THE ENDOCRINE SOCIETY 2010 LAUREATE AWARDS

Citation for the 2010 Fred Conrad Koch Award of The Endocrine Society to Dr. Kathryn B. Horwitz

Kathryn Bloch Horwitz began her scientific career in the late 1970’s with groundbreaking work on progesterone receptors (PR) in breast cancers that are positive for estrogen receptors (ER). Horwitz discovered PRs in breast cancers and demonstrated that when PRs are present in ER-positive tumors, the cancers are less aggressive and more responsive to hormone therapies. Even before her study was published, word of it made waves in the scientific community. The news reached the White House, where First Lady Betty Ford was battling breast cancer. A sample of Ford’s tumor was sent to Horwitz, who found it to be strongly PR-positive; a good sign¹. In the years since, PR content has been used to aid treatment decisions in millions of breast cancer cases.

Horwitz, the daughter of refugees, was born in Sosua, Dominican Republic and immigrated to the United States at age 11. She attended the Bronx High School of Science and is a graduate of Barnard College at Columbia University. She holds a Masters Degree in marine biology from New York University and a PhD in medical physiology from the University of Texas, Southwestern Medical School. Graduate studies included work on androgen receptors in benign prostatic hypertrophy with Jean Wilson (Dallas) and on PR in breast cancer with William McGuire (San Antonio), with whom she also worked on ER as a postdoctoral fellow. In 1979, she joined the faculty of the Endocrinology Division of the Department of Medicine at the University of Colorado’s School of Medicine, where she has risen through the ranks and now holds the title of University of Colorado Distinguished Professor.

Horwitz has done seminal research on the action of steroid receptors in breast cancers at both basic and clinical levels, making her work “translational” before such studies became popular. Her research continues to center on the molecular biology and clinical role of ER and PR. With regard to PR, her lab published initial reports that human PR consist of two natural isoforms, PR-A and PR-B, which differ in their gene regulatory properties. If expressed unequally in breast cancers, they differentially influence patient survival. Extensive studies have dealt with antiprogestins, including the mixed agonist/antagonist RU486 and the molecular mechanisms for its duality. Horwitz collaborated in generating the first anti-PR monoclonal antibodies, which fundamentally altered methods for experimental and clinical receptor measurements. Her group also was the first to define a third PR isoform, PR-C, now thought to trigger onset of labor at parturition. Horwitz has published extensively on PR isoform protein structure, covalent receptor modifications, and crosstalk with growth factor signaling.

Horwitz has also authored seminal papers on ER, including initial reports describing functional ER resistance; ligand-dependent ER downregulation and its relationship to transcriptional activity; and the ways in which phytoestrogens bind ER, an issue of concern with regard to soy and other natural food products. In partnership with her husband, Dr. Lawrence Horwitz, she published the first studies demonstrating ER and PR in cardiovascular tissues, explaining why they are targets of women’s hormones. She showed that antagonist effects of tamoxifen are due to recruitment of corepressors and that tamoxifen’s agonist properties are associated with enhanced growth-factor signaling. Additionally, in translational studies of aromatase inhibitor/tamoxifen combination therapies, she showed that the agonist gene-regulatory properties of tamoxifen are dominant—thus explaining why ER-positive patients who are on combination hormone therapies exhibit treatment resistance and have a poorer response than those on monotherapies.

Horwitz believes that her current research—exploring the role of estrogens and progestins on metastatic engraftment of breast cancers and on expansion of breast cancer stem cells—has great potential. Her lab’s recent demonstration that progestins increase the number of tumor-initiating cells in pre-existing PR-positive malignancies suggests an explanation for the increased risk of breast cancer among women taking estrogen/progestin combinations for menopausal hormone-replacement therapies.

Equally noteworthy are Horwitz’s contributions to the Endocrine Society. Among other roles, she has served as chair of the Nominating, Awards, and Women in Endocrinology Awards committees and on the Publications and Journals steering sections of Council. Her value to the Society was confirmed in 1998, when she was elected president. In that yearlong post, her contributions included introducing focus topics to the annual meeting and becoming the first president to actively partner with pharmaceutical companies to support the Society’s programs.

For Kate’s extraordinary contributions to endocrinology and to the Endocrine Society, she is being presented with the Society’s highest award: the Fred Conrad Koch Medal.

John A. Cidlowski

Citation for the 2010 Ernst Oppenheimer Award of The Endocrine Society for Professor Wiebke Arlt

Wiebke Arlt is quite simply an outstanding Clinical Investigator. She received her training with Bruno Allolio in Wurzburg, Germany, Walter Miller at UCSF, USA and latterly Paul Stewart in Birmingham, UK where she now leads an independent research group of International Excellence, largely funded by the UK Medical Research Council (MRC).

Wiebke got “hooked” on Endocrinology as a medical student at the University of Cologne and undertook an MD degree on the adrenotoxic properties of suramin, a drug routinely used in the treatment of sleeping sickness, and investigated its effects on adrenocortical carcinoma. In 1990, as a final year student supported by WHO, she spent several months in Uganda investigating whether suramin treatment affected adrenal function in patients infected with sleeping sickness. Her MD thesis was obtained in 1993 and marked as outstanding (“summa cum laude”).

Having completed her basic medical training, she joined the group of Professor Bruno Allolio at the University of Wurzburg, Germany, to undertake specialist training in Endocrinology. Her initiative and motivation to pursue a research career was evident and she systematically explored the significance of adrenal androgens, namely dehydroepiandrosterone (DHEA). At that time, the significance of DHEA was unknown but in several highly cited landmark publications from 1998 to 2001 she documented the role of DHEA as a crucial sex steroid precursor, and, in a randomized controlled clinical trial published in NEJM, the beneficial effects of DHEA replacement in women with adrenal insufficiency.

From 1998 to 2000 she spent 2 years in the Molecular Endocrinology Research Group of Professor Walter Miller at the University of California in San Francisco, expanding her expertise in molecular and cellular endocrinology and focussing on the regulation of DHEA biosynthesis, namely the role of the enzyme P450c17. This time yielded several highly cited publications, including papers in Endocrinology and Journal of Biological Chemistry. Most importantly, this time provided Wiebke with the laboratory skills and mindset for discoveries to come.

