Showing papers by "University of Rochester published in 2020"
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23 Feb 2020
TL;DR: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper, where a brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
Abstract: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
3,111 citations
United States Department of Health and Human Services1, Centers for Disease Control and Prevention2, Colorado Department of Public Health and Environment3, Yale University4, Veterans Health Administration5, Emory University6, Alabama Department of Public Health7, Maryland Department of Health8, New Mexico Department of Health9, New York State Department of Health10, University of Rochester11, Ohio Department of Health12, Vanderbilt University13, Lake County14
TL;DR: It is suggested that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with CO VID-19 have underlying medical conditions, which underscore the importance of preventive measures to protect older adults and persons with underlyingmedical conditions, as well as the general public.
Abstract: Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.
2,016 citations
TL;DR: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation.
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldw...
1,939 citations
TL;DR: In this article, the authors review research from self-determination theory and show that both intrinsic motivation and well-internalized (and thus autonomous) forms of extrinsic motivation predict an array of positive outcomes across varied educational levels and cultural contexts and are enhanced by supports for students' basic psychological needs for autonomy, competence, and relatedness.
1,195 citations
TL;DR: In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.
Abstract: In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18–55 years of age), who were randomized to receive 2 doses—separated by 21 days—of 10 μg, 30 μg or 100 μg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9–4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate. In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.
1,140 citations
Université Paris-Saclay1, Commonwealth Scientific and Industrial Research Organisation2, Goddard Space Flight Center3, Stanford University4, Yale University5, National Oceanic and Atmospheric Administration6, VU University Amsterdam7, Netherlands Institute for Space Research8, Chiba University9, Japan Agency for Marine-Earth Science and Technology10, Linköping University11, University of California, Irvine12, National Institute of Water and Atmospheric Research13, New York University14, Seconda Università degli Studi di Napoli15, École Polytechnique16, Stockholm University17, Skidmore College18, University of Victoria19, Babeș-Bolyai University20, National Institute of Geophysics and Volcanology21, California Institute of Technology22, Met Office23, University of Reading24, International Institute for Applied Systems Analysis25, National Institute for Environmental Studies26, City University of New York27, University of Bern28, Max Planck Society29, Purdue University30, European Centre for Medium-Range Weather Forecasts31, Lund University32, University of Bristol33, Geophysical Fluid Dynamics Laboratory34, University of Leicester35, Université du Québec à Montréal36, Peking University37, Massachusetts Institute of Technology38, Lawrence Berkeley National Laboratory39, Southern Cross University40, Auburn University41, Joint Global Change Research Institute42, Food and Agriculture Organization43, Finnish Meteorological Institute44, Technical University of Crete45, Imperial College London46, University of Rochester47, Royal Netherlands Meteorological Institute48, Scripps Institution of Oceanography49, University of Toronto50, University of Maryland, College Park51, Hohai University52
TL;DR: The second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modeling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations) as discussed by the authors.
Abstract: Understanding and quantifying the global methane (CH4) budget is important for assessing realistic pathways to mitigate climate change. Atmospheric emissions and concentrations of CH4 continue to increase, making CH4 the second most important human-influenced greenhouse gas in terms of climate forcing, after carbon dioxide (CO2). The relative importance of CH4 compared to CO2 depends on its shorter atmospheric lifetime, stronger warming potential, and variations in atmospheric growth rate over the past decade, the causes of which are still debated. Two major challenges in reducing uncertainties in the atmospheric growth rate arise from the variety of geographically overlapping CH4 sources and from the destruction of CH4 by short-lived hydroxyl radicals (OH). To address these challenges, we have established a consortium of multidisciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate new research aimed at improving and regularly updating the global methane budget. Following Saunois et al. (2016), we present here the second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations).
