Showing papers by "Johns Hopkins University published in 2016"
TL;DR: In this article, the authors present a cosmological analysis based on full-mission Planck observations of temperature and polarization anisotropies of the cosmic microwave background (CMB) radiation.
Abstract: This paper presents cosmological results based on full-mission Planck observations of temperature and polarization anisotropies of the cosmic microwave background (CMB) radiation. Our results are in very good agreement with the 2013 analysis of the Planck nominal-mission temperature data, but with increased precision. The temperature and polarization power spectra are consistent with the standard spatially-flat 6-parameter ΛCDM cosmology with a power-law spectrum of adiabatic scalar perturbations (denoted “base ΛCDM” in this paper). From the Planck temperature data combined with Planck lensing, for this cosmology we find a Hubble constant, H0 = (67.8 ± 0.9) km s-1Mpc-1, a matter density parameter Ωm = 0.308 ± 0.012, and a tilted scalar spectral index with ns = 0.968 ± 0.006, consistent with the 2013 analysis. Note that in this abstract we quote 68% confidence limits on measured parameters and 95% upper limits on other parameters. We present the first results of polarization measurements with the Low Frequency Instrument at large angular scales. Combined with the Planck temperature and lensing data, these measurements give a reionization optical depth of τ = 0.066 ± 0.016, corresponding to a reionization redshift of . These results are consistent with those from WMAP polarization measurements cleaned for dust emission using 353-GHz polarization maps from the High Frequency Instrument. We find no evidence for any departure from base ΛCDM in the neutrino sector of the theory; for example, combining Planck observations with other astrophysical data we find Neff = 3.15 ± 0.23 for the effective number of relativistic degrees of freedom, consistent with the value Neff = 3.046 of the Standard Model of particle physics. The sum of neutrino masses is constrained to ∑ mν < 0.23 eV. The spatial curvature of our Universe is found to be very close to zero, with | ΩK | < 0.005. Adding a tensor component as a single-parameter extension to base ΛCDM we find an upper limit on the tensor-to-scalar ratio of r0.002< 0.11, consistent with the Planck 2013 results and consistent with the B-mode polarization constraints from a joint analysis of BICEP2, Keck Array, and Planck (BKP) data. Adding the BKP B-mode data to our analysis leads to a tighter constraint of r0.002 < 0.09 and disfavours inflationarymodels with a V(φ) ∝ φ2 potential. The addition of Planck polarization data leads to strong constraints on deviations from a purely adiabatic spectrum of fluctuations. We find no evidence for any contribution from isocurvature perturbations or from cosmic defects. Combining Planck data with other astrophysical data, including Type Ia supernovae, the equation of state of dark energy is constrained to w = −1.006 ± 0.045, consistent with the expected value for a cosmological constant. The standard big bang nucleosynthesis predictions for the helium and deuterium abundances for the best-fit Planck base ΛCDM cosmology are in excellent agreement with observations. We also constraints on annihilating dark matter and on possible deviations from the standard recombination history. In neither case do we find no evidence for new physics. The Planck results for base ΛCDM are in good agreement with baryon acoustic oscillation data and with the JLA sample of Type Ia supernovae. However, as in the 2013 analysis, the amplitude of the fluctuation spectrum is found to be higher than inferred from some analyses of rich cluster counts and weak gravitational lensing. We show that these tensions cannot easily be resolved with simple modifications of the base ΛCDM cosmology. Apart from these tensions, the base ΛCDM cosmology provides an excellent description of the Planck CMB observations and many other astrophysical data sets.
10,728 citations
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TL;DR: DeepLab as discussed by the authors proposes atrous spatial pyramid pooling (ASPP) to segment objects at multiple scales by probing an incoming convolutional feature layer with filters at multiple sampling rates and effective fields-of-views.
