Showing papers by "Case Western Reserve University 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: The theory of SEM, which allows for the analysis of independent observations for both unrelated and family data, the available software for SEM, and an example of SEM analysis are reviewed.
Abstract: Structural equation modeling (SEM) is a multivariate statistical framework that is used to model complex relationships between directly observed and indirectly observed (latent) variables. SEM is a general framework that involves simultaneously solving systems of linear equations and encompasses other techniques such as regression, factor analysis, path analysis, and latent growth curve modeling. Recently, SEM has gained popularity in the analysis of complex genetic traits because it can be used to better analyze the relationships between correlated variables (traits), to model genes as latent variables as a function of multiple observed genetic variants, and to assess the association between multiple genetic variants and multiple correlated phenotypes of interest. Though the general SEM framework only allows for the analysis of independent observations, recent work has extended SEM for the analysis of data on general pedigrees. Here, we review the theory of SEM for both unrelated and family data, describe the available software for SEM, and provide examples of SEM analysis.
4,203 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
Carnegie Mellon University1, Leibniz Institute for Astrophysics Potsdam2, Lawrence Berkeley National Laboratory3, New Mexico State University4, Sternberg Astronomical Institute5, Ohio State University6, University of Utah7, Yale University8, Autonomous University of Madrid9, University of Barcelona10, Harvard University11, Aix-Marseille University12, Pierre-and-Marie-Curie University13, University of Paris14, Max Planck Society15, University of California, Berkeley16, University of California, Irvine17, University of Portsmouth18, University of Cambridge19, University of La Laguna20, Spanish National Research Council21, Institut d'Astrophysique de Paris22, Princeton University23, University of Edinburgh24, Sejong University25, Kansas State University26, Pennsylvania State University27, National Scientific and Technical Research Council28, National University of La Plata29, Ohio University30, Brookhaven National Laboratory31, New York University32, University of St Andrews33, National Autonomous University of Mexico34, Open University35, University of Wisconsin-Madison36, Chinese Academy of Sciences37, University of Pittsburgh38, Case Western Reserve University39
TL;DR: In this article, the authors present cosmological results from the final galaxy clustering data set of the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III.
Abstract: We present cosmological results from the final galaxy clustering data set of the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III. Our combined galaxy sample comprises 1.2 million massive galaxies over an effective area of 9329 deg^2 and volume of 18.7 Gpc^3, divided into three partially overlapping redshift slices centred at effective redshifts 0.38, 0.51 and 0.61. We measure the angular diameter distance and Hubble parameter H from the baryon acoustic oscillation (BAO) method, in combination with a cosmic microwave background prior on the sound horizon scale, after applying reconstruction to reduce non-linear effects on the BAO feature. Using the anisotropic clustering of the pre-reconstruction density field, we measure the product D_MH from the Alcock–Paczynski (AP) effect and the growth of structure, quantified by fσ_8(z), from redshift-space distortions (RSD). We combine individual measurements presented in seven companion papers into a set of consensus values and likelihoods, obtaining constraints that are tighter and more robust than those from any one method; in particular, the AP measurement from sub-BAO scales sharpens constraints from post-reconstruction BAOs by breaking degeneracy between D_M and H. Combined with Planck 2016 cosmic microwave background measurements, our distance scale measurements simultaneously imply curvature Ω_K = 0.0003 ± 0.0026 and a dark energy equation-of-state parameter w = −1.01 ± 0.06, in strong affirmation of the spatially flat cold dark matter (CDM) model with a cosmological constant (ΛCDM). Our RSD measurements of fσ_8, at 6 per cent precision, are similarly consistent with this model. When combined with supernova Ia data, we find H_0 = 67.3 ± 1.0 km s^−1 Mpc^−1 even for our most general dark energy model, in tension with some direct measurements. Adding extra relativistic species as a degree of freedom loosens the constraint only slightly, to H_0 = 67.8 ± 1.2 km s^−1 Mpc^−1. Assuming flat ΛCDM, we find Ω_m = 0.310 ± 0.005 and H_0 = 67.6 ± 0.5 km s^−1 Mpc^−1, and we find a 95 per cent upper limit of 0.16 eV c^−2 on the neutrino mass sum.
