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Subjects were exposed to two aversive experiences: in the short trial, they immersed one hand in water at 14 °C for 60 s; in the long trial, they immersed the other hand at 14 °C for 60 s, then kept the hand in the water 30 s longer as the temperature of the water was gradually raised to 15 °C, still painful but distinctly less so for most subjects. Subjects were later given a choice of which trial to repeat. A significant majority chose to repeat the long trial, apparently preferring more pain over less. The results add to other evidence suggesting that duration plays a small role in retrospective evaluations of aversive experiences; such evaluations are often dominated by the discomfort at the worst and at the final moments of episodes.

This article presents seven principles that have guided our thinking about emotional intelligence, some of them new. We have reformulated our original ability model here guided by these principles, clarified earlier statements of the model that were unclear, and revised portions of it in response to current research. In this revision, we also positioned emotional intelligence amidst other hot intelligences including personal and social intelligences, and examined the implications of the changes to the model. We discuss the present and future of the concept of emotional intelligence as a mental ability.

Private-sector efforts help drive decoupling of emissions and economic growth

In an unusual instance of lay participation in biomedical research, U.S. AIDS treatment activists have constituted themselves as credible participants in the process of knowledge construction, thereby bringing about changes in the epistemic practices of biomedical research. This article examines the mechanisms or tactics by which these lay activists have constructed their credibility in the eyes of AIDS researchers and government officials. It considers the inwlications of such interventions for the conduct of medical research; examines some of the ironies, tensions, and limitations in the process; and argues for the importance of studying social movements that engage with expert knowledge.

Nonpharmaceutical interventions (NPIs) intended to reduce infectious contacts between persons form an integral part of plans to mitigate the impact of the next influenza pandemic. Although the potential benefits of NPIs are supported by mathematical models, the historical evidence for the impact of such interventions in past pandemics has not been systematically examined. We obtained data on the timing of 19 classes of NPI in 17 U.S. cities during the 1918 pandemic and tested the hypothesis that early implementation of multiple interventions was associated with reduced disease transmission. Consistent with this hypothesis, cities in which multiple interventions were implemented at an early phase of the epidemic had peak death rates approximately 50% lower than those that did not and had less-steep epidemic curves. Cities in which multiple interventions were implemented at an early phase of the epidemic also showed a trend toward lower cumulative excess mortality, but the difference was smaller (approximately 20%) and less statistically significant than that for peak death rates. This finding was not unexpected, given that few cities maintained NPIs longer than 6 weeks in 1918. Early implementation of certain interventions, including closure of schools, churches, and theaters, was associated with lower peak death rates, but no single intervention showed an association with improved aggregate outcomes for the 1918 phase of the pandemic. These findings support the hypothesis that rapid implementation of multiple NPIs can significantly reduce influenza transmission, but that viral spread will be renewed upon relaxation of such measures.

IMPORTANCE: The Affordable Care Act is the most important health care legislation enacted in the United States since the creation of Medicare and Medicaid in 1965. The law implemented comprehensive reforms designed to improve the accessibility, affordability, and quality of health care. OBJECTIVES: To review the factors influencing the decision to pursue health reform, summarize evidence on the effects of the law to date, recommend actions that could improve the health care system, and identify general lessons for public policy from the Affordable Care Act. EVIDENCE: Analysis of publicly available data, data obtained from government agencies, and published research findings. The period examined extends from 1963 to early 2016. FINDINGS: The Affordable Care Act has made significant progress toward solving long-standing challenges facing the US health care system related to access, affordability, and quality of care. Since the Affordable Care Act became law, the uninsured rate has declined by 43%, from 16.0% in 2010 to 9.1% in 2015, primarily because of the law's reforms. Research has documented accompanying improvements in access to care (for example, an estimated reduction in the share of nonelderly adults unable to afford care of 5.5 percentage points), financial security (for example, an estimated reduction in debts sent to collection of $600-$1000 per person gaining Medicaid coverage), and health (for example, an estimated reduction in the share of nonelderly adults reporting fair or poor health of 3.4 percentage points). The law has also begun the process of transforming health care payment systems, with an estimated 30% of traditional Medicare payments now flowing through alternative payment models like bundled payments or accountable care organizations. These and related reforms have contributed to a sustained period of slow growth in per-enrollee health care spending and improvements in health care quality. Despite this progress, major opportunities to improve the health care system remain. CONCLUSIONS AND RELEVANCE: Policy makers should build on progress made by the Affordable Care Act by continuing to implement the Health Insurance Marketplaces and delivery system reform, increasing federal financial assistance for Marketplace enrollees, introducing a public plan option in areas lacking individual market competition, and taking actions to reduce prescription drug costs. Although partisanship and special interest opposition remain, experience with the Affordable Care Act demonstrates that positive change is achievable on some of the nation's most complex challenges.

