated assessments of transition readiness are needed. Findings suggest EF may be an important target for adherence‐promoting interventions in youth with T1D.
P148
FETAL EXPOSURE TO SYNTHETIC OXYTOCIN AND INFANT PREFEEDING CUES WITHIN ONE HOUR POSTBIRTH
Bell A 1, White‐Traut R1, Rankin K1
1University of Illinois at Chicago, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Prefeeding cues are self‐regulating neurobehavioral cues that communicate feeding readiness and the ability to self‐comfort. Various birth‐care procedures have related to frequency and emergence of prefeeding cues after birth. Intrapartum synthetic oxytocin (synOT) is commonly used for labor induction/augmentation in the US, yet there is scarce research on its potential effect on infant neurobehavioral cues. Given that (1) fetal oxytocin is neuroprotective during birth and may be dependent on concentration, and (2) animal findings suggest dose‐dependent changes in offspring behavior after perinatal synOT, our aim was to identify whether fetal exposure to synOT was associated with infant prefeeding organization shortly after birth. METHODS/STUDY POPULATION: We studied a convenience sample of 47 healthy full‐term infants (36 exposed and 11 unexposed to intrapartum synOT). Exclusion criteria: fetal distress, vacuum/forceps, cesarean, and low APGAR. Videotapes of infants (45–50 minutes postbirth) were coded for low, medium, and high levels of prefeeding cues, and analyzed by level of prefeeding organization. RESULTS/ANTICIPATED RESULTS: Prefeeding cues, in descending order of frequency, included mouthing/rooting, tonguing, empty sucking, hand to mouth without sucking, and sucking on the hand. Forty‐four percent of exposed infants displayed a low level of prefeeding organization, compared to 0% from the unexposed group. Twenty‐five percent of exposed infants displayed a high level of prefeeding organization, compared to 64% from the unexposed group. After adjusting for birthweight, sex, labor length and epidural exposure, infants exposed to synOT were at 11 times (95% CI: 1.55–86.72) the odds of displaying low/medium versus high levels of prefeeding organization compared to unexposed infants. DISCUSSION/SIGNIFICANCE OF IMPACT: Newborn neurobehavioral cues may be sensitive to intrapartum synOT.
P149
GLOBAL PERIPHERAL BLOOD GENE EXPRESSION IN MEROSIN‐DEFICIENT CONGENITAL MUSCULAR DYSTROPHY
Collins J 1, Aronow B1, Horn P1, Bonnemann C2
1Cincinnati Children’s Medical Center, Cincinnati, OH, USA; 2National Institute of Health/National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
OBJECTIVES/SPECIFIC AIMS: To measure peripheral blood gene expression profiles in MDC1A subjects as a noninvasive measure of disease. METHODS/STUDY POPULATION: Affymetrix gene expression arrays were used to compare MDC1A human peripheral blood global gene expression to age‐, gender‐ matched controls. RESULTS/ANTICIPATED RESULTS: The microarray hierarchical cluster analysis revealed a distinct expression profile in peripheral blood of MDC1A patients compared to the controls. The majority of differential expression genes were down‐regulated in MDC1A. Functional enrichment analysis demonstrated genes involved in immune pathways, protein regulation, autophagy, and apoptosis. DISCUSSION/SIGNIFICANCE OF IMPACT: Taken together these results suggest a wealth of both biomarkers, potentially important pathways, and potential targets of therapeutic benefit that could impact on the rate of merosin deficiency disease progression. Focused testing of these pathways in mouse models or further evaluation in patients that differ in their rate of disease progression will need to be done for validation of these results.
P150
GRAFT SURVIVAL IN PEDIATRIC KIDNEY TRANSPLANTATION: TRENDS OVER TIME
Van Arendonk K 1, James N1, Boyarsky B1, Orandi B1, Garonzik Wang J1, Montgomery R1, Colombani P1, Segev D1
1Johns Hopkins University School of Medicine, Baltimore, MD, USA
OBJECTIVES/SPECIFIC AIMS: The field of pediatric kidney transplantation has evolved considerably over the past 20 years, including changes in immunosuppression, surgical technique, organ allocation policy, and rates of living donor transplantation. We investigated how these changes have impacted graft survival over time. METHODS/STUDY POPULATION: Using the Scientific Registry of Transplant Recipients, death‐censored graft survival was compared according to year of transplantation in 16,266 pediatric (<18 years old) kidney‐only transplants performed between 1987 and 2010 using Kaplan‐Meier analysis and multivariable Cox models. RESULTS/ANTICIPATED RESULTS: Graft survival has improved over time, with 1‐, 5‐, and 10‐year graft survival of 80.9, 58.3, and 44.5% for transplants performed in 1987 compared to 93.4, 73.6, and 55.5% for transplants performed in 2000. These improvements remained after adjusting for concurrent changes in recipient, donor, and transplant characteristics over time. With each more recent year of transplantation, the hazard of graft loss decreased by 4% (aHR: 0.96, 95% CI: 0.95–0.97; p < 0.001). A similar trend was found for both living donor (aHR: 0.97, 95% CI: 0.96–0.99; p = 0.001) and deceased donor (aHR: 0.95, 95% CI: 0.94–0.96; p < 0.001) transplants. Graft survival improvements were significantly greater in the first year after transplantation (aHR: 0.92, 95% CI: 0.91–0.93; p < 0.001) compared to beyond one year (aHR: 0.98, 95% CI: 0.97–0.99; p = 0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Pediatric kidney graft survival has improved over time for both living donor and deceased donor transplants. Although these results are encouraging, most improvement has come in the first year after transplantation, while achieving progress in long‐term graft survival remains a challenge.
P151
IMPACT OF GASTROPARESIS SEVERITY ON PATIENTS’ AND CAREGIVERS’ QOL
Moshiree B 1, Samuel M2,1, Lagorio L1, Carnaby‐Mann G1, Douglas JY1, Badillo R1, Talley NJ3
1University of Florida, Gainesville, FL, USA; 2Beth Israel Medical Center Program, New York City, NY, USA; 3University of Newcastle, Callaghan, NSW, Australia
OBJECTIVES/SPECIFIC AIMS: Gastroparesis results in a myriad of symptoms which may significant impact both patient and caregiver quality of life (QOL). Our study quantifies this relationship in both patients and caregivers quantifying symptoms perceived to be most disabling. METHODS/STUDY POPULATION: Twenty‐one patients with gastroparesis diagnosed by gastric emptying (GE) scintigraphy; (mean age = 48.43 ± 17.07 years) and their caregivers (n = 13, mean age = 55.38 ± 11.38 years) were recruited. Participants completed the GCSI and the Gastroparesis Quality of Life Assessment (GQOLA). The latter is a newly developed gastroparesis‐specific quality of life measurement tool that explores QOL across physical, social, emotional and financial domains. Simple and multiple linear regression analyses of results were performed to identify predictive factors for patient and caregiver disability. RESULTS/ANTICIPATED RESULTS: Patients: Average GE half‐time was 182 ± 66.1 minutes. Correlation between GE time and GSCI trended toward significance (p = 0.08); GE time was not significantly correlated with GQOLA. GCSI total was significantly correlated with GQOLA (p = 0.011) and GSCI total was predictive of QOL after controlling for age, gender, and alcohol use (p = 0.004). Six of the 9 individual GSCI items, nausea, vomiting, not finishing a meal, feeling full after a meal, bloating, and stomach looking larger, were significantly predictive of GQOLA. Caregivers: GCSI score was not significantly correlated with GQOLA. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study demonstrates a direct relationship between GCSI score and patient disability score. Unique to our study is inclusion of caregivers’ assessment of their disability and their perception of the patient’s disability.
P152
INCREASED PREVALENCE OF SLEEP APNEA IN PATIENTS WITH PSORIASIS COMPARED TO MATCHED CONTROLS
Duffin KC 1, Woodcock J1, Walsh J1, Penrod J1, Krueger G1, Wong B1
1University of Utah, Salt Lake City, UT, USA
OBJECTIVES/SPECIFIC AIMS: to assess the prevalence of obstructive sleep apnea (OSA) and cardiovascular risk factors in patients with psoriasis compared to controls. METHODS/STUDY POPULATION: Patients with untreated moderate‐severe plaque psoriasis (Ps) and age, gender, and BMI‐matched controls were recruited. Demographics, medical history, psoriasis characteristics, fasting serum, and home overnight polysomnography were obtained at baseline. RESULTS/ANTICIPATED RESULTS: 16 patients with psoriasis and 16 matched controls were enrolled. Ps patients had a mean body surface area of 13.4% and four had psoriatic arthritis. Ps and control groups had a mean age of 43.1 and 42.4 years, and mean BMI of 33.2 and 32.5, respectively. Compared to controls, Ps patients had a significantly higher mean apnea/hypopnea index (20.9 vs. 8.1, p = 0.018), longer REM duration (67.0 vs. 24.3 minutes, p = 0.01), and shorter NREM duration (326.2 vs. 407.7 minutes, p = 0.018). Although patients with Ps had a shorter total sleep time (393.2 vs. 428.5 minutes) and more awakening after sleep onset (73.3 vs. 49.1 minutes) these differences were not significant. Ps patients had borderline significantly higher mean hemoglobin A1C (6.2 vs. 5.6, p = 0.062) and frequency of smoking (44% vs. 6%, p = 0.07). Frequency of hypertension, hyperlipidemia, and other cardiovascular comorbidities did not differ between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: In this study, Ps patients had significantly more apnea events suggesting higher risk of OSA that is not attributable to BMI, age or gender. The Ps patients also have significantly different REM and NREM sleep patterns and trended toward more cardiovascular risk. It is possible that the pro‐inflammatory cytokine milieu of psoriasis increases the risk of OSA, although the reverse may also be true. Screening for OSA should be strongly considered in this population.
P153
LIMITED ENGLISH PROFICIENCY AND ACUTE HEALTHCARE UTILIZATION AMONG PATIENTS WITH CKD
Tuot D 1,3, Plantinga L2, Grubbs V1,3, Powe N1,3
1University of California, San Francisco, San Francisco, CA, USA; 2Emory University, Atlanta, GA, USA; 3San Francisco General Hospital, San Francisco, CA, USA
OBJECTIVES/SPECIFIC AIMS: Communication is a key component of healthcare delivery. Language barriers are associated with decreased access to care, but the impact of limited English proficiency (LEP) on acute healthcare utilization among patients with chronic kidney disease (CKD) is unknown. METHODS/STUDY POPULATION: We examined the impact of LEP status on rates of emergency department (ED) visits, hospital admissions (HA), ambulatory care sensitive hospitalizations (ACSC‐HA) and CKD‐sensitive hospitalizations (CKD‐HA) among a cohort of 2249 adults with CKD and ≥2 primary care visits within the San Francisco Department of Public Health Community Health Network, between 2005 and 2010. LEP was defined by preferentially speaking a non‐English language. CKD was defined by an average estimated glomerular filtrate rate (eGFR) < 60 ml/ min/1.73 m2 among ≥2 creatinine measurements ≥ 3 months apart. Incidence rate ratios (IRRs) were calculated with negative binomial regressions, adjusting for sociodemographics, comorbidities and eGFR. RESULTS/ANTICIPATED RESULTS: Nearly a third of the cohort (32%) had LEP, of which 11% spoke Spanish and 13% spoke Chinese. LEP patients had lower rates of ED visits than English‐speaking patients [IRR = 0.82, (95%CI, 0.68–0.97)] with similar rates of HA overall [1.11(0.91,1.37)]. Rates of ACSC‐HA and CKD‐HA were greater among LEP patients than English‐speaking patients [1.65 (1.38, 2.0) and 1.18(1.0,1.41)]. Associations were strongest among Chinese speakers, with the exception of CKD‐HA. DISCUSSION/SIGNIFICANCE OF IMPACT: Among patients with CKD within a safety‐net system, LEP is associated with greater rates of ACSC‐HA and CKD‐HA, despite lower ED visit rates. Efforts to improve communication with LEP patients may help diminish disparate use of acute healthcare services.
P154
LOW STROKE VOLUME INDEX IS ASSOCIATED WITH A LOW TRANSVALVULAR GRADIENT AND PREDICTS SURVIVAL IN PATIENTS WITH SEVERE AORTIC STENOSIS
Lindman BR 1, Arnold SV1, Madrazo JA1, Johnson SN1, Novak E1, Holland MR1, Hohn TA1, Zajarias A1, Miller JG1, Perez JE1
1Washington University School of Medicine, St. Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: A low transvalvular mean gradient (MG) is associated with worse outcomes in patients with severe aortic stenosis (AS) (AVA <1.0 cm2), but the factors that impact the MG remain incompletely understood. We explored the importance of stroke volume index (SVI) and afterload in determining the MG and survival. METHODS/STUDY POPULATION: Data were prospectively obtained on 168 patients with severe AS. Multivariable linear regression models investigated predictors of MG and SVI and a Cox proportional hazards model examined predictors of mortality. RESULTS/ANTICIPATED RESULTS: Of these patients, 55% had a MG < 40 mmHg and 39% had EF < 50%. After controlling for AVA index and ejection time, a low SVI was associated with a reduced MG (β=−1.92, p < 0.001), whereas vascular afterload variables were not associated with MG. However, in a separate model predicting SVI, after controlling for AVA index and variables reflecting LV preload, remodeling, and function, the vascular afterload variables were associated with SVI (p < 0.001 for all). Patients with a low SVI (<30.7 ml/m2) had reduced 1‐year survival versus normal SVI patients (65% vs. 85%, p = 0.006). After multivariable adjustment, every 5 ml/m2 reduction in SVI was associated with a 45% increase in the hazard of death (95% CI 1.01–2.08), whereas afterload variables were not. DISCUSSION/SIGNIFICANCE OF IMPACT: In patients with severe AS, increased vascular afterload does not appear to directly influence MG but does so indirectly via its effect on SVI. Low SVI is not only a predictor of a low MG, it is also associated with worse survival. Routinely assessing SVI, a simple echocardiographic measurement, in patients with severe AS may assist in the clinical management of these patients.
P155
MEDICATION USE IN BREAST CANCER SURVIVORS
Otte JL 1, Skaar T1, Wu J1, Wu M1, Ryker K1, Burns D1, Carpenter J1
1Indiana University‐Purdue University, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: Breast cancer survivors (BCS) are potentially taking multiple prescriptions and over the counter (OTC) medications for health problems associated with cancer and unrelated comorbidities. The use of prescription medications, OTC, and herbal supplements has ramifications for medication adherence/compliance, discontinuation, pharmacogenetics, and drug‐drug interactions. This information has not been documented to our knowledge. The purpose of this study was to describe the types of prescription, herbal, and over‐the‐counter medications taken by BCS and midlife women. METHODS/STUDY POPULATION: Descriptive study of medication use in BCS and noncancer midlife women. Baseline data (N = 236) on BCS (n = 98) and midlife women (MW) (n = 138) enrolled between 04/01/09 and 02/01/11 in a RCT comparing two breathing interventions to usual care for treating hot flashes. RESULTS/ANTICIPATED RESULTS: Demographics, noncancer comorbidities, and medications were analyzed using frequencies and descriptive statistics. BCS were taking a mean 3.30 OTC and 2.70 prescription medications versus midlife women taking 2.72 OTC and 1.94 prescription medications. Of the medications taken by BCS, 43% were vitamin, mineral, or herbal supplements, 7% antidepressants, 5% SERMS, and 5% were antiinflammatories. 39% of BCS and 44% of MW were taking CYP P450 inhibitors or inducers. DISCUSSION/SIGNIFICANCE OF IMPACT: BCS are taking a vast array of prescription and nonprescription medications during survivorship. The majority of medications are OTC vitamin and herbal supplements used for various purposes. It is unclear if prescription medications are managed by a single physician or several practitioners. Clinical implications are to monitor for possible interactions among the various prescription, herbal, and OTC medications. Implications for behavioral and biomedical research are to carefully assess and account for medication use.
P156
MELANOMA‐SPECIFIC SURVIVAL IN THICK CUTANEOUS MELANOMA WITH OR WITHOUT SENTINEL LYMPH NODE BIOPSY
Daylami R 1, Shah DR1, Yang AD1, Maverakis E1, Martinez SR1
1University of California, Sacramento, CA, USA
OBJECTIVES/SPECIFIC AIMS: To assess if patients who underwent SLNB for a thick primary cutaneous melanoma were at a survival advantage or disadvantage compared to those who did not have a SLNB. METHODS/STUDY POPULATION: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for thick primary cutaneous melanoma (known Breslow thickness > 4.00 mm) from 2004 to 2008. We used multivariate Cox proportional hazards models to assess melanoma‐specific survival among patients who received SLNB and those who did not. Covariates examined included: age sex, race/ethnicity, Breslow depth, tumor histology, tumor location, and ulceration status. A subanalysis compared sentinel lymph node negative patients (SLN (‐)) to those that had no SLNB. RESULTS/ANTICIPATED RESULTS: Among 1,981 patients with thick cutaneous melanoma, 1,158 (58.2%) received a SLNB. On multivariate analysis of the entire cohort, those not undergoing SLNB did not demonstrate inferior melanoma‐specific mortality (HR 1.16, CI 0.91–1.47). Factors associated with an increased risk of melanoma‐specific mortality included: female sex (HR 0.69, CI 0.54–0.88), arm primary site (HR 0.66, CI 0.47–0.93), desmoplastic histology (HR 0.52, CI 0.37–0.75), and no tumor ulceration (HR 0.52, CI 0.40–0.66). Increased risk of melanoma‐specific mortality was predicted by increasing Breslow thickness (per hundredth mm: HR 1.01, CI 1.00–1.01). In a subanalysis, patients who did not have a SLNB had poorer survival (HR 1.73, CI 1.28–2.34) relative to those who had a SLNB and were SLN(‐). DISCUSSION/SIGNIFICANCE OF IMPACT: Use of SLNB did not improve melanoma‐specific survival in the overall population. However, when comparing those that underwent SLNB and were SLN(‐) to those that did not undergo SLNB, those undergoing SLNB had superior melanoma‐specific survival.
P157
NEIGHBORHOOD CONTEXT AND STRESS: ENGAGING COMMUNITY AND HEALTHCARE PROVIDER PERCEPTIONS OF CONTEXTUAL INFUENCES ON CHILDHOOD ASTHMA
Yonas M 1, Moore R2, Miller E3, Marsland A1, Wenzel S1
1University of Pittsburgh, Pittsburgh, PA, USA; 2Community College Allegheny County, Pittsburgh, PA, USA; 3Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: Disproportionately high asthma morbidity and mortality exists among socioeconomically disadvantaged children. Evidence indicates that exposure to social and structural risk factors predict future asthma exacerbations. However, identification of modifiable neighborhood‐level factors influencing childhood asthma morbidity remains poorly understood. METHODS/STUDY POPULATION: This mixed methods community‐partnered study engaged residents of two underserved communities, as well as primary healthcare providers to generate and prioritize neighborhood factors perceived to influence childhood asthma. Each of the three groups independently participated in brainstorming, sorting, rating and cluster mapping activities that characterized perceptions of neighborhood items into groupings perceived to influencing the care and control of childhood asthma. RESULTS/ANTICIPATED RESULTS: Participants organized and prioritized 81 discrete and diverse social and contextual items into common cluster groupings, including constructs such as home and environmental triggers, community awareness and understanding of asthma, and acute and chronic stressors. Specific items generated covered a spectrum of factors including pollution, smoking, lack of asthma knowledge, domestic and community violence, bullying, abandoned housing and lack healthcare and medication. Pathways by which factors influence childhood asthma were documented within each expert group. DISCUSSION/SIGNIFICANCE OF IMPACT: Results provide unique insight to integrated neighborhood‐level and primary care interventions, generated testable hypotheses and cultivated the development of translational interdisciplinary relationships necessary for future intervention and epidemiologic research.
P158
PATIENTS’ SAFETY TOOLBOX: DATA VISUALIZATION OF HEALTH‐CARE ACQUIRED INFECTIONS
Shara NM 1,2, Libin AV3,2, Millo Y3
1MedStar Health Research Institute, Hyattsville, MD, USA; 2Georgetown‐Howard Universities Center for Clinical and Translational Science (GHUCCTS/CTSA), Washington, DC, USA; 3Simulation and Training Environment Laboratory, MedStar Health, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: The proposed Data Visualization of Health‐care Acquired Infections (DAVAI) Model is to explore the utility of the clinical data mining algorithm with the embedded statistical assessment of the just‐in‐time medical information collected via EHR focusing on patient safety indicators. METHODS/STUDY POPULATION: MHRI uses a health data repository developed by Explorys, Inc. to mine clinical data in near‐real time in a cloud‐based data warehouse. The DAVAI Model is a pilot implementation study conducted across the MedStar Health inpatient clinical institutions (MedStar Health Research Institute, Washington Hospital Center, National Rehabilitation Hospital, and data acquisition centers including GHUCCTS cores and Simulation and Training Environment Laboratory (SiTEL), which is a MedStar‐wide simulation and education research hub. RESULTS/ANTICIPATED RESULTS: Electronic Health Records (EHR) used as decision making tools by both clinicians and patients are restricted by system’s accessibility and interface usability. Patients’ safety monitoring with regard to timely interventions can be greatly enhanced by the development of proper data visualization modalities and statistical modeling capability. DISCUSSION/SIGNIFICANCE OF IMPACT: Using data visualization, summary statistics and prediction models the Patients’ Safety Toolbox will have the algorithms to discover hidden patterns, unexpected trends or associations between the patients’ satisfaction reports and HAI in graphic formats by the immediate survey from patients after services, which allows decision makers to detect gaps and areas of improvement.
P159
PROGNOSTIC SIGNIFICANCE OF FREQUENCY AND MORPHOLOGY OF PREMATURE VENTRICULAR COMPLEXES DURING AMBULATORY HOLTER MONITORING
Ephrem G 1, Levine M2, Friedmann, P3, Schweitzer, P2
1Department of Medicine, Beth Israel Medical Center, New York, NY, USA; 2Division of Cardiovascular Disease, Beth Israel Medical Center, New York, NY, USA; 3Department of Cardiovascular and Thoracic Surgery, Albert Einstein College of Medicine, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Multiform premature ventricular complexes (PVCs) are associated with an adverse prognosis in patients with structural heart disease. Very frequent PVCs are associated with ventricular dysfunction. Our hypothesis is that multiform PVCs confer an adverse prognosis in the general population. METHODS/STUDY POPULATION: We performed a retrospective cohort study of patients ≥ 18 years old referred to our institution for 24‐hour ambulatory Holter monitoring between July 1, 2008 and December 31, 2009. Holters without PVCs or with couplets, triplets, or nonsustained ventricular tachycardia were excluded. Clinical and adverse event (AE) data (“major adverse cardiovascular event” or new/worsening heart failure) were gathered from chart review. Data was analyzed by PVC frequency (rare, occasional, or frequent) and pattern (uniform or multiform). RESULTS/ANTICIPATED RESULTS: 222 patients (43% male, mean age 55 ± 16 years) were evaluated (median follow‐up 2.3 years (IQR 2.0–2.6)). Median frequency was 2 PVC/hr (IQR 1–13). Multiform PVCs were noted in 48%. Patients with multiform PVCs were older, and had a higher prevalence of CAD, CHF and previous MI. During follow‐up, 39 AE were noted. Patients with an AE were younger, had a higher prevalence of HTN, diabetes, CAD, CHF, and previous MI. The multiform group had a higher incidence of AE (28%) compared to the uniform group (8%) (p < 0.001). Increasing PVC frequency was associated with higher incidence of AE (8% vs. 24% vs. 35% respectively). In a Cox regression analysis, the multiform pattern but not frequency predicted AE. DISCUSSION/SIGNIFICANCE OF IMPACT: Multiform PVCs were associated with AE.
P160
RED BLOOD CELL DISTRIBUTION WIDTH AS A PREDICTOR OF READMISSION IN PATIENTS WITH UNSTABLE ANGINA OR NON–ST ELEVATION MYOCARDIAL INFARCTION
Ephrem G 1
1Beth Israel Medical Center, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Three quarters of rehospitalizations (yearly estimated cost 44 billion) may be avoidable. A screening tool for potential cases is necessary to optimize case management. The hypothesis is that an elevated red blood cell distribution width (RDW) is an independent predictor of hospital readmission in patients with unstable angina (UA) or non–ST elevation myocardial infarction (NSTEMI). METHODS/STUDY POPULATION: This was a retrospective observational cohort study of adults admitted in 2007 with UA or NSTEMI and undergoing coronary angiography. Data was gathered by inpatient chart review. Rate of 30‐day nonelective readmission and time to nonelective readmission were recorded till November 1, 2011 and compared by RDW group (95th percentile (16.3%) cutoff). RESULTS/ANTICIPATED RESULTS: Median follow‐up time of the 503 subjects (mean age 65 ± 13 years, 56% male) was 3.8 years (IQR 0.3–4.3). Those readmitted within 30 days were older, had more comorbidities, higher RDW, and were more likely to have had an intervention. Subjects with any readmission were also likely to be African American or Hispanics and Medicaid or Medicare beneficiaries. At 3.8 years subjects with normal RDW (#16.3%) were more likely to be readmission‐free compared to those with high RDW (40.05% versus 27.72%; p = 0.003). In multivariable analyses high RDW was a statistically significant predictor of readmission in general (HR 1.41 (1.08–1.83)) but not of 30‐day rehospitalization (OR 1.28 (0.69–2.37)). DISCUSSION/SIGNIFICANCE OF IMPACT: An elevated RDW was an independent predictor of hospital readmission but not of 30 day‐rehospitalization in patients with UA or NSTEMI. RDW may be considered as an inexpensive, readily available, additional tool for detecting patients requiring more elaborate case management to prevent readmission.
P161
SIDE EFFECTS FROM OUTPATIENT ANALGESICS FOR OLDER EMERGENCY DEPARTMENT PATIENTS WITH MUSCULOSKELETAL PAIN
Platts‐Mills TF 1, MacKuen C1, Cameron IG1, Dickey R1, Hunold K1, Viera AJ1, McLean SA1
1University of North Carolina Chapel Hill, Chapel Hill, NC, USA
OBJECTIVES/SPECIFIC AIMS: Side effects are a frequent concern when prescribing analgesics for older adults with acute musculoskeletal pain. The purpose of this study was to describe the frequency and severity of side effects of analgesics during the first week after discharge among older emergency department (ED) patients with musculoskeletal pain. METHODS/STUDY POPULATION: Patients age 65 years or older with a primary reason for ED visit of musculoskeletal pain and moderate or severe pain (defined by numeric rating scale score ≥4) during the ED evaluation were identified from electronic medical records. Patients were contacted by telephone one week after their ED visit. Moderate or severe side effects were defined by a score >4 on a 0–10 point scale. RESULTS/ANTICIPATED RESULTS: Of 233 eligible patients, 110 were reached by phone. Eighty seven patients (56/87 female, 56/87 white, 51/87 acute injury as cause of pain) completed the research interview. An opioid was prescribed for 61 (70%) and subsequently taken by 53 patients, an NSAID was recommended for 10 (11%) and taken by 9, and acetaminophen was recommended for 10 (11%) and taken by all 10. Six patients did not receive either a prescription or a recommendation for an analgesic. At least one moderate or severe side effect was reported in 36 of the 53 (68%, 95% CI 55–79%) patients who took opioids versus 3 of the 19 (16%, 6–38%, p < .01) patients taking nonopioids. Side effects caused 10 of 53 (16%, 9–28%) patients to discontinue the medication, and 8 of these 10 patients reported moderate or severe pain at one week. DISCUSSION/SIGNIFICANCE OF IMPACT: Opioid side effects are common in older adults discharged after an ED visits for musculoskeletal pain, and frequently result in medication discontinuation.
P162
SURVIVAL AFTER SEGMENTECTOMY AND WEDGE RESECTION FOR STAGE I NON–SMALL CELL LUNG CANCER
Smith CB 1, Wisnivesky J1
1Mount Sinai School of Medicine, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Although lobectomy is considered the standard surgical treatment for stage IA non–small cell lung cancer (NSCLC), wedge resection or segmentectomy are frequently performed to treat patients with poor lung function or high operative risk. The objective of this study was to compare survival among patients with stage IA NSCLC undergoing these procedures. METHODS/STUDY POPULATION: Using the Surveillance, Epidemiology and End Results registry we identified 3,525 cases of stage IA NSCLC that underwent wedge resection or segmentectomy. We used logistic regression to determine propensity scores for patients undergoing segmentectomy based on preoperative characteristics. Overall and lung cancer‐specific survival of patients treated with wedge resection versus segmentectomy was compared after adjusting, stratifying, or matching patients based on their propensity score. Secondary analyses was performed when the cohort was limited to patients with tumors #2 cm, #70, or >70 years of age. RESULTS/ANTICIPATED RESULTS: Overall, 704 (20%) patients underwent segmentectomy. Analyses adjusting for propensity scores showed that segmentectomy was associated with significant improvement in overall (Hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.69–0.93) and lung cancer‐specific survival (HR: 0.72, 95% CI: 0.59–0.88) when compared to wedge resection. Secondary analyses showed that overall (HR: 0.81, 95% CI: 0.67 – 0.99) and lung cancer‐specific survival (HR: 0.75, 95% CI: 0.58 – 0.98) was also better after segmentectomy among patients with tumors #2 cm in size (T1a tumors). For patients #70 years of age, overall and lung cancer–specific survival advantage of segmentectomy persisted. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that segmentectomy should be the preferred technique for limited resection of patients with stage IA NSCLC. These findings should be confirmed in prospective studies.
P163
TENDENCIES TO ADVERSE DRUG EVENTS AMONG THE ELDERLY IN PUERTO RICO
Ramos‐Fernandez MR 1, Jimenez I1
1University of Puerto Rico, San Juan, Puerto Rico
OBJECTIVES/SPECIFIC AIMS: The geriatric population, defined as people 65 years and older, constitutes 13% of the population of United States (US).They are projected to account for approximately 25% of the total population by 2040 and are at particular risk for adverse drug events (ADE). An ADE is any incident in which the use of a medication at any dose, a medical device, or a special nutritional product may have resulted in an adverse outcome in a patient. Poison centers are in a unique position to capture data on medication errors since data is collected on patients seen in healthcare facilities and from people who remain at home. us data is analyzed as a whole but statistics from the elderly population in PR have never been analyzed. Our aim is to identify reasons for ADE, describe the medications involved, and assess the medical outcomes related to ADE. METHODS/STUDY POPULATION: Retrospective medical record review from the Poison Control Center (PCC) in Puerto Rico from January 1, 2001 until December 31, 2011 will be completed. All calls made to the PCC to report adverse drug events in patients over 65 years old will be reviewed. Data will be collected from the electronic database of the PCC of Puerto Rico. Collected data will be analyzed by frequency distributions. RESULTS/ANTICIPATED RESULTS: There is awareness that ADE are growing problem that will worsen as the population ages, but no formal studies have been done to know the burden of ADE on the elderly population of PR. We will attempt to establish tendencies of ADE, types of medications that are most frequently involved in therapeutic errors, and medical outcomes related to these ADEs. DISCUSSION/SIGNIFICANCE OF IMPACT: Research in this population is warranted to establish targeted strategies for decreasing medication errors in older adults. Also, we hope to design and implement patient education policies in Puerto Rico.
P164
THE ROLE OF INTIMATE PARTNER VIOLENCE (IPV) IN PREDICTING ADVERSE NEONATAL OUTCOMES AMONG A SAMPLE OF LOW INCOME, PREDOMINANTLY AFRICAN AMERICAN WOMEN: A MIXED METHODS STUDY
Alhusen J 1, Hayat MJ2, Gross D1
1Johns Hopkins University School of Nursing, Baltimore, MD, USA; 2Rutgers University School of Nursing, Newark, NJ, USA
OBJECTIVES/SPECIFIC AIMS: IPV during pregnancy affects 0.9% to 17% of women and significantly impacts maternal mental health and neonatal health with higher rates of low birth weight and preterm birth. Gaps in the literature remain concerning the relationships between maternal mental health, experiences of IPV, and adverse neonatal outcomes. This mixed methods study is one of the first to examine these associations in a sample of low SES minority women at higher risk for disparate birth outcomes. METHODS/STUDY POPULATION: A longitudinal, mixed methods design was used. 166 women between 24–28 weeks gestation were recruited from three urban obstetric clinics. Using criterion sampling, a subsample of 12 African Americans participated in individual interviews. Chart review was conducted to collect neonatal outcomes. Multiple logistic regression was used to examine relationships between IPV, mental health and neonatal outcomes. RESULTS/ANTICIPATED RESULTS: 19% (n = 32) of participants reported IPV. Infants of women experiencing IPV were six times more likely to experience adverse outcomes (OR 6.08, 95% CI [2.23, 15.88], p < 0.001). Women with worse mental health were 3.7 times more likely to experience an adverse neonatal outcome (OR 3.66, 95% CI [2.34, 5.72], p < 0.001). Participants discussed how IPV influenced their unborn children. “The bruises were one thing but the constant stress made me vomit all the time. I had to get IVs…my poor baby will probably be small.”DISCUSSION/SIGNIFICANCE OF IMPACT: Reported prevalence rates for IPV, depression and PTSD were higher than previously reported. Given the high prevalence of IPV and its strong association in compromising a mother’s mental health, practitioners are urged to incorporate consideration of this into their practice.
P165
TRANSLATION AND EVALUATION OF EVIDENCE‐BASED TELEPHONE COACHING PROGRAM TO IMPROVE HEART FAILURE (HF) SELF‐MANAGEMENT
Piamjariyakul U 1, Smith CE1, Russell C2
1University of Kansas School of Nursing, Kansas City, KS, USA; 2Mid America Cardiology, University of Kansas Medical Center, Kansas City, KS, USA
OBJECTIVES/SPECIFIC AIMS: This project describes critical steps in translating an evidence‐based nursing intervention program into practice. Data and national clinical guidelines were used to develop caregiver telephone educational program. Coaching and teach‐back methods were used. METHODS/STUDY POPULATION: The project was completed in 3 interrelated phases: (1) a qualitative research study described key factors that patients (n = 24), healthcare professionals (n = 17), and family caregivers (n = 17) perceived as most helpful in HF self‐management; (2) educational materials and strategies for caregivers in managing the complexities of HF were integrated; (3) pilot testing the feasibility, acceptability, and cost of the program, using 5 nurses’ focus group data and 12 caregivers’ program evaluation interviews. The program tested was nurse‐led, conducted in 4 telephone coaching sessions with family caregivers of patients with HF. The program included ACC/AHA clinical guidelines content and AHA handouts and a home caregiving text that described emergencies, medication, diet and actively engaging with healthcare professionals for dealing with HF at home. RESULTS/ANTICIPATED RESULTS: Nurse and caregivers rated the program as convenient, acceptable to transmit over the telephone, and extremely helpful in HF home management. Coaching and teach‐back was rated as powerful techniques to deliver the program. Total cost of the program per caregiver was ≥350. There were fewer HF readmissions for 6 months following the program. DISCUSSION/SIGNIFICANCE OF IMPACT: The program improved daily HF self‐management skills and revealed a promising HF rehospitalization reduction. Effectiveness and efficacy of the intervention program should be tested in a large population with a randomized longitudinal design.
P166
VALIDATION OF THE SYSTEMIC LUPUS ERYTHEMATOSUS RESPONDER INDEX FOR USE IN JUVENILE SYSTEMIIC LUPUS ERYTHEMATOSUS
Mina R 1, Brunner H1
1University of Cincinnati/Cincinnati Children’s Hospital, Cincinnati, OH, USA
OBJECTIVES/SPECIFIC AIMS: Composite indices are useful to assess improvement in heterogenous diseaseas such as juvenile systemic lupus erythematosus (jSLE). The SLE Responder Index (SRI) is a composite index that considers changes of the SELENA‐SLEDAI, BILAG index, and a 3‐cm visual analog scale of physician‐rated disease activity to determine patient improvement. The aim of this study is to determine the concurrent validity of the SLE Responder Index (SRI) in assessing improvement in jSLE. METHODS/STUDY POPULATION: Using prospectively collected data from 1,437 unique follow‐up visits of 308 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician‐rated major improvement (MD‐change), patient/parent‐rated major improvement of well‐being (Patient‐change), and decrease of prescribed systemic corticosteroids (Steroid‐change). Modifications of the SRI that considered different thresholds for the SELENA‐SLEDAI, BILAG, and 10‐cm PGA were explored, and agreement with the ACR/PRINTO Provisional Criteria for Improvement of jSLE (PCI) was examined. RESULTS/ANTICIPATED RESULTS: The sensitivity/specificity in capturing major improvement by the MD‐change was 70%/85% for the SRI and 83%/81% for the PCI, respectively. There was moderate agreement between the SRI and PCI (K = 0.49) for capturing MD‐change. Modified versions of the SRI improved its accuracy. All improvement criteria tested had lower sensitivity when considering Patient‐change and Steroid‐change as external standards. DISCUSSION/SIGNIFICANCE OF IMPACT: The SRI and its modified versions based on meaningful changes in jSLE are highly specific for capturing jSLE improvement. Modifications of the SRI for jSLE can increase its sensitivity but the PCI remains more sensitive for identifying clinically relevant improvement of jSLE, irrespective of the external standard considered.
P167
WEIGHT LOSS EXPERIENCES OF AFRICAN AMERICAN WOMEN WITH PREDIABETES
Hays LM 1, Rawl SM1, Ackermann RT2
1Indiana University School of Nursing, Indianapolis, IN, USA; 2Northwestern University Feinberg School of Medicine, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Modest weight loss achieved through diet and physical activity has been shown to reduce the risk of diabetes. African American (AA) women are disproportionately affected by diabetes and lose less weight than Caucasians receiving similar interventions. Effective interventions are needed to promote lifestyle change among AA women. Focus groups were conducted to explore weight loss experiences of AA women with prediabetes to determine the types of support needed to achieve and maintain a healthy weight. METHODS/STUDY POPULATION: Six focus groups were conducted with 29 low‐income, overweight AA women who were participating in a community‐based diabetes prevention program. As part of the larger study, women were randomly assigned to brief advice plus lifestyle intervention or brief advice along (control). AA women participated in focus groups based on their intervention status (control vs. intervention) and weight loss at 6 months (met goal vs. did not meet goal). RESULTS/ANTICIPATED RESULTS: Focus group participants had a mean age of 52.3 years and an average BMI of 35. Preliminary content analyses of data revealed that, prior to study participation, women who met weight loss goals at 6 months had experienced a distressing weight‐related event that triggered small steps toward behavior change. Women who modified lifestyle behaviors described relatively greater changes in confidence and self‐awareness. Consistent with previous research with Caucasian women, successful participants experienced a shift in identity that strengthened the maintenance of behavioral changes. DISCUSSION/SIGNIFICANCE OF IMPACT: Identified themes will be used to inform both a conceptual model and a community‐based peer support intervention to promote lifestyle change among AA women at risk for developing type 2 diabetes.
RESOURCES
P168
CLASSIFICATION OF CT IMAGING REPORTS USING NATURAL LANGUAGE PROCESSING AND DATA MINING TECHNIQUES
Yadav K 1, Sarioglu E1, Smith MA1, Choi H1
1The George Washington University, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Free text electronic clinical data, which is of particular interest for comparative effectiveness research (CER), is often inaccessible without laborious manual review and coding for outcomes of interest. With limited prior success of text recognition software using natural language processing (NLP) for this task, our objective is to demonstrate improved free non‐standard text classification performance by combining NLP and modern data mining techniques. METHODS/STUDY POPULATION: We performed secondary analysis of de‐identified data from a previous diagnostic CER study on blunt facial trauma victims. That prospective cohort study collected 3,710 consecutive CT imaging reports over 26 months at two urban academic EDs, with the outcome of acute orbital fracture manually abstracted (positive in 460 reports [12.4%]). Reports were randomly divided into equal training and testing data sets. The Medical Language Extraction and Encoding NLP system codes for certainty, temporal status, and Unified Medical Language System diagnostic codes. Filtered findings are combined with their associated outcomes as input to the open‐source data mining tool WEKA 3.7.5 for classification. Data undergoes conversion to a word vector representation and decision tree classification with 10‐fold stratified cross‐validation is applied. Model performance is evaluated using the testing data set. RESULTS/ANTICIPATED RESULTS: Performance of our predictive model using data mining alone are better than most prior NLP studies, and the combined use of NLP and data mining shows further improvement. DISCUSSION/SIGNIFICANCE OF IMPACT: Combining NLP and data mining shows promise in coding free non‐standard text electronic clinical data to support large‐scale CER. Future work will refine NLP tools and investigate different classification algorithms using other data sets to demonstrate accurate and generalizable results.
P169
DEVELOPING FUTURE CLINICIAN SCIENTISTS AND SUPPORTING THE RESEARCH INFRASTRUCTURE OF AN ACADEMIC MEDICAL CENTER
Holsti M 1, Adelgais KM2, Willis L1, Jacobsen K1, Clark EB1, Byington CL1
1University of Utah, Salt Lake City, UT, USA; 2University of Colorado, Denver, CO, USA
OBJECTIVES/SPECIFIC AIMS: Describe an innovative undergraduate course that supports clinical research in an AMC. METHODS/STUDY POPULATION: Clinical Research Methods and Practice, an undergraduate course, offers students the opportunity to participate in clinical research through didactic and practical experiences. The students in turn support clinician scientists’ conduct of clinical studies in an AMC. Clinician scientists developed the curriculum with input from medical ethicists, and the Institutional Review Board. Students receive didactic training on the principles of clinical research and devote 6 hours/week identifying and enrolling patients for clinical studies. Clinician scientists receive research support and participate in didactic/mentoring sessions for students. RESULTS/ANTICIPATED RESULTS: Since 2009, 128 students have participated over 7 semesters. Students assisted in 21 clinical studies located in various areas of an AMC. Many of the clinician scientists have met their enrollment goals and several have been top‐enrollers in multicenter clinical trials. DISCUSSION/SIGNIFICANCE OF IMPACT: The Clinical Research Methods and Practice class addresses barriers to clinical research in AMC. This may be a model for institutions committed to mentorship of students early in their career and to developing infrastructures for clinical research.
P170
EXPERIENCE DEVELOPING A COMMUNITY PHARMACY PRACTICE‐BASED RESEARCH NETWORK
Snyder ME 1, Frail CK1, Seel LV1, Hultgren KE1
1Purdue University College of Pharmacy, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: To describe the evidence‐based approach used in the establishment of the Medication Safety Research Network of Indiana (Rx‐SafeNet). METHODS/STUDY POPULATION: The Medication Safety Research Network of Indiana (Rx‐SafeNet) is a statewide practice‐based research network (PBRN) of community pharmacies in Indiana administered by the Purdue University College of Pharmacy. Rx‐SafeNet was established in 2010 and is registered as an affiliate practice‐based research network with the Agency for Healthcare Research and Quality PBRN Resource Center. RESULTS/ANTICIPATED RESULTS: Prior to launching Rx‐SafeNet, network leadership surveyed community pharmacy employees statewide regarding their experience and opinions related to research and network participation and met with University and community pharmacy stakeholders to gain support. Since its formation, a formal network governance structure has been established, consisting of an executive committee, advisory board, and project review team. Network policies and procedures have also been established. Numerous outreach activities have been conducted state‐wide to encourage pharmacy participation. To date, 22 community pharmacies in Indiana have joined the PBRN and two project ideas have formally been submitted to the network’s executive committee. Currently, Rx‐SafeNet is preparing to initiate data collection for the first project to be conducted in collaboration with the network. DISCUSSION/SIGNIFICANCE OF IMPACT: Rx‐SafeNet is the only PBRN in Indiana comprised solely of community pharmacies. For researchers, the network may provide a unique avenue for collaborative exploration of research questions pertaining to pharmacy practice and safe medication use.
P171
MEDICATION SAFETY AND THE ELECTRONIC HEALTH INFORMATION INFRASTRUCTURE
Adam T 1
1University of Minnesota, Minneapolis, MN, USA
OBJECTIVES/SPECIFIC AIMS: The electronic health information infrastructure expansion is creating medication safety research and patient care opportunities. Medication safety depends on high quality electronic clinical data which aggregates problem list, medication, laboratory and clinical notes. The Sentinel Initiative has recognized the importance of electronic clinical data to facilitate drug surveillance but lacks core medical record data elements. This project focuses on the identification and quality assessment of key data elements in the growing electronic medical record infrastructure with the goal of creating a data science driven approach for the next generation of medication safety. METHODS/STUDY POPULATION: A Minimal Clinical Data Set (MCDS) methodology framework was used including structured clinical evidence assessment, practitioner evaluation, and incorporation of translational science data management resources. The MCDS identifies the elements of the existing drug safety data and can incorporate new electronic health data infrastructure data elements. A gap analysis identified the data science techniques needed to facilitate the evaluation of medication events for epidemiological evaluation and medication adverse event surveillance. RESULTS/ANTICIPATED RESULTS: Several clinical data resources were identified in existing research databases, clinical data warehouses, administrative claims and electronic medical records with relevance for drug safety evaluation. Data quality results have identified a lack of data standards, particularly for medication identification, and nonstandard free text both in research databases and clinical records. DISCUSSION/SIGNIFICANCE OF IMPACT: The lack of standardized drug and problem list data is a major challenge for research and event monitoring. Enhanced standardization of data and data harmonization are needed to facilitate event identification and data aggregation.
P172
MEDSIMS: ENHANCING MEDICAL EDUCATION AND CLINICAL CARE THROUGH TRANSLATIONAL SCIENCES APPROACH
Libin A 1,2, Millo Y1
1SiTEL of MedStar Health, Washington, DC, USA; 2MedStar Health Research Institute and GHUCCTS/CTSA, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Medical Simulations (MedSims) are developed for the purposes of educational training in allied health professionals ranging from medical student and residents to clincians refining the best practices technologies. METHODS/STUDY POPULATION: The simulation and education research and practice efforts at SiTEL, a training laboratory that is part of MedStar Health and affiliated GHUCCTS/CTSA infrastructure, are focused on developing high fidelity virtual relaity and medical simulation applications such as electronic fetal monitoring (EFM) and SiTEL Bronchoscopy simulation (S‐BRONCH). RESULTS/ANTICIPATED RESULTS: Newly developed Embedded Assessment Algorithm (EMA) to be implemented across MedSims and other online educational modules, focuses on developing two types of scoring systems: application specific, or just‐in‐time, to provide scores immediately after the training (like in the S‐BRONCH and EFM), and postanalysis data that would be transferred to the Common Elements System (COMMONS) as both raw and indexed data to be used for pilot data and cross‐application analysis regardless of where exactly across MedStar and CTSA participating organizations the pilot study was conducted and research data were generated. DISCUSSION/SIGNIFICANCE OF IMPACT: Emerging framework makes it possible for the system‐wide core element (SiTEL), as a designated simulation and education data hub, to communicate with CTSA/GHUCCTS investigators through statistical and knowledge repository cores including context specific knowledge at points of care and health service delivery teams.
P173
MURDOCK STUDY COMMUNITY REGISTRY AND BIOREPOSITORY: DESIGN AND RATIONALE
Bhattacharya S 1, Dunham AA1, Cornish MA1, Tenenbaum J1, Ginsburg GS1, Udayakumar K1, Pieper CF1, Nahm M1, McHutchison JG1, Christian V1, Miranda M1, Dolor RJ1, Califf RM1, Newby L1
1Duke University, Durham, NC, USA
OBJECTIVES/SPECIFIC AIMS: Refinements of disease classification are possible using ‐omic technologies, electronic health records, and epidemiological methods. The MURDOCK Study Community Registry and Biorepository is part of a study designed to address this issue. METHODS/STUDY POPULATION: Persons 18 years or older, residing in Cabarrus County, NC are recruited by open enrollment (35,000 volunteers; ongoing) and a population random sample (15,000 respondents; planned). At baseline, participants complete a questionnaire (general demographics, health‐related quality of life, brief activity survey and diet). Vital signs and waist circumference are obtained, and blood and urine samples are stored for future research. Participants consent to yearly follow‐up, geospatial mapping and access to electronic health records. RESULTS/ANTICIPATED RESULTS: Of the first 6000 of participants, median age is 54 (42, 65) years and 64% are female (vs. 37 years and 51% female in County estimates). The racial composition is 78% Caucasian, 12% African American and 5% Hispanic, reflecting County estimates. Median BMI is 28 (24, 33), indicating nearly 50% were overweight/obese, though 27% self‐reported obesity. On self‐report, 16% had diabetes, 38% hypertension, 40% hyperlipidemia, 5% coronary disease, 4% COPD, 23% depression and 10% were current smokers. Six of 7 factors outlined by the American Heart Association to improve cardiovascular health were collected; a median of 4 were met. DISCUSSION/SIGNIFICANCE OF IMPACT: The MURDOCK Study Community Registry and Biorepository is creating an enduring and powerful scientific resource with a combination of well‐annotated, banked biospecimens matched with demographic and clinical information, and a large sample size available to enable molecular exploration of chronic diseases.