Wiebke joined the Endocrine Group at the University of Birmingham, initially as a prestigious Heisenberg Senior Research Fellow and from 2004 onwards supported by an MRC Senior Research Fellowship, the highest award bestowed upon a Clinician Scientist in the UK. She rapidly established a highly productive group that has described the molecular and clinical basis for new forms of congenital adrenal hyperplasia. A major success was the identification of the first human P450 oxidoreductase mutations published in the Lancet and Nature Genetics. She subsequently worked on genotype-phenotype correlations in this fascinating new variant of congenital adrenal hyperplasia and, in a simply beautiful set of experiments confirmed an alternative androgen pathway in human androgen biosynthesis as the explanation for the puzzling phenotype in this disorder-severe female virilisation despite low circulating androgens. Many clinical scientists are humbled to discover a single disease – not deterred Wiebke’s productivity continued and reached new heights in 2009 with the discovery of another monogenic form of hyperandrogenism related to defective DHEA sulphation, again published in NEJM.

Wiebke is a true translational researcher who is committed to improve the health and wealth of her patients. She is an outstanding clinician who has already developed International standards for the care of patients with adrenal disease, hyperandrogenism, congenital adrenal hyperplasia, disordered sex development and importantly the devastating disease adrenocortical cancer. Here she is developing urinary steroid gas chromatography/mass spectrometry analysis as a biomarker tool for diagnosing and monitoring patients with a variety of adrenal tumours (incidentalomas, Cushings and Conns, Carcinoma). Other translational outcomes continue to be ongoing work on DHEA replacement therapy that now focuses on the beneficial immune effects and a vital leadership role in a Multicentre clinical trial to improve outcome of patients with adrenocortical cancer (www.firm-act.org/uk) and active roles in European research networks focussing on adrenal tumours (www.ensat.org) and disordered sexual differentiation (www.eurodsd.eu). Her leadership, motivation and mentorship has greatly facilitated the training of young researchers under her wing, supporting fellows from Spain, Greece, France, Netherlands, Germany, Ireland and USA, thereby promoting European and International collaboration.

With these advances have already come many accolades, prizes and plenary lectures at major meetings, reflecting, in part, her outstanding ability to communicate and disseminate her research findings. Wiebke Arlt is truly an International Endocrinologist of excellence and a most worthy recipient of the Ernst Oppenheimer Award.

Paul M. Stewart

Citation for the 2010 Robert H. Williams Distinguished Leadership Award of The Endocrine Society to Dr. Bert W. O'Malley

Dr. Bert O'Malley was born in Pittsburgh, graduated from the University of Pittsburgh and received the M.D. degree from the University of Pittsburgh School of Medicine. He subsequently did his clinical training in Internal Medicine under Dr. E.A. Stead at Duke University Medical Center.

It was his move to the NIH in the mid 1960s and his introduction by Stan Korenman and to the chick oviduct model that laid the foundation for his seminal work that defined the molecular mechanism(s) underlying the actions of steroidal hormones. During his four year tenure at the National Cancer Institute, he not only performed cutting edge research but served also as Molecular Biology Section Head at NCI; emerging as a key opinion leader in a very new field. He accepted his first academic position as Professor of Ob-Gyn at Vanderbilt Medical School where he established the first NICHD-supported Reproductive Biology Center. He populated this Center with an outstanding group of faculty and fellows who, spurred on by Bert and his indomitable enthusiasm and drive, played a dominant role in the emergence of the field of molecular endocrinology as we know it today.

After four years at Vanderbilt he moved to Baylor College of Medicine as the Chair of a new department called “Cell Biology” where, over the course of the next 30 years, he built one of the finest basic science departments in the country. That department was the first of a new generation of departments that combined the merging disciplines of cell structure, molecular biology, regulatory biology, and developmental biology into a unified Department of Molecular and Cellular Biology. While it has been a major center of learning in all of those fields, it is undeniably the world’s premier center for the study of hormone action, attracting trainees of the highest caliber from all over the world. Many of those trainees now hold leadership positions in academics, the private sector and in government both here and abroad. In these days when classical departmental structures are under pressure, there are few who would deny that the multidisciplinary department established by Dr. O'Malley was visionary and will endure.

His laboratory has been a leader in uncovering the mode of action of the female sex steroids progesterone and estrogen. Using the chick oviduct system originally, he uncovered the pathway for steroid hormone action and defined the mechanism by which steroid receptors act at the level of DNA to bind coactivators, remodel chromatin, recruit general transcription factors to the promoter, and stimulate the initiation of gene expression and mRNA processing and accumulation. This work led to our molecular understanding of how tissue-selective modulators and therapeutic hormonal antagonists work. His discoveries have had major importance to the fields of endocrinology, reproduction, genetic disease, and endocrine cancers of the breast and prostate. Not many scientists in any discipline have had such a prolonged and pivotal impact on their respective fields.

Few individuals in the history of endocrinology have provided the leadership and impact that Bert has brought. His sustained research leadership has resulted in over 700 peer-reviewed publications and 22 patents. His research continues unabated; just last year in 2009 he published twenty research articles. This body of work, together with his insatiable scientific curiosity, legendary work ethic and his enthusiastic acknowledgement of scientific excellence, have served as benchmarks and motivators for trainees and colleagues alike.

Having mentored over 300 students, fellows and faculty, he stands as a celebrated leader who has enriched our field through his research, commitment to education and dedication to faculty development. At Baylor College of Medicine he is a noted teacher and has been a major force in shaping its rise to prominence. His outstanding service to The Endocrine Society includes Council membership, chair of multiple committees, and President. He received the Oppenheimer and Koch awards and, while president, launched the journal Molecular Endocrinology. In national service, he has served as Chair of Endocrine and ACS Study Sections, popularized the Hormone Action Gordon Conferences, and organized over 30 national and international meetings in molecular endocrinology. Bert was the first NICHD Center Director in the US, initiating a new era in the Centers Programs that exists across the country to this day. He initiated and currently serves as the P.I. of the very successful Nuclear Receptor Signaling Atlas established by the NIDDK. He is a member and ex-chair of Section 42 of the National Academy of Sciences; has and holds memberships in other major societies, including the Institute of Medicine. Bert has received numerous major awards for his outstanding work and leadership in Endocrinology, culminating in last year’s National Medal of Science, our nation’s highest award in science.

The leadership record of Bert O'Malley is without peer, and thus he is a most deserving recipient of the 2010 Robert H. Williams Distinguished Leadership Award.

