Showing papers by "National Institutes of Health published in 2017"
Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
TL;DR: Canu, a successor of Celera Assembler that is specifically designed for noisy single-molecule sequences, is presented, demonstrating that Canu can reliably assemble complete microbial genomes and near-complete eukaryotic chromosomes using either Pacific Biosciences or Oxford Nanopore technologies.
Abstract: Long-read single-molecule sequencing has revolutionized de novo genome assembly and enabled the automated reconstruction of reference-quality genomes. However, given the relatively high error rates of such technologies, efficient and accurate assembly of large repeats and closely related haplotypes remains challenging. We address these issues with Canu, a successor of Celera Assembler that is specifically designed for noisy single-molecule sequences. Canu introduces support for nanopore sequencing, halves depth-of-coverage requirements, and improves assembly continuity while simultaneously reducing runtime by an order of magnitude on large genomes versus Celera Assembler 8.2. These advances result from new overlapping and assembly algorithms, including an adaptive overlapping strategy based on tf-idf weighted MinHash and a sparse assembly graph construction that avoids collapsing diverged repeats and haplotypes. We demonstrate that Canu can reliably assemble complete microbial genomes and near-complete eukaryotic chromosomes using either Pacific Biosciences (PacBio) or Oxford Nanopore technologies and achieves a contig NG50 of >21 Mbp on both human and Drosophila melanogaster PacBio data sets. For assembly structures that cannot be linearly represented, Canu provides graph-based assembly outputs in graphical fragment assembly (GFA) format for analysis or integration with complementary phasing and scaffolding techniques. The combination of such highly resolved assembly graphs with long-range scaffolding information promises the complete and automated assembly of complex genomes.
4,806 citations
Valery L. Feigin1, Amanuel Alemu Abajobir2, Kalkidan Hassen Abate3, Foad Abd-Allah4 +267 more•Institutions (138)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions as discussed by the authors.
Abstract: Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.
2,995 citations
Icahn School of Medicine at Mount Sinai1, Pure Earth2, World Bank3, University of Arizona4, McGill University5, Indian Ministry of Environment and Forests6, Qatar Airways7, Ludwig Maximilian University of Munich8, University of Health Sciences Antigua9, Johns Hopkins University10, Boston College11, Chulabhorn Research Institute12, University of Maryland, College Park13, University of Ghana14, Centro Nacional de Investigaciones Cardiovasculares15, University of Chicago16, University of London17, University of Oxford18, Indian Institute of Technology Delhi19, Simon Fraser University20, Consortium of Universities for Global Health21, University of Ottawa22, Columbia University23, Stockholm Resilience Centre24, Massachusetts Institute of Technology25, University of Queensland26, University of California, Berkeley27, New York University28, National Institutes of Health29, Public Health Research Institute30, United Nations Industrial Development Organization31, Renmin University of China32
TL;DR: This book is dedicated to the memory of those who have served in the armed forces and their families during the conflicts of the twentieth century.
2,628 citations
Newcastle University1, University of Sydney2, Mayo Clinic3, National Institutes of Health4, University of Pennsylvania5, Houston Methodist Hospital6, Veterans Health Administration7, Stavanger University Hospital8, King's College London9, University of Exeter10, Van Andel Institute11, Nagoya University12, Rush University Medical Center13, Harvard University14, Columbia University15, University College London16, University of North Carolina at Chapel Hill17, University of Barcelona18, Thomas Jefferson University19, University of Washington20, Cleveland Clinic21, Khalifa University22, University of California, San Diego23, Stanford University24, University of Strasbourg25, University of Michigan26, University of Chieti-Pescara27, United States Department of Veterans Affairs28
TL;DR: The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade.
Abstract: The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.
2,558 citations
University of Marburg1, Temple University2, NewYork–Presbyterian Hospital3, University of Texas Health Science Center at San Antonio4, National Institutes of Health5, McGill University Health Centre6, Brigham and Women's Hospital7, Guangzhou Medical University8, Katholieke Universiteit Leuven9, University of Modena and Reggio Emilia10, Flinders University11, Royal Devon and Exeter Hospital12, University of the Republic13, Hokkaido University14, University of Paris15, University of Barcelona16, University of British Columbia17, University of Manchester18
TL;DR: The assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation, and the concept of deescalation of therapy is introduced in the treatment assessment scheme.