Abstract: In this work we address the task of semantic image segmentation with Deep Learning and make three main contributions that are experimentally shown to have substantial practical merit. First, we highlight convolution with upsampled filters, or 'atrous convolution', as a powerful tool in dense prediction tasks. Atrous convolution allows us to explicitly control the resolution at which feature responses are computed within Deep Convolutional Neural Networks. It also allows us to effectively enlarge the field of view of filters to incorporate larger context without increasing the number of parameters or the amount of computation. Second, we propose atrous spatial pyramid pooling (ASPP) to robustly segment objects at multiple scales. ASPP probes an incoming convolutional feature layer with filters at multiple sampling rates and effective fields-of-views, thus capturing objects as well as image context at multiple scales. Third, we improve the localization of object boundaries by combining methods from DCNNs and probabilistic graphical models. The commonly deployed combination of max-pooling and downsampling in DCNNs achieves invariance but has a toll on localization accuracy. We overcome this by combining the responses at the final DCNN layer with a fully connected Conditional Random Field (CRF), which is shown both qualitatively and quantitatively to improve localization performance. Our proposed "DeepLab" system sets the new state-of-art at the PASCAL VOC-2012 semantic image segmentation task, reaching 79.7% mIOU in the test set, and advances the results on three other datasets: PASCAL-Context, PASCAL-Person-Part, and Cityscapes. All of our code is made publicly available online.
10,120 citations
TL;DR: The 2016 edition of the World Health Organization classification of tumors of the hematopoietic and lymphoid tissues represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition.
7,147 citations
TL;DR: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express PD-L1 as mentioned in this paper.
Abstract: BackgroundPembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non–small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). MethodsIn this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator’s choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. ResultsMedi...
7,053 citations
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.
For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.
Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
5,187 citations
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T. Prusti1, J. H. J. de Bruijne1, Anthony G. A. Brown2, Antonella Vallenari3 +621 more•Institutions (93)
TL;DR: Gaia as discussed by the authors is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach.
Abstract: Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
5,164 citations
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.
4,804 citations
TL;DR: The meta-analyses indicate protection against child infections and malocclusion, increases in intelligence, and probable reductions in overweight and diabetes, and an increase in tooth decay with longer periods of breastfeeding.
4,291 citations
TL;DR: This protocol describes all the steps necessary to process a large set of raw sequencing reads and create lists of gene transcripts, expression levels, and differentially expressed genes and transcripts.
Abstract: High-throughput sequencing of mRNA (RNA-seq) has become the standard method for measuring and comparing the levels of gene expression in a wide variety of species and conditions. RNA-seq experiments generate very large, complex data sets that demand fast, accurate and flexible software to reduce the raw read data to comprehensible results. HISAT (hierarchical indexing for spliced alignment of transcripts), StringTie and Ballgown are free, open-source software tools for comprehensive analysis of RNA-seq experiments. Together, they allow scientists to align reads to a genome, assemble transcripts including novel splice variants, compute the abundance of these transcripts in each sample and compare experiments to identify differentially expressed genes and transcripts. This protocol describes all the steps necessary to process a large set of raw sequencing reads and create lists of gene transcripts, expression levels, and differentially expressed genes and transcripts. The protocol's execution time depends on the computing resources, but it typically takes under 45 min of computer time. HISAT, StringTie and Ballgown are available from http://ccb.jhu.edu/software.shtml.
3,755 citations
TL;DR: It is emphasized that sex is a biological variable that should be considered in immunological studies and contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females.
Abstract: Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies.
TL;DR: In this article, the authors used a Bayesian hierarchical model to estimate trends in diabetes prevalence, defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs in 200 countries and territories in 21 regions, by sex and from 1980 to 2014.
TL;DR: The history of the development of PEGylated nanoparticle formulations for systemic administration is described, including how factors such as PEG molecular weight, PEG surface density, nanoparticle core properties, and repeated administration impact circulation time.
University of Nebraska Medical Center1, University of Connecticut2, Harvard University3, Queen's University4, University of California, San Diego5, Stony Brook University6, University of Michigan7, National Institutes of Health8, Johns Hopkins University9, University of Barcelona10, University at Buffalo11, Summa Health System12, University of Texas Health Science Center at San Antonio13, University of Queensland14, Royal Brisbane and Women's Hospital15, University of Western Australia16, University of Colorado Denver17, McMaster University18
TL;DR: These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia.