Donald P. McDonnell

Citation for the 2010 Edwin B. Astwood Award Lecture of The Endocrine Society for Dr. Myles Brown

Myles Brown was raised in Bethesda, Maryland where as a high school student he received his first introduction to medical research with the late George Khoury working at the NIH on the transcriptional program of the DNA tumor virus SV40. Dr. Brown received his undergraduate degree in biology from Yale in 1978 and his M.D. from Johns Hopkins in 1982. He completed house staff training in Internal Medicine in the Research Residency Program at the Brigham and Women’s Hospital under the guidance of David Livingston at the Dana-Farber Cancer Institute. While in the Livingston lab he studied the role of the SV40 T-antigens in transformation and in addition developed one of the first recombinant systems for regulated gene expression in mammalian cells using the bacterial lac repressor.

Following his Internal Medicine training Dr. Brown completed subspecialty training in Medical Oncology at the Dana-Farber Cancer Institute where his experience with the endocrine treatment of breast cancer let to his interest in the mechanism of transcriptional control by steroid hormones. This led to a post-doctoral fellowship in Phil Sharp’s lab at MIT where using the recently developed electrophoretic mobility shift assay he demonstrated the existence of multiple ligand-dependent complexes of the estrogen receptor (ER) with DNA.

Dr. Brown moved back to a faculty position at the Dana-Farber Cancer Institute and Harvard Medical School in 1990 where he established his own lab to study the role of steroid hormones and their receptors in cancer. He is currently Professor of Medicine and Chief of the Division of Molecular and Cellular Oncology. Dr. Brown’s lab has made a number of fundamental contributions to the understanding of the molecular mechanisms underlying steroid hormone action.

The first of his seminal discoveries was the central role played by coactivators in hormone action. In the early 1990’s a critical question in the steroid receptor field was how ligand binding led to increased transcriptional activity. Dr. Brown postulated the existence of transcriptional regulatory molecules that interact with the receptors in the presence of activating ligands but not antagonists. In 1994 he reported, in Science, the discovery of proteins whose interaction with estrogen receptor was dependent on agonist ligands and prevented by antagonists such as tamoxifen. These presaged the coactivator concept that is now widely accepted.

Dr. Brown’s second major discovery came in 2000. By then, the coactivator concept that he pioneered was widely accepted. The dogma was that these molecules bound stably to receptors in the presence of ligand. Dr. Brown discovered that even in the constant presence of ligand, coactivators cycle on and off the receptors. These findings, published in Cell, are now part of the accepted model of hormone action.

The next important contribution coming from the Brown lab involved the role of coregulators in defining the tissue specificity of selective estrogen receptor modulators or SERMs. Tamoxifen, a drug used widely in the treatment of ER+ breast cancer, was known to exhibit tissue selectivity in its action. While it acted as an ER antagonist in the breast, it manifested agonist activity in other tissues including the uterus. This agonist activity in the uterus was responsible for one of the important side-effects of tamoxifen therapy, namely endometrial hyperplasia and cancer. A molecular understanding for the tissue-selecitive of SERMs was lacking however. In a paper published in Science in 2002, Dr. Brown’s lab demonstrated a role for differential coactivator recruitment in the tissue selectiveiy of SERMs.

Dr. Brown’s most recent innovation has been the elucidation of principles of hormone receptor interactions with the genome. In a landmark series of papers in Cell, Nature Genetics, and Molecular Cell, he made the striking observation that steroid receptors bind to thousands of genomic sites far from the start sites of genes. He showed that a significant proportion of these sites are cell-type specific and that in breast and prostate cancer cells this involves the function of pioneer Forkhead transcription factors.

Myles Brown’s remarkable body of work has bridged the worlds of Endocrinology and Oncology, forming the basis for much of our current understanding of the mechanism of steroid hormone action as well as cancer therapies that target steroid hormone receptors. He has also been an outstanding mentor to a large number of very successful trainees. These contributions have been recognized by election to the American Society for Clinical Investigation, the American Association of Physicians, and by the NAMS/Wyeth Pharmaceuticals SERM Research Award. The Endocrine Society is proud to recognize Myles Brown’s accomplishments with the 2010 Edwin B. Astwood Award Lecture.

Mitchell A. Lazar

Citation for the 2010 Clinical Investigator Award Lecture of The Endocrine Society to Dr. Sundeep Khosla

Sundeep Khosla is the Dr. Francis Chucker and Nathan Landow Research Professor and a Distinguished Investigator of the College of Medicine, Mayo Clinic. He received his A.B. degree (summa cum laude) from Harvard College and his M.D. (cum laude) from Harvard Medical School. He did his medical residency and endocrine fellowship at the Massachusetts General Hospital, where he trained in the laboratory of Dr. Henry Kronenberg. In 1988, he joined the faculty of Mayo Clinic and, subsequently, has published over 270 papers spanning the spectrum of basic cell and molecular biology, use of genetically-altered mouse models, intensive human metabolic investigations, and population-based studies on age-related bone loss and fractures.

Throughout his career, Sundeep’s research has had continuous NIH funding. He has been Chair of the NIH Skeletal Biology, Development, and Disease Study Section and currently serves on the National Advisory Council of the NIA. He is President-Elect of the American Society for Bone and Mineral Research (ASBMR), Associate Editor for the Journal of Bone and Mineral Research and a member of several editorial boards, including the Journal of Clinical Investigation. He has been elected to Phi Beta Kappa, the American Society for Clinical Investigation and the Association of American Physicians. He has received the Frederic C. Bartter Award for outstanding clinical investigation from the ASBMR and the Innovation Award in osteoporosis research from the National Osteoporosis Foundation.

The primary focus of Sundeep’s research has been a comprehensive assessment of all aspects of osteoporosis and, in these studies, he has been a key member of the Mayo group that included Joe Melton and me. In a population-based sample, he demonstrated that the principal cause of bone loss in elderly men was a substantial decrease in serum bioavailable estrogen (Bio-E) due to age-related increases in binding and sequestration of E by sex hormone-binding globulin. This was extended by an intensive metabolic study in older men in which endogenous productions of E and testosterone (T) were suppressed by GnRH administration and then were replaced factorially. This demonstrated that E, but not T, was the dominant regulator of bone resorption, whereas both steroids were regulators of bone formation.

In other studies, he showed that E-deficiency enhanced early postmenopausal bone loss mainly by withdrawal of its direct effects on bone cells whereas in elderly women it enhanced bone loss mainly by impairing calcium conservation by the gut and kidney, leading to secondary hyperparathyroidism. In a series of population-based studies, Sundeep and his colleagues have defined the natural history of bone loss and age-related fractures in women and men and identified important associated risk-factors. More recently, using central quantitative CT and high resolution peripheral QCT, he has assessed the pattern of trabecular and cortical bone loss with aging and employed finite element analysis to quantify true bone strength.