For the 2008–2017 decade, global methane emissions are estimated by atmospheric inversions (a top-down approach) to be 576 Tg CH4 yr−1 (range 550–594, corresponding to the minimum and maximum estimates of the model ensemble). Of this total, 359 Tg CH4 yr−1 or ∼ 60 % is attributed to anthropogenic sources, that is emissions caused by direct human activity (i.e. anthropogenic emissions; range 336–376 Tg CH4 yr−1 or 50 %–65 %). The mean annual total emission for the new decade (2008–2017) is 29 Tg CH4 yr−1 larger than our estimate for the previous decade (2000–2009), and 24 Tg CH4 yr−1 larger than the one reported in the previous budget for 2003–2012 (Saunois et al., 2016). Since 2012, global CH4 emissions have been tracking the warmest scenarios assessed by the Intergovernmental Panel on Climate Change. Bottom-up methods suggest almost 30 % larger global emissions (737 Tg CH4 yr−1, range 594–881) than top-down inversion methods. Indeed, bottom-up estimates for natural sources such as natural wetlands, other inland water systems, and geological sources are higher than top-down estimates. The atmospheric constraints on the top-down budget suggest that at least some of these bottom-up emissions are overestimated. The latitudinal distribution of atmospheric observation-based emissions indicates a predominance of tropical emissions (∼ 65 % of the global budget, < 30∘ N) compared to mid-latitudes (∼ 30 %, 30–60∘ N) and high northern latitudes (∼ 4 %, 60–90∘ N). The most important source of uncertainty in the methane budget is attributable to natural emissions, especially those from wetlands and other inland waters.
Some of our global source estimates are smaller than those in previously published budgets (Saunois et al., 2016; Kirschke et al., 2013). In particular wetland emissions are about 35 Tg CH4 yr−1 lower due to improved partition wetlands and other inland waters. Emissions from geological sources and wild animals are also found to be smaller by 7 Tg CH4 yr−1 by 8 Tg CH4 yr−1, respectively. However, the overall discrepancy between bottom-up and top-down estimates has been reduced by only 5 % compared to Saunois et al. (2016), due to a higher estimate of emissions from inland waters, highlighting the need for more detailed research on emissions factors. Priorities for improving the methane budget include (i) a global, high-resolution map of water-saturated soils and inundated areas emitting methane based on a robust classification of different types of emitting habitats; (ii) further development of process-based models for inland-water emissions; (iii) intensification of methane observations at local scales (e.g., FLUXNET-CH4 measurements) and urban-scale monitoring to constrain bottom-up land surface models, and at regional scales (surface networks and satellites) to constrain atmospheric inversions; (iv) improvements of transport models and the representation of photochemical sinks in top-down inversions; and (v) development of a 3D variational inversion system using isotopic and/or co-emitted species such as ethane to improve source partitioning.
1,047 citations
University of North Carolina at Chapel Hill1, Cleveland Clinic2, University of Washington3, American Society of Clinical Oncology4, BC Cancer Agency5, University of Granada6, Dartmouth–Hitchcock Medical Center7, Penn State Cancer Institute8, Emory University9, University of Rochester10, University College London11, McMaster University12, University of Southern California13, University of California, San Francisco14, Fred Hutchinson Cancer Research Center15, University of Milan16
TL;DR: An Expert Panel convened an Expert Panel to review the evidence and revise previous recommendations as needed to provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.
Abstract: PURPOSETo provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.METHODSPubMed and the Cochrane Library were searched for randomized...
900 citations
University of Texas MD Anderson Cancer Center1, University of South Florida2, Harvard University3, Cleveland Clinic4, University of California, Los Angeles5, Texas Oncology6, Ohio State University7, Sarah Cannon Research Institute8, Stanford University9, Centre Hospitalier Universitaire de Bordeaux10, Fox Chase Cancer Center11, University of Würzburg12, University of Miami13, University of Rochester14
TL;DR: KTE-X19 induced durable remissions in a majority of patients with relapsed or refractory mantle-cell lymphoma, and led to serious and life-threatening toxic effects that were consistent with those reported with other CAR T-cell therapies.
Abstract: Background Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton’s tyrosine kinase (BTK) inhibitor therapy have a poo...
875 citations
TL;DR: This single clinical report updates the 2007 American Academy of Pediatrics clinical reports on the evaluation and treatment of ASD in one publication with an online table of contents and section view available to help the reader identify topic areas within the report.