Abstract: It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
TL;DR: The annual estimates of child mortality by cause to 2000–15 are updated to reflect on progress toward the MDG 4 and consider implications for the Sustainable Development Goals (SDG) target for child survival.
TL;DR: In this paper, the authors used the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST) to reduce the uncertainty in the local value of the Hubble constant from 3.3% to 2.4%.
Abstract: We use the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST) to reduce the uncertainty in the local value of the Hubble constant from 3.3% to 2.4%. The bulk of this improvement comes from new near-infrared (NIR) observations of Cepheid variables in 11 host galaxies of recent type Ia supernovae (SNe Ia), more than doubling the sample of reliable SNe Ia having a Cepheid-calibrated distance to a total of 19, these in turn leverage the magnitude-redshift relation based on ∼300 SNe Ia at z < 0.15. All 19 hosts as well as the megamaser system NGC 4258 have been observed with WFC3 in the optical and NIR, thus nullifying cross-instrument zeropoint errors in the relative distance estimates from Cepheids. Other noteworthy improvements include a 33% reduction in the systematic uncertainty in the maser distance to NGC 4258, a larger sample of Cepheids in the Large Magellanic Cloud (LMC), a more robust distance to the LMC based on late-type detached eclipsing binaries (DEBs), HST observations of Cepheids in M31, and new HST-based trigonometric parallaxes for Milky Way (MW) Cepheids. We consider four geometric distance calibrations of Cepheids: (i) megamasers in NGC 4258, (ii) 8 DEBs in the LMC, (iii) 15 MW Cepheids with parallaxes measured with HST/FGS, HST/WFC3 spatial scanning and/or Hipparcos, and (iv) 2 DEBs in M31. The Hubble constant from each is 72.25 ± 2.51, 72.04 ± 2.67, 76.18 ± 2.37, and 74.50 ± 3.27 km s(−)(1) Mpc(−)(1), respectively. Our best estimate of H (0) = 73.24 ± 1.74 km s(−)(1) Mpc(−)(1) combines the anchors NGC 4258, MW, and LMC, yielding a 2.4% determination (all quoted uncertainties include fully propagated statistical and systematic components). This value is 3.4σ higher than 66.93 ± 0.62 km s(−)(1) Mpc(−)(1) predicted by ΛCDM with 3 neutrino flavors having a mass of 0.06 eV and the new Planck data, but the discrepancy reduces to 2.1σ relative to the prediction of 69.3 ± 0.7 km s(−)(1) Mpc(−)(1) based on the comparably precise combination of WMAP+ACT+SPT+BAO observations, suggesting that systematic uncertainties in CMB radiation measurements may play a role in the tension. If we take the conflict between Planck high-redshift measurements and our local determination of H (0) at face value, one plausible explanation could involve an additional source of dark radiation in the early universe in the range of ΔN (eff) ≈ 0.4–1. We anticipate further significant improvements in H (0) from upcoming parallax measurements of long-period MW Cepheids.
TL;DR: The Prostate Imaging - Reporting and Data System Version 2 (PI-RADS™ v2) simplifies and standardizes terminology and content of reports, and provides assessment categories that summarize levels of suspicion or risk of clinically significant prostate cancer that can be used to assist selection of patients for biopsies and management.
Anthony G. A. Brown1, Antonella Vallenari2, T. Prusti2, J. H. J. de Bruijne3 +587 more•Institutions (89)
TL;DR: The first Gaia data release, Gaia DR1 as discussed by the authors, consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the Hipparcos and Tycho-2 catalogues.
Abstract: Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims: A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods: The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results: Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the Hipparcos and Tycho-2 catalogues - a realisation of the Tycho-Gaia Astrometric Solution (TGAS) - and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of 3000 Cepheid and RR Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr-1 for the proper motions. A systematic component of 0.3 mas should be added to the parallax uncertainties. For the subset of 94 000 Hipparcos stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr-1. For the secondary astrometric data set, the typical uncertainty of the positions is 10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to0.03 mag over the magnitude range 5 to 20.7. Conclusions: Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data.