We use cosmological gasdynamic simulations to investigate the accuracy of galaxy cluster mass estimates based on X-ray observations. The experiments follow the formation of clusters in different cosmological models and include the effects of gravity, pressure gradients, and hydrodynamical shocks. A subset of our ensemble also allows for feedback of mass and energy from galactic winds into the intracluster medium. We find that mass estimates based on the hydrostatic, isothermal β- model are remarkably accurate when evaluated at radii where the cluster mean density is between 500 and 2500 times the critical density. At lower densities, radial temperature information becomes important. In the quoted radial regime, the distribution of the estimated-to-true mass ratio, derived from 174 artificial images constructed from the simulations, is nearly unbiased and has a standard deviation of 14%-29%. The scatter can be considerably reduced (to 8%-15%) by using an alternative mass estimator that exploits the tightness of the mass- temperature relation found in the simulations. The improvement over β-model estimates is due to the elimination of the variance contributed by the gas outer slope parameter. We discuss these findings and their implications for recent measurements of cluster baryon fractions.

Distinguishing Alzheimer's disease (AD) and frontotemporal dementia (FTD) currently relies on a clinical history and examination, but positron emission tomography with [(18)F] fluorodeoxyglucose (FDG-PET) shows different patterns of hypometabolism in these disorders that might aid differential diagnosis. Six dementia experts with variable FDG-PET experience made independent, forced choice, diagnostic decisions in 45 patients with pathologically confirmed AD (n = 31) or FTD (n = 14) using five separate methods: (1) review of clinical summaries, (2) a diagnostic checklist alone, (3) summary and checklist, (4) transaxial FDG-PET scans and (5) FDG-PET stereotactic surface projection (SSP) metabolic and statistical maps. In addition, we evaluated the effect of the sequential review of a clinical summary followed by SSP. Visual interpretation of SSP images was superior to clinical assessment and had the best inter-rater reliability (mean kappa = 0.78) and diagnostic accuracy (89.6%). It also had the highest specificity (97.6%) and sensitivity (86%), and positive likelihood ratio for FTD (36.5). The addition of FDG-PET to clinical summaries increased diagnostic accuracy and confidence for both AD and FTD. It was particularly helpful when raters were uncertain in their clinical diagnosis. Visual interpretation of FDG-PET after brief training is more reliable and accurate in distinguishing FTD from AD than clinical methods alone. FDG-PET adds important information that appropriately increases diagnostic confidence, even among experienced dementia specialists.

Microglial activation is central to the inflammatory response in Alzheimer's Disease (AD). A recently described mouse line, Tg(HuAPP695.K670N/M671L)2576, expressing human amyloid precursor protein with a familial AD gene mutation, age-related amyloid deposits, and memory deficits, was found to develop a significant microglial response using Griffonia simplicifolia lectin or phosphotyrosine probe to identify microglia Both Griffonia simplicifolia lectin and phosphotyrosine staining showed increased numbers of intensely labeled, often enlarged microglia clustered in and around plaques, consistent with microglial activation related to beta-amyloid formation. Using quantitative image analysis of coronal phosphotyrosine-immunostained sections, transgene-positive 10- to 16-month-old, hemizygous, hybrid Tg2576 (APPsw) animals showed significantly increased microglial density and size in plaque-forming areas of hippocampus and frontal, entorhinal, and occipital cortex. Quantitative analysis of microglia as a function of distance from the center of plaques (double labeled for A beta peptide and microglia) revealed highly significant, two- to fivefold elevations in microglial number and area within plaques compared with neighboring regions. Tg2576 beta-amyloid-plaque-forming mice should be a useful system for assessing the consequences of the microglial-mediated inflammatory response to beta-amyloid and developing anti-inflammatory therapeutic strategies for Alzheimer's disease. These results provide the first quantitative link between beta-amyloid plaque formation and microglial activation in an animal model with neuritic plaques and memory deficits.