Abstract: This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 report focuses primarily on the revised and novel parts of the document. The most significant changes include: (1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (2) for each of the groups A to D, escalation strategies for pharmacologic treatments are proposed; (3) the concept of deescalation of therapy is introduced in the treatment assessment scheme; (4) nonpharmacologic therapies are comprehensively presented; and (5) the importance of comorbid conditions in managing chronic obstructive pulmonary disease is reviewed.
2,547 citations
Gregory A. Roth1, Catherine O. Johnson1, Amanuel Alemu Abajobir2, Foad Abd-Allah3 +170 more•Institutions (99)
TL;DR: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden, finding that CVDs remain a major cause of health loss for all regions of the world.
2,525 citations
TL;DR: NCBI's Conserved Domain Database (CDD) aims at annotating biomolecular sequences with the location of evolutionarily conserved protein domain footprints, and functional sites inferred from such footprints.
Abstract: NCBI's Conserved Domain Database (CDD) aims at annotating biomolecular sequences with the location of evolutionarily conserved protein domain footprints, and functional sites inferred from such footprints. An archive of pre-computed domain annotation is maintained for proteins tracked by NCBI's Entrez database, and live search services are offered as well. CDD curation staff supplements a comprehensive collection of protein domain and protein family models, which have been imported from external providers, with representations of selected domain families that are curated in-house and organized into hierarchical classifications of functionally distinct families and sub-families. CDD also supports comparative analyses of protein families via conserved domain architectures, and a recent curation effort focuses on providing functional characterizations of distinct subfamily architectures using SPARCLE: Subfamily Protein Architecture Labeling Engine. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.
2,052 citations
TL;DR: A Cas13a-based molecular detection platform, termed Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK), is used to detect specific strains of Zika and Dengue virus, distinguish pathogenic bacteria, genotype human DNA, and identify mutations in cell-free tumor DNA.
Abstract: Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting clustered regularly interspaced short palindromic repeats (CRISPR) effector Cas13a (previously known as C2c2) exhibits a “collateral effect” of promiscuous ribonuclease activity upon target recognition. We combine the collateral effect of Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity. We use this Cas13a-based molecular detection platform, termed Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK), to detect specific strains of Zika and Dengue virus, distinguish pathogenic bacteria, genotype human DNA, and identify mutations in cell-free tumor DNA. Furthermore, SHERLOCK reaction reagents can be lyophilized for cold-chain independence and long-term storage and be readily reconstituted on paper for field applications.
1,946 citations
Imperial College London1, Anglia Ruskin University2, University of New South Wales3, Brien Holden Vision Institute4, International Agency for the Prevention of Blindness5, Moorfields Eye Hospital6, York Hospital7, Heidelberg University8, L V Prasad Eye Institute9, Massachusetts Eye and Ear Infirmary10, Nova Southeastern University11, University of KwaZulu-Natal12, National Health and Medical Research Council13, World Health Organization14, National University of Singapore15, University of Melbourne16, Selçuk University17, University of Miami18, University of Adelaide19, Queen's University Belfast20, Harvard University21, The George Institute for Global Health22, University of Washington23, University of Michigan24, Universiti Tunku Abdul Rahman25, University of Alabama at Birmingham26, National Institutes of Health27, Johns Hopkins University28, University of São Paulo29, Henry Ford Health System30, University College London31, Sankara Nethralaya32, University of Nairobi33, University of Georgia34, University of Utah35, Federal University of São Paulo36, Yale University37, Alberta Children's Hospital38, University of Illinois at Chicago39, Medical College of Wisconsin40, Novartis41, University of Udine42, University of Illinois at Urbana–Champaign43, Royal Children's Hospital44, University of Missouri45, Centers for Disease Control and Prevention46, University of Milan47, Icahn School of Medicine at Mount Sinai48, Mayo Clinic49, Pan American Health Organization50, University of Indonesia51, University of Pennsylvania52, University of Crete53, University of Southern California54, University of Florence55, Capital Medical University56, Leipzig University57
TL;DR: A series of regression models were fitted to estimate the proportion of moderate or severe vision impairment and blindness by cause, age, region, and year, and found that world regions varied markedly in the causes of blindness and vision impairment in this age group.