Boston University1, Cornell University2, Johns Hopkins University3, University of Miami4, University of California, San Francisco5, Texas A&M Health Science Center College of Medicine6, Centers for Disease Control and Prevention7, University of Washington8, Case Western Reserve University9, University of Pennsylvania10, Denver Health Medical Center11, University of Michigan12, University of California, Davis13, University of California, Los Angeles14, United States Department of Veterans Affairs15, Washington University in St. Louis16, Wake Forest University17, University of Utah18, Memorial Sloan Kettering Cancer Center19
TL;DR: These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
Abstract: Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
Oregon Health & Science University1, University of Washington2, University at Buffalo3, University of Michigan4, University of California, San Diego5, University of Iowa Hospitals and Clinics6, University of Cincinnati7, United States Department of Veterans Affairs8, Harvard University9, United States Department of the Army10, Walter Reed Army Medical Center11, University of Connecticut12, University of Colorado Denver13, Johns Hopkins University14, Veterans Health Administration15, Boston Children's Hospital16, University of Iowa17, University of Texas at Austin18, Virginia Mason Medical Center19, Thomas Jefferson University20, Seattle Children's21, Children's Hospital of Wisconsin22
TL;DR: The American Pain Society, with input from the American Society of Anesthesiologists, developed a clinical practice guideline to promote evidence-based, effective, and safer postoperative pain management in children and adults.
TL;DR: Galaxy seeks to make data-intensive research more accessible, transparent and reproducible by providing a Web-based environment in which users can perform computational analyses and have all of the details automatically tracked for later inspection, publication, or reuse.
Abstract: High-throughput data production technologies, particularly 'next-generation' DNA sequencing, have ushered in widespread and disruptive changes to biomedical research. Making sense of the large datasets produced by these technologies requires sophisticated statistical and computational methods , as well as substantial computational power. This has led to an acute crisis in life sciences, as researchers without informatics training attempt to perform computation-dependent analyses. Since 2005, the Galaxy project has worked to address this problem by providing a framework that makes advanced computational tools usable by non experts. Galaxy seeks to make data-intensive research more accessible , transparent and reproducible by providing a Web-based environment in which users can perform computational analyses and have all of the details automatically tracked for later inspection, publication , or reuse. In this report we highlight recently added features enabling biomedical analyses on a large scale.
University of Texas Health Science Center at San Antonio1, University of California, Davis2, University Hospital of South Manchester NHS Foundation Trust3, Harvard University4, Tufts University5, University of Strasbourg6, University of Texas MD Anderson Cancer Center7, Johns Hopkins University8, University of Minnesota9, University of Pittsburgh10, Roswell Park Cancer Institute11, Duke University12, Cornell University13, University of Florida14, National Institutes of Health15
TL;DR: IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Abstract: It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
University of Cambridge1, Harvard University2, Peking University3, National Institutes of Health4, University of Oxford5, Curtin University6, Australian National University7, Imperial College London8, American Cancer Society9, University of Southern California10, University of Sydney11, Johns Hopkins University12, Vanderbilt University13, Chinese Center for Disease Control and Prevention14, University of Bristol15, Capital Medical University16, Erasmus University Rotterdam17, Yonsei University18, Fred Hutchinson Cancer Research Center19, University of Turin20, University of Glasgow21, University of North Carolina at Chapel Hill22, Shiga University of Medical Science23, Innsbruck Medical University24, International Agency for Research on Cancer25, University of Hong Kong26, Massey University27
TL;DR: The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents and supports strategies to combat the entire spectrum of excess adiposity in many populations.
Centers for Disease Control and Prevention1, University of Utah2, Medical University of South Carolina3, Washington University in St. Louis4, University of North Carolina at Chapel Hill5, University of Wisconsin-Madison6, University of Arizona7, Johns Hopkins University8, University of Colorado Denver9, University of Arkansas for Medical Sciences10, Colorado Department of Public Health and Environment11, University of Alabama at Birmingham12, Rutgers University13
TL;DR: ASD prevalence estimates for children aged 8 years living in catchment areas of the ADDM Network sites in 2012 are provided, overall and stratified by sex, race/ethnicity, and the type of source records (education and health records versus health records only).