Abstract: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with reported prevalence in the United States of 1 in 59 children (approximately 1.7%). Core deficits are identified in 2 domains: social communication/interaction and restrictive, repetitive patterns of behavior. Children and youth with ASD have service needs in behavioral, educational, health, leisure, family support, and other areas. Standardized screening for ASD at 18 and 24 months of age with ongoing developmental surveillance continues to be recommended in primary care (although it may be performed in other settings), because ASD is common, can be diagnosed as young as 18 months of age, and has evidenced-based interventions that may improve function. More accurate and culturally sensitive screening approaches are needed. Primary care providers should be familiar with the diagnosticcriteria for ASD, appropriate etiologic evaluation, and co-occurring medical and behavioral conditions (such as disorders of sleep and feeding, gastrointestinal tract symptoms, obesity, seizures, attention-deficit/hyperactivity disorder, anxiety, and wandering) that affect the child’s function and quality of life. There is an increasing evidence base to support behavioral and other interventions to address specific skills and symptoms. Shared decision making calls for collaboration with families in evaluation and choice of interventions. This single clinical report updates the 2007 American Academy of Pediatrics clinical reports on the evaluation and treatment of ASD in one publication with an online table of contents and section view available through the American Academy of Pediatrics Gateway to help the reader identify topic areas within the report.
582 citations
Australian National University1, Argonne National Laboratory2, Scripps Health3, Iowa State University4, Western New England University5, Michigan State University6, National Institute of Advanced Industrial Science and Technology7, Microsoft8, University of Colorado Denver9, Oak Ridge National Laboratory10, Pacific Northwest National Laboratory11, University of Nebraska–Lincoln12, Nanjing University13, Sandia National Laboratories14, Moscow State University15, Kyocera16, Cray17, Purdue University18, Old Dominion University19, University of Rochester20
TL;DR: A discussion of many of the recently implemented features of GAMESS (General Atomic and Molecular Electronic Structure System) and LibCChem (the C++ CPU/GPU library associated with GAMESS) is presented, which include fragmentation methods, hybrid MPI/OpenMP approaches to Hartree-Fock, and resolution of the identity second order perturbation theory.
Abstract: A discussion of many of the recently implemented features of GAMESS (General Atomic and Molecular Electronic Structure System) and LibCChem (the C++ CPU/GPU library associated with GAMESS) is presented. These features include fragmentation methods such as the fragment molecular orbital, effective fragment potential and effective fragment molecular orbital methods, hybrid MPI/OpenMP approaches to Hartree-Fock, and resolution of the identity second order perturbation theory. Many new coupled cluster theory methods have been implemented in GAMESS, as have multiple levels of density functional/tight binding theory. The role of accelerators, especially graphical processing units, is discussed in the context of the new features of LibCChem, as it is the associated problem of power consumption as the power of computers increases dramatically. The process by which a complex program suite such as GAMESS is maintained and developed is considered. Future developments are briefly summarized.
575 citations
TL;DR: Superconductivity is reported in a photochemically transformed carbonaceous sulfur hydride system, starting from elemental precursors, with a maximum superconducting transition temperature of 287.7 ± 1.2 kelvin.
Abstract: One of the long-standing challenges in experimental physics is the observation of room-temperature superconductivity1,2. Recently, high-temperature conventional superconductivity in hydrogen-rich materials has been reported in several systems under high pressure3–5. An important discovery leading to room-temperature superconductivity is the pressure-driven disproportionation of hydrogen sulfide (H2S) to H3S, with a confirmed transition temperature of 203 kelvin at 155 gigapascals3,6. Both H2S and CH4 readily mix with hydrogen to form guest–host structures at lower pressures7, and are of comparable size at 4 gigapascals. By introducing methane at low pressures into the H2S + H2 precursor mixture for H3S, molecular exchange is allowed within a large assemblage of van der Waals solids that are hydrogen-rich with H2 inclusions; these guest–host structures become the building blocks of superconducting compounds at extreme conditions. Here we report superconductivity in a photochemically transformed carbonaceous sulfur hydride system, starting from elemental precursors, with a maximum superconducting transition temperature of 287.7 ± 1.2 kelvin (about 15 degrees Celsius) achieved at 267 ± 10 gigapascals. The superconducting state is observed over a broad pressure range in the diamond anvil cell, from 140 to 275 gigapascals, with a sharp upturn in transition temperature above 220 gigapascals. Superconductivity is established by the observation of zero resistance, a magnetic susceptibility of up to 190 gigapascals, and reduction of the transition temperature under an external magnetic field of up to 9 tesla, with an upper critical magnetic field of about 62 tesla according to the Ginzburg–Landau model at zero temperature. The light, quantum nature of hydrogen limits the structural and stoichiometric determination of the system by X-ray scattering techniques, but Raman spectroscopy is used to probe the chemical and structural transformations before metallization. The introduction of chemical tuning within our ternary system could enable the preservation of the properties of room-temperature superconductivity at lower pressures. Room-temperature superconductivity is observed in a photochemically synthesized ternary carbonaceous sulfur hydride system at 15 °C and 267 GPa.