1,909 citations
TL;DR: Improvements to the NHGRI-EBI GWAS Catalog improved the data release frequency by increasing automation of curation and providing scaling improvements, allowing the Catalog to adapt to the needs of evolving study design, genotyping technologies and user needs in the future.
Abstract: The NHGRI-EBI GWAS Catalog has provided data from published genome-wide association studies since 2008. In 2015, the database was redesigned and relocated to EMBL-EBI. The new infrastructure includes a new graphical user interface (www.ebi.ac.uk/gwas/), ontology supported search functionality and an improved curation interface. These developments have improved the data release frequency by increasing automation of curation and providing scaling improvements. The range of available Catalog data has also been extended with structured ancestry and recruitment information added for all studies. The infrastructure improvements also support scaling for larger arrays, exome and sequencing studies, allowing the Catalog to adapt to the needs of evolving study design, genotyping technologies and user needs in the future.
A. Gordon Robertson1, Jaegil Kim2, Hikmat Al-Ahmadie3, Joaquim Bellmunt4 +167 more•Institutions (16)
TL;DR: An analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms identified 5 expression subtypes that may stratify response to different treatments and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology.
TL;DR: Although stroke incidence, prevalence, mortality, and disability-adjusted life-years rates tend to decline from 1990 to 2013, the overall stroke burden has increased across the globe and provides a strong argument that "business as usual" for primary stroke prevention is not sufficiently effective.
Abstract: On the basis of the GBD (Global Burden of Disease) 2013 Study, this article provides an overview of the global, regional, and country-specific burden of stroke by sex and age groups, including trends in stroke burden from 1990 to 2013, and outlines recommended measures to reduce stroke burden. It shows that although stroke incidence, prevalence, mortality, and disability-adjusted life-years rates tend to decline from 1990 to 2013, the overall stroke burden in terms of absolute number of people affected by, or who remained disabled from, stroke has increased across the globe in both men and women of all ages. This provides a strong argument that "business as usual" for primary stroke prevention is not sufficiently effective. Although prevention of stroke is a complex medical and political issue, there is strong evidence that substantial prevention of stroke is feasible in practice. The need to scale-up the primary prevention actions is urgent.
TL;DR: The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries, and the contributions of changes in prevalence versus population growth and ageing to the increase.
Institute for Health Metrics and Evaluation1, Jimma University2, University of Alabama at Birmingham3, University of Oxford4, University of Cartagena5, University College London6, Harvard University7, Wellcome Trust8, University of Canterbury9, Madawalabu University10, Ottawa Hospital Research Institute11, University of Valencia12, Auckland University of Technology13, University of Coimbra14, Bielefeld University15, Mekelle University16, University of Massachusetts Boston17, University of Western Australia18, Harry Perkins Institute of Medical Research19, Heidelberg University20, New Generation University College21, Southern University College22, Simmons College23, Brown University24, University of Melbourne25, University of São Paulo26, University of Adelaide27, National Institutes of Health28, Columbia University29, Southern Illinois University Carbondale30, Ministry of Health and Social Welfare31, Teikyo University32, University of British Columbia33, Marshall University34, South African Medical Research Council35, Addis Ababa University36, Arba Minch University37, University of Edinburgh38, Northumbria University39, James Cook University40, Monash University41, University of Calgary42, University of Copenhagen43, University of Warwick44, National Research University – Higher School of Economics45, Duke University46, Northwestern University47
TL;DR: In international surveys, although there is uncertainty in some estimates, the rate of elevatedSBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased.
Abstract: Importance Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 95.9 million (95% UI, 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.