Abstract: PROBLEM/CONDITION Autism spectrum disorder (ASD). PERIOD COVERED 2012. DESCRIPTION OF SYSTEM The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that provides estimates of the prevalence and characteristics of ASD among children aged 8 years whose parents or guardians reside in 11 ADDM Network sites in the United States (Arkansas, Arizona, Colorado, Georgia, Maryland, Missouri, New Jersey, North Carolina, South Carolina, Utah, and Wisconsin). Surveillance to determine ASD case status is conducted in two phases. The first phase consists of screening and abstracting comprehensive evaluations performed by professional service providers in the community. Data sources identified for record review are categorized as either 1) education source type, including developmental evaluations to determine eligibility for special education services or 2) health care source type, including diagnostic and developmental evaluations. The second phase involves the review of all abstracted evaluations by trained clinicians to determine ASD surveillance case status. A child meets the surveillance case definition for ASD if one or more comprehensive evaluations of that child completed by a qualified professional describes behaviors that are consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnostic criteria for any of the following conditions: autistic disorder, pervasive developmental disorder-not otherwise specified (including atypical autism), or Asperger disorder. This report provides ASD prevalence estimates for children aged 8 years living in catchment areas of the ADDM Network sites in 2012, overall and stratified by sex, race/ethnicity, and the type of source records (education and health records versus health records only). In addition, this report describes the proportion of children with ASD with a score consistent with intellectual disability on a standardized intellectual ability test, the age at which the earliest known comprehensive evaluation was performed, the proportion of children with a previous ASD diagnosis, the specific type of ASD diagnosis, and any special education eligibility classification. RESULTS For 2012, the combined estimated prevalence of ASD among the 11 ADDM Network sites was 14.5 per 1,000 (one in 69) children aged 8 years. Estimated prevalence was significantly higher among boys aged 8 years (23.4 per 1,000) than among girls aged 8 years (5.2 per 1,000). Estimated ASD prevalence was significantly higher among non-Hispanic white children aged 8 years (15.3 per 1,000) compared with non-Hispanic black children (13.1 per 1,000), and Hispanic (10.2 per 1,000) children aged 8 years. Estimated prevalence varied widely among the 11 ADDM Network sites, ranging from 8.2 per 1,000 children aged 8 years (in the area of the Maryland site where only health care records were reviewed) to 24.6 per 1,000 children aged 8 years (in New Jersey, where both education and health care records were reviewed). Estimated prevalence was higher in surveillance sites where education records and health records were reviewed compared with sites where health records only were reviewed (17.1 per 1,000 and 10.4 per 1,000 children aged 8 years, respectively; p<0.05). Among children identified with ASD by the ADDM Network, 82% had a previous ASD diagnosis or educational classification; this did not vary by sex or between non-Hispanic white and non-Hispanic black children. A lower percentage of Hispanic children (78%) had a previous ASD diagnosis or classification compared with non-Hispanic white children (82%) and with non-Hispanic black children (84%). The median age at earliest known comprehensive evaluation was 40 months, and 43% of children had received an earliest known comprehensive evaluation by age 36 months. The percentage of children with an earliest known comprehensive evaluation by age 36 months was similar for boys and girls, but was higher for non-Hispanic white children (45%) compared with non-Hispanic black children (40%) and Hispanic children (39%). INTERPRETATION Overall estimated ASD prevalence was 14.5 per 1,000 children aged 8 years in the ADDM Network sites in 2012. The higher estimated prevalence among sites that reviewed both education and health records suggests the role of special education systems in providing comprehensive evaluations and services to children with developmental disabilities. Disparities by race/ethnicity in estimated ASD prevalence, particularly for Hispanic children, as well as disparities in the age of earliest comprehensive evaluation and presence of a previous ASD diagnosis or classification, suggest that access to treatment and services might be lacking or delayed for some children. PUBLIC HEALTH ACTION The ADDM Network will continue to monitor the prevalence and characteristics of ASD among children aged 8 years living in selected sites across the United States. Recommendations from the ADDM Network include enhancing strategies to 1) lower the age of first evaluation of ASD by community providers in accordance with the Healthy People 2020 goal that children with ASD are evaluated by age 36 months and begin receiving community-based support and services by age 48 months; 2) reduce disparities by race/ethnicity in identified ASD prevalence, the age of first comprehensive evaluation, and presence of a previous ASD diagnosis or classification; and 3) assess the effect on ASD prevalence of the revised ASD diagnostic criteria published in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2 +679 more•Institutions (268)
TL;DR: In this paper, the authors used the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.
