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Showing papers by "University of Virginia published in 2014"


Journal ArticleDOI
Keith A. Olive1, Kaustubh Agashe2, Claude Amsler3, Mario Antonelli  +222 moreInstitutions (107)
TL;DR: The review as discussed by the authors summarizes much of particle physics and cosmology using data from previous editions, plus 3,283 new measurements from 899 Japers, including the recently discovered Higgs boson, leptons, quarks, mesons and baryons.
Abstract: The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.

7,337 citations


Journal ArticleDOI
01 Sep 2014
TL;DR: XSEDE's integrated, comprehensive suite of advanced digital services federates with other high-end facilities and with campus-based resources, serving as the foundation for a national e-science infrastructure ecosystem.
Abstract: Computing in science and engineering is now ubiquitous: digital technologies underpin, accelerate, and enable new, even transformational, research in all domains. Access to an array of integrated and well-supported high-end digital services is critical for the advancement of knowledge. Driven by community needs, the Extreme Science and Engineering Discovery Environment (XSEDE) project substantially enhances the productivity of a growing community of scholars, researchers, and engineers (collectively referred to as "scientists"' throughout this article) through access to advanced digital services that support open research. XSEDE's integrated, comprehensive suite of advanced digital services federates with other high-end facilities and with campus-based resources, serving as the foundation for a national e-science infrastructure ecosystem. XSEDE's e-science infrastructure has tremendous potential for enabling new advancements in research and education. XSEDE's vision is a world of digitally enabled scholars, researchers, and engineers participating in multidisciplinary collaborations to tackle society's grand challenges.

2,856 citations


Journal ArticleDOI
TL;DR: Recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults and coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy are provided.
Abstract: Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.

2,795 citations


Journal ArticleDOI
TL;DR: It is proposed that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease.
Abstract: In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.

2,581 citations


Journal ArticleDOI
TL;DR: First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma, and progression-free survival was prolonged but did not reach the prespecified improvement target.
Abstract: Background Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. Methods In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary ...

2,181 citations


Journal ArticleDOI
TL;DR: The BEDTools toolkit as discussed by the authors is a toolkit for the exploration of high-throughput genomics datasets, which can be combined to create bespoke pipelines addressing complex questions.
Abstract: Technological advances have enabled the use of DNA sequencing as a flexible tool to characterize genetic variation and to measure the activity of diverse cellular phenomena such as gene isoform expression and transcription factor binding Extracting biological insight from the experiments enabled by these advances demands the analysis of large, multi-dimensional datasets This unit describes the use of the BEDTools toolkit for the exploration of high-throughput genomics datasets Several protocols are presented for common genomic analyses, demonstrating how simple BEDTools operations may be combined to create bespoke pipelines addressing complex questions

1,716 citations


Journal ArticleDOI
TL;DR: A vision for how IoT could change the world in the distant future is presented and eight key research topics are enumerated and research problems within these topics are discussed.
Abstract: Many technical communities are vigorously pursuing research topics that contribute to the Internet of Things (IoT). Nowadays, as sensing, actuation, communication, and control become even more sophisticated and ubiquitous, there is a significant overlap in these communities, sometimes from slightly different perspectives. More cooperation between communities is encouraged. To provide a basis for discussing open research problems in IoT, a vision for how IoT could change the world in the distant future is first presented. Then, eight key research topics are enumerated and research problems within these topics are discussed.

1,700 citations


Journal ArticleDOI
TL;DR: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015, with evidence of continued acceleration in the MMR, and MMR was highest in the oldest age groups in both 1990 and 2013.