The human T cell leukemia Jurkat was used as a model to examine the requirements of T cell activation. These studies demonstrated that antibodies reactive with the T cell-specific T3 antigen were insufficient to result in the activation of Jurkat cells, determined by the secretion of IL 2. IL 2 production occurred only in the presence of a second stimulus, the phorbol ester PMA. With the use of an IL 2-specific cDNA probe, the appearance of IL 2 RNA, similarly, occurred only when cells were stimulated with both anti-T3 antibodies and PMA. These results demonstrate a two-stimulus requirement for gene expression in human T cells.

BACKGROUND: Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism. OBJECTIVES: We evaluated whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. METHODS: The CHARGE study is a population-based case-control study of ASD, DD, and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997-2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25-km, 1.5-km, and 1.75-km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316). RESULTS: Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified. CONCLUSIONS: This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates.

To determine whether data available to physicians in the emergency room can accurately identify which patients with acute chest pain are having myocardial infarctions, we analyzed 482 patients at one hospital. Using recursive partitioning analysis, we constructed a decision protocol in the format of a simple flow chart to identify infarction on the basis of nine clinical factors. In prospective testing on 468 other patients at a second hospital, the protocol performed as well as the physicians. Moreover, an integration of the protocol with the physicians' judgments resulted in a classification system that preserved sensitivity for detecting infarctions, significantly improved the specificity (from 67 per cent to 77 per cent, P less than 0.01) and positive predictive value (from 34 per cent to 42 per cent, P = 0.016) of admission to an intensive-care area. The protocol identified a subgroup of 107 patients among whom only 5 per cent had infarctions and for whom admission to non-intensive-care areas might be appropriate. This decision protocol warrants further wide-scale prospective testing but is not ready for routine clinical use.

One view of the coevolution of parasites and their hosts is that of a gene-for-gene arms race between host defenses and parasite counterdefenses. We have incorporated mutations into a model of the ecological interactions between bacteria and virulent phage to determine rates of mutation that would be consistent with this scenario. The model assumes an open habitat (e.g., a chemostat) in which virulent phage and sensitive bacteria can coexist. Equilibrium densities of bacteria and phage are inversely proportional to the efficiency with which phage irreversibly adsorb to their hosts. The absolute rate at which mutations appear is proportional to the product of habitat size, population density, rate of increase, and mutation rate. The bacterium Escherichia coli B readily evolved resistance to virulent phage T4 in our chemostat experiments. Approximately 100 h was required for the appearance, establishment, and attainment of a resource-limited population of these T4-resistant mutants; this time period is close to that predicted from the model when the parameters of the model are estimated independently. No host-range phage T4 mutants appeared, yet the phage persisted even after the resistant bacteria had become resource-limited. We hypothesized that the failure to observe corresponding phage mutants indicates mutational constraints on the coevolutionary potential of this phage. We also hypothesized that the persistence of the wild-type phage indicates the presence of a minority population of sensitive bacteria that persists because of selective constraints which produce a competitive disadvantage for resistant bacteria under resource-limiting conditions. Both of these hypotheses were verified. Host-range T4 mutants occurred at a rate on the order of 10^-12 or less, and could not be expected in the chemostats for several years. T4-sensitive and -resistant bacteria had very nearly the same exponential growth rates, but at steady state the latter had approximately a 50% disadvantage. We also examined the interactions of E. coli B and virulent phages T2, T5, and T7 for evidence of selective and mutational constraints on the bacteria and phage, respectively. Under the conditions of our experiments, T2-resistant and T7-resistant (but not T5-resistant) bacteria also had clear competitive disadvantages to sensitive bacteria under resource-limiting conditions. We were able to isolate T2 and T7 (but not T5) host-range mutants. Even with T2 and T7, however, we could not select indefinitely for host-range mutants active against higher-order resistant bacteria. This general asymmetry in the coevolutionary potential of bacteria and phage occurs because mutations conferring resistance may arise by either the loss or alteration of gene function, while host-range mutations depend on specific alterations of gene function. These constraints preclude observing endless arms races between bacteria and virulent phage. Instead, because of the asymmetry in coevolutionary potential of these hosts and parasites, we anticipate that natural communities of coliform bacteria and virulent coliphage are dominated by bacterial clones resistant to all co-occurring virulent phage. If virulent phage to which the dominant clones are sensitive should appear, then bacteria will either rapidly evolve resistance or be replaced by existing clones resistant to the phage. Thus, the role of virulent phage in structuring communities of bacteria is seen as important in determining clonal composition but unimportant in determining overall bacterial densities.