2,413 citations
Seattle Children's1, Case Western Reserve University2, University of Maryland, Baltimore3, University of Missouri–Kansas City4, Indiana University5, University of Colorado Denver6, Boston Children's Hospital7, University of British Columbia8, Thomas Jefferson University9, American Academy of Pediatrics10, Alfred I. duPont Hospital for Children11, Morehouse College12, Harvard University13, University of Texas Health Science Center at Houston14, University of Pittsburgh15, Columbia University Medical Center16, Cincinnati Children's Hospital Medical Center17
TL;DR: These pediatric hypertension guidelines are an update to the 2004 report and include revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy.
Abstract: These pediatric hypertension guidelines are an update to the 2004 “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” Significant changes in these guidelines include (1) the replacement of the term “prehypertension” with the term “elevated blood pressure,” (2) new normative pediatric blood pressure (BP) tables based on normal-weight children, (3) a simplified screening table for identifying BPs needing further evaluation, (4) a simplified BP classification in adolescents ≥13 years of age that aligns with the forthcoming American Heart Association and American College of Cardiology adult BP guidelines, (5) a more limited recommendation to perform screening BP measurements only at preventive care visits, (6) streamlined recommendations on the initial evaluation and management of abnormal BPs, (7) an expanded role for ambulatory BP monitoring in the diagnosis and management of pediatric hypertension, and (8) revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy. These guidelines include 30 Key Action Statements and 27 additional recommendations derived from a comprehensive review of almost 15 000 published articles between January 2004 and July 2016. Each Key Action Statement includes level of evidence, benefit-harm relationship, and strength of recommendation. This clinical practice guideline, endorsed by the American Heart Association, is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient diagnoses and outcomes, support implementation, and provide direction for future research.
2,082 citations
Case Western Reserve University1, University of Wisconsin-Madison2, Imperial College London3, South Dakota School of Mines and Technology4, University of Maryland, College Park5, University of California, Berkeley6, Lawrence Livermore National Laboratory7, University of Coimbra8, University of South Dakota9, Yale University10, University of California, Santa Barbara11, Brown University12, University of California, Davis13, Lawrence Berkeley National Laboratory14, University College London15, University of Rochester16, SLAC National Accelerator Laboratory17, Texas A&M University18, State University of New York System19, University of Edinburgh20
TL;DR: This search yields no evidence of WIMP nuclear recoils and constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4} kg day exposure of the Large Underground Xenon experiment are reported.
Abstract: We report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4} kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50 GeV c^{-2}, WIMP-nucleon spin-independent cross sections above 2.2×10^{-46} cm^{2} are excluded at the 90% confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1×10^{-46} cm^{2} at 50 GeV c^{-2}.
1,844 citations
TL;DR: This guideline establishes clinical practice recommendations for the diagnosis of obstructive sleep apnea (OSA) in adults and is intended for use in conjunction with other American Academy of Sleep Medicine guidelines on the evaluation and treatment of sleep-disordered breathing in adults.
Abstract: Introduction:This guideline establishes clinical practice recommendations for the diagnosis of obstructive sleep apnea (OSA) in adults and is intended for use in conjunction with other American Aca...
1,547 citations
TL;DR: In a recent special issue on digital innovation management as mentioned in this paper, the authors proposed four new theorizing logics, or elements, that are likely to be valuable in constructing more accurate explanations of innovation processes and outcomes in an increasingly digital world.
Abstract: Rapid and pervasive digitization of innovation processes and outcomes has upended extant theories on innovation management by calling into question fundamental assumptions about the definitional boundaries for innovation, agency for innovation, and the relationship between innovation processes and outcomes. There is a critical need for novel theorizing on digital innovation management that does not rely on such assumptions and draws on the rich and rapidly emerging research on digital technologies. We offer suggestions for such theorizing in the form of four new theorizing logics, or elements, that are likely to be valuable in constructing more accurate explanations of innovation processes and outcomes in an increasingly digital world. These logics can open new avenues for researchers to contribute to this important area. Our suggestions in this paper, coupled with the six research notes included in the special issue on digital innovation management, seek to offer a broader foundation for reinventing innovation management research in a digital world.