1,383 citations


Journal ArticleDOI
TL;DR: Because soluble toxic aggregates of both Aβ and tau can self-propagate and spread throughout the brain by prionlike mechanisms, successful therapeutic intervention for AD would benefit from detecting these species before plaques, tangles, and cognitive impairment become evident and from interfering with the destructive biochemical pathways that they initiate.
Abstract: The defining features of Alzheimer disease (AD) include conspicuous changes in both brain histology and behavior. The AD brain is characterized microscopically by the combined presence of 2 classes of abnormal structures, extracellular amyloid plaques and intraneuronal neurofibrillary tangles, both of which comprise highly insoluble, densely packed filaments. The soluble building blocks of these structures are amyloid-β (Aβ) peptides for plaques and tau for tangles. Amyloid-β peptides are proteolytic fragments of the transmembrane amyloid precursor protein, whereas tau is a brain-specific, axon-enriched microtubule-associated protein. The behavioral symptoms of AD correlate with the accumulation of plaques and tangles, and they are a direct consequence of the damage and destruction of synapses that mediate memory and cognition. Synapse loss can be caused by the failure of live neurons to maintain functional axons and dendrites or by neuron death. During the past dozen years, a steadily accumulating body of evidence has indicated that soluble forms of Aβ and tau work together, independently of their accumulation into plaques and tangles, to drive healthy neurons into the diseased state and that hallmark toxic properties of Aβ require tau. For instance, acute neuron death, delayed neuron death following ectopic cell cycle reentry, and synaptic dysfunction are triggered by soluble, extracellular Aβ species and depend on soluble, cytoplasmic tau. Therefore, Aβ is upstream of tau in AD pathogenesis and triggers the conversion of tau from a normal to a toxic state, but there is also evidence that toxic tau enhances Aβ toxicity via a feedback loop. Because soluble toxic aggregates of both Aβ and tau can self-propagate and spread throughout the brain by prionlike mechanisms, successful therapeutic intervention for AD would benefit from detecting these species before plaques, tangles, and cognitive impairment become evident and from interfering with the destructive biochemical pathways that they initiate.

1,265 citations


Journal ArticleDOI
TL;DR: The 10th public data release (DR10) from the Sloan Digital Sky Survey (SDSS-III) was released in 2013 as mentioned in this paper, which includes the first spectroscopic data from the Apache Point Observatory Galaxy Evolution Experiment (APOGEE), along with spectroscopy data from Baryon Oscillation Spectroscopic Survey (BOSS) taken through 2012 July.
Abstract: The Sloan Digital Sky Survey (SDSS) has been in operation since 2000 April. This paper presents the Tenth Public Data Release (DR10) from its current incarnation, SDSS-III. This data release includes the first spectroscopic data from the Apache Point Observatory Galaxy Evolution Experiment (APOGEE), along with spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS) taken through 2012 July. The APOGEE instrument is a near-infrared R ~ 22,500 300 fiber spectrograph covering 1.514-1.696 μm. The APOGEE survey is studying the chemical abundances and radial velocities of roughly 100,000 red giant star candidates in the bulge, bar, disk, and halo of the Milky Way. DR10 includes 178,397 spectra of 57,454 stars, each typically observed three or more times, from APOGEE. Derived quantities from these spectra (radial velocities, effective temperatures, surface gravities, and metallicities) are also included. DR10 also roughly doubles the number of BOSS spectra over those included in the Ninth Data Release. DR10 includes a total of 1,507,954 BOSS spectra comprising 927,844 galaxy spectra, 182,009 quasar spectra, and 159,327 stellar spectra selected over 6373.2 deg2.