Medical histories of the 15,924 male twin pairs in the National Academy of Sciences-National Research Council Twin Registry were examined to determine, within pairs, concordances for alcoholism and its medical end points. Prevalences per 1,000 among individual twin subjects were 29.6 for alcoholism, 4.1 for alcoholic psychosis, 14.2 for liver cirrhosis, and 2.1 for pancreatitis. Prevalences were similar to monozygotic (MZ) and dizygotic (DZ) twins. Prevalences in percent among co-twins of diagnosed subjects, that is case-wise twin concordance rates, were, respectively, by diagnosis: alcoholism: 26.3 (MZ), 11.9 (DZ); alcoholic psychosis: 21.1 (MZ), 6.0 (DZ); and liver cirrhosis: 14.6 (MZ), 5.4 (DZ). No twin pairs concordant for pancreatitis were found. The greater concordance for alcoholic psychosis and for liver cirrhosis among MZ than DZ twins could not be explained by the difference in alcoholism concordance between them. The difference in concordance between MZ and DZ twins persisted when, in addition, it was assumed that only half of the actually occurring cases of alcoholism and of each of the end points have been ascertained. These results provide evidence in favor of genetic predisposition to organ-specific complications of alcoholism and should serve to stimulate searches for the underlying biochemical mechanisms.

As the world grows less biologically diverse, it is becoming less linguistically and culturally diverse as well. Biologists estimate annual loss of species at 1,000 times or more greater than historic rates, and linguists predict that 50-90% of the world's languages will disappear by the end of this century. Prior studies indicate similarities in the geographic arrangement of biological and linguistic diversity, although conclusions have often been constrained by use of data with limited spatial precision. Here we use greatly improved datasets to explore the co-occurrence of linguistic and biological diversity in regions containing many of the Earth's remaining species: biodiversity hotspots and high biodiversity wilderness areas. Results indicate that these regions often contain considerable linguistic diversity, accounting for 70% of all languages on Earth. Moreover, the languages involved are frequently unique (endemic) to particular regions, with many facing extinction. Likely reasons for co-occurrence of linguistic and biological diversity are complex and appear to vary among localities, although strong geographic concordance between biological and linguistic diversity in many areas argues for some form of functional connection. Languages in high biodiversity regions also often co-occur with one or more specific conservation priorities, here defined as endangered species and protected areas, marking particular localities important for maintaining both forms of diversity. The results reported in this article provide a starting point for focused research exploring the relationship between biological and linguistic-cultural diversity, and for developing integrated strategies designed to conserve species and languages in regions rich in both.

PURPOSE: Many medical students experience distress during medical school. If matriculating medical students (MMSs) begin training with similar or better mental health than age-similar controls, this would support existing concerns about the negative impact of training on student well-being. The authors compared mental health indicators of MMSs versus those of a probability-based sample of the general U.S. population. METHOD: In 2012 all MMSs at six U.S. medical schools were invited to participate in a survey during orientation. The research team surveyed a probability-based sample of U.S. individuals using the same questions in 2011. Individuals from the population sample who completed a four-year college degree and matched within the appropriate age strata (< 30, 31-35, 36-40, > 40) were compared with MMSs. Surveys included demographics and validated instruments to measure burnout; depression symptoms; and mental, emotional, physical, and overall of quality of life (QOL). RESULTS: Demographic characteristics of the 582/938 (62%) responding MMSs were similar to U.S. MMSs. Relative to 546 age-similar college graduates, MMSs had lower rates of burnout (27.3% versus 37.3%, P < .001) and depression symptoms (26.2% versus 42.4%, P < .0001) and higher scores across the four QOL domains assessed relative to controls (all P < .0001). These findings persisted on multivariate analysis after adjusting for age, sex, relationship status, and race/ethnicity. CONCLUSIONS: These findings, along with high rates of distress reported in medical students and residents, support concerns that the training process and environment contribute to the deterioration of mental health in developing physicians.

