Showing papers by "University of Washington published in 2015"
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
12,661 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.
5,792 citations
Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
Alexander A. Aarts, Joanna E. Anderson1, Christopher J. Anderson2, Peter Raymond Attridge3 +287 more•Institutions (116)
TL;DR: A large-scale assessment suggests that experimental reproducibility in psychology leaves a lot to be desired, and correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
Abstract: Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
5,532 citations
Massachusetts Institute of Technology1, Broad Institute2, University of California, Los Angeles3, University of British Columbia4, Baylor College of Medicine5, Howard Hughes Medical Institute6, University of Washington7, Ludwig Institute for Cancer Research8, University of California, San Francisco9, University of Connecticut10, University of Zagreb11, University of Texas at Austin12, Washington University in St. Louis13, University of Queensland14, Harvard University15, Cold Spring Harbor Laboratory16, University of Southern California17, University of California, Santa Cruz18, Simon Fraser University19, Morgridge Institute for Research20, University of Texas at Dallas21, National Institutes of Health22
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
5,037 citations
Memorial Sloan Kettering Cancer Center1, Institut Gustave Roussy2, Harvard University3, Roswell Park Cancer Institute4, Johns Hopkins University5, Stanford University6, University of Washington7, Vanderbilt University8, Fox Chase Cancer Center9, Macquarie University10, Aarhus University11, University of Helsinki12, The Royal Marsden NHS Foundation Trust13, University of Duisburg-Essen14, Niigata University15, Swansea University16, University of British Columbia17, Bristol-Myers Squibb18, University of Texas MD Anderson Cancer Center19
TL;DR: Overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus among patients with previously treated advanced renal-cell carcinoma.
Abstract: BackgroundNivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. MethodsA total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. ResultsThe median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The haz...
4,643 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
4,510 citations
Harvard University1, Genentech2, Fred Hutchinson Cancer Research Center3, State University of Campinas4, University of Maryland, College Park5, National Institutes of Health6, University of Cambridge7, University of California, Riverside8, Novartis9, Johns Hopkins University10, University of Washington11, Walter and Eliza Hall Institute of Medical Research12, City University of New York13
TL;DR: An overview of Bioconductor, an open-source, open-development software project for the analysis and comprehension of high-throughput data in genomics and molecular biology, which comprises 934 interoperable packages contributed by a large, diverse community of scientists.
Abstract: Bioconductor is an open-source, open-development software project for the analysis and comprehension of high-throughput data in genomics and molecular biology. The project aims to enable interdisciplinary research, collaboration and rapid development of scientific software. Based on the statistical programming language R, Bioconductor comprises 934 interoperable packages contributed by a large, diverse community of scientists. Packages cover a range of bioinformatic and statistical applications. They undergo formal initial review and continuous automated testing. We present an overview for prospective users and contributors.
2,818 citations
University of Michigan1, Massachusetts Institute of Technology2, Harvard University3, Memorial Sloan Kettering Cancer Center4, University of Washington5, Institute of Cancer Research6, The Royal Marsden NHS Foundation Trust7, Cornell University8, Brigham and Women's Hospital9, Beth Israel Deaconess Medical Center10, University of Washington Medical Center11, University of Trento12, Wayne State University13, Johns Hopkins University14
TL;DR: This cohort study provides clinically actionable information that could impact treatment decisions for affected individuals and identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF.
2,713 citations
Baylor College of Medicine1, Stanford University2, University of Pittsburgh3, University of California, Los Angeles4, Sapienza University of Rome5, Loyola University Chicago6, University of Texas at Austin7, University of Texas Southwestern Medical Center8, Boston Children's Hospital9, University of Chicago10, Johns Hopkins University School of Medicine11, Georgetown University12, University of Toronto13, Gannon University14, American Academy of Pediatrics15, University of Louisville16, University of Washington17, Eastern Virginia Medical School18
TL;DR: A scientifically rigorous update to the National Sleep Foundation's sleep duration recommendations, determined expert recommendations for sufficient sleep durations across the lifespan using the RAND/UCLA Appropriateness Method.
2,568 citations
Shadab Alam1, Franco D. Albareti2, Carlos Allende Prieto3, Carlos Allende Prieto4 +360 more•Institutions (102)
TL;DR: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrogram, and a novel optical interferometer.