P174
PREDICTORS OF A SAFE ATTENDING PHYSICIAN WORKLOAD: RESULTS FROM A NATIONAL HOSPITALIST SURVEY
Michtalik HJ 1, Pronovost P1, Driscoll B2, Paskavitz M2, Brotman D1
1Johns Hopkins University, Baltimore, MD, USA; 2Quantia Communications, Waltham, MA, USA
OBJECTIVES/SPECIFIC AIMS: We examined the relationship between workload and patient safety via a survey of an online community of hospitalists. This analysis examines the predictors of reporting an “unsafe” workload. METHODS/STUDY POPULATION: We surveyed 890 Hospitalists enrolled in QuantiaMD.com, an online physician community. The survey queried physician and practice characteristics, workload, and frequency of an unsafe census. “Safe” was defined as “with minimal potential for error or harm.” We categorized physicians into those reporting unsafe patient workload less than once a month versus at least monthly. We performed logistic regression to determine which characteristics were associated with report of an unsafe census. RESULTS/ANTICIPATED RESULTS: Of the 890 physicians contacted, 506 (57%) responded. Physicians had an average age of 38 years (SD: ±8) and were in practice for a median of 6 years [IQR: 3, 10]. Physicians practiced as part of a community (54%) or teaching (28%) hospital. Forty percent of physicians reported that their census exceeded safe levels at least monthly. Higher frequency of an unsafe census was associated with higher percentages of clinical (p = 0.004) and inpatient (p < 0.001) responsibilities and less assistance (p = 0.03). Lower frequency was associated with more years in practice (p = 0.02) and assistance by housestaff (p = 0.002), and with having any census control system (p = 0.007). There was no association between unsafe census and age, area, organization type, or compensation. DISCUSSION/SIGNIFICANCE OF IMPACT: Less experience and assistance, more responsibilities, and no systems for census control were strongly associated with unsafe workload. Providing hospitalists with greater assistance and systems to deal with census fluctuations may improve the safety and quality of patient care.
P175
PROJECT DEVELOPMENT TEAMS: A NOVEL PROCEDURE FOR FACILITATING TRANSLATIONAL RESEARCH
Sajdyk T 1, Hunt J1, Shekhar A1, Denne S1
1Indiana Clinical and Translational Sciences Institute, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: The pathway from initial research hypothesis to first clinical trial is fraught with potholes. Some of these holes are much larger than others and are referred to as “Valleys of Death.” The Indiana Clinical and Translational Sciences Institute (ICTSI) established several programs to address these weaknesses. One key program is the Project Development Teams (PDTs). The PDTs are committees of multidisciplinary researchers who assist investigators in developing ideas/hypotheses into well‐designed translational research projects. The teams serve as “one stop shops” by providing investigators access to protocol development; pilot funding; biostatistics; IRB/regulatory and nursing support; bioethics; subject recruitment; electronic medical records data mining; Intellectual Property support; Community Health Engagement; facilitation of collaboration with other investigators and access to over 60 Core Resources on the IUPUI, IU, Purdue and Notre Dame campuses, all in one meeting. There are currently seven PDTs within the Indiana CTSI: Preclinical Sciences, Clinical Sciences, Pediatric Sciences, Imaging Sciences, Behavior and Population Sciences, Purdue and Notre Dame. These teams represent all stages of research from basic research (T1) to community engagement (T4) and, after three years of working with the researchers, the impacts on the “Valleys of Death” are emerging. METHODS/STUDY POPULATION: NA RESULTS/ANTICIPATED RESULTS: NA DISCUSSION/SIGNIFICANCE OF IMPACT: NA
P176
VIRTUAL CLINICAL RESEARCH CENTER/QUESTIONARIUM (VCRC/Q): AN INQUIRY‐BASED TRANSLATIONAL SCIENCE “TRAINING GRID”
Witte MH 1, Crown P1, Bernas M1, Daley S1, Hall J2, Garcia F3
1UA – Surgery, Tucson, AZ, USA; 2UA – Biomed Commun, Tucson, AZ, USA; 3UA – Ob‐Gyn, Tucson, AZ, USA
OBJECTIVES/SPECIFIC AIMS: Develop a customizable, scalable, interactive virtual CTSA/CRC platform and accompanying curriculum to explore both expanding Unknowns/questions (“ignoramics”) and exploding Knowns (informatics) in translational science to showcase and enhance research training, networking, subject recruitment, and community outreach. METHODS/STUDY POPULATION: Progressive iterations of the VCRC/Q virtual space were designed and tested for user friendliness, functionality, and efficacy including to transfer the face‐to‐face UAz Curriculum on Medical Ignorance (CMI) to a more versatile and transportable online format. NIH‐funded CMI involved ~800 medical student and 500 disadvantaged high school student researchers over 25 years and thousands more at multiple educational levels in worldwide conferences and workshops. RESULTS/ANTICIPATED RESULTS: Visitors navigated VCRC/Q through a Resource Library offering translational research videos by experts and students, a Questionarium with exercises in asking research questions, a Multimedia Presentation Space, and Tool Boxes of basic, clinical, and population research technologies. Links were available for Think Tank conferences (including one on Curiosity and Questioning held in Second Life on 12/9/11) and remote outreach. CMI assessment showed that students gained awareness of the unknown/uncertainty in medical science and improved questioning skills while also experiencing long‐term impact on medical/research career choices. CMI components were transferable to the online format. DISCUSSION/SIGNIFICANCE OF IMPACT: VCRC/Q promises to be a user‐friendly customizable, scalable “grid” for promoting clinical/translational research and training and questioning. It is also a useful, adaptable vehicle for offering and assessing CMI or other online translational/clinical science curricula.
P177
WHY CLINICAL STUDIES ARE OFTEN UNSUCCESSFUL IN MEETING RECRUITMENT GOALS: PERSPECTIVES FROM RESEARCH PERSONNEL
Wilets I 1, Ortiz JM1, Richardson LD1
1Mount Sinai School of Medicine, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: This research has two specific aims: (1) to identify factors impeding successful study recruitment, as indicated by investigators, research coordinators and recruitment personnel in academic medicine; and (2) to identify variables facilitating enrollment in clinical trials. METHODS/STUDY POPULATION: The study involves 25 research professionals across disciplines at the Mount Sinai School of Medicine in New York. Eight clinical areas are represented within this collaboration: Medicine, Emergency Medicine, Health Policy, Oncology, Cardiology, Pediatrics, Anesthesiology and Psychiatry. These areas were selected in consideration of their high patient volume and significant research activity. A 30‐minute structured interview was administered to research professionals within these disciplines. The interview consisted of Likert‐scale items as well as open‐ended questions designed to pinpoint variables impacting study recruitment. RESULTS/ANTICIPATED RESULTS: Twenty‐five research professionals participated in the interview. Study‐related recruitment challenges were discussed including stringent inclusion criteria, randomization, placebos, and invasive study procedures. Institutional barriers, such as cumbersome IRB or Grants and Contracts processes, were also addressed. DISCUSSION/SIGNIFICANCE OF IMPACT: The findings from this inquiry will provide an in‐depth understanding of the various challenges related to subject enrollment in clinical and translational research. These data will be analyzed on an aggregate level, as well as between disciplines, to identify barriers and facilitators linked to specific types of research and target populations. We will disseminate our findings among CTSAs to inform the development of studies more likely to meet planned recruitment goals.
TRANSLATIONAL BASIC‐TO‐CLINICAL
P178
DIFERULOYLMETHANE (CURCUMIN) IS RENO‐PROTECTIVE IN DIABETIC NEPHROPATHY BY ANTIINFLAMMATORY AND ANTIOXIDANT EFFECTS
Park S 1, Sohal D1, Pandey S1, Prabhakar S1
1Texas Tech University Health Sciences Center, Lubbock, TX, USA
OBJECTIVES/SPECIFIC AIMS: The current treatment options for diabetic nephropathy (DN) are not optimal. Recent studies suggest that curcumin (CUR) is effective in experimental cancer and cardiac disease although precise mechanisms are unclear. The aims of our study are to evaluate the CUR effects in experimental DN and seek mechanisms underlying such effects. METHODS/STUDY POPULATION: ZSF1 rat, a model for DN was used to test the effects of CUR. Rats were given plain water or CUR at 2 mg/ml or losartan (LOS) at 25 mg/ L from 8 wks to 26 wks of age. Body weights, water intake were monitored wkly. Blood and urine samples were collected at 8 and 26 wks. The rats were euthanized at 26 wks, kidneys harvested and homogenates examined for the expression of TGF‐β, TNF‐α, IL‐6. The urine samples were analyzed for creatinine clearance (Ccr), protein excretion rates (PER), TNF‐α, 8‐OHdG and CRP levels. RESULTS/ANTICIPATED RESULTS: CUR was well tolerated by ZSF1 rats. Both LOS and CUR lowered PER versus control [615 ± 43* and 780 ± 55* vs. 1225 ± 87 mg/G cr respectively]. Ccr increased in both LOS and CUR versus control [4.7 ± 0.7* and 4.5 ± 0.7* vs. 3.6 ± 0.4 L/Kg BW/d]. 8‐OHdG, an indicator of mitochondrial oxidative stress was lowered by CUR more than LOS versus controls [2125 ± 133* and 3608 ± 155 vs. 5345 ± 237 ng/KG/BW]. TNF‐α levels in the urine were lowered by CUR and LOS versus control [256.3 and 227 vs. 732.3 pg/ml]. Urinary CRP levels were also decreased by both agents [0.53 and 0.43 vs. 5.03 mg/dl]. Renal expression of TGF‐β, TNF‐α, IL‐6 were reduced by both agents compared to controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Our observations indicated that CUR was comparable to angiontensin blockade with LOS in its protective effects in the diabetic kidney. The mechanisms underlying such reno‐protection may involve pathways of inflammation, mitochondrial oxidative stress and fibrosis in the kidney.
P179
NEUROIMAGING THE REGULATION OF CRAVING IN COCAINE DEPENDENCE
Kober H 1, DeLeone C1, Marino D1, Carroll K1
1yale university, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Previous research has demonstrated that drug craving predicts drug use, and therefore, cognitive behavioral therapy (CBT) (one of the most effective therapies available) focuses on teaching regulation of craving. However, it is a commonly held view that substance‐dependent individuals have a brain‐based deficit in inhibitory control and regulation. We have previously shown that cigarette smokers can regulate their craving for cigarettes using a cognitive strategies, and that a set of prefrontal regions is implicated in this ability. In this study, we sought to investigate whether cocaine‐dependent (CD) individuals can regulate their craving using a cognitive strategy from CBT, and to identify the neural correlates of this ability. METHODS/STUDY POPULATION: Cocaine dependent (CD) individuals completed the Regulation of Craving (ROC) task while undergoing functional magnetic resonance imaging. Participants were presented with pictures of food and cocaine, and on each trial instructed to think about either (1) the immediate sensory experience of consuming the item (i.e., the “good” things about it; “NOW”) or (2) the long‐term negative consequences of consuming the item (i.e., how it will affect them negatively later on; “LATER”). RESULTS/ANTICIPATED RESULTS: Self‐reports suggested that these individuals were able to reduce craving for cocaine on LATER compared to NOW trials. Furthermore, this resulted in deactivation in a distributed network of subcortical/limbic regions associated with craving, including the ventral striatum and amygdala, and increased prefrontal activity in regions previously associated with cognitive control and regulation of emotion, including dorsolateral prefrontal cortex (dlPFC). DISCUSSION/SIGNIFICANCE OF IMPACT: Results are consistent with an association between dlPFC recruitment and “regulation of craving” skills learned during CBT.
P180
A GENOME‐WIDE ASSOCIATION STUDY IN 4,000 LATINO CHILDREN IDENTIFIES SEVERAL CANDIDATE REGIONS FOR ASTHMA AND REPLICATES THE ASSOCIATION IN 17q21
Galanter JM 1, Gignoux CR1, Drake K1, Sen S1, Roth LA1, Huntsmann S1, Eng C1, Nguyen E1, Rodriguez‐Santana J2, Kumar R3, Rodriguez Cintrón W4, Avila P5, Farber HJ6, Serebrisky D7, Borrell L8, Buenaventura E9, Burchard EG1
1University of California, San Francisco, San Francisco, CA, USA; 2Centro de Neumologia Pediatrica, San Juan, Puerto Rico; 3Children’s Memorial Hospital, Chicago, IL, USA; 4VA Caribbean Medical Center, San Juan, Puerto Rico; 5Northwestern University, Chicago, IL, USA; 6Baylor College of Medicine, Houston, TX, USA; 7Albert Einstein College of Medicine, New York, NY, USA; 8City University New York, New York, NY, USA; 9Kaiser Permanent, Vallejo, CA, USA
OBJECTIVES/SPECIFIC AIMS: A recent meta‐analysis by Torgerson et al. suggested that there may be ethnic specific variants in asthma. Herein we report the results of a GWAS in a large, well‐characterized population of Latinos from multiple ethnicities. METHODS/STUDY POPULATION: Three thousand nine hundred eighty‐one Latino children were recruited in Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area as part of the Gene‐Environment and Ancestry in Latino Asthmatics (GALA II) study. Subjects were genotyped with a custom Affymetrix Axiom genome‐wide array containing 817,810 SNPs. We performed a genome‐wide association for asthma using logistic regression. RESULTS/ANTICIPATED RESULTS: We confirmed the association between SNPs in the 17q21 region and asthma (most significant SNP rs907092: OR 0.68, 95% CI: 0.61 – 0.75, p = 1.5 × 10–13). Four additional regions suggested an association: rs3804327 on chromosome 6 (OR 1.37, 95% CI: 1.21 – 1.56, p = 1.4 × 10–6), rs7086533 on chromosome 10 (OR 1.43, 95% CI: 1.24 – 1.67, p = 1.6 × 10–6), KG_14_33639557 on chromosome 14 (OR 0.37, 95% CI 0.24 – 0.56, p = 3.8 × 10–6). DISCUSSION/SIGNIFICANCE OF IMPACT: We confirmed the association between the 17q21 region and asthma, and found several regions suggestive of associationl. These findings will need to be replicated in additional populations.
P181
A MUTATION IN THE HUMAN UNCOORDINATED 119 GENE IMPAIRS TCR SIGNALING AND IS ASSOCIATED WITH CD4 LYMPHOPENIA
Gorska MM 1,2, Alam R1,2
1National Jewish Health, Denver, CO, USA; 2University of Colorado Denver, Aurora, CO, USA
OBJECTIVES/SPECIFIC AIMS: Idiopathic CD4 lymphopenia (ICL) is an immunodeficiency syndrome of unclear etiology. Lck is a major T cell receptor (TCR)‐linked kinase. Lck activity was reported to be reduced in ICL. We hypothesized that ICL was associated with a defect of the recently described Lck activator—Uncoordinated 119 (Unc119). METHODS/STUDY POPULATION: CD4 T cells from three ICL patients were analyzed for Lck activity (immune‐complex kinase assay), the Unc119 protein level (western blotting) and sequence of the Unc119 cDNA and exons. The identified mutant cDNA was expressed in normal CD4 T cells by retroviral infection and the cells were examined for Lck activation and proliferation. RESULTS/ANTICIPATED RESULTS: All ICL patients demonstrated reduced Lck activity. The level of the Unc119 protein and its molecular weight were normal. One patient had heterozygous missense mutation (codon 22 GGC→GTC; V22G) in the Unc119 cDNA and gene. The patient was a 32‐year‐old female with <300 CD4 T cells/μl, recurrent sinusitis/otitis media, recurrent shingles, fungal skin and nail infection, oral herpetic lesions and BOOP following two episodes of bacterial pneumonia. The reduced Lck activity was accompanied by decreased T cell proliferation. Transduction of the mutant but not wild type Unc119 into normal T cells reproduced signaling and proliferation defects. The mutation disrupted the Unc119‐Lck interaction, which is essential for Lck activation. The mutant also caused mislocalization of Lck to endosomes. The mutation was not present in two other ICL patients, patients with secondary CD4 lymphopenia or 60 healthy subjects. DISCUSSION/SIGNIFICANCE OF IMPACT: We identified a novel genetic defect—a dominant negative missense mutation in the Unc119 gene in ICL.
P182
A NOVEL REGULATOR OF BONE HEALING
Kacena MA 1, Milikan PD1, Wessel AR1, Bethel M1, Cheng Y1, Burr DB1, Fuchs RK2, Chu TG3
1Indiana University School of Medicine, Indianapolis, IN, USA; 2Indiana University School of Health and Rehabilitation Sciences, Indianapolis, IN, USA; 3Indiana University School of Dentistry, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: Despite advances in surgical techniques and implants, orthopedic surgeons are still challenged to obtain fracture union, spine fusion, or bridging of segmental defects. Critical‐size defects in bones do not heal spontaneously and usually require the use of grafts. Unfortunately, the use of grafts poses several limitations including harvest site morbidity with autografts and concerns about disease transmission with allografts. To improve bone formation, many clinicians now use bone morphogenetic proteins (BMP), particularly in spinal fusion, fracture healing, and in critical‐size defect regeneration. However, multiple side effects of BMP treatment have been uncovered including increased incidence of cancer, greater risks in radiculities, ectopic bone formation, and osteolysis. With the high cost of BMP and concerns for side effects, there is great interest in investigating other alternatives that allow for safe and effective bone regeneration. METHODS/STUDY POPULATION: Here we examined the ability of thrombopoietin (TPO), the main megakaryocyte growth factor, to heal critical‐size femoral defects in both rat and mouse models. RESULTS/ANTICIPATED RESULTS: Compared to BMP‐2, TPO simultaneously stimulates osteoblastogenesis and osteoclastogenesis and allowed a faster restoration of the original bone contour. DISCUSSION/SIGNIFICANCE OF IMPACT: The therapeutic potential of TPO is high and may be utilized in the near future as it has already been tested in humans and could be moved into phase 2 studies quickly.
P183
A NOVEL SUBSET OF CD4 T CELLS THAT HELPS HUMAN MEMORY B CELLS
Kim ST 1,2, Choi J1, Lainez B1, Craft JE1,2
1Section of Rheumatology, Yale Univ, New Haven, CT, USA; 2Dept of Immunobiology, Yale Univ, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Follicular helper T (Tfh) cells help B cells in germinal centers (GCs) of secondary lymphoid organs (SLOs) following antigen challenge, with formation of memory B and plasma cells. When memory B cells are recalled, they regenerate GCs with robust maturation. Memory B cells function better with T cell help; however, the nature of the T cells providing such help is unclear, with the role of Tfh cells unknown. Our goal is to identify and characterize memory B helper T cells in SLOs. METHODS/STUDY POPULATION: Tonsils from tonsillectomies (2–18 y; Yale New Haven Hospital; IRB waived) were used for flow cytometry, qPCR, cytokines and confocal microscopy. Syngeneic CD4 T and B cells were cocultured for immunoglobulin (Ig), as readout for T cell help. RESULTS/ANTICIPATED RESULTS: Tfh cells, defined as CXCR5hiPD1hi, can be divided based on expression of P‐selectin glycoprotein ligand‐1 (PSGL‐1), a surface protein dictating CD4 T cell location in SLOs. PSGL‐1loCXCR5hiPD1hi Tfh cells reside in B cell follicles, with PSGL‐1hiCXCR5hiPD1hi (called triple hi) cells extrafolliclular. Consistent with their location, triple hi cells expressed more of the T cell homing maker (CCR7) with less of the follicular homing marker CXCR5 than Tfh cells. Both subsets produced IL‐21; however, Tfh cells produced more IL‐4 while triple hi cells exclusively made IL‐10. Memory B cells produced Ig better when cultured with triple hi cells than Th cells, with help reliant on CD40L, IL‐21, and IL‐10. Triple hi cells and memory B cells are in contact at the T‐B border as found by flow cytometry and microscopy. DISCUSSION/SIGNIFICANCE OF IMPACT: Triple hi cells help memory B cells at the T‐B border in a contact‐ and cytokine‐dependent manner. Their characterization will pave ways for understanding development and maintenance of human immune memory responses.
P184
ABBREVIATED DYSTROPHINS RESTORE THE PASSIVE PROPERTIES OF THE EXTENSOR DIGITORUM LONGUS MUSCLE IN DYSTROPHIN‐NULL MICE
Hakim C 1, Duan D1
1University of Missouri, Columbia, MO, USA
OBJECTIVES/SPECIFIC AIMS: Muscle and joint stiffness is a major clinical feature in Duchenne muscular dystrophy (DMD) patients. DMD is one of the most common lethal inherited muscle wasting diseases in childhood and it is caused by the loss of the dystrophin protein. We recently showed that the extensor digitorum longus (EDL) muscle of mdx mice (a DMD mouse model) exhibits disease‐associated muscle stiffness. Abbreviated forms of the dystrophin gene (micro and mini‐dystrophin) are the leading candidate genes for DMD gene therapy. Unfortunately, it has never been clear whether these abbreviated genes can mitigate muscle stiffness. METHODS/STUDY POPULATION: To address this critical question, we examined the passive properties (elastic and viscous properties) of the EDL muscle in transgenic mdx mice that express either a representative minigene (DH2‐R15) or one of the two most promising microgenes (DR2–15/DR18–23/DC or DR4–23/DC). The passive properties were measured in 6, 14, and 20‐month‐old transgenic mice and the results were compared to those of age and sex‐matched normal and mdx mice. RESULTS/ANTICIPATED RESULTS: Surprisingly, despite significant truncation of the gene, the elastic and viscous properties were completely normalized in every strain of transgenic mice we examined. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results demonstrate for the first time that abbreviated dystrophin genes can effectively treat muscle stiffness in a DMD model. Our findings provide important support to further develop mini‐/micro‐dystrophin gene therapy.
P185
ALTERNATIVE LENGTHENING OF TELOMERES (ALT) IN EMBRYONIC DEVELOPMENT AND CANCER
Kalmbach K 1, Okuka M2, Liu L1, Keefe D1
1New York University, New York, NY, USA; 2University of South Florida, College of Medicine, Tampa, FL, USA
OBJECTIVES/SPECIFIC AIMS: Telomeres consist of repeat‐enriched DNA and specialized proteins that comprise the chromosomal cap. Oxidative stress, chemical insults and mitotic cell division shorten telomeric DNA. Highly proliferative cell types, such as cancer and stem cells, maintain telomere length through the activation of telomerase. Murine embryos, however, establish a reserve of telomere length through a telomerase‐independent, recombination‐dependent pathway. Particular cancer cells also rely upon the ALT pathway. METHODS/STUDY POPULATION: ALT‐associated telomere dynamics were characterized by fluorescent in‐situ hybridization in murine embryos and ALT‐positive (ALT+) cancer cells. RESULTS/ANTICIPATED RESULTS: Early embryos demonstrated the same heterogeneity of telomere length and dependence upon DNA recombination and DNA polymerase machinery as ALT cancer cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Murine embryonic development may represent a natural model of telomere lengthening whose mechanism is usurped by telomerase‐negative, ALT‐associated cancers.
P186
ALVEOLAR MACROPHAGE PHENOTYPE IS AGE‐DEPENDENT FOLLOWING RSV INFECTION
Empey KM 1, Ross TM1, Clancy NJ1, Kolls JK1
1University of Pittsburgh, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: To determine if immunologically immature alveolar macrophages (AM) and lung environment during RSV infection contribute to age‐dependent differences in AM phenotype. Based on a Th2‐dominant (IL‐4, IL‐5) and Th‐1 deficient (lacking IFNγ) response following infant RSV infection, we predicted neonatal AM would differentiate to alternatively activated macrophages (AAM) and reduce expression of classically activated macrophages (CAM). METHODS/STUDY POPULATION: Using a novel neonatal mouse model of RSV infection, we interrogated the extent to which age influences phenotypic response of AM exposed to RSV. We used flow cytometry to discriminate between infant, 7 day‐old, and adult Balb/c mouse CAM and AAM following RSV infection at multiple days postinfection. Prior to flow cytometry we isolated AM from bronchoalveolar lavage fluid and stainined them with antibodies specific to CAM or AAM. RESULTS/ANTICIPATED RESULTS: Our data shows the neonatal lung environment, namely absence of IFNγ, and immaturity of age contribute to expression of an AAM phenotype during RSV infection. Seven‐day‐old and adult mouse AM expressed increasing markers of CAM following RSV infection. Ongoing functional studies will determine if immature infant AM provide less anti‐viral activity and allow more viral replication while adult AM are more antiviral and less permissive to viral replication. DISCUSSION/SIGNIFICANCE OF IMPACT: Functional heterogeneity of AM phenotype is critical as their roles are distinct. CAM, induced by IFNγ, kill intracellular organisms, secrete inflammatory cytokines and chemokines, and initiate adaptive immunity. AAM, induced by IL‐4 and IL‐13, do not kill organisms or secret inflammatory mediators. These data show immature AM are promising and feasible therapeutic targets for a significant global disease that currently has no effective treatment.
P187
ANTAGONISM BETWEEN AZITHROMYCIN AND TOBRAMYCIN WHEN TARGETING PSEUDOMONAS AERUGINOSA (P.A.)
Nichols D 1,2, Nick J1,2
1National Jewish Health, Denver, CO, USA; 2University of Colorado School of Medicine, Aurora, CO, USA
OBJECTIVES/SPECIFIC AIMS: Chronic inhaled tobramycin and oral azithromycin are mainstays of treatment for P.a. airway infection in cystic fibrosis (CF). Registry data show that at least 2/3 people with CF in the US are prescribed TOBI and 2/3 are prescribed chronic azithromcyin. Most receive both therapies. We sought to determine the interaction of azithromycin and tobramycin in vivo using animal models of persistent P.a. infection. METHODS/STUDY POPULATION: Using IACUC approved protocols to minimize stress and discomfort, partial‐thickness cutaneous thermal injury (i.e. burn wound) was established in C57Bl/6 mice. Two hours after injury, wounds were infected with PA01. At predetermined intervals following injury, animals were treated intraperitoneally with azithromycin, ciprofloxacin, and/or tobramycin, alone or in combination, at doses relevant to human use. Antibiotics were subsequently tested in a mouse model of primary airway infection using a CF clinical mucoid strain of P.a. At predetermined time points following infection, animals were euthanized for tissue collection. RESULTS/ANTICIPATED RESULTS: A single dose of azithromycin administered 4 hours after infection significantly reduced P.a. infection in both the burn wound and primary airway infection models up to 72 hours after infection. Effects were similar to repeated doses of ciprofloxacin or tobramycin. Azithromycin was additive with ciprofloxacin but antagonistic when combined with tobramycin. DISCUSSION/SIGNIFICANCE OF IMPACT: Azithromycin inhibits P.a. infection in models of infected burn and airway. This was additive when combined with ciprofloxacin, but antagonistic in combination with tobramycin. These are the first in vivo data showing this effect, which supports published in vitro studies. Reviewed mechanisms of action for these compounds provides biological plausibility to these data.
P188
ANTI–HIV‐1 ERYTHROCYTE VIRAL TRAP
Ramezani A 1, Karandish S1, Hawley TS1, Hawley R1
1George Washington University, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: The long‐term goal of this research is to develop a safe and effective gene therapy approach for treatment of HIV‐1 infection. METHODS/STUDY POPULATION: HIV‐1 infection of cells is mediated by engagement between viral envelope glycoproteins and a receptor complex comprising CD4 and a chemokine receptor expressed on the surface of target cells. Selective expression of the receptor molecules on cells that cannot support HIV‐1 infection could be used as a means of protecting the susceptible target cells. In this proposal, a novel anti–HIV‐1 gene therapy strategy, which is based on selective expression of HIV‐1 receptor and coreceptors, is used to redirect the virus to bind and enter erythrocytes which are unable to support HIV‐1 replication. RESULTS/ANTICIPATED RESULTS: A safety‐modified SIV‐derived lentiviral vector has been engineered for delivery of the HIV‐1 receptor and coreceptor genes to hematopoietic stem cells (HSCs). This vector utilizes an erythroid‐specific enhancer‐promoter element and has been shown to restrict gene expression to erythrocytes both in vitro and in vivo. The efficacy of the receptor and coreceptor expressing erythrocytes in binding and neutralizing HIV‐1 will be determined in vitro in a series of HIV‐1 challenge assays using various susceptible human cell lines and primary cells, and in vivo in humanized mice, and the findings will be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: Ex vivo HSC gene transfer followed by autologus nonmyeloablative transplantation is an attractive alternative treatment for HIV/AIDS patients and could provide lifelong therapeutical effects without the toxicity and complications associated with prolonged multiple drug therapy.
P189
ANTIAPOPTOTIC EFFECTS OF DIETARY SUPPLEMENTS IN PANCREATIC ISLET BETA CELLS
Wang Z 1, DiMeglio L1, Mather K1, Thurmond D1
1Indiana University, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: Type 2 diabetes is ultimately a result of pancreatic beta cell dysfunction linked to beta cell apoptosis. Over‐the‐counter supplements polyunsaturated fatty acids (PUFA), L‐Arginine, Ginseng and phytosphingosine (PS) have been shown to be of benefit in treatment of type 2 diabetes. However how they impact beta cell survival remains unclear. Toward this we endeavored to characterize the molecular effects of these supplements and determine the mechanism(s) by which they impart benefits. METHODS/STUDY POPULATION: MIN6 pancreatic beta‐cells and human islets were cultured with designated supplements. Protein or mRNA levels were determined by Western analysis or RT‐PCR. RESULTS/ANTICIPATED RESULTS: In MIN6 beta cells, Ginsenoside Rb1 was found to enhance glucose‐induced phosphorylation of p21‐activated kinase (PAK1), an event correlated with improved 2nd‐phase insulin secretion. Rb1 treatment also led to an increased protein level of Survivin. Importantly, human islets treated with Rb1 resisted hyperglycemic‐induced expression of the pro‐apoptotic protein Bad. Another supplement L‐arginine significantly increased Survivin protein levels in MIN6 cells. A third supplement, DHA, a form of PUFA protected against cleavage of total caspase‐3 in MIN6 cells, however it did not alter Survivin expression, indicating that DHA may inhibit apoptosis via a mechanism distinct from that of Rb1 and L‐Arginine. Lastly phytosphingosine also protected against caspase‐3 cleavage in MIN6 cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data imply that the tested supplements may mediate pancreatic beta cell survival through regulation of moleculars like PAK1, Survivin and Bcl‐2 family proteins. The effects of the combination of these supplements as well as their roles in vivo are currently under investigation.Utilization of dietary supplements be of significant benefit to the therapy of type 2 diabetes.
P190
ANTIGEN PRESENTATION AND B‐CELL DEVELOPMENT PATHWAYS ARE DOWN‐REGULATED IN RECALCITRANT COMPARED TO HEALING CHRONIC WOUNDS
Shanmugam VK 1, Tassi E1, McNish S1, Deselattes Mays A1, Attinger CE1, Wellstein A1
1Georgetown University, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to identify differentially expressed genes and associated pathways in healing compared to recalcitrant chronic wounds. METHODS/STUDY POPULATION: Wound tissue was obtained at surgical debridement, processed in RNAlater and stored at −80°C. Samples were grouped by clinical outcome based on % reduction in wound surface area (SA) 4 weeks after debridement. Wounds exhibiting >40% SA reduction were classified as healing (n = 2); those exhibiting <40% SA reduction were recalcitrant (n = 4). RNA was extracted using RNeasy for fibrous tissues. An Affymetrix Human U133A 2.0 gene expression array was followed by Ingenuity Pathway Analysis to identify differentially expressed genes and associated canonical pathways. Genes of interest were selected based on >4‐fold down‐regulation or >2‐fold up‐regulation in recalcitrant compared to healing samples. RESULTS/ANTICIPATED RESULTS: Canonical pathway analysis identified B‐cell development (p = 5.54E‐17), immunodeficiency (p = 2.87E‐13) and T‐ and B‐cell signalling (p = 1.65E‐5) as the pathways most altered relative to controls. Concordant down‐regulation was seen in 83 genes including TNF super family receptor 17 (mean log ratio −7.17) immunoglobulin components and critical antigen presentation molecules. Of the 23 concordantly up‐regulated genes, prostaglandin‐endoperoxide synthase 2 (inducible cyclo‐oxygenase 2) exhibited the greatest increase (mean log ratio 2.56). DISCUSSION/SIGNIFICANCE OF IMPACT: In recalcitrant chronic wounds, antigen presentation and immune response pathways were down‐regulated and prostaglandin pathways were up‐regulated. Further investigation of the interactions between the wound microbiome, host immune response and pain pathways are warranted.
P191
ANTIVIRAL EFFECT OF SORAFENIB IN HCV‐RELATED HEPATOCELLULAR CARCINOMA
Cabrera R 1, Horne P1, Mills R1, Soldevila‐Pico C1, Firpi R1, Morelli G1, Clark V1, Nelson DR1
1University of Florida, Gainesville, FL, USA
OBJECTIVES/SPECIFIC AIMS: The subanalysis from the SHARP phase III study suggests that hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC) patients derive more clinical benefit from sorafenib (Sor) treatment than other subgroups. In addition, in vitro data support an antiviral effect of Sor. We evaluate the antiviral activity of Sor in a cohort of HCV patients receiving sorafenib treatment for advanced HCC. METHODS/STUDY POPULATION: We prospectively evaluated sequential patients with HCV related advanced HCC receiving sorafenib. Clinical and virologic data were collected at various treatment time points. HCV RNA was evaluated at baseline and available time points including weeks 4, 8, 12 and 24. RESULTS/ANTICIPATED RESULTS: A total of eighteen patients were identified with baseline HCV viral load and subsequent HCV levels available for analysis (n = 18). Baseline characteristics included: mean age of 57.1 years (range; 46–76); 89% male; ECOG PS was 0–1 in 95%; Child‐Pugh status (Child A 45%, B 55%); mean MELD was 10.4 (6–17); BCLC stage (stage B 36%, C 64%); and mean AFP was 8,919 ng/mL. Mean baseline AST, ALT, ALK, and total bilirubin were 92 U/L, 64 U/L, 160 U/L and 1.4 mg/dL, respectively. The majority of the patients had genotype 1 HCV infection (82%). The baseline HCV viral load was 1,032,438 IU/ml (range; 6,200–4,825,040). The mean HCV viral load log change while patients received full dose sorafenib was 0.12 log (range −0.125–0.9825) with the average change at week 4 being −0.17 (n = 10; range −1–1), week 8 −0.2 (n = 6; range −0.43–0.05), week 12 −0.125 (n = 5; range −1.2–1), week 24 0.9825 (n = 4; range −0.07–3). Four patients (22%) had > 1.0 log drop in the HCV viral load. Data set will be updated with additional follow‐up. DISCUSSION/SIGNIFICANCE OF IMPACT: In this observational cohort, sorafenib has minimal antiviral activity in HCV patients with HCC.
P192
ASSOCIATION BETWEEN FUSOBACTERIUM SPECIES AND LOW‐ AND HIGH‐GRADE COLONIC ADENOMAS
Cho I 1, Hwang J1, Chuang P1, Walsh E1, Ni J1
1New York University School of Medicine, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: The potential role of microbes in the pathogenesis of colorectal cancer remain unclear. Recent studies suggest that Fusobacterium species are associated with CRC but did not provide evidence of causation. The objective of this study was to determine the relationship between Fusobacterium and adenomas found on screening colonoscopies. METHODS/STUDY POPULATION: Patients were enrolled at the New York Harbor VA Hospital Screening Colonoscopy Clinic. Stool specimens were obtained from patients prior to undergoing bowel preparation. Study subjects were matched by age, gender, and ethnicity to normal controls (n = 5/group). High‐grade adenoma was defined as size >1 cm or villous features on histology while low‐grade was defined as fewer than three adenomas <1 cm. DNA was extracted from stool and quantitative PCR performed using degenerate primers targeting the 16S rDNA and Fusobacterium species. Fusobacterium gene copies were normalized to total 16S DNA. Comparisons amongst the groups were performed using the Mann‐Whitney U test. RESULTS/ANTICIPATED RESULTS: There were no significant differences in total 16S gene copies amongst the control, low‐grade adenoma, and high‐grade adenoma groups. Fusobacterium gene copies were significantly lower in patients with high‐grade than with low‐grade adenomas (p < 0.05). Fusobacterium gene copies were lower in high‐grade adenomas compared to controls but the difference was not statistically significant. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data indicates that there is no positive association between Fusobacteria and low‐ or high‐grade premalignant colonic adenomas. Fusobacteria appear to be decreased in high‐grade adenomas. These findings suggest that Fusobacteria may not play a causative role in the development of colorectal cancer from adenomas but may preferentially colonize the mucosal surface of colorectal cancers.
P193
BEDSIDE FUNCTIONAL‐CONNECTIVITY DIFFUSE OPTICAL TOMOGRAPHY (fc‐DOT) IN NEONATES
Liao S 1, Ferradal SL2, Inder TE1, Culver JP2
1Washington University School of Medicine, Saint Louis, MO, USA; 2Washington University School of Engineering, Saint Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: We developed a noninvasive technique (fc‐DOT, based on near infrared spectroscopy) to map functional connectivity in preterm infants with varying degrees of brain injuries at the bedside. METHODS/STUDY POPULATION: This is a pilot study showing the feasibility of our novel functional neuroimaging technique. Preterm infants with varying degrees of anatomical brain injuries were recruited from the NICU at St. Louis Children’s Hospital. Each infant was studied in the crib or isolette during quiet state. The imaging cap (32 sources x 34 detectors) was placed on infant’s head and optical measurements were taken for 5–10 minutes (sampling rate = 10.8 Hz). We used seed‐based analysis to identify functional networks similar to established fMRI methods. RESULTS/ANTICIPATED RESULTS: In relatively healthy preterm infants without obvious anatomical injuries (n = 6), we were able to identify up to three distinct functional networks showing bilateral connectivity in medial, lateral occipital regions, and temporal‐parietal regions. Infants with significant parenchymal injuries showed only unilateral connectivity pattern. DISCUSSION/SIGNIFICANCE OF IMPACT: We were able to identify distinct functional networks in preterm infants using our novel bedside fc‐DOT technique. The connectivity patterns in preterm infants at term‐equivalent age may be different than in healthy term‐born infants. The fc‐DOT technique is well‐suited to routinely track functional brain development at the bedside.
P194
BIOLOGICAL MARKERS OF THE EFFECTS OF INTRAVENOUS METHYLPHENIDATE ON IMPROVING INHIBITORY CONTROL IN COCAINE‐DEPENDENT PATIENTS
Li C 1, Morgan P1, Matuskey D1, Malison R1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Prior research points to the importance of psychostimulants in improving self‐control. However, the neural substrates underlying such improvement remain unclear. Here, in a pharmacological functional MRI study of the stop signal task, we show that methylphenidate (as compared with placebo) robustly decreased stop signal reaction time (SSRT), an index of improved control, in cocaine‐dependent patients (a population in which inhibitory control is impaired). METHODS/STUDY POPULATION: Ten non–treatment seeking cocaine dependent individuals participated in 2 sessions of fMRI of the stop signal task, in which they received intravenous methylphendiate (0.5 mg/Kg BW) or placebo, the order of which was counter‐balanced across subjects. Vital signs were taken at baseline and during fMRI. The results were compared to a separate cohort of healthy control subjects, who were scanned without medications. RESULTS/ANTICIPATED RESULTS: Methylphenidate‐induced decreases in SSRT were positively correlated with inhibition‐related activation of left middle frontal cortex (MFC) and negatively with activation of the ventromedial prefrontal cortex (vmPFC) in whole brain linear regressions. Inhibition‐related MFC but not vmPFC activation distinguished individuals with short and long SSRT in 36 demographically matched healthy individuals, whereas vmPFC but not MFC activation, along with improvement in SSRT, was correlated with a previously implicated biomarker of methylphenidate response (systolic blood pressure). DISCUSSION/SIGNIFICANCE OF IMPACT: These results implicate a specific neural (i.e., vmPFC) mechanism whereby stimulants improve inhibitory control. Altered ventromedial prefrontal activation and increased blood pressure may represent useful CNS and peripheral biomarkers in individualized treatment with methylphenidate for patients with cocaine dependence.
P195
BIOMIMETIC 3D POROUS NANOSTRUCTURED BONE SUBSTITUTES WITH EXCELLENT CYTOCOMPATIBILITY AND MECHANICAL PROPERTIES
Zhang L 1, Castro N1, O’Brien JR2
1The George Washington University, Department of Mechanical and Aerospace Engineering and Institute for Biomedical Engineering, Washington, DC, USA; 2The George Washington University, Departments of Orthopaedic Surgery, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Although various traditional orthopedic therapies have been performed for many years, none of them are perfect due to limited donor tissues and numerous complications along implantations. Therefore, the objective of this study is to design and evaluate the feasibility of a biomimetic 3D nanostructured bone substitute with excellent cytocompatibility and mechanical properties for treating severe bone defects. METHODS/STUDY POPULATION: We designed a novel 3D nanostructured scaffold based on biomimetic hydrothermally treated nanocrystalline hydroxyapatites (nHA), magnetically synthesized single‐walled carbon nanotubes (SWCNTs), and a biocompatible natural hydrogel (chitosan) for improving bone regeneration. 3D porous chitosan scaffolds with different concentrations of nHA and magnetically synthesized SWCNTs were created via lyophilization to support the growth of human osteoblasts and mesenchymal stem cells. RESULTS/ANTICIPATED RESULTS: The results showed that chitosan hydrogel containing magnetically treated SWCNTs or nHA had superior cytocompatibility. In addition, our study provided the first evidence that the chitosan nanocomposite with both magnetically treated SWCNTs and nHA can achieve a synergic effect to significantly improve osteoblast and stem cell functions. DISCUSSION/SIGNIFICANCE OF IMPACT: Our 3D porous chitosan nano scaffolds with nHA and SWCNTs have biomimetic nanostructure, excellent osteoconductivity and mechanical properties, thus making them intriguing materials for further study in orthopedic applications.
P196
BREAST TUMOR CELLS WITH PI3K MUTATION OR HER2 AMPLIFICATION ARE SELECTIVELY DEPENDENT ON AKT SIGNALING
She Q 1, Ye Q1, Rosen N2
1University of Kentucky, Lexington, KY, USA; 2Memorial Sloan‐Kettering Cancer Center, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Dysregulated PI3K/AKT signaling occurs commonly in breast cancers and is due to HER2 amplification, PI3K mutation or PTEN inactivation. The objective of this study was to determine the role of AKT activation in breast cancer as a function of mechanism of activation and whether inhibition of AKT signaling is a feasible approach to therapy. METHODS/STUDY POPULATION: A selective allosteric inhibitor of AKT kinase, a variety of molecular techniques and tissue culture and in vivo xenograft models were used to interrogate a panel of breast cancer cell lines characterized for genetic lesions that activate PI3K/AKT signaling: HER2 amplification or PI3K or PTEN mutations in order to determine the biochemical and biologic consequences of inhibition of this pathway. RESULTS/ANTICIPATED RESULTS: We showed that tumors with mutational activation of AKT signaling were selectively dependent on the pathway. In sensitive cells, pathway inhibition resulted in D‐cyclin loss, G1 arrest and induction of apoptosis, whereas cells without pathway activation were unaffected. Most importantly, the drug effectively inhibited AKT kinase and its downstream effectors in vivo and caused complete suppression of the growth of breast cancer xenografts with PI3K mutation or HER2 amplification, including models of the latter selected for resistance to Herceptin. Furthermore, chronic administration of the drug was well‐tolerated. DISCUSSION/SIGNIFICANCE OF IMPACT: These data demonstrate that breast cancers with PI3K mutation or HER2 amplification are selectively dependent on AKT signaling, and that effective inhibition of AKT in tumors is feasible and effective in vivo. These findings suggest that direct inhibition of AKT may represent a therapeutic strategy for breast and other cancers that are addicted to the pathway including tumors with resistant to Herceptin.
P197
BRISK WALKING ALTERS POSTPRANDIAL LIPEMIA AFTER FRUCTOSE INGESTION DIFFERENTLY IN NORMAL‐WEIGHT AND OBESE INDIVIDUALS
Heden T 1, Liu Y1, Kearney ML1, Sims L1, Dellsperger KC1, Whaley‐Connell AT1, Chockalingam A1, Kanaley JA1
1University of Missouri, Columbia, MO, USA
OBJECTIVES/SPECIFIC AIMS: Ingestion of fructose rich mixed meals amplifies the postprandial triacylglycerol (TAG) response compared to fructose‐free mixed meals. The objective of this study was to determine the effect of 1 hour of brisk walking performed 12 hours prior to ingestion of a fructose rich mixed meal on postprandial lipemia in normal‐weight (NW) and obese (Ob) individuals. METHODS/STUDY POPULATION: On two separate occasions 10 NW and 10 Ob individuals ingested a 600 calorie meal (45% carbohydrate [7.3% fructose], 40% fat, and 15% protein) in the morning, 12 hours after performing 1 hour of brisk walking at 50–55% of their maximal oxygen consumption (EX) or remaining sedentary (NoEX). Blood samples were taken at baseline and 1, 2, 3, 4, and 6 hours after the meal and analyzed for TAG, total cholesterol (TC), high density lipoprotein cholesterol (HDL‐C), and low density lipoprotein cholesterol (LDL‐C). Incremental area under the curve (iAUC) was used to quantify postprandial responses. A mixed model ANOVA with Bonferroni post hoc tests were used to compare iAUC values. RESULTS/ANTICIPATED RESULTS: In NW individuals, EX significantly reduced the postprandial TC response 150% (p = 0.02) and LDL‐C response 143% (p = 0.02) compared to NoEX. In Ob individuals, EX significantly reduced the postprandial TAG response 18% (p = 0.02) and attenuated the reduction in HDL‐C (p = 0.02) compared to NoEX. Postprandial TAGs were lower in NW compared to Ob, regardless of condition (p = 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Collectively, brisk walking prior to ingestion of a fructose rich mixed meal differentially, but beneficially, alters postprandial lipemia in NW and Ob individuals. For individuals that consume a high fructose diet, brisk walking may be an effective therapy to prevent fructose induced dyslipidemia.
P198
BUILDING THE COGNITIVE CONNECTOME: TRANSLATING FUNCTIONAL NEUROIMAGING INTO PERSONALIZED MEDICINE
James GA 1, Fausett JS1, Gess JL1, Greenfield LJ1, Kilts CD1
1University of Arkansas for Medical Sciences, Little Rock, AR, USA
OBJECTIVES/SPECIFIC AIMS: The greatest barrier to using functional neuroimaging in clinical practice is its lack of large normative samples. Neuroimaging’s small sample sizes (usually n < 30) have precluded detailed study of how the brain encodes cognitive variability. We address this limitation by building the Cognitive Connectome—a comprehensive exploration of normative variability in cognition and brain function, which, like the Human Genome Project, will integrate functional neuroimaging into patient‐oriented care. METHODS/STUDY POPULATION: We have developed a battery of neuropsychological and functional MRI tasks spanning 8 cognitive modalities: motor, visuospatial awareness, attention, language, memory, affective processing, decision making, and executive function. We demonstrate the tests’ utility for exploring memory and language with healthy subjects (n = 20; 5 enrolled) and temporal lobe epilepsy patients (n = 15; 1 enrolled). RESULTS/ANTICIPATED RESULTS: Initial results give novel insight into how the brain encodes cognition. For example, the Controlled Oral Word Association Task is a test of language function in which participants view a letter and must generate in a short time as many words as they can starting with that letter. Control participants’ performance strongly correlated with brain activity in Wernicke’s area (r = 0.97, p < 0.01), a region involved in speech comprehension; the epilepsy patient differed from controls (p < 0.05), consistent with compromised temporal lobe function. DISCUSSION/SIGNIFICANCE OF IMPACT: A sizable sample (n = 200) will allow nuanced exploration of cognitive variability and the interplay between cognitive modalities. Inferences drawn from this sample will allow translation of fMRI into personalized medicine—e.g., planning surgical approaches to avoid cognitive impairment or predicting treatment response from baseline brain scans.
P199
CALORIC RESTRICTION UP‐REGULATES HIPPOCAMPAL CA1 NEUROPROTECTIVE GENE EXPRESSION AND REDUCES AMYLOID BURDEN IN AN ALZHEIMER'S DISEASE MOUSE MODEL
Schafer MJ 1,2, Ginsberg SD1,2
1New York University, New York, NY, USA; 2Nathan Kline Institute, Orangeburg, NY, USA
OBJECTIVES/SPECIFIC AIMS: There is no successful treatment or preventative measure for Alzheimer’s disease (AD), a disorder characterized by altered amyloid‐beta precursor (APP) processing, amyloid‐beta (Aβ) aggregation, cell‐type specific vulnerability, and cognitive deficits. Caloric restriction (CR) is a noninvasive dietary intervention that may prevent AD pathology. Previous studies have documented CR‐induced AD pathology prevention through regional, low‐resolution analysis. The effects of CR in selectively vulnerable hippocampal CA1 pyramidal neurons have not been demonstrated. METHODS/STUDY POPULATION: Through laser capture microdissection (LCM) and microarray analysis, we will investigate gene expression profiles of CA1 neurons isolated during pathology onset and later progression (5 and 15 mos.) from Tg2576 AD mice and nontransgenic littermates maintained on a 30% CR regimen versus ad libitum (AL) feeding. Aβ burden and APP metabolism are assessed as indicators of pathology and for correlation with high‐throughput gene expression changes. RESULTS/ANTICIPATED RESULTS: We have identified CR‐induced decreases in transcripts implicated in autophagy, synaptic transmission, transcription, and metabolism, as well as CR‐specific increases in several kinase and phosphatase transcripts and qualitative reduction in Aβ peptides in CR‐Tg2576 mice. We expect further characterization to support the hypothesis that CR induces increased neuronal efficiency, up‐regulation of neuroprotective pathways, and decreased Aβ deposition in aged AL‐Tg2576 mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Alterations identified by these experiments may serve as targets in the development of therapeutic interventions. Additionally, this work may serve as the basis for further studies of CR‐based dietary regimens as an AD pathology prevention option.