Anglia Ruskin University1, University of Oxford2, Heidelberg University3, L V Prasad Eye Institute4, Massachusetts Eye and Ear Infirmary5, Nova Southeastern University6, Brien Holden Vision Institute7, University of KwaZulu-Natal8, Flinders University9, University of New South Wales10, Royal Liverpool University Hospital11, World Health Organization12, National University of Singapore13, University of Melbourne14, Selçuk University15, University of Burgundy16, University of Miami17, University of Adelaide18, Queen's University Belfast19, Harvard University20, The George Institute for Global Health21, University of Washington22, University of Michigan23, Universiti Tunku Abdul Rahman24, University of Alabama25, National Institutes of Health26, Johns Hopkins University27, University of São Paulo28, Henry Ford Health System29, University College London30, University of Nairobi31, University of Georgia32, University of Utah33, Federal University of São Paulo34, Yale University35, Alberta Children's Hospital36, University of Pennsylvania37, Medical College of Wisconsin38, Novartis39, University of Udine40, University of Illinois at Urbana–Champaign41, Royal Children's Hospital42, University of Missouri43, University of Milan44, Centers for Disease Control and Prevention45, Singapore National Eye Center46, Icahn School of Medicine at Mount Sinai47, Mayo Clinic48, Pan American Health Organization49, University of Indonesia50, University of Crete51, Erasmus University Rotterdam52, University of Southern California53, University of Florence54, Stellenbosch University55, Capital Medical University56, Leipzig University57, Moorfields Eye Hospital58
TL;DR: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected, highlighting the need to scale up vision impairment alleviation efforts at all levels.
Queen's University1, European Organisation for Research and Treatment of Cancer2, Merck & Co.3, NewYork–Presbyterian Hospital4, Columbia University Medical Center5, Mayo Clinic6, Harvard University7, National Institutes of Health8, VU University Medical Center9, Memorial Sloan Kettering Cancer Center10, Genentech11, Cornell University12, Ludwig Institute for Cancer Research13, University Medical Center Groningen14
TL;DR: This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used and defines the minimum datapoints required from future trials to facilitate the compilation of a data warehouse to later validate iRECIST.
Abstract: Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden-a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline-iRECIST-was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.
TL;DR: OpenMM is a molecular dynamics simulation toolkit with a unique focus on extensibility, which makes it an ideal tool for researchers developing new simulation methods, and also allows those new methods to be immediately available to the larger community.
Abstract: OpenMM is a molecular dynamics simulation toolkit with a unique focus on extensibility. It allows users to easily add new features, including forces with novel functional forms, new integration algorithms, and new simulation protocols. Those features automatically work on all supported hardware types (including both CPUs and GPUs) and perform well on all of them. In many cases they require minimal coding, just a mathematical description of the desired function. They also require no modification to OpenMM itself and can be distributed independently of OpenMM. This makes it an ideal tool for researchers developing new simulation methods, and also allows those new methods to be immediately available to the larger community.
TL;DR: The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease and confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms.
Abstract: The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease (DED). A meta-analysis of published prevalence data estimated the impact of age and sex. Global mapping of prevalence was undertaken. The prevalence of DED ranged from 5 to 50%. The prevalence of signs was higher and more variable than symptoms. There were limited prevalence studies in youth and in populations south of the equator. The meta-analysis confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms. Women have a higher prevalence of DED than men, although differences become significant only with age. Risk factors were categorized as modifiable/non-modifiable, and as consistent, probable or inconclusive. Asian ethnicity was a mostly consistent risk factor. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable, particularly costs due to reduced work productivity. Questionnaires used to evaluate DED vary in their utility. Future research should establish the prevalence of disease of varying severity, the incidence in different populations and potential risk factors such as youth and digital device usage. Geospatial mapping might elucidate the impact of climate, environment and socioeconomic factors. Given the limited study of the natural history of treated and untreated DED, this remains an important area for future research.
TL;DR: The NF-κB was discovered 30 years ago as a rapidly inducible transcription factor and has been found to have a broad role in gene induction in diverse cellular responses, particularly throughout the immune system as mentioned in this paper.
Stanford University1, Baylor College of Medicine2, Rice University3, Broad Institute4, Harvard University5, New York University6, University of California, San Diego7, New York University Shanghai8, Courant Institute of Mathematical Sciences9, National Institutes of Health10, Massachusetts Institute of Technology11
TL;DR: In this paper, the effects of degrading cohesin were explored, showing that loop domains can be eliminated and re-formed in under an hour, consistent with a model where loop extrusion is rapid.