Abstract: The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 sq. deg of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-Object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include measured abundances of 15 different elements for each star. In total, SDSS-III added 2350 sq. deg of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 sq. deg; 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5,513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra.
Institute for Health Metrics and Evaluation1, University of Washington2, Iran University of Medical Sciences3, King's College London4, Arabian Gulf University5, University of North Texas6, Auckland University of Technology7, Alaska Native Tribal Health Consortium8, Columbia University9, Wuhan University10, Imperial College London11, University of Alabama at Birmingham12, University at Albany, SUNY13, City University of New York14, University of California, San Francisco15, Griffith University16, Environment Agency17, New York University18, Southern University College19, Emory University20, University of Ottawa21, Kosin University22, University of Toronto23, University of British Columbia24, United Arab Emirates University25, Albert Einstein College of Medicine26, University of São Paulo27, Nova Southeastern University28, University of Sydney29, Heidelberg University30, Cancer Treatment Centers of America31, Case Western Reserve University32, University of Oxford33, George Mason University34, James Cook University35, University of Trieste36, University of Calgary37, Wageningen University and Research Centre38, University of Gothenburg39, University of the Witwatersrand40, Harvard University41, Jackson State University42, University of Arizona43, University of Hong Kong44, Tehran University of Medical Sciences45, University of Western Australia46, Aintree University Hospitals NHS Foundation Trust47, Veterans Health Administration48, University of Colorado Denver49, University of Melbourne50, Royal Children's Hospital51, Australian National University52, University of Marburg53, Charité54, Health Canada55, College of Health Sciences, Bahrain56, Karolinska Institutet57, Northumbria University58, University of Edinburgh59, National Research University – Higher School of Economics60, Queen Mary University of London61, Addis Ababa University62, Northwestern University63, Northeastern University64, Mario Negri Institute for Pharmacological Research65, Arak University of Medical Sciences66, University of Nottingham67, University of Tokyo68, Public Health Foundation of India69, University of Groningen70, University of the Philippines Manila71, University of Bologna72, Kyung Hee University73, Brighton and Sussex Medical School74, University of Bergen75, Stavanger University Hospital76, University of Queensland77, National Centre for Disease Control78, University of Sheffield79, Universidad Autónoma Metropolitana80, University College London81, Genentech82, Universiti Tunku Abdul Rahman83, Norwegian Institute of Public Health84
TL;DR: To estimate mortality, incidence, years lived with disability, years of life lost, and disability-adjusted life-years for 28 cancers in 188 countries by sex from 1990 to 2013, the general methodology of the Global Burden of Disease 2013 study was used.
Abstract: Importance Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and Relevance Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.
University of Washington1, University of Maryland, Baltimore2, Harvard University3, Broad Institute4, Mayo Clinic5, Yale University6, Washington University in St. Louis7, University of Michigan8, University of Texas Health Science Center at Houston9, Louisiana State University10, University of North Carolina at Charlotte11, Wellcome Trust12, University of Texas MD Anderson Cancer Center13, Boston College14, Yeshiva University15, Bilkent University16, University of California, San Diego17, National Institutes of Health18, Leiden University19, Baylor College of Medicine20, Cornell University21, University of Oxford22, Utrecht University23, Icahn School of Medicine at Mount Sinai24, Kyoto University25, Virginia Commonwealth University26, Heidelberg University27, Ewha Womans University28
TL;DR: In this paper, the authors describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which are constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations.
Abstract: Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.
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TL;DR: The capabilities of all the tools within the MEME suite are described, advice on their best use is given and several case studies are provided to illustrate how to combine the results of various MEME Suite tools for successful motif-based analyses.
Abstract: The MEME Suite is a powerful, integrated set of web-based tools for studying sequence motifs in proteins, DNA and RNA. Such motifs encode many biological functions, and their detection and characterization is important in the study of molecular interactions in the cell, including the regulation of gene expression. Since the previous description of the MEME Suite in the 2009 Nucleic Acids Research Web Server Issue, we have added six new tools. Here we describe the capabilities of all the tools within the suite, give advice on their best use and provide several case studies to illustrate how to combine the results of various MEME Suite tools for successful motif-based analyses. The MEME Suite is freely available for academic use at http://meme-suite.org, and source code is also available for download and local installation.