1,188 citations


Journal ArticleDOI
10 Sep 2014-JAMA
TL;DR: Hydxyurea and transfusion therapy are strongly recommended for many individuals with SCD and many other recommendations are based on quality of evidence that is less than high due to the paucity of clinical trials regarding screening, management, and monitoring for individuals withSCD.
Abstract: Importance Sickle cell disease (SCD) is a life-threatening genetic disorder affecting nearly 100 000 individuals in the United States and is associated with many acute and chronic complications requiring immediate medical attention. Two disease-modifying therapies, hydroxyurea and long-term blood transfusions, are available but underused. Objective To support and expand the number of health professionals able and willing to provide care for persons with SCD. Evidence Review Databases of MEDLINE (including in-process and other nonindexed citations), EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, TOXLINE, and Scopus were searched using prespecified search terms and keywords to identify randomized clinical trials, nonrandomized intervention studies, and observational studies. Literature searches of English-language publications from 1980 with updates through April 1, 2014, addressed key questions developed by the expert panel members and methodologists. Findings Strong recommendations for preventive services include daily oral prophylactic penicillin up to the age of 5 years, annual transcranial Doppler examinations from the ages of 2 to 16 years in those with sickle cell anemia, and long-term transfusion therapy to prevent stroke in those children with abnormal transcranial Doppler velocity (≥200 cm/s). Strong recommendations addressing acute complications include rapid initiation of opioids for treatment of severe pain associated with a vasoocclusive crisis, and use of incentive spirometry in patients hospitalized for a vasoocclusive crisis. Strong recommendations for chronic complications include use of analgesics and physical therapy for treatment of avascular necrosis, and use of angiotensin-converting enzyme inhibitor therapy for microalbuminuria in adults with SCD. Strong recommendations for children and adults with proliferative sickle cell retinopathy include referral to expert specialists for consideration of laser photocoagulation and for echocardiography to evaluate signs of pulmonary hypertension. Hydroxyurea therapy is strongly recommended for adults with 3 or more severe vasoocclusive crises during any 12-month period, with SCD pain or chronic anemia interfering with daily activities, or with severe or recurrent episodes of acute chest syndrome. A recommendation of moderate strength suggests offering treatment with hydroxyurea without regard to the presence of symptoms for infants, children, and adolescents. In persons with sickle cell anemia, preoperative transfusion therapy to increase hemoglobin levels to 10 g/dL is strongly recommended with a moderate strength recommendation to maintain sickle hemoglobin levels of less than 30% prior to the next transfusion during long-term transfusion therapy. A strong recommendation to assess iron overload is accompanied by a moderate strength recommendation to begin iron chelation therapy when indicated. Conclusions and Relevance Hydroxyurea and transfusion therapy are strongly recommended for many individuals with SCD. Many other recommendations are based on quality of evidence that is less than high due to the paucity of clinical trials regarding screening, management, and monitoring for individuals with SCD.

Journal ArticleDOI
TL;DR: It is shown that LUMPY yields improved sensitivity, especially when SV signal is reduced owing to either low coverage data or low intra-sample variant allele frequency, as well as a set of 4,564 validated breakpoints from the NA12878 human genome.
Abstract: Comprehensive discovery of structural variation (SV) from whole genome sequencing data requires multiple detection signals including read-pair, split-read, read-depth and prior knowledge. Owing to technical challenges, extant SV discovery algorithms either use one signal in isolation, or at best use two sequentially. We present LUMPY, a novel SV discovery framework that naturally integrates multiple SV signals jointly across multiple samples. We show that LUMPY yields improved sensitivity, especially when SV signal is reduced owing to either low coverage data or low intra-sample variant allele frequency. We also report a set of 4,564 validated breakpoints from the NA12878 human genome. https://github.com/arq5x/lumpy-sv.

Journal ArticleDOI
TL;DR: The abundance and size distribution of lakes is critical to quantifying limnetic contributions to the global carbon cycle as discussed by the authors, however, estimates of global lake abundance are not accurate and are unreliable.
Abstract: An accurate description of the abundance and size distribution of lakes is critical to quantifying limnetic contributions to the global carbon cycle. However, estimates of global lake abundance are ...

Journal ArticleDOI
13 Mar 2014-Cell
TL;DR: It is proposed that ASC-dependent inflammasomes in both families share a unified assembly mechanism that involves two successive steps of nucleation-induced polymerization.