European Bioinformatics Institute1, University of Manchester2, University of California, San Francisco3, Swiss Institute of Bioinformatics4, Eötvös Loránd University5, University of Bristol6, J. Craig Venter Institute7, University of Delaware8, University of Southern California9, National Institutes of Health10, Georgetown University Medical Center11, University of Padua12, University College London13
TL;DR: Recent developments with InterPro are reported, including the addition of two new databases, and the functionality to include residue-level annotation and prediction of intrinsic disorder, which enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences.
Abstract: InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences.
TL;DR: In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergy therapy.
Abstract: The complexity, diversity, and heterogeneity of tumors seriously undermine the therapeutic potential of treatment. Therefore, the current trend in clinical research has gradually shifted from a focus on monotherapy to combination therapy for enhanced treatment efficacy. More importantly, the cooperative enhancement interactions between several types of monotherapy contribute to the naissance of multimodal synergistic therapy, which results in remarkable superadditive (namely “1 + 1 > 2”) effects, stronger than any single therapy or their theoretical combination. In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergistic therapy as well as the intensive exploration of the underlying synergistic mechanisms for explaining the significant improvements in synergistic therapeutic outcome. Furtherm...
Cornell University1, University of Porto2, Imperial College London3, National Institutes of Health4, Memorial Sloan Kettering Cancer Center5, Princeton University6, Lawrence Berkeley National Laboratory7, Garvan Institute of Medical Research8, Stanford University9, University of Copenhagen10, Fred Hutchinson Cancer Research Center11
TL;DR: This Review summarizes the main processes and new mechanisms involved in the formation of the pre-metastatic niche and describes the main mechanisms used to modify organs of future metastasis.
Abstract: It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche.
Leibniz Association1, University of Zurich2, James Hutton Institute3, Murdoch University4, University of Minnesota5, National Institutes of Health6, University of California, Riverside7, European Bioinformatics Institute8, University of Udine9, University of Helsinki10, Norwich University11, Zhejiang University12, Kansas State University13, University of Adelaide14, University of East Anglia15, National Institute of Agricultural Botany16, Technische Universität München17, Lund University18, Government of Western Australia19, Yangtze University20, University of Dundee21, University of Western Australia22
TL;DR: The importance of the barley reference sequence for breeding is demonstrated by inspecting the genomic partitioning of sequence variation in modern elite germplasm, highlighting regions vulnerable to genetic erosion.
Abstract: Cereal grasses of the Triticeae tribe have been the major food source in temperate regions since the dawn of agriculture. Their large genomes are characterized by a high content of repetitive elements and large pericentromeric regions that are virtually devoid of meiotic recombination. Here we present a high-quality reference genome assembly for barley (Hordeum vulgare L.). We use chromosome conformation capture mapping to derive the linear order of sequences across the pericentromeric space and to investigate the spatial organization of chromatin in the nucleus at megabase resolution. The composition of genes and repetitive elements differs between distal and proximal regions. Gene family analyses reveal lineage-specific duplications of genes involved in the transport of nutrients to developing seeds and the mobilization of carbohydrates in grains. We demonstrate the importance of the barley reference sequence for breeding by inspecting the genomic partitioning of sequence variation in modern elite germplasm, highlighting regions vulnerable to genetic erosion.
Brigham and Women's Hospital1, Harvard University2, Emory University3, Centers for Disease Control and Prevention4, University of Pittsburgh5, University of Michigan6, National Institutes of Health7, Hospital Corporation of America8, Texas A&M Health Science Center College of Medicine9, Washington University in St. Louis10
TL;DR: In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsi nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014.
Abstract: Importance Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, −2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (−1.3%/y [95% CI, −3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (−7.0%/y [95% CI, −8.8% to −5.2%], P P P P = .23). Conclusions and Relevance In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.