TL;DR: Major tumour regressions are reported in a subset of patients with metastatic melanoma treated with an anti-CTLA4 antibody and radiation and reproduced this effect in mouse models, showing that PD-L1 on melanoma cells allows tumours to escape anti- NCTLA4-based therapy, and the combination of radiation, anti- CTLA4 and anti-PD-L 1 promotes response and immunity through distinct mechanisms.
Abstract: Immune checkpoint inhibitors result in impressive clinical responses, but optimal results will require combination with each other and other therapies. This raises fundamental questions about mechanisms of non-redundancy and resistance. Here we report major tumour regressions in a subset of patients with metastatic melanoma treated with an anti-CTLA4 antibody (anti-CTLA4) and radiation, and reproduced this effect in mouse models. Although combined treatment improved responses in irradiated and unirradiated tumours, resistance was common. Unbiased analyses of mice revealed that resistance was due to upregulation of PD-L1 on melanoma cells and associated with T-cell exhaustion. Accordingly, optimal response in melanoma and other cancer types requires radiation, anti-CTLA4 and anti-PD-L1/PD-1. Anti-CTLA4 predominantly inhibits T-regulatory cells (Treg cells), thereby increasing the CD8 T-cell to Treg (CD8/Treg) ratio. Radiation enhances the diversity of the T-cell receptor (TCR) repertoire of intratumoral T cells. Together, anti-CTLA4 promotes expansion of T cells, while radiation shapes the TCR repertoire of the expanded peripheral clones. Addition of PD-L1 blockade reverses T-cell exhaustion to mitigate depression in the CD8/Treg ratio and further encourages oligoclonal T-cell expansion. Similarly to results from mice, patients on our clinical trial with melanoma showing high PD-L1 did not respond to radiation plus anti-CTLA4, demonstrated persistent T-cell exhaustion, and rapidly progressed. Thus, PD-L1 on melanoma cells allows tumours to escape anti-CTLA4-based therapy, and the combination of radiation, anti-CTLA4 and anti-PD-L1 promotes response and immunity through distinct mechanisms.
TL;DR: A plateau in the survival curve was observed, beginning at approximately 3 years, which was independent of prior therapy or ipilimumab dose, and added to the evidence supporting the durability of long-term survival in ipILimumab-treated patients with advanced melanoma.
Abstract: Purpose To provide a more precise estimate of long-term survival observed for ipilimumab-treated patients with advanced melanoma, we performed a pooled analysis of overall survival (OS) data from multiple studies. Methods The primary analysis pooled OS data for 1,861 patients from 10 prospective and two retrospective studies of ipilimumab, including two phase III trials. Patients were previously treated (n = 1,257) or treatment naive (n = 604), and the majority of patients received ipilimumab 3 mg/kg (n = 965) or 10 mg/kg (n = 706). We also conducted a secondary analysis of OS data (n = 4,846) with an additional 2,985 patients from an expanded access program. OS rates were estimated using the Kaplan-Meier method. Results Among 1,861 patients, median OS was 11.4 months (95% CI, 10.7 to 12.1 months), which included 254 patients with at least 3 years of survival follow-up. The survival curve began to plateau around year 3, with follow-up of up to 10 years. Three-year survival rates were 22%, 26%, and 20% for...
TL;DR: The grain boundaries were dimmer and exhibited faster nonradiative decay, and energy-dispersive x-ray spectroscopy showed a positive correlation between chlorine concentration and regions of brighter PL, whereas PL imaging revealed that chemical treatment with pyridine could activate previously dark grains.
Abstract: The remarkable performance of hybrid perovskite photovoltaics is attributed to their long carrier lifetimes and high photoluminescence (PL) efficiencies. High-quality films are associated with slower PL decays, and it has been claimed that grain boundaries have a negligible impact on performance. We used confocal fluorescence microscopy correlated with scanning electron microscopy to spatially resolve the PL decay dynamics from films of nonstoichiometric organic-inorganic perovskites, CH3NH3PbI3(Cl). The PL intensities and lifetimes varied between different grains in the same film, even for films that exhibited long bulk lifetimes. The grain boundaries were dimmer and exhibited faster nonradiative decay. Energy-dispersive x-ray spectroscopy showed a positive correlation between chlorine concentration and regions of brighter PL, whereas PL imaging revealed that chemical treatment with pyridine could activate previously dark grains.