Parenteral nutrition represents standard therapy for children with short bowel syndrome and other causes of intestinal failure. Most infants with short bowel syndrome eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for protracted periods. However, a subset of children with intestinal failure remaining dependent on parenteral nutrition will develop life-threatening complications arising from therapy. Intestinal transplantation (Tx) can now be recommended for this select group. Life-threatening complications warranting consideration of intestinal Tx include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access. Because a critical shortage of donor organs exists, waiting times for intestinal Tx are prolonged. Therefore, it is essential that children with life-threatening complications of intestinal failure and parenteral nutrition therapy be identified comparatively early, i.e. in time to receive suitable donor organs before they become critically ill. Children with liver dysfunction should be considered for isolated intestinal Tx before irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a combined liver and intestinal transplant is necessary. Irreversible liver disease is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins; esophageal varices, ascites, and impaired synthetic function are not always present. Death resulting from complications of liver failure is especially common during the wait for a combined liver and intestinal transplant, and survival following combined liver and intestinal Tx is probably lower than following an isolated intestinal transplant. The incidence of morbidity and mortality following intestinal Tx is greater than that following liver or kidney Tx, but long-term survival following intestinal Tx is now at least 50-60%. It is probable that outcomes shall improve in the future with continued refinements in operative technique and post-operative management, including immunosuppression.

BACKGROUND: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. OBJECTIVE: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. DESIGN: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440). SETTING: 31 liver disease and transplant centers in the United States. PATIENTS: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). MEASUREMENTS: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). RESULTS: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P < 0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P < 0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. LIMITATIONS: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. CONCLUSION: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study. PRIMARY FUNDING SOURCE: National Institutes of Health.

BACKGROUND AND PURPOSE: Our purpose was to characterize the findings of MR imaging of the brain of adult male fragile X premutation carriers with a recently identified disorder characterized by ataxia, tremor, rigidity, and cognitive dysfunction. METHODS: MR imaging studies of the brain of 17 male patients were characterized for signal intensity and for size of ventricles, cerebral and cerebellar sulci, and brain stem. Comparison was made with age- and sex-matched control participants. Southern blot and/or polymerase chain reaction methods were used to analyze CGG trinucleotide repeats in the fragile X mental retardation 1 gene. RESULTS: Fifteen of 17 patients showed symmetrically decreased T1 and increased T2 signal intensity in cerebellar white matter lateral, superior, and inferior to the dentate nuclei. Fourteen of 17 had similar signal intensity alterations in the middle cerebellar peduncles. Cerebellar cortical atrophy was present in 16 of 17 and cerebral atrophy in 17 of 17. Evan's Index as a measure of ventricular size averaged 0.35 (range, 0.25-0.46), with that for age-matched control participants averaging 0.28 (range, 0.24-0.31) (P <.005). The mean third ventricle width was 11 mm (for control participants, 6 mm; P <.01). Corpus callosum was thinned in 14 of 16 participants. Middle cerebellar peduncles were atrophic when compared with those of control participants (P <.005). Pontine transverse dimension was 25 mm (for control participants, 31 mm; P <.005), and rostral-caudal length averaged 26 mm (for control participants, 29 mm; P <.005). CGG repeats clustered in the low to mid premutation range (86 +/- 10 CGG repeats) in the 17 patients. CONCLUSION: MR imaging findings in symptomatic male fragile X premutation carriers are characteristic of this disorder. Recognition of these alterations may support a specific diagnosis and may have implications for the potential occurrence of fragile X syndrome in the children of reproductive age female relatives.

Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines such as IL-1. We report here that leptin, injected into rats intracerebroventricularly or peripherally, induces significant dose-dependent increases in core body temperature as well as suppression of appetite. Leptin failed to affect food intake or body temperature in obese (fa/fa) Zucker rats, which posses a defective leptin receptor. Furthermore, injection of leptin increased levels of the proinflammatory cytokine IL-1beta in the hypothalamus of normal Sprague-Dawley rats. Central injection of IL-1 receptor antagonist (IL-1ra) inhibited the suppression of food intake caused by central or peripheral injection of leptin (60 and 84%, respectively) and abolished the leptin-induced increase in body temperature in both cases. Mice lacking (gene knockout) the main IL-1 receptor (80 kDa, R1) responsible for IL-1 actions showed no reduction in food intake in response to leptin. These data indicate that leptin actions in the brain depend on IL-1, and we show further that the effect of leptin on fever, but not food intake, is abolished by a cyclooxygenase inhibitor. Thus, we propose that in addition to its role in body weight regulation, leptin may mediate neuroimmune responses via actions in the brain dependent on release of IL-1 and prostaglandins.