1,274 citations
TL;DR: The recent development of this concept is reviewed here and a novel principle for the design of oxygen electrocatalysts is proposed and an overview of the defects in carbon-based, metal-free electrocatalysis for ORR and various defects in metal oxides/selenides for OER is provided.
Abstract: Oxygen electrocatalysis, including the oxygen-reduction reaction (ORR) and oxygen-evolution reaction (OER), is a critical process for metal-air batteries Therefore, the development of electrocatalysts for the OER and the ORR is of essential importance Indeed, various advanced electrocatalysts have been designed for the ORR or the OER; however, the origin of the advanced activity of oxygen electrocatalysts is still somewhat controversial The enhanced activity is usually attributed to the high surface areas, the unique facet structures, the enhanced conductivities, or even to unclear synergistic effects, but the importance of the defects, especially the intrinsic defects, is often neglected More recently, the important role of defects in oxygen electrocatalysis has been demonstrated by several groups To make the defect effect clearer, the recent development of this concept is reviewed here and a novel principle for the design of oxygen electrocatalysts is proposed An overview of the defects in carbon-based, metal-free electrocatalysts for ORR and various defects in metal oxides/selenides for OER is also provided The types of defects and controllable strategies to generate defects in electrocatalysts are presented, along with techniques to identify the defects The defect-activity relationship is also explored by theoretical methods
1,222 citations
University of Alabama at Birmingham1, University of Hohenheim2, College of Health Sciences, Bahrain3, Jimma University4, University of Queensland5, Queensland Government6, Mekelle University7, Institute for Health Metrics and Evaluation8, University of Cartagena9, Komfo Anokye Teaching Hospital10, University of Manitoba11, University of Gondar12, University of São Paulo13, Aga Khan University14, New Generation University College15, Public Health Foundation of India16, Duy Tan University17, Centers for Disease Control and Prevention18, Bielefeld University19, Imperial College London20, Swiss Tropical and Public Health Institute21, University of Basel22, Boston Children's Hospital23, Baylor College of Medicine24, Yonsei University25, Tehran University of Medical Sciences26, Jordan University of Science and Technology27, University of London28, University of Melbourne29, Aintree University Hospitals NHS Foundation Trust30, University of Liverpool31, Martin Luther University of Halle-Wittenberg32, United Nations Population Fund33, Iran University of Medical Sciences34, University of Ulm35, University of Sydney36, University of Porto37, University of British Columbia38, A.T. Still University39, Golestan University40, Harvard University41, Case Western Reserve University42, Marshall University43, University of KwaZulu-Natal44, Utkal University45, AIIMS, New Delhi46, Haramaya University47, Queensland University of Technology48, Jagiellonian University Medical College49, Wrocław Medical University50, Hanoi Medical University51, Johns Hopkins University52, National Research University – Higher School of Economics53, Norwegian Institute of Public Health54, University of Bergen55, Karolinska Institutet56, University of Tromsø57, Kyoto University58, Jackson State University59, Wuhan University60, University of Washington61
TL;DR: In this article, the authors report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol, and an “other” group that encompasses residual causes.
Abstract: Importance Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. Objective To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes. Design, Settings, and Participants Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. Main Outcomes and Measures Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. Results There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. Conclusions and Relevance Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts.
1,208 citations
Michael R. Blanton1, Matthew A. Bershady2, Bela Abolfathi3, Franco D. Albareti4 +412 more•Institutions (91)
TL;DR: SDSS-IV as mentioned in this paper is a project encompassing three major spectroscopic programs: the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA), the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and the Time Domain Spectroscopy Survey (TDSS).
Abstract: We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
Kyriaki Michailidou1, Kyriaki Michailidou2, Sara Lindström3, Sara Lindström4 +393 more•Institutions (127)
TL;DR: A genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry finds that heritability of Breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2–5-fold enriched relative to the genome- wide average.
Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
Johns Hopkins University1, Seattle Cancer Care Alliance2, University of Colorado Boulder3, University of Utah4, Fox Chase Cancer Center5, Brigham and Women's Hospital6, Duke University7, Northwestern University8, University of South Florida9, University of Alabama at Birmingham10, Washington University in St. Louis11, University of California, San Francisco12, Roswell Park Cancer Institute13, Vanderbilt University14, University of Texas MD Anderson Cancer Center15, Harvard University16, University of Wisconsin-Madison17, Yale Cancer Center18, University of Michigan19, Stanford University20, Ohio State University21, City of Hope National Medical Center22, Memorial Sloan Kettering Cancer Center23, Mayo Clinic24, Case Western Reserve University25, University Of Tennessee System26
TL;DR: This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastasis disease.