P200
CELLULAR AND MOLECULAR ORCHESTRATION OF PREMALIGNANT INFLAMMATION
Blaisdell A 1, Daikoku T3, Tay C1, Dey SK3, Erlebacher A1,2
1Department of Pathology, NYU School of Medicine, New York, NY, USA; 2Cancer Institute, NYU School of Medicine, New York, NY, USA; 3Division of Reproductive Sciences, Cincinnati Children’s Hospital Center, University of Cincinnati College of Medicine, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Inflammation can both inhibit and promote carcinogenesis by eliciting immunogenic T‐cell responses to tumor antigens while simultaneously fostering DNA damage and angiogenesis. Rational use of pro‐ or anti‐inflammatory treatments as cancer prophylactics and therapeutics, however, is currently limited by an incomplete understanding of how each component of the inflammatory tumor microenvironment combats or enhances tumor growth. Most critically, the cellular and molecular circuitry that drives inflammation during premalignancy remains largely undefined, in part due to a lack of tractable animal models. METHODS/STUDY POPULATION: We have addressed this issue using an autochthonous mouse model of endometrial carcinoma that has well‐defined stages of premalignancy and malignancy. RESULTS/ANTICIPATED RESULTS: Premalignant but not malignant lesions showed robust inflammation, characterized by a massive intraepithelial accumulation of neutrophils, increased expression of IL‐23 and COX2, and an increased density of IL‐17A‐producing lymphocytes – most of which were γδ T cells. Furthermore, γδ T cells infiltrated premalignant lesions prior to neutrophils, while pharmacologic COX2 inhibition abrogated neutrophil accumulation in tumor‐bearing uteri. DISCUSSION/SIGNIFICANCE OF IMPACT: Together, these results suggest a complex interplay between γδ T cells and the IL‐23‐IL‐17A and COX2‐prostaglandin signaling axes in orchestrating premalignant inflammation. Supported by a grant from the American Cancer Society (RSG‐10–158‐01‐LIB to A.E.)
P201
CELLULAR BIOLOGY: EXPLORING COMPLEMENTARY APPROACHES TO ATYPICAL CERVICAL CELLS
Leaver CA 1, St. John L2, Yuan H3, Wallen GR4
1NINR, Bethesda, MD, USA; 2NINR, Bethesda, MD, USA; 3Georgetown University Medical Center, Washington, DC, USA; 4NIH/Clinical Center, Bethesda, MD, USA
OBJECTIVES/SPECIFIC AIMS: Clinical case studies of Sanguinaria and zinc chloride (ZnCl2) support a potential role for these compounds in management of atypical cervical cells (atypia). Complementary modalities are used clinically to mitigate HPV risk but mechanisms of action and clinical outcomes are not clearly documented and require investigation. METHODS/STUDY POPULATION: HeLa (HPV 18), SiHa (HPV 16), CaSki (HPV 16 and 18), C33A (cervical cancer, HPV negative) and HFK (normal cell control) were seeded into 96‐well plates to 70–80% confluence. Cells were treated with serial titrations of sanguinarine chloride (SC) 0.0 uM–16.32 uM; and, ZnCl2 0.0 uM – 5.0 uM. Viability was determined at 24 hours by Cell Titer‐glo Luminescent Cell Viability Assay. RESULTS/ANTICIPATED RESULTS: Cell viability assay of HeLa, SiHa, CaSki, C33A and HFK exposed to SC and ZnCl2 identified cell death from both compounds. Specifically, cell death of HFK occurs with exposure to both compounds. The viability assay at 24 hrs with high doses, SC 16.32 uM and ZnCl2 5.0 uM, killed almost 100% of HPV positive and negative cells. Low doses of SC 2.04 uM, killed 50–60% of HPV positive and negative cells; ZnCl2 0.63 uM–0.16 uM, killed 60% of the immortalized cell lines, ZnCl2 0.08 uM killed 60% of HFK. Microscopic plate inspection revealed morphologic signs of cell death including cell shrinkage, round up and detachment from plate surface. DISCUSSION/SIGNIFICANCE OF IMPACT: Both SC and ZnCl2 induce cell death in HFK, as well as HeLa, SiHa, CaSki, and C33A. This bench knowledge can be transferred to naturopath’s knowledge base leading a clearer path for integrating complementary modalities in the management of cervical atypia. To build on this bench research a Delphi study is underway to delineate consensus for naturopathic management of cervical atypia.
P202
CEREBROSPINAL FLUID MONOCYTE CHEMOATTRACTANT PROTEIN‐1 LEVELS IN ALCOHOLICS IS CORRELATED WITH LIVER INFLAMMATION
Umhau JC 1, Schwandt M1, George DT1, Heilig M1
1nih, Bethesda, MD, USA
OBJECTIVES/SPECIFIC AIMS: The clinical features of alcoholism may be in part initiated by the development of liver inflammation. This liver inflammation is has been hypothesized to influence the development of a neuroinflammatory process in the brain characterized by neurodegeneration and altered cognitive function. Monocyte chemoattractant protein 1 (MCP‐1/ CCL2) elevations found in the alcoholic brain at autopsy suggest that this cytokine may have a role in this process. We sought to explore this possibility. METHODS/STUDY POPULATION: We obtained cerebrospinal fluid (CSF) from 28 alcoholics during week one and four following detoxification. We measured levels of MCP‐1 in CSF and levels of liver enzymes in plasma to quantify brain and liver inflammation, respectively. RESULTS/ANTICIPATED RESULTS: Compared to healthy volunteers, MCP‐1 levels were significantly higher in alcoholics on day 4 and day 24; p < 0.0001. Using multiple regression, we found that MCP‐1 concentrations were positively associated with the liver enzymes gamma glutamyltransferase (GGT, p = 0.04) and aspartate aminotransferase (AST/GOT, p = 0.004). DISCUSSION/SIGNIFICANCE OF IMPACT: These preliminary findings are consistent with the hypothesis that neuroinflammation as indexed by CSF MCP‐1 is associated with alcohol induced liver inflammation. The measurement of cytokines in CSF may prove to be a useful index of neuroinflammation in alcoholism.
P203
CHARACTERIZATION OF BACTERIAL COMMUNITIES IN CHRONIC WOUNDS BY USE OF MOLECULAR DIAGNOSTIC METHODS
Tuttle MS 1, Mostow E1, Dowd S2, Ghannoum M1
1Case Western Reserve University & University Hospitals Case Medical Center, Cleveland, OH, USA; 2Research and Testing Laboratory, Lubbock, TX, USA
OBJECTIVES/SPECIFIC AIMS: Microbial infections delay wound healing, but the effect of the composition of the wound microbial communities (or microbiome) on healing parameters is unknown. Further determination of the relationship between microbes and delayed healing is critical for development of more evidence‐based diagnostic and treatment strategies. METHODS/STUDY POPULATION: We analyzed debridement samples from lower extremity venous insufficiency ulcers using 454 FLX Titanium Series pyrosequencing of the 16s ribosomal subunit. Wound debridement samples were obtained from ten patients monitored clinically for at least six months, at which point five of the ten sampled wounds had healed. RESULTS/ANTICIPATED RESULTS: Pyrosequencing data showed that wounds of patients with delayed healing had striking increases in bacterial abundance and diversity. Additionally, Actinomycetales was increased in wounds that had not healed, and Pseudomonadaceae was increased in wounds that had healed at six‐month follow‐up. Baseline wound surface area or duration did not reveal significant differences between wounds that healed by six months and those that did not. DISCUSSION/SIGNIFICANCE OF IMPACT: Pyrosequencing of wound debridement samples identified distinctive baseline microbiome characteristics of wounds that did not heal at six‐month follow‐up, furthering our understanding of potentially unique microbiome characteristics of chronic wounds. As chronic wounds often follow a nonlinear path to healing—with phases of wound expansion, stalled healing, and resolution—more study is needed to understand the evolution of the microbiome as the wound progresses through different phases of repair. Such studies have potential to lead to sophisticated chronic wound diagnostics and therapeutics.
P204
CHEMICAL EXCHANGE SATURATION TRANSFER (CEST) IMAGING AS A CANCER BIOMARKER
Dula AN 1, Gore JC1
1Vanderbilt Medical Center, Nashville, TN, USA
OBJECTIVES/SPECIFIC AIMS: Chemical exchange saturation transfer (CEST), is sensitive to solute/water proton exchange, and the modulation of this exchange by the hydrogen ion concentration. CEST‐derived metrics have successfully differentiated tumor core from edema in animal models and at low field. This may provide early time point information that is distinct from, and more specific than, established techniques. The objective of this study is to use CEST MRI at high field to characterize healthy and tumor tissue of the brain and breast. We hypothesize that CEST measures at high field will be sensitive to variations in mobile protein content and pH, unique to cancerous tissue and potentially characteristic to different stages or progression. METHODS/STUDY POPULATION: CEST MRI will be used to distinguish healthy neural and fibroglandular (FG) breast tissue from pathology. In particular, we will acquire CEST data in conjunction with conventional MRI scans on healthy controls and tumor patients to compare with established biomarkers. RESULTS/ANTICIPATED RESULTS: Application of CEST MRI at 7T results in structural delineation of white/gray matter of the brain. CEST MRI of breast at 3T produces clear images of healthy FG tissue. Preliminary scans of brain and breast tumors show a relative decrease in the CEST measures. DISCUSSION/SIGNIFICANCE OF IMPACT: Clinical decisions are based on imaging metrics that are typically poor surrogates for underlying tissue pathophysiology. Contrary to the conventional morphological evaluation used to assess treatment response; CEST measurements are reflective of the underlying molecular composition and can be applied for the purposes of detection, diagnosis, treatment monitoring, and resection planning.This sensitivity presents the potential to observe tissue changes far earlier in the pathological and treatment‐response processes than standard and even advanced MRI methods.
P205
CHILDREN WITH FOOD ALLERGY EXHIBIT DECREASED REGULATORY T CELLS
Singh AM 1,2, Erickson KA2, Bryce PJ2, Schleimer RP2
1Northwestern Feinberg School of Medicine, Chicago, IL, USA; 2Northwestern Feinberg School of Medicine, Department of Medicine, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Food allergy (FA) can be life threatnening and is an early expression of the atopic march, a progression that may lead to the development of asthma. Regulatory T cells (Tregs) balance inflammation in a variety of disease states. However, the precise role of Tregs in FA is not known. METHODS/STUDY POPULATION: Twenty‐four children with or without FA were enrolled. Children were categorized as having FA by a pediatric‐allergist with evidence of specific IgE and typical symptoms within 2 hours of food ingestion. Peripheral blood mononuclear cells were isolated, and flow cytometry was completed on unstimulated cells and cells stimulated with PHA (5 mcg/ml) × 48 hours for CD4, CD25, CD127, Helios, Foxp3. Intracellular cytokine staining was completed for IL‐10 and IL‐17. RESULTS/ANTICIPATED RESULTS: Of the 24 children enrolled, 14 (58%) had a diagnosis of food allergy. Children with FA had fewer%Foxp3+/CD4+ cells (12.57% vs. 5.69%, p = 0.02), and decreased%Helios+/CD4+ cells (14.7% vs. 0.46%). A subset of Foxp3+ cells also express IL‐17. There was no difference in%IL‐10+ or%IL‐17+ cells in the CD4+ gate. DISCUSSION/SIGNIFICANCE OF IMPACT: Children with FA exhibited decreased Tregs. Decreased regulatory responses provide mechanistic evidence for the loss of oral tolerance and for systemic immune dysregulation in food allergy, and may in part explain progression of the atopic march.
P206
CIGARETTE SMOKE ENHANCES INTERLEUKIN‐15 DURING RESPIRATORY VIRAL INFECTIONS
Dela Cruz C 1, Ghimire A1, Liiu W1, Sauler M1, Siner J1, Elias J1
1Yale School of Medicine, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Viral infections are implicated as a major cause of cigarette smoke (CS) related diseases such as chronic obstructive pulmonary disease (COPD). Our preclinical animal data show that CS interacts in a synergistic manner with respiratory viruses to cause an exaggerated pulmonary inflammation and emphysema. This interaction is mediated by the cytokine interleukin −15 (IL‐15). We hypothesize that patients exposed to CS, with or without COPD, have elevated IL‐15 in response to virus. METHODS/STUDY POPULATION: The study was a prospective cohort of adult patients admitted with respiratory symptoms and tested positive for respiratory viruses using direct immunofluorescence and/or PCR studies performed on nasopharyngeal samples. Clinical data were collected by questionnaire and chart review. Serum IL‐15 levels were measured by ELISA. RESULTS/ANTICIPATED RESULTS: 107 patients were enrolled. 45% of the patients were infected with Influenza; 38% were infected with RSV; 18% were infected with human metapneumovirus (hMPV). Serum IL‐15 was significantly elevated in virally infected patients who were either former or current smokers (p < 0.001, compared with virally infected never smokers). This was the case in influenza‐infected patients (p < 0.001), and in RSV‐ and hMPV‐infected patients (both p < 0.05). There was a positive dose‐dependent relationship between the smoking status and serum IL‐15 (p < 0.05). Influenza‐infected patients with COPD had significantly elevated levels of serum IL‐15, compared with patients with asthma or with no lung diseases (p < 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: CS exposure and respiratory virus infection interact to induce IL‐15 in patients with respiratory symptoms, confirming our preclinical data highlighting the importance of this cytokine in the exaggerated viral responses seen in CS‐exposed individuals, including those with COPD.
P207
CIRCULATING miRNA IN ACUTE MYELOID LEUKEMIA (AML): A PILOT STUDY
Quintana‐Ortiz RA 1, Tirado‐Gomez M3, Bernabe‐Dones R2
1UPR, RCM, San Juan, Puerto Rico; 2UPR, Comprehensive Cancer Center, San Juan, Puerto Rico; 3UPR Medical Sciences Campus Cancer Center, San Juan, Puerto Rico
OBJECTIVES/SPECIFIC AIMS: (1) Asses the expression levels of circulating miRNA related to hematopoiesis, apoptosis and cell cycle regulation in plasma of AML patients and aged and sex matched controls. We hypothesize that patients with AML in our study group will present different and higher relative quantity expression patterns of miRNA related to hemopoietic control in plasma than control subjects. Samples will be processed in a blinded fashion for QRTPCR‐ to detect and quantify miRNA present in plasma. (2) Identify miRNA expression patterns associated with clinicopathologic characteristics, treatment response and survival of AML patients. We hypothesize that miRNA expression levels will be useful to group AML patients by clinic‐pathological features treatment response and survival. METHODS/STUDY POPULATION: Study design: Case‐control. Sample: AML patients attending the “Hospital Universitario” UPR, RCM and their match controls. Method: qRTPCR from plasma micro‐RNA. microRNA’s patterns will be analyzed with patient’s match controls and their clinicopathological characteristics. Statistical analysis: SPSS and STATA. RESULTS/ANTICIPATED RESULTS: We expect to identify the significance of selected circulating miRNA in AML patients, with and without genetic abnormalities, regarding its practical use as a potential test to classify and support treatment selection for AML patients. DISCUSSION/SIGNIFICANCE OF IMPACT: Results from this pilot project will have important implications by expanding current knowledge of miRNA epigenetics in AML and its correlation with AML pathophysiology. Outcomes will also enhance prospective and translational studies to assess the etiologic role of circulating miRNA in AML carcinogenesis and targeted treatment selection.
P208
CIRCULATING miRNAS IN IBS
Peace RM 1, Del Valle‐Pinero A1, Patel N1, Martino A1, Majors B1, Reddy S1, Henderson WA1
1NINR, NIH, DHHS, Bethesda, MD, USA
OBJECTIVES/SPECIFIC AIMS: Irritable bowel syndrome (IBS) affects 10–15% of people worldwide. We demonstrated that Chemokine C‐C motif ligand 16 (CCL‐16) was up‐regulated in IBS using quantitative real time‐PCR arrays. The aim of this study was to evaluate the relative contribution of miRNAs in differentially phenotyping IBS patients from healthy controls. METHODS/STUDY POPULATION: Caucasian patients (n = 10, 50% male, ages 22–45 years) that fulfilled Rome III criteria were compared to age, gender, race, and weight matched healthy controls (n = 10). Peripheral whole blood from fasting participants was collected and RNA extracted using the PAXgene Blood RNA tubes and kit. Customized PCR array and miRNA quantification were performed with the Qiagen and nCounter Human miRNA Sample Preparation Kit (Nanostring) followed by digital detection and quantification of 735X miRNA withnCounter® Human miRNA Expression Assay Kit (Nanostring). RESULTS/ANTICIPATED RESULTS: 340 miRNAs were identified via the random variance estimation procedure (85% with miRNA quantification ≥10 calls) of which 271 passed filtering criteria. A Randomized block design with a random variance model was used for group comparisons. The multiplex targeted profiling revealed seven miRNAs that had parametric significance at p = 0.05 including miR‐335, mi‐574‐3p, miR‐342‐3p, miR‐1252, ebv‐mi‐BART6‐5p, miR‐569, and miR‐185. The most interesting was miR‐574‐3p (p = 0.01, 1.94 fold change). A similar association was found for miR‐574‐5p when correlating to the PCR CCL‐16 mRNA expression using RT‐PCR. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings demonstratethe ability to discriminate IBS from healthy phenotypes with combined novel biomarker profiles may which may aid in the discovery of novel miRNA targets for treatment of IBS patients.
P209
COLD PLASMA CANCER THERAPY
Keidar M 1, Srinivasan P2, Sandler A2
1George Washington University, Washington, DC, USA; 2Childrens Hospital, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Plasma is an ionized gas that is typically generated in high‐temperature conditions. Cold nonthermal atmospheric plasma is a potentially exciting breakthrough as it could lead to new paradigms in cancer therapy by offering a minimally invasive surgical technique that allows targeted cell removal without damage to normal surrounding tissue. In contrast to laser surgery, cold plasma interaction with tissue may allow for specific cell removal without necrosis. METHODS/STUDY POPULATION: In order to assess the potential of cold plasma treatment we will study its use in murine tumor models both in vitro and in vivo. RESULTS/ANTICIPATED RESULTS: Preliminary results show that (1) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and (2) significantly reduces tumor size in vivo. DISCUSSION/SIGNIFICANCE OF IMPACT: The development of cold plasma tumor ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by the utilization of another state of matter.
P210
COLORECTAL CANCER STROMAL CELLS CONTRIBUTE TO THE TUMOR MICROENVIRONMENT VIA EXPANSION OF CD4+ FOXP3+IL‐17+ T CELLS
Pinchuk I 1, Beswick EJ2, Johnsrud AJ1, Saada JI1, Wood K1, Qiu S1, Mifflin RC1, Reyes VE1, Powell DW1
1UTMB, Galveston, TX, USA; 2UNM, Albuquerque, NM, USA
OBJECTIVES/SPECIFIC AIMS: Colorectal cancer (CRC) progression is associated with increased CD4+ CD25highFoxP3+ IL‐17+ T cells with dual function: suppression of antitumor immunity and promotion of local inflammation. The mechanism responsible for this T cell imbalance is unknown. Colonic myofibroblasts (CMFs) represent a significant fraction of the tumor stroma. Our initial data showed that CRC derived (C)‐CMFs produce high levels of IL‐6, a Th17 promoting cytokine, and enhance induction of CD4+CD25highFoxP3+ cells. Thus, we hypothesized that during CRC abnormal activation of C‐CMFs contributes to tumor immune escape via induction of CD4+CD25highFoxP3+ IL‐17+ T cells. METHODS/STUDY POPULATION: Confocal microscopy was used to analyze IL‐6 expression by C‐CMF. CD4+ T cell phenotype primed by CMFs was determined using flow cytometry and Luminex arrays. RESULTS/ANTICIPATED RESULTS: Increase in activated C‐CMFs expressing IL‐6 was observed in situ in tumor stroma and correlated with the drastic decrease in alcohol dehydrogenase 1B (ADH1B) expression, which negatively regulates IL‐6 production through vitamin A metabolism. Coculture of the CD3/CD28 preactivated CD4+ T cells with C‐CMFs, but not with normal syngeneic CMFs enhanced the generation of the CD4+CD25high T cells that express both Treg (FoxP3) and Th17 (RORγτ) transcription factors and produce IL‐17, which wasIL‐6 dependent. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest that C‐CMFs are crucial contributors to the tumor‐growth promoting microenvironment. Further, abnormal activation of C‐CMFs resulting in enhanced IL‐6 expression and decreased ADH1B expression contributes to an antitumor immune evasion and local inflammation via generation of CD4+ CD25highFoxP3+ IL‐17+ T cells.
P211
COMBINATION ECMO‐VASOPRESSIN‐DOPAMINE THERAPY AMELIORATES PULMONARY HYPERTENSION IN ENDOTOXIC SHOCK
Clark AJ 1, Palmer EG1, Klui AM1, Uyehara CF2
1Pediatrics, Tripler Army Medical Center, Honolulu, HI, USA; 2Clin Inv, TAMC, Honolulu, HI, USA
OBJECTIVES/SPECIFIC AIMS: Severe endotoxic shock involves peripheral vasodilation and cardiac depression leading to hypoxemia and pulmonary hypertension (PHTN). Effective therapy requires restoration of mean arterial pressure (MAP) with pressor agents and fluids, yet this can lead to a vicious cycle of worsening PHTN and further hypoxemia. This study aims to determine whether ECMO could ameliorate PHTN of endotoxic shock when used in conjunction with pressor therapy. METHODS/STUDY POPULATION: A 40% decrease in MAP was induced with E.coli endotoxin (ETX; i.v.) in 6 anesthetized, cardiac catheterized, mechanically ventilated 8 kg piglets (n = 6). Hemodynamic parameters were measured at baseline, after established shock, and after one hour treatments with vasopressin (VP; 30 ng/kg/min i.v.), VP plus dopamine (DA; 6 mcg/kg/min i.v.), and veno‐arterial ECMO while on VP+DA. RESULTS/ANTICIPATED RESULTS: MAP was normalized with VP, VP+DA, and while on ECMO. ETX induced a dramatic increase in pulmonary pressure (16 ± 1 vs. 30 ± 2 mm Hg). VP or VP+DA for systemic pressor support did not worsen PHTN due to VP relatively sparing the pulmonary bed of its vasoconstrictive effect. The pulmonary to systemic vascular resistance ratio (PVR/SVR) at baseline (0.16 ± 0.02) increased in ETX shock (0.56 ± 0.07) but was not further increased with pressor treatment (VP = 0.43 ± 0.03; VP+DA = 0.26 ± 0.03). ECMO in addition to this combination of pressors completely normalized PVR/SVR (0.11 ± 0.04) and PAP to baseline levels. DISCUSSION/SIGNIFICANCE OF IMPACT: Septic shock causes significant morbidity and mortality in the neonatal and pediatric population. Our results demonstrate that VP and the combination of VP+DA can normalize MAP without exacerbation of PHTN, and that ECMO can be utilized as an important adjunct to pressor therapy for refractory PHTN associated with septic shock.
P212
COMMON GENETIC VARIANTS AND ACUTE RESPONSE TO VITAMIN D SUPPLEMENTATION: A PHARMACOGENOMIC STUDY
Arora P 1, Allicia R1, Ghorbani A1, Newton‐Cheh C1, Wang TJ1
1Cardiology Division, Massachusetts General Hospital, Boston, MA, USA
OBJECTIVES/SPECIFIC AIMS: The response to vitamin D supplementation is highly variable. Common variants in vitamin D‐related genes are associated with resting vitamin D (25OH D) levels, but the influence of genotype on 25OH D levels after supplementation is not well described. We examined the association of genetic variation with 25OH D levels before and after supplementation. METHODS/STUDY POPULATION: Healthy, nonobese subjects (n = 73) with 25OH D levels were given a single oral dose of 100,000 IU of cholecalciferol. Serum 25OH D levels were measured on Days 0, 4, 7 and 30. SNPs rs10741657 (near CYP2R1), rs12785878 (near DHCR7), rs2282679 (near GC), rs6013897 (near CYP24A1), rs4588 (in GC) and rs7041 (in GC) were genotyped using the TaqMan method. A weighted genotype score was constructed based on the number of risk alleles across all SNPs. Repeated measures ANOVA was used to assess the effect of genotype on 25OH D levels before and after supplementation. RESULTS/ANTICIPATED RESULTS: Serum 25OH D levels increased significantly after supplementation (mean ± SD of 32 ± 11 and 51 ± 14 ng/ml on Days 0 and 7 respectively, p < 0.0001). The genotype score was significantly associated with 25OH D levels before and after supplementation (p for genotype = 0.007). The rise in 25OH D levels with supplementation, however, was not associated with genotype (p for interaction = 0.17). On Day 0, mean 25OH D levels in individuals in the top versus bottom tertile of the genotype score were 27 and 35 ng/ml, respectively. Corresponding values on day 7 were 45 and 56 ng/ml. DISCUSSION/SIGNIFICANCE OF IMPACT: Common genetic variants are associated with 25OH D levels before and after vitamin D supplementation. We did not detect variation in the response to vitamin D supplementation according to genotype, suggesting that the effects of supplementation are independent of the common genetic variants examined.
P213
COMMONALITIES IN CARDIAC miRNA EXPRESSION IN BABOON FETUSES BORN TO OVER‐ AND UNDERNOURISHED MOTHERS
Maloyan A 1, Gelfond J2, Nijland MJ1, Nathanielsz PW1, Myatt L1
1UTHSCSA, San Antonio, TX, USA; 2UTHSCSA,Department of Epidemiology and Biostatistics, San Antonio, TX, USA
OBJECTIVES/SPECIFIC AIMS: Both maternal under‐ and overnutrition predispose offspring to cardiovascular disease (CVD) suggesting that these two paradigms share common pathological pathways. MicroRNAs (miRNAs) are small noncoding RNAs, which involvement in CVD has been well documented. We hypothesized that the similar cardiovascular phenotypic outcome of maternal under‐ and overnutrition would arise from commonalities in fetal cardiac miRNA expression. METHODS/STUDY POPULATION: Healthy female baboons were assigned to one of three diets carried throughout the pregnancy: (1) Control (C); (2) Maternal nutrient restriction (MNR) – 70% of control, and (3) High fat/high fructose diet (HFD). All baboons underwent c‐section, and fetal hearts were collected. Fetal cardiac RNA was isolated, and miRNA sequenced and profiled. RESULTS/ANTICIPATED RESULTS: We identified 70 differentially expressed miRNAs in HFD compared to C hearts, 50 up‐ and 20 down‐regulated. Compared to C, 53 miRNAs were differentially expressed in MNR hearts with 39 up‐ and 14 down‐regulated. Of all the differentially expressed miRNAs that were homologous to those of humans, 7 were common between two paradigms, and have been previously linked to CVD: miR‐143, 145, miR‐378, miR‐30, miR‐133, miR‐1–2, and miR‐342. For all 7 miRNAs, 250 target genes were identified and input into Ingenuity Pathways Analysis to retrieve the target genes association with CVD. Most of them were linked to coronary artery disease, cardiac hypertrophy, or heart failure. DISCUSSION/SIGNIFICANCE OF IMPACT: Significant alterations occur in cardiac miRNA expression in the fetuses of both under‐ and over‐nourished baboons with 7 of them being common suggesting that miRNAs may play a role in the fetal programming of CVD shared by both conditions of poor maternal nutrition.
P214
COMPARISON OF CYTOKINE EXPRESSION BY HUMAN MYELOID DENDRITIC CELL SUBSETS IN RESPONSE TO RSV AND TLR AGONISTS
Gupta MR 1, Kolli D1, Garofalo RP1
1UTMB, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: Dendritic cell (DC)‐respiratory syncytial virus (RSV) interactions determine the immunologic consequence of infection. Toll‐like receptors (TLRs) convert pathogen recognition into signals controlling the outcome of immunity. How RSV responses are tailored by TLRs in human myeloid DC (mDC) subsets remains unknown. Identifying overlapping cytokine patterns induced by RSV and TLR agonists in each subset may help identify TLR pathways utilized by RSV. METHODS/STUDY POPULATION: Using FACS sorting, mDC subsets (BDCA‐1+ and BDCA‐1−) were isolated from peripheral blood of healthy volunteers and incubated with RSV, Poly I:C (TLR3 agonist), LPS (TLR4 agonist), and ssRNA (TLR8 agonist). Two‐way ANOVA was used to determine statistically significant differences in cytokine profiles induced by agonists between subsets and by RSV versus TLR agonists in each subset. RESULTS/ANTICIPATED RESULTS: BDCA‐1+ and BDCA‐1− mDCs produced similar cytokine profiles in response to RSV (F = 0.44, p = 0.50) and ssRNA (F = 0.0,p = 0.99), but distinct cytokine profiles in response to Poly I:C (F = 10.03, p = 0.002) and LPS (F = 7.14, p = 0.008). Overlapping cytokine profiles were induced by RSV and Poly I:C (F = 0.24, p = 0.63) in BDCA‐1+ mDCs; and RSV and LPS (F = 0.83, p = 0.36) in BDCA‐1− mDCs. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest a common signaling pathway for RSV and Poly I:C (TLR3) in BDCA‐1+ mDCs; and RSV and LPS (TLR4) in BDCA‐1− mDCs. The combination of cytokines produced in response to infection is TLR‐specific. Thus, TLR signaling pathways utilized by RSV may have important implications in the outcome of resulting immune responses. To our knowledge, this is one of the first studies to identify potential TLR pathways activated by RSV in human mDC subsets.
P215
CSF BIOMARKERS OF ALZHEIMER'S DISEASE AS A TOOL TO PREDICT POSTOPERATIVE DELIRIUM IN PATIENTS UNDERGOING HIP SURGERY
Oh E 1, Rosenberg P1, Lee H1, Carlson A1, O’Brien R1, Lyketsos C1, Sieber F1, Mears S1
1Johns Hopkins, Baltimore, MD, USA
OBJECTIVES/SPECIFIC AIMS: Background: Delirium is a common postoperative complication in patients undergoing hip surgery. One of the strongest risk factors for delirium is underlying dementia status such as Alzheimer’s disease (AD). The purpose of this study was to determine whether preoperative cerebrospinal fluid biomarkers suggestive of underlying AD pathology correlate with postoperative delirium severity. METHODS/STUDY POPULATION: Methods: CSF samples were taken from 20 patients who had elective hip replacement (N = 14) or hip fracture repair surgery (N = 6) during spinal anesthesia. 10 male and 10 female patients were studied, with mean age of 78.5 ± 8.6. CSF samples were analyzed for full‐length amyloid‐beta (Aβ1‐42), total tau and tau phosphorylated on threonine 181 (p‐tau181) using the Innogenetics AlzBio3 kit. Pearson correlation coefficients were estimated for CSF levels of Aβ 42, t‐tau and p‐tau181 and Delirium Rating Scale‐Revised 98. Statistical analyses were conducted using GraphPad Prism version, GraphPad Software, San Diego, CA, USA. RESULTS/ANTICIPATED RESULTS: Results: Lower CSF Aβ42 levels (r =−0.57, p = 0.01), higher CSF t‐tau (r = 0.75, p = 0.0003) and p‐tau181 (r = 0.47, p = 0.04) levels were associated with higher DRS‐R‐98 scores respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: In the present study, we demonstrate that preoperative CSF levels of AD biomarkers Aβ42, and tau (t‐tau, p‐tau181) may be associated with the severity of postoperative delirium (DRS‐R‐98) after hip surgery. Due to the limited number of patients who had delirium as determined by Confusion Assessment Method (CAM), we were not able to examine the association of these CSF biomarkers and incidence of delirium. However, we have demonstrated that there may be an association between the levels of CSF biomarkers and postoperative delirium severity as determined by DRS‐R‐98.
P216
CYSTINE/GLUTAMATE TRANSPORTERS AS PROGNOSTIC and THERAPEUTIC MARKERS FOR PRIMARY BRAIN TUMORS
Robert S 1, Ogunrinu T1, Sontheimer H1
1University of Alabama Birmingham, Birmingham, AL, USA
OBJECTIVES/SPECIFIC AIMS: Glioblastoma multiforme (GBM) is the most prevalent and aggressive malignant brain tumor. This project examines the role of the cystine/glutamate exchanger, system xc‐ (SXC) and EAAT glutamate transporters in tumor growth, malignancy, and peritumoral seizure activity. METHODS/STUDY POPULATION: From Xenografts, in which patient tumors were propagated by ectopic implantation into nude mice flanks, we selected 4 glioma samples with different SXC and EAAT expression. Tissue microarrays from 37 patients were examined by histochemistry to compare tumor and normal brain. RESULTS/ANTICIPATED RESULTS: Examination of 37 patient samples show two subpopulations of gliomas, those expressing high levels of SXC and those expressing low levels; 64% and 36%, respectively. Cystine and glutamate uptake assays indicate that low SXC expressing tumors have an alternative transporter to supply intracellular cystine for GSH synthesis and redox protection. EAAT1 and EAAT3, two candidate transporters identified by PCR and Western blot analysis, could contribute to cystine and glutamate transport. Tumors with high SXC expression proliferate faster, show increased radiation resistance and, through glutamate release, exhibit neurotoxicity in vitro, which is decreased with SXC inhibition. Further studies investigating the properties of these GBM subpopulations are underway. DISCUSSION/SIGNIFICANCE OF IMPACT: Sulfasalazine (SAS), an FDA approved drug used for Crohn’s disease, is an inhibitor of SXC. In preclinical studies SAS has shown promise slowing tumor growth and has been suggested as an adjuvant in GBM treatment. Hence, determining if expression of SXC contributes to peritumoral seizures, or confers a growth advantage and/or radiation resistance will be important in treatment decisions for GBM patients. Our studies are therefore aimed at defining system xc‐ as a therapeutic and diagnostic/prognostic marker.
P217
DECREASED APOLIPOPROTEIN B AFTER TRAUMA PREDICTS DELAYED INFECTIONS
Femling J 1, Hauswald E1, Gresham H1,2, West S1, Hall P1
1University of New Mexico, Albuquerque, NM, USA; 2VAMC, Albuquerque, NM, USA
OBJECTIVES/SPECIFIC AIMS: Infections are the primary cause of late morbidity and mortality in victims of trauma. Early identification of those at risk of infection would allow for targeted interventions. We hypothesized that reductions in apolipoprotein B (apoB) could identify patients at risk of infection. ApoB is the structural component of very low density lipoprotein and low density lipoprotein and is an innate immune barrier against Staphylococcus aureus. Our objective was to determine if reduced apoB levels after trauma were predictive of delayed infections in patients who had suffered severe trauma. METHODS/STUDY POPULATION: We performed a prospective cohort study on severely injured trauma patients admitted to our trauma intensive care unit (ICU) with an Injury Severity Score greater than 16. Plasma apolipoproteins B, AI, AII, E, CII, and CIII were all measured during the first 3 days after trauma. Levels were correlated to the 30 day incidence of infection. Infections were defined using CDC criteria. RESULTS/ANTICIPATED RESULTS: Apolipoproteins B, AI, and AII concentrations were significantly lower in patients that had suffered infections within 30 days after trauma. Generation of receiver operating characteristics curves revealed that all three of these apolipoproteins were significantly able to predict later infection. This was greatest with apoB. First day apoB levels less than 18.5 mg/dL were associated with an increased likelihood ratio of infection of 6.5. The predictive value of apoB was similar to calculating an APACHEII score and was simpler to measure. DISCUSSION/SIGNIFICANCE OF IMPACT: Apo B levels measured within the first day after trauma are able to identify patients at increased risk of infection. These findings identify a potential role for apoB measurement in post trauma care and offer insights into the disruptions in innate host defenses after severe trauma.
P218
DEFINING NOVEL THERAPEUTIC TARGETS TO OVERCOME STEROID RESISTANCE IN SEVERE ASTHMA
Pazdrak K 1, Straub C1, Kurosky A1
1The University of Texas Medical Branch, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: The absence of therapeutic alternatives in severe asthma with resistance to glucocorticosteroids (GC) poses a genuine health challenge and financial burden as steroid‐resistant patients account for more than 50% of asthma‐related healthcare costs. The mechanism that causes dysfunctional GC response in asthma is not understood. Using comparative proteomics we identified over 200 differentially expressed proteins in GC‐resistant eosinophils that may serve as biomarkers of steroid insensitivity and have potential for development of therapeutic targets. With recently established proteomic map of eosinophil, deciphering the molecular machinery underlying the eosinophil’s resistance to GC can now begin in earnest. METHODS/STUDY POPULATION: Expression of phosphatases PP5 and MKP1 and kinases p38 and PKCβII was tested in eosinophils obtained from severe asthmatics and in cells with in vitro induced steroid resistance. Cell function assays upon inhibition of PP5 or p38 were performed to assess responsiveness to GC. RESULTS/ANTICIPATED RESULTS: We found that steroid‐resistant eosinophils are characterized with increased expression of PP5, enhanced phosphorylation of p38, and PKCβII and decreased expression of MKP1. Inhibition of PP5 expression or p38 phosphorylation restored function of MKP1 and restored antiinflammatory effect of GC on eosinophils. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the next step in a continuum of our translational research that is expected to lead to discovery of mechanisms of steroid resistance beyond a narrow focus on asthma and allergy. Once such strategies are available, other chronic inflammatory diseases associated with steroid insensitivity could be efficiently treated. Decreasing expression phosphatase PP5 or kinase p38 alone may prove to be sufficient for this purpose.
P219
DEVELOPMENT AND VALIDATION OF A WIRELESS ACTIVITY AND HEART RATE SENSOR IN OVERWEIGHT CHILDREN
Martino SA 1, Brittelli J1, Morelli PJ2, Das SR1, Gouzman M1, Sisto SA1
1Stony Brook University, Stony Brook, NY, USA; 2Columbia University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: The prevalence of childhood obesity has reached epidemic proportions with subsequent comorbidities such as hypertension, dyslipidemia and type 2 diabetes. Reduced physical activty (PA) is a contributing factor. Overestimation of PA by overweight (ovwt) pts has been shown. Ovwt individuals may expend greater energy when moving due to a larger mass but overall have decreased PA levels. Objective assessment of PA levels and energy expenditure in this population is essential. Spec Aim 1: To develop a wireless PA and HR sensor for use among ovwt children. Spec Aim 2: To determine if children will reliably report levels of PA and exertion as compared to the sensor. METHODS/STUDY POPULATION: The PA sensor has been developed and is being refined and validated on a populaton of ovwt and age matched normal wt children. This project is being conducted by a multidisciplinary team of physical/respiratory therapists, computer science/wireless sensor faculty, and electrical engineers. Energy expenditure will be quantified by indirect calorimetry. A clinical trial of children enrolled in an existing lifestyle modification program will ensue. RESULTS/ANTICIPATED RESULTS: Translational in nature, this project will result in the development, refinement and validation of a miniaturized PA and HR sensor for overweight children in the lab, clinc and community setting. This pilot data/sensor will support a future grant application. DISCUSSION/SIGNIFICANCE OF IMPACT: Annual cost for obesity related illness is ~≥147 billion in America. This points to the need for prevention and treatment of this disease. Monitoring of PA is an effective tool to combat obesity. Future use of wireless PA monitoring systems in classrooms/ community settings combined with structure lifestyle modification programs may prove beneficial in combating the childhood obesity epidemic.
P220
DEVELOPMENT OF A PRECLINICAL PEDIATRIC MODEL OF PULMONARY ARTERY STENOSIS
Breinholt JP 1, Byrd JP1, Sturek M1
1Indiana University School of Medicine, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: (1) Develop a preclinical animal model of pulmonary artery stenosis (PAS). (2) Determine time course and severity of PAS elicited by intravascular injury methods. METHODS/STUDY POPULATION: Prior studies of PAS have used surgical, external compression methods of stenosis. For evaluation of stent implantation, this method or native vessels have been used. We attempted multiple intravascular methods to determine the optimal modality to induce vessel injury. Pulmonary artery overdilation was initially selected due to prior studies in coronary artery disease. A novel drug delivery balloon was utilized to deliver a sclerosant (first 70% ethanol, then morrhuate sodium (MS)). Cutting balloons were used to create a controlled, intimal tear in the vessel, resulting in scar formation. RESULTS/ANTICIPATED RESULTS: Sixteen Ossabaw piglets underwent cardiac catheterization. Alcohol sclerosant was administered in 1 piglet with no result. Five piglets received MS. In 3/5 of the MS piglets, mild tapering of the pulmonary artery was noted, but no discrete stenosis. Histology demonstrated a mild inflammatory response relative to control vessels. Angioplasty balloon overdilation was used in 6 piglets (2 received MS to the contralateral lung). No stenosis was noted from overdilation acutely or at follow‐up. Cutting balloon injury was used in 6 piglets of which 1 was available for histology. Mild stenosis was noted at follow‐up angiography and moderate inflammation was noted on histology. Four mortalities have occurred; 2 from cutting balloon injury, 2 from overdilation injury to the pulmonary artery. DISCUSSION/SIGNIFICANCE OF IMPACT: Using these modalities, we demonstrated mild stenosis generated by a chemical sclerosant and cutting balloons. Future directions include use of radiofrequency energy to generate injury. This model then will be used to implant stents at injury sites.
P221
DIFFERENTIAL EXPRESSION OF HSP90AA1 ASSOCIATED WITH FIBROMYALGIA
Majors B 1, Saligan LN1, Wang D1, Walitt B2
1National Institute of Nursing Research, NIH, Bethesda, MD, USA; 2MedStar Health Research Institute, Washington Hospital Center, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Fibromyalgia is a complex disorder characterized most commonly by chronic widespread pain, sleep disturbance, and fatigue. It affects approximately 1–2% of the population, and is seen predominantly in females. The underlying physiologic cause(s) of fibromyalgia are unknown, thus impeding development of consistently effective treatment options. The present study was designed to identify differential gene expression in patients with fibromyalgia. METHODS/STUDY POPULATION: Participants (N = 23, 100% female, 100% Caucasian, ages 30–50) were recruited and consented at the Georgetown University Medical Center’s General Research Clinical Center. The fibromyalgia diagnosis was confirmed by a credentialed rheumatologist using the 2011 American College of Rheumatology’s Diagnostic Criteria for Fibromyalgia. Age‐matched healthy, pain‐free controls were used to compare differential gene expression. Whole blood was collected via venipuncture using PAXgene RNA tubes, RNA was isolated and purified, and the Affymetrix GeneChip 39 IVT Express Kit and GeneChip Human Genome U133 Plus 2.0 Array were used to prepare samples and analyze gene expression. RESULTS/ANTICIPATED RESULTS: There was a significant >2‐fold (p < 0.001) up‐regulation of HSP90AA1 in patients with fibromyalgia compared to controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Heat‐shock protein 90 kDa alpha, class A member 1 (HSP90AA1) is one of a family of heat‐shock proteins which play a vital role in signal transduction, folding of new proteins, and stabilization of denatured proteins. It is a molecular chaperone that has been noted to have an impact on the aging process. In an animal study, HSP90AA1 is associated with environmental adaptation. The up‐regulation of HSP90AA1, the gene encoding this protein, may have implications regarding the mechanisms behind fibromyalgia.
P222
DIFFERENTIAL PROTEIN EXPRESSION IN SMALL INTESTINAL CARCINOIDS AND LIVER METASTASES
Kim M 1, Wang D1, Cui M1, Curran T1, Ward S1, Warner RR1, Roayaie S1, Shafir M1, Schwartz M1, Zhang D1, Itzkowitz S1
1Mount Sinai School of Medicine, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Small intestinal carcinoids (SICs) are often detected late in their clinical course. We have recently developed a Protein Pathway Array to screen for changes in protein and phosphoprotein expression in primary and metastatic tumors. The objective of our study was to identify key pathways important in the mechanism of SIC metastasis development. METHODS/STUDY POPULATION: Primary tumors and liver metastases from 5 patients undergoing surgical resection for metastatic SIC were harvested. Extracted proteins were separated by SDS gel, and Western blots were performed with 136 antibodies. Band densities were determined using BioRad Image system. Significant Analysis of Microarray (SAM) was used to select the proteins differentially expressed between different groups. Tissue microarray (TMA) was constructed from archived specimens and stained by immunohistochemistry. RESULTS/ANTICIPATED RESULTS: Nine proteins were up‐regulated in primary SICs compared with matched normal small bowel mucosa. Cyclin E was down‐regulated in primary SIC tissue compared to normal small bowel mucosa. SIC liver metastases demonstrated up‐regulation of P‐ERK and p27 but down‐regulation of CDK2 and CDC25B. When comparing primary SIC with their paired liver metastases, cyclin E demonstrated a significant up‐regulation in the liver metastasis. Tissue microarray demonstrated higher p38 expression and lower Cdc 25b expression in SICs versus liver metastases and confirmed higher expression of p27 in liver metastases versus normal liver. DISCUSSION/SIGNIFICANCE OF IMPACT: Few studies have compared gene or protein expression in primary and metastatic SIC tumors resected simultaneously. Our findings using Protein Pathway Array reveal changes in a limited number of proteins, suggesting that these may be targets for therapy.
P223
DNA METHYLATION DYNAMICS IN SCHIZOPHRENIA
Gavin DP 1, Guidotti A1
1The University of Illinois at Chicago, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Lower GAD67 expression in postmortem brain samples from schizophrenia (SZ) patients is perhaps the most replicated finding in SZ research. Reports from our lab and others have indicated an abnormally epigenetically restrictive chromatin state may contribute to this reduction. Recently, we reported increased mRNA and protein expression of a gene involved in removing the restrictive 5‐methylcytosine (5MC) mark, GADD45b, in psychotic postmortem brain samples, but reduced binding to a BDNF promoter. METHODS/STUDY POPULATION: In fresh frozen parietal samples (nonpsychiatric = 15; SZ = 15) we measured expression of GAD67, and three histone methyltransferases (GLP, G9a, SETDB1) that catalyze the formation of the transcription silencing modification of dimethylated lysine 9 of histone 3 (H3K9me2) using qRT‐PCR with normalization to β‐Actin and TFRC. We used ChIP to measure GADD45b promoter binding and its association with 5‐hydroxymethylation (5HMC) and 5MC using methylated DNA immunoprecipitation (MeDIP). RESULTS/ANTICIPATED RESULTS: In SFNC cortical parietal samples there is decreased GADD45b binding to the GAD67 promoter (p = 0.020) with increased 5HMC (p = 0.042), and reduced GAD67 mRNA expression (p = 0.042) in SZ. We also find increased GLP mRNA expression in SZ (p = 0.009), but no differences in G9a or SETDB1. DISCUSSION/SIGNIFICANCE OF IMPACT: We reported less GADD45b binding to GAD67 despite increased GADD45b expression. A possible explanation is restrictive histone modifications barring GADD45b promoter access. We find increases in an enzyme that catalyzes H3K9me2 formation, GLP, in SZ postmortem brains. Other GADD45 proteins interact with gene promoters by binding acetylated histones. The highly durable H3K9me2 blocks H3K9 acetylation (H3K9ac). This may lead to lower GADD45b binding and higher DNA methylation in SZ.
P224
DUAL‐WAVELENGTH PHOTOTHERMAL OCT FOR DEPTH‐RESOLVED MEASUREMENT OF MICROVASCULAR HEMOGLOBIN OXYGEN SATURATION
Kuranov RV 1, Kazmi S2, McElroy AB2, Kiel JW1, Dunn AK2, Milner TE2, Duong TQ1
1University of Texas Health Science Center San Antonio, San Antonio, TX, USA; 2University of Texas, Austin, TX, USA
OBJECTIVES/SPECIFIC AIMS: Objective of this study was to estimate depth resolution of Dual‐Wavelength Photothermal Optical Coherence Tomography (DWP‐OCT) for measuring hemoglobin oxygenation saturation (SaO2) in a murine brain model. METHODS/STUDY POPULATION: DWP‐OCT was used to measure photothermal‐induced optical pathlength (op) variations versus depth in murine brain in vivo. The DWP‐OCT probe was directed at a 30 μm diameter arteriole under guidance of a surgical microscope. Blood in the arteriole in vivo was excited with intensity‐modulated light at 770 nm and 800 nm. Ratio of op changes normalized by fluence of photothermal excitation light can be used to compute in vivo SaO2 levels. We investigated depth resolution provided by DWP‐OCT for measuring in vivo SaO2 levels. RESULTS/ANTICIPATED RESULTS: DWP‐OCT depth resolution can be estimated from depth‐resolved op measurements in tissue containing a single arteriole. Amplitude of op variation per mW of photothermal excitation light (800 nm) with depth was measured. We approximate depth dependence of op by assuming spatial variation of temperature increase is Guassian so that op varies as an error function: op ~ Erf(a[z‐z0]), where z0 = 568 μm is the center of absorption (arteriole) and a = 0.031 μm−1 is inversely proportional to the effective longitudinal size of the temperature increase. The longitudinal full width at half maximum (FWHM) of the temperature increase z* = 2(ln2)0.5/a = 45 μm gives DWP‐OCT depth resolution to measure SaO2 levels. DISCUSSION/SIGNIFICANCE OF IMPACT: This study provides a numerical estimate of depth resolution of DWP‐OCT to measure SaO2 levels. DWP‐OCT may be useful in layer‐specific quantification of abnormal tissue oxygenation in several retinal disorders such as diabetic retinopathy.