Sundeep has made extensive clinical and basic studies to define direct effects of E on bone cells as well as indirect effects mediated by E-regulation of bone resorbing cytokines. Using flow-cytometry of marrow cells from postmenopausal women and cultured human cell lines, he showed E both suppressed differentiation of osteoclast precursors and inhibited the action of mature osteoclasts, in part by increasing production of osteoprotegerin and decreasing production of RANK ligand. He also showed that treating early postmenopausal women with specific blockers of TNF-α and interleukin-1 action led to a reduction in bone resorption. He used genetically-modified mice with deletion of the steroid receptor coactivators-1 and −2 to define their role in E-action on bone and used mice with E receptor mutations in the DNA-binding domain to define components involved in E-action in the non-classical pathway. He also demonstrated that osteoblast lineage cells circulate in the humans and increase with pubertal growth or after fractures. This novel observation has opened up an exciting new area of research on the potential role of these cells as heretofore unsuspected facilitators of the bone remodeling process. Sundeep and colleagues also have demonstrated that circulating cells with markers for both the osteoblast and endothelial lineages were increased in subjects with calcific coronary artery disease as compared with normal controls.

Sundeep Khosla has had a remarkable career as a clinical investigator of bone and mineral disorders. He has attempted to answer fundamental questions on the pathophysiology of osteoporosis and the basic biology of bone cells by combining multiple basic and clinical investigative approaches, thereby achieving an overall synthesis that would not have been otherwise possible. Thus, his selection for the 2010 Clinical Investigator Award Lecture of the Endocrine Society is most appropriate.

B. Lawrence Riggs

Citation for the 2010 Gerald D. Aurbach Award Lecture of The Endocrine Society to Dr. Barbara B. Kahn

Barbara B. Kahn, M.D. is Chief of the Division of Endocrinology, Diabetes and Metabolism at Beth Israel Deaconess Medical Center (BIDMC) and the George Richards Minot Professor of Medicine at Harvard Medical School. She is a world-renowned investigator in the area of obesity and type 2 diabetes. Her lab investigates the molecular physiology of insulin resistance and the mechanisms underlying the regulation of food intake and energy balance.

Dr. Kahn received both BA and MD degrees from Stanford University and an MS in Health and Medical Sciences from the University of California, Berkeley. After completing training in internal medicine at the University of California, Davis Medical Center, Dr. Kahn began her career in molecular research as a Fellow at the National Institutes of Health where she studied the cell biology and molecular physiology of insulin-stimulated glucose transport. She joined BIDMC in 1986 and served as Chief of the Diabetes Unit from 1990 to 2000 before assuming her current position.

Dr. Kahn’s research has had a major impact on understanding the molecular mechanisms underlying type 2 diabetes and the cellular and physiologic processes that render obesity a major risk factor for type 2 diabetes. She was one of the first investigators to establish the concept of the adipocyte as an endocrine organ. Through her novel mouse models with tissue-specific alterations in Glut4 glucose transporter expression, she developed the concept of “inter-tissue communication” in the pathogenesis of insulin resistance and diabetes before the idea was popular. Her discovery that retinol-binding protein 4 (RBP4) is a novel adipocyte-secreted protein that is linked to insulin resistance and risk for type-2 diabetes and cardiovascular disease, has uncovered an important new drug-target for metabolic syndrome. Dr. Kahn has “translated” her discoveries to humans and stimulated clinical studies world-wide to determine whether RBP4 could be a new biomarker for type-2 diabetes.

Dr. Kahn’s lab also made the seminal discovery that regulation of the AMP-kinase pathway is critical for leptin action on both fatty acid oxidation in muscle and food intake and body weight control via the hypothalamus. Her recent studies showed a crucial role for hypothalamic AMP-kinase in the counterregulatory response to hypoglycemia.

Dr. Kahn has received numerous awards including the Eli Lilly Award for Outstanding Scientific Achievement and the Mosenthal Award for outstanding contributions in the field of diabetes, both from the American Diabetes Association; the prestigious Jacobaeus Prize from the Novo Nordisk Foundation and the Karolinska Institute in Stockholm; and the Charles H. Best Award from the University of Toronto. Dr. Kahn is an elected member of the Institute of Medicine of the National Academy of Sciences, the American Society for Clinical Investigation, and the Association of American Physicians and she is a Fellow of the American Association for the Advancement of Science. She has served on Endocrine Society and American Diabetes Association committees and on the Diabetes and Obesity Committees of the American Heart Association. Dr. Kahn is a dedicated mentor in both research and clinical diabetes and endocrinology. Many of her former trainees have successful independent research careers throughout the world.

In summary, Dr. Kahn is an innovative world-leader in diabetes and metabolism research. Her seminal discoveries and their clinical translation are leading to development of exciting new strategies to prevent and treat obesity and type-2 diabetes.

Christin Carter-Su

Citation for the 2010 Sidney H. Ingbar Distinguished Service Award of The Endocrine Society to Dr. Martin I. Surks

The Endocrine Society is pleased to announce that the 2010 Sidney H. Ingbar Distinguished Service Award is being given to Dr. Martin Surks in recognition of distinguished service in the field of endocrinology. Dr. Surks graduated from Columbia College (1956) and from New York University School of Medicine (1960). He took his Internal Medicine Training at Montefiore Hospital (1960-1962) and the Bronx VA (1962–1963). His Endocrine Fellowship was at Montefiore Hospital under the tutelage of Dr. Jack Oppenheimer (1963–1964). He is a Professor, Department of Medicine and Pathology, and Program Director, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, NY (1997–current) and former Chief, Division of Endocrinology and Metabolism, Montefiore Medical Center, Bronx, New York (1976–1997).