Abstract: This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.
University of California, San Francisco1, Moffitt Cancer Center2, University of Michigan3, Mayo Clinic4, Roswell Park Cancer Institute5, University of Tennessee Health Science Center6, Northwestern University7, Washington University in St. Louis8, Vanderbilt University9, Yale Cancer Center10, Seattle Cancer Care Alliance11, City of Hope National Medical Center12, Duke University13, Ohio State University14, Fox Chase Cancer Center15, Harvard University16, Case Western Reserve University17, University of Texas MD Anderson Cancer Center18, Stanford University19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Memorial Sloan Kettering Cancer Center23, University of Alabama at Birmingham24, University of Utah25, University of Colorado Boulder26, Dana Corporation27
TL;DR: The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection, as well as on management of locally advanced unresectable and metastatic disease.
Abstract: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.
University of Toronto1, German Cancer Research Center2, University of Düsseldorf3, University of Pittsburgh4, Ontario Institute for Cancer Research5, Seoul National University6, University of Warsaw7, University of Lyon8, Mayo Clinic9, The Chinese University of Hong Kong10, Johns Hopkins University11, University of Alabama at Birmingham12, University of Washington13, Fred Hutchinson Cancer Research Center14, University of California, San Francisco15, Hamilton Health Sciences16, McMaster University17, Vanderbilt University18, University of Colorado Denver19, Semmelweis University20, Erasmus University Rotterdam21, University of Ulsan22, Kitasato University23, Mexican Social Security Institute24, Masaryk University25, Emory University26, University of Debrecen27, University of Naples Federico II28, Washington University in St. Louis29, McGill University30, Montreal Children's Hospital31, Virginia Commonwealth University32, Chonnam National University33, University of Queensland34, University of Calgary35, University of São Paulo36, University of Cincinnati37, University of Arkansas for Medical Sciences38, The Catholic University of America39, University of California, Los Angeles40, University of Sydney41, Kumamoto University42, Saint Louis University43, Case Western Reserve University44
TL;DR: Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes.
TL;DR: Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
TL;DR: The name of MSCs should be changed to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative) meaning thatThese cells make therapeutic drugs in situ that are medicinal.
Abstract: Mesenchymal stem cells (MSCs) were officially named more than 25 years ago to represent a class of cells from human and mammalian bone marrow and periosteum that could be isolated and expanded in culture while maintaining their in vitro capacity to be induced to form a variety of mesodermal phenotypes and tissues. The in vitro capacity to form bone, cartilage, fat, etc., became an assay for identifying this class of multipotent cells and around which several companies were formed in the 1990s to medically exploit the regenerative capabilities of MSCs. Today, there are hundreds of clinics and hundreds of clinical trials using human MSCs with very few, if any, focusing on the in vitro multipotential capacities of these cells. Unfortunately, the fact that MSCs are called "stem cells" is being used to infer that patients will receive direct medical benefit, because they imagine that these cells will differentiate into regenerating tissue-producing cells. Such a stem cell treatment will presumably cure the patient of their medically relevant difficulties ranging from osteoarthritic (bone-on-bone) knees to various neurological maladies including dementia. I now urge that we change the name of MSCs to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative) meaning that these cells make therapeutic drugs in situ that are medicinal. It is, indeed, the patient's own site-specific and tissue-specific resident stem cells that construct the new tissue as stimulated by the bioactive factors secreted by the exogenously supplied MSCs. Stem Cells Translational Medicine 2017;6:1445-1451.
Mayo Clinic1, Yale University2, Case Western Reserve University3, Children's National Medical Center4, University of California, San Diego5, University of Miami6, Virginia Commonwealth University7, University of Calgary8, Cleveland Clinic9, University of Gothenburg10, University of British Columbia11, Saint Louis University12, Johns Hopkins University13, Dartmouth College14, University of Washington15, University of Texas MD Anderson Cancer Center16, Veterans Health Administration17, Royal Melbourne Hospital18, Cedars-Sinai Medical Center19, University of Colorado Denver20
TL;DR: Fred M. Kusumoto,MD, FHRS, FACC, Chair, Mark H. Schoenfeld, MD, F hrs, F ACC, FAHA, CCDS, Vice-Chair, Bruce L. Wilkoff, MD; Ulrika M. Birgersdotter-Green, MD.