Centers for Disease Control and Prevention1, University of California, Berkeley2, Anschutz Medical Campus3, Colorado Department of Public Health and Environment4, Yale University5, Veterans Health Administration6, Emory University7, United States Department of Veterans Affairs8, Alabama Department of Public Health9, Maryland Department of Health10, New Mexico Department of Health11, New York State Department of Health12, University of Rochester13, Ohio Department of Health14, Oregon Health Authority15, Vanderbilt University16, Lake County17, United States Department of Health and Human Services18
TL;DR: The cumulative rate of pediatric COVID-19-associated hospitalization remains low compared with that among adults, but weekly rates increased during the surveillance period, and one in three hospitalized children were admitted to the ICU, similar to the proportion among adults.
Abstract: Most reported cases of coronavirus disease 2019 (COVID-19) in children aged <18 years appear to be asymptomatic or mild (1). Less is known about severe COVID-19 illness requiring hospitalization in children. During March 1-July 25, 2020, 576 pediatric COVID-19 cases were reported to the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system that collects data on laboratory-confirmed COVID-19-associated hospitalizations in 14 states (2,3). Based on these data, the cumulative COVID-19-associated hospitalization rate among children aged <18 years during March 1-July 25, 2020, was 8.0 per 100,000 population, with the highest rate among children aged <2 years (24.8). During March 21-July 25, weekly hospitalization rates steadily increased among children (from 0.1 to 0.4 per 100,000, with a weekly high of 0.7 per 100,000). Overall, Hispanic or Latino (Hispanic) and non-Hispanic black (black) children had higher cumulative rates of COVID-19-associated hospitalizations (16.4 and 10.5 per 100,000, respectively) than did non-Hispanic white (white) children (2.1). Among 208 (36.1%) hospitalized children with complete medical chart reviews, 69 (33.2%) were admitted to an intensive care unit (ICU); 12 of 207 (5.8%) required invasive mechanical ventilation, and one patient died during hospitalization. Although the cumulative rate of pediatric COVID-19-associated hospitalization remains low (8.0 per 100,000 population) compared with that among adults (164.5),* weekly rates increased during the surveillance period, and one in three hospitalized children were admitted to the ICU, similar to the proportion among adults. Continued tracking of SARS-CoV-2 infections among children is important to characterize morbidity and mortality. Reinforcement of prevention efforts is essential in congregate settings that serve children, including childcare centers and schools.
Mayo Clinic1, Yeshiva University2, University of Texas MD Anderson Cancer Center3, National Institutes of Health4, Medical College of Wisconsin5, Washington University in St. Louis6, Emory University7, Université de Montréal8, Wayne State University9, University of Rochester10, University of Wisconsin-Madison11, University of Arizona12, Northwestern University13, University of Chicago14, Thomas Jefferson University15, Vanderbilt University16
TL;DR: HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.
Abstract: PURPOSERadiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy dur...
University of Texas MD Anderson Cancer Center1, University of South Florida2, Stanford University3, Washington University in St. Louis4, Mayo Clinic5, University of Maryland, Baltimore6, University of Nebraska Medical Center7, University of Miami8, University of Rochester9, Vanderbilt University10, University of Kansas11, Wayne State University12, University of Pittsburgh13, Cleveland Clinic14, University of California, San Francisco15
TL;DR: The safety and efficacy of axi-cel in the standard-of-care (SOC) setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.
Abstract: PURPOSEAxicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of ...
14 Jun 2020
TL;DR: Experimental results demonstrate that theTDAN is capable of alleviating occlusions and artifacts for temporal alignment and the TDAN-based VSR model outperforms several recent state-of-the-art VSR networks with a comparable or even much smaller model size.