Martin Surks has an extraordinary history of service in multiple areas of endocrinology regarding patients, students, colleagues, education and scientific organizations. He was elected for membership in the American Society of Clinical Investigation (1972). He has served on NIH study sections (ad hoc 1976–1981; member 1981–1985), and on editorial boards (Endocrinology 1974–1978; Journal of Clinical Endocrinology and Metabolism 1991–1994; Thyroid 2001-present; American Journal of Physiology: Endocrinology and Metabolism 1982–1985); as Associate Editor, Endocrinology 1986–1987, as chair of the endocrinology subspecialty ABIM committee (1991–1995) and as President (1999–2000) and Secretary/COO (1993–1998) of the American Thyroid Association. He is a national leader within APDEM serving on Council (1995–1997) and as President (1997–1999). Dr. Surks has been a Director, American Board of Internal Medicine (1991–1995), and Chair, Subspecialty Committee on Endocrinology, Diabetes & Metabolism (1991–1995). He was on the Council (1997–2001) and served as Treasurer (2000–2001) and President (1997–1999) of the Association of Program Directors of Endocrinology and Metabolism. He has served a consultant to the Institute of Medicine (1998) and to the World Health Organization (1998). He is a Master in the American College of Physicians (2002) and was given the Distinguished Service Award (2002) by the American Thyroid Association.

Dr. Surks has served as Program Director, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, NY (1997–current) and has trained over 60 Endocrine Fellows who have had productive careers and have made significant contributions to endocrinology.

Dr. Surks has also made significant contributions to the Endocrine Society. He has served on the follow committees: Manpower Liaison, 1983–1986, Advisory Committee on Scientific Programs, 1985–1987, Central Committee of International Society of Endocrinology, 1995–2000, Finance Committee, 1995–1998; Chairman, 1998–2002, Editorial Board, Endocrine Self-Assessment Program (ESAP), 1997–2002, Endocrine Self-Assessment Program, Editor-in-Chief, 2002–2007, Strategic Plan Implementation Committee, 2002–2003, and Investment Advisory Task Force, 1998–2008.

Further, Dr. Surks has published extensively in the area of thyroid disease. Over his distinguished research career has increased our understanding and has made seminal observations in the areas of thyroid hormone metabolism and receptor mediated action and has analyzed factors that affect thyroid hormone levels and their measurement. He recently has been studying TSH and thyroid hormone measurements in elderly patients and has generated data that has changed our clinical approach to these patients. He also served as Chair of the Guideline Committee on Subclinical Thyroid Disease (JAMA, 2004; 291: 228; JAMA 2004; 291: 239).

Given these outstanding contributions it is not surprising that Dr. Surks has been a frequent invited lecturer for national and international symposium or conferences and has also had over 150 scientific presentations at meetings.

In addition to these important contributions to endocrinology in the areas of service, education, clinical care, research and administration, Dr. Surks is internationally respected for his intelligence, eagerness to help students and colleagues, dedication, compassion and amiable demeanor. His accomplishments, in cooperation with his personal attributes, make him an outstanding recipient of the Sydney H. Ingbar Distinguished Service Award.

Kenneth D. Burman

Citation for the 2010 Roy O. Greep Award Lecture of The Endocrine Society to Dr. Martin M. Matzuk

Martin M. Matzuk, M.D., Ph.D. is the Endocrine Society’s 2010 Roy O. Greep Award Lecturer, presented in recognition of his innovative and novel contributions to our understanding of the hormonal and TGFβ superfamily signaling pathways in the hypothalamic-pituitary-gonadal axis.

Dr. Matzuk received his B.A. with Honors in Biology from the University of Chicago in 1982. Undergraduate research with the late Dr. Nicholas R. Cozzarelli resulted in several excellent publications on the characterization of topisomerases and recombination enzymes. Marty received his M.D./Ph.D. from Washington University School of Medicine in 1989. His thesis work was entitled “Structure-function studies of the glycoprotein hormones using mutagenesis, chimeric genes, and gene-transfer” under the supervision of Dr. Irving Boime in the Department of Pharmacology. At that time, Dr. Matzuk became fascinated with endocrinology and gave his first presentation at the Endocrine Society’s 70th Annual Meeting. Dr. Matzuk underwent residency training at the University of Pennsylvania and Baylor College of Medicine and is board-certified in Clinical Pathology. In addition to his clinical training, Dr. Matzuk was a Lalor Foundation and NICHD-supported postdoctoral fellow in the laboratory of Dr. Allan Bradley at Baylor College of Medicine. He then joined the permanent faculty at Baylor College of Medicine in 1993, and has occupied the Stuart A. Wallace Chair and Professorship in the Departments of Pathology, Molecular and Cellular Biology, and Molecular and Human Genetics at Baylor for more than a decade.

At all stages of his career, Dr. Matzuk has been highly successful. During his Ph.D. studies, he was intimately involved in the production of all 4 human glycoprotein hormones from Chinese Hamster Ovary cells, and his human glycoprotein hormone α subunit minigene is used for the production of recombinant FSH for the clinic. During his postdoctoral studies at Baylor College of Medicine, he operated at the forefront of gene-knockout technology in mice to study the hypothalamic-pituitary-gonadal axis. He produced mice with a null mutation in the inhibin α gene and showed that these mice develop ovarian, testicular, and adrenal cancers at an early age. These studies were the first to identify an endocrine peptide hormone, inhibin, as a secreted tumor suppressor (published as an article in Nature in 1992). In his own laboratory, Dr. Matzuk continued to study the inhibin α knockout mice, and, in the process, identified the major hormonal and cell cycle modifiers of the cancer phenotype. Dr. Matzuk also investigated the essential functions of additional molecular components of the TGFβ superfamily signaling pathways as well as other regulators of reproductive function. His laboratory was the first to show that activins signal specifically through activin receptor type 2 to regulate FSH synthesis, that FSH was required for female but not male fertility, and that oxytocin was required for milk ejection but not parturition.

In the late 1990’s, Dr. Matzuk’s laboratory began using multiple strategies to identify and discover novel gonadal genes with unknown functions. Two oocyte-expressed TGFβ family members that Marty studied were growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15). Whereas mammalian oocytes were initially thought to be merely passengers rather than drivers in ovarian development, Dr. Matzuk demonstrated that GDF9 and BMP15 regulate granulosa cell function at several stages of ovarian folliculogenesis. These initial insights with GDF9 and BMP15 heralded an entire new field of study that uncovered the existence of a ‘germ cell-somatic cell’ dialog that orchestrates the many steps in folliculogenesis.

Dr. Matzuk’s contributions to male reproduction have led to the discovery of key genes involved in multiple steps of spermatogenesis. He identified the first essential mammalian germ cell intercellular bridge protein, TEX14. He also demonstrated that GASZ is an essential protein in piRNA synthesis. This work led to the development of novel diagnostic screening strategies for infertile men.