P225
EFFECT OF INTRAVENOUS ALCOHOL ON HPA AXIS HORMONES IN HEALTHY MALES
Coe MA 1, Schwandt ML1, Umhau J1, Sun H1, Heilig M1, Ramchandani VA1
1NIH/NIAAA, Bethesda, MD, USA
OBJECTIVES/SPECIFIC AIMS: The objective of this study was to examine the effect of IV alcohol on HPA axis hormones and the influence of a functional mu‐opioid receptor polymorphism (OPRM1 A118G) on this effect in healthy males. METHODS/STUDY POPULATION: Healthy male social drinkers were screened to obtain two groups: (1) subjects homozygous for the major 118A allele (118AA); and (2) subjects carrying 1 or 2 copies of the variant 118G allele (118GX). Subjects were challenged in separate sessions, one with IV alcohol to a target breath alcohol level of 0.08% and one placebo, and plasma levels of ACTH (adrenocorticotropic hormone) and cortisol were measured at four timepoints. Repeated measures ANOVA was conducted to examine the effect of treatment, time, genotype, and baseline levels on change in hormone levels. RESULTS/ANTICIPATED RESULTS: There was a significant main effect of treatment and time for change in ACTH, with a greater decrease in ACTH following alcohol compared to placebo. There was a treatment by baseline level interaction for ACTH, suggesting that baseline ACTH level is an important determinant of the ACTH‐lowering effect of alcohol. Alcohol had no effect on change in cortisol, although there was a significant effect of baseline levels. OPRM1 A118G genotype was not a significant predictor of change in ACTH or cortisol. DISCUSSION/SIGNIFICANCE OF IMPACT: The greater decrease in ACTH following alcohol is consistent with the stress‐lowering effects of alcohol. Given the strong baseline effects for ACTH, this study highlights the importance of basal ACTH hormone levels in regards to alcohol consumption and possibly vulnerability to alcohol use disorders.
P226
EMBRYONIC STEM CELL AS TUMOR VACCINE: EFFICACY AND MECHANISM
Liu B 1, Li Z1
1Medical University of South Carolina, Charleston, SC, USA
OBJECTIVES/SPECIFIC AIMS: We have previously demonstrated that human embryonic stem cells (ESCs) can be used as a tumor vaccine against murine colon cancer. This study aimed to determine the efficacy and mechanism of ESC vaccine against cancer by using mouse ESCs from syngeneic and allogenic source in a murine transplantable CT26 colon cancer model. METHODS/STUDY POPULATION: For tumor rejection assays, mice were immunized subcutaneously with 1×106 irradiated mESCs (15 Gy) or CT26 tumor cells (75 Gy) twice at a 1‐week interval. At 1 week after immunization, mice were challenged with 5×105 live CT26 cells subcutaneously. Tumor growth was monitored every 3 days. The primary tumor was also excised and weighed after the mice were sacrificed. Cell surface staining and analysis for immunophenotype on a FACSCalibur and results were analyzed with FlowJo software. RESULTS/ANTICIPATED RESULTS: We found that BALB/c mice immunized with irradiated ESCs derived from both 129Sv and BABL/c mice were conferred protection against live tumor challenge. Alteration of macrophages, MDSCs and activation status of T cells were observed in ESC‐immunized mice. We also observed a shift of dendritic cells (DCs) status to a proinflammatory phenotype by coculture mESCs and bone marrow–derived DCs. DISCUSSION/SIGNIFICANCE OF IMPACT: We demonstrate mouse ES cells to effectively immunize against murine colon cancer and the effects of ESCs on maturing bone marrow–derived DCs. This suggests that ESCs holds promise as an emerging cancer vaccine platform via delivering both cross‐reactive embryonic antigens and an immunoadjuvant effect.
P227
ETHNIC DIFFERENCES IN PAIN‐RELATED PHYSIOLOGICAL MEASURES
Sibille KT 1, Millard WJ1, Fillingim RB1
1University of Florida, Gainesville, FL, USA
OBJECTIVES/SPECIFIC AIMS: Examine ethnic differences in pain‐related physiological measures and associations with pain sensitivity. METHODS/STUDY POPULATION: Two hundred sixty‐seven healthy adults, 85 African Americans (AA), 91 non‐Hispanic whites (NHW), and 81 Hispanic whites (H) completed cold pressor (CP), ischemic (IS), heat, and pressure pain testing with blood pressure (BP), heart rate, and cortisol (CO) collected at: baseline, posttest, and after 20 minutes. RESULTS/ANTICIPATED RESULTS: Ethnic differences in pain responses and physiological measures were demonstrated. Ethnic groups differed on baseline BPs, AA having higher BP compared to NHW and H. Changes in BP following CP were similar across group, but SBP increases were positively associated with CP tolerance in AA, while changes in DBP following CP were negatively associated with CP tolerance in NHW (p < 0.015), and there were no associations between BP and CP measures in H. During IS testing, NHW showed a greater increase in SBP and DBP from baseline compared to AA and H. IS tolerance was positively correlated with IS baseline BP and negatively correlated with BP changes following IS testing in AA but not in NHW or H (p < 0.05). Ethnic group differences in CO were also observed. In general, NHW had higher baseline CO levels and showed greater increases in CO post‐CP testing compared to AA and H. Post‐test CO changes were positively associated with IS tolerance across all groups and IS threshold in AA and NHW but not H. Posttest CO changes were positively related to CP tolerance in AA and H but not NHW. DISCUSSION/SIGNIFICANCE OF IMPACT: Results extend prior findings of ethnic differences in experimental pain sensitivity and pain‐related physiological measures. Associations between pain sensitivity and pain‐related physiological measures encourage further examination of the complex array of factors contributing to ethnic differences in pain sensitivity.
P228
EVALUATING AN ECoG‐BASED BRAIN‐COMPUTER INTERFACE IN AN INDIVIDIUAL WITH TETRAPLEGIA
Wang W 1, Collinger JL1, Degenhart AD1, Wodlinger B1, Tyler‐Kabara EC1, Boninger ML1
1University of Pittsburgh, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: Brain‐computer interface (BCI) technology aims to establish a direct link for transmitting information between the brain and external devices. It has the potential to offer a natural and rich control signal for robotic devices, prosthetic limbs, or functional electrical stimulators to reanimate paralyzed limbs. Our group’s clinical research interest is to translate basic BCI research into clinically viable BCI devices. One of the major challenges in translating this technology from laboratory research into clinical practice is to develop a minimally invasive technique for obtaining reliable long‐term neural recording with high spatial and temporal resolution. We propose ECoG as a realistic approach that strikes an optimal balance in the tradeoffs associated with neural signal quality, invasiveness, system complexity, and maintenance. METHODS/STUDY POPULATION: We conducted a translational ECoG‐based BCI study in an individual with tetraplegia caused by cervical spinal cord injury. We implanted a high‐density ECoG grid of 32 platinum disc electrodes over the hand and arm area of left motor cortex. RESULTS/ANTICIPATED RESULTS: The participant achieved reliable control of two‐ and three‐ dimensional (2D and 3D) movements of a cursor in a virtual environment using ECoG signals. Per FDA regulation, the ECoG grid was explanted 28 days postimplantation with no adverse effect. DISCUSSION/SIGNIFICANCE OF IMPACT: To our knowledge the current study is the first demonstration of the efficacy and clinical viability of ECoG‐based BCI technology in an individual with tetraplegia.
P229
EVALUATING KETOPROFEN AS PREVENTIVE PHARMACOTHERAPY FOR ACQUIRED LYMPHEDEMA
Feroze A 1, Kim J1, Begaye A1, Jacome‐Roche L1, Yang N1, Rockson S1
1Stanford University School of Medicine, Stanford, CA, USA
OBJECTIVES/SPECIFIC AIMS: (1) To evaluate ketoprofen as a prophylactic measure for lymphedema given its previously noted properties at ameliorating symptoms of acquired lymphedema. (2) To compare the specific treatment effect observed using ketoprofen with other NSAIDs to further elucidate its mechanism of action. METHODS/STUDY POPULATION: Based upon findings of our lab demonstrating the ability of ketoprofen to ameliorate lymphatic vascular insufficiency in a murine tail lymphedema model mimicking human acquired lymphedema (Nakamura et al, PLoS 2009), we are currently conducting phase II studies on human subjects to study the drug in treating secondary lymphedema. Simultaneously, our lab is exploring potential prophylactic properties of ketoprofen in similar mouse models. In addition, we are exploring whether the therapeutic potential of treating lymphedema is specific to ketoprofen alone or is seen in other therapeutic agents with overlapping characteristics. RESULTS/ANTICIPATED RESULTS: Our studies suggest potential for prophylactic therapy for high‐risk patients. Treated specimens demonstrated qualitative histological improvement of the tissue and decreased tail volumes compared to controls, similar to the response seen in human lymphedema skin biopsy specimens. Data comparing ketoprofen to ibuprofen, another nonselective COX1/COX2 inhibitor, suggests the treatment effect seen is specific to ketoprofen. Studies with similar agents are planned. DISCUSSION/SIGNIFICANCE OF IMPACT: Acquired lymphedema is a common and disabling state of vascular insufficiency lacking satisfactory pharmacotherapeutics. Four hundred thousand Americans suffer from lymphedema of the upper extremity alone, primarily due to lymph node dissection and radiation therapy secondary to cancer therapies. The repurposing of a safe and inexpensive noninflammatory drug such as ketoprofen could revolutionize treatment approaches for this disease.
P230
EVALUATION OF THE UPPER AIRWAY AND LUNG MICROBIOMES
Segal LN 1, Kulkarni R1, Rom W1, Weiden M1
1NYU School of Medicine, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: The lung is classically thought to be sterile although molecular techniques for microbial identification are now suggesting the existence of a human airway microbiota. The study of the microbiome has now opened an opportunity to characterize resident microbial flora without the need for bacterial culture although the lung microbiome in smokers has not been characterized. We therefore tested the hypothesis that in smokers, the upper and lower airways contain a distinct microbiota. METHODS/STUDY POPULATION: We obtained supraglotic and broncho‐alveolar lavage (BAL) samples in 8 subjects. Bacterial quantification of supraglotic aspirate and BAL was determined by qPCR using universal primers for 16S rDNA. Dilution was corrected by urea. We defined bacteria OTU by 454 sequencing. We performed cluster analysis, principal coordinate analysis and weighted UniFrac to determine microbiome. RESULTS/ANTICIPATED RESULTS: Subjects were 55 ± 13 yo, 4/8 female and 7/8 significant smokers (>10 pack/year). FEV1 was 94 ± 11%, FVC 108 ± 10% and FEV1/FVC was 71 ± 8. Bacteria rDNA was higher in the supraglotic area than BAL (1.5e9 ± 3.2e9 vs. 1e7 ± 8.2e6 copies/mL of adjusted fluid, p < 0.001). Clustering of the bacterial community at the family level showed distinct microbiome in the upper airway and the lung (BAL). While Prevotellaceae, Veillonellaceae and Fusobacteriaceae predominated in the supraglotic sample, Micrococcaceae, Propionibacteriaceae and Staphylococcaceae among others predominated in BAL. UniFrac calculated distances showed no overlapping circle of inertia between supraglotic and BAL (p < 0.0001 for first principal axis). DISCUSSION/SIGNIFICANCE OF IMPACT: In the absence of signs or symptoms of infection, subjects had significant airway resident bacteria. This supports the existence of a bacterial reservoir in the lung, which might be influenced by smoking and/or innate immunity.
P231
EVIDENCE OF AXONAL INJURY IN CHILDREN WITH MILD TRAUMATIC BRAIN INJURY
Babcock L 1, Yuan W1, McClanahan N1, Wang Y1, Bazarian J2, Wade S1
1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 2University of Rochester Medical Center, Rochester, NY, USA
OBJECTIVES/SPECIFIC AIMS: To examine acute anisotropic diffusion properties based on diffusion tensor imaging (DTI) in youth with mild traumatic brain injury (mTBI) relative to orthopedic controls and to examine associations between white matter (WM) integrity and post concussion symptoms (PCS). METHODS/STUDY POPULATION: Interim analysis of a prospective case‐control cohort involving 12 youth ages 11–16 years with mTBI and 10 orthopedic controls. Demographics, clinical information, and symptoms were collected in the ED. Within 72 hours of injury, symptoms were reassessed and a 61 direction, diffusion weighted, spin‐echo imaging scan was performed. DTI images were analyzed using tract‐based spatial statistics. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured. RESULTS/ANTICIPATED RESULTS: There were no group demographic differences between mTBI cases and controls. PCS symptoms were greater in mTBI cases than in the controls at ED visit (30.1 ± 17.0 vs. 15.5 ± 16.8, p < 0.06) and at the time of scan (19.1 ± 12.9 vs. 5.7 ± 6.5, p < 0.01). The mTBI group displayed decreased FA in cerebellum and increased MD and AD in the cerebral WM relative to controls (uncorrected p < 0.05). Increased FA in cerebral WM was also observed in mTBI patients but the group difference was not significant. PCS symptoms at the time of the scan were positively correlated with FA and inversely correlated with RD in extensive cerebral WM areas (p < 0.05, uncorrected). In addition, PCS symptoms in mTBI patients were also found to be inversely correlated with MD, AD, and RD in cerebellum (p < 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: DTI detected axonal damage in youth acutely following mTBI which correlated with PCS symptoms. DTI may augment detection of injury and help prediction of those with worse outcomes.
P232
EXECUTIVE FUNCTION AND HYPOTHALAMIC‐PITUITARY‐ADRENAL AXIS ACTIVATION IN CIVILIAN TRAUMA AND POSTCOMBAT PTSD
Lapiz‐Bluhm M 1
1University of Texas Health Science Center, San Antonio, TX, USA
OBJECTIVES/SPECIFIC AIMS: Posttraumatic stress disorder (PTSD) is a chronic anxiety disorder that develop following a traumatic stress exposure. PTSD may be associated with changes in prefrontal cognitive function and HPA axis dysregulation, reflected by changes in cortisol and DHEA (dehydroepiandrosterone). The nature of this association is not fully understood. This study aims to characterize the prefrontal cognitive functioning and HPA axis involvement in individuals with PTSD following combat and civilian trauma. METHODS/STUDY POPULATION: Individuals (N = 36) who experienced civilian or combat trauma in the past 12 months and normal healthy controls completed the demographics survey and PTSD Symptom Scale‐Interview (PSSI). They then took the Wisconsin Card Sorting Test (WCST), a cognitive test for executive prefrontal function. They collected salivary samples at 6 time points: (1) early evening; (2) before bed; (3) immediately upon wake‐up; (4) 30 minutes after wake‐up; (5) mid‐morning, and (6) early evening the next day, for 3 consecutive days. Samples were analyzed for cortisol and DHEA levels. RESULTS/ANTICIPATED RESULTS: Individuals who were exposed to trauma scored significantly higher (p < 0.05) in the PSSI test compared to controls. Individuals with high PSSI scores had more perserverative errors in the WCST (p < 0.05). The cortisol and DHEA levels and patterns in individuals with PTSD following civilian trauma and combat trauma were significantly different compared to controls (p < = 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: The development of PTSD symptoms seems to be associated with changes in executive function and differential pattern of cortisol and DHEA activation. The results provide basis to further understand the neurobiological mechanisms of PTSD, and may inform on how these can be restored or overcome by treatment.
P233
FK506 LOADED DENDRITIC CELLS: A CELLULAR APPROACH TO ANTIGEN SPECIFIC DRUG DELIVERY
Orange DE 1,2, Blachere N2, Fak J2, Herre M2, Darnell R2
1Hospital for Special Surgery, New York, NY, USA; 2Rockefeller University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: (1) To determine if FK506 treated DCs are capable of antigen presentation. (2) To determine if FK506 treated DCs lack a necessary stimulatory signal or produce a T cell inhibitor. (3) To determine the effect of FK506 treated DCs in an animal model of arthritis. METHODS/STUDY POPULATION: Pbmc derived DCs were treated with FK506, washed extensively and compared to untreated DCs in their ability to stimulate allogeneic or memory T cells and express cell surface maturation markers. To determine if FKDCs produced an inhibitory molecule, they were mixed with untreated DCs and tested for their ability to activate T cell responses. FK506 was measured from washed FKDC supernatants at time points via ELISA. FKDCs or untreated DCs were pulsed with relevant or irrelevant antigen and infused in mice after induction of collagen induced arthritis and mean arthritis severity score was measured. RESULTS/ANTICIPATED RESULTS: (1) FKDCs are poor stimulators of T cell responses despite adequate expression of signal one and signal two. Although FKDCs express normal levels of maturation markers and costimulatory molecules, they are poor activators of allogeneic T cells as well as memory T cells, however are able to serve as targets of flu specific CTLs. (2) Mixing FKDCs with untreated DCs leads to inhibition of T cell activation implying FKDCs generate a T cell inhibitor. Direct measurement of FK506 from FKDC supernatants demonstrated that although FK506 was not detectable after the last wash, 6 hours later, supernatants contained 10 nM FK506. (3) FKDC loaded with relevant antigen, but not irrelevant antigen suppress arthritis in the collagen induced arthritis mouse model of rheumatoid arthritis. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings provide proof of concept that drug loaded DCs can be used as an antigen specific drug delivery system.
P234
FKS MUTATIONS ARE MORE SENSITIVE THAN ECHINOCANDIN MICS IN PREDICTING THERAPEUTIC FAILURES AMONG PATIENTS WITH INVASIVE CANDIDIASIS DUE TO CANDIDA GLABRATA
Shields RK 1, Nguyen M1, Press EG1, Clancy CJ1
1University of Pittsburgh, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: To correlate clinical responses to echinocandin therapy with echinocandin (EC) minimum inhibitory concentrations (MIC) and FKS gene mutations. METHODS/STUDY POPULATION: We tested 39 C. glabrata isolates recovered from pts with invasive candidiasis for susceptibility to caspofungin (CSP), anidulafungin (ANF) and micafungin (MCF) and determined if MIC correlated with the response to therapy. We also evaluated FKS1 and 2 mutations and linked their presence to MICs and outcomes. RESULTS/ANTICIPATED RESULTS: Thirty‐five pts had candidemia and 4 had abdominal abscesses. All patients were treated with an EC and intravascular catheters were removed at the diagnosis. 26% (10/39) of pts failed EC therapy. The range of CSP, ANF, and MCF MICs were 0.5–8, 0.03–1, and 0.015–0.5 μg/mL. Median CSP and ANF MICs were higher in cases of failure (p = 0.04 and 0.006, respectivlely). FKS mutations were detected in 7 isolates, and were associated with higher CSP (1.5 vs. 0.5; p < 0.0001), ANF (0.38 vs. 0.04 μg/mL; p < 0.0001) and MCF (0.25 vs. 0.03 μg/mL p < 0.0001) mean MICs. ROC analysis identified the optimal breakpoint (bp) for CSP MIC to be ≥0.5 μg/mL. At this bp, sensitivity, specificity, and likelihood ratio (LR) were 60%, 86%, and 0.69. ROC analysis suggested optimal bp ≥0.06 and ≥0.03 for ANF and MCF, respectively. Sensitivity, specificity, and LR were 50%, 97%, and 14.5 for the ANF bp, and 40%, 90%, and 3.9 for MCF. The corresponding values for FKS mutations were 60%, 97%, and 17.4, respectively. Moreover, FKS mutation was the only independent risk factor for therapeutic failure. DISCUSSION/SIGNIFICANCE OF IMPACT: Detection of FKS mutations is more sensitive than EC MICs in predicting therapeutic failure. Clinical use of MICs is further limited by clustering of values within a narrow range.
P235
FUNCTIONAL SYNERGY BETWEEN THE KLF6‐SV1 AND c‐MYC ONCOGENES IN DRIVING PROSTATE CANCER METASTASIS
Izadmehr S 1, Fernandez H1, Lee C1, Hatami R1, Kirschenbaum A1, Levine A1, Difeo A1, Narla G1
1Mount Sinai School of Medicine, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Prostate cancer (PCa) is the second leading cause of cancer‐related deaths among men in the United States. Many prostate tumors remain indolent and localized, while others result in metastatic and castrate‐resistant disease. This transition is considered to be clinically relevant as our ability to distinguish between indolent and lethal metastatic forms of PCa has led to either undertreatment of potentially poor behaving tumors or overtreatment of otherwise indolent disease. We are interested in elucidating a gene signature that may differentiate between indolent and lethal disease. METHODS/STUDY POPULATION: Previous studies have shown that high levels of c‐MYC and KLF6‐SV1 play an important role in PCa. Overexpression of c‐MYC results in the development of both high‐grade PIN and moderately differentiated PCa. KLF6‐SV1 overexpression has been observed in locally invasive and metastatic PCa. Therefore, the synergistic role of these genes may cause the progression of moderately differentiated prostate cancer to poorly differentiated prostate cancer. To define c‐MYC and KLF6‐SV1’s functional role, we have developed a novel KLF6‐SV1/c‐MYC PCa mouse model. RESULTS/ANTICIPATED RESULTS: Our model faithfully recapitulates the entire spectrum of human PCa development. KLF6‐SV1/c‐MYC mice present with highly aggressive and metastatic adenocarcinoma. This is not observed in wild‐type, c‐MYC or KLF6‐SV1 mice. Given these results, we will further validate our findings in PCa patient samples through correlation studies of KLF6‐SV1/c‐MYC levels and the outcome of disease. DISCUSSION/SIGNIFICANCE OF IMPACT: This data provides preliminary support that increased c‐MYC and KLF6‐SV1 expression may drive a gene signature that can act as a prognostic indicator of aggressive and potentially metastatic PCa.
P236
GENOMIC VARIATION, ANXIETY, AND STRESS IN CHILDREN HAVING MEDICAL PROCEDURES
Ersig A 1, Standley J2, Kleiber C1, McCarthy A1, Murray J2
1University of Iowa College of Nursing, Iowa City, IA, USA; 2University of Iowa Carver College of Medicine, Iowa City, IA, USA
OBJECTIVES/SPECIFIC AIMS: Children having painful medical procedures [e.g., intravenous catheter (IV) insertion] experience varying levels of distress; high levels of child anxiety are associated with greater procedural distress and pain. Child anxiety is influenced by genetics and the environment. Previous research has explored associations between genotype and pathological anxiety in children, but has not examined the association of genotype with procedural anxiety. The purpose of this study is to explore the association of genomic variation with high levels of anxiety in children having an IV inserted. METHODS/STUDY POPULATION: A secondary data analysis used an existing dataset with DNA and phenotype data from over 1000 children ages 4–10 years who had an IV placed for a diagnostic procedure. The primary outcome of interest was child anxiety related to the medical procedure. Child and parent DNA was obtained from whole blood, buccal swabs, or saliva. Single nucleotide polymorphisms (SNPs) of interest were selected based on prior association with anxiety phenotypes. Analyses examined association of SNP genotype with anxiety measures. RESULTS/ANTICIPATED RESULTS: Twenty‐five SNPs were selected for initial analysis, based on previous research. Genes of interest included GABRA2, SLC6A4, BDNF, and CRHR1, among others. Results of analyses examining associations of selected SNPs with procedural anxiety will be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: Results of this and future analyses will inform studies exploring methods to predict which children are at risk of high levels of procedural anxiety, and the development of personalized interventions to improve procedural anxiety.
P237
HIGH EXTRACELLULAR GLUCOSE ASSOCIATED WITH TYPE 1 DIABETES MODULATES BONE CELL MECHANOTRANSDUCTION
Thi MM 1,2, Spray DC2, Suadicani SO3,2
1Dept of Surgery, Division of Orthopaedic Surgery, Albert Einstein College of Medicine, Bronx, NY, USA; 2Dept of Neuroscience, Bronx, NY, USA; 3Dept of Urology, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: Although patients with Type 1 diabetes display higher bone loss and risk for osteoporosis, the underlying mechanisms are still unclear. Given that maintenance of skeletal integrity in response to physical activity relies on regulation of the bone forming cells, osteoblasts, and the primary load sensing cells, osteocytes, we hypothesized that bone loss in diabetes is due to compromised ability of bone cells to sense and respond to mechanical loading as a result of changes in bone cells pericellular matrix (PCM) and altered expression of purinoceptors (P2Rs) and pannexin1 (Panx1) channels. METHODS/STUDY POPULATION: MOB‐C (osteoblastic cells) and MLO‐Y4 (osteocytic cells) were cultured for 10 days in media with 100 and 450 mg/dL glucose to simulate in vitro the glucose levels to which bone cells are exposed in healthy versus diabetic bones. PCM thickness was determined by heparan sulfate staining; P2Rs and Panx1 expression was analyzed by Western blot. To simulate loading cells were subjected to oscillatory fluid shear stress in a flow chamber. RESULTS/ANTICIPATED RESULTS: Exposure to high glucose (HG) altered PCM thickness in both cell types. P2Y1R expression remained the same but HG exposure differentially regulated P2Y2R, P2Y4R and P2X7R and Panx1 expression. The P2X7R and Panx1 in MLO‐Y4 was down‐regulated in HG while P2Y2R and P2Y4R in MOB‐C were up‐regulated. Moreover, FSS‐induced ATP release and FSS‐induced Ca2+ transients were lower in HG compared to control condition. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings indicate that HG‐induced thickening of bone PCM and altered P2R and Panx1 expression impair proper sensing and transduction of FSS, which modify the adaptive response of bone cells to mechanical loading. (Supported by RO1DK 091466).
P238
HIGH RESOLUTION IMAGING AND ABLATION FOR DIAGNOSIS AND TREATMENT OF AIRWAY CANCER
Zhang J 1, Chou D1, Chen Z1
1University of California, Irvine, Irvine, CA, USA
OBJECTIVES/SPECIFIC AIMS: Development of a diagnostic‐therapeutic airway endoscope platform prototype combining fast acquisition 3D high‐resolution optical coherence tomography (OCT), white‐light endoscopy (WLE) and therapeutic ND:YAG laser delivery in a single integrated endoscopic probe capable of precise computer controlled treatment and delivery in order to optimize airway cancer diagnosis and treatment and minimize collateral damage to normal airway tissue. METHODS/STUDY POPULATION: We developed a high speed, high resolution endoscopic Fourier domain OCT (FDOCT) system and a GPU/multicore‐CPU engine for real‐time imaging. We also developed rigid diagnostic/therapeutic endoscopes with the ability to precisely control laser beam position, aim, focus, with high resolution imaging of the target tissue. RESULTS/ANTICIPATED RESULTS: The FDOCT system can achieve high speeds (>100 A‐line scan), and a high axial resolution (5 μm) simultaneously. Real time imaging and display of FDOCT systems with 200 kHz A‐line acquisition can be achieved by the use of a GPU based algorithm combined with a dual‐quad‐core high speed CPU processor implementing Intel hyperthreading technology. The develooped prototype diagnostic/therapeutic endoscope is based on a 1 pitch long GRIN lens with two relay lenses placed in front of it. DISCUSSION/SIGNIFICANCE OF IMPACT: The combined high resolution real‐time OCT airway imaging therapeutics endoscopic approach raises the possibility of precise, predetermined computer guided therapeutic airway surgical procedures, externally controlled with real‐time feedback differentiation of target and collateral tissue, and precise directional and power density control. On a broader scale, these are enabling technology approaches for a wide range of malignant and benign pathologic conditions at other sites.
P239
HYPOTHALAMIC NEUROCHEMICAL SUBSTRATES REGULATING CIRCADIAN FLUCTUATIONS IN INTRAOCULAR PRESSURE
Samuels BC 1, Hammes NM1, Johnson PL1, Shekhar A1
1Indiana University School of Medicine, Eugene and Marilyn Glick Eye Institute (BCS/NMH), Department of Psychiatry (PLJ/AS), Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: Circadian fluctuations in intraocular pressure (IOP) correlate with sympathetic activity and have recently been identified as an independent risk factor for progression of glaucoma. The perifornical hypothalamus (PeF) regulates circadian rhythms and sympathetic outflow; therefore, in this study we sought to: (1) determine if stimulating the PeF increased IOP; and (2) identify the neurotransmitters that mediate PeF evoked increases in IOP. METHODS/STUDY POPULATION: The PeF was stimulated by local stereotaxically guided microinjections of a GABAA receptor antagonist bicuculline methoidide (30 pmol/75 nL). Intracranial pressure (ICP) and cardiovascular activity were continuously monitored in isoflurane‐anesthetized rats using an ADI PowerLab system. An iCareLab tonometer was used to record IOP every 2 minutes. RESULTS/ANTICIPATED RESULTS: Chemical stimulation of the perifornical hypothalamus evoked significant increases IOP that followed a cardioexcitatory response and increase in ICP, thus firmly establishing a reproducible hypothalamic model of IOP regulation. Further, this model provides the framework for us to begin examining the role of specific local neuropeptides in evoking these IOP increases using pharmacological and genetic manipulations. DISCUSSION/SIGNIFICANCE OF IMPACT: The neurons in the perifornical region receive strong direct and indirect projections from the suprachiasmatic nucleus and have extensive efferent projections to autonomic sympathetic relays. Therefore, these perifornical neurons are ideally situated to modulate circadian fluctuations in IOP. Broadening our understanding of this pathway may shed light on the neural mechanisms that underlie circadian fluctuations in IOP and may provide novel therapeutic targets for glaucoma therapy.
P240
IDENTIFICATION OF NOVEL INVASIVE MARKERS IN ADIPOSE‐DERIVED MESENCHYMAL STEM CELLS
Lin A 1, Semon J1, Santoke T3, McFerrin H3, Gimble J2, Strong T1, Bunnell B1
1Tulane University, New Orleans, LA, USA; 2Pennington Biomedical Research Center, Baton Rouge, LA, USA; 3Xavier University, New Orleans, LA, USA
OBJECTIVES/SPECIFIC AIMS: Epidemiological evidence supports a correlation between obesity and breast cancer in women. Adipose‐derived mesenchymal stem cells (ASCs) isolated from adipose tissue have been shown to influence the cellular signaling of breast cancer cells. We aimed to determine the homing potential of ASCs isolated from women with abdominal obesity towards breast cancer and identify the mechanism of action. METHODS/STUDY POPULATION: ASCs were isolated from women based on obesity status and deposit site. ASCs were plated in transwell plates to investigate homing potential towards breast cancer. Protease inhibitors were used to identify the family of proteases involved, and RNA and protein analysis was utilized to identify differences among ASCs. RNAi technology was used to confirm the protease involved in invasion. RESULTS/ANTICIPATED RESULTS: ASCs isolated from the abdomen of obese patients (Ob+Ab+) demonstrated a robust increase in invasion, while their migratory potential remained consistent with other ASCs. Ob+Ab+ ASCs expressed decreased calpastatin and increased calpain‐4 and MMP‐15 that correlated with enhanced invasion of ASCs. DISCUSSION/SIGNIFICANCE OF IMPACT: ASCs isolated from the abdomen of obese patients represent a population of cells that were more invasive than other ASCs. Here, we report for the first time the role of calpain‐4, MMP‐15, and calpastatin on ASC invasion. In particular, decreased calpastatin expression contributed to increased ASC invasion. As ASCs have been shown to be recruited to the site of injury and incorporate into the tumor stoma and influence tumor progression, delivery of calpastatin may inhibit ASC invasion. ASCs engineered to knockout calpastatin may also be utilized for cell‐based therapy for cancer treatment.
P241
IL‐33 AND ST‐2 SINGLE NUCLEOTIDE GENE POLYMORPHISMS AND THEIR ASSOCIATION WITH ASTHMA AMONG PUERTO RICANS
Mendez JA 1, Nazario S1, Laureano A1
1University Of Puerto Rico, San Juan, Puerto Rico
OBJECTIVES/SPECIFIC AIMS: Puerto Ricans have the highest asthma prevalence and mortality rates in the United States, but previous studies have been unable to identify genes associated with asthma in this ethnic group. Interleukin‐33 and its receptor ST‐2 are components of the innate immunity that have been strongly associated with asthma in other populations. The aims of this study are to determine if IL‐33 and ST‐2 are associated with asthma among Puerto Ricans and if they are associated with atopic as well as nonatopic asthma. METHODS/STUDY POPULATION: 60 Puerto Rican asthmatics and 60 ethnically matched controls will be enrolled at the Allergy and Pneumology clinics of the Medical Sciences Campus, University of Puerto Rico. Saliva samples will be obtained from each subject for DNA analyses and single nucleotide polymorphisms (SNPs) of the IL‐33 and ST‐2 genes will be genotyped using reverse transcription polymerase chain reaction (RT‐PCR). Skin allergy testing will be performed on asthmatic subjects to further stratify them into having atopic or non‐atopic asthma. Statistical analyses using logistic regression will be done to determine associations between IL‐33 and ST‐2 SNPs and asthma. RESULTS/ANTICIPATED RESULTS: We anticipate that the IL‐33 and ST‐2 genes will be associated with asthma among Puerto Ricans and that an association will also be found between these genes and nonatopic asthma. DISCUSSION/SIGNIFICANCE OF IMPACT: We attempt to identify genetic pathways that may serve as future therapeutic targets for asthma. We also attempt to understand why asthma is so frequent among Puerto Ricans and find ways to address this health disparity. The IL‐33–ST‐2 pathway may represent a future therapeutic target for atopic asthmatics that respond poorly to inhaled steroid therapy and nonatopic patients with moderate to severe asthma that are not candidates for omalizumab or allergen immunotherapy.
P242
INCREASED DIETARY PHOSPHATE INTAKE INDUCES ECTOPIC CALCIFICATIONS IN A MOUSE MODEL OF FAMILIAL TUMORAL CALCINOSIS
Ichikawa S 1, Padgett LR1, Reilly AM1, Gray AK1
1Indiana University School of Medicine, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: Inactivating mutations in the GALNT3 gene cause familial tumoral calcinosis characterized by persistent hyperphosphatemia, leading to ectopic calcifications. We recently developed Galnt3 knockout mice, which developed hyperphosphatemia, but not ectopic calcifications. The main objective of the present study was to modulate the phenotype of Galnt3 knockout mice with increased dietary phosphate. METHODS/STUDY POPULATION: From three weeks of age, Galnt3 knockout mice and their wild‐type and heterozygous littermates were fed normal (0.60%) or high (1.65%) phosphate diets (N = 20–25 per group). Development and growth of ectopic calcifications were monitored every four weeks, using x‐ray radiography of the whole mice. Serums were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, and blood urine nitrogen. RESULTS/ANTICIPATED RESULTS: On both normal and high phosphate diets, Galnt3 knockout mice had higher phosphorus and calcium levels and lower alkaline phosphatase than littermate controls. However, increased dietary phosphate intake did not elevate serum phosphorus concentrations. None of the mice on the normal phosphate diet had radiographic evidence of calcifications. On the high phosphate diet, one of 43 littermate controls developed calcifications, whereas approximately half of Galnt3 knockout mice (13 out of 25 mice) developed large ectopic calcifications, reminiscent of tumoral calcinosis in humans. DISCUSSION/SIGNIFICANCE OF IMPACT: The development of ectopic calcifications makes Glant3 knockout mice on the high phosphate diet an excellent animal model to study familial tumoral calcinosis. As a potential therapy for this disease, Galnt3 knockout mice are currently being treated with nicotinamide, which is known to suppress phosphate absorption in the intestine.
P243
INCREASED SYMPATHETIC NERVOUS SYSTEM TONE IN AUTISM SPECTRUM DISORDERS WITH COMORBID GASTROINTESTINAL SYMPTOMATOLOGY
Ferguson BJ 1, Day JR1, Wexler BR1, Lavoy RE1, Foster PS2, Beversdorf DQ1
1University of Missouri‐Columbia, Columbia, MO, USA; 2Middle Tennessee State University, Murfreesboro, TN, USA
OBJECTIVES/SPECIFIC AIMS: There appears to be a high prevalence of gastrointestinal (GI) symptomatology in children with autism spectrum disorders (ASD), and evidence suggests that the response to stress in ASD is augmented. Furthermore, an association exists between stress and GI disorders. In addition, sensory dysfunction is commonly linked to core symptomatology in ASD and may interact with stress in the maintenance of GI disorders in ASD. However, despite this knowledge, the relationship between stress indices, GI disturbances, and sensory functioning has not been explored in ASD. METHODS/STUDY POPULATION: For the present study, galvanic skin response (GSR), a measure of eccrine gland activity, and electrocardiogram (ECG), a measure of the electrical signals of the heart, were used as indicators of sympathetic nervous system activation. Data were recorded for a baseline condition as well as in response to auditory and vibrotactile stimulation as well as cold temperature. Sensory functioning was assessed by parental report. RESULTS/ANTICIPATED RESULTS: An omnibus one‐way ANOVA across all stress conditions, including baseline exposure to the testing environment, indicated that mean GSR was significantly higher for the ASD GI group. The same effect was revealed for ECG, where mean RR interval was lower (i.e., faster heart rate) for the ASD GI group. The effects on GSR and ECG remained significant after controlling for the effect of sensory functioning. DISCUSSION/SIGNIFICANCE OF IMPACT: Although our data indicate differences in physiological responding among the groups, a larger sample size is needed to determine if the effects can be substantiated. Identifying the aspects contributing to GI problems in ASD will be important for optimizing future treatment strategies.
P244
INGESTION OF A SUCRALOSE‐SWEETENED BEVERAGE PRELOAD ALTERS POSTPRANDIAL PLASMA GLUCOSE BUT NOT LIPIDS IN OBESE ADOLESCENTS
Sylvetsky AC 1,2, Welsh JA2, Jin R2, Le A2, Vos MB2,3
1Emory University, Atlanta, GA, USA; 2NIH, NIDDK, Bethesda, MD, USA; 3Children’s Healthcare of Atlanta, Atlanta, GA, USA
OBJECTIVES/SPECIFIC AIMS: Due to their noncaloric nature, artificial sweeteners were previously believed to be metabolically inert. However, recent studies in both humans and animals have suggested that artificial sweeteners may influence glucose homeostasis. We aimed to evaluate if ingestion of a sweet, but noncaloric beverage alters circulating levels of insulin, glucose, and lipids following a test meal in obese adolescents. METHODS/STUDY POPULATION: Ten obese adolescents underwent a breakfast meal challenge during two separate visits. Subjects were given sucralose‐sweetened diet soda or carbonated water, in randomized order, prior to consuming a breakfast bar. Glucose and insulin were measured every 30 minutes over the course of 3 hours. Random effects mixed modeling was used to account for the repeated measures, within subjects design. RESULTS/ANTICIPATED RESULTS: After 90 minutes, glucose levels were elevated following consumption of the sucralose‐sweetened diet soda, compared to carbonated water (p = 0.005). Insulin also increased following the sucralose‐sweetened beverage, but did not reach statistical significance. No differences were seen in triglycerides, NEFA, HDL, or LDL levels over the 3 hours. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased plasma glucose may result from interaction with the intestinal sweet taste receptor by sucralose. Further research examining the effects of repeated consumption of sucralose on glycemic control is necessary, to evaluate if sucralose may contribute to sustained hyperglycemia and increase risk for diabetes and cardiovascular disease within an already high‐risk obese population.
P245
IN SILICO MODELING FOR PERIPHERAL VASCULAR DISEASE
Young M 1, Bennetts C1, Bishop P1, Erdemir A1, Graham L1
1Cleveland Clnic, Cleveland, OH, USA
OBJECTIVES/SPECIFIC AIMS: For patients with peripheral vascular disease, endovascular stenting can be a promising therapy that alleviates plaque obstruction and restores blood flow. Stent designs should be take into account vascular complexities such as branching, individual patient geometries, and disease severity. The goal of this study is the development of patient specific computer models to predict patient specific stent outcome, allowing selection of the optimal stents with reduced potential for stent fracture and failure. METHODS/STUDY POPULATION: Representative clinical intravascular ultrasound (IVUS) datasets were obtained from the Peripheral Vascular Core Laboratory at the Cleveland Clinic. Subjects for this study were 18 years and above, with a gender and racial mix characteristic of the population with PAD, included in the Cleveland Clinic, Vascular Surgery IRB‐approved Registry. RESULTS/ANTICIPATED RESULTS: An automated model generation platform was devised to develop meshes inferred from patient specific IVUS imaging, which defined the histological disease condition of the arteries. Combined with stent modeling, this platform is targeted at the development of virtual evaluation of stent performance in a specific arterial setting. DISCUSSION/SIGNIFICANCE OF IMPACT: Stent fracture is a serious problem because it could lead to vascular complications such as restenosis, stent occlusion, and re‐interventional procedures. Stent fracture is influenced by type of stent and local mechanical forces that are influenced by arterial wall compositions including degree of calcification. A computer tool that could be used to predict vascular issues that could influence stent function, and recommend specific stent designs best for individual patients, could be a cost effective and guide optimal treatment of patients with peripheral vascular disease.
P246
INSULIN RESISTANCE PROMOTES INCREASED NEURAL RESPONSE TO FOOD CUES AND STRESS IN OBESE HUMANS
Jastreboff AM 1, Sinha R1, Lacadie C1, Small D2,1, Hong K1, Sherwin RS1, Potenza MN1
1Yale University, New Haven, CT, USA; 2The John B. Pierce Laboratory, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Food cues and stress increase food cravings and may contribute to the pathogenesis of obesity. Additionally, obesity is associated with changes in motivational neural pathways and alterations in insulin sensitivity. We examined whether insulin resistance in obese individuals promotes increased neural activation in motivation‐reward and emotion‐regulating regions of the brain in response to brief guided‐imagery of favorite foods and to stress scenarios. METHODS/STUDY POPULATION: Twenty‐five obese and 25 lean individuals of varying insulin sensitivity, as characterized by homeostatic model assessment of insulin resistance (HOMA‐IR), participated in six trials of brief exposure to personalized food‐cue, stress, and neutral‐relaxing situations using a validated, functional MRI (fMRI) paradigm. RESULTS/ANTICIPATED RESULTS: In contrast maps, using the neutral‐relaxing comparison state, obese, but not lean individuals, demonstrated corticolimbic‐striatal activations in the putamen, insula, hypothalamus, and parahippocampus, during food‐cue and stress conditions (p < 0.01, FWE‐whole brain corrected). Additionally, in obese, but not lean individuals, increased fasting insulin and HOMA‐IR each correlated with increased activation in the dorsal striatum and insula during food cue exposure and increased activation in the ventral and dorsal striatum and insula in the stress condition (p < 0.05, FWE‐whole brain corrected). DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that obesity‐induced reductions in insulin sensitivity promote increased neural responses in corticolimbic (insula) and motivation‐reward (striatal) brain regions to food cues and stress. Such changes in neural activation in obese individuals may contribute to excessive weight gain due to increased motivation to consume desirable foods.
P247
INTERACTIONS BETWEEN DENDRITIC CELLS AND POLYMORPHONUCLEAR LEUKOCYTES
Scisci E 1, Cutler CW1
1Stony Brook University, Stony Brook, NY, USA
OBJECTIVES/SPECIFIC AIMS: The PMN inflammatory response is followed by an influx of dendritic cells (DCs) which clear effete PMNs and cross‐present antigens to T cells. However, very little is understood about the ability of DCs to kill oral‐mucosal‐pathogens (e.g., P. gingivalis [Pg]) and the overall role of the PMN‐DC interaction in resolution of oral mucosal inflammation (e.g. chronic periodontitis) and at other sites of localized inflammation (e.g. atherosclerosis). METHODS/STUDY POPULATION: We analyzed the fate of Pg within monocyte‐derived DCs (MoDCs), compared to PMNs by infecting cells and attempting to recover Pg on blood agar. MoDCs were probed with conjugated monoclonal antibody to Pg mfa‐1 and DC‐SIGN and analyzed by scanning laser confocal and electron microscopy. Using mutant strains of Pg lacking one or both fimbriae, we established the role of the minor fimbriae as an inhibitor to DC‐PMN interaction via cocultures of primary isolated cells as well as a cell line transfected to express DC‐SIGN. Cell associations were shown via flow cytometry. We also examined the ability of Pg to affect PMN‐DC conjugation by modulating PMN integrin expression. RESULTS/ANTICIPATED RESULTS: Inside MoDCs, Pg maintained viability for up to 24 hrs. PMNs effectively killed Pg, as none was recovered after 4 hrs. Laser confocal and electron microscopy confirms intracellular localization of Pg within DC‐SIGN‐rich vesicles. We showed Pg mfa‐1 to be necessary for inhibition of DC‐PMN conjugation. Pg also triggers PMN activation and initiates apoptosis in a fimbriae‐dependent manner. DISCUSSION/SIGNIFICANCE OF IMPACT: These data indicate that Pg survives within DCs. In addition, PMNs are effective at killing Pg, however Pg infection may alter PMN phenotype and activate these cells exacerbating inflammation and prohibiting PMN clearance by DCs.
P248
INVESTIGATION OF GENETIC RISK FACTORS FOR CHRONIC ADULT DISEASES IN PRETERM BIRTH
Falah N 1, McElroy J1, Snegovskikh V2, Lockwood C2, Kuczynski E2, Norwitz E2, Murray J3, Menon R4, Muglia L1, Morgan T1
1Vanderbilt U, Nashville, TN, USA; 2Yale U, New Haven, CT, USA; 3U of Iowa, Iowa City, IA, USA; 4PRC, Nashville, TN, USA
OBJECTIVES/SPECIFIC AIMS: Preterm birth (PTB) is the leading cause of infant mortality. The pathophysiology of PTB overlaps with that of chronic adult disease (CAD), with common mechanisms including inflammation, immunotolerance, thrombosis, and nutrient metabolism. We hypothesized that highly validated genetic associations with CAD may also be associated with PTB. METHODS/STUDY POPULATION: Case‐control study of women with spontaneous preterm (n = 673) versus term delivery (n = 1119), in 4 diverse cohorts (US white, US black, US Hispanic, Finnish). Genotyping of 35 SNPs was performed using Sequenom and Taqman, with statistical analysis in PLINK. RESULTS/ANTICIPATED RESULTS: We found 13 statistically significant associations (p < 0.05), which was more than expected (p = 0.02). In US white mothers (307 cases/342 controls), the G allele of HLA‐DQA1 (A/G) rs9272346 was protective for PTB in the discovery cohort (p = 0.02; OR = 0.65; 95% CI: 0.46, 0.94). This protective association replicated (p = 0.02; OR = 0.85(95% CI; 075–0.97) in the Danish Cohort (883 cases, 959 controls), but did not survive multiple testing correction (p = 0.21). DISCUSSION/SIGNIFICANCE OF IMPACT: We observed surplus of statistically significant associations between CAD‐related genetic risk variants and PTB than expected, suggesting that one or more may be valid. In particular, a protective association of the G allele of HLA‐DQA1 was found in two independent cohorts of mothers, and in previous studies, this same allele was found to protect against type I diabetes (meta p 5.52 × 10–219). Previous investigations have implicated HLA phenotypic variation in recurrent fetal loss as well as in chronic chorioamnionitis. Given the limited sample size in this study, we suggest larger studies to further investigate possible HLA genetic involvement in PTB.
P249
ISOLATION OF RHEUMATOID FACTORS THAT CROSS‐REACT WITH HEPATITIS C VIRUS
Charles E 1, Nishiuichi E1, Dustin LB1
1Rockefeller University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Hepatitis C virus (HCV) is the most frequent cause of mixed cryoglobulinemia (MC), which is characterized by endothelial deposition of rheumatoid factor (RF)‐containing immune complexes (ICs) and end‐organ vasculitis. MC is a B‐cell lymphoproliferative disorder, yet its precise antigenic stimulus is unknown. We have reported that HCV MC patients have clonal expansions of B cells expressing RFs. We have proposed that these RFs are cross‐reactive with HCV and play a role in clearing virus. METHODS/STUDY POPULATION: Igs were cloned and expressed from HCV MC patients’ singly‐sorted B cells as previously described. Antihuman IgG1 RF activity was determined by ELISA. Anti‐HCV activity was determined by surface plasmon resonance. Neutralization of HCV was measured by assessing inhibition of infection of Huh 7.5 cells. IC formation was determined by sucrose density gradient centrifugation. Complement‐mediated lysis of viral envelope was measured with an HCV core ELISA. RESULTS/ANTICIPATED RESULTS: Clonal Igs from HCV MC patients had RF activity, with a preference for IgG1>IgG2~IgG4>IgG3. They reacted with HCV envelope; KD ranged from 10–100 nM. RFs did not neutralize HCV in the cell‐based assay. However, they lysed HCV in a complement‐dependent manner when they were incubated with immune complexes of HCV and IgG. DISCUSSION/SIGNIFICANCE OF IMPACT: RFs from HCV MC patients have moderate affinities for HCV. Although they do not directly neutralize HCV, they lyse HCV in the presence of complement. These data suggest that HCV, as well as self‐IgG, drives the formation of these pathologic RFs in vivo.