Abstract: Video super-resolution (VSR) aims to restore a photo-realistic high-resolution (HR) video frame from both its corresponding low-resolution (LR) frame (reference frame) and multiple neighboring frames (supporting frames). Due to varying motion of cameras or objects, the reference frame and each support frame are not aligned. Therefore, temporal alignment is a challenging yet important problem for VSR. Previous VSR methods usually utilize optical flow between the reference frame and each supporting frame to warp the supporting frame for temporal alignment. However, both inaccurate flow and the image-level warping strategy will lead to artifacts in the warped supporting frames. To overcome the limitation, we propose a temporally-deformable alignment network (TDAN) to adaptively align the reference frame and each supporting frame at the feature level without computing optical flow. The TDAN uses features from both the reference frame and each supporting frame to dynamically predict offsets of sampling convolution kernels. By using the corresponding kernels, TDAN transforms supporting frames to align with the reference frame. To predict the HR video frame, a reconstruction network taking aligned frames and the reference frame is utilized. Experimental results demonstrate that the TDAN is capable of alleviating occlusions and artifacts for temporal alignment and the TDAN-based VSR model outperforms several recent state-of-the-art VSR networks with a comparable or even much smaller model size. The source code and pre-trained models are released in https://github.com/YapengTian/TDAN-VSR.
University of Colorado Denver1, University of South Florida2, National Institutes of Health3, University of Leicester4, Federal University of Paraná5, Monash University6, Emory University7, University of Rochester8, University of Newcastle9, McMaster University10, Wake Forest University11, Cochrane Collaboration12, University of Bern13, University of Arizona14, Laval University15, University of California, San Francisco16, Washington University in St. Louis17, University of Southampton18, Boston Children's Hospital19, University of Wisconsin-Madison20, Hokkaido University21, Zhejiang University22, University of Pittsburgh23
TL;DR: Clinical recommendations for the management of severe asthma are provided and the use of novel therapies for severe asthma, specifically biologicals for type 2 high asthma, and antimuscarinic agents and macrolides, as well as on biomarkers for predicting treatment response are made.
Abstract: This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force9s questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 μL−1 to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 μL−1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4–5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
TL;DR: A Krt8+ transitional stem cell state that precedes the regeneration of AT1 cells and persists in human lung fibrosis is uncovered and it is proposed that in lungs fibrosis, perturbed molecular checkpoints on the way to terminal differentiation can cause aberrant persistence of regenerative intermediate stem cell states.
Abstract: The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single cell RNA-seq of the bleomycin lung injury model, we resolved transcriptional dynamics for 28 cell types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional stem cell state during alveolar regeneration. These cells have squamous morphology, feature p53 and NFkB activation and display transcriptional features of cellular senescence. The Krt8+ state appears in several independent models of lung injury and persists in human lung fibrosis, creating a distinct cell-cell communication network with mesenchyme and macrophages during repair. We generated a model of gene regulatory programs leading to Krt8+ transitional cells and their terminal differentiation to alveolar type-1 cells. We propose that in lung fibrosis, perturbed molecular checkpoints on the way to terminal differentiation can cause aberrant persistence of regenerative intermediate stem cell states.
Memorial Sloan Kettering Cancer Center1, Kyoto University2, Harvard University3, University of Pavia4, Leeds Teaching Hospitals NHS Trust5, University of Göttingen6, Karolinska Institutet7, University of Düsseldorf8, Paris Descartes University9, University of Bologna10, Hannover Medical School11, Federal University of Ceará12, University of Florence13, Democritus University of Thrace14, University of Oxford15, Gifu University16, Chulalongkorn University17, University of Rochester18, Vanderbilt University19, Carlos III Health Institute20, University of Paris21, University of York22, Leipzig University23, Medical University of Vienna24, University of Tsukuba25, Nagasaki University26, University of Rome Tor Vergata27, Chang Gung University28, Radboud University Nijmegen29, Howard Hughes Medical Institute30, University of California, San Diego31, Stanford University32
TL;DR: Clinical sequencing across a large prospective cohort of patients with myelodysplasic syndrome uncovers distinct associations between the mono- and biallelic states of TP53 and clinical presentation.
Abstract: Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6–8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response. Clinical sequencing across a large prospective cohort of patients with myelodysplasic syndrome uncovers distinct associations between the mono- and biallelic states of TP53 and clinical presentation
TL;DR: For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.