Finally, Dr. Matzuk is an outstanding colleague. He has been extremely generous with his mouse knockout models, depositing them at the Jackson Laboratory and freely distributing them to investigators around the world. Marty is an important senior member of Baylor’s Center for Reproductive Biology and educator of students and postdoctoral fellows. He participated on multiple national peer review panels and chaired the NIH CMIR study section. His research accomplishments include an impressive publication record of over 250 papers in top tier journals, with over 50 in Endocrine Society journals. For his scientific contributions, Marty received multiple awards including the 1996 Richard E. Weitzman Memorial Award. It is the Endocrine Society’s honor to have Dr. Matzuk as the 2010 Roy O. Greep Awardee and Lecturer.

Bert W. O’Malley

Citation for the 2010 Distinguished Educator Award of The Endocrine Society to Dr. Janet A. Schlechte

The Endocrine Society is proud to honor Dr. Janet Schlechte with the Distinguished Educator Award for 2010 in recognition of her exceptional achievements as an educator in the discipline of endocrinology and metabolism.

Dr. Schlechte graduated from the University of Nebraska and received a Master’s degree at the University of California before receiving her M.D. with Distinction from The University of Nebraska (1975). She completed an Internship and Residency in Internal Medicine at the University of Iowa, and then remained in Iowa City as a Fellow in Endocrinology. She joined the faculty of the Endocrine division at the University of Iowa in 1982.

Today, Dr. Schlechte is Professor of Endocrinology and Metabolism and Director of the Endocrine Diagnostic Laboratory. In recognition of her contributions to the educational, clinical and research missions of the institution she was awarded the College of Medicine Faculty Service Award and the Ernest O. Theilen Clinical Teaching and Service Award.

Janet has been actively involved in the teaching of medical students, residents and Endocrine fellows throughout her career. She has taught case-based learning to first year medical students and has served as a preceptor for second year students learning the basics of the history and physical examination. For many years, she directed and participated in the Endocrine section of the Foundations of Clinical Practice course for pre-clinical students, and was recognized by the students as an outstanding educator. Her lectures and educational materials have been used as models by other teaching faculty.

As Director of Postgraduate Programs, Janet supervised the training of over 400 medicine residents, and chaired the Advisory Committee, which oversees house staff education at the University of Iowa. She developed a Board Review course for residents in Internal Medicine and taught the Endocrine section of that course for 8 years. She also was responsible for the growth of a curriculum designed to enhance the outpatient experience for residents.

Janet’s clinical and research interests are in the biology of prolactin secreting pituitary tumors. She has supervised research programs for 10 endocrine fellows and/or junior faculty. While Director of the General Clinical Research Center at the University of Iowa, she developed an educational program entitled Principles of Clinical Research for fellows and junior faculty interested in patient oriented research. This program has now become part of an institution wide program for individuals pursuing careers in clinical investigation.

Janet’s clinical and teaching skills are well recognized outside the University of Iowa. Notably, she has given over 200 regional, national and international invited lectures, and has authored 70 peer reviewed manuscripts and 18 chapters.

Nationally, Dr. Schlechte has served on the American College of Physicians Postgraduate Education Committee and has been regularly invited to present the Update in Endocrinology at the national meeting of the American College of Physicians. For 6 years she served on the American Board of Internal Medicine Subspecialty Board of Endocrinology, Diabetes and Metabolism and was Chair of that Board from 2003–2007. She was also a member of the NIH Clinical Research Review Committee from 2002–2007.

Janet’s service to the Endocrine Society has been extensive, including membership on Council (1995–1998), the Manpower Liaison Committee (1985–1989, Chair 1989), Nominating Committee (2004–2005), Clinical Endocrinology Initiatives Committee (Chair) (1989–1991), Finance Committee (1999–2001), Annual Meeting Steering Committee (2002), and the Direction V Task Force. She recently completed 5 years as an Associate Editor for the Journal of Clinical Endocrinology and Metabolism.

Janet’s most important contributions to the Society have been in the educational arena. She was Clinical Chair for the Annual Meetings in 1993, 1994, and 2000. It was at the 1993 meeting that she initiated the Meet the Professor sessions which have become such a popular and important component of the clinical program at ENDO. In 2005 she was appointed Chair of the Meetings and Educational Programs committee now known as the Scientific and Educational Programs committee. Dr. Schlechte was co-chair of the 2005 ENDO Task Force, which created new sessions and broadened the scope of the Society’s most important educational endeavor. She directed a task force, which redesigned the Society’s Clinical Endocrinology Update, and has developed and presented new educational programs for endocrinologists participating in maintenance of certification.

Dr. Janet Schlechte’s commitment to education and her contributions to the Endocrine Society and our field are exemplary. She is truly deserving of this award.

Carol A. Lange

Citation for the 2010 Distinguished Physician Award of The Endocrine Society to Dr. Hossein Gharib

Hossein Gharib was born in Tehran, Iran, in 1940 where his early role model was his father, Dr. Mohammad Gharib, Professor and Chair of Pediatrics at Tehran University Medical School, generally regarded as the “Father of Pediatrics in Iran.” He received his B.S. degree from Ohio State University, his M.D. degree from University of Michigan Medical School, and completed his internal medicine residency and endocrinology fellowship at Mayo Clinic (1967–1972). He was immediately recruited as a consultant for the Division of Endocrinology and Metabolism and was promoted to the rank of Professor of Medicine at College of Medicine, Mayo Clinic, in 1994.

Hossein is an internationally known authority on thyroid disorders. During an active investigative career spanning almost four decades, he has published more than 100 peer-reviewed original papers, over 50 review articles, 10 Guidelines for medical practice, 30 textbook chapters, and presented approximately 80 abstracts at national and international meetings. Dr. Gharib co-edited the first Evidence-Based Endocrinology Textbook, initially published in 2003, and the second edition in 2008. He has also co-edited EndoText, a free online endocrine textbook. He has lectured at more than 250 regional, national, and international endocrine events. His extensive bibliography does justice to a full-time academician, and yet for nearly 40 years, he has been designated as a full-time clinician with no time formally protected for academic pursuits. This is the result of a tireless working schedule, including nights, evenings, and weekends, as well as through his mentorship of bright residents and fellows infused with his enthusiasm for new knowledge on thyroid matters.