P250
LINEAGE AND AGE DIFFERENCES IN THE METHYLOME OF MLL‐r LEUKEMIAS
Schafer ES 1, Murakami P2, Negi S1, Figueroa ME3, Melnick A4, Brown P1
1Johns Hopkins U. SOM, Baltimore, MD, USA; 2JHSPH, Baltimore, MD, USA; 3U. Michigan SOM, Ann Arbor, MI, USA; 4Weill Cornell Medical College, NY, NY, USA
OBJECTIVES/SPECIFIC AIMS: MLL‐rearrangements are seen in ALL and AML of all ages. Leukemogenic cooperating lesions have been difficult to identify. MLL‐r infant ALL can be defined by hypermethylated CpGs leading to tumor suppressor gene silencing, suggesting that DNMT inhibitors should be investigated in this disease. In the present study we aimed to discover whether the epigenetic signature seen in MLL‐r infant ALL was MLL‐r intrisnic or might be a cooperating event. METHODS/STUDY POPULATION: The methylome of 102 diagnostic ALL or AML patient samples of all ages, common MLL fusion partners and wild type and 12 normal controls was explored with the second generation HELP assay. The samples underwent unsupervised hierarchical clustering and supervised biostatistical analyses. RESULTS/ANTICIPATED RESULTS: There was near perfect bimodal separation of leukemia samples into their lineage specific (ALL/AML) groups and within ALL, B and T cell samples clustered seprerately. While the T‐cell cluster did not separate by MLL status, the B‐cell samples showed distinct separation into MLL‐r and MLL‐wt subclusters. Within the MLL‐r subcluster, samples separated more by age than by fusion partner; this phenomenon held in pair‐wise analyses. In the AML group, clusters were driven both by age and genotype. For example, in a single cluster 7/11 samples were MLL‐AF9 with sub‐clustering evident by age. In another cluster, 4/9 samples were MLL‐ELL samples. DISCUSSION/SIGNIFICANCE OF IMPACT: The primary determinant of methylation signatures in MLL‐r leukemias is lineage. However, within lineages the MLL‐r plays a large, but unique, role in promoting methylation patterns. The MLL fusion influences but does not drive methylation patterns in leukemia. Generalities should not be made when considering epigenetic treatment of these leukemias.
P251
LRP6 COOPERATES WITH LDLR FOR LDL ENDOCYTOSIS
Go G 1, Ye Z1,2, Singh R1, Liu W1, Keramati AR1, Mani A1,3
1The Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; 2Third Military Medical University, Chongqing, China; 3The Departments of Genetics, Yale University School of Medicine, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: The Departments of Internal Medicine and Genetics, Yale University School of Medicine. Genetic variations in LRP6 are associated with elevated serum LDL level, perturbed glucose homoeostasis, and atherosclerosis in human. We have previously demonstrated that LDL clearance in peripheral B‐lymphocytes of the LRP6R611C mutation carriers is significantly impaired. There is substantial interest in understanding whether LRP6 has a role in LDLR mediated LDL uptake. METHODS/STUDY POPULATION: The role of wild‐type LRP6 (LRP6WT) and LRP6R611C in both LDLR‐mediated and LDLR independent LDL uptake was examined in this study. RESULTS/ANTICIPATED RESULTS: Binding and uptake of I125‐LDL were increased in LDLR deficient CHO (ldlA7) cells when LRP6WT was overexpressed and modestly reduced when it was knocked down with RNAi. These results indicated the role LRP6 in LDLR‐independent cellular LDL binding and uptake. Yet, LRP6 knockdown in wild‐type CHO cells resulted in a much greater reduction in LDL binding and uptake, suggesting interaction between LRP6 and LDLR in LDLR mediated LDL uptake. Further investigation showed LDLR internalization was severely diminished when LRP6 was knocked down and was restored after LRP6 was reintroduced. Further investigation showed LRP6 forms a complex with LDLR, clathrin, and ARH and undergoes endocytosis after stimulation with LDL. LDLR and LRP6 internalizations as well as LDL uptake were all impaired in CHO‐k1 cells expressing LRP6R611C as well as in skin fibroblasts of LRP6R611C mutation carriers. DISCUSSION/SIGNIFICANCE OF IMPACT: In conclusion, this study implicates LRP6 as a critical modulator of LDLR‐mediated LDL endocytosis and introduces a mechanism by which variation in LRP6 may contribute to elevated serum LDL levels.
P252
MACRODELETIONS THAT INCLUDE CLCN5 CAUSE DENT'S DISEASE WITH EXTRA‐RENAL FEATURES: A NOVEL CONTIGUOUS DELETION SYNDROME
Lemaire M 1, Cheong H2, Ji W1, Park H3, Chung H3, Shin J4, Lifton RP1
1Yale University School of Medicine, New Haven, CT, USA; 2Seoul National University Children’s Hospital, Seoul, Republic of Korea; 3Seoul National University Bundang Hospital, Seongnam City, Republic of Korea; 4Yonsei University College of Medicine, Seoul, Republic of Korea
OBJECTIVES/SPECIFIC AIMS: Inability to amplify most CLCN5 exons in 2 unrelated Korean boys with atypical Dent’s disease suggests a novel contiguous deletion syndrome (no mutation identified in OCRL1). METHODS/STUDY POPULATION: The 2 unrelated Korean boys meet diagnostic criteria for Dent’s disease. They also presented with stunted growth, developmental delay and cryptorchisdism. Additional features exclusive to subject #1 include recurrent seizures, cleft palate and growth hormone deficiency while skeletal anomalies stand out for subject #2. SNP genotyping was done on Illumina 650K or 1M Duo SNP genotyping platforms. Deletion boundaries were defined as the genomic intervals between the last remaining SNPs versus controls. The exact deletion boundaries were identified with long‐range PCR. RESULTS/ANTICIPATED RESULTS: SNP genotyping of both subjects revealed ~3.5 Mb deletions at Xp11.22 with distinct boundaries. Both deletions result in deficits of the same 15 genes. Of these, two may explain some of the shared nonrenal features. Common variants in DGKK are associated with urogenital anomalies (hypospadias, cryptorchidism). Rare variants in SHROOM4 cause Stocco dos Santos syndrome (mental retardation and stunted growth). Fine mapping of the deletion breakpoints for Subject 1 revealed two distant direct repeats flanking the breakpoint, with an intervening inverted repeat. This motif is in keeping with “slipped mispairing” as the deletion mechanism. DISCUSSION/SIGNIFICANCE OF IMPACT: We report a hitherto undescribed contiguous deletion syndrome — with complete loss of CLCN5 and ~15 other genes — in two unrelated Korean boys with Dent’s disease associated with numerous extra‐renal findings.
P253
MAGNETIC RESONANCE SPECTROSCOPY FOR EVALUATION OF IRRADIATION‐INDUCED BRAIN INJURY IN A JUVENILE MOUSE MODEL
Brown RJ 1, Love J1, Warburton D1, McBride W2, Bluml S1
1Children’s Hospital Los Angeles, Los Angeles, CA, USA; 2University of California Los Angeles, Los Angeles, CA, USA
OBJECTIVES/SPECIFIC AIMS: Children undergoing therapeutic cranial irradiation are at increased risk of permanent long‐term neurocognitive sequelae in addition to stroke and secondary malignancies. The mechanism of these side effects are poorly understood and adequate biomarkers for chronic injury are lacking. Magnetic resonance spectroscopy is a noninvasive, nonirradiation modality that can be performed on children with little or no additional risk to standard disease surveillance MRI. Purpose: We investigated the utility of magnetic resonance spectroscopy in a mouse model of juvenile irradiation injury to characterize the metabolite profile derangements following cranial irradiation with the intention of correlating these profiles with histological evidence of irradiation‐induced brain injury. METHODS/STUDY POPULATION: 4‐week old juvenile wild‐type mice were given single 16 Gray or sham fraction of irradiation and examined at baseline, 3‐, 6‐, 9, and 12‐months post irradiation. The MR spectroscopy was compared to controls and correlated with histological characteristics. RESULTS/ANTICIPATED RESULTS: Lipid‐based metabolites generally decreased with age while both macromolecules and neuronal metabolites increased with age up to one year in the mouse model. Irradiation at 1 month of age demonstrated detectable alterations in metabolites by 6 months of age and correlated with histological evidence of irradiation‐induced brain injury. DISCUSSION/SIGNIFICANCE OF IMPACT: Magnetic resonance spectroscopy is a useful noninvasive modality for identifying irradiation‐induced brain injury in a mouse model which can be used to evaluate interventions. In addition, MRS may be a useful tool in identifying early postirradiation brain injury in children treated for brain tumors.
P254
MARKERS OF TOXIN STATUS AND HOST RESPONSE IN CLOSTRIDIUM DIFFICILE DIARRHEA
Polage CR 1, Cohen SH1, Solnick JV1
1UC Davis, Sacramento, CA, USA
OBJECTIVES/SPECIFIC AIMS: Clostridium difficile (CD) is an important cause of healthcare associated diarrhea and death, but 10–20% of hospitalized patients are immune carriers that are not actively infected. Toxins mediate host injury and response but diagnostic testing for CD is shifting towards methods such as PCR that do not distinguish toxin‐positive (toxin+) patients from carriers. We hypothesized that CD quantitation, fecal calprotectin, and plasma procalcitonin, as markers of CD fecal load and host inflammatory response, respectively, could aid in the discrimination of toxin+ and toxin2 patients. METHODS/STUDY POPULATION: Inpatients tested for CD had stool and plasma samples collected as part of a prospective clinical trial. All stool samples were tested for CD toxins and DNA by immunoassay and quantitative PCR. A subset had procalcitonin or calprotectin measured by immunoassay. RESULTS/ANTICIPATED RESULTS: Toxin2 patients had 10^1–10^4 less C. difficile DNA copies/mL than toxin+ patients (p < 0.001), suggesting that CD load predicts toxin status. Plasma procalcitonin values were generally low and not significantly different between toxin+ and toxin2 groups. Preliminary results suggest that fecal calprotectin is elevated more often in toxin+ patients versus toxin2 patients. DISCUSSION/SIGNIFICANCE OF IMPACT: CD testing is evolving towards more sensitive but less specific test methods that may lead to overdiagnosis of noninfected carriers. Quantitation of CD fecal load and/or fecal calprotectin may be useful in distinguishing infected patients from immune carriers. Procalcitonin is increasingly being used as a marker of a systemic response to bacterial infection, but it appears to add little or no additional information in patients with CD.
P255
MOLECULAR AND FUNCTIONAL EVALUATION OF MRP TRANSPORTER IN GLAUCOMA DRUG EFFLUX
Karla PK 1, Ako‐Adouno A1
1Howard University, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: The objective of the study is to screen for the molecular expression of MRPs at gene and protein level on cornea, which forms the primary barrier for anterior segment drug delivery. Secondary objective is to perform a functional evaluation of glaucoma drug (Timolol) efflux by flow cytometry. METHODS/STUDY POPULATION: Real time polymerase chain Reaction and Western blot analysis were employed for gene and protein expression. Flow cytometry screening employing fluorescent substrate, Rhodamine‐123 was employed to evaluate efflux transporter substrate specificity of Timolol. RESULTS/ANTICIPATED RESULTS: RT‐PCR indicated specific bands (277 bp) and (331 bp), confirming the presence of MRP4 and MRP6 at gene level. Immunoprecipitation followed by Western blot analysis indicated distinct band (160 kDa) confirming the expression of MRP4 at protein level. Mean fluorescence detected in corneal cell sample treated with Timolol was 153.12, MK571 was 86.41 and control was 50.28. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results indicated for the first time that “Timolol,” a major glaucoma drug is an excellent substrate for drug efflux transporters on cornea. The results confirm the molecular expression of MRP4 and 6 on cornea. Timolol, being a major drug widely employed for the treatment of glaucoma and drug resistance leading to treatment failure being a common symptom in glaucoma patients, these research findings are predicted to lead to the development of ophthalmic formulation strategies for drug efflux modulation and improved bioavailability.
P256
MOLECULAR MECHANISMS OF ADVERSE METABOLIC RESPONSES AFTER SURGERY
Ko FC 1, Siu AL1, Mobbs CV1,2
1Department of Geriatrics and Palliative Medicine, Mount Sinai School of Medicine, New York, NY, USA; 2Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Surgery precipitates adverse postoperative metabolic responses associated with poor physical function, immobility, and increased mortality in vulnerable older adults. Molecular mechanisms mediating these responses remain poorly understood. This knowledge gap has limited the development of reliable biomarkers to predict, and effective interventions to treat, physical decline after surgery in vulnerable elderly. We hypothesize that surgery‐induced oxidative stress, particularly in the presence of altered inflammation and sympathetic (SNS) activity, mediates adverse metabolic responses after surgery. Thus, we are examining relationships between oxidative stress, inflammation, and SNS and their influence on postsurgery metabolic responses in mice and human subjects using a translational (basic‐to‐clinical) approach. METHODS/STUDY POPULATION: First, we are determining the effects of surgical protocols (isoflurane ± laparotomy) on monocyte oxidative stress gene expression in B6 mice. Second, we are assessing the influence of interleukin 6 and SNS on oxidative stress gene expression after surgery in genetically modified mice with attenuated inflammation and SNS activity. Third, we are exploring whether inflammatory, SNS, and oxidative stress mediators measured on postoperative day 3 in a cohort of older hip fracture patients at Mount Sinai Hospital are associated with physical and functional decline 3 days to 6 weeks post–hip fracture surgery. RESULTS/ANTICIPATED RESULTS: We anticipate identifying molecular mechanisms mediating metabolic responses to surgery and potential biomarkers of adverse surgical outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings will facilitate future development of mechanism‐driven interventions that optimize surgical procedures in vulnerable older adults.
P257
mTORC2 REGULATES HNRNPE1‐DRIVEN CYTOSKELETAL ORGANIZATION IN BLADDER CANCER CELLS
Hansel DE 1, Gupta S1
1Cleveland Clinic, Cleveland, OH, USA
OBJECTIVES/SPECIFIC AIMS: Urothelial carcinoma (UCC) utilize mammalian target of rapamycin (mTOR) signaling to drive migration, although the downstream mechanism is unknown. Herein, we investigated the role of heterogenous nuclear‐ribonucleoprotein E1 (hnRNPE1), which forms a ribonucleoprotein (mRNP) complex that binds to the 39‐UTR of target genes to silence the translation of select genes involved in epithelial to mesenchymal transition (EMT), as a target of the mTORC2 complex. METHODS/STUDY POPULATION: siRNA was used to disrupt mTORC2 in aggressive UCC‐derived J82 cells. Consequent changes in hnRNPE1 phosphorylation, cell migration and Vimentin intermediate filament (IF) assembly were assessed. Conversely, shRNA mediated knockdown of hnRNPE1 and the resultant changes in Vimentin organization was evaluated by immunostaining. RESULTS/ANTICIPATED RESULTS: J82 cells exhibited constitutively high levels of hnRNPE1 phosphorylation, which was correlated with a pro‐invasive (mesenchymal) phenotype. Knocking down hnRNPE1 to further promote EMT led to Vimentin IF reorganization into higher order filaments extending to the cell periphery. This is similar to what has been reported for the stabilization of microtentacles in circulating tumor cells (CTCs), which are critical for CTC aggregation and capillary endothelial reattachment. Disrupting mTORC2 led to a significant reduction in hnRNPE1 phosphorylation status. This was correlated with reduced cell migration and a perinuclear collapse of the Vimentin IFs. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest a novel mechanism by which mTORC2 regulates cytoskeletal architecture and migration in bladder cancer cells and further validates mTORC2 as an important target for the treatment of UCCs.
P258
MYOCARDIAL ISCHEMIA IN RESPONSE TO MENTAL STRESS: GENDER DIFFERENCES IN IMMUNO/NEURO‐HORMONAL RESPONSES IN CAD
Ranjbaran H 1, Burg M1, Collins D1, Soufer R1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: The role of inflammation in the provocation of mental stress ischemia (MSI) and gender differences in emotional stress responses have been suggested in recent studies. We have investigated gender differences in MSI and in the concomitant immunologic and neuro‐hormonal responses. METHODS/STUDY POPULATION: One hundred ten patients with documented CAD (22 women, 88 men) underwent myocardial perfusion imaging during a laboratory mathematical mental stress (MS) protocol. Myocardial perfusion, serum cytokines (IL‐1β, IL‐6, ET‐1, TNF‐ α, and ADMA) and neuro‐hormonal molecules (norepinephrine (NE), epinephrine (Epi), and cortisol) were measured at baseline and peak stress and were analyzed with ELISA and HPLC. RESULTS/ANTICIPATED RESULTS: Men (51 of 88) were 2.24 more likely to develop MSI than women (8 of 22). Compared to women, men had lower baseline IL‐1β (0.04 (±0.17) pg/ml versus 0.18(±0.24) pg/ml, p < 0.0001). With induction of MS IL‐1β levels decreased in women (−0.06 pg/ml) but increased in men (0.01 pg/ml) (p = 0.003). Baseline catecholamine levels were higher in men compared to women (NE: 466 pg/ml vs. 300 pg/ml and Epi: 39 pg/ml vs. 23 pg/ml, p < 0.05) and with MS, epinephrine levels in men increased 10 fold more than in women (average change of 30.7 pg/ml vs. 3.2 pg/ml, p = 0.0005). There were no significant gender differences in ADMA, cortisol, IL‐6, ADMA, TNF‐α and ET‐1 with MS. DISCUSSION/SIGNIFICANCE OF IMPACT: Men are more likely to exhibit reversible myocardial ischemia in response to a cognitive MS challenge than women. These preliminary data suggest that men have a lower threshold for MSI, which may in part be secondary to the neuro‐hormonal and immunologic response. These preliminary data support conceptual constructs for larger studies concerning the role of gender in MSI.
P259
NEURONAL CORRELATES OF EXECUTIVE DYSFUNCTION IN PARKINSON'S DISEASE
Kluger BM 1, Wang C2, Rajagovindan R2, Proemsey J2, Ding M2
1University of Colorado, Aurora, CO, USA; 2University of Florida, Gainesville, FL, USA
OBJECTIVES/SPECIFIC AIMS: To determine the underlying neurophysiological basis for executive function impairments in Parkinson’s Disease (PD) and to determine if these deficits are related to fatigability. METHODS/STUDY POPULATION: To date, eight nondemented PD patients (56 + 12 years) and six healthy controls (61 + 14 years) have participated in this experiment. Subjects performed a prolonged (three hour) continuous cued Stroop task while having brain activity recorded using electroencephalography (EEG). For this task, subjects are shown a preparatory cue indicating whether to read or name the upcoming stimulus. The stimulus may be either congruent (e.g. red written in red letters) or incongruous (e.g. red written in blue letters). RESULTS/ANTICIPATED RESULTS: While there was a trend towards slower reaction times in PD patients at baseline this was not statistically significant. However, PD patients performance showed significantly greater fatigability (slowing of reaction times and increasing errors) over time than control subjects. At baseline, EEG revealed impairments in preparatory allocation of cerebral resources based on cues and in conflict detection of incongruous stimuli in PD subjects. Similar deficits were found in healthy controls only with fatigue. Fatigability in PD subjects correlated with subjective ratings of fatigue. DISCUSSION/SIGNIFICANCE OF IMPACT: PD patients have deficits in executive dysfunction compared to age matched controls. This data suggests that fatigability may contribute to and exaggerate these differences. EEG recordings demonstrate that even when PD subjects are performing at a level comparable to age matched controls, they are not using cerebral resources as efficiently, potentially also contributing to greater potential for decompensation and fatigue.
P260
NOD‐LIKE RECEPTORS AND THE INDUCTION OF RED CELL ALLOIMMUNIZATION
Eisenbarth S 1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Antibody formation to transfused red blood cells (RBCs) is a clinically significant problem that results in morbidity and occasionally in mortality from hemolytic transfusion reactions. Every nonautologous RBC unit has numerous antigens foreign to the transfused recipient; however it is unclear why some patients become alloimmunized after transfusion; possibly more intriguing, it is unclear why most recipients do not become immunized to those foreign antigens. We hypothesize that one or more NLRs might be triggered during the transfusion of sterile RBCs that potentially contain products of cell damage and that the activation of this innate pathway dictates the subsequent T and B cell alloimmune response. In particular release of ATP has been shown to activate the Nlrp3 Inflammasome—a multimolecular complex composed of Nlrp3, the adaptor molecule ASC and the effector enzyme Caspase‐1. METHODS/STUDY POPULATION: Using a model transfusion system of transgenic RBCs into wild type versus Nlrp3‐deficient mice we are able to assess the immunologic response to allogeneic cells containing foreign blood group antigens. RESULTS/ANTICIPATED RESULTS: Our preliminary data indicate that the NLR Nlrp3 is not required for the generation of alloantibodies to foreign RBC antigens, although future work will delineate the T versus B lymphocyte response to allogeneic red cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Identifying the innate immune receptors that regulate immunization to foreign antigens on RBCs will enable us to identify potential immune triggers of alloimmunization during transfusion and, as an extension, targets to inhibit during these therapies to promote immunological tolerance.
P261
PERIODONTAL DISEASE AND THE ORAL MICROBIOTA IN NEW‐ONSET RHEUMATOID ARTHRITIS
Scher JU 1, Ubeda C2, Abramson S1, Pamer E2, Bretz W3
1NYU School of Medicine, New York, NY, USA; 2Memorial Sloan‐Kettering Cancer Center, New York, NY, USA; 3NYU College of Dentistry, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: To profile the subgingival oral microbiota abundance and diversity in never‐treated, new‐onset rheumatoid arthritis (NORA) patients. METHODS/STUDY POPULATION: Periodontal disease (PD) status, clinical activity and sociodemographic factors were determined in patients with NORA, chronic RA (CRA) and healthy subjects. Massively parallel pyrosequencing technologies were used to compare the composition of microbial communities in subgingival biofilms and establish correlations between presence/abundance of bacteria and disease phenotypes. RESULTS/ANTICIPATED RESULTS: The more advanced forms of periodontitis are already present at onset of clinical disease in NORA patients. The subgingival biofilm community composition of NORA patients is distinct from controls. In most cases, however, these differences can be attributed to PD severity and are not inherent to RA. The presence and abundance of the genus Porphyromonas and species P. gingivalis are directly associated with PD severity as well, are not unique to RA, and do not correlate with anticitrullinated peptide antibody (ACPA) titers. Anaeroglobus geminatus correlated with ACPA and RF presence. Prevotella spp. and Leptotrichia. DISCUSSION/SIGNIFICANCE OF IMPACT: NORA patients in our cohort exhibit a high prevalence of PD at disease onset, despite their young age and paucity of smoking history. The oral microbiota of NORA patients is similar to CRA and healthy subjects of comparable periodontal disease severity. The genus Porphyromonas is found in all patients with moderate to severe periodontitis but is not unique to RA. The role of A. geminatus and Prevotella/Leptotrichia species in this process merits further study.
P262
PHARMACOGENOMICS IN PULMONARY ARTERIAL HYPERTENSION: TOWARD A MECHANISTIC, TARGET‐BASED APPROACH TO THERAPY
Hamidi S 1, Said S1
1SUNY at Stony Brook, Stony Brook, NY, USA
OBJECTIVES/SPECIFIC AIMS: Recognition of the importance of pharmacogenomics in oncology has led to dramatic increases in therapeutic success, along with reduction in drug toxicity. At the same time, it is becoming increasingly apparent that Pulmonary Arterial Hypertension (PAH) is a heterogeneous disorder, and may thus benefit from application of the principle of pharmacogenomics. In this study we had 2 objectives: 1) Identify genetic variations in 2 experimental models of PAH: VIP KO mice, and SD rats injected with monocrotaline (MCT, 60 mg/kg); and 2) compare the efficacy of response of the 2 models to treatment with one drug, VIP. METHODS/STUDY POPULATION: Lungs from 5 male VIP KO and 5 male WT mice were subjected to gene microarray analysis. Microarray data were validated by quantitative RT PCR. Lungs from 5 MCT and 5 normal control male rats were collected and treated in the same way for gene array and RT PCR. VIP was administered by ip injection of 500 μg/kg, every other day, for 3 wks. RESULTS/ANTICIPATED RESULTS: In VIP KO mice, the PAH phenotype was associated with up‐regulation of proliferative/vasoconstrictor, and inflammatory genes, together with down‐regulation of antiproliferative/vasodilator genes. Both phenotypic and genetic alterations were fully corrected by treatment with VIP. In MCT rats, however, there were 2 different sets of genotypic alterations: one, similar to that in VIP KO mice, which tended to promote the development of PAH, and another that suggested an effort to modulate it. Both phenotypic and genotypic abnormalities in MCT rats were only partially corrected by VIP. DISCUSSION/SIGNIFICANCE OF IMPACT: In 2 experimental models of PAH, correlation of gene expression with the response to VIP, demonstrated the dependence of the therapeutic response on the underlying genomic characteristics, thus validating the potential usefulness of pharmacogenomics in the treatment of clinical PAH.
P263
PHARMACOGENOMICS OF CLOPIDOGREL IN STROKE
Chan Y 1, Richardson L1, Peter I1, Tuhrim S1, Gottesman O1, Ellis S1, Hulot J1
1Mount Sinai School of Medicine, Washington Township, NJ, USA
OBJECTIVES/SPECIFIC AIMS: African American (AA) and Hispanics (H) are disproportionately more affected by stroke than whites (W). The CYP2C19 (C19) variant genes are significant and independent predictors of reduced clopidogrel (clpg) efficacy. Cardiac patients treated with clpg with C19 loss‐of‐function (LOF) gene have increased risk of major adverse cardiovascular events compared with noncarriers. Clpg is a first line antiplatelet therapy options for the prevention of ischemic stroke (IS) and transient ischemic attack (TIA). We are investigating the impact of C19 polymorphism on the stroke (CVA) and the H populations in our ethnically diverse Biobank cohort. (1) Compare the H& AA C19 allele frequencies in the CVA and a stroke free cohort. (2) Investigate the additive effect of clpg treatment and C19 LOF genotype on outcomes (i.e. effectiveness and safety) while adjusting for potential confounders. (3) Assess how race affects clpg effectiveness and C19 polymorphism. METHODS/STUDY POPULATION: A case‐control study of our Biobank patients. (1) Conduct a comprehensive EMR review to investigate whether these C19 variants are associated with the effectiveness or safety outcomes in the presence of clpg treatment while adjusting for potential confounders. (2) Assess the effect of race on these outcomes via ethnicity‐stratified analyses. RESULTS/ANTICIPATED RESULTS: There is varying C19 allele distribution in the different racial groups of our sample Biobank CVA cohort. There is an association between C19 LOF genotype and clpg effectiveness/ cerebrovascular disease prevalence. DISCUSSION/SIGNIFICANCE OF IMPACT: The valuable data generated from this exploratory study will serve as an essential next step in a line of inquiry that may lead to a larger prospective stroke PG trial. Our goal is to aid physicians make more informed decisions regarding the choice of antiplatelet agents in the Stroke as well as the H and AA populations.
P264
PHOTOGRAPHY TO DETECT MISLABELING ERRORS IN RADIOLOGY
Tridandapani S 1,2, Galgano S1, Ramamurthy S1, Bhatti PT2,1, Provenzale JM1,3
1Emory University, Atlanta, GA, USA; 2Georgia Institute of Technology, Atlanta, GA, USA; 3Duke University, Durham, NC, USA
OBJECTIVES/SPECIFIC AIMS: To evaluate if the presence of patient photographs obtained simultaneously with chest radiographs increases radiologists’ detection rate of mislabeling errors. METHODS/STUDY POPULATION: In this IRB‐approved prospective study 41 patients admitted to two cardiothoracic intensive care units were recruited and 166 photographs were obtained from these patients when they were undergoing portable chest radiographs. Eighty‐one pairs (new and prior for comparison) of radiographs were generated from this data. Study lists containing 20 pairs of radiographs only were generated and in each list, between 10% and 20% errors were introduced. Errors are defined as radiographic pairs belonging to different patients. Ten general radiologists were each asked to interpret 20 pairs of radiographs with no knowledge of the errors. Interpretation was based on evaluation of support lines and tubes, change in patient status, image quality; radiologists could also note any other comments. Following this, the ten radiologists were asked to interpret a second set of 20 radiograph pairs, each of which also included the patient photographs which were obtained at the time of radiograph acquisition. The Fisher’s exact test was used to evaluate the difference in number of mismatches identified between the two phases. A p‐value of <0.05 was considered to be significant. RESULTS/ANTICIPATED RESULTS: There was a significant difference (p = 0.0005) in the number of mislabeling errors detected without photographs (3/24 = 12.5%) and with photographs (16/25 = 64%). DISCUSSION/SIGNIFICANCE OF IMPACT: Our study has shown that the presence of photographs obtained at the point‐of‐care can lead to a significant increase in the detection rate of mislabeling/misidentification errors. This can have a significant impact on patient safety.
P265
PHYSIOLOGICAL DECREMENTS IN GLUCOSE LEVELS ARE ASSOCIATED WITH HUNGER AND DEACTIVATION OF THE PRE–FRONTAL CORTEX (PFC)
Belfort De Aguiar RD 1, Naik S1, Seo D1, Lacadie C1, Constable T1, Sinha R1, Sherwin R1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Hypoglycemia stimulates hunger, but whether small physiological changes in plasma glucose (PG) levels influence food‐seeking behavior is unclear. METHODS/STUDY POPULATION: Twenty healthy subjects (mean age 29 ± 7, A1c 5.4 ± 0.3, BMI 24 ± 2) underwent a 2 mU/kg.min hyperinsulinemic euglycemic clamp (goal = PG ~95 mg/dl) while viewing food and nonfood pictures combined with functional MRI. Hunger ratings were collected at baseline and 2 h. An age and BMI matched control group of 10 subjects was studied using a 0.9% saline infusion instead of a clamp. RESULTS/ANTICIPATED RESULTS: During the clamp, PG rose from 85 ± 11 at baseline to 93 ± 13 mg/dL at 10 min. During the next 10–60 min interval PG showed some variability (85 ± 11 to 99 ± 11): PG decreased In 10 subjects by 14 ± 10 (G.Fall group) and increased (G.Inc group) in 10 subjects by 12 ± 12. PG subsequently stabilized at 95 ± 8 in both groups until the end. Hunger ratings significantly increased from 2 ± 2 at baseline to 5 ± 3 at 2 h (p < 0.01). Change in hunger was associated with the drop in PG between 10 and 60 min (r =−0.59, p < 0.01). Hunger was associated with increased activation in the insula, thalamus and striatum. The G.Fall compared to the G.Inc group showed deactivation of the ventral medial PFC. The changes in PG were not associated with glucagon, cortisol or ghrelin levels. Brain activation was not different between the two groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Small decrements in PG within the normal range provoked increased hunger, activation of the striatal‐limbic system, and deactivation of the PFC (cognitive control) when individuals were exposed to visual food cues. This suggest that the capacity of the brain to control desire for food and reward‐motivation pathways is impaired by small decrements in PG and might contribute to inappropriate overeating and weight gain in healthy individuals.
P266
PLATELETS PRESENT ANTIGEN IN THE CONTEXT OF MHC CLASS I IN EXPERIMENTAL CEREBRAL MALARIA
Chapman LM 1, Aggrey AA1, Field DJ1, Srivastava K1, Baldwin WM2, Yui K3, Tophman DJ1, Morrell CN1
1University of Rochester Medical Center, Rochester, NY, USA; 2Cleveland Clinic, Cleveland, OH, USA; 3Nagasaki University, Nagasaki, Japan
OBJECTIVES/SPECIFIC AIMS: Our lab and others have shown an important role for platelets in initiating and sustaining vascular inflammation in many mouse model systems and human diseases. We propose that platelets have a direct role in driving an acquired immune response by functioning as antigen presenting cells (APCs). We also predict that platelets initiate T‐cell responses to Plasmodium infection and that platelets may provide a novel basis for cell based vaccine development. METHODS/STUDY POPULATION: Mouse and human platelet antigen presentation machinery was detected by Western blots and flow cytometry. Mouse platelets from wild‐type or OVA‐transgenic mice were co‐incubated with T cells from WT or OT‐1 mice (T cell receptor transgenic for OVA‐MHC class I). T‐cell activation was determined by ELISA and flow cytometry. Using the cerebral malaria mouse model, we were able to further demonstrate the role of platelets in driving immune responses during infection, and the ability for platelets to be used in cell based vaccines. RESULTS/ANTICIPATED RESULTS: We found that platelets express T‐cell co‐stimulatory molecules, present antigen in the context of MHC class I, and activate T cells both in vitro and in vivo. We also have found that platelets present Plasmodium derived antigen and activate T‐cells in the P. berghei model of cerebral malaria. We have also used platelets as a vehicle to deliver a protective cell based vaccine in this disease model. DISCUSSION/SIGNIFICANCE OF IMPACT: Platelets present antigen to T cells in a MHC class I dependent manner to induce naive T‐cell responses and platelets have a direct role in initiating T‐cell responses to Plasmodium infection. These findings may provide a novel basis for the development of cell‐based vaccines.
P267
PRECLINICAL ASSESSMENT OF MULTIMODAL IMAGEABLE FORMULATION FOR THERMO‐CHEMOEMBOLIZATION OF LIVER CANCER
Liapi E 1, Mirpour S1, Wabler M1, Seshadri M1, Gholamrezanezhad A1, Zhou H1, Zhang Y1, Ivkov R1
1Johns Hopkins University, Baltimore, MD, USA
OBJECTIVES/SPECIFIC AIMS: Magnetic hyperthermia is an anticancer therapy that requires targeted deposition of magnetic nanoparticles (MN) inside the tumor, followed by application of an alternating magnetic field (AMF), causing the particles to modestly heat. We have developed a novel hybrid procedure involving the combination of intra‐arterial chemoembolization with AMF hyperthermia with injection of a single thermo‐chemoembolization (T‐C) formulation. Moreover, the T‐C formulation provides MR and CT visibility for tumor targeting validation. METHODS/STUDY POPULATION: T‐C formulation contains doxorubicin (16 mg/ml), lipiodol and MN. In vitro characterization of the T‐C formulation included doxorubicin measurements following AMF heating, and formulation temperature measurements with varying concentrations of iron or varying AMF field strengths. For in vivo studies, 0.5 ml of T‐C containing 5 mg/ml of iron were injected through a 2.7 Fr microacatheter into the hepatic artery of liver VX2 tumor bearing rabbit. RESULTS/ANTICIPATED RESULTS: Doxorubicin degradation was minimal after 1 hour of AMF heating. There was a linear relationship between iron concentrations and heating efficiency. Standard T1W and T2W scans on 3.0 T MRI successfully detected various concentrations of T‐C formulations in gelatin phantoms. In the rabbit Vx‐2 tumor postprocedural standard T1W and T2W scans revealed marked peritumoral hypointensity. Unenhanced CT scans showed marked positive peritumoral hyperdensity. DISCUSSION/SIGNIFICANCE OF IMPACT: The T‐C formulation shows physical properties that may enhance the outcome of thermo‐chemoembolization. The T‐C procedure may serve as a novel therapeutic strategy against liver cancer and a dual‐imaging probe for image‐guided tumor targeting.
P268
PRECLINICAL EFFICACY OF A BIFUNCTIONAL ANTIBODY RECRUITING MOLECULE TARGETING PROSTATE CANCER
Hoimes CJ 1, Zhang AX1, Murelli R2, Saltzman WM1, Spiegel D1
1Yale Univ, New Haven, CT, USA; 2Brooklyn Coll, Brooklyn, NY, USA
OBJECTIVES/SPECIFIC AIMS: Immunotherapy has demonstrated an improved survival in patients with castrate resistant prostate cancer. We have developed a small molecule immunotherapeutic for prostate cancer (ARM‐P) that exploits prostate specific membrane antigen for endogenous antibody‐directed targeting and killing. METHODS/STUDY POPULATION: The antibody recruiting molecule targeting prostate cancer (ARM‐P) was rationally designed, HPLC purified, and prepared in water for use. Mice bearing LNCaP xenografts were immunized with dinitrophenyl‐ficoll and treated with ARM‐P every other day, docetaxel weekly, or the combination intraperitoneally for 28 days and monitored. RESULTS/ANTICIPATED RESULTS: ARM‐P produced at least 50% cytotoxicity of LNCaP cells in a calcein release ADCC assay in the presence of human PBMCs and anti‐DNP IgG antibody. Toxicity studies in nude mice showed no electrolyte, hepatic, renal, or histologic evidence of toxicity. ARM‐P inhibits growth of human prostate cancer PSMA positive xenografts and prolongs survival in the presence of anti‐DNP antibody with an efficacy comparable to that of docetaxel (median survival 55 days or 27 days post therapy cessation). In contrast, combination therapy with ARM‐P and docetaxel afforded partial responses not seen with single agent treatment and improved median survival to 71 days, or 43 days post–treatment cessation. ARM‐P had no effect on PSMA‐negative xenografts and those xenografts without DNP immunization. Immunohistochemistry showed lymphocyte infiltration in xenograft tumors immunized for DNP and treated with ARM‐P. DISCUSSION/SIGNIFICANCE OF IMPACT: The novel small molecule immunotherapeutic ARM‐P is as effective as docetaxel for controlling prostate cancer growth and has enhanced antitumor effects given in combination with docetaxel in xenografts. Further characterization of in vivo mechanism is ongoing.
P269
PREMOTOR‐MOTOR INHIBITION EXHIBITS TASK SPECIFICITY IN FOCAL HAND DYSTONIA
Pirio Richardson S 1,2, Beck S2, Bliem B2,3, Hallett M2
1University of New Mexico, Albuquerque, NM, USA; 2National Institutes of Health, Bethesda, MD, USA; 3International Graduate School of Neuroscience, Ruhr University, Bochum, Germany
OBJECTIVES/SPECIFIC AIMS: Dystonia is a neurological disorder characterized by abnormal posturing due to sustained muscle contractions, which interferes with the performance of motor tasks. In focal hand dystonia (FHD), a deficient interaction between premotor and motor cortex could impair the ability of the motor cortex to execute a task‐specific movement. We hypothesize that a deficient premotor‐motor inhibitory network contributes to the unwanted involuntary movements in dystonia. METHODS/STUDY POPULATION: We studied five control subjects and seven patients with FHD. Premotor‐motor intracortical inhibition (PICI) was tested by applying conditioning transcranial magnetic stimulation to the premotor cortex and then a test pulse to the ipsilateral motor cortex 6 ms later. PICI was tested at rest, with contraction, and during a pen‐holding task. RESULTS/ANTICIPATED RESULTS: Our preliminary results show that patients with FHD exhibited PICI at rest (87.6%, the ratio of conditioned test pulse to unconditioned test pulse) in contrast to our control subjects who did not show PICI (99%). With contraction compared to rest, PICI decreased by 14% in FHD patients. With writing compared to rest, PICI decreased markedly by 25% in the patient group. In the control group PICI was not modulated by contraction or writing. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that abnormal premotor‐motor interactions may play a role in the pathophysiology of focal dystonia. The marked decrease in PICI in FHD patients during task‐specific movement suggests that a deficient premotor‐motor inhibitory network contributes to the unwanted movements. By contrast, the enhanced PICI at rest in FHD compared to controls may represent a compensatory mechanism that is overwhelmed when the motor system is activated.
P270
PROBENECID COADMINISTRATION INCREASES N‐ACETYLCYSTEINE CONCENTRATIONS FOLLOWING EXPERIMENTAL PEDIATRIC TRAUMATIC BRAIN INJURY
Empey PE 1, Alexander HL2, Ocque AJ1, Oberly PJ1, Minnigh MB1, Nolin TD1, Poloyac SM1, Kochanek PM2, Clark RS2
1School of Pharmacy, U of Pittsburgh, Pittsburgh, PA, USA; 2Safar Center for Resuscitation Research, U of Pittsburgh, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: Oxidative stress plays an important role in the pathophysiology of traumatic brain injury(TBI) but antioxidants have not shown clinical efficacy possibly due to poor brain penetration. Xenobiotic transporters are well known to impact entry of drugs into the brain. We hypothesized that co‐administration of the transporter inhibitor, probenecid(PB), would increase plasma levels of the antioxidant, N‐acetylcysteine (NAC), in a preclinical model of pediatric TBI. This study aimed to determine if this approach has the potential for direct clinical application to improve outcomes in pediatric TBI patients. METHODS/STUDY POPULATION: Juvenile rats (16–18 days old; ≥5/group) received a controlled cortical injury (2.5 mm deformation at 4 m/s) and intraperitoneal doses of NAC (163 mg/kg), PB (150 mg/kg), or the combination 10 min postinjury. Novel liquid chromatography tandem mass spectrometry assays were developed for both drugs and serial plasma concentrations were quantified. RESULTS/ANTICIPATED RESULTS: Drug assays were linear (NAC: 100–10000 ng/mL, R2= 0.9991; PB: 25–800μg/mL, R2= 0.9926), accurate(inter‐/intra‐assay variation #7.2%), and precise (inter‐/intra‐assay variation #8.4%). Coadministration of PB and NAC increased plasma NAC exposure ~2‐fold (AUC1–6h: 1.16 ± 0.21×105 vs. 2.13 ± 0.40×105 ng/mL*h; p = 0.006); PB levels were unchanged. DISCUSSION/SIGNIFICANCE OF IMPACT: PB coadministration increases systemic NAC exposure in juvenile rats following experimental TBI; suggesting that NAC is a transporter substrate and that brain levels may also increase. Transporter inhibition is a promising therapeutic strategy for future studies in pediatric TBI patients. Support: KL2RR024154, NS069247, NS030318, S10RR023461.
P271
PROBLEMATIC VIDEO GAMING IN ADOLESCENTS: BEHAVIORAL, STRESS DIATHESIS, AND NEUROPHYSIOLOGICAL CORRELATES
Hammond CJ 1, Mayes LC1, Potenza MN1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Aim 1: To characterize relationships between video gaming, problematic video gaming, and health functioning, psychological, environmental, risk‐taking, delay discounting, and substance use correlates in 12 to 17 year olds. Aim 2: To study relations between stress reactivity, chronic stress, and problematic video gaming in adolescents. Aim 3: To examine the effects of problematic video gaming on EEG‐based event‐related potentials(ERPs) including P300 and feedback error‐related negativity(fERN) amplitude. METHODS/STUDY POPULATION: Cross‐sectional study design to compare adolescents with problematic video gaming to age‐gender‐IQ matched controls on EEG and stress measures. RESULTS/ANTICIPATED RESULTS: HYPOTHESIS 1: We hypothesize that adolescent problematic video gaming will be associated with anxiety, depression, risk‐taking behaviors, low parental monitoring, and health/functional impairment. We hypothesize that problematic video gaming will be associated with earlier age of onset of alcohol/drug use. We hypothesize that adolescent problematic gamers compared to low‐frequency gamers and nongamers will have steeper delay discounting curves, preferring smaller immediate rewards instead of larger delayed rewards, and exhibit greater behavioral risk taking. HYPOTHESIS 2: We hypothesize that adolescents with a greater stress dysregulation and chronic stress will be more likely to demonstrate problematic video gaming. HYPOTHESIS 3: We hypothesize that P300 and fERN amplitude will be associated with problematic video gaming in adolescents. DISCUSSION/SIGNIFICANCE OF IMPACT: As adolescent problematic video gaming has been associated with adverse measures like depression and substance abuse, more research is needed to characterize these adolescents behaviorally and biologically and develop effective prevention and intervention strategies for problematic video gaming.
P272
PROGNOSTIC INDICATORS ASSOCIATED WITH BREAST CANCER SUBTYPES IN AFRICAN AMERICAN WOMEN
Ricks‐Santi LJ 1, Esnakula AK1, Frederick WA1, Naab TJ1
1Howard University College of Medicine, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Overexpression of Fascin, CD105, and beta‐catenin are associated with unfavorable prognosis and progression in hormone‐receptor negative breast carcinomas. The objective of this study was to correlate fascin, CD105, and beta‐catenin protein expression with clinicopathological factors such as grade, stage, survival, and breast cancer subtypes (luminal A, luminal B, HER2 positive, and Triple Negative [TN]). METHODS/STUDY POPULATION: Tissue microarrays (TMAs) were constructed from optimally‐fixed formalin‐fixed, paraffin‐embedded tumor blocks from primary breast carcinomas in 203 African American females. Sections were stained with antibodies against fascin, CD105, and beta‐catenin. The sections were evaluated for the intensity of reactivity and the percentage of reactive cells. Bivariate analysis was done via chi‐square analysis and survivability data was calculated via the generation of Kaplan‐Meier curves. RESULTS/ANTICIPATED RESULTS: On the TMA, there were 67 TNs, 88 Luminal As, 29 Luminal Bs, and 18 Her2 overexpressing cancers. Fascin expression was significantly linked to the TN subtype (p < 0.0001), ER negativity (p < 0.0001), PR negativity (0.0001), and Grade III differentiation (p = 0.03). CD105 cytoplasmic expression significantly correlated with HER2 positive subtype (p < 0.0001), Luminal B subtype (0.01), HER2 positivity (p < 0.0001), tumor size (p < 0.01) and was associated with decreased disease‐free survival (p = 0.038). Cytoplasmic beta‐catenin expression was significantly associated with TN subtype (p < 0.03), HER2+ subtype (p < 0.001), ER negativity (p < 0.001), PR negativity (p < 0.001), and HER2 negativity (p = 0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that fascin, CD105, and beta‐catenin may be potential markers of aggressive breast cancer subtypes and predictors of recurrence and survival.
P273
PROSTAGLANDIN E2 OPPOSES IL‐23 PLUS IL‐1b IN THE INDUCTION OF THE Th1 IMMUNE RESPONSE AND INSTEAD PROMOTES AN IL‐17A PREDOMINANT Th17/Th2 IMMUNE RESPONSE
Barrie A 1, Henkel M1, Scott R1, Porter M1, Zhang Y1, Kloke J1, Park S1, Ray A1, Duerr R1
1University of Pittsburgh Department of Medicine, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: Inflammatory bowel disease is propagated by IL‐17 producing CD4+ T helper (Th17) cells, which are modulated by IL‐23, IL‐1β, and prostaglandin E2 (PGE2). Previous studies examining memory T‐cell expression traits in response to the three mediators have been limited. We sought to define the mRNA and protein expression profiles of activated human peripheral CD4+ effector memory T cells treated with PGE2 and/or IL‐23 plus IL‐1β. METHODS/STUDY POPULATION: We characterized the mRNA expression of activated human CD4+ effector memory T cells from 14 blood donors treated with PGE2 and/or IL‐23 plus IL‐1β using a commerically available Th17 pathway real‐time quantitative PCR array. To verify our mRNA expression findings, we measured related protein production of 9 additional blood donors using multiplex and individual ELISA analyses. RESULTS/ANTICIPATED RESULTS: We discovered that PGE2 and IL‐23 plus IL‐1β differentially regulate Th17 gene expression and synergize to induce IL‐8 and IL‐17A but not IL‐17F. PGE2 concurrently induces IL‐5, IL‐9, and IL‐13 while repressing the IL‐23 plus IL‐1β‐mediated induction of GM‐CSF, IFN‐γ, TNF‐α, and the mRNA expression of IL23R. DISCUSSION /SIGNIFICANCE OF IMPACT: We conclude that PGE2 opposes IL‐23 plus IL‐1β in the induction of the Th1 immune response and instead promotes an IL‐17A predominant Th17/Th2 immune response that potentially favors host defense and protects against chronic inflammatory disease.
P274
RACIAL DIFFERENCES IN LUNG CANCER SURVIVAL AMONG LOW‐INCOME U.S. ADULTS
Aldrich MC 1,2, Grogan EL1, Munro HM3, Signorello LB2,3, Blot WJ2,3
1Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; 2Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA; 3International Epidemiology Institute, Rockville, MD, USA
OBJECTIVES/SPECIFIC AIMS: Few lung cancer studies have focused on lung cancer survival in underserved populations. METHODS/STUDY POPULATION: We conducted a prospective cohort study among 73,382 racially diverse and medically underserved adults enrolled in the Southern Community Cohort Study throughout a 12‐state area of the Southeast from March 2002 to September 2009. Using linkages with cancer registries, we identified 413 incident non–small cell lung cancer cases. We applied Cox proportional hazards models to estimate hazard ratios for lung cancer mortality among black and white lung cancer patients. RESULTS/ANTICIPATED RESULTS: The mean observed survival (the time from diagnosis to death or end of follow‐up) was 1.3 years (range 0–8.4 years) and 78% (N = 323) were deceased. Mean survival times were lower among blacks (1.2 years) than whites (1.5 years), but the difference was not statistically significant (p = 0.11). Blacks were more likely to be diagnosed at distant stage than whites (p = 0.04) despite having similar health insurance status (p = 0.32), income (p = 0.85) and education (p = 0.16). In multivariable analyses adjusted for pack‐years of smoking, stage, health insurance and socioeconomic status, the lung cancer mortality hazard ratio for blacks versus whites was 1.22, 95% confidence interval: 0.91–1.64. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings confirm blacks are more likely to present with distant stage of disease despite similar socioeconomic and health insurance status and highlight the need to determine reasons for this disparity.
P275
REDUCING LATENCY AND ENHANCING PATHOPHYSIOLOGY OF A MURINE MODEL OF PEDIATRIC BRAINSTEM GLIOMA
Nazarian J 1, Kambhampati M1, Yadavilli S1
1Children’s National Medical Center, Washington, DC, USA
OBJECTIVES/SPECIFIC AIMS: Diffuse intrinsic pontine gliomas (DIPGs) are high grade brainstem gliomas (BSGs) that remain uniformly fatal. Factors contributing to the lack of progress include tissue unavailability, and lack of robust animal models of the disease. A murine model of pediatric BSG has been genetically engineered that developes high grade gliomas due to PDGFβ overexpression. However, the high latency (2–4 months) of tumor development hinders rapid preclinical testing. Our aim has been to reduce the latency of tumor development in this murine model. METHODS/STUDY POPULATION: Fresh tumor specimen from BSG mouse were harvested and cultured to obtain neurospheres. Neurospheres (150K) were then intracranially injected into brainstem of 2‐day‐old (P2) mice. Animal were observed for signs of tumor development including ataxia, lethargy and motor function. Mice that exhibited signs of tumor development were sacked and brain specimen were fixed in formalin and analyzed by immunohistochemical assays. RESULTS/ANTICIPATED RESULTS: We show that neurosphere injected mice develop brainstem tumors within 3–4 weeks post injection. These mice develop a highly infiltrative tumor that is highly proliferative and causes death within 4–5 weeks post injection. To characterize the tumor, we have generated preliminary protein profiles of these neurospheres and show up‐regulation of gliomagenesis pathways in the neurospheres. DISCUSSION/SIGNIFICANCE OF IMPACT: Inspired by the NIH “bench‐to‐bedside approach,” we have been trying to develop a murine model for rapid drug test. We show that we have been able to reduce latency of tumor development in an existing murine model of BSG. This model is suitable for rapid preclinical testing for investigating efficacy, sensitivity and specificity of candidate therapeutics.