Abstract: New sets of CMS underlying-event parameters (“tunes”) are presented for the pythia8 event generator. These tunes use the NNPDF3.1 parton distribution functions (PDFs) at leading (LO), next-to-leading (NLO), or next-to-next-to-leading (NNLO) orders in perturbative quantum chromodynamics, and the strong coupling evolution at LO or NLO. Measurements of charged-particle multiplicity and transverse momentum densities at various hadron collision energies are fit simultaneously to determine the parameters of the tunes. Comparisons of the predictions of the new tunes are provided for observables sensitive to the event shapes at LEP, global underlying event, soft multiparton interactions, and double-parton scattering contributions. In addition, comparisons are made for observables measured in various specific processes, such as multijet, Drell–Yan, and top quark-antiquark pair production including jet substructure observables. The simulation of the underlying event provided by the new tunes is interfaced to a higher-order matrix-element calculation. For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.
TL;DR: It is found that within minutes of ischemic stroke, CSF flowed rapidly into brain tissue along perivascular spaces and the cerebral ventricles compared with regions deep in the brain that were far from large CSF reservoirs, and CSF was the earliest contributor of both fluid and ions.
Abstract: Stroke affects millions each year. Post-stroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents, to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of post-stroke edema needs to be revised and these findings could provide a conceptual basis for development of alternative treatment strategies.
Baqiyatallah University of Medical Sciences1, Medical University of Białystok2, University of Basilicata3, University of Greenwich4, Gazi University5, University of Salerno6, University of Pavia7, University of Macau8, University of Vigo9, University of Santiago de Compostela10, Kermanshah University of Medical Sciences11, Tabriz University of Medical Sciences12, University of Reims Champagne-Ardenne13, University of Rochester14
TL;DR: In this review, flavonoids as classical examples of secondary metabolites are employed to highlight recent advances in understanding how valuable compounds can be regulated at various levels.
TL;DR: This article surveys the existing and emerging technologies that can enable this vision for the future of healthcare, particularly, in the clinical practice of healthcare and discusses the emerging directions, open issues, and challenges.
Abstract: In combination with current sociological trends, the maturing development of Internet of Things devices is projected to revolutionize healthcare. A network of body-worn sensors, each with a unique ID, can collect health data, that is, orders-of-magnitude richer than what is available today from sporadic observations in clinical/hospital environments. When databased, analyzed, and compared against information from other individuals using data analytics, Healthcare Internet of Things data enables the personalization and modernization of care with radical improvements in outcomes and reductions in cost. In this article, we survey the existing and emerging technologies that can enable this vision for the future of healthcare, particularly, in the clinical practice of healthcare. Three main technology areas underlie the development of this field: 1) sensing, where there is an increased drive for miniaturization and power efficiency; 2) communications, where the enabling factors are ubiquitous connectivity, standardized protocols, and the wide availability of cloud infrastructure; and 3) data analytics and inference, where the availability of large amounts of data and computational resources is revolutionizing algorithms for individualizing inference and actions in health management. Throughout this article, we use a case study to concretely illustrate the impact of these trends. We conclude this article with a discussion of the emerging directions, open issues, and challenges.
25 Jan 2020
TL;DR: PASE+ is proposed, an improved version of PASE that better learns short- and long-term speech dynamics with an efficient combination of recurrent and convolutional networks and learns transferable representations suitable for highly mismatched acoustic conditions.
Abstract: Despite the growing interest in unsupervised learning, extracting meaningful knowledge from unlabelled audio remains an open challenge. To take a step in this direction, we recently proposed a problem-agnostic speech encoder (PASE), that combines a convolutional encoder followed by multiple neural networks, called workers, tasked to solve self-supervised problems (i.e., ones that do not require manual annotations as ground truth). PASE was shown to capture relevant speech information, including speaker voice-print and phonemes. This paper proposes PASE+, an improved version of PASE for robust speech recognition in noisy and reverberant environments. To this end, we employ an online speech distortion module, that contaminates the input signals with a variety of random disturbances. We then propose a revised encoder that better learns short- and long-term speech dynamics with an efficient combination of recurrent and convolutional networks. Finally, we refine the set of workers used in self-supervision to encourage better cooperation.Results on TIMIT, DIRHA and CHiME-5 show that PASE+ significantly outperforms both the previous version of PASE as well as common acoustic features. Interestingly, PASE+ learns transferable representations suitable for highly mismatched acoustic conditions.