Hossein has made important contributions to clinical practice. In 1971, he confirmed the utility of the TSH radioimmunoassay in thyroid practice (Ann Intern Med), and developed the first radioimmunoassay to measure T3 in human serum (JCEM, 1970–1971). Later studies emphasized the importance of thyroid nodules in clinical practice (NEJM, 1985); the technique, accuracy, and impact of thyroid fine-needle aspiration biopsy in the management of nodules (Acta Cytol, 1987; Ann Intern Med, 1993); and the limitations of cytologic diagnosis (Ann Inter Med, 1984). His landmark paper on thyroxine therapy for thyroid nodules initially sparked much controversy, but eventually changed our practice (NEJM, 1987). Later, a series of reports illustrated changing concepts in the diagnosis of medullary thyroid carcinoma (Ann Surg, 1990; Surg, 1994; JCEM, 1994 & 1995; AJM, 1997), including a description of new paradigms for genetic testing in MTC syndromes (Ann Intern Med, 1995). He was one of the first to draw attention to the prevalence and management of incidentally discovered thyroid nodules (Arch Intern Med, 1995; Ann Intern Med, 1997, 2005).

Hossein is a gifted teacher and a quintessential clinician. He has been actively involved in undergraduate and graduate medical education for 4 decades, and is currently the Dean of the “Endocrine University.” This annual 6-day course, sponsored by the American College of Endocrinology and offered at Mayo Clinic Rochester campus, was attended in 2009 by 238 fellows representing 130 endocrine programs in the United States; he was also an invited Trainee Day Lecturer at Endo ‘08 & ‘09. He is admired for his integrity, caring approach to patients, and formidable fund of general medical knowledge. Hossein is among a handful of senior endocrinologists who have been honored with a Mastership from both the American College of Physicians (MACP) and the American College of Endocrinology (MACE). His other honors include the American Thyroid Association’s prestigious Paul Starr Award (2002), the Laureate Award from the Department of Medicine at Mayo Clinic (2004), the 2006 International Clinician Award of the Italian Endocrine Society (AME), and the 2009 SBEM (Sociedade Brasileira de Endocrinologia e Metabologia) award for contributions to clinical endocrinology.

Hossein’s role as a leader in endocrinology is established and substantial. For example, he has served as program chair, co-chair, or member of 12 program committees for major national or international endocrine societies. He is held in high regard by his colleagues, having served as the President of the American Association of Clinical Endocrinologists (AACE) in 2002–2003 and the President of the American College of Endocrinology in 2008–2009. He has served on the editorial boards of Endocrine Practice (1995–2005) and JCEM (2003–2008), and is currently a member of the editorial boards of Thyroid, Acta Endocrinologica (Romania), and International Journal of Endocrinology.

In summary, Dr. Hossein Gharib, a warm, generous and humble person, a highly accomplished clinician and educator, and a long-time member of The Endocrine Society, is truly deserving of recognition as the Society’s 2010 recipient of the Distinguished Physician Award.

Ernest L. Mazzaferri

Citation for the 2010 Richard E. Weitzman Memorial Award of The Endocrine Society to Dr. Mark O. Goodarzi

Dr. Goodarzi completed undergraduate studies in Biochemical Sciences at Harvard University, and obtained his medical degree at the University of California San Francisco. He came to the University of California Los Angeles for internal medicine residency, after which he enrolled in UCLA’s Specialty Training and Research (STAR) program, which involved clinical fellowship in Endocrinology and simultaneous graduate studies towards a PhD in Human Genetics under the mentorship of Dr. Jerome Rotter. In 2004, Dr. Goodarzi was recruited to the Division of Endocrinology, Diabetes, and Metabolism at Cedars-Sinai Medical Center. Since 2007 he has served as Associate Director of the Division.

Dr. Goodarzi devotes his time to research in genetic epidemiology of common metabolic and hormonal disorders. His contributions have garnered numerous awards, including the Outstanding Investigator Award of the American Federation for Medical Research, Western Section. The two major lines of his research are genetics of insulin-related traits in Hispanic Americans and genetics of polycystic ovary syndrome (PCOS).

Dr. Goodarzi has focused on genetic investigation of insulin-related traits in Hispanic Americans because they have high rates of insulin resistance and type 2 diabetes, and therefore are an ideal population for study to better understand abnormalities in insulin action and metabolism. This line of research began with his dissertation work on the role of the lipoprotein lipase (LPL) gene in insulin resistance and atherosclerosis, which ultimately resulted in five publications in this area, establishing LPL as a gene for insulin resistance and the metabolic syndrome in Hispanics, and for other traits including lipid response to statin treatment. The importance of the LPL gene has been recently emphasized by genome wide association studies; Dr. Goodarzi’s work presaged the latest results.

Dr. Goodarzi was among the first to examine the metabolic clearance rate of insulin from a genetic perspective. His 2005 Diabetes paper was the first to report that insulin clearance is a highly heritable trait in Hispanics. In that study, he described association of variants in the adenosine monophosphate deaminase-1 (AMPD1) gene with variation in insulin clearance, leading him to hypothesize that adenine nucleotide metabolism genes/cellular energy genes are likely key genetic factors for insulin clearance. He has identified chromosomal regions that may harbor genes for insulin clearance, and is currently pursuing these loci.

In collaboration with Dr. Ricardo Azziz, Dr. Goodarzi has produced 15 original peer-reviewed publications in PCOS genetics. He brought modern genetic concepts to the field, including haplotype analysis and genotyping multiple variants to encompass (via linkage disequilibrium) variation across entire gene regions. Prior to Dr. Goodarzi’s entry into the field, most PCOS genetics papers analyzed only one variant per gene, resulting in inadequate genome coverage. Dr. Goodarzi’s contributions to the field have been recognized nationally by thought leaders in PCOS in the form of the Young Investigator Award of the Androgen Excess and PCOS Society, bestowed to Dr. Goodarzi for two years in a row.

Dr. Goodarzi’s work has suggested that PCOS may in part be determined by inherited heightened androgen sensitivity. A central feature of PCOS is androgen excess; however, up to a third of women have normal androgen levels. This suggested to Dr. Goodarzi that these women manifest symptoms of androgen excess because they are genetically predisposed to heightened androgen sensitivity. Testosterone is converted to dihydrotestosterone in target tissues by 5-alpha reductase type 1 and type 2, encoded by the genes SRD5A1 and SRD5A2. Dr. Goodarzi found that variants in both genes influence risk of PCOS and that variation in SRD5A1 also affected the amount of hirsutism present in affected women. Dr. Goodarzi also examined the androgen receptor, where prior work had produced conflicting results regarding the effect of the exon 1 CAG repeat. Dr. Goodarzi examined this variant in the largest number of PCOS subjects ever genotyped for this variant, and provided the most conclusive evidence that shorter CAG repeats (more active androgen receptors) do increase PCOS susceptibility. A novel genetic risk factor for PCOS identified by Dr. Goodarzi is SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha), which binds to androgen receptors and inhibits their action.