Journal ArticleDOI
TL;DR: Gneezy et al. as discussed by the authors conducted a meta-analysis of the relationship of financial literacy and of financial education to financial behaviors in 168 papers covering 201 prior studies, and found that interventions to improve financial literacy explain only 0.1% of the variance in financial behaviors studied, with weaker effects in low-income samples.
Abstract: Policy makers have embraced financial education as a necessary antidote to the increasing complexity of consumers' financial decisions over the last generation. We conduct a meta-analysis of the relationship of financial literacy and of financial education to financial behaviors in 168 papers covering 201 prior studies. We find that interventions to improve financial literacy explain only 0.1% of the variance in financial behaviors studied, with weaker effects in low-income samples. Like other education, financial education decays over time; even large interventions with many hours of instruction have negligible effects on behavior 20 months or more from the time of intervention. Correlational studies that measure financial literacy find stronger associations with financial behaviors. We conduct three empirical studies, and we find that the partial effects of financial literacy diminish dramatically when one controls for psychological traits that have been omitted in prior research or when one uses an instrument for financial literacy to control for omitted variables. Financial education as studied to date has serious limitations that have been masked by the apparently larger effects in correlational studies. We envisage a reduced role for financial education that is not elaborated or acted upon soon afterward. We suggest a real but narrower role for “just-in-time” financial education tied to specific behaviors it intends to help. We conclude with a discussion of the characteristics of behaviors that might affect the policy maker's mix of financial education, choice architecture, and regulation as tools to help consumer financial behavior. This paper was accepted by Uri Gneezy, behavioral economics.

Journal ArticleDOI
19 Jun 2014-Nature
TL;DR: The results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions.
Abstract: Bacterial species whose representation defines healthy postnatal assembly of the gut microbiota in Bangladeshi children during their first 2 years are identified, and a model is constructed to compare healthy children to those with severe acute malnutrition (SAM); results show that SAM is associated with microbiota immaturity that is only partially ameliorated by existing nutritional interventions. Childhood malnutrition is a major health problem in many low-income countries, and although mortality can be reduced by therapeutic food interventions, it is difficult to achieve complete restoration of healthy growth in cases of severe acute malnutrition. Here Jeffrey Gordon and colleagues identify a group of 24 bacterial species whose proportional representation in the microbiota defines how a healthy microbiota assembles over the course of the first two postnatal years in a cohort of healthy children in Bangladesh. They define a 'relative microbiota maturity index' and 'microbiota-for-age Z-score' that allow comparison across individuals and use these indices to demonstrate that severe malnutrition is associated with significant relative microbiota immaturity that is only partially ameliorated by two widely used nutritional interventions. This work suggests that more prolonged food-based interventions and/or addition of gut microbes may be needed to achieve durable repair of microbiota immaturity in childhood malnutrition and improved clinical outcomes. Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem1,2. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare postnatal assembly (defined here as maturation) of a child’s faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.

Journal ArticleDOI
TL;DR: The current understanding of the complex process of apoptotic cell clearance in physiology and pathology is reviewed, and how this knowledge could be harnessed for new therapeutic strategies are discussed.
Abstract: Prompt removal of apoptotic cells by phagocytes is important for maintaining tissue homeostasis. The molecular and cellular events that underpin apoptotic cell recognition and uptake, and the subsequent biological responses are increasingly better defined. The detection and disposal of apoptotic cells generally promote an anti-inflammatory response at the tissue level, as well as immunological tolerance. Consequently, defects in apoptotic cell clearance have been linked with a variety of inflammatory diseases and autoimmunity. Conversely, under certain conditions such as killing tumour cells by specific cell death inducers, the recognition of apoptotic tumour cells can promote an immunogenic response and anti-tumour immunity. Here, we review the current understanding of the complex process of apoptotic cell clearance in physiology and pathology, and discuss how this knowledge could be harnessed for new therapeutic strategies.

Journal ArticleDOI
TL;DR: A new light-measurement strategy taking account of the complex photoreceptive inputs to these non-visual responses is proposed for use by researchers, and simple suggestions for artificial/architectural lighting are provided for regulatory authorities, lighting manufacturers, designers, and engineers.