P276
REGIONAL NETWORK DISRUPTION IN TEMPORAL LOBE EPILEPSY
Maccotta L 1, Corbetta M1, Hogan R1
1Washington University, St. Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: The medial temporal lobe is anatomically connected with the contralateral medial temporal lobe and other temporal brain regions. Extratemporal regions (e.g., the insula) have a clear role in the ictal period, both semiologically and electrographically. It is unclear whether the medial temporal cortex and other temporal or extratemporal brain regions form a functional network, and how temporal lobe epilepsy (TLE) affects these connections. Here we investigated the functional connections of the medial temporal region with contralateral temporal and extratemporal brain regions in TLE patients and controls using resting state BOLD functional MRI. METHODS/STUDY POPULATION: 32 TLE patients and matched controls underwent resting‐state BOLD fMRI. Seizure localization was based on video‐EEG. Regions of interest were defined anatomically a priori and functioned as seeds in a functional connectivity analysis. RESULTS/ANTICIPATED RESULTS: TLE is associated with changes in the functional connections of the medial temporal region. Healthy hippocampal and parahippocampal regions are strongly coupled across hemispheres. With TLE this connectivity is decreased (p < 0.05), resulting in a functional decoupling between medial temporal regions. Local decoupling is also observed within each medial temporal region. Conversely, the medial temporal region ipsilateral to the epileptogenic focus exhibits significantly increased coupling with the bilateral insulae. DISCUSSION/SIGNIFICANCE OF IMPACT: An increased functional connection in the face of a pathologic/destructive process has several potential explanations, including maladaptive‐pathologic (e.g., representing abnormal circuitry that is involved in seizure generation) or compensatory etiologies, such as an attempt at down‐modulation of a pathologically excitable circuit. These additional nodes in the functional network of TLE may provide future pharmacologic or surgical targets.
P277
RENAL TUBULAR CELLS INDUCE EARLY PRO‐INFLAMMATORY AND LATE ALTERNATIVE ACTIVATION IN MACROPHAGES
Huen SC 1, Cantley LG1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Macrophage infiltration into the kidney after ischemia reperfusion can contribute to both the initial injury and subsequent recovery. A classically activated inflammatory phenotype predominates early after reperfusion while an alternatively activated antiinflammatory phenotype predominates later during the repair phase. How paracrine signals from renal tubular cells influence these macrophage phenotypes is unknown. METHODS/STUDY POPULATION: Mouse proximal tubular (MPT) cells were cultured in serum free media for 48 hours to generate MPT conditioned media (CM). Bone marrow–derived macrophages (BMM) were cultured ± MPT CM and harvested for protein or mRNA analysis. RESULTS/ANTICIPATED RESULTS: NF‐κB was rapidly activated in wild‐type BMM cultured in MPT CM, followed by increased expression of pro‐inflammatory markers Il‐1β, Tnfα, Il‐6, and Csf3 within 2 hours. By 12 hours after MPT CM incubation, the pro‐inflammatory genes were down‐regulated, whereas alternative activation markers Arg1 and MR were highly up‐regulated. The early pro‐inflammatory response was prevented in BMM lacking MyD88. The late expression of Arg1 and MR was not prevented in BMM lacking the Il‐4rα receptor or the downstream effector Stat6, suggesting that tubular cell‐mediated alternative macrophage activation occurs via an Il‐4/Stat6 independent pathway. Stat3 is activated in BMM at 30 minutes and 24 hours after exposure to MPT CM, identifying this as a potential mediator of tubular cell‐dependent alternative activation. DISCUSSION/SIGNIFICANCE OF IMPACT: Secreted tubular factors induce sequential macrophage activation from a NF‐κB dependent pro‐inflammatory phenotype to an antiinflammatory phenotype. This sequential macrophage activation is similar to that seen in vivo after renal ischemia reperfusion injury, suggesting that tubular cells themselves can regulate the phenotype of infiltrating macrophages.
P278
REVERSIBLE EPIGENETIC MECHANISM OF TRASTUZUMAB RESISTANCE
Cao J 1, Zou MR1, Liu Z1, Harris LN2, Yan Q1
1Department of Pathology, Yale University School of Medicine, New Haven, CT, USA; 2Department of Clinical Oncology, Yale University School of Medicine, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Drug resistance is a major issue in cancer treatment, but its mechanisms are just being discovered. There is growing evidence that some drug resistance mechanisms are due to epigenetic changes. The aim of this study is to determine the contribution of epigenetic alterations to trastuzumab resistance of HER2+ breast cancer. METHODS/STUDY POPULATION: We planned to set up cell based models to mimic the in vivo situation of trastuzumab resistance. Through long‐term treatment of trastuzumab sensitive HER2+ cells with increasing concentrations of trastuzumab, we aimed to generate trastuzumab resistant cells. These cells will be compared with the parental cells to determine the roles of epigenetic changes in trastuzumab resistance. RESULTS/ANTICIPATED RESULTS: Trastuzumab resistant clones we generated retain the drug resistant property in short‐term culture without trastuzumab, but revert back to drug sensitive states after long‐term passage without trastuzumab. These studies suggest that these cells are epigenetically reprogrammed as they become drug resistant. Furthermore, we showed that the JARID1 histone demethylases are essential for drug resistance of these cells. More importantly, using gene expression profiles of tissue samples from a cohort of 80 early stage HER2+ breast cancer patients treated with preoperative trastuzumab and chemotherapy, we showed that high expression level of some JARID1 genes or their target genes predicts poor trastuzumab response of these patients. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies demonstrated that reversible epigenetic changes contribute significantly to trastuzumab resistance and suggest that inhibitors of the JARID1 demethylases can be developed for clinical use.
P279
ROLE OF C‐REACTIVE PROTEIN IN REGULATORY MONOCYTE INDUCTION AND ACTIVATION IN TRAUMA PATIENTS
West SD 1, Mold C1, DuClos TW1,2
1University of New Mexico, Albuquerque, NM, USA; 2VA Medical Center, Albuquerque, NM, USA
OBJECTIVES/SPECIFIC AIMS: C‐reactive protein (CRP) is an acute phase reactant. Its plasma concentration increases from <5 to >100 μg/ml within 48 h of injury due to increased synthesis by hepatocytes responding to IL‐6. Highly elevated CRP levels are seen in trauma, and maintenance of these levels is associated with a poor prognosis, but the role of CRP in trauma is poorly understood. METHODS/STUDY POPULATION: We measured a panel of monocyte markers and cytokines in 27 trauma patients for 3 days following admission and analyzed their correlation with CRP levels. All samples were obtained in accordance with guidelines and under protocols approved by the Human Research Review Committee at the University of New Mexico Health Sciences Center. RESULTS/ANTICIPATED RESULTS: We identified a subpopulation of monocytes expressing high levels of CD14 and CD16 that were not found in healthy volunteers. These cells also expressed CD163 and HLA‐DR. The percentage of monocytes found in this subpopulation was highly correlated to plasma CRP levels (p = 0.0001) and to intracellular heme oxygenase (HO‐1) (p = 0.0009). CRP levels also correlated with monocyte HO‐1, and plasma antiinflammatory cytokines, IL‐10, IL‐1RA, and TGF‐β. We hypothesized that CRP activates monocytes to a regulatory phenotype as part of the compensatory antiinflammatory response in trauma. Incubation of isolated monocytes with trauma plasma, but not CRP‐depleted trauma plasma, increased CD16 and HO‐1. Differentiation of monocytes with M‐CSF also induced CD16 and HO‐1, and M‐CSF‐differentiated monocytes responded to CRP by secretion of IL‐10 and IL‐1RA. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest a role for CRP in the generation and activation of regulatory monocytes during the acute phase response.
P280
SCREENING OF INHIBITORY SMALL MOLECULES FOR CHRONIC BERYLLIUM DISEASE
Dai S 1
1National Jewish Health, Denver, CO, USA
OBJECTIVES/SPECIFIC AIMS: Chronic beryllium disease (CBD) is a fibrotic lung disorder caused by beryllium (Be) exposure. Genetic susceptibility to CBD has been associated with certain alleles of the MHCII molecule, HLA‐DP, especially HLA DPB1*0201 (DP2) and other alleles that contain a glutamic acid residue at position 69 of the β‐chain (β69Glu). We will screen small molecules, that can bind the unique pocket of HLA‐DP2. Our hypothesis is that these small molecules could, by blocking Be binding to HLA‐DP2, prevent the activation of pathogenic Be‐responsive T cells that drive the fibrotic response. METHODS/STUDY POPULATION: Screen small molecules, based on our crystal structure of DP2, to identify promising compounds. Test on the ability of these small molecules to inhibit activation of T cell hybridomas expressing Be‐responsive T cell receptors (TCRs). Test the drug candidates on Be‐responsive human cells and in a mouse model of Be‐induced disease. RESULTS/ANTICIPATED RESULTS: We have performed virtual library screening on several small molecule drug databases, and identified a number of promising small molecule compounds. We used the T cell hybridomas that express TCR genes from some of the Be‐specific human T cells to test these small molecules. Some inhibitory effects were observed at the high concentration for several compounds. Structural investigation of the complex models of these compounds and DP2 is in progress. They will be used as the basis for further virtual library screening to identify even stronger inhibitors. DISCUSSION/SIGNIFICANCE OF IMPACT: Once a patient is sensitized to Be compounds, Be stays in the human body forever and can lead to potentially fatal disease. Currently, there are no medications or procedures available that effectively eliminate this “allergic” reaction to Be. Our study potentially will develop these compounds for treatment of CBD patients.
P281
SELECTIVE FUNCTIONAL RELATIONSHIP BETWEEN THE HUMAN RETROSPLENIAL CORTEX AND MEDIAL TEMPORAL LOBE DURING SELF‐REFERENTIAL COGNITIVE TASKS
Kaveh AH 1, Foster BL1, Parvizi J1
1Stanford University, Stanford, CA, USA
OBJECTIVES/SPECIFIC AIMS: Self‐referential tasks such as episodic recall typically produce clear functional activation in the ventral region of the human posteromedial cortex (PMC) with neuroimaging methods. The aim of the current study was to examine the functional relationship between the retrosplenial cortex (RSC), constituting the ventral region of the PMC, with the medial temporal lobe (MTL) using intracranial electrophysiological recordings. METHODS/STUDY POPULATION: RSC and MTL activity was recorded from patients during self‐paced true/false judgments of arithmetic and autobiographical stimuli. All patients provided full written consent and were implanted with subdural electrodes for seizure monitoring as part of their treatment for refractory epilepsy. RESULTS/ANTICIPATED RESULTS: Event‐related time‐frequency analysis revealed strong and selective phase coherence between the RSC and the MTL in the theta band during autobiographical judgments. Arithmetic judgments did not produce any theta phase synchrony, instead increasing coherence in the alpha band. These were absent between random electrodes chosen from other regions of the brain. DISCUSSION/SIGNIFICANCE OF IMPACT: Due to its deep, interhemispheric location in the brain, the RSC’s function is poorly understood despite neuroimaging studies showing its loss of activity in diseases of memory such as Alzheimer’s dementia. The unknown function of the RSC represents a large gap in medical knowledge, and our findings are the first to report (1) RSC activity in a memory network with this level of temporal and spatial resolution, and (2) functional relationship with brain regions known to be involved in memory processing. Our findings will provide crucial knowledge about the functional involvement of the RSC in memory processing and will help us understand the symptomology of memory dysfunction due to retrosplenial problems.
P282
Th17 DEVELOP IN THE HUMAN GASTRIC TUMOR MICROENVIRONMENT AND PROMOTE PRO‐CARCINOGENIC EVENTS
Beswick EJ 1, Morris KT1, Earley RB1, Nofchissey RA1, Ma TY1, Pinchuk IV2
1University of New Mexico Health Sciences Center, Albuquerque, NM, USA; 2University of Texas Medical Branch, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: Gastric cancer is associated with chronic inflammation and H. pylori infection. Th17 cells are a CD4+ T cell phenotype up‐regulated during infections and inflammation, but their role and mechanism of induction during carcinogenesis is not known. We have shown that gastric epithelial cells (GEC) and myofibroblasts (GMF) express class II MHC, act as antigen presenting cells, and produce cytokines that influence the local T‐cell response. We hypothesize that Th17 develop in the gastric tumor microenvironment and produce IL‐17A, which in turn induces pro‐carcinogenic events. METHODS/STUDY POPULATION: Th17 and IL‐17RA were examined in matched normal and tumor tissues by Real Time PCR. GMF isolated from normal tissues, H. pylori infected cells, and cancer tissues and incubated with activated naïve CD4+ T cells to examine Th17 development by flow cytometry. GEC were examined for IL‐17RA expression and proliferation and migration in response to IL‐17A. RESULTS/ANTICIPATED RESULTS: Th17 and IL‐17RA were increased in human tumor tissues compared to matched normal tissues. GMF isolated from human gastric cancer tissues induced much higher levels of Th17 than GMF isolated from matched normal tissues. GEC infected with H. pylori also induced Th17 from naïve CD4+ T cells in coculture. IL‐17A induced gastric carcinoma cell proliferation and migration. DISCUSSION/SIGNIFICANCE OF IMPACT: Th17 cells develop during H. pylori infection and in the human gastric tumor microenvironment by CD4+ T‐cell interaction with GMF and GEC suggesting an important link between chronic infection, inflammation, and gastric carcinogenesis. IL‐17A produced by Th17 induced proliferation and migration of gastric carcinoma cells suggesting the need to develop therapeutics to target Th17 in gastric cancer.
P283
THE EFFECTS OF SIMVASTATIN ON HUMAN AIRWAY EPITHELIAL CELL VIABILITY AND MORPHOLOGY
Zeki AA 1, Ghavami S2, Halayko A2, Wu R1
1University of California, Davis School of Medicine, Sacramento, CA, USA; 2University of Manitoba, Section of Respiratory Medicine, Winnipeg, MB, Canada
OBJECTIVES/SPECIFIC AIMS: To determine whether simvastatin causes airway epithelial cytotoxicity and whether such changes are dependent on mevalonate (MA). METHODS/STUDY POPULATION: The HBE1 cell line and primary normal human bronchial epithelial (NHBE) cells were treated with simvastatin (Sim) ± MA (2 mM) in serum‐starved cell culture conditions. After treatment with low‐ (2.5, 5, 10 μM) versus high‐dose Sim (20 μM) for 24, 48, 72, and/or 96 hrs, we assessed for cell viability using the Alamar blue and MTT assays, cell death using Trypan blue exclusion and total cell counts, and cell morphological changes using light microscopy. RESULTS/ANTICIPATED RESULTS: Low‐dose Sim treatment of HBE1 cells (24 and 48 hrs) did not decrease cell viability, but high‐dose Sim treatment decreased cell viability in a MA‐dependent manner without causing cell death. High‐dose Sim treatment (24 and 48 hrs) altered cell morphology in a MA‐dependent manner. In primary NHBE cells there was a time‐ and dose‐dependent decrease in cell viability. After 24 hrs of Sim treatment there was no significant decline in cell viability at any statin dose. But after 48, 72, and 96 hrs treatment, there was a dose‐dependent decrease in cell viability at all statin doses. Both low‐ and high‐dose Sim treatment (40 or 96 hrs) altered cell morphology. DISCUSSION/SIGNIFICANCE OF IMPACT: Simvastatin may be cytotoxic to human airway epithelial cells at the micromolar doses used. Although there was no detectible cell death at the time points observed, Sim reduced cell viability and altered cell morphology. Some of these statin effects were MA‐dependent, indicating that HMG‐CoA reductase inhibition mediated some of these effects. Future studies are needed to determine the optimal therapeutic statin dose that preserves cell viability and barrier integrity.
P284
THE ROLE OF PEAR1 GENE ON DUAL ANTIPLATELET THERAPY AMONG CORONARY PATIENTS
Scott S 1, Peter I1, Martis S1, Shuldiner AR2, Collet J3, Montalescot G3, Hulot J1,3, Desnick RJ1
1Mount Sinai School of Medicine, New York, NY, USA; 2University of Maryland School of Medicine, Baltimore, MD, USA; 3Pitié‐Salpêtrière University Hospital, Paris, France
OBJECTIVES/SPECIFIC AIMS: The aim of this study is to identify additional genetic variants associated with dual antiplatelet therapy (DAPT; clopidogrel and aspirin) response in addition to variant CYP2C19 alleles. METHODS/STUDY POPULATION: The PEAR1 gene was recently associated with platelet aggregation and preliminary studies strongly suggest an association between PEAR1 and aspirin and/or clopidogrel response. To assess the role of PEAR1 in DAPT response, three candidate PEAR1 polymorphisms (rs12041331, rs11264579, rs11264581) have been genotyped in the 106 CLOVIS2 (NCT00822666) clinical trial participants. RESULTS/ANTICIPATED RESULTS: Initial PEAR1 analyses did not identify a statistically significant association between the three tested variants and clopidogrel pharmacodynamics. However, additional PEAR1 variants are now being genotyped as well as forthcoming PEAR1 haplotype analyses in this population. Moreover, selected PEAR1 variants and haplotypes will be assessed for association with DAPT clinical responses by genotyping the ~1500 ARCTIC (NCT00827411) clinical trial subjects. Finally, PEAR1 allele and haplotype frequencies will be determined in the African‐American, Asian, Caucasian, Hispanic, and Ashkenazi Jewish populations. DISCUSSION/SIGNIFICANCE OF IMPACT: By evaluating the independent and additive roles of PEAR1 among DAPT‐treated coronary patients, this translational study has the potential to significantly advance the field of antiplatelet pharmacogenetics and could facilitate the adoption of genetically‐guided antiplatelet therapy into routine interventional cardiology practice for more personalized and effective care.
P285
THE ROLE OF THE HYPOTHALAMIC OREXIN SYSTEM IN MENOPAUSE‐ASSOCIATED SYMPTOMS
Johnson PL 1, Federici LM1, Fitz SD1, Shekhar A1, Carpenter J1, Skaar T1
1Indiana University School of Medicine, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: Menopause is a condition where severely depleted estrogen levels lead to “hot flashes,” anxiety, and sleep disturbances (Freeman et al., 2005; Seritan et al., 2010). Estrogen replacement is effective in treating menopausal symptoms, but there are significant risks (e.g., breast cancer). Although the limited scientific understanding of these symptoms has hindered the development of alternative nonhormonal therapies, it is commonly accepted that the hypothalamus plays a critical role (Miller and Li, 2004). Recently we determined that a hypothalamic neuropeptide orexin (ORX) system is hyperactive in rats and humans with increased anxiety states (Johnson et al., 2010, Nat Med). Similarly, menopausal women (compared to controls) have 300% higher central ORX levels which are rescued with estrogen replacement (El‐Sedeek et al., 2010). Therefore, we predict that a hyperactive ORX system contributes to menopausal symptoms. METHODS/STUDY POPULATION: In order to test this hypothesis, we: (1) ovariectomized (OVEX) female rats to model a menopausal state; (2) induced “hot flashes” utilizing peripheral vasodilators (i.e., inverse benzodiazepine agonist, hypercapnic gas, and yohimbine), then (3) screened a centrally active ORX1 receptor antagonist. RESULTS/ANTICIPATED RESULTS: These vasodilators induced greater tail flushes in OVEX rats compared to SHAM rats. Furthermore, systemically pretreating OVEX rats with an ORX1 receptor antagonist attenuated: (1) OVEX‐induced anxiety behavior; and (2) an exacerbated “hot flash”‐associated increase in tail temperature. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that loss of estrogen inhibition of the ORX system may lead to menopause‐related symptoms, and that ORX1 receptor antagonists could constitute a novel method of treating menopausal symptoms.
P286
TRANSFORMING GROWTH FACTOR BETA (TGFB) SIGNALING IS REQUIRED FOR DISTAL LUNG DEVELOPMENT
Ahlfeld SK 1, Poindexter E1, Gao Y1, Wang J1, Conway SJ1
1Indiana University School of Medicine, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: Bronchopulmonary Dysplasia (BPD), a chronic lung disease of preterm infants, is characterized by interrupted saccular lung development. Using a hyperoxia model of BPD, we have observed decreased TGFB signaling coincident with the earliest evidence of BPD. Therefore, we genetically inhibited TGFB superfamily signaling in the lung epithelium during alveolar development to test the hypothesis that loss of TGFB signaling simplifies distal lung structure. METHODS/STUDY POPULATION: Neonatal mice carrying a Tet‐On myc‐tagged Smad7 transgene as well as a doxycycline‐inducible SPC‐rtTA were generated. At birth, nursing dams were given dox‐feed continuously to activate the transgene and overexpress Smad 7 in Type II alveolar cells to inhibit TGFB signaling. At P14, distal lung structure was analyzed and compared to single transgenic (TetO‐Smad7‐/SPC‐rtTA+) control pups. RESULTS/ANTICIPATED RESULTS: Double transgenic pups had marked elevation of c‐myc, indicating activation of the myc‐tagged Smad7 transgene, and reduced expression of periostin, a downstream product of TGFB signaling. Distal lung structure was simplified with reduced septal development, as evidenced by a nearly 10% increase in mean linear intercept, 15% increase in airspace‐to‐septal ratio, and 15% decrease in nodal density. DISCUSSION/SIGNIFICANCE OF IMPACT: Inhibition of TGFB signaling in Type II alveolar cells alone during postnatal distal lung morphogenesis sufficiently phenocopies the lung structural changes in BPD. These results indicate that loss of TGFB signaling during a critical window of saccular lung development may contribute to BPD pathogenesis. Understanding BPD pathogenesis will aid in designing appropriate therapies to treat and prevent BPD.
P287
UNDERSTANDING SURFACE COLONIZATION AND MOTILITY OF PSEUDOMONAS AERUGINOSA
Shrout JD 1
1University of Notre Dame, Notre Dame, IN, USA
OBJECTIVES/SPECIFIC AIMS: Many bacteria use motility described as swarming to colonize surfaces in groups that allows these bacteria to survive external stresses including exposure to antibiotics. Pseudomonas aeruginosa is an opportunistic pathogenic bacterium that infects surfaces of the lung, skin, intestine, or eye. P. aeruginosa often, but not always, forms branched tendril patterns during swarming; this physical phenomena occurs only when bacteria produce rhamnolipid, which is regulated by intercellular quorum sensing signaling. We investigated the surface cues and conditional response of P. aeruginosa swarming. METHODS/STUDY POPULATION: Swarming was investigated using semisolid agar plate assays and ex vivo skin samples. Images were acquired using fluorescence microscopy at various scales. RESULTS/ANTICIPATED RESULTS: We found that that P. aeruginosa quorum sensing and rhamnolipid production is impaired when growing on harder semi‐solid surfaces and this limits tendril formation. Despite large populations of cells on these harder surfaces, cell populations near the advancing swarm edge were not induced for quorum sensing. We were unable to artificially stimulate rhamnolipid tendril formation with added acyl‐homoserine lactone signals or increasing the carbon nutrients. We continue to research regulation of P. aeruginosa surface motility and have begun studying P. aeruginosa colonization and motility using human skin as an ex vivo model system. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggests that quorum sensing on surfaces is controlled in a manner that is not solely population dependent. We continue to investigate P. aeruginosa motility as this has implications to better understand colonization. Greater insight into colonization and the onset of P. aeruginosa infection will be useful to improve therapeutic strategies.
P288
VARIATION IN STREPTOCOCCUS PYOGENES VIRULENCE GENES IS ASSOCIATED WITH INVASIVE INFECTIONS AND TISSUE TROPISM
Riddle DJ 1, Hunstad DA1, Caparon MG1
1Washington University in St. Louis, St. Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: We hypothesize that polymorphisms in Streptococcus pyogenes virulence genes contribute to invasive infections or to the organism’s tissue tropism. We will identify the genetic differences between strains that cause invasive and noninvasive infections and reveal patient characteristics that increase the risk of invasive streptococcal disease. METHODS/STUDY POPULATION: Invasive and noninvasive S. pyogenes strains isolated from patients at Saint Louis Children’s Hospital will be matched by emm pattern (marker for tissue tropism), emm type, and housekeeping gene similarities. Polymorphisms associated with invasive diseases or tissue tropism will be uncovered. Patient characteristics associated with invasive streptococcal infections will be identified with a case control study design. Susceptibility to infections with specific virulence factor polymorphisms will also be studied. RESULTS/ANTICIPATED RESULTS: Analysis of spn revealed that it is diverging into NAD+ glycohydrolase (NADase)‐active and ‐inactive subtypes. NADase activity did not correlate with invasive diseases but was associated with tissue tropism. These data, in addition to the finding that spn retains the characteristics of a functional gene even after the loss of NADase activity in the product, suggest that SPN has other roles in pathogenesis. Through the application of similar analyses with other virulence genes, we anticipate uncovering novel functionally significant polymorphisms that are clinically relevant. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will identify virulence factor polymorphisms and patient characteristics that are associated with invasive streptococcal disease and form a basis for the development of targeted antivirulence therapies or infection prevention techniques.
P289
VITAMIN D SUFFICIENCY IS ASSOCIATED WITH AN ANTIINFLAMMATORY MONOCYTE PHENOTYPE
Riek AE 1, Oh J1, Timpson A1, Bernal‐Mizrachi C1
1Washington University School of Medicine, Saint Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: We tested the hypothesis that monocytes from 25‐hydroxy vitamin D [25(OH)D]‐deficient subjects will have a pro‐inflammatory phenotype compared to those from 25(OH)D‐sufficient subjects. METHODS/STUDY POPULATION: We performed a cross‐sectional study in 43 outpatients with self‐reported diagnosis of type 2 diabetes (T2DM). Monocytes were subjected to assays for adhesion, migration, membrane receptor expression, and mRNA expression. RESULTS/ANTICIPATED RESULTS: Serum 25(OH)D level was inversely associated with monocyte adhesion and migration (p < 0.05 for all). 25(OH)D level was also associated with the ratio of macrophage M1/M2 markers (expression of CCR7 + CD86 to CD163 + mannose receptor) in monocytes (p < 0.002), and the M1/M2 ratio correlated inversely with monocyte adhesion and migration (p < 0.03 for all). Patients with 25(OH)D >30 ng/mL had lower monocyte endoplasmic reticulum (ER) stress and decreased mRNA expression of adhesion molecules β1‐integrin, β2‐integrin, and PSGL‐1 and migration receptor CCR2 compared to those with 25(OH)D <20 ng/mL (p < 0.001 for all). In culture‐derived macrophages, 1,25(OH)2D3 suppressed ER stress, increased the M1/M2 phenotype ratio, and reduced adhesion and migration compared to cells cultured without 1,25(OH)2D3. DISCUSSION/SIGNIFICANCE OF IMPACT: T2DM is a chronic inflammatory disease characterized by increased ER stress in metabolic tissues and a high prevalence of vascular complications and vitamin D deficiency. We show that vitamin D is a natural ER stress reliever that induces an antiinflammatory monocyte/macrophage phenotype in patients with type 2 diabetes, and further interventional trials are needed.
Research Professionals Abstracts
BEST PRACTICES
P290
ASSESSING CLINICAL RESEARCH PARTICIPANTS’ EXPERIENCES
Kost RG 1, Lee LM2, Yessis J3, Henderson DK2, Coller BS1
1The Rockefeller University, New York, NY, USA; 2NIH Clinical Center, Bethesda, MD, USA; 3The Propel Centre for Population Health Impact, University of Waterloo, Waterloo, ON, Canada
OBJECTIVES/SPECIFIC AIMS: Few validated quantitative measures of research participants’ experiences exist. Based on results from focus groups, we developed and fielded a research participant perception survey to 18,890 participants at 15 academic medical centers (AMC) to assess participant‐centered outcomes. We report responses from 4961 participants. METHODS/STUDY POPULATION: We drafted a 77 item survey evaluating aspects of motivation, recruitment, consent, and communication. We conducted face and content validation and obtained IRB approval at AMCs. A commercial survey vendor, NRC Picker, managed logistics and analyzed sample validity, reliability of dimensions, and response outcomes. AMCs received confidential local results. RESULTS/ANTICIPATED RESULTS: Four thousand nine hundred sixty‐one surveys were returned (29%); trust, informed consent, information, respect for patient preferences, and coordination of care formed robust conceptual groupings (Cronbach alpha 0.68 – 0.85). Respondents were 85% Caucasian, 12% African American, 3% Asian, and 5% Hispanic. Two‐thirds were affected by diseases under study. Altruism was a common motivation for participation (64%); 73% rated research experiences highly; 60% reported feeling well prepared for research experiences by the informed consent process; 95% understood they could leave a study at will. DISCUSSION/SIGNIFICANCE OF IMPACT: Respondents had positive experiences and understood participation was voluntary. Forty percent of participants did not feel prepared for their experiences by informed consent processes. Use of a validated survey to assess research conduct offers insights into the research experience and efficacy of human protections from participant’s perspectives, and provides a tool to measure impact of improvement strategies.
P291
COMPARISON OF ANTIDEPRESSANT SIDE EFFECTS IN TELEMEDICINE‐BASED VERSUS PRACTICE‐BASED COLLABORATIVE CARE
Hudson TJ 1,2, Fortney JC1,2, Lu L1, Pyne JM1,2, Mittal D1,2
1Psychiatric Research Institute, Translational Research Intitute (CTSA Award 1 UL1RR029884), University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2VA HSR&D Center for Mental Healthcare and Outcomes Research, VA South Central MIRECC, North Little Rock, AR, USA
OBJECTIVES/SPECIFIC AIMS: This study compared medication side effects in a NIH‐funded, multisite, trial comparing depression treatment using telemedicine based collaborative care (TBCC) with practice based collaborative care (PBCC). METHODS/STUDY POPULATION: Patients who screened positive for depression were randomized to either TBCC or PBCC. Telephone interviews were completed at 6, 12 and 18 months and included assessment of depression severity, comorbid conditions, number of medication side effects and antidepressant adherence. This analysis uses data from patients (n = 217) who reported adhering to antidepressants (taking the prescribed dose at least 80% of days in the previous month). The number of side effects in the TBCC group was compared to the PBCC group. RESULTS/ANTICIPATED RESULTS: The majority of patients were female (12.4%) and Caucasian (66.9%); mean age was 47.7 years (SD = 12.4). The only statistically significant group differences were insurance coverage (PBCC had more uninsured subjects) and number of chronic physical illnesses [TBCC mean(SD) = 5.1(2.6), PBCC mean (SD) = 4.2(2.6), p = 0.01]. Controlling for demographic characteristics, the TBCC group reported fewer side effects (incidence rate ratio = 0.60, β=−.51, p = 0.01). Depression severity was also a significant predictor (p = 0.046). There were no significant differences with regard to antidepressant medication or comorbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: Patients receiving TBCC had more care manager encounters, perhaps leading to better side effect management. TBCC provided pharmacotherapy with fewer side effects than the more traditional PBCC model. This may contribute to improved quality of life.
P292
CREW RESOURCE AND QUALITY MANAGEMENT WILL REDUCE CLINICAL RESEARCH ERRORS
Ottenbacher M 1, Inniss A1, Lynch H1, Pfannenstiel T1, Vining C1, Rivera R1, Ruiz L1, Sheffield‐Moore M1, Anderson K1, Powell D1
1University of Texas Medical Branch, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: Errors in research specimen collection result in increased costs, loss of data, and may increase risks to research participants and decrease investigator satisfaction. To improve the quality and integrity of research data acquired on the UTMB Clinical Research Center and the UTMB/NASA Flight Analog Research Unit, we developed baseline measures of data integrity, identifying problems leading to erroneous data, and implemented changes through crew resource and quality management. METHODS/STUDY POPULATION: In 2009, we initiated crew resource management (CRM) and a Quality Management Program to reduce errors in the collection and processing of body fluid samples and the proper delivery of fixed composition meals. A uniform set of tools: checklists, cross‐checks, and time outs were developed and refined, with unique tools created for certain protocols. Metrics that portray Administrative, Nursing Services, Core Laboratory, Bionutrition, and Subject Safety activity are displayed monthly on a dashboard. Bi‐monthly quality management meetings are attended by CRC staff, leadership, hospital QM, with liaison from the IRB. RESULTS/ANTICIPATED RESULTS: The combined census on our CRCs is approximately 1800 outpatient visits and 1500 inpatient days per year. We process ~22,500 urine, 15,000 blood samples and 4300 fixed composition meals annually. Errors have been significantly reduced from 4–5 per week to 4–5 per month. DISCUSSION/SIGNIFICANCE OF IMPACT: Training in concepts originally introduced by the aviation industry has allowed staff an active role in tool design and monitoring. Unit leaders promote CRM and QM in all areas. Investigator satisfaction has increased. Crew resource and quality management are effective in reducing research errors.
P293
DATA COLLECTION PROCESS FOR A COMPREHENSIVE HUMAN SUBJECT STUDY REGISTRY AND RESEARCH PARTICIPANT WEBSITE
Turner A 1, McMurray A1, Conlon M1
1University of Florida, Gainesville, FL, USA
OBJECTIVES/SPECIFIC AIMS: In partnership with University of Florida’s (UF) four Institutional Review Boards (IRB) and UF&Shands Information Technology, the UF Clinical and Translational Science Institute (CTSI) is developing a comprehensive study registry of over 8,266 human subject research studies approved by the UF IRBs from 2008 to the present. The UF CTSI is committing resources to maintain the registry until the data collection process can be automated as part of an electronic IRB submission process. METHODS/STUDY POPULATION: Each IRB maintains its own records in its own formats. The study registry team is compiling and coding 37 standard data elements on each study. Data collection is done manually from paper IRB records. The six‐step primary data collection process will be described in depth: 1‐IRB files, 2‐Data Dictionary and Code Book, 3‐Mentoring, 4‐Data Collection, 5‐Quality Assurance, 6‐PI Review. RESULTS/ANTICIPATED RESULTS: Nine of the 37 data elements for actively enrolling studies will be publicly available on a new Website called UF StudyConnect, which can be used to search for research studies that are enrolling participants. The full Study Registry will enable the CTSI and other stakeholders to analyze aspects of UF’s human subject research portfolio such as areas of research, types of research and translational stages of research (T1‐T4). DISCUSSION/SIGNIFICANCE OF IMPACT: The CTSI study registry includes data elements that are not consistently available in other registries, which creates a fundamental new capability for UF researchers: a comprehensive registry of all human subject research at UF. UF StudyConnect expands access to information about UF’s actively enrolling research studies, which include but are not limited to clinical trials, and the full Study Registry improves the university’s ability to understand, promote and strengthen UF’s portfolio of human subject research.
P294
DEVELOPMENT OF A MULTICAMPUS, PREDOCTORAL CTSA PROGRAM: THE INDIANA‐CTSI
Story JA 1,2, Kroenke K1,3, Gabauer CL1,2
1Indiana‐CTSI, Indianapolis, IN, USA; 2Purdue University, West Lafayette, IN, USA; 3Indiana University School of Medicine, Indianapolis, IN, USA
OBJECTIVES/SPECIFIC AIMS: Indiana‐CTSI includes 4 campuses, Indiana University School of Medicine, IU Bloomington, Purdue University, and the University of Notre Dame. The predoctoral (TL1) program currently supports 22 Ph.D. students on 4 campuses and has developed a program aimed at providing insight into the meaning and process of translational research. METHODS/STUDY POPULATION: Our plan includes: (1) A course, “Tools and Techniques of Translational Science,” taught by distance on all campuses during the first year; (2) Program leaders meet with the students and their primary mentors to explain the goals of the program and to introduce the first and second year students; (3) Students meet in January and first year students give short presentations of their research accomplishments and plans; (4) Students present posters or oral papers to various groups including the Annual I‐CTSI Meeting, the Annual National Clinical and Translational Sciences Predoctoral Meeting and I‐CTSI events at their local campus; (5) Students meet in the spring with second year student’s mentors and presentations by these second year students. RESULTS/ANTICIPATED RESULTS: Administratively we have overcome a series of institutional fiscal and policy issues to provide a seamless program for the students. A survey of students completing the program indicated that all of them felt that participation in the program increased their understanding of the translational nature of their research and their appreciation of translational research. They also reported an improvement in their relationship with their mentor increased the likelihood that they will engage in collaborative research in the future. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest a very positive response to our efforts to integrate translational research into this complex organizational structure.
P295
IMPORTANCE OF DATA MANAGEMENT PROFESSIONALS IN ACADEMIC RESEARCH SETTINGS
King EC 1, Akers R1, Ittenbach R1, Macaluso M1
1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
OBJECTIVES/SPECIFIC AIMS: To develop a comprehensive Data Management Center (DMC) premised upon Good Clinical Data Management Practices applicable to academic research settings, with policies and practices that are aligned with the Center for Clinical and Translational Science and Training. METHODS/STUDY POPULATION: To determine institutional needs, we funded a formal evaluation of capabilities by industry leader in data management (DM); identified infrastructure needs and placed RFP for clinical data management system (CDMS); focused recruitment on DM professionals with significant experience in industry and related academic settings; identified standard operating procedures (SOPs) required; identified training needs for all researchers at CCHMC; and financially supported DM professional society membership and preparation for Certified Clinical Data Management (CCDM) exam. RESULTS/ANTICIPATED RESULTS: Since the completion of the assessment, we have hosted seminars by external leaders in DM; developed position descriptions and career paths for professional data managers; expanded DMC from 4 individuals to 11 individuals including 6 with industry experience and two members with CCDM certification; currently evaluating 21CFR Part 11 compliant CDMS; providing evaluation of REDCap data bases to assure structure is optimized; developing online training course in good DM practices for all researchers; finalizing DM SOPs; and assumed DM leadership for multisite clinical trials and disease specific patient registries. DISCUSSION/SIGNIFICANCE OF IMPACT: The DMC has become a resource to all researchers for information on DM standards and best practices. Initial evaluations of DMC activities indicate that the operational model of the DMC is effective and can close the gap in data quality that often exists between academic research programs and industry‐based research.
P296
MENTORING JUNIOR FACULTY ACROSS THE CTSA INSTITUTIONS
Abedin Z 1, Tillman R1, Jang S1, Richards B1, Pincus HA1
1Columbia University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Mentoring junior faculty is a key element in developing the skills and competencies for independent research, increased job and career satisfaction, retention, and productivity. To facilitate the gathering of evidence on effective mentoring practices, Columbia University’s Irving Institute for Clinical and Translational Research surveyed the current CTSA institutions on the programmatic elements of their mentoring practices. In the context of this broader survey, we compare actual reported features of mentoring programs with the perceived importance of these features. METHODS/STUDY POPULATION: Using a framework developed by Keyser et al. (2008), survey items focused in parallel on features of mentoring at the KL2 and institutional levels. Two additional items solicited perceptions about the relative importance of program features and mentor characteristics. We administered the survey to all 55 CTSAs in November 2011. We rank ordered program features both according to their frequency of inclusion in mentoring programs and their perceived importance and organized them into the three domains of the Keyser framework: strategies to enhance qualifications of mentors, to enhance motivation of mentors, and to enhance the mentee‐mentor relationship. RESULTS/ANTICIPATED RESULTS: Rankings according to frequency of program features versus perceptions of the relative importance of those features reveal similar rankings across the three domains in the Keyser framework. At least one feature in each domain received a high rank suggesting the importance of all three domains. Qualifications to enhance mentoring received the highest ranking for both frequency of use and perceived importance. DISCUSSION/SIGNIFICANCE OF IMPACT: We found that features of mentoring programs are not equally included or perceived to be of equal importance. Programs might consider including strategies from each of the three domains in the conceptual framework.
P297
NAVIGATING TRANSLATION AND RESEARCH AS ESSENTIAL AND INDEPENDENT MODELS OF MEDICAL PROGRESS
Gingles B 1, Arndt G2, Stossel TP3
1Cook Medical, Inc., Bloomington, IN, USA; 2University of Wisconsin, Madison, WA, USA; 3Harvard University, Boston, MA, USA
OBJECTIVES/SPECIFIC AIMS: (1) Identify practical distinctions between translation and research as key elements of medical progress. (2) Suggest strategies to reconcile these differences in order to enable successful translational research. METHODS/STUDY POPULATION: Translational research represents both scientific and economic incentives to accelerate medical progress. Federal research grants and academic peer‐review may be incompatible with models of patent‐dependent royalties and postmarket commercialization. Incentives to scientific enquiry and generation of knowledge are often irreconcilable with incentives to generate therapeutic outcomes. Applied science may have discounted value in peer‐review and this may impede an important component of university‐derived translational research. RESULTS/ANTICIPATED RESULTS: Translational research only yields optimal economic utility once it is unitized, monetized, taxable, exportable and recovered as a public good. Disparate models of research and translation may be impediments to productivity. DISCUSSION/SIGNIFICANCE OF IMPACT: Federal funding for translational research is an economic experiment whose future may largely depend on demonstration of tangible benefits to public health. Reconciliation of scientific and economic incentives may accelerate cures and stabilize a pool of funding for translational research in the years ahead.
P298
RESEARCH PROTOCOL NAVIGATION
Brassil D 1, Hurley A1, Dowd K1, Whalen V1, Kost R1, Coller B1
1Rockefeller University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Clinical research protocol development is complex, especially for inexperienced investigators. Structured supportive guidance through the process of protocol development can accelerate translational research. We report our 4 year experience with Research Protocol Navigation. METHODS/STUDY POPULATION: We constructed a seven‐step Research Protocol Navigation process consisting of concept initiation, concept refinement, biostatistics review, protocol drafting, expert consultation, interdisciplinary input, and protocol finalization/submission. Specific goals and core educational elements relevant to clinical investigation and GCP were defined for each stage. Content experts from biostatistics, research pharmacy, research nursing, regulatory support, etc. contributed to protocol refinement. Protocol feasibility was assessed relative to recruitment, staffing, training, facilities, and finances. A structured electronic platform, configured to support protocol writing and GCP, was used throughout Navigation. Utilization and investigator and protocol demographics were collected. RESULTS/ANTICIPATED RESULTS: Since 2008, 107 new studies (83 investigators) have undergone Navigation. In 2011, Navigation was provided for 24 new studies originating in 12 different laboratory groups, (half of which previously conducted T1 level research) involving 6 experienced investigators, 7 Clinical Scholar trainees and 11 investigators new to clinical research. Navigation was provided to support protocol amendments/renewals for previously navigated protocols (25 investigators; 32 protocols). DISCUSSION/SIGNIFICANCE OF IMPACT: Navigation provides investigators coordinated access to expert input and CTSA resources designed support rapid development of a scientifically robust, ethical and feasible protocol. Navigation support is especially relevant for trainees, new investigators and basic scientists new to clinical translational research.
P299
RESEARCHER RESILIENCE THROUGH MULTIDIMENSIONAL MENTORING
Martina CA 1, Lewis V1
1University of Rochester, Rochester, NY, USA
OBJECTIVES/SPECIFIC AIMS: Study the role of 2 forms of trainee and faculty mentoring interventions to promote resilience of underrepresented minorities in research. We use Self‐Determination Theory as a foundation to develop: (1) an educational intervention for mentors to support protégé’s autonomy, competence, and relatedness (enhanced mentoring); (2) protégé peer intervention to increase academic community ties and relatedness (peer mentoring). Aim 1: Assess enhanced mentoring interventions and protégé peer mentoring in a randomized study Aim 2: Assess academic productivity. METHODS/STUDY POPULATION: Our randomized study includes: (1) enhanced mentoring; (2) peer mentoring; (3) combination of both enhanced and peer mentoring; (4) control/delayed intervention. Participants are mentors and their protégés at 6 academic medical centers and universities, who are randomized in dyads. The enhanced mentoring intervention is an interactive workshop and individual interview one month later. The peer mentoring groups complete 2 formal workshops followed by self‐directed learning. Protégé participants are graduate students, postdoctoral fellows and early career faculty who are underrepresented by race, ethnicity, gender, disability or socioeconomic status. RESULTS/ANTICIPATED RESULTS: The primary outcome is change in protégé responses to a standardized questionnaire measuring career satisfaction and intent to remain in their field over the course of one year. The secondary outcome is documented protégé academic productivity. Focus groups and mentor interviews will describe qualitative outcomes including fostering inclusiveness and perceptions of integration into academic culture. To date, we have recruited 105 of 152 planned dyads and will present data from the first 36 dyads. DISCUSSION/SIGNIFICANCE OF IMPACT: Results will identify evidence‐based mentoring models to improve retention and advancement of minorities and women in biomedical research.
P300
THE ROCKEFELLER UNIVERSITY CTSA GRADUATE TRACKING SYSTEM SURVEY
Romanick M 1, Lee G1, Ng K1, Coller B1
1Rockefeller University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: The CTSA educational programs are crucial components of the CTSA program. It is essential to track the careers and accomplishments of the graduates to assess and improve these programs. The major obstacle to tracking graduates is a lack of a data‐gathering methodology that can collect comprehensive and standardized information to assess individual graduates’ accomplishments and make it possible to aggregate the data within and across institutions. The Graduate Tracking System Survey (GTSS), a Web‐based electronic questionnaire prepopulates the graduate’s information on publications, clinical trials, grants, and patents by downloading the information in standardized format from public databases, which simplifies completion for graduates, insures a uniform format of important information, and facilitates aggregation of data. METHODS/STUDY POPULATION: The GTSS obtains information on whether trainees go on to improve human health, as well as related surrogate indicators of career development, and it is applicable to all training programs involving translational scientists. The Initial and Annual Survey are supported by a Web‐based system created by the Rockefeller University CTSA using open source technologies. When a graduate enters the Web‐based survey, she or he finds prepopulated fields for publications, grants, patents), and participation in clinical protocols, and need only confirm that the information from these sources is correct instead of entering the data manually. RESULTS/ANTICIPATED RESULTS: None DISCUSSION/SIGNIFICANCE OF IMPACT: If adopted broadly, the GTSS has the potential for aggregating standardized CTSA‐wide data training for reporting to NIH and the public, providing benchmarks for assessing the success of individual training programs, and identifying opportunities to improve training programs.
P301
VASOPRESSOR CHOICE IN PRONE SPINE SURGERY: AN EXAMINATION OF INTRAOPERATIVE BLOOD PRESSURE CONTROL IN THE ELDERLY. A RETROSPECTIVE STUDY
Nair SR 1, Boone LR1, Abramowicz AE1
1Albert Einstein College of Medicine Montefiore Medical Center Department of Anesthesiology, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: In this retrospective study we will compare the efficacy and safety of phenylephrine with that of vasopressin in treating intraoperative hypotension (IH) in geriatric patients undergoing spinal fusion surgery in the prone position. Aims: (1) Compare the duration of hypotension after treatment with either vasopressin or phenylephrine. (2) Find the one‐week incidence of postoperative ischemic complications, delirium or post operative cognitive dysfunction, and 30 day mortality. METHODS/STUDY POPULATION: The charts of patients who had posterior spinal fusion surgeries at Montefiore Medical Center from January 2009 through November 2011 will be reviewed. Emergency surgeries and patients with a diagnosis of hypotension will be excluded. Demographics, intraoperative blood pressure management, past and current medications, other comorbid conditions, lab results, and other interventions will be recorded. Univariate analysis will be conducted to compare the two groups. All patients will be matched by propensity score. The treatment effect will be analyzed using either a paired sample t‐test or by Wilcoxon rank‐sum test. Complication rates will be analyzed using McNemar’s test. An odds ratio for postoperative complications will be created with a conditional logistic regression. RESULTS/ANTICIPATED RESULTS: We anticipate a significant difference in the duration of hypotension in the two treatment options and also in the long‐term consequences of this hypotension. DISCUSSION/SIGNIFICANCE OF IMPACT: Proper management of IH is very important in long‐term patient outcomes. Different pharmacological interventions and effects of vasopressors on anesthetic agents may have unexplored consequences. One of the limitations of the study may be underreporting of adverse events.