University of Washington1, University of Cape Town2, University of Melbourne3, All India Institute of Medical Sciences4, Children's National Medical Center5, Harvard University6, Case Western Reserve University7, Universidade Federal de Minas Gerais8, National Institutes of Health9, Telethon Institute for Child Health Research10, Princess Margaret Hospital for Children11
TL;DR: The health‐related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world.
Abstract: BackgroundRheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low-income and middle-income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study. MethodsWe systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod-MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty. ResultsWe estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age-standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age-stand...
Queen Mary University of London1, University of Chicago2, Institut Gustave Roussy3, Sarah Cannon Research Institute4, University of California, San Francisco5, Case Western Reserve University6, University of Ulsan7, Ottawa Hospital8, Princess Margaret Cancer Centre9, Stanford University10, Georgia Regents University11, MedImmune12, AstraZeneca13, Johns Hopkins University14
TL;DR: Durvalumab, 10 mg/kg every 2 weeks, demonstrates favorable clinical activity and an encouraging and manageable safety profile in patients with locally advanced/metastatic UC, resulting in its recent US approval.
Abstract: Importance The data reported herein were accepted for assessment by the US Food and Drug Administration for Biologics License Application under priority review to establish the clinical benefit of durvalumab as second-line therapy for locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent US approval. Objective To report a planned update of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC. Design, Setting, and Participants This is an ongoing phase 1/2 open-label study of 191 adult patients with histologically or cytologically confirmed locally advanced/metastatic UC whose disease had progressed on, were ineligible for, or refused prior chemotherapy from 60 sites in 9 countries as reported herein. Intervention Patients were administered durvalumab intravenous infusion, 10 mg/kg every 2 weeks, for up to 12 months or until progression, starting another anticancer therapy, or unacceptable toxic effects. Main Outcomes and Measures Primary end points were safety and confirmed objective response rate (ORR) per blinded independent central review (Response Evaluation Criteria In Solid Tumors [RECIST], version 1.1). Results A total of 191 patients with UC had received treatment. As of October 24, 2016 (90-day update), the median follow-up was 5.78 months (range, 0.4-25.9 months). The median age of patients was 67.0 years and most were male (136 [71.2%]) and white (123 [71.1%]). All patients had stage 4 disease, and 190 (99.5%) had prior anticancer therapy (182 [95.3%] postplatinum). The ORR was 17.8% (34 of 191; 95% CI, 12.7%-24.0%), including 7 complete responses. Responses were early (median time to response, 1.41 months), durable (median duration of response not reached), and observed regardless of programmed cell death ligand-1 (PD-L1) expression (ORR, 27.6% [n = 27; 95% CI, 19.0%-37.5%] and 5.1% [n = 4; 95% CI, 1.4%-12.5%] in patients with high and low or negative expression of PD-L1, respectively). Median progression-free survival and overall survival were 1.5 months (95% CI, 1.4-1.9 months) and 18.2 months (95% CI, 8.1 months to not estimable), respectively; the 1-year overall survival rate was 55% (95% CI, 44%-65%), as estimated by Kaplan-Meier method. Grade 3/4 treatment-related adverse events (AEs) occurred in 13 patients (6.8%); grade 3/4 immune-mediated AEs occurred in 4 patients (2.1%); and treatment-related AEs led to discontinuation of 3 patients (1.6%), 2 of whom had immune-mediated AEs that led to death (autoimmune hepatitis and pneumonitis). Conclusions and Relevance Durvalumab, 10 mg/kg every 2 weeks, demonstrates favorable clinical activity and an encouraging and manageable safety profile in patients with locally advanced/metastatic UC. Trial Registration clinicaltrials.gov Identifier:NCT01693562
TL;DR: The multifunctional electrocatalytic activities originate from a synergistic effect of the N, S heteroatom doping and unique SHG architecture, which provide a large surface area and efficient pathways for electron and electrolyte/reactant transports.