Journal ArticleDOI
Jacy R Crosby1, Gina M. Peloso2, Gina M. Peloso3, Paul L. Auer4, David R. Crosslin5, Nathan O. Stitziel6, Leslie A. Lange7, Yingchang Lu8, Zheng-Zheng Tang7, He Zhang9, George Hindy10, Nicholas G. D. Masca11, Kathleen Stirrups12, Stavroula Kanoni12, Ron Do2, Ron Do3, Goo Jun9, Youna Hu9, Hyun Min Kang9, Chenyi Xue9, Anuj Goel13, Martin Farrall13, Stefano Duga14, Pier Angelica Merlini, Rosanna Asselta14, Domenico Girelli15, Oliviero Olivieri15, Nicola Martinelli15, Wu Yin16, Dermot F. Reilly16, Elizabeth K. Speliotes9, Caroline S. Fox17, Kristian Hveem18, Oddgeir L. Holmen19, Majid Nikpay20, Deborah N. Farlow2, Themistocles L. Assimes21, Nora Franceschini7, Jennifer G. Robinson22, Kari E. North7, Lisa W. Martin23, Mark A. DePristo2, Namrata Gupta2, Stefan A. Escher10, Jan-Håkan Jansson24, Natalie R. van Zuydam25, Colin N. A. Palmer25, Nicholas J. Wareham26, Werner Koch27, Thomas Meitinger27, Annette Peters, Wolfgang Lieb28, Raimund Erbel, Inke R. König29, Jochen Kruppa29, Franziska Degenhardt30, Omri Gottesman8, Erwin P. Bottinger8, Christopher J. O'Donnell17, Bruce M. Psaty5, Bruce M. Psaty31, Christie M. Ballantyne32, Christie M. Ballantyne33, Gonçalo R. Abecasis9, Jose M. Ordovas34, Jose M. Ordovas35, Olle Melander10, Hugh Watkins13, Marju Orho-Melander10, Diego Ardissino, Ruth J. F. Loos8, Ruth McPherson20, Cristen J. Willer9, Jeanette Erdmann29, Alistair S. Hall36, Nilesh J. Samani11, Panos Deloukas37, Panos Deloukas38, Panos Deloukas12, Heribert Schunkert27, James G. Wilson39, Charles Kooperberg40, Stephen S. Rich41, Russell P. Tracy42, Danyu Lin7, David Altshuler2, David Altshuler3, Stacey Gabriel2, Deborah A. Nickerson5, Gail P. Jarvik5, L. Adrienne Cupples43, L. Adrienne Cupples26, Alexander P. Reiner40, Alexander P. Reiner5, Eric Boerwinkle33, Sekar Kathiresan2, Sekar Kathiresan3 
TL;DR: Rare mutations that disrupt AP OC3 function were associated with lower levels of plasma triglycerides and APOC3, and carriers of these mutations were found to have a reduced risk of coronary heart disease.
Abstract: Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10 − 20 ), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8×10 − 10 ). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4×10 − 6 ). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)

Journal ArticleDOI
TL;DR: The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

Posted Content
TL;DR: A meta-analysis of the relationship of financial literacy and of financial education to financial behaviors in 168 papers covering 201 prior studies finds that interventions to improve financial literacy explain only 0.1% of the variance in financial behaviors studied, with weaker effects in low-income samples.
Abstract: Policy makers have embraced financial education as a necessary antidote to the increasing complexity of consumers’ financial decisions over the last generation. We conduct a meta-analysis of the relationship of financial literacy and of financial education to financial behaviors in 168 papers covering 201 prior studies. We find that interventions to improve financial literacy explain only 0.1% of the variance in financial behaviors studied, with weaker effects in low-income samples. Like other education, financial education decays over time; even large interventions with many hours of instruction have negligible effects on behavior 20 months or more from the time of intervention. Correlational studies that measure financial literacy find stronger associations with financial behaviors. We conduct three empirical studies and we find that the partial effects of financial literacy diminish dramatically when one controls for psychological traits that have been omitted in prior research or when one uses an instrument for financial literacy to control for omitted variables. Financial education as studied to date has serious limitations that have been masked by the apparently larger effects in correlational studies. We envisage a reduced role for financial education that is not elaborated or acted upon soon afterward. We suggest a real but narrower role for “just in time” financial education tied to specific behaviors it intends to help. We conclude with a discussion of the characteristics of behaviors that might affect the policy maker’s mix of financial education, choice architecture, and regulation as tools to help consumer financial behavior.