McMaster University1, University of Montpellier2, Transylvania University3, Ghent University Hospital4, University of Sydney5, Humanitas University6, University of South Florida7, Leiden University Medical Center8, RMIT University9, Federal University of Bahia10, Pierre-and-Marie-Curie University11, Saint Louis University12, University of Porto13, Katholieke Universiteit Leuven14, Medical University of Łódź15, University of Tartu16, Oslo University Hospital17, Royal College of Surgeons in Ireland18, University of California, San Diego19, University of Barcelona20, University of Padua21, Monash University22, Charles University in Prague23, University of Manchester24, Ajou University25, University of Genoa26, Nippon Medical School27, University of Aberdeen28, University of Edinburgh29, Kerman Medical University30, Medical University of Warsaw31, National Institutes of Health32, Vilnius University33, University of Turku34, Nova Southeastern University35, Boston Children's Hospital36, Beijing Tongren Hospital37, Charité38
TL;DR: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR, addressing the relative merits of using oral H1‐antihistamines, intranasal H1-antihistsamines, IntranasAL corticosteroids, and leukotriene receptor antagonists either alone or in combination.
Abstract: Background Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. Objective We sought to provide a targeted update of the ARIA guidelines. Methods The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. Results The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. Conclusions Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.
Cornell University1, Paris Descartes University2, University of Massachusetts Medical School3, Spanish National Research Council4, Boston Children's Hospital5, University of Rome Tor Vergata6, University of Pittsburgh7, National Scientific and Technical Research Council8, National University of Cuyo9, Albert Einstein College of Medicine10, University of California, San Francisco11, University of New Mexico12, Goethe University Frankfurt13, University of Split14, University of Helsinki15, University of Salento16, German Cancer Research Center17, Virginia Commonwealth University18, St. Jude Children's Research Hospital19, Discovery Institute20, Harvard University21, University of Tromsø22, Hungarian Academy of Sciences23, Eötvös Loránd University24, New York University25, University of Vienna26, Babraham Institute27, University of South Australia28, Howard Hughes Medical Institute29, University of Texas Southwestern Medical Center30, University of Oviedo31, University of Graz32, National Institutes of Health33, City University of New York34, Queens College35, University of Tokyo36, University of Zurich37, Novartis38, Austrian Academy of Sciences39, University of Groningen40, University of Cambridge41, University of Padua42, University of Oxford43, University of Bern44, University of Oslo45, Foundation for Research & Technology – Hellas46, University of Crete47, Francis Crick Institute48, Osaka University49, Icahn School of Medicine at Mount Sinai50
TL;DR: A panel of leading experts in the field attempts here to define several autophagy‐related terms based on specific biochemical features to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagic research.
Abstract: Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research.
University of Freiburg1, University of Bergen2, Northumbria University3, University of Oxford4, Stavanger University Hospital5, Karolinska Institutet6, University of Copenhagen7, Paris Descartes University8, University of Parma9, National Institutes of Health10, University of Antwerp11, University of Bucharest12, Frederiksberg Hospital13
TL;DR: In this article, a European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia.
Abstract: This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).
TL;DR: The incidences of both type 1 and type 2 diabetes among youths increased significantly in the 2002–2012 period, particularly among youths of minority racial and ethnic groups.
Abstract: BackgroundDiagnoses of type 1 and type 2 diabetes in youths present a substantial clinical and public health burden. The prevalence of these diseases increased in the 2001–2009 period, but data on recent incidence trends are lacking. MethodsWe ascertained cases of type 1 and type 2 diabetes mellitus at five study centers in the United States. Denominators (4.9 million youths annually) were obtained from the U.S. Census or health-plan member counts. After the calculation of annual incidence rates for the 2002–2012 period, we analyzed trends using generalized autoregressive moving-average models with 2-year moving averages. ResultsA total of 11,245 youths with type 1 diabetes (0 to 19 years of age) and 2846 with type 2 diabetes (10 to 19 years of age) were identified. Overall unadjusted estimated incidence rates of type 1 diabetes increased by 1.4% annually (from 19.5 cases per 100,000 youths per year in 2002–2003 to 21.7 cases per 100,000 youths per year in 2011–2012, P=0.03). In adjusted pairwise comparis...