Mohammad H. Forouzanfar1, Lily Alexander1, H. Ross Anderson2, Victoria F Bachman1 +718 more•Institutions (295)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
University of Texas Health Science Center at Houston1, Medical College of Wisconsin2, Oregon Health & Science University3, University of Washington4, University of California, San Francisco5, University of Tennessee Health Science Center6, University of Southern California7, University of Alabama at Birmingham8, University of Cincinnati9, University of Arizona10, University of Toronto11, University of Maryland, Baltimore12, Sunnybrook Health Sciences Centre13, American College of Surgeons14, National Institutes of Health15
TL;DR: In this article, the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1 :1:2 ratio was evaluated.
Abstract: Importance Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. Objective To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Design, Setting, and Participants Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Interventions Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Main Outcomes and Measures Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. Results No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, −4.2% [95% CI, −9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, −3.7% [95% CI, −10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, −5.4% [95% CI, −10.4% to −0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P P Conclusions and Relevance Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. Trial Registration clinicaltrials.gov Identifier:NCT01545232
Christopher J L Murray1, Ryan M Barber, Kyle J Foreman2, Ayse Abbasoglu Ozgoren +608 more•Institutions (251)
TL;DR: Patterns of the epidemiological transition with a composite indicator of sociodemographic status, which was constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population, were quantified.
National University of Cordoba1, Addis Ababa University2, National Autonomous University of Mexico3, State University of Campinas4, United Nations Environment Programme5, UNESCO6, United States Department of Agriculture7, Indiana University8, University of British Columbia9, Commonwealth Scientific and Industrial Research Organisation10, University of Paris-Sud11, Landcare Research12, University College London13, Autonomous University of Madrid14, University of Cambridge15, Council for Scientific and Industrial Research16, University of Southern Denmark17, United Nations University18, Virginia Tech College of Natural Resources and Environment19, The Nature Conservancy20, University of the South Pacific21, University of East Anglia22, Kyushu University23, King Abdulaziz City for Science and Technology24, University of Washington25, Budapest University of Technology and Economics26, Environmental Law Institute27, Ankara University28, University of Portsmouth29, Chinese Academy of Sciences30, Indian Institute of Technology Bombay31, Kyoto University32, Joseph Fourier University33, National Scientific and Technical Research Council34, University of Yaoundé35, Polish Academy of Sciences36, University of São Paulo37, École Normale Supérieure38, University of Otago39, Stanford University40, University of Queensland41, Azim Premji University42, Helmholtz Centre for Environmental Research - UFZ43, University of Ghana44, Corvinus University of Budapest45, Stockholm University46, Lakehead University47, Indian Institute of Forest Management48, Seoul National University49, Sofia University50
TL;DR: The first public product of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) is its Conceptual Framework as discussed by the authors, which will underpin all IPBES functions and provide structure and comparability to the syntheses that will produce at different spatial scales, on different themes, and in different regions.
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
TL;DR: A comparison with different topologies of dynamic neural networks as well as other prevailing parametric and nonparametric algorithms suggests that LSTM NN can achieve the best prediction performance in terms of both accuracy and stability.
Abstract: Neural networks have been extensively applied to short-term traffic prediction in the past years. This study proposes a novel architecture of neural networks, Long Short-Term Neural Network (LSTM NN), to capture nonlinear traffic dynamic in an effective manner. The LSTM NN can overcome the issue of back-propagated error decay through memory blocks, and thus exhibits the superior capability for time series prediction with long temporal dependency. In addition, the LSTM NN can automatically determine the optimal time lags. To validate the effectiveness of LSTM NN, travel speed data from traffic microwave detectors in Beijing are used for model training and testing. A comparison with different topologies of dynamic neural networks as well as other prevailing parametric and nonparametric algorithms suggests that LSTM NN can achieve the best prediction performance in terms of both accuracy and stability.
University College London1, University of London2, Johns Hopkins University3, Rockefeller Foundation4, United Nations University5, University of Washington6, Tsinghua University7, Harvard University8, Wildlife Conservation Society9, Duke University10, United States Environmental Protection Agency11, World Bank12
TL;DR: In this paper, the authors identify three categories of challenges that have to be addressed to maintain and enhance human health in the face of increasingly harmful environmental trends: conceptual and empathy failures (imagination challenges), such as an overreliance on gross domestic product as a measure of human progress, the failure to account for future health and environmental harms over present day gains, and the disproportionate eff ect of those harms on the poor and those in developing nations.