Abstract: Rationally designed N, S co-doped graphitic sheets with stereoscopic holes (SHG) act as effective tri-functional catalysts for the oxygen reduction reaction, hydrogen evolution reaction, and oxygen evolution reaction, simultaneously. The multifunctional electrocatalytic activities originate from a synergistic effect of the N, S heteroatom doping and unique SHG architecture, which provide a large surface area and efficient pathways for electron and electrolyte/reactant transports.
TL;DR: Increased prepregnancy maternal insulin resistance and accompanying hyperinsulinemia, inflammation, and oxidative stress seem to contribute to early placental and fetal dysfunction in obese women.
Abstract: Obesity is the most common medical condition in women of reproductive age. Obesity during pregnancy has short term and long term adverse consequences for both mother and child. Obesity causes problems with infertility, and in early gestation it causes spontaneous pregnancy loss and congenital anomalies. Metabolically, obese women have increased insulin resistance in early pregnancy, which becomes manifest clinically in late gestation as glucose intolerance and fetal overgrowth. At term, the risk of cesarean delivery and wound complications is increased. Postpartum, obese women have an increased risk of venous thromboembolism, depression, and difficulty with breast feeding. Because 50-60% of overweight or obese women gain more than recommended by Institute of Medicine gestational weight guidelines, postpartum weight retention increases future cardiometabolic risks and prepregnancy obesity in subsequent pregnancies. Neonates of obese women have increased body fat at birth, which increases the risk of childhood obesity. Although there is no unifying mechanism responsible for the adverse perinatal outcomes associated with maternal obesity, on the basis of the available data, increased prepregnancy maternal insulin resistance and accompanying hyperinsulinemia, inflammation, and oxidative stress seem to contribute to early placental and fetal dysfunction. We will review the pathophysiology underlying these data and try to shed light on the specific underlying mechanisms.
TL;DR: The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson’s disease, and alpha-1 antitrypsin deficiency.
TL;DR: This is the first report of a combined implanted FES+iBCI neuroprosthesis for restoring both reaching and grasping movements to people with chronic tetraplegia due to spinal cord injury, and represents a major advance, with a clear translational path, for clinically viable Neuroprostheses for restoration of reaches and grasping after paralysis.
Fox Chase Cancer Center1, Ohio State University2, University of Tennessee Health Science Center3, University of Utah4, University of Alabama5, Brigham and Women's Hospital6, Duke University7, Northwestern University8, University of Colorado Boulder9, Stanford University10, University of Texas MD Anderson Cancer Center11, University of California, San Diego12, University of Michigan13, Memorial Sloan Kettering Cancer Center14, Moffitt Cancer Center15, Harvard University16, University of Washington17, Case Western Reserve University18, Roswell Park Cancer Institute19, City of Hope National Medical Center20, Mayo Clinic21, Vanderbilt University22, National Comprehensive Cancer Network23
TL;DR: The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer.
Abstract: The NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling for hereditary cancer syndromes and risk management recommendations for patients who are diagnosed with a syndrome. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer. The NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer.
TL;DR: In this paper, a review article summarizes progress in high-performance supercapacitors based on carbon nanomaterials with an emphasis on the design and fabrication of electrode structures and elucidation of charge-storage mechanisms.
Abstract: The advancement of modern electronic devices depends strongly on the highly efficient energy sources possessing high energy density and power density. In this regard, supercapacitors show great promise. Due to the unique hierarchical structure, excellent electrical and mechanical properties, and high specific surface area, carbon nanomaterials (particularly, carbon nanotubes, graphene, mesoporous carbon and their hybrids) have been widely investigated as efficient electrode materials in supercapacitors. This review article summarizes progress in high-performance supercapacitors based on carbon nanomaterials with an emphasis on the design and fabrication of electrode structures and elucidation of charge-storage mechanisms. Recent developments on carbon-based flexible and stretchable supercapacitors for various potential applications, including integrated energy sources, self-powered sensors and wearable electronics, are also discussed.
TL;DR: Recommendations for the clinical and research use of gadolinium-based contrast agents are presented and might evolve as new evidence becomes available.