01 Jul 2020
TL;DR: Fine-tuning MAG-BERT and MAG-XLNet significantly boosts the sentiment analysis performance over previous baselines as well as language-only fine- Tuning of BERT and XLNet.
Abstract: Recent Transformer-based contextual word representations, including BERT and XLNet, have shown state-of-the-art performance in multiple disciplines within NLP. Fine-tuning the trained contextual models on task-specific datasets has been the key to achieving superior performance downstream. While fine-tuning these pre-trained models is straight-forward for lexical applications (applications with only language modality), it is not trivial for multimodal language (a growing area in NLP focused on modeling face-to-face communication). Pre-trained models don't have the necessary components to accept two extra modalities of vision and acoustic. In this paper, we proposed an attachment to BERT and XLNet called Multimodal Adaptation Gate (MAG). MAG allows BERT and XLNet to accept multimodal nonverbal data during fine-tuning. It does so by generating a shift to internal representation of BERT and XLNet; a shift that is conditioned on the visual and acoustic modalities. In our experiments, we study the commonly used CMU-MOSI and CMU-MOSEI datasets for multimodal sentiment analysis. Fine-tuning MAG-BERT and MAG-XLNet significantly boosts the sentiment analysis performance over previous baselines as well as language-only fine-tuning of BERT and XLNet. On the CMU-MOSI dataset, MAG-XLNet achieves human-level multimodal sentiment analysis performance for the first time in the NLP community.
University of Padua1, University of Amsterdam2, Utrecht University3, University College London4, Hamad Medical Corporation5, St George's, University of London6, University of Zurich7, University Hospitals Bristol NHS Foundation Trust8, University of Toronto9, University of Oslo10, Johns Hopkins University11, Medical University of South Carolina12, University of Texas Southwestern Medical Center13, University of Pennsylvania14, University of Pavia15, Anschutz Medical Campus16, Lund University17, St Bartholomew's Hospital18, Harvard University19, University of Rochester20, University of Arizona21
TL;DR: Domenico Corrado *, Peter J. van Tintelen, William J. McKenna, Richard N.W. Hauer, Aris Anastastakis, Angeliki Asimaki, Cristina Basso, Barbara Bauce, Corinna Brunckhorst, Chiara Bucciarelli-Ducci, Firat Duru, Perry Elliott, Robert M. Hamilton, Kristina H. Haugaa, Cynthia A.
Abstract: Domenico Corrado *, Peter J. van Tintelen, William J. McKenna, Richard N.W. Hauer, Aris Anastastakis, Angeliki Asimaki, Cristina Basso, Barbara Bauce, Corinna Brunckhorst, Chiara Bucciarelli-Ducci, Firat Duru, Perry Elliott, Robert M. Hamilton, Kristina H. Haugaa, Cynthia A. James, Daniel Judge, Mark S. Link, Francis E. Marchlinski, Andrea Mazzanti, Luisa Mestroni, Antonis Pantazis, Antonio Pelliccia, Martina Perazzolo Marra, Kalliopi Pilichou, Pyotr G.A. Platonov, Alexandros Protonotarios,
Memorial Sloan Kettering Cancer Center1, Columbia University Medical Center2, NewYork–Presbyterian Hospital3, Hackensack University Medical Center4, Karolinska Institutet5, Northwestern University6, University of Colorado Boulder7, Yale University8, Harvard University9, University of Belgrade10, National Institutes of Health11, Syracuse University12, University of Rochester13, Fred Hutchinson Cancer Research Center14, University of São Paulo15, University of Pennsylvania16, Duke University17, Roswell Park Cancer Institute18, Rush University Medical Center19, Wayne State University20, Nottingham University Hospitals NHS Trust21, St James's University Hospital22, Royal Bournemouth Hospital23, Western General Hospital24, Leicester Royal Infirmary25, The Royal Marsden NHS Foundation Trust26, University of Birmingham27, Beatson West of Scotland Cancer Centre28, King's College London29, University of Oslo30, University of Oxford31
TL;DR: The data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death.