CLINICAL EPIDEMIOLOGY
P302
COMMUNITY‐ACADEMIC PARTNERSHIP FOR A CA‐MRSA SURVEILLANCE SYSTEM IN COMMUNITY HEALTH CENTERS: EARLY RESULTS
Tobin JN 2, Kost RG1, Balachandra S2, Chinea C2, Khalida C2, Rumala BB1, Pastagia M1, Evering T1, Holt P1, de Lencastre HM1, Tomasz A1, Pardos M1, Coller BS1
1Rockefeller University, New York, NY, USA; 2Clinical Directors Network, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Methicillin‐resistant Staphylococcus aureus (MRSA) infection among persons without recent exposure to a hospital/healthcare facility defines community‐acquired MRSA (CA‐MRSA). This project builds a research/learning collaborative among 6 NYC‐area Community Health Centers (CHCs), Clinical Directors Network and Rockefeller University Center for Clinical and Translational Science. METHODS/STUDY POPULATION: Six CHCs adjacent to a NYC Hospital MRSA Surveillance Network are collaborating to prospectively: (1) enroll patients with suspected CA‐MRSA skin and soft tissue infections; (2) integrate research and data collection into CHCs while minimizing disruption to clinical services; (3) collect demographic, clinical history, physical exam, photo and quality of life data; (4) develop procedures for clinical wound and nasal samples collection, preparation and transport to a clinical lab for microbiologic culture/antibiotic sensitivity and to a research lab for whole genome analysis/identification of genetic determinants of antimicrobial resistance. RESULTS/ANTICIPATED RESULTS: All community‐based clinicians and lab partners are actively engaged through team meetings and CME activities. At month 2, 67% of CHCs are recruiting, 31 patients have been screened, 20 have been consented and enrolled. All (n = 20) wounds (40% MRSA+) and nasal specimens (15% MRSA+) have been cultured and tested for antibiotic sensitivity. DISCUSSION/SIGNIFICANCE OF IMPACT: This community‐academic partnership is developing methods for clinical, microbiologic, and molecular evaluation of CA‐MRSA, serves as a model for academic community collaborations, and will enable future comparative effectiveness research studies in CHCs.
P303
OBESITY'S EFFECT ON JOINT REPLACEMENT: A RETROSPECTIVE REVIEW OF EARLY POSTOPERATIVE COMPLICATIONS
Lee W 1, Boone L1, Widyn J1, Nair S1, Delphin E1
1Albert Einstein College of Medicine, Montefiore Medical Center, Department of Anesthesiology, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: Study Objective: evaluation of the relationship between obesity and 30‐day postoperative adverse outcomes after total hip replacement. Specific Aims: identify patients with an adverse event within 30 days after total hip replacement. Adverse events were defined as deep vein thrombosis, pulmonary embolism, joint or surgical site infection, joint dislocation, fracture, or death. METHODS/STUDY POPULATION: Clinical Looking Glass (CLG), a hospital‐based database identified 308 patients, 4 were excluded for incomplete records, 1 for medical history which could predispose to the adverse event. Exclusion criteria were patients with major or bilateral joint replacement or revision surgery, or history of hypercoagulability. Univariate analyses were conducted for comparison of baseline characteristics. Odds ratio were calculated for each stratified BMI group and also calculated as obese versus nonobese. RESULTS/ANTICIPATED RESULTS: Twelve of the remaining 303 patients had a complication of interest without prior history. After stratification by BMI, prevalence of adverse outcomes was reviewed.The 159 patients with nonobese BMI had 8 adverse events, compared with 4 for the 144 obese patients. When grouped as normal and underweight versus obese, there was a nonsignificant increase in the risk an adverse event for a nonobese patient (OR 3.15, CI 0.99–10.10). DISCUSSION/SIGNIFICANCE OF IMPACT: From our data we observe that obesity confers no effect on 30‐day complication rates. One of the limitations of the study is that the subjects were identified indirectly, via ICD‐9 codes using CLG software. There is a minimal possibility for selection bias. While there are multiple studies that link obesity to long term complication rates, a direct relationship between surgical outcomes and obesity requires clarification.
P304
OUTCOMES FOLLOWING DIRECT DEFIBRILLATION DURING CARDIAC SURGERY: A RETROSPECTIVE STUDY
Snyder M 1, Leff J1
1Albert Einstein College of Medicine, Montefiore Medical Center Department of Anesthesiology, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: Determine if a difference in postoperative morbidity and mortality exists between patients receiving defibrillation during cardiac surgery and those not defibrillated. Aims:Mortality rate within 30‐days following surgery. Morbidity (i.e., heart failure and development of arrhythmias) rates within 30‐days. Examination of intergroup differences in length of stay, number of readmissions, and need for redo surgery. METHODS/STUDY POPULATION: A hospital database was examined to identify all on‐pump cardiac surgery patients from 2008–2011. Thirty‐day morbidity and mortality rates were identified from medical charts and compared between patients who required direct defibrillation and those who were not defibrillated. Demographic data, comorbidities, time to extubation, length of stay, number of readmissions, and need for redo surgery was collected. Patients with a history of arrhythmias or prior defibrillation were excluded. A logistic regression model was built to predict mortality and morbidity, adjusting for confounders. RESULTS/ANTICIPATED RESULTS: We anticipate finding a significant difference in morbidity/mortality between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Ventricular tachyarrythmias requiring direct defibrillation upon withdrawal of cardiopulmonary bypass during cardiac surgery are common. The MADIT‐II trial showed that patients who received at least 1 successful shock by an implantable cardioverter‐defibrillator (ICD) were at increased risk for subsequent heart failure and non–sudden cardiac death. ICDs are similar to intraoperative defibrillation in that low‐energy intrathoracic shocks are used. Since a correlation was found between ICD discharge and increased morbidity/mortality, we expect similar outcomes. If a correlation exists, future studies may focus on methods to decrease the occurrence of tachyarrythmias while coming off bypass.
P305
RACIAL DIFFERENCES IN OBESITY RISK KNOWLEDGE AMONG LOW INCOME REPRODUCTIVE‐AGE WOMEN
Justiss A 1, Rahman M1, Berenson A1
1UTMB, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: Although racial disparities in obesity prevalence in adult women exist, studies with regard to racial difference in obesity risk knowledge have not been reported yet. METHODS/STUDY POPULATION: We conducted this study based on cross‐sectional data gathered from 1,377 females (16–40 years old) attending three clinics in Texas between July 2010 and Jan. 2011. Demographics, obesity risk knowledge (ORK), and other information were assessed in the self administered questionnaire. We used ORK‐10 scale (10 questions; one point for each correct response and zero for incorrect or “do not know” responses) to measure ORK. Logistic regression model was used to examine the association between race/ethnicity and ORK score (#5 low vs. >5 high). RESULTS/ANTICIPATED RESULTS: In total, 1,153 women completed the ORK‐10 questions, including 310 Whites, 491 Blacks, 335 Hispanics, and 17 others. Possible score ranged from 0–10, with mean score of 5.89, 5.29, and 5.31 for whites, blacks, and Hispanics respectively. Multivariate logistic regression analysis showed that blacks (adjusted odds ratio [AOR] = 0.605; 95% confidence interval [CI], 0.437–0.836, p < 0.002), and Hispanics (AOR = 0.691; 95% CI, 0.479–0.997, p < 0.048) were more likely to have higher (>5) ORK score than whites even after adjusting for confounders. Women who had some college level education (AOR = 1.513; 95% CI, 1.002–2.287, p < 0.049), consumed more than one alcoholic beverage in a typical day (AOR = 1.666; 95% CI, 1.273–2.182, p < 0.001) and used the internet during the past 30 days (AOR = 1.511; 95% CI, 1.088–2.099, p < 0.014) were also more likely to have higher ORK scores. Body mass index status was not associated with ORK score. DISCUSSION/SIGNIFICANCE OF IMPACT: Differences in obesity knowledge score may help explain racial differences in obesity prevalence among women. The findings of this study could help formulate obesity awareness and prevention strategies in the United States.
P306
THE IMPACT OF GLYCEMIC STATUS IN A CANCER ENVIRONMENT
Hammer MJ 1, Melkus GD1
1New York University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Abnormal glycemic status, termed malglycemia, is a risk for adverse outcomes among patients with cancer. Risks for malglycemic states include older age, high body mass index, nutritional imbalances, low physical activity, stress, various medications, and infections. Reciprocally, malglycemia puts patients at risk for infections and related complications including nonmalignancy related death. The underlying physiology of malglycemia’s contribution to adverse events in a cancer environment has not been readily detailed. Evidence based practice for optimizing healthy glycemic levels is lacking. This study aims to evaluate glycemic status, inflammatory cytokine expression, and infection rates in patients with hematological malignancies receiving autologous hematopoietic cell transplantation (HCT). This preliminary phase describes blood glucose (BG) trends and white blood cell (WBC) counts, as an indicator of immune function. METHODS/STUDY POPULATION: Glycemic levels and WBCs from daily laboratory tests were evaluated among adult (ages 18+) autologous HCT recipients. Descriptive statistics and the Pearson’s correlation were used to assess trends and associations between BG and WBCs from 5 days prior to transplant through 14 days post transplant. RESULTS/ANTICIPATED RESULTS: BG and WBC levels fluctuate over time during the HCT process. An inverse association between BG levels and WBCs (p < 0.001) was shown in this early phase evaluation. DISCUSSION/SIGNIFICANCE OF IMPACT: In this preliminary phase of a larger study, the hyperglycemic component of malglycemia was associated with reduced WBCs in autologous HCT recipients. This early finding reinforces the underlying physiological processes of how glycemic status influences immune function in cancer. Ultimately, better glycemic control may decrease the risk for adverse outcomes, including non‐malignancy related death, among individuals diagnosed with cancer.
P307
THE TEXAS CKD STUDY—A PROSPECTIVE RANDOM SCREENING OF GENERAL POPULATION FOR CHRONIC KIDNEY DISEASE
Prabhakar S 1, Orozco R1, Moeller J1
1Texas Tech University Health Sciences Center, Lubbock, TX, USA
OBJECTIVES/SPECIFIC AIMS: Recent reports indicated that the prevalence of CKD may be as high as 16% in general population in the US (NHANES 2006). However, such reports are based on retrospective sampling and the true prevalence of CKD remains unclear. The Texas CKD study is an initiative funded by the Texas Department of Health to address the same. METHODS/STUDY POPULATION: The study was organized by Texas Tech University and conducted in the West Texas population with a goal to screen a total of 2,000 adult subjects (age > 21 yrs). The subjects were recruited by a random digit dialing (RDD) methodology. Appropriate approvals were obtained to comply with IRB and HIPAA regulations. Risk factors for CKD were noted by personal questionnaire while GFR was estimated using both MDRD and CKD‐EP1 formulae from serum creatinine values. Urine microalbumin and urine prot/creat ratio were also determined. CKD was defined using KDOQI guidelines. Individual results were discussed with the subjects to be relayed to their primary physicians for follow‐up as needed. RESULTS/ANTICIPATED RESULTS: Of a total 1,607 subjects screened, 1,579 completed the evaluation. Using the K‐DOQI guidelines and MDRD formula 269 had CKD giving a prevalence of 17.1%. Of them, 147 (55%) had stage 3 or worse CKD. Only 12.2% with CKD were aware that they had CKD. Hypertension was present in 564 subjects (35%), diabetes in 268 (17%) and smoking in 20%. Furthermore 1,277 (80%) were overweight (BMI > 25 Kg/m2) with about 50% being clearly obese (BMI > 30 Kg/m2). Using the CKD‐EPI formula the CKD prevalence was slightly lower (155 or 15.2%). DISCUSSION/SIGNIFICANCE OF IMPACT: CKD is very common in West Texas with a prevalence of 17.1% with a high presence of risk factors for CKD especially obesity. Awareness of the condition is dismally low underscoring the need for widespread screening and prevention by addressing the risk factors.
CLINICAL TRIAL
P308
CARDIOHEMODYNAMIC CHANGES IN PATIENTS WITH REFRACTORY HYPERTENSION
Dudenbostel T 1, Acelajado M1, Oparil S1, Calhoun DA1
1University of Alabama, Birmingham, AL, USA
OBJECTIVES/SPECIFIC AIMS: Within the population of resistant hypertension (RHTN), some patients remain uncontrolled despite optimal medical therapy. This so‐called refractory hypertension (RefHTN) may have different underlying mechanisms. This study prospectively compares arterial compliance and cardiohemodynamic parameters between both groups. METHODS/STUDY POPULATION: Refractory patients were identified in a referral hypertension clinic using the following criteria: uncontrolled BP on ≥3 antihypertensive agents including a diuretic and mineralocorticoid receptor antagonist after ≥3 visits from 2009 to present. These refractory patients along with matched RHTN patients underwent 24 hr ambulatory blood pressure monitoring (ABPM), pulse wave analysis (PWA), aortic pulse pressure (APP), pulse wave velocity (PWV), flow‐mediated dilation (FMD) and echocardiography. RESULTS/ANTICIPATED RESULTS: Baseline characteristics were similar between both groups. ABPM confirmed a significant difference between both SBP and DBP in both groups (SBP (mm Hg): 141 ± 17.8 versus 171 ± 21.6, p < 0.001; DBP (mm Hg): 72.1 ± 9.2 versus 95 ± 13.8, p < 0.001, MAP (mm Hg): 97 ± 13.1 versus 121 ± 15.5, p < 0.001). Average heart rate (HR) 69 ± 7.4 versus 77.8 ± 7.6 (p = 0.03), PWV 9.5 ± 1.9 versus 11.7 ± 2.67 m/s (p = 0.03), AIx75 (%) 17.8 ± 12.1 versus 27.5 ± 10.5 A P (mm Hg) 11.3 ± 10.7 versus 18.3 ± 13.5 (p = 0.041), APP (mmHg) 40.7 ± 15.7 versus 61 ± 27.9 (p < 0.001). FMD 6.6% versus 9.4%. Echocardiography showed left ventricular hypertrophy in both groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Patients with RefHTN showed increased arterial stiffness, higher central BP, left ventricular hypertrophy and decreased FMD compared to patients with controlled RHTN. Although underlying mechanisms contributing to RefHTN seem to differ from RHTN and need to be elucidated, this study provides new insights into changes of arterial stiffness and endothelial function in refractory patients.
ETHICS
P309
INFORMATIONAL RISKS: IS IT THE NEW BAD BLOOD?
McKinney E” 1
1University of Texas Medical Branch, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: The specific aims of this analysis are to assess the meanings and implications of the term informational risks as used in the Advance Notice of Proposed Rule Making for the Common Rule. METHODS/STUDY POPULATION: Legal, ethical, and medical humanities methods are used to examine the question of whether the term information risks fulfills and important need or obfuscated and confuses. RESULTS/ANTICIPATED RESULTS: This exploration will show that use of the term holds potential for misleading or confusing investigators and human subjects alike and may contribute to failure to adequately inform human subjects of the foreseeable risks they face by participating in studies in the age of whole genome research. DISCUSSION/SIGNIFICANCE OF IMPACT: In the infamous Tuskegee Study, scientists used the term “bad blood” to mean syphilis, while the uneducated and vulnerable human subjects understood the term to mean something closer to malaise. When the abuses of the study came to light, the use of the term cam to be seen as part of a pattern of deceit and to signify the distrust felt toward the scientific community by large segments of the population. The scientific community must beware of using terms that have special meaning for some and not others to avoid misunderstandings. Any use of a term that may be perceived as obscuring negative impacts on human subjects is likely to undermine the scientific enterprise.
P310
RESEARCH ETHICS CONSULTATION: STANDARDIZATION AND DATA SHARING
Wilfond B 1, Taylor H2, Cho M3
1University of Washington, Seattle, WA, USA; 2Johns Hopkins University, Baltimore, MD, USA; 3Stanford University, Stanford, CA, USA
OBJECTIVES/SPECIFIC AIMS: Thirty‐three CTSA institutions have established research ethics consultation services.The Clinical Research Ethics KFC created a working group whose objective is to advance the goal of creating a system for CTSAs to share consultation data across institutions. METHODS/STUDY POPULATION: The working group identified (1) minimal data elements consult services should collect, (2) operating policies to facilitate communication with consult requestors about data sharing; (3) legal and policy barriers to data sharing; and (4) informatics strategies for data sharing. RESULTS/ANTICIPATED RESULTS: A repository was created using REDCAP that includes descriptive data about the (1) research project (research activities, project stage, translational research phase); (2) consult issues (specific research categories that have distinct ethical issues and the specific ethical concerns); (3) consult process (amount of interaction and specific additional services provided). The repository also includes a narrative description of the reason for the consult. Eleven institutions began entering data in Jan 2012 for one year as a demonstration project. All consultants at these institutions have access to the repository to identify specific consults for which they can contact the consultant who submitted the consult to learn more about the details. A CTSA consultation Web forum was created to discuss ongoing cases and issues for advice. There are 50 Web forum users. DISCUSSION/SIGNIFICANCE OF IMPACT: The demonstration project will allow an assessment of these approaches for facilitating CTSA ethics consultants soliciting input about ongoing consults and share novel solutions,identifying recurring issues that warrant further examination, and can lead to CTSA‐wide empirical research efforts, and can aid in the development educational materials.
P311
TEACHING THE RESPONSIBLE CONDUCT OF RESEARCH AT THE UNIVERSITY OF PITTSBURGH
Schenker Y 1, Yonas M1, Callan J2, Empey PE3, Wang W1, Peck‐Palmer OM1, Rubio DM1
1University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 2University of Pittsburgh School of Nursing, Pittsburgh, PA, USA; 3University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: The University of Pittsburgh Clinical Research Scholars Program (CRSP) aims to provide instruction in the Responsible Conduct of Research (RCR) for its KL2 Scholars during the course of their training. METHODS/STUDY POPULATION: The CRSP supports 20 KL2 Scholars for up to five years. During the course of their career development award, the program provides training in RCR through biweekly meetings with the scholars and the multidisciplinary advisory committee. During these meetings, two Scholars report on their research and career progress. In addition, university experts present on specific issues in RCR, as recommended by the National Institutes of Health. Training is longitudinal; each session either builds on the previous topic or introduces a new one. The experts briefly introduce the topic for discussion, and the Scholars engage in the ensuing discussion. In addition, scholars are required to take a course in the ethics of clinical research. RESULTS/ANTICIPATED RESULTS: During the course of their training, we anticipate that Scholars will be well trained in the RCR. By being introduced to the material through group discussion with experts, the Scholars are able to obtain a clear understanding of the information. DISCUSSION/SIGNIFICANCE OF IMPACT: RCR training is critical for Scholars who are embarking on careers in Clinical and Translational Science. By providing this training early in their careers, we are expecting that they will be better, more responsible researchers.
P312
THE RESTORING PROFESSIONALISM AND INTEGRITY IN RESEARCH (REPAIR) PROGRAM
DuBois JM 1,2
1Saint Louis University, St. Louis, MO, USA; 2Washington University School of Medicine, St. Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: (1) Determine the need for a remediation training program for investigators who have committed violations of research integrity. (2) Develop evidence‐based training materials that promote thinking patterns, decision making skills, and work habits that support ethical research. METHODS/STUDY POPULATION: (1) Survey research integrity officers and institutional review board chairs at US schools of medicine and comprehensive doctoral institutions (n = 195) to assess the frequency and kinds of wrongdoing investigated by the institution, current ways of responding to wrongdoing, and interest in a remediation training program. (2) A team of ethicists and developmental, cognitive, and industrial‐organizational psychologists is developing evidence‐based materials for use in onsite group training sessions on Research Integrity and Human Subject Protections. CITI will host complementary online training modules tailored to individuals’ needs. RESULTS/ANTICIPATED RESULTS: (1) Preliminary data (n = 58) indicate a need for RePAIR. Institutions report an average of 6 research integrity violations over the past 2 years; 11% report 11 or more violations. (2) Course materials will be complete by December 2012; onsite training sessions will begin in January 2013. Materials will not be available outside of the onsite training program because they are designed for group training of individuals who have committed serious violations of research ethics by trained facilitators. DISCUSSION/SIGNIFICANCE OF IMPACT: With funding from an administrative supplement award to the Washington University CTSA (3UL1RR024992‐05S2), RePAIR will be the first training program that will draw heavily from psychological data to provide remediation training to researchers. Extensive pre‐ and posttraining assessment data will be gathered to determine participant needs and program efficacy.
P313
THE UTILITY OF METHOD INTUITION IN TRANSLATIONAL ETHICS
Crowder JW 1, Farroni JS2, Bhavnani SK2, McKinney E1,2, Carter MA1,2
1Institute for the Medical Humanities, Univeristy of Texas Medical Branch at Galveston, Galveston, TX, USA; 2Institute for Translational Sciences, Univeristy of Texas Medical Branch at Galveston, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: Team‐based, collaborative research presents challenges to developing common goals and shared values. Research aims and capacity for trust‐building may be compromised if conflicts arise during the conduct of science. Often, conflicts arise due to miscommunication between team members stemming from the use of jargon and disparate methodological assumptions. New techniques are needed to address these problems. METHODS/STUDY POPULATION: We developed an approach called Method Intuition (MInt) to assist translational researchers understand the goals, procedures, limitations, and research issues related to the methods they use. RESULTS/ANTICIPATED RESULTS: Preliminary results show that the approach leads to unexpected research insights due to the increased transparency and comprehension of discipline‐specific methods. For example, new insights emerged when a member of a multidisciplinary team presented his social science methods to a group of primarily biomedical researchers. These insights resulted in novel strategies for increasing study enrollment and greater subject retention. DISCUSSION/SIGNIFICANCE OF IMPACT: The practical implications are that the study would be completed in a shorter amount of time. Such insights would have been nearly impossible had this technique not been employed. Beyond the practical applications of this process, we believe this is an effective instrument for a broader dialogical approach to translational ethics that builds stronger bonds within the translational team. This is an important mechanism for relationship development and encourages the multidisciplinary team to coalesce around common values, goals and outcomes thus yielding both better scientific output and enhanced opportunities to improve health impact.
P314
TRAINING K SCHOLARS TO BE FUTURE RCR MENTORS
Anderson L 1, Steneck N1, Eakin B1, Mayes K1
1University of Michigan, Ann Arbor, MI, USA
OBJECTIVES/SPECIFIC AIMS: K scholars have unique needs for training in the responsible conduct of research (RCR). METHODS/STUDY POPULATION: A 4 module interactive seminar was developed that meets the NIH requirement of 8 hours of face‐to‐face RCR education. Content was based on mentoring a scholar through an RCR project related to their own research and tailored to professional circumstances of K awardees. Seminar elements were based on theory, structured to appeal to adult learners, and demonstrated relevant benefit to trainees. RESULTS/ANTICIPATED RESULTS: During the 8‐week program 23 scholars selected and carried out a small research project addressing topics such as authorship, data sharing, subject recruitment, bias, and vulnerable international populations. They followed a six step decision process and with help from five diverse mentors. They observed peers overcoming uncertainties and used factual knowledge and resources provided. At the last session scholars presented their experiences and plans to share the approach with others. DISCUSSION/SIGNIFICANCE OF IMPACT: This program impacts K scholar training by preparing them to be responsible researchers and research mentors. This mentored project approach will be compared to standard RCR education in a multi site evaluation.
P315
TRANSLATIONAL ETHICS: AN EMERGING MORAL FRAMEWORK IN CLINICAL RESEARCH PRACTICE
Carter MA 1,2, Farroni JS2
1Institute for the Medical Humanities, Univeristy of Texas Medical Branch at Galveston, Galveston, TX, USA; 2Institute for Translational Sciences, Univeristy of Texas Medical Branch at Galveston, Galveston, TX, USA
OBJECTIVES/SPECIFIC AIMS: Translational science is a collaborative venture aimed at enhancing therapeutic discovery, practical innovation, and advancements in public health. It introduces new forms of relationships, interactions, and partnerships, each of which embodies collaborative, team‐based commitments and obligations. This transformation of scientific endeavor is creating new roles and responsibilities for the ethicist which extend beyond the traditional challenges associated with human subject research. It is increasingly necessary to broaden the scope of research ethics to accommodate these dynamic changes and align them with the goals of translational science. METHODS/STUDY POPULATION: We propose a framework of translational ethics that assists ethicists, scientists, and the communities they serve to better understand the values that embody translational science and to cultivate skills of ethical sensitivity and effective deliberation. RESULTS/ANTICIPATED RESULTS: We describe a unique relationship‐based method in which translational ethicists are imbedded as collaborative partners into multidisciplinary teams of translational scientists. They function as facilitators of change, fostering shared understandings of team‐based science culture, improving research design, outcomes and impact, and providing opportunities for ethical inquiry and consultation. DISCUSSION/SIGNIFICANCE OF IMPACT: Moving away from the compliance model of research ethics and adopting a relationship‐based approach will guide the development of translational science as a virtuous practice. By aligning the normative values of scientists and ethicists, we believe this moral framework will imbue integrity and trust into the translational enterprise.
HEALTH SERVICES RESEARCH
P316
ENHANCING COMMUNITY RESEARCH ENGAGEMENT: FACTORS AND CHALLENGES ASSOCIATED WITH BUILDING COMMUNITY HEALTH CENTER RESEARCH CAPACITY
Proser M 1, Payne P2, Shin P2, Tobin JN3, Weir R4, Jester M1, Merrill C5, Young V6, Brandt H7, Campbell D7, Felder T7, Rachman F8
1National Association of Community Health Centers, Washington, DC, USA; 2George Washington University, Washington, DC, USA; 3Clinical Directors Network, New York, NY, USA; 4Association of Asian Pacific Community Health Organizations, Oakland, CA, USA; 5Children’s National Medical Center, Washington, DC, USA; 6South Carolina Primary Health Care Association, Columbia, SC, USA; 7University of South Carolina, Columbia, SC, USA; 8Alliance of Chicago Community Health Services LLC., Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Community Health Centers (CHCs) are facing more opportunities for research partnerships with mixed results. Little is known about the state of research at CHCs. METHODS/STUDY POPULATION: The Clinical and Translational Science Institute at Children’s National Medical Center, in partnership with The George Washington University, the National Association of Community Health Centers (NACHC), the Community Health Applied Research Network, and the South Carolina Primary Health Care Association developed a national baseline of CHC research participation. We surveyed over 1,000 CHCs regarding their involvement in research and their research needs. RESULTS/ANTICIPATED RESULTS: With over one‐third of respondents reporting, although more than half of CHCs (53%) participate in research, most (94%) has been undertaken in partnership with external researchers due to a lack of staff time, funding, and expertise. Although the partnerships are viewed as successful, CHCs’ roles in research relate more to participant recruitment and data collection rather than selecting, developing, shaping, or disseminating the research project. DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, CHCs are interested in participating in research but face imminent barriers to involvement. Education is needed on both sides to eliminate barriers and to develop more equitable and sustainable partnerships.
METHODOLOGY
P317
ACTIVE STAND VERSUS PASSIVE TILT IN DIAGNOSING POSTURAL TACHYCARDIA SYNDROME
Plash W 1, Diedrich A1, Biaggioni I1, Paranjape S1, Black B1, Raj S1
1Vanderbilt University School of Medicine, Nashville, TN, USA
OBJECTIVES/SPECIFIC AIMS: Postural tachycardia syndrome (POTS) is characterized by a heart rate increase (dHR) of ≥ 30 beats per min (bpm) within 10 min of upright posture with orthostatic symptoms. Some have proposed extending tilt to 30 min to diagnose “late POTS.” Active stand (STAND) and passive stand with a tilt table (TILT) cause different physiologic responses. We hypothesized the tests would produce different dHR, causing variation in achieving the POTS dHR criterion. METHODS/STUDY POPULATION: Patients with POTS (n = 15, 13F, age 37 ± 3) and healthy volunteers (n = 34, 14F, age 31 ± 1) underwent a 30 min STAND and TILT (60–75°). Max dHR were analyzed at 5 min intervals. Data (mean ± SEM) were analyzed with paired t‐tests. ROC analysis was performed to determine the optimal dHR criteria for STAND and TILT at 10 and 30 min. RESULTS/ANTICIPATED RESULTS: STAND and TILT dHR were similar at 10 min (30 ± 2 bpm vs. 32 ± 3 bpm; p = 0.21). dHR was greater with TILT than STAND at all 5 min intervals from 15 min (30 ± 2 bpm vs. 37 ± 3 bpm; p = 0.001) to 30 min (32 ± 3 bpm vs. 43 ± 3 bpm; p < 0.001). The 30 bpm criterion had similar sensitivity (Sn) and specificity (Sp) at 10 min for STAND (93% and 81%) and TILT (93% and 77%) but lower Sp at 30 min for TILT (32%) than STAND (71%). The optimal dHR threshold after 10 min TILT was 38 bpm (area under curve [AUC] = 0.92; Sn = 80% and Sp = 88%), and after 10 min stand was 33 bpm (AUC = 0.89; Sn = 80% and Sp = 82%). The optimal dHR after 30 min TILT was 47 bpm (AUC = 0.95; Sn = 87% and Sp = 91%) compared to 34 bpm (AUC = 0.92; Sn = 93% and Sp = 79%) for 30 min STAND. DISCUSSION/SIGNIFICANCE OF IMPACT: Orthostatic tachycardia was similar with STAND and TILT within 10 minutes, but TILT showed larger dHR than STAND after 30 min. STAND and TILT had similar POTS diagnostic characteristics using a 30 bpm threshold at 10 min. Specificity of the 30 bpm POTS criterion is maintained with STAND but drops significantly for TILT.
P318
APPLICATION OF FIBROMYALGIA SURVEY CRITERIA TO A FIBROMYALGIA REGISTRY
Whipple MO 1, Hawkins ES1, Cha SS1, Luedtke CA1, Oh TH1, Thompson JM1, Vincent A1
1Mayo Clinic, Rochester, MN, USA
OBJECTIVES/SPECIFIC AIMS: The Fibromyalgia (FM) Survey Criteria is a validated instrument that can be utilized without the presence of an examiner. We utilized this survey in an existing registry of patients with FM to evaluate the percentage meeting survey criteria and to provide descriptive characteristics of these participants. METHODS/STUDY POPULATION: The FM Survey Criteria were mailed to 10,651 patients who were part of the FM registry. The questionnaire included demographics and the FM Survey Criteria. The FM Survey Criteria is modified from the 2010 American College of Rheumatology Clinical Criteria for FM. The two subscales of the FM Survey Criteria are Widespread Pain Index (WPI) and Symptom Severely Scale (SS). WPI scores range from 0–19 and SS scores range from 0–12. Positive criteria are defined by WPI ≥7 and SS ≥5, or WPI ≥3 or #6 and SS ≥9. RESULTS/ANTICIPATED RESULTS: Of survey responders, 2,109 (84.8%) met criteria. Among those that met criteria, the mean age was 54.9 (±23.8) years, 93% were female, and the mean BMI was 29.7 (±7.3). The mean WPI was 12.4 (±3.8) and the mean SS score was 8.8 (±1.9). Moderate to severe fatigue, unrefreshing sleep, and cognitive difficulties were reported by 93%, 91%, and 66% respectively. Pain or cramps in the lower abdomen were reported by 72%, depression by 70%, and headache by 87%. DISCUSSION/SIGNIFICANCE OF IMPACT: Pain, fatigue, unrefreshing sleep, and cognitive difficulties occur frequently in patients with the syndrome complex of FM. Researchers and clinicians who evaluate FM should mindfully assess and manage these symptoms as they could be potential targets to decrease overall symptom burden.
P319
BED REST IS AN ANALOG TO STUDY THE PHYSIOLOGIC CHANGES OF SPACEFLIGHT AND TO EVALUATE COUNTERMEASURES
Pfannenstiel T 1, Ottenbacher M1, Inniss A1, Ware D1, Anderson K1, Stranges S2, Keith K3, Cromwell R4, Neigut J5, Powell D1
1UTMB, Galveston, TX, USA; 2Wyle, Houston, TX, USA; 3Lockheed Martin, Houston, TX, USA; 4USRA, Houston, TX, USA; 5NASA/JSC, Houston, TX, USA
OBJECTIVES/SPECIFIC AIMS: The UTMB/NASA Flight Analog Research Unit is equipped with a metabolic kitchen and unique testing areas for studying subjects in nonhorizontal bed rest for prolonged periods as an analog for reduced gravity. Bed rest allows the study of physiologic changes, performance of functional tasks representative of critical interplanetary mission operations, and efficacy of countermeasures designed to protect against the deleterious effects of extended stays in reduced gravity. METHODS/STUDY POPULATION: Subjects are healthy adults 24–55 yrs; 60–75 in. tall; BMI 18.5–30; and normal bone mineral density by DXA scan. Proposed exercise countermeasures combine high‐intensity interval aerobic exercises on alternating days with continuous aerobic exercise. Resistance exercise is performed 3 days per week. Subjects are tested on an integrated suite of functional and interdisciplinary physiologic tests before and after 70 days of total nonhorizontal bed rest. RESULTS/ANTICIPATED RESULTS: We anticipate that post–bed rest functional performance will be predicted by a weighted combination of sensorimotor, cardiovascular, and muscle physiologic factors. Control subjects who do not participate in the exercise countermeasure will have significantly greater decreases in these parameters. DISCUSSION/SIGNIFICANCE OF IMPACT: Astronauts experience alterations in multiple physiologic systems due to microgravity exposure, leading to disruption in the ability to perform functional tasks after reintroduction to a gravitational environment. Current flight exercise countermeasures are not fully protective of cardiovascular, muscle, and bone health. There is a need to refine and optimize countermeasures to mitigate health risks associated with long‐term space missions.
P320
COMPARISON OF MULTIVARIATE REGRESSION ANALYSIS METHODS FOR RELATIVE RISK ESTIMATION IN COHORT STUDIES AND CLINICAL TRIALS
Kyriacou DN 1, Jovanovic B1
1Northwestern University, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Regression model structural forms (log‐binomial, logistic, Poisson, and Cox) are specified for different study designs resulting in estimates (risk, odds, rate, and hazards ratios) that vary biologic interpretation. We assess relative risk estimations based on structural form specification. METHODS/STUDY POPULATION: We used a RCT comparing ED discharge methods on outpatientl clinic follow‐up compliance. We compared crude and adjusted relative risk estimations using closed and open cohort analyses. We included 3 potential confounders. We conducted MH stratified analyses to compare differences in estimates reflecting data versus structural from specification. RESULTS/ANTICIPATED RESULTS: With closed cohort analyses, univariate estimates from log‐binomial risk ratio and Poisson rate ratio provided equivalent relative risk estimates (1.605) as tabular analysis risk ratios, but the logistic odds ratio estimate was significantly greater (2.47). The log‐binomial and Poisson multivariate estimates and CIs were similar to the MH stratified analysis estimates for all the covariates, but logistic regression significantly overestimated or underestimated the covariate estimates. With open cohort analyses, the univariate Poisson rate ratio was equivalent (1.600) to the tabular analysis rate ratio, but the Cox hazard ratio estimate was slightly different (1.616). Multivariate estimates and CIs from Poisson and Cox regression were similar to the MH stratified analysis for all the covariates. Logistic regression overestimated or underestimated the covariate relative risk estimates. DISCUSSION/SIGNIFICANCE OF IMPACT: Misspecification of regression model structural form can lead to misinterpretation of causal relations. Logistic regression overestimates or underestimates true relative risks when the outcome event is common.
P321
CREATING A NEW PERSONALIZED MEDICINE METHODOLOGY: PERSON‐SPECIFIC CAUSES AND TREATMENTS
Davidson KW 1,2, Shaffer JA1, Edmondson D1, Kronish I1, Shimbo D1, Burg M1, Whang W1, Begg MD2,3, Schwartz JE1
1Columbia University Department of Medicine, New York, NY, USA; 2Columbia University Irving Institute (CTSA), New York, NY, USA; 3Columbia University Department of Biostatistics, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: A prevailing consensus holds that normative designs satisfactorily identify putative causes, provide data on treatment dose and duration, and ultimately elucidate ways to treat specific patients’ health problems. Normative designs presume that the putative causes identified for a group apply to most (if not all) persons, and that by comparing (with randomization) one group’s treatment response to another’s placebo or alternative response, we will know how the ‘average’ person responds to the treatment. We respectfully challenge this conventional assumption, at least for a subset of complex human health problems. METHODS/STUDY POPULATION: We will present person‐specific methods needed for identifying the types of treatment targets, the timing, and the dose that can uniquely operate in one patient with chronic, relapsing, remitting disease. Using nonadherence, paroxysmal atrial fibrillation episodes, and ambulatory coronary ischemia as three exemplar health problems, we will show how to decide when these new methods should be applied. RESULTS/ANTICIPATED RESULTS: We hypothesize that for certain highly prevalent, burdensome health problems, a person‐specific, or within‐subject, design will ultimately lead to more successful treatments for more patients than has been accomplished using between‐subject designs. DISCUSSION/SIGNIFICANCE OF IMPACT: Although this novel person‐specific approach is characterized by conceptual, multidisciplinary and technical risks, it could dramatically propel the field forward and shed light on why we have had difficulty effectively treating a number of chronic health problems that plague our public.
P322
DEFINING THE IMPACT OF CLINICAL RESEARCH NURSING: AN EVALUATION FRAMEWORK
Hastings C 1
1NIH Clinical Center, Bethesda, MD, USA
OBJECTIVES/SPECIFIC AIMS: This presentation reports the first steps in a formal inquiry into the benefits and anticipated outcomes of clinical research nursing practice. After a brief overview of the international work to date in documenting and describing the various roles of clinical nurses in research study implementation, a set of possible measures of study effectiveness that could be sensitive to nursing input will be proposed. Discussion of each measure will include conceptual and operational definitions, published work to date proposing or reporting the use of the indicator as a study quality criterion, rationale for the use of the indicator to assess the impact of nursing on study outcomes, and possible overall utility of the measure for general evaluation of study cost effectiveness and quality. The audience will be engaged in structured discussion to further understand the utility and possible application of proposed indicators. METHODS/STUDY POPULATION: The session will engage the audience through discussion, debate and overall consensus building. RESULTS/ANTICIPATED RESULTS: The session will assess perspectives of various interdisciplinary team members regarding how best to evaluate the impact of nurses as members of the clinical research team on key study effectiveness outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: There has been significant progress over the past several years in describing the various roles taken by nurses in support of clinical research and the potential value of their contributions. However there continues to be debate over the cost effectiveness of nurses versus other possibly less costly research support staff. This debate will likely intensify as the current fiscal climate continues to put pressure on research budgets and staffing plans. The availability of agreed upon measures of the impact of nurses on research quality and efficiency outcomes should facilitate staffing decisions when proposing and planning clinical studies.
P323
DEVELOPING HEALTH DISPARITIES RESEARCHERS THROUGH A MULTIDISCIPLINARY SUMMER IMMERSION PROGRAM
Eakin B 1, Coombe CM2, Piechowski P1, Anderson E1
1University of Michigan – MICHR, Ann Arbor, MI, USA; 2University of Michigan School of Public Health, Ann Arbor, MI, USA
OBJECTIVES/SPECIFIC AIMS: Researchers are needed to conduct health disparities research (HDR) that translates into individual, community and policy interventions. The Summer Immersion Program in Health Disparities Research engages students in HDR to inspire them to pursue a career focused on eliminating health disparities and incorporating HDR into future clinical practice. METHODS/STUDY POPULATION: Designed for graduate students from the University of Michigan and throughout the U.S., the 10‐week program includes mentored research work; weekly seminars to explore key issues in HDR and research methods; observation of an IRB meeting; site visits to 2 cities in which community‐based participatory research is conducted and theoretical research project proposals developed in small groups. RESULTS/ANTICIPATED RESULTS: Sixteen students representing public health, medicine, social work, dentistry, pharmacy and nursing participated in the program. The students were from diverse socioeconomic, ethnic, educational and geographic backgrounds. Nine presented at local or national meetings; 4 continue to work long‐distance with their mentors to summarize their research findings for publication; 11 have expressed interest in or committed to obtaining additional HDR experience. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a unique program focused specifically on immersing predoctoral graduate students in health disparities research. Participants valued the practical experience, mentoring and small group discussion with experts and peers in a multidisciplinary program.
P324
HARMONIZATION OF THE HSDB ADMINISTRATIVE DATA ELEMENTS WITH THE BRIDG MODEL
Chakraborty S 1, Sandberg S4, Carini S2, Tu SW3, Sim I2, Nahm M1
1Duke University, Durham, NC, USA; 2UCSF, San Fransisco, CA, USA; 3Stanford University, Stanford, CA, USA; 4ScenPro Inc., Richardson, TX, USA
OBJECTIVES/SPECIFIC AIMS: The objective is to harmonize the list of common administrative data elements of Human Studies Database (HSDB), synthesized from various Institutional Review Board (IRB) and Clinical Trial Management Systems (CTMS) with Biomedical Research Integrated Domain Group (BRIDG) Model. METHODS/STUDY POPULATION: HSDB administrative subgroup collaboratively produced a list of common administrative data elements through vetting process and gap analysis amongst five CTSA organizations and also with Clinical Trials Reporting Program (CTRP), as the central database for the National Cancer Institute (NCI). It was also vetted with larger HSDB group and harmonized with the Ontology of Clinical Research (OCRe) upon which HSDB is founded. On harmonization request to BRIDG Semantic Coordination Committee(SCC), BRIDG Board of Directors assigned a point of contact to help with the mapping process beyond the SCC session held in June 2011. RESULTS/ANTICIPATED RESULTS: The harmonization process led to changes in both OCRe and BRIDG for optimum reusability and overlap between approx. 145 data elements and BRIDG release 3.0.3 resulting in over 90% mapping. The new release of BRIDG model 3.1 in February 2012 will show the HSDB OCRe data elements mappings as a separate tag similar to ClinicalTrials.gov and SDTM. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first step to make HSDB OCRe publicly available through BRIDG model enabling institutions to systematically characterize and identify HSDB data elements in the research workflow and promote interoperability across research institutions and vendor community like the CTMS and IRB. We expect to continue both innovation and implementations work with the researchers, subject matter experts, ontologist, and information technologist.
P325
LEVERAGING LONGITUDINAL ELECTRONIC HEALTH RECORD DATA TO RECLASSIFY CHRONIC DISEASES
Wixted D 1, Nahm ML1, Smerek M1, Walden A1, Chakraborty S1, Waters A1, Dunham A1, Tenenbaum J1, Dolor R1, Newby L1, Califf RM1
1Duke University, Durham, NC, USA
OBJECTIVES/SPECIFIC AIMS: Import longitudinal electronic health record (EHR) data for participants in the MURDOCK Community Registry and Biorepository, and reconcile these data with subject‐reported information. METHODS/STUDY POPULATION: The MURDOCK Study (Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis) is a multitiered epidemiology study. The registry and biorepository is a key component comprising clinical and demographic information and biospecimens for ‐omics analysis from 50,000 participants. Longitudinal clinical data are obtained by annual questionnaire and, through consent and partnership with local medical providers, from participants’ EHRs. Approximately 85% of the catchment area population is covered by three major providers using different enterprise EHR systems. A preidentified set of system‐specific data elements will be requested from each provider in compliance with the institution’s patient information protection policies. Efforts will be made to obtain EHR data through the NC Health Information Exchange (HIE) for participating providers. Data will be imported into a protected staging environment for quality assurance and reconciliation prior to integration into the MURDOCK Integrated Data Repository. RESULTS/ANTICIPATED RESULTS: A pilot effort to integrate EHR data for a subset of participants is underway and will inform subsequent transfers. Clinical data retrieved from EHRs will be compared with corresponding patient‐reported data. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased adoption of certified EHR technology resulting from HITECH legislation presents an unprecedented opportunity for research. The MURDOCK Study seeks to overcome widely recognized technical challenges and privacy considerations to open doors for innovative epidemiological methods.
P326
RANKING DIAGNOSTIC POWER OF BIOMARKERS USING A MODEL‐BASED ROC APPROACH
Ma S 1
1Yale University, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: In cancer genomic studies, a common task is to rank the diagnostic power of biomarkers. Here a biomarker can be a gene, SNP, mutation, a composite marker representing a pathway, or an interaction term between a gene and an environmental risk factor. Most existing studies adopt a (semi)parametric model based approach, which assumes a (semi)parametric model (e.g., logistic regression model for categorical outcome/phenotype, Cox proportional hazards model for survival outcome) and uses the estimated odds ratio (hazard ratio) or its significance level as the ranking statistic. METHODS/STUDY POPULATION: In a recent study, we show that biomarkers with estimation significance not necessarily have diagnostic power and vice versa. To directly target the diagnostic performance, we propose using the ROC (receiver operating characteristic) based measures, including AUC for categorical outcome and time‐integrated AUC for survival outcome, as ranking statistics. Multiple model‐based methods are developed for constructing the underlying regression models and composite diagnostic markers when confounders are present along with biomarkers. A resampling approach is proposed to obtain unbiased estimates of AUCs. RESULTS/ANTICIPATED RESULTS: Simulations and analysis of lymphoma and breast cancer studies show that the proposed methods can better identify biomarkers with diagnostic power, and the identified biomarkers differ significantly from those using existing approaches. DISCUSSION/SIGNIFICANCE OF IMPACT: Targeting directly the diagnostic power may lead to the identification of new cancer biomarkers.
P327
SIMULTANEOUS CORRECTIONS OF RESPIRATORY AND CARDIAC MOTION FOR A DEDICATED CARDIAC SPECT SYSTEM
Liu C 1, Chan C1, Volokh L2, Harris M3, Le M3, Biondi J3, Sinusas A1
1Yale University, New Haven, CT, USA; 2GE Healthcare, Haifa, Israel; 3Ivy Biomedical Systems, Branford, CT, USA
OBJECTIVES/SPECIFIC AIMS: Respiratory and cardiac motions can degrade myocardial perfusion SPECT image quality and quantitative accuracy. In this study, we developed methods to simultaneously correct respiratory and cardiac motions for a stationary cardiac SPECT. METHODS/STUDY POPULATION: Respiratory motion was monitored by a compressive sensor pillow that is connected to a dual respiratory‐cardiac gating box (Ivy Biomedical Systems), which sends cardiac triggers to GE Discovery 530c/570c systems only during end‐expiration phases. The respiratory trace acquired on the dual gating box was validated against an Anzai system. The phantom listmode data was binned into end‐expiration frames, and patient data were binned into 8 cardiac gates only during end‐expiration phases to correct for both respiratory and cardiac motions. A nonrigid registration method (Morphing, GE Healthcare) was used to register all dual‐gated images to a reference gate to reduce noise while retaining motion reduction. Image quality improvement was evaluated using a torso phantom driven by a motion platform and patient data in terms of myocardium‐to‐blood pool contrast and visual perception. RESULTS/ANTICIPATED RESULTS: The traces acquired using the sensor pillow matched well with the Anzai system. In phantom study, end‐expiration gating increased myocardium‐to‐blood pool contrast from 2.3 in the ungated image to 6.2, which is close to 6.6 in the motion‐free image. Additional cardiac gating in patient study further reduced motion blurring effect at the expense of increased noise. The Morphing approach improved tradeoff between motion correction and noise increase. DISCUSSION/SIGNIFICANCE OF IMPACT: The proposed methods can effectively reduce respiratory and cardiac motion effects and may lead to more accurate defect detection and quantification.
OUTCOMES RESEARCH
P328
CORONARY LEVELS OF ANGIOTENSIN II AND ENDOTHELIN I IN DIABETIC PATIENTS WITH CORONARY ARTERY DISEASE
Altieri PI 1,2, Marcial J1, Banchs HL1,2, Escobales N1, Crespo M1
1University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico; 2Cardiovascular Center of Puerto Rico and the Caribbean, San Juan, Puerto Rico
OBJECTIVES/SPECIFIC AIMS: The causes of angiopathy in diabetics are relatively unknown. The involvement of angiotensin II (Ang II) and endothelin I (El) in the development of coronary atherosclerosis suggests that these hormones could play an important role in the etiology of this condition. The objective is to study these peptides in the coronary artery disease circulation and correlate with the degree of coronary artery disease. METHODS/STUDY POPULATION: We catheterized 8 type 2 diabetics patients with coronary disease and determined the levels of Ang II and El in the coronary sinus (coronary efflux) and the aorta. RESULTS/ANTICIPATED RESULTS: The levels of Ang II in the coronary sinus were similar to those in the aorta (46 ± 18 vs. 35 ± 15 pg/ml, respectively). However, these values were significantly higher when compared to normal individuals (10 pg/ml, p < 0.001). Similarly, El levels were elevated in the coronary sinus and aorta (14 ± 4 and 13 ± 6 pg/ml, respectively) when compared to normal individuals (3 ± 1 pg/ml, p < 0.00l). When the patients were grouped according to the severity of coronary disease. The Ang ll levels were 42% lower in the mild‐disease group when compared to those with moderate and/or severe disease (29 ± 2 vs. 52 ± 18 pg/ml, respectively). The El levels were similar in these groups (16 ± 2 vs. 13 ± 4 pg/ml, respectively). DISCUSSION/SIGNIFICANCE OF IMPACT: In conclusion, this study suggests that the incidence of coronary disease in diabetic patients is probably related to the higher levels of Ang II and El in the coronary arteries.
P329
CrohnsPROMISE: A MODEL FOR PATIENTS TO REPORT QUALITY INDICATORS AND QUALITY OF LIFE INDICATORS
Atreja A 1
1Cleveland Clinic, Cleveland, OH, USA
OBJECTIVES/SPECIFIC AIMS: There is high administrative burden associated with capturing quality indicators and quality of life in routine clinical practice. The purpose of this study is to assess the feasibility and accuracy of utilizing patient reported outcomes (PRO) for determining quality indicators and quality of life in Crohn’s disease (CD) patients. METHODS/STUDY POPULATION: CrohnsPROMISE is a Web‐based platform to measure PRO and quality indicators directly from the patients. CD patients are requested to enter information about disease summary and quality indicators at crohnspromise.org. This information is then compared to physician documentation and results in electronic health records (EHR) to determine concordance rates for different patient reported variables, quality indicators, CD disease phenotype and medication use. RESULTS/ANTICIPATED RESULTS: A total of 126 patients were given access to enter data prospectively at crohnspromise.org, and, of these, 122 patients (97%) were able to enter data on their own. Concordance rates for CD Phenotype and Quality Indicators were: Year of diagnosis, 106 (86.9%); Phenotype, 65 (53.27%); Last colonoscopy year, 96 (78.7%); Dysplasia, 102 (83.61%); Cancer,114 (93.44%); Smoking,116 (95.08%); Bone Scan year, 59 (48.36%) and Bone Scan result, 81 (66.4%). DISCUSSION/SIGNIFICANCE OF IMPACT: The majority of the CD patients can independently report PRO using a Web‐based tool. Information on many quality indicators (including colonoscopy, findings of dysplasia or cancer, smoking, adherence and medication use) can be accurately captured from patients. Relying on patients to report quality indicators and quality of life will reduce the administrative burden of capturing these measures and allow incorporation of quality improvement efforts in routine clinical practice.