Abstract: Emerging evidence has linked MRI signal changes in deep nuclei of the brain with repeated administration of gadolinium-based contrast agents. Gadolinium deposits have been confirmed in brain tissue, most notably in the dentate nuclei and globus pallidus. Although some linear contrast agents appear to cause greater MRI signal changes than some macrocyclic agents, deposition of gadolinium has also been observed with macrocyclic agents. However, the extent of gadolinium deposition varies between agents. Furthermore, the clinical significance of the retained gadolinium in the brain, if any, remains unknown. No data are available in human beings or animals to show adverse clinical effects due to the gadolinium deposition in the brain. On behalf of the International Society for Magnetic Resonance in Medicine, we present recommendations for the clinical and research use of gadolinium-based contrast agents. These recommendations might evolve as new evidence becomes available.
Franco D. Albareti1, Franco D. Albareti2, Carlos Allende Prieto3, Carlos Allende Prieto1 +397 more•Institutions (95)
TL;DR: Data Release 13 (DR13) as discussed by the authors provides the first 1390 spatially resolved integral field unit observations of nearby galaxies from the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2), Mapping Nearby Galaxies at APO (MaNGA), and the Extended Baryon Oscillation Spectroscopic Survey (eBOSS).
Abstract: The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in 2014 July. It pursues three core programs: the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2), Mapping Nearby Galaxies at APO (MaNGA), and the Extended Baryon Oscillation Spectroscopic Survey (eBOSS). As well as its core program, eBOSS contains two major subprograms: the Time Domain Spectroscopic Survey (TDSS) and the SPectroscopic IDentification of ERosita Sources (SPIDERS). This paper describes the first data release from SDSS-IV, Data Release 13 (DR13). DR13 makes publicly available the first 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA. It includes new observations from eBOSS, completing the Sloan Extended QUasar, Emission-line galaxy, Luminous red galaxy Survey (SEQUELS), which also targeted variability-selected objects and X-ray-selected objects. DR13 includes new reductions of the SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification, and new reductions of the SDSS-III APOGEE-1 data, improving stellar parameters for dwarf stars and cooler stars. DR13 provides more robust and precise photometric calibrations. Value-added target catalogs relevant for eBOSS, TDSS, and SPIDERS and an updated red-clump catalog for APOGEE are also available. This paper describes the location and format of the data and provides references to important technical papers. The SDSS web site, http://www.sdss.org, provides links to the data, tutorials, examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ∼6 yr operations of SDSS-IV.
City of Hope National Medical Center1, Memorial Sloan Kettering Cancer Center2, Washington University in St. Louis3, Northwestern University4, Seattle Cancer Care Alliance5, Stanford University6, University of Michigan7, Ohio State University8, Case Western Reserve University9, Harvard University10, University of California, San Diego11, Mayo Clinic12, Yale Cancer Center13, University of Wisconsin-Madison14, Fox Chase Cancer Center15, University of South Florida16, University of Tennessee Health Science Center17, Duke University18, University of California, San Francisco19, University of Alabama at Birmingham20, University of Colorado Boulder21, Johns Hopkins University22, University of Texas MD Anderson Cancer Center23, University of Utah24, Brigham and Women's Hospital25, Vanderbilt University26, Roswell Park Cancer Institute27, National Comprehensive Cancer Network28
TL;DR: This portion of the NCCN Guidelines for AML focuses on management and provides recommendations on the workup, diagnostic evaluation, and treatment options for younger and older adult patients.
Abstract: Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. Recent advances have resulted in an expansion of treatment options for AML, especially concerning targeted therapies and low-intensity regimens. This portion of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML focuses on the management of AML and provides recommendations on the workup, diagnostic evaluation and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.
University of Pennsylvania1, University of Chicago2, Memorial Sloan Kettering Cancer Center3, University of Michigan4, Georgetown University5, Vanderbilt University6, Emory University7, University of North Carolina at Chapel Hill8, Harvard University9, Wayne State University10, Johns Hopkins University11, Case Western Reserve University12, University of Texas MD Anderson Cancer Center13, Valley Hospital14, Merck & Co.15
TL;DR: Pembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status.
Abstract: PurposeThere are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti–programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis.MethodsEligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status.ResultsAmong 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) ...