Goddard Institute for Space Studies1, Columbia University2, National Oceanic and Atmospheric Administration3, University of Colorado Boulder4, Goddard Space Flight Center5, University of Washington6, Massachusetts Institute of Technology7, New York University8, University of Rochester9, Barcelona Supercomputing Center10, Catalan Institution for Research and Advanced Studies11, Duke University12
TL;DR: There have been specific improvements in representations of modes of variability (such as the Madden‐Julian Oscillation and other modes in the Pacific) and significant improvements in the simulation of the climate of the Southern Oceans, including sea ice.
Abstract: This paper describes the GISS-E2.1 contribution to the Coupled Model Intercomparison Project, Phase 6 (CMIP6). This model version differs from the predecessor model (GISS-E2) chiefly due to parameterization improvements to the atmospheric and ocean model components, while keeping atmospheric resolution the same. Model skill when compared to modern era climatologies is significantly higher than in previous versions. Additionally, updates in forcings have a material impact on the results. In particular, there have been specific improvements in representations of modes of variability (such as the Madden-Julian Oscillation and other modes in the Pacific) and significant improvements in the simulation of the climate of the Southern Oceans, including sea ice. The effective climate sensitivity to 2 × CO2 is slightly higher than previously at 2.7-3.1°C (depending on version) and is a result of lower CO2 radiative forcing and stronger positive feedbacks.
TL;DR: It is found that job vacancies collapsed in the second half of March, and this set of facts suggests the economic collapse was not caused solely by the stay-at-home orders, and is therefore unlikely to be undone simply by lifting them.
TL;DR: The results, all based on searches for a cumulative neutrino signal integrated over the 10 years of available data, motivate further study of these and similar sources, including time-dependent analyses, multimessenger correlations, and the possibility of stronger evidence with coming upgrades to the detector.
Abstract: This Letter presents the results from pointlike neutrino source searches using ten years of IceCube data collected between April 6, 2008 and July 10, 2018. We evaluate the significance of an astrophysical signal from a pointlike source looking for an excess of clustered neutrino events with energies typically above ∼1 TeV among the background of atmospheric muons and neutrinos. We perform a full-sky scan, a search within a selected source catalog, a catalog population study, and three stacked Galactic catalog searches. The most significant point in the northern hemisphere from scanning the sky is coincident with the Seyfert II galaxy NGC 1068, which was included in the source catalog search. The excess at the coordinates of NGC 1068 is inconsistent with background expectations at the level of 2.9σ after accounting for statistical trials from the entire catalog. The combination of this result along with excesses observed at the coordinates of three other sources, including TXS 0506+056, suggests that, collectively, correlations with sources in the northern catalog are inconsistent with background at 3.3σ significance. The southern catalog is consistent with background. These results, all based on searches for a cumulative neutrino signal integrated over the 10 years of available data, motivate further study of these and similar sources, including time-dependent analyses, multimessenger correlations, and the possibility of stronger evidence with coming upgrades to the detector.
TL;DR: The findings underscore the substantial burden of PD to society, payers, patients, and caregivers and suggest interventions to reduce PD incidence, delay disease progression, and alleviate symptom burden may reduce the future economic burden.
Abstract: Parkinson’s disease (PD) is one of the world’s fastest growing neurological disorders. Much is unknown about PD-associated economic burdens in the United States (U.S.) and other high-income nations. This study provides a comprehensive analysis of the economic burdens of PD in the U.S. (2017) and projections for the next two decades. Multiple data sources were used to estimate the costs of PD, including public and private administrative claims data, Medicare Current Beneficiary Survey, Medical Expenditure Panel Survey, and a primary survey (n = 4,548) designed for this study. We estimated a U.S. prevalence of approximately one million individuals with diagnosed Parkinson’s disease in 2017 and a total economic burden of $51.9 billion. The total burden of PD includes direct medical costs of $25.4 billion and $26.5 billion in indirect and non-medical costs, including an indirect cost of $14.2 billion (PWP and caregiver burden combined), non-medical costs of $7.5 billion, and $4.8 billion due to disability income received by PWPs. The Medicare program bears the largest share of excess medical costs, as most PD patients are over age 65. Projected PD prevalence will be more than 1.6 million with projected total economic burden surpassing $79 billion by 2037. The economic burden of PD was previously underestimated. Our findings underscore the substantial burden of PD to society, payers, patients, and caregivers. Interventions to reduce PD incidence, delay disease progression, and alleviate symptom burden may reduce the future economic burden of PD.