Mass spectrometry may help guide brain tumor surgery

Intraoperative mass spectrometry platform for image-guided surgery. Image courtesy of Brigham and Women’s Hospital (Boston).
Surgical resection of tumors often requires diagnostic information, currently obtained through pathologists’ painstaking and time-consuming microscopic examination of biopsies. Sandro Santagata et al. (pp. 11121–11126) used a technique called desorption electrospray ionization mass spectrometry (DESI-MS), rapidly performed in the operating room with minimal sample processing, to detect 2-HG, a metabolite found in human brain tumors with mutations in the IDH-1 and IDH-2 genes, which encode enzymes implicated in cell growth and differentiation. The authors used DESI-MS to distinguish human brain tumors with and without IDH mutations within minutes, and the metabolite to sharply delineate tumor margins and detect infiltrating tumor cells—capabilities thought to be crucial to optimal tumor resection and the surgery’s outcome. Using a mass spectrometer installed in an operating room at Brigham and Women’s Hospital, Boston, the authors measured 2-HG during surgery in biopsies from two patients with a brain tumor called oligoastrocytoma, hinting at the method’s potential for real-time diagnosis and removal of tumor cells that might be otherwise left behind. According to the authors, DESI-MS instruments, which can help characterize tumors more efficiently than histopathological reviews, could be installed in operating rooms at a fraction of the cost of intraoperative MRI machines, used to guide neurosurgical navigation. — P.N.
Well integrity and methane leakage

Bubbling due to impaired cementing in an unconventional gas well. Image courtesy of the Pennsylvania Department of Environmental Protection (Harrisburg, PA).
Elevated levels of methane in Pennsylvania aquifers near unconventional oil and gas wells, such as hydrofractured wells, have prompted an assessment of whether methane may be leaking from unconventional wells. Anthony Ingraffea et al. (pp. 10955–10960) examined compliance reports from more than 41,000 conventional and unconventional wells drilled in Pennsylvania between January 2000 and December 2012. The authors found that incidents of impairment of either a well’s casing or its cement seal occurred 6 times more often in unconventional shale gas wells than in conventional wells. Using a risk assessment approach, the authors found that unconventional wells drilled after 2009 carried a 1.57 times higher risk of cement or casing impairment than conventional wells drilled during the same time. The authors observed temporal trends in well impairment risk that may be due either to development of stringent inspection procedures or differences in well structural integrity stemming from well construction methods. Cumulative risk of impairment in all wells in northeastern Pennsylvania was 8.5 times greater than in the rest of the state. The results suggest that faults in well casings or concrete seals may constitute a pathway of methane migration into the atmosphere or into local groundwater, according to the authors. — P.G.
Evaluating the accuracy of strategic intelligence

Assessing the accuracy of strategic intelligence. Image courtesy of Defence Research and Development Canada (Ottawa).
Despite tens of billions of dollars spent on strategic intelligence every year in the United States, the forecasting accuracy of intelligence analysts remains largely unclear. David Mandel and Alan Barnes (pp. 10984–10989) used subject matter experts to analyze the quality of 1,514 forecasts encompassing nearly 6 years’ worth of intelligence reports from a division of the Canadian government’s strategic intelligence analysis unit, which provides assessments and trends to policymakers. The authors report that senior forecast analysts, generally defined as having more than 4 years of experience, produced 68% of the forecasts and were better than junior analysts, with 0–4 years of experience, at discriminating between the occurrence and nonoccurrence of events—an ability that was also correlated with the difficulty level of forecasts. Underconfidence, which emphasizes judgment over informational value in forecasts, was more commonly associated with difficult rather than easy forecasts and with more versus less policy-relevant forecasts. The authors recalibrated forecasts to reduce underconfidence, suggesting that postforecast corrective measures might improve the quality of intelligence reports distributed to consumers. According to the authors, the analysts aimed to maximize the informational content of forecasts while avoiding overstatement, providing a basis for cautious optimism about the accuracy of intelligence forecasts. — P.N.
Hundreds of species likely obscured by lichen’s name

Some species of Cora are found uniquely in subandine forests such as here, near Bogotá, Colombia.
The lichen-forming fungus Dictyonema glabratum is an ecologically important denizen of tropical mountainous and southern temperate scrublands and forests. The fungus, which thrives abundantly in symbiosis with photosynthetic partners in the endangered paramos ecosystems of South America, for example, was long considered a single taxonomic unit. After recently reclassifying the fungus as two separate genera—Cora and Corella—encompassing a total of 16 species, Robert Lücking et al. (pp. 11091–11096) used DNA barcoding and phylogenetic analysis, and found that D. glabratum is in fact composed of at least 126 morphologically distinct species, with noticeable differences in morphology and habitat preferences as well as a high degree of endemism. Further, the authors used grid maps of Central and South America and the Caribbean, across the main range of the fungus, and grid-based modeling, and found even greater predicted species richness for the fungus—up to 452 individual species hitherto obscured by a single name. Because the cyanobacterial partners of D. glabratum fix atmospheric nitrogen and the lichens act as biological fertilizers, the findings may have implications for species conservation and suggest that the Andean paramos might be a hotbed of evolution, according to the authors. — P.N.
Paradoxical thinking and conflict resolution
Strategies for conflict intervention often involve presenting information that destabilizes the beliefs of conflicting sides and inspires a change in perspective. However, such strategies can threaten societal beliefs, causing individuals to ignore new information and cling to established beliefs. Boaz Hameiri et al. (pp. 10996–11001) explored an alternative strategy that employs paradoxical thinking, in which individuals receive information that is consistent with their beliefs but presented in a way that makes the beliefs appear extreme or irrational. For 1 month, the authors showed videos to 161 Jewish Israeli participants that depicted a control scenario or a scenario suggesting that an end to the Palestinian conflict would jeopardize Jewish Israelis’ values of justice, morality, and unity. Individuals who viewed the videos designed to encourage paradoxical thinking reported feeling more willing to reevaluate their positions on the conflict, more willing to compromise, and less blameful of Palestinians for continuation of the conflict than individuals who had viewed videos of generic television commercials. Compared with the control group, the experimental group was also more likely to vote for peace-seeking parties in the 2013 Israeli general election and had maintained a greater willingness to compromise when surveyed a year later. According to the authors, the results suggest that paradoxical thinking may promote long term conflict resolution. — J.P.J.
Prion protein structure and pathogenesis

Normal brain tissue of deer (Left) and abnormal prion protein deposition (Right).
Neurodegenerative prion diseases in humans and animals are fatal, yet research suggests that susceptibility to infection by the causative agent—abnormally conformed prion proteins (PrPSc)—may be influenced by sequence variations in hosts’ normal, cellular prion protein (PrP). Rachel Angers et al. (pp. 11169–11174) studied the influence of variations at four locations on the gene encoding PrP on the pathogenesis of the prion diseases chronic wasting disease (CWD) and scrapie. The authors created transgenic mice that expressed deer, elk, or sheep PrP variants, infected the mice with either CWD or scrapie, and observed disease progression. The transgenic mice demonstrated that the deer PrPs may be susceptible to cross-species infection by scrapie, a disease caused by sheep PrPSc; elk are resistant to scrapie infection because of a single variation in the protein-coding sequence of the gene for PrP. Other variations in the sequence encoding four amino acids in the gene for PrP of sheep, elk, and deer yielded a variety of differences in infection resistance, incubation period, and disease severity. According to the authors, the results suggest that small variations in the structure of cellular prion proteins within different animal species may influence susceptibility to infection by diseased prion proteins. — J.P.J.