Journal ArticleDOI
TL;DR: The authors compared variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants and found that the results of these experiments are more dependent on the effect itself than on the sample and setting used to investigate the effect.
Abstract: Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently. One effect – imagined contact reducing prejudice – showed weak support for replicability. And two effects – flag priming influencing conservatism and currency priming influencing system justification – did not replicate. We compared whether the conditions such as lab versus online or US versus international sample predicted effect magnitudes. By and large they did not. The results of this small sample of effects suggest that replicability is more dependent on the effect itself than on the sample and setting used to investigate the effect.

Journal ArticleDOI
TL;DR: Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-arterY stenosis and hypertension or chronic kidney disease.
Abstract: BACKGROUND Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. METHODS We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). RESULTS Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P = 0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (−2.3 mm Hg; 95% CI, −4.4 to −0.2; P = 0.03). CONCLUSIONS Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.) abstr act

Journal ArticleDOI
TL;DR: Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes.
Abstract: Background Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. Methods We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. Results At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, −6.6 and −6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement g...

Book
21 Apr 2014
TL;DR: The central nervous system syndromes mediated by bacterial toxins: botulism, J.J. Whitley and S. Stagno neurological manifestations of infection with the human immunodeficiency viruses, B.K. Plotkin Guillain-Barre syndrome and D.G. McLone.
Abstract: Part 1 Viral infections of the central nervous system and related disorders: pathogenesis and pathophysiology of viral infections of the central nervous system, M. Schlitt et al viral meningitis and the aseptic meningitis syndrom, H.A. Rotbart encephalitis caused by herpesviruses, including B virus, R.J. Whitley and M. Schlitt arthropod-borne encephalitides, R.J. Whitley meningitis and encephalitis caused by mumps virus, J.W. Gnann, Jr et al slow viral infections of the human nervous system, D.M. Asher perinatal viral infections R.J. Whitley and S. Stagno neurological manifestations of infection with the human immunodeficiency viruses, B.K. Evans et al viral vaccines that protect the central nervous system, M.F. Mangano and S.A. Plotkin Guillain-Barre syndrome, G. Tenorio et al. Part 2 Mycoplasmal infections of the central nervous system: mycoplasmal diseases of the central nervous system, W.A. Clyde, Jr. Part 3 Bacterial infections of the central nervous system: pathogenesis and pathophysiology of bacterial infections of the central nervous system, A.R. Tunkel and W.M. Scheld neonatal bacterial meningitis, A.L. Smith and J. Haas acute bacterial meningitis in children and adults, K.L. Roos et al rickettsiae and the central nervous system, J.H. Kim and D.T. Durack tuberculosis of the central nervous system, A. Zuger and F.D. Lowy brain abscess, B. Wispelwey et al subdural empyema, D.C. Hefgott et al epidural abscess, B.G. Gellin et al central nervous system complications of infective endocarditis, P. Francioli infections of the cerebrospinal fluid shunts, B.A. Kaufman and D.G. McLone. Part 4 Central nervous system syndromes mediated by bacterial toxins: botulism, J.M. Hughes tetanus, T.P. Bleck bordetella pertussis and the central nervous system, E.L. Hewlett. Part 5 Spriochetal infections of the central nervous system: central nervous system syphilis, E.W. Hook, III Lyme disease, L. Reik, Jr. Part 6 Fungal infections of the central nervous system: pathogenesis and pathophysiology of fungal infections, J. R. Perfect and D.T. Durack chronic meningitis, T. Tucker and J.J. Ellner diagnosis and treatment of fungal meningitis, J.R. Perfect space-occupying fungal lesions of the central nervous system, K. Sepkowitz and D. Armstrong. Part 7 Protozoal and helminthic infections of the central nervous system: protozoal infections, J.P. Cegielski and D.T. Durack toxoplasmosis, C.S. Dukes et al helminthic infections, M.L. Cameron and D.T. Durack.