TL;DR: Patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab were having a rare, potentially fatal, T-cell-driven drug reaction, according to Pharmacovigilance studies.
Abstract: Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle. Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction. (Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.).
TL;DR: The open-source FALCON and FALcon-Unzip algorithms are introduced to assemble long-read sequencing data into highly accurate, contiguous, and correctly phased diploid genomes.
Abstract: While genome assembly projects have been successful in many haploid and inbred species, the assembly of noninbred or rearranged heterozygous genomes remains a major challenge. To address this challenge, we introduce the open-source FALCON and FALCON-Unzip algorithms (https://github.com/PacificBiosciences/FALCON/) to assemble long-read sequencing data into highly accurate, contiguous, and correctly phased diploid genomes. We generate new reference sequences for heterozygous samples including an F1 hybrid of Arabidopsis thaliana, the widely cultivated Vitis vinifera cv. Cabernet Sauvignon, and the coral fungus Clavicorona pyxidata, samples that have challenged short-read assembly approaches. The FALCON-based assemblies are substantially more contiguous and complete than alternate short- or long-read approaches. The phased diploid assembly enabled the study of haplotype structure and heterozygosities between homologous chromosomes, including the identification of widespread heterozygous structural variation within coding sequences.
James Bentham1, Mariachiara Di Cesare2, Mariachiara Di Cesare1, Gretchen A Stevens3 +787 more•Institutions (246)
TL;DR: The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Abstract: Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Stanford University1, Icahn School of Medicine at Mount Sinai2, Indiana University3, Memorial Sloan Kettering Cancer Center4, Mayo Clinic5, National Institutes of Health6, University of Utah7, Fred Hutchinson Cancer Research Center8, Johns Hopkins University9, NorthShore University HealthSystem10, University of Michigan11, University of North Carolina at Chapel Hill12, University of Turku13, Translational Genomics Research Institute14, Wayne State University15, University of Paris16, University of Melbourne17, Cancer Council Victoria18, University of Ulm19, University of Southern California20, Karolinska Institutet21, Northwestern University22, McGill University23, LSU Health Sciences Center New Orleans24
TL;DR: This work developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, LRT, GERP, SiPhy, phyloP, and phastCons.
Abstract: The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery of disease variants from exome sequencing studies. We developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. REVEL was trained with recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. When applied to two independent test sets, REVEL had the best overall performance (p −12 ) as compared to any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies
TL;DR: In this paper, the authors considered the possibility that the black-hole binary detected by LIGO may be a signature of dark matter and showed that there remains a window for masses 20M⊙ √ √ m −1 −2 m −3 m −2 n −1 where primordial black holes (PBHs) may constitute the dark matter.
Abstract: We consider the possibility that the black-hole (BH) binary detected by LIGO may be a signature of dark matter. Interestingly enough, there remains a window for masses 20M_{⊙}≲M_{bh}≲100M_{⊙} where primordial black holes (PBHs) may constitute the dark matter. If two BHs in a galactic halo pass sufficiently close, they radiate enough energy in gravitational waves to become gravitationally bound. The bound BHs will rapidly spiral inward due to the emission of gravitational radiation and ultimately will merge. Uncertainties in the rate for such events arise from our imprecise knowledge of the phase-space structure of galactic halos on the smallest scales. Still, reasonable estimates span a range that overlaps the 2-53 Gpc^{-3} yr^{-1} rate estimated from GW150914, thus raising the possibility that LIGO has detected PBH dark matter. PBH mergers are likely to be distributed spatially more like dark matter than luminous matter and have neither optical nor neutrino counterparts. They may be distinguished from mergers of BHs from more traditional astrophysical sources through the observed mass spectrum, their high ellipticities, or their stochastic gravitational wave background. Next-generation experiments will be invaluable in performing these tests.