University of Washington1, Pacific Northwest National Laboratory2, University of Wisconsin-Madison3, Radcliffe Institute for Advanced Study4, Eindhoven University of Technology5, University of Minnesota6, Lawrence Berkeley National Laboratory7, Northwestern University8, University of California, Berkeley9, University of Houston10, University of California, Davis11, University of Delaware12, Virginia Tech13, University of Leeds14, University of Konstanz15
TL;DR: The current understanding of CPA is described, some of the nonclassical thermodynamic and dynamic mechanisms known to give rise to experimentally observed pathways are examined, and the challenges to the understanding of these mechanisms are highlighted.
Abstract: Field and laboratory observations show that crystals commonly form by the addition and attachment of particles that range from multi-ion complexes to fully formed nanoparticles. The particles involved in these nonclassical pathways to crystallization are diverse, in contrast to classical models that consider only the addition of monomeric chemical species. We review progress toward understanding crystal growth by particle-attachment processes and show that multiple pathways result from the interplay of free-energy landscapes and reaction dynamics. Much remains unknown about the fundamental aspects, particularly the relationships between solution structure, interfacial forces, and particle motion. Developing a predictive description that connects molecular details to ensemble behavior will require revisiting long-standing interpretations of crystal formation in synthetic systems, biominerals, and patterns of mineralization in natural environments.
TL;DR: An overview of machine learning applications for the analysis of genome sequencing data sets, including the annotation of sequence elements and epigenetic, proteomic or metabolomic data is provided.
Abstract: The field of machine learning, which aims to develop computer algorithms that improve with experience, holds promise to enable computers to assist humans in the analysis of large, complex data sets. Here, we provide an overview of machine learning applications for the analysis of genome sequencing data sets, including the annotation of sequence elements and epigenetic, proteomic or metabolomic data. We present considerations and recurrent challenges in the application of supervised, semi-supervised and unsupervised machine learning methods, as well as of generative and discriminative modelling approaches. We provide general guidelines to assist in the selection of these machine learning methods and their practical application for the analysis of genetic and genomic data sets.
TL;DR: This work demonstrates optical pumping of interlayer electric polarization, which may provoke further exploration of inter layer exciton condensation, as well as new applications in two-dimensional lasers, light-emitting diodes and photovoltaic devices.
Abstract: Monolayer transition metal dichalcogenide heterostructures with type II band alignment have generated wide interest in device physics at the two-dimensional limit. Here, Rivera et al. observe interlayer excitons in vertically stacked MoSe2–WSe2 heterostructures and demonstrate tunability of the energy and luminescence.
TL;DR: In this paper, the authors review the performance of the LIGO instruments during this epoch, the work done to characterize the detectors and their data, and the effect that transient and continuous noise artefacts have on the sensitivity of the detectors to a variety of astrophysical sources.
Abstract: In 2009–2010, the Laser Interferometer Gravitational-Wave Observatory (LIGO) operated together with international partners Virgo and GEO600 as a network to search for gravitational waves (GWs) of astrophysical origin. The sensitivity of these detectors was limited by a combination of noise sources inherent to the instrumental design and its environment, often localized in time or frequency, that couple into the GW readout. Here we review the performance of the LIGO instruments during this epoch, the work done to characterize the detectors and their data, and the effect that transient and continuous noise artefacts have on the sensitivity of LIGO to a variety of astrophysical sources.
Stanford University1, Baylor College of Medicine2, University of Pittsburgh3, University of California, Los Angeles4, Sapienza University of Rome5, Loyola University Chicago6, University of Texas at Austin7, University of Texas Southwestern Medical Center8, Boston Children's Hospital9, University of Chicago10, Johns Hopkins University School of Medicine11, Georgetown University12, University of Toronto13, Gannon University14, American Academy of Pediatrics15, University of Louisville16, University of Washington17, Eastern Virginia Medical School18
TL;DR: Consensus using a multidisciplinary expert Panel lends robust credibility to the results and the self-designated basis for duration selection and critical discussions are provided.
University of Washington1, Fred Hutchinson Cancer Research Center2, American Society of Clinical Oncology3, Cleveland Clinic4, University of British Columbia5, Pennsylvania State University6, Duke University7, Emory University8, University of Rochester9, University of North Carolina at Chapel Hill10, McMaster University11, University of Southern California12, University of California, San Francisco13, University of Michigan14
TL;DR: Current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer and oncology professionals should educate patients about the signs and symptoms of VTE.
Abstract: Purpose To provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.