Journal ArticleDOI
TL;DR: Mapping genome-wide binding sites of catalytically inactive Cas9 in HEK293T cells and analysis of off-target binding sites showed the importance of the PAM-proximal region of the sgRNA guiding sequence and that dCas9 binding sites are enriched in open chromatin regions, and it is shown that ChIP-seq allows unbiased detection of Cas9 binding Site-wide.
Abstract: ChIP-seq for Cas9 shows varying amounts of off-target binding with different guide RNAs and low levels of indels at some off-target sites.

Posted ContentDOI
14 May 2014-bioRxiv
TL;DR: The qqman package enables the flexible creation of manhattan plots, both genome-wide and for single chromosomes, with optional highlighting of SNPs of interest.
Abstract: Summary: Genome-wide association studies (GWAS) have identified thousands of human trait-associated single nucleotide polymorphisms. Here, I describe a freely available R package for visualizing GWAS results using Q-Q and manhattan plots. The qqman package enables the flexible creation of manhattan plots, both genome-wide and for single chromosomes, with optional highlighting of SNPs of interest. Availability: qqman is released under the GNU General Public License, and is freely available on the Comprehensive R Archive Network (http://cran.r-project.org/package=qqman). The source code is available on GitHub (https://github.com/stephenturner/qqman).

Journal ArticleDOI
Haidong Wang1, Chelsea A. Liddell1, Matthew M Coates1, Meghan D. Mooney1  +228 moreInstitutions (123)
TL;DR: Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa, and rising income per person and maternal education and changes in secular trends led to 4·2 million fewer deaths.

Journal ArticleDOI
09 May 2014-Science
TL;DR: This study tested 1162 Han Chinese participants in six sites and found that rice-growing southern China is more interdependent and holistic-thinking than the wheat-growing north, and it is found that modernization and pathogen prevalence theories do not fit the data.
Abstract: Cross-cultural psychologists have mostly contrasted East Asia with the West. However, this study shows that there are major psychological differences within China. We propose that a history of farming rice makes cultures more interdependent, whereas farming wheat makes cultures more independent, and these agricultural legacies continue to affect people in the modern world. We tested 1162 Han Chinese participants in six sites and found that rice-growing southern China is more interdependent and holistic-thinking than the wheat-growing north. To control for confounds like climate, we tested people from neighboring counties along the rice-wheat border and found differences that were just as large. We also find that modernization and pathogen prevalence theories do not fit the data.

Journal ArticleDOI
TL;DR: Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis, and were prevented by coinjection with nonmutated (but not with mutated) human C ECR1.
Abstract: BACKGROUND We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood. METHODS We performed whole-exome sequencing in the initial three patients and their unaffected parents and candidate-gene sequencing in three patients with a similar phenotype, as well as two young siblings with polyarteritis nodosa and one patient with small-vessel vasculitis. Enzyme assays, immunoblotting, immunohistochemical testing, flow cytometry, and cytokine profiling were performed on samples from the patients. To study protein function, we used morpholino-mediated knockdowns in zebrafish and short hairpin RNA knockdowns in U937 cells cultured with human dermal endothelial cells. RESULTS All nine patients carried recessively inherited mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), encoding adenosine deaminase 2 (ADA2), that were predicted to be deleterious; these mutations were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations, whereas the three patients with polyarteritis nodosa or small-vessel vasculitis were homozygous for the p.Gly47Arg mutation. Patients had a marked reduction in the levels of ADA2 and ADA2-specific enzyme activity in the blood. Skin, liver, and brain biopsies revealed vasculopathic changes characterized by compromised endothelial integrity, endothelial cellular activation, and inflammation. Knockdown of a zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia — phenotypes that were prevented by coinjection with nonmutated (but not with mutated) human CECR1. Monocytes from patients induced damage in cocultured endothelial-cell layers. CONCLUSIONS Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. (Funded by the National Institutes of Health Intramural Research Programs and others.)