In addition to running a successful research program, Dr. Goodarzi is also a key educator at Cedars-Sinai Medical Center. He runs the core seminar series for the endocrine fellows. Dr. Goodarzi’s trainees appreciate his ability to convey complex endocrine and genetic concepts in a clear manner.

Recognizing his contributions of important knowledge in the pathophysiology and genetics of metabolic disease, this talented young investigator is highly deserving of the Endocrine Society’s Richard E. Weitzman Award.

Shlomo Melmed

Citation for The Endocrine Society & Pfizer, Inc. International Award For Excellence in Published Clinical Research in The Journal of Clinical Endocrinology & Metabolism in 2009

“Clinically Distinct Epigenetic Subgroups in Silver-Russell Syndrome: The Degree of H19 Hypomethylation Associates with Phenotype Severity and Genital and Skeletal Anomalies” Vol. 94, No. 2, p. 579–587. Authors: Sara Bruce, Katariina Hannula-Jouppi, Jari Peltonen, Juha Kere and Marita Lipsanen-Nyman. Department of Biosciences and Nutrition (S.B., J.K.), Karolinska Institutet, S-141 57 Huddinge, Sweden; Department of Medical Genetics (S.B., K.H.-J., J.K.), University of Helinski, 00014 Helinski, Finland; Folkhälsan Institute of Genetics (S.B., K.H.-J., J.K.), Biomedicum Helinski, 00014 Helinski, Finland; and Hospital for Children and Adolescents (J.P., M.L.-N.), University of Helinski, 00029 Helinski, Finland.

“Anti-Melanocortin-4 Receptor Autoantibodies in Obesity” Vol. 94, No. 3, p. 793–800. Authors: Jean-Christophe Peter, Akkiz Bekel, Anne-Catherine Lecourt, Géraldine Zipfel, Pierre Eftekhari, Maya Nesslinger, Matthias Breidert, Sylviane Muller, Laurence Kessler and Karl G. Hofbauer. Applied Pharmacology (J.-C.P., A.B., A.-C.L., G.Z., K.G.H.), Biozentrum, University of Basel, CH 4056 Basel, Switzerland; Centre National de la Recherche Scientifique, Unité Propre de Recherche 9021 (P.E., S.M.), Laboratoire d’Immunologie et Chimie Thérapeutiques. Institut de Biologie Moleculaire et Cellulaire, F 67000 Strasbourg, France; Forenap Therapeutic Discovery (P.E.), F 67000 Strasbourg, France; Medizinische Klinik I (M.N., M.B.), Stadtklinik Baden-Baden, D 76532 Baden-Baden, Germany; and Endocrinology, Nutritional Diseases (L.K.), Hopitaux Universitaires de Strasbourg, F 67000 Strasbourg, France.

“The Effects of Recombinant Human Leptin on Visceral Fat, Dyslipidemia, and Insulin Resistance in Patients with Human Immunodeficiency Virus-Associated Lipoatrophy and Hypoleptinemia” Vol. 94, No. 4, p. 1137–1144. Authors: Kathleen Mulligan, Hootan Khatami, Jean-Marc Schwarz, Giorgos K. Sakkas, Alex M. DePaoli, Viva W. Tai, Michael J. Wen, Grace A. Lee, Carl Grunfeld and Morris Schambelan. Department of Medicine, University of California, San Francisco (K.M., H.K., J.-M.S., G.K.S., V.W.T., M.J.W., G.A.L., C.G., M.S.), San Francisco, California 94143; San Francisco General Hospital (K.M., H.K., J.-M.S., G.K.S., V.W.T., M.J.W., M.S.), San Francisco, California 94110; Department of Basic Sciences, Touro University (J.-M.S.), Vallejo, California 94592; Amgen Inc. (A.M.D.), Thousand Oaks, California 91320; and San Francisco Veterans Affairs Medical Center (G.A.L., C.G.), San Francisco, California 94121.

“The Succinate Dehydrogenase Genetic Testing in a Large Prospective Series of Patients with Paragangliomas” Vol. 94, No. 8, p. 2817–2827. Authors: Nelly Burnichon, Vincent Rohmer, Laurence Amar, Philippe Herman, Sophie Leboulleux, Vincent Darrouzet, Patricia Niccoli, Dominique Gaillard, Gérard Chabrier, Frédéric Chabolle, Isabelle Coupier, Philippe Thieblot, Pierre Lecomte, Jérôme Bertherat, Nelly Wion-Barbot, Arnaud Murat, Annabelle Venisse, Pierre-François Plouin, Xavier Jeunemaitre, Anne-Paule Gimenez-Roqueplo for the PGL.NET network. Hôpital Européen Georges Pompidou (N.B., A.V., X.J., A.-P.G.-R.), Paris, France; INSERM, Unité 970 (N.B., L.A., P.-F.P., X.J., A.-P.G.-R.), Paris, France; Collège de France (N.B., L.A., P.-F.P., X.J., A.-P.G.-R.), Paris, France; Université Paris Descartes (N.B., L.A., P.-F.P., X.J., A.-P.G.-R.), Paris, France; Service d’Endocrinologie (V.R.), Centre Hospitalier Universitaire (CHU), Angers, France; Hôpital Européen Georges Pompidou s (L.A., P.-F.P.), Paris, France; Hôpital Lariboisière (P.H.), Paris, France; Institut Gustave Roussy (S.L.), Villejuif, France; Hôpital Pellegrin (V.D.), Talence, France; CHU de La Timone (P.N.), Marseille, France; Centre Hospitalier Régional Universitaire de Reims (D.G.), Reims, France; CHU de Strasbourg (G.C.), Strasbourg France; Hôpital Foch (F.C.), Suresnes, France; CHU de Montpellier (I.C.), Montpellier, France; CHU de Clermont-Ferrand (P.T.), Clermont-Ferrand, France; CHU de Tours (P.L.), Tours, France; Hôpital Cochin (J.B.), Paris, France; CHU Albert Michallon (N.W.-B.), Grenoble, France; and CHU de Nantes (A.M.), Nantes, France.

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