P330
EXPERIENCES OF A CANCER EDUCATION AND SCREENING PROGRAM FOR UNDERSERVED INDIVIDUALS
Robertson LB 1, Simon B2
1University of Pittsburgh, Pittsburgh, PA, USA; 2UPMC Cancer Centers, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: This project examines education and screening programs implemented by our cancer outreach team. A prior survey (n = 72) indicated that individuals living in underserved communities in our area had not been participating in cancer screening programs, although they reported being interested in learning how to protect and improve their health. METHODS/STUDY POPULATION: Individual and community based needs assessments are being conducted in several underserved communities. Educational programs are developed based on the assessments, cancer screenings are facilitated and navigation services are made available to clients in need. A survey was developed to collect additional information on health behaviors, insurance/employment status, and motivational factors in individuals who participate in the screening and/or educational programs. RESULTS/ANTICIPATED RESULTS: Thirty‐one individuals have been surveyed to date, in 3 community agencies. Seventy‐four percent were African American, 68% reported a family history of cancer, 78% were current smokers and 65% were overweight. Most (77%) reported being unemployed and 44% were uninsured. Seventy‐one percent were not adhering to current guidelines for cancer screening, however of these, 77% received onsite screening when offered or expressed the intent to be screened. The major motivating factor for screening was concern for health, when other barriers (convenience and cost) were eliminated. DISCUSSION/SIGNIFICANCE OF IMPACT: The screening compliance rate for individuals participating in the program is 98%, which is higher than the national average of 60%. Individuals who attended the targeted educational programs demonstrated it is possible to motivate individuals to comply with recommended screenings.
RESOURCES
P331
COLLABORATION AND RESEARCH DISCOVERY WITH VIVO
Conlon M 1, Holmes KL2, Börner K3, Ding Y3
1University of Florida, Gainesville, FL, USA; 2Washington University in St. Louis School of Medicine, St. Louis, MO, USA; 3Indiana University, Bloomington, IN, USA
OBJECTIVES/SPECIFIC AIMS: VIVO (http://vivoweb.org/) is an open source semantic Web application that enables the discovery of research and scholarship across disciplinary and administrative boundaries through interlinked profiles of people and other research‐related information. VIVO is populated with authoritative information about researchers, allowing individuals to highlight areas of expertise, display academic credentials, visualize academic and social networks and display information such as publications, grants, teaching, and service. VIVO offers a way to stay up to date in a field and follow the efforts of colleagues and competitors, alike. VIVO can serve as a vital resource for building distinctive interdisciplinary teams for a wide range of efforts. METHODS/STUDY POPULATION: n/a. RESULTS/ANTICIPATED RESULTS: VIVO enables the research networking recommendations endorsed by CTSA Consortium. By storing data in VIVO in RDF and using standard ontologies, the information in VIVO can be displayed in a human‐readable Web page or delivered to other systems as RDF. The data in VIVO can be re‐purposed and shared to highlight expertise and facilitate discovery at many levels. Across implementations, VIVO provides a uniform semantic structure to enable a new class of tools which use the rich data to advance science. DISCUSSION/SIGNIFICANCE OF IMPACT: There are a number of ways to get involved with VIVO efforts, including: adoption, application development, and data provision/consumption. Currently, there are over 50 VIVO implementations in the United States and well over 20 international VIVO projects. VIVO enjoys a robust open source community space on SourceForge at http://vivo.sourceforge.net and the community site resources support a wide range of VIVO activities. The third annual VIVO Conference will be held August 22–24, 2011 in Miami, FL.
P332
CONSTRUCTION OF A FIBROMYALGIA REGISTRY
Hawkins ES 1, Whipple MO1, Cha SS1, Luedtke CA1, Oh TH1, Thompson JM1, Vincent A1
1Mayo Clinic, Rochester, MN, USA
OBJECTIVES/SPECIFIC AIMS: Billing records indicate a considerable number of patients with a diagnosis or history of fibromyalgia (FM) sought care at our tertiary medical center from 2001 to 2010. Utilizing this resource, we endeavored to create a FM research registry and describe the phenotype of registry participants. METHODS/STUDY POPULATION: Patients seen between 2001 and 2010 at our tertiary medical center with a diagnosis or history of FM were identified through billing data and medical index retrieval services. Diagnosis or history of FM was confirmed by review of each patient’s medical record. A survey was mailed to eligible participants that included a demographic questionnaire and the modified 2010 American College of Rheumatology FM Criteria. RESULTS/ANTICIPATED RESULTS: Of the 11,273 patients identified, 10,651 had a diagnosis or histories of FM confirmed by medical record review and were mailed a survey. Completed surveys were received from 2,499 participants. The mean age of participants was 55.2 (±29.3) years, and 93% were female. The mean BMI was 29.5 (±7.3). The most frequent pain locations reported included low back (83%), neck (80%), and shoulders (76%), and the least frequent pain locations included the abdomen, right jaw, and left jaw (<40%). Moderate to severe fatigue, unrefreshing sleep, and cognitive difficulties were reported by 86%, 84%, and 59% respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Using a systematic process we successfully created a FM registry. This registry of well‐phenotyped participants provides us an excellent sampling frame for future clinical studies.
P333
EMERGING GOVERNANCE AND ENGAGEMENT ISSUES IN BIOBANKING: AN UPDATE FROM THE CRE KFC BIOBANK WORKING GROUP
Edwards K 1, Solomon S2
1University of Washington, Seattle, WA, USA; 2St. Louis University, St. Louis, MO, USA
OBJECTIVES/SPECIFIC AIMS: (1) Provide an update on Biobank Working Group activities. (2) Inform and advance research practices utilizing biobanks and other data sharing practices. METHODS/STUDY POPULATION: The Biobank Working Group (BWG) formed in November 2010 in response to growing need and activity around the country at all CTSA institutions. Our membership includes 61 individuals drawing from both the Clinical Research Ethics and Community Engagement KFCs. We have key informant interviews from BWG members identifying common challenges, best practices, and emerging opportunities for national efforts seeking to improve biobank governance and community engagement practices. RESULTS/ANTICIPATED RESULTS: Common issues include: informed consent (timing, content), returning results, effective engagement strategies, productive uses of community advisory boards, managing commercial interests, data ownership, and benefit sharing. Novel innovations include participatory governance models, consult services to develop mandated community engagement plans, and dynamic consent models. Some areas remain deeply divisive, and will be resolved in context‐specific ways, such as: opt‐in versus opt‐out models of consent, when re‐consent should be required, and nature and frequency of results communication with participants. Underdeveloped areas include: how to engage researchers and institutions in both data or specimen sharing, and how to assure resources, once built, are utilized effectively and productively. DISCUSSION/SIGNIFICANCE OF IMPACT: The BWG shares resources and best practices through an openly available Website, and is pursuing research agendas to advance particular issues in biobanking that would benefit from multisite studies.
P334
FRONTIERS RESEARCH PARTICIPANT REGISTRY
Denton J 1, Blackwell K1, Waitman LR1, Choudhary A1, Bott M1, Brooks W1, Greiner A1, Jamison R1, Klaus S2, O’Brien‐Ladner A3, Latinis K1, Aaronson L1, Burns J1, Barohn R1
1University of Kansas Medical Center, Kansas City, KS, USA; 2University of Kansas Hospital, Kansas City, KS, USA; 3University of Kansas Physicians, Kansas City, KS, USA
OBJECTIVES/SPECIFIC AIMS: To facilitate recruitment for researchers without a patient base or for research across specialties. METHODS/STUDY POPULATION: In 2009, the Frontiers CTSA initiative at the University of Kansas Medical Center started a pilot study to create a registry of potential study participants. We record the patient’s willingness to be contacted with a checkbox in the EMR. Creating a registry with an EMR checkbox, instead of a database, is not considered human subject research by the Office of Human Research Protections and does not require IRB approval. Clinic patients sign an authorization form at clinic registration. The HIPAA‐compliant authorization provides a mechanism for contact by investigators without a treatment relationship. Permission may be withdrawn at any time. The registry is linked to an i2b2‐based data repository containing clinical and biomedical data from inpatient and outpatient encounters. A multidisciplinary committee reviews requests for access to the registry. IRB‐approved researchers can query the registry for ICD9 codes, CPT codes, demographics, BMI, lab results and medications. RESULTS/ANTICIPATED RESULTS: Successful in four clinics, the registry is now in 11 clinics with 7,667 registered. Overall, 65% of clinic patients agree to participate. Since June 2011, nine researchers have used the registry to recruit for 12 studies, and 68 staff have used the registry for cohort ID. Challenges include implementation in varied clinic settings, refined search parameters and transition to electronic format. Immediate goals include expansion into all clinics and introduction to a regional affiliate hospital. DISCUSSION/SIGNIFICANCE OF IMPACT: Enhanced participant enrollment.
P335
HIREC: ENDOWMENT FUNDING TO FOSTER CLINICAL AND TRANSLATIONAL RESEARCH THROUGH CAREER DEVELOPMENT
Huertas A 1, Estape ES1, Soto LE1, Diaz C1, Frontera W1
1University of Puerto Rico,Medical Sciences Campus, San Juan, Puerto Rico
OBJECTIVES/SPECIFIC AIMS: To identify effective pathways in maximizing resources for educational and career development programs, creating a new generation of clinical and translational researchers, effective collaborations and partnerships to strengthen research capacity to eliminate health disparities. METHODS/STUDY POPULATION: In 2008 the UPR‐MSC Schools of Health Professions and Medicine were awarded a 15 m NIH‐NIMHD Endowment “Hispanics‐In‐Research Capability: SoHP & SoM Partnership (HiREC)” to increase research in diabetes, asthma, stroke and autism. The core program for accomplishing its goals is the postdoctoral Master of Science in Clinical Research (MSc). RESULTS/ANTICIPATED RESULTS: Some results are: (1) Creation of a multi institutional new course in translational research in health disparities and a scientific article published in CTS; (2) A curriculum revision of the MSc to be offered as a postdoctoral Master of Science in Clinical and Translational Research (MCTR); (3) Technology infrastructure strengthened to facilitate analysis of complex data and support distance learning; (4) A Visiting Professorship Program; (5) A Visiting endowed Chair to promote mentoring and new funding resources; (6) HiREC’ first Scholar Awards to study in the MSc program. to 3 scholars, one from UPR‐MSC, Ponce School of Medicine, and Universidad Central del Caribe, increasing our scope of research in health disparities in Puerto Rico. DISCUSSION/SIGNIFICANCE OF IMPACT: This endowment is a key funding resource to enable our institution to increase collaboration and partnerships in research training and career development with the skills and competencies needed to help facilitate the transfer of scientific advances at a faster pace and improve current health policy and practice. NIH grants NIMHD: S21MD001830 and CRECD R25RR17589.
P336
INFORMATICS ARCHITECTURE FOR PERSONALIZED MEDICINE AT THE UNIVERSITY OF FLORIDA
Conlon M 1, Nessl D1, Liu F1, Ebel C1, Elsey A1, Johnson JA1
1University of Florida, Gainesville, FL, USA
OBJECTIVES/SPECIFIC AIMS: Our objective is to create an informatics architecture and system to support an information pathway for the use of patient‐specific genomic information in the guidance of treatment for patients undergoing cardiac catheterization. See Nelson, et al. CTS, 4(6), 2011 for a program description. METHODS/STUDY POPULATION: An information pathway for personalized medicine has been developed that begins with physician/patient discussion and consent, proceeds through sample collection and processing, genotyping 254 genetic polymorphisms (SNPs), data storage and transmission, and ends with treatment guidance for the physician. The pathway is implemented through iterations as an information system. RESULTS/ANTICIPATED RESULTS: The pathway will initially support genetic‐guided pharmacotherapy for an estimated 600 patients who undergo a percutaneous coronary intervention (PCI) during their cardiac catheterization at UF per year. The approximately 900 additional patients who undergo a cardiac catheterization but no PCI will also have genetic information generated and the pathway will support use of that genetic information if the relevant pharmacotherapy is prescribed in the future. Alerts in the Epic EMR will be used to guide physician’s treatment decisions for clopidogrel versus alternative therapy based on CYP2C19 genotype. UF will store additional SNP data in its integrated data repository for research purposes. SNP data will also be held in a pathology database in anticipation of future clinical utilization. The EMR contains actionable clinical findings. DISCUSSION/SIGNIFICANCE OF IMPACT: This approach will support the first systematic use of genetic information in the treatment of patients in the University of Florida Health System, guiding choice of medication for patients, and will serve as a model for additional UF personalized medicine applications, clinical care, and research partners.
P337
ONLINE TRAINING RESOURCES TO ENHANCE COMMUNITY‐ENGAGED RESEARCH
Proser M 1, Payne P2, Shin P2, Tobin JN3, Jester M1, Weir R4, Merrill C5, Young V6, Brandt H7, Felder T7, Rachman F8
1National Association of Community Health Centers, Washington, DC, USA; 2George Washington University, Washington, DC, USA; 3Clinical Directors Network, New York, NY, USA; 4Association of Asian Pacific Community Health Organizations, Oakland, CA, USA; 5Children’s National Medical Center, Washington, DC, USA; 6South Carolina Primary Health Care Association, Columbia, SC, USA; 7University of South Carolina, Columbia, SC, USA; 8Alliance of Chicago Community Health Services LLC, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: Community Health Centers (CHCs) are facing an increasing number of research opportunities and partnerships to improve healthcare quality, often with mixed results. Little is known about the state of research at CHCs and their research needs. METHODS/STUDY POPULATION: The Clinical and Translational Science Institute at Children’s National Medical Center, in partnership with The George Washington University (CTSI‐CN), the National Association of Community Health Centers (NACHC), the Association of Asian Pacific Community Health Organizations (AAPCHO), and Clinical Directors Network (CDN) developed and enhanced an online training portal to resources that facilitate and support CHCs engaging in research. These resources were selected based on responses to a national survey conducted by the CTSI‐CN on CHCs’ research participation and needs. RESULTS/ANTICIPATED RESULTS: In addition to updating AAPCHO’s Community‐Based Participatory Research Toolkit (http://cbprtoolkit.aapcho.org), this collaborative has also created a new Website (http://www.CDNetwork.org/NACHC) that organizes free training resources. DISCUSSION/SIGNIFICANCE OF IMPACT: The resources provided on these two Webistes are designed to enhance CHCs’ skills in all steps of the research process, from designing and implementing studies to analyzing and disseminating results, such that CHCs can both conduct research and enter into sustainable and equitable partnerships with academic researchers.
P338
PILOT PROJECT FOR THE IMPLEMENTATION OF THE TRANSLATIONAL RESEARCH IN HEALTH DISPARITIES DISTANCE LEARNING COURSE
Soto LE 1, Estape ES1, Ortiz C1, Shaheen M2, Quarshie A5, Harrigan R3, White RO4, Frontera W1
1University of Puerto Rico, San Juan, Puerto Rico; 2Charles Drew University, California, CA, USA; 3University of Hawaii, Manoa, HI, USA; 4Meharry University, Atlanta, GA, USA; 5Morehouse School of Medicine, Atlanta, GA, USA
OBJECTIVES/SPECIFIC AIMS: To start the dialogue and discussion that can be shared among a distance learning course, from March to June 2012, across all institutions interested in developing clinical researchers with health disparities competencies. METHODS/STUDY POPULATION: The implementation of this course during a pilot project with 10 different academic institutions will promote collaboration among leaders from minority and majority institutions, as well as from research related industry and organizations. At the same time the adoption of NIH competencies in translational research as defined by NIH will strengthen and expand the research capacity. RESULTS/ANTICIPATED RESULTS: To implement the pilot project a Distance Learning Networking Group collaborative initiative was organized by the UPR clinical and translational research leadership, cosponsored by NIH (CRECD, HiREC and PRCTRC) programs to support the development of the multiinstitutional Translational Research in Health Disparities course. The anticipated result of this network is to help in the dissemination and sharing of clinical and translational training and educational resources among multiple institutions through various technological methods. DISCUSSION/SIGNIFICANCE OF IMPACT: A broad multidisciplinary and multiinstitutional approach was used as an advance method for the course design in Translational Research in Health Disparities. The adoption of NIH competencies in translational research will strengthen and expand the research capacity of the postdoctoral Master of Science in Clinical Research (MSc) program through bringing orientation, training and guidance in health disparities research.
P339
THE IMPROVEMENT SCIENCE RESEARCH NETWORK: A NATIONAL LABORATORY FOR T3‐T4 RESEARCH
Stevens KR 1, Patel D1, Willard G1, Puga F1
1UT Health Science Center San Antonio, San Antonio, TX, USA
OBJECTIVES/SPECIFIC AIMS: Improvement Science (IS) is a nascent field of research focused on healthcare quality improvement (QI). The Improvement Science Research Network (ISRN) creates a robust research environment that brings together a network of academic‐practice partners to collaborate on IS studies. This project describes how the ISRN serves as a unique virtual laboratory for T3‐T4 translational research and provides resources and opportunities for clinicians, faculty, and graduate students interested in conducting multisite, IS studies. METHODS/STUDY POPULATION: The ISRN created study‐specific protocol implementation kits that support research sites in conducting Network studies. A cyber infrastructure was also used for virtual collaboration across the study sites, along with ISRN Website and phone assistance that allowed for constant communication between the coordinating center and the study site. Finally associates were engaged in a number of ways to grow scientific capacity and disseminate research results, including annual research methods conferences,and multichannel dissemination through print and electronic media. RESULTS/ANTICIPATED RESULTS: Anticipated results of using the ISRN as a laboratory for T3 and T4 research include moving local improvement strategy testing to a national, landmark level and contributing to rapid advancement of IS to transform healthcare. DISCUSSION/SIGNIFICANCE OF IMPACT: Studies using the ISRN’s national laboratory contribute directly to clinical practice, population health, and healthcare policy by producing evidence on interventions for improvement and patient safety at a level of rigor and generalizability that promotes spread. By engaging multiple settings as study collaborators and by including academic and practice partners, research results will be widely representative and actionable.
P340
THE INTERNATIONAL FANCONI ANEMIA REGISTRY (IFAR): A VASTLY IMPROVED SECOND GENERATION OFFERING
Barbour E 1, Auerbach A1, Sanborn E1, Lach FP1, Wrobel M1, Sengupta M1, Smogorzewska A1
1The Rockefeller University, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: The International Fanconi Anemia Registry (IFAR) was established at The Rockefeller University in 1982 to collect Fanconi anemia (FA) patient and familial data. Objective: The ultimate goal of the IFAR is to help move FA research forward by collecting as much genotypic and phenotypic data as possible, displaying these data in a comprehensible, user‐friendly manner, and making this application and underlying data available to other FA clinicians and researchers. METHODS/STUDY POPULATION: Methods: There are three important aspects to our methodology. First, is working more closely with families to obtain more detailed longitudinal phenotypic data. Secondly, we have formed important collaborations with the Cancer Genetics Branch at the National Human Genome Research Institute (NHGRI) and the Broad Institute to deepen our genotypic data. Lastly, the technology is a Java‐based, ontology‐driven application. RESULTS/ANTICIPATED RESULTS: Results: We have revamped the second generation application to be more user‐friendly and to display data in a more cohesive table‐based format. The application will be made available to FA clinicians and researchers in one of two formats, either full access or de‐identified access. In addition, we have built the ontology to reflect and connect many concepts about FA, genotypic and phenotypic, as well as, diagnostic and anatomic components. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Included in the IFAR are all genotypic data available from our collaborations with NHGRI, as well as, the most up‐to‐date, streamlined, ontology driven phenotypic information. Now with all of the information about FA in one place we can start to learn more about genotype/phenotype correlations, the role of the FA proteins in damage repair, the role of FA proteins in cancer, and the implications of mosaicism.
P341
THE MURDOCK STUDY: MOLECULAR RECLASSIFCATION OF COMMON CHRONIC DISEASES
Tenenbaum J 1, Christian V1, Burrell G1, Cornish M1, Dunham A1, Ginsburg GS1, Kraus VB1, Nahm ML1, Newby K1, McCarthy J1, McHutchison J2, Svetkey L1, Udayakumar K1, Califf RM1
1Duke, Durham, NC, USA; 2Gilead Pharmaceuticals, Foster City, CA, USA
OBJECTIVES/SPECIFIC AIMS: The MURDOCK Study is a long‐term epidemiological study that applies high throughput biomarker discovery to major chronic illnesses, helping to improve disease classification and population health. METHODS/STUDY POPULATION: The MURDOCK study consists of distinct project “horizons” or stages. Horizon 1 involves the generation and analysis of high throughput molecular data for existing large, clinically well‐annotated cohorts of four different diseases. Statistical methods have been applied to these datasets to identify biomarker signatures predictive of disease outcomes. Horizon 1.5 involves the creation of a 50,000 volunteer registry. Blood and urine are collected, along with a clinical data questionnaire, access to electronic health records, and consent to follow‐up contact. Horizon 2 projects leverage Horizon 1.5 volunteers and extends the study to additional disease areas of interest. Horizon 3 entails the formation of partnerships nationally and internationally, enabling validation in diverse populations and cross‐registry meta‐analyses. RESULTS/ANTICIPATED RESULTS: Clinical data collected through the case report forms for the four individual Horizon 1 studies have been mapped to common data elements, where such overlap exists. Preliminary molecular and imaging data analysis has yielded promising biomarkers. More than 7,000 subjects have been enrolled in the Horizon 1.5 registry. DISCUSSION/SIGNIFICANCE OF IMPACT: With interdisciplinary investigators, cutting edge technology, and strategic partnerships, the MURDOCK study represents a true team science effort, and a whole much greater than the sum of its parts. The MURDOCK Study is actively seeking collaborators for novel extensions to, and analysis of, this rich data and biospecimen resource.
TRANSLATIONAL BASIC‐TO‐CLINICAL
P342
A CANDIDATE GENE STUDY OF SNPS ASSOCIATED WITH FIBROSIS PROGRESSION POST HCV RELATED LIVER TRANSPLANTATION
Layden J 1, Cotler S1, Baraoidan MK1, Clark N1
1Univ Illinois, Chicago, IL, USA
OBJECTIVES/SPECIFIC AIMS: HCV is the main indication for LT in the US. While HCV recurrence is universal, the severity of fibrosis progression is highly variable. HCV‐infected African American recipients have worse post‐LT outcomes. The purpose of this study was to assess the association of LT recipient SNPs of fibrosis‐related genes with post‐LT fibrosis progression. METHODS/STUDY POPULATION: 112 (72 Caucasian, 40 African American) HCV LT recipients were included. Rapid fibrosis progression (RFP) was defined as F2 by 12 months, or F3 or F4 at any time point with the first two years. DNA was extracted from a pre‐LT biopsy and mass array was used for genotyping. RESULTS/ANTICIPATED RESULTS: 59 patients were classified as having RFP and 53 as slow progressors. Three SNPs were independently associated with RFP in univariable logistic regression. The risk genotype (AG/AA) of RS4969168 (suppressor of cytokine signaling‐3 [SOC‐3] gene) had an odds ratio (OR) of 4.1 (1.8–9.5); p = 0.001. The OR for the risk genotype (AA) of RS19914101 (DDX5 gene) was 3.3 (1.3–7.6; p = 0.004), while the OR for the risk genotype (TT) of RS8099917 (IL28B gene) was 3.1 (1.3–7.1; p = 0.008). Each of these risk genotypes exhibited significant variation in frequency by race, with the risk genotypes significantly more common in African Americans. Adjusting for race in multivariable regression, each of the 3 SNPs remained highly associated with RFP, with the following adjusted ORs: RS4969168 (SOC‐3): 3.3 (1.3–8.4; p = 0.02); RS19914101 (DDX5 gene): 2.4 (1.0–6.1; p = 0.05); and RS8099917 (IL28B gene): 2.4 (1.0–5.7; p = 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: In conclusion, recipient SNPs of the SOC3, DDX5, and IL28B genes are associated with RFP post‐LT. Further studies are needed to elucidate the potential mechanisms associated with these findings.
P343
BASELINE SERUM INTERFERON BETA/ALPHA RATIO PREDICTS RESPONSE TO TUMOR NECROSIS FACTOR ALPHA INHIBITION IN RHEUMATOID ARTHRITIS
Niewold TB 1, Aggrawal R1, Franek BS1, Kern M2, Gregersen PK2
1Univ of Chicago, Chicago, IL, USA; 2Feinstein Institute for Medical Research, Manhasset, NY, USA
OBJECTIVES/SPECIFIC AIMS: Response to tumor necrosis factor alpha (TNF‐α) inhibition is heterogenous in rheumatoid arthritis (RA). Previous studies have suggested that circulating type I interferon (IFN) levels may predict treatment response to TNF‐α inhibitors and other biological agents in RA. Prediction of likely responders prior to initiating therapy would represent a major advance in biological treatment strategies for RA. METHODS/STUDY POPULATION: We studied sera from 32 RA patients from the ABCoN Consortium pretreatment and 4–6 weeks after beginning treatment with TNF‐α inhibitors, selecting patients who either had a good response or no response at 14 weeks by EULAR criteria. Total serum type I IFN activity as well as IFN‐α versus IFN‐β activity were measured using a functional reporter cell assay. RESULTS/ANTICIPATED RESULTS: An increased ratio of IFN‐β/IFN‐α >1.3 in the pretreatment serum sample was associated with lack of response by EULAR criteria at 14 weeks (p = 0.009). Similarly, higher IFN‐β/IFN‐α ratio was positively correlated with higher DAS score at 14 weeks (Spearman’s rho = 0.57, p = 0.0075). Anti‐CCP antibody titer and type of TNF‐α inhibitor did not influence this relationship. In follow‐up sera at 4–6 weeks, the EULAR nonresponders were more likely to have increased total type I IFN activity than good responders (p = 0.008), and this increase was characterized by a shift toward increased IFN‐α as compared to good responders (p = 0.039). DISCUSSION/SIGNIFICANCE OF IMPACT: Increased pretreatment serum IFN‐β/IFN‐α ratio was strongly associated with nonresponse to TNF‐α inhibition by EULAR criteria at 14 weeks. Our data support the potential utility of serum type I IFN in predicting outcome of TNF‐α inhibition in RA.
P344
CAIRN LEARNING PARADIGM (CLP)—AN OBESITY MANAGEMENT STRATEGY IN RURAL APPALACHIA
Hanks S 1, Morton‐McSwain C1, Chester A1, Paulsen S2, Branch R2
1West Virginia University, Morgantown, WV, USA; 2University of Pittsburgh, Pittsburgh, PA, USA
OBJECTIVES/SPECIFIC AIMS: To capture the energy of adolescents to increase health knowledge of all stakeholders to reduce obesity in the community. METHODS/STUDY POPULATION: The WV Health Science and Technology Academy’s (HSTA) network of 79 after‐school science clubs for 800 9th–12th graders, their families, teachers, community board members and Clinical Translational Scientists form the Community Appalachian Investigation Research Network. In 2011, we introduced a novel, tiered, diffusion model of learning (CLP) in which adolescents are the change agents in their communities. Community Research Associates (CRA), a new career path, have been added to link scientists and students. Students assimilate information from CAIRN and do research projects on community health issues. They disseminate health information and recommendations to family and community via projects and regional symposia. RESULTS/ANTICIPATED RESULTS: The CAIRN Paradigm has excited HSTA teachers, students and communities about conducting CBPR focused on obesity. The Community Governing Board has adopted a new mission with priorities that focus on health through education. Teachers have an increased interest in the principles of CBPR and are using it in their clubs. Student projects have increased in relevancy, rigor and focus, with real interventions aimed at impacting their family’s and community’s health. Since launching the Paradigm, and introducing the concept of the CRA, students have been engaged in 369 healthcare projects which have risen from 34% to 72% of the total HSTA projects per year. DISCUSSION/SIGNIFICANCE OF IMPACT: This consortium has pioneered a novel strategy to harness a previously untapped workforce of enthusiastic adolescents to conduct CBPR. This provides access to underserved families and communities for translation of biomedical knowledge into obesity reduction.
P345
COMPARISON OF THE EFFICACY OF TWO CELL PERMEANT MK2 INHIBITOR PEPTIDES IN BLEOMYCIN‐INDUCED PULMONARY FIBROSIS
Vittal R 1, Panitch A2, Lander C2, Wilkes DS1
1Indiana School of Medicine, Indianapolis, IN, USA; 2Moerae Matrix, Inc., New Brunswick, NJ, USA
OBJECTIVES/SPECIFIC AIMS: Mitogen‐activated protein kinase activated protein kinase 2 (MAPKAPK2 or MK2) has been implicated in many inflammatory diseases that result in fibrosis. There is an urgent clinical need for therapeutic agents for pulmonary fibrosis. The current study tests comparative efficacy of the MK2 inhibitors MMI‐0100 and MMI‐0200 in the prevention of fibrosis. METHODS/STUDY POPULATION: C57‐BL/6 mice (6–8 wk‐old) were intra‐tracheally instilled with PBS or 0.025U of bleomycin at day 0. MMI‐0100 or MMI‐0200 (25, 50, 75 μg/kg) was administered daily by intra‐peritoneal injections, beginning at day 7. On day 21, the mice were sacrificed. Histopathological examinations were made by H&E staining. Proliferative capacity of splenic T cells cocultured with antigen presenting cells (APCs) was assessed by H3‐thymidine incorporation. Cytokine expression profile in the plasma was analyzed by cytokine bead assay. Quiescent human fetal lung fibroblasts (IMR‐90) were pretreated with MMI‐0100 (1, 5, 10, 20, 50 μM) for 1 h and then treated with or without TGF‐β (2 ng/ml) for 72 h and lysates were immunoblotted for mesenchymal differentiation marker, α‐smooth muscle actin. RESULTS/ANTICIPATED RESULTS: MMI‐0100 but not MMI‐0200, significantly inhibited bleomycin‐induced fibrosis at day 21. Autologous APC‐induced proliferation of splenic T cells was reduced significantly in MMI‐0100‐treated mice. TNF‐α and IL‐6 levels were significantly lower in the MMI‐0100 and MMI‐0200 treated groups than the bleomycin group. In vitro, MMI‐0100 dose‐dependently attenuated fibroblast differentiation. DISCUSSION/SIGNIFICANCE OF IMPACT: MMI‐0100 but not MMI‐0200 effectively prevents bleomycin‐induced fibrosis. Analysis of comparative mechanisms of these two inhibitors might help further evaluate specific pathways involved in protection against fibrosis.
P346
DIMENSIONAL CLASSIFICATION OF SCHIZOPHRENIA
Estani PB 1
1Professor Dr. Leon S.Morra Neuropsychiatric Medical Hospital, Córdoba, Argentina
OBJECTIVES/SPECIFIC AIMS: The objective of this research is to propose a simple, dimensional classification of schizophrenia, based on the concept of endophenotypes (Gottesman, 2003). METHODS/STUDY POPULATION: A total of 1,200 participants with a diagnosis of schizophrenia were the subjects. Neuropsychological tests were applied. We operationalized two neurocognitive endophenotypes: sensorial gating and cognitive performance. RESULTS/ANTICIPATED RESULTS: A: Dimensional Classification of Schizophrenia: Structural dimensions: A1: Genetically‐defined Dimensions, as a Working Group 1. Negative Schizophrenia and 2. Positive Schizophrenia B. The Longitudinal Diagnosis of the Disease: Longitudinal Dimensions: B1. The Continuous Dimensions: The dimensions as phases of a continuum from a preclinical state to a more chronic, pathological state. 1. the schizophrenia prodrome 2. first episode of illness 3. The Spontaneous Amileoration Syndrome: of the typically active phase or positive symptoms 4. A progressive neurodegeneration and neurodeterioration phase 5. Deficit Syndrome. DISCUSSION/SIGNIFICANCE OF IMPACT: The classification allows full inclusion of the neurocognitive endophenotypes in the classification of schizophrenia, defining the genotypes to benefit the understanding and treatment of schizophrenia. The full explanation of this categorization will be presented along with the results of this pilot sample.
P347
LACK OF NORMAL MITOTIC SYNCHRONY IN REGENERATING ASTHMATIC AIRWAY EPITHELIUM DRIVES BASOLATERAL SECRETION OF TGF‐b1
Freishtat RJ 1, Alcala SD1, Benton AS1, Watson AM1, Kureshi S1, Reeves E2, Damsker J2, Wang Z1, Nagaraju K1, Hayes K1, Lee A1, Rose MC1, Hoffman EP1
1Center for Genetic Medicine Research, Children’s National Medical Center, Washington, DC, USA; 2ReveraGen Biopharma, Rockville, MD, USA
OBJECTIVES/SPECIFIC AIMS: We recently published that injured asthmatic fully‐differentiated primary in vitro airway epithelia, lacking immune cells, show poorly‐synchronized mitotic regeneration accompanied by basolateral secretion of TGF‐β1. Now, we aim to establish the directionality of cause (lack of normal mitotic synchrony) and effect (secretion of TGF‐β1). METHODS/STUDY POPULATION: Normal and asthmatic bronchial epithelia were differentiated at air‐liquid interface. Cultures were incubated in glucocorticoid‐free medium beginning at −48 h. They were pulsed with mitotic synchrony‐inducing compounds [i.e. dexamethasone, simvastatin, and aphidicolin] for 2 h at −26, −2, +22, and +46 h. Cultures were mechanically scrape‐wounded at 0 h to induce mitotic regeneration and thereafter exposed continuously to BrdU. RESULTS/ANTICIPATED RESULTS: Asthmatic epithelial mitosis was dyssynchronous (G1, S, G2/M: 47.4 ± 3.8, 23.9 ± 6.3, 28.7 ± 5.7%) compared to normal epithelia (71 ± 1, 12 ± 2, 17 ± 2%). Dexamethasone, simvastatin, and aphidicolin pulses all improved mitotic synchrony in correlation (R2 = 0.8, 0.4, 0.6 respectively) with reductions in the peak of TGF‐β1 secretion. In addition, secretions from regenerating asthmatic epithelium applied to regenerating normal epithelium had no effect on normal mitotic synchrony. Finally, induced‐dyssynchronous mitosis in normal epithelial cells stimulated TGF‐β1 secretion. DISCUSSION/SIGNIFICANCE OF IMPACT: Taken together, these data show that airway epithelial mitotic dyssynchrony is the cause and not the effect of asthmatic epithelial TGF‐β1 secretion. Our model establishes a foundation for novel drug development in asthma targeting epithelial repair rather than immune‐mediated inflammation.
P348
LRP6 INFLUENCES BODY FAT AND GLUCOSE HOMEOSTASIS IN MOUSE BY ACTIVATING mTOR PATHWAY AND INHIBITING MITOCHONDRIAL ENERGY EXPENDITURE
Liu W 1, Singh R1, Choi C1, Young L1, Keramati AR1, Samuel VT1, Lifton RP1, Shulman GI1, Mani A1
1Yale University School of Medicine, New Haven, CT, USA
OBJECTIVES/SPECIFIC AIMS: Body fat, insulin resistance and type2 diabetes are often linked together. Wnt signaling regulates adipogenesis and its altered activity has been implicated in the pathogenesis of type 2 diabetes and metabolic syndrome. Mutations in Wnt coreceptor LRP6 have been associated with diabetes, coronary heart disease and metabolic syndrome in humans, but the molecular mechanisms are largely unknown. METHODS/STUDY POPULATION: We study the role of LRP6 in regulation of glucose and energy metabolism in heterozygote LRP6 knockout mice on high fat diet by using glucose tolerance test, hyperinsulinemic‐euglycemic clamp studies and dissection of insulin signaling pathway. RESULTS/ANTICIPATED RESULTS: Results: LRP6+/− mice on high fat diet were protected against diet ‐induced obesity and hepatic and adipose tissue insulin resistance compared to wild‐type littermates. Brown adipose tissue insulin sensitivity and lean body of LRP6+/− mice were caused by diminished Wnt‐dependent mTORC1/S6K activity and enhanced expression of brown adipose tissue PGC1‐α and UCP1. LRP6+/− mice also exhibited reduced endogenous hepatic glucose output which was due to diminished FoxO1‐dependent activity of G6Pase. In addition, in vivo and in vitro studies showed that loss of LRP6 allele is associated with tissue specific increase of leptin receptor expression, which is a likely cause of hepatic insulin sensitivity in LRP6+/− mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study identifies LRP6 as a nutrient‐sensitive regulator of the body weight and glucose metabolism and as a potential target for pharmacological interventions in obesity and diabetes.
P349
MAGE‐A INHIBITS APOPTOSIS IN PROLIFERATING MULTIPLE MYELOMA CELLS
Nardiello T 1,2, Mei A2, Jungbluth AJ3, Cho HJ2
1New York University Medical School, New York, NY, USA; 2Mount Sinai School of Medicine, New York, NY, USA; 3Ludwig Institute for Cancer Research, New York, NY, USA
OBJECTIVES/SPECIFIC AIMS: Type I Melanoma Antigen GEne (MAGE)‐A3 was commonly detected in primary tumor cells from multiple myeloma (MM) patients. MAGE‐A3 expression correlated with progression of disease and proliferation, suggesting a potential pathogenic role in this disease. MAGE‐A complex with the RING domain protein Kap1 to form E3 ubiquitin ligases that can inactivate p53. We investigated pathogenic activity by silencing MAGE‐A expression in primary MM cells and human myeloma cell lines (HMCL) by shRNA interference. Targeted lentiviral shRNA transduction efficiently knocked down MAGE‐A mRNA and protein in p53‐expressing MM.1r and H929 cells, and in p53‐null ARP‐1 and patient cells. METHODS/STUDY POPULATION: HMCL and MM patient samples. RESULTS/ANTICIPATED RESULTS: This analysis showed that MAGE‐A was not required for cell cycle progression. In contrast, MAGE‐A was required for survival of proliferating myeloma cells. Silencing of MAGE‐A led to activation of intrinsic apoptosis within 48–72 hrs, as shown by increased annexin V staining, loss of mitochondrial membrane polarization, and cleavage/ activation of caspase‐9 and ‐3. Apoptosis was reversed by the pan‐caspase inhibitor Q‐VD‐OPh. MAGE‐A appeared to regulate p53‐dependent and independent mechanisms of apoptosis. Silencing of MAGE‐A resulted in loss of p53 ubiquitinylation and modulated expression of the p53 targets Bax and survivin. These changes were reversed by dual silencing of MAGE‐A and p53. In p53‐null HMCL, loss of MAGE‐A still resulted in decreased survivin. Silencing MAGE‐A also increased sensitivity to melphalan‐induced apoptosis. DISCUSSION/SIGNIFICANCE OF IMPACT: These results demonstrate that MAGE‐A plays a novel role in the survival of proliferating MM cells through the regulation of p53‐dependent and independent mechanisms of apoptosis.
P350
PATELLAR TENDON TEAR DETECTION USING MACHINE LEARNING
Syed S 1, Attarzadeh D2, Biswal S3
1Stanford Univ Dept Comp Sci, Stanford, CA, USA; 2Stanford Univ Sch of Medicine, Stanford, CA, USA; 3Stanford Univ Dept Radiology, Stanford, CA, USA
OBJECTIVES/SPECIFIC AIMS: The widespread availability of magnetic resonance imaging (MRI) creates vast amounts of hires imagery of the human body. While radiologists are quite good at identifying anomalous regions in these scans, they lack quantitative metrics on how to precisely classify the extent of damage, and may overlook unexpected anomalies. Our group believes that computer vision may be beneficial in assisting doctors with analyzing MRI data sets quantitatively. Here, we present a novel algorithm for classifying tendon tears, inspired by the spatial pyramid approach of Lazebnik et al. METHODS/STUDY POPULATION: Manual segmentation was performed on sagittal MR images of the knee. The tendon region was circumscribed and classified by a human. A feature representation was extracted from the segmented tendon region using a spatial pyramid of intensity histograms. Texton based features were also explored. A Random Forest classifier was then used to distinguish between torn and nontorn MRI slice features. RESULTS/ANTICIPATED RESULTS: Intensity histograms appeared to provide the best results. Utilizing 3 levels of subdivision and 8 histogram buckets, images were accurately classified ~75% of the time (i.e. injured vs. noninjured). Less than 8 buckets, in addition to higher dimensionality histograms and subdivisions, appeared to yield less accurate results. Texton based feature extraction did not result in improved results (accuracy 63–65%). DISCUSSION/SIGNIFICANCE OF IMPACT: Here we demonstrate an accurate method for classifying patellar tendon injury using a machine learning approach. As a valuable tool in our on‐going research, we anticipate using this method to classify pathological tendons and determine the efficacy of Platelet‐Rich Plasma treatment. A comparative analysis with physician classified images is planned.
P351
PLATELET‐RICH PLASMA FOR THE TREATMENT OF TENDON INJURIES: A RADIOLOGIC ANALYSIS
Attarzadeh DO 1, Syed S2, Biswal S3
1Stanford Univ Sch of Medicine, Stanford, CA, USA; 2Stanford Univ Dept Comp Sci, Stanford, CA, USA; 3Stanford Univ Dept Radiology, Stanford, CA, USA
OBJECTIVES/SPECIFIC AIMS: Musculoskeletal (MSK) diseases are the most commonly reported medical conditions in the United States. Current treatment includes both surgical and nonsurgical methods such as therapeutic exercise, medication, and injections. However, the time to full healing remains significant. Our group is radiologically studying the benefits of Platelet‐Rich Plasma (PRP). Despite wide usage, little imaging research has been done to evaluate the efficacy of PRP. Here, we present a novel approach utilizing computer vision algorithms to evaluate the effectiveness of PRP treatment and compare this to physician evaluation of injury. METHODS/STUDY POPULATION: (See associated poster “Patellar Tendon Tear Detection Using Machine Learning” for algorithm development methodology.) Magnetic resonance (MR) images of patients with/without PRP treatment following injury were evaluated via machine learning algorithms. Additionally, physicians were asked to assess the degree of injury of patellar tendons and provide selected measurements. RESULTS/ANTICIPATED RESULTS: A novel algorithm for assessing the severity of patellar tendon injury was developed using machine learning techniques. Imaging assessment by physicians has not been completed at this time. Once assessment and evaluation of data is completed, a comparative analysis can be performed to determine the usefulness of our computer vision algorithm in gauging injury severity. DISCUSSION/SIGNIFICANCE OF IMPACT: We hope to determine the utility of PRP in the treatment of patellar tendon injuries from a radiologic perspective. Here, we also demonstrate the novel application of machine learning algorithms to evaluate MSK injury. It is feasible that our research represents the first application of computer vision to the assessment of tendinous, and possibly musculoskeletal, injuries.
P352
RAPID RESUSCITATION WITH WHOLE BLOOD NORMALIZES OXYGEN METABOLISM IN A PIG MODEL OF SEVERE HEMORRHAGE
Golden P 1, Elliott CL1, Uyehara CF2
1Tripler AMC, Honolulu, HI, USA; 2Dpt of Clin Inv, Honolulu, HI, USA
OBJECTIVES/SPECIFIC AIMS: In recognizing that large volume crystalloid resuscitation of severe hemorrhage is associated with coagulopathy, resuscitation with whole blood (WB) has come back into focus for the US military. However, the timing and amount of blood needed have not been clearly defined for sufficient resuscitation and oxygen delivery. This study aimed to determine the effectiveness of WB resuscitation in the setting of severe hemorrhage. METHODS/STUDY POPULATION: Nine 30 kg pigs were hemorrhaged (3 ml/kg/min for 7 mins followed by 1 ml/kg/min until goal hemorrhage of 30 ml/kg) resulting in a 60% decrease in mean arterial pressure. Hemodynamic and oxygen metabolism measurements were obtained before, during, and after a 60 min hemorrhage period. Resuscitation with donor pig WB was administered over 30 minutes until shed volume was replaced. RESULTS/ANTICIPATED RESULTS: 3 of the 9 pigs did not survive this rapid hemorrhage which induced an oxygen dept of 68.9 ± 9.1 ml/kg over 1 hour in survivors and 100.7 ± 8.8 ml/kg in nonsurvivors. Interestingly, within 10 mins of hemorrhage, plasma potassium (pK+) levels started increasing from a baseline of 4.2 ± 0.2 to 6.1 ± 0.3 mEq/L by the end of hemorrhage in the survivors. In nonsurvivors, pK+ rose over 8 mEq/L. Oxygen delivery, oxygen consumption, oxygen extraction, and pK+ rapidly returned to baseline levels by the end of resuscitation and remained there for 6 hours post resuscitation. DISCUSSION/SIGNIFICANCE OF IMPACT: Results indicate that rapid replacement with WB of shed volume within 30 minutes can improve hemodynamics and oxygen utilization for up to 6 hours after hemorrhage. In addition early hyperkalemia may be an indicator of circulatory collapse before changes in hemodynamic parameters. Comparisons with other crystalloid/pressor agent resuscitation regimens remain to be studied.
P353
REVERSAL OF ABNORMAL ATAXIA TELANGIECTASIA MUTATED (ATM) SIGNALING IN ACETAMINOPHEN (APAP)‐INDUCED ACUTE LIVER FAILURE (ALF) IMPROVED OUTCOMES IN MICE
Viswanathan P 1, Bandi S2, Gonzalez J1, Gupta S2
1Division of Pediatric Gastroenterology, Childrens Hospital at Montefiore, Bronx, NY, USA; 2Departments of Medicine and Pathology, Marion Bessin Liver Research Centre Albert Einstein College of Medicine, Bronx, NY, USA
OBJECTIVES/SPECIFIC AIMS: As the leading cause of ALF, APAP‐induced hepatotoxicity is of extensive interest, although molecular mechanisms of liver injury need to be better understood. We studied ATM signaling since this was important in liver injury. METHODS/STUDY POPULATION: n/a RESULTS/ANTICIPATED RESULTS: n/a DISCUSSION/SIGNIFICANCE OF IMPACT: C57BL/6 mice given 500 mg/kg APAP i.p. showed encephalopathy, abnormal liver tests, hepatic necrosis, and mortalities. qRT‐PCR arrays showed changes in liver gene expression, including cytokines/chemokines, oxidative/metabolic stress, DNA damage/repair, and cell cycle genes. Incrimination of ATM signaling was verified by expression of H2AX, indicating oxidative DNA damage, and of p21, indicating cell growth‐arrest. Assays with genetically‐modified Huh‐7 cells expressing human ATM promoter followed by APAP confirmed DNA strand breaks and increased ATM activity.This assay identified ATM signaling modifiers, e.g., G‐CSF, which reversed APAP toxicity, including in mouse hepatocytes. G‐CSF decreased H2AX activation and DNA strand breaks. Moreover, G‐CSF treatment in mice with APAP‐induced ALF improved encephalopathy, liver tests, histology, and increased survival. Gene expression abnormalities were substantially restored. H2AX activation and p21 expression decreased. Ki67 staining indicated increased liver regeneration. Conclusions: Identification of abnormalities in ATM signaling in APAP‐induced ALF permitted development of drug therapy. Amelioration of APAP‐induced liver injury by G‐CSF through restoration of ATM signaling offers further opportunities for drug development besides offering a clinically translatable approach for rescue in ALF.
P354
SPARK: A COST‐EFFECTIVE MODEL TO PROMOTE TRANSLATIONAL RESEARCH
Grimes K 1, Egeler E1, Mochly‐Rosen D1
1Stanford University, Stanford, CA, USA
OBJECTIVES/SPECIFIC AIMS: The SPARK Translational Research Program at Stanford University is a partnership between academia and local biotechnology, pharmaceutical and investment communities dedicated to promoting an efficient, cost‐effective, innovative approach to discovery and development of novel therapeutics and diagnostics. SPARK has a two‐fold mission: first, to educate faculty, postdoctoral fellows and graduate students regarding the translational research process so that development of promising new discoveries becomes second nature at our institution; second, to help academic investigators overcome the obstacles intrinsic to moving research discoveries from bench to bedside. METHODS/STUDY POPULATION: Selected projects must target an unmet clinical need using a novel approach, with the possibility of advancing to the clinic or commercial sector within two years. While SPARK accepts proposals for any clinical indication, special consideration is granted for projects targeting orphan or neglected diseases. SPARK provides funding, education, access to facilities, expert advice, and mentorship. RESULTS/ANTICIPATED RESULTS: By bringing basic science researchers together with a dedicated cadre of advisors with expertise in basic research, clinical research, drug and diagnostic development, regulatory and intellectual property law, and commercialization, SPARK has enjoyed an impressive success rate with over 50% of projects either entering clinical trials or commercially licensed after two years of SPARK funding. DISCUSSION/SIGNIFICANCE OF IMPACT: We believe SPARK provides a cost‐effective way to advance the clinical adoption of many new therapeutic and diagnostic discoveries that will result in improved public health and lower costs to our healthcare system. The SPARK model for bridging the divide between academic discovery and commercial interest can be replicated at other universities and institutions and for any clinical indication.