Showing papers by "New York University published in 2020"
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.
5,802 citations
01 Oct 2020
TL;DR: Transformers is an open-source library that consists of carefully engineered state-of-the art Transformer architectures under a unified API and a curated collection of pretrained models made by and available for the community.
Abstract: Recent progress in natural language processing has been driven by advances in both model architecture and model pretraining. Transformer architectures have facilitated building higher-capacity models and pretraining has made it possible to effectively utilize this capacity for a wide variety of tasks. Transformers is an open-source library with the goal of opening up these advances to the wider machine learning community. The library consists of carefully engineered state-of-the art Transformer architectures under a unified API. Backing this library is a curated collection of pretrained models made by and available for the community. Transformers is designed to be extensible by researchers, simple for practitioners, and fast and robust in industrial deployments. The library is available at https://github.com/huggingface/transformers.
4,798 citations
New York University1, University of Chicago2, Mackenzie Presbyterian University3, Middlesex University4, University of Kent5, Nicolaus Copernicus University in Toruń6, Harvard University7, Yale University8, Stanford University9, Northwestern University10, University of Sussex11, Utrecht University12, University of California, San Diego13, University of Maryland, College Park14, McGovern Institute for Brain Research15, University of Queensland16, University of Michigan17, California Institute of Technology18, Lehigh University19, University of Regina20, University of Oregon21, Ohio State University22, Massachusetts Institute of Technology23, University of St Andrews24, University of Cambridge25, University of British Columbia26, University of Illinois at Chicago27, University of California, Berkeley28, Carleton University29, VU University Amsterdam30, Cornell University31
TL;DR: Evidence from a selection of research topics relevant to pandemics is discussed, including work on navigating threats, social and cultural influences on behaviour, science communication, moral decision-making, leadership, and stress and coping.
Abstract: The COVID-19 pandemic represents a massive global health crisis. Because the crisis requires large-scale behaviour change and places significant psychological burdens on individuals, insights from the social and behavioural sciences can be used to help align human behaviour with the recommendations of epidemiologists and public health experts. Here we discuss evidence from a selection of research topics relevant to pandemics, including work on navigating threats, social and cultural influences on behaviour, science communication, moral decision-making, leadership, and stress and coping. In each section, we note the nature and quality of prior research, including uncertainty and unsettled issues. We identify several insights for effective response to the COVID-19 pandemic and highlight important gaps researchers should move quickly to fill in the coming weeks and months.
3,223 citations
Book•
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
Christopher J L Murray1, Christopher J L Murray2, Christopher J L Murray3, Aleksandr Y. Aravkin1 +2269 more•Institutions (286)
TL;DR: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure.
3,059 citations
TL;DR: ‘weighted-nearest neighbor’ analysis is introduced, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities.
Abstract: The simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single-cell genomics and necessitates new computational methods that can define cellular states based on multiple data types. Here, we introduce ‘weighted-nearest neighbor’ analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of hundreds of thousands of human white blood cells alongside a panel of 228 antibodies to construct a multimodal reference atlas of the circulating immune system. We demonstrate that integrative analysis substantially improves our ability to resolve cell states and validate the presence of previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets, and to interpret immune responses to vaccination and COVID-19. Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets, including paired measurements of RNA and chromatin state, and to look beyond the transcriptome towards a unified and multimodal definition of cellular identity. Availability Installation instructions, documentation, tutorials, and CITE-seq datasets are available at http://www.satijalab.org/seurat
2,924 citations
Proceedings Article•
30 Apr 2020TL;DR: This work presents two parameter-reduction techniques to lower memory consumption and increase the training speed of BERT, and uses a self-supervised loss that focuses on modeling inter-sentence coherence.
Abstract: Increasing model size when pretraining natural language representations often results in improved performance on downstream tasks. However, at some point further model increases become harder due to GPU/TPU memory limitations, longer training times, and unexpected model degradation. To address these problems, we present two parameter-reduction techniques to lower memory consumption and increase the training speed of BERT. Comprehensive empirical evidence shows that our proposed methods lead to models that scale much better compared to the original BERT. We also use a self-supervised loss that focuses on modeling inter-sentence coherence, and show it consistently helps downstream tasks with multi-sentence inputs. As a result, our best model establishes new state-of-the-art results on the GLUE, RACE, and SQuAD benchmarks while having fewer parameters compared to BERT-large.
2,367 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
United States Public Health Service1, Emory University2, Rutgers University3, Harvard University4, Central Michigan University5, Westchester Medical Center6, Icahn School of Medicine at Mount Sinai7, New York University8, Saint Barnabas Medical Center9, University of Pennsylvania10, SUNY Downstate Medical Center11, Yale University12, University of Colorado Denver13, Boston Children's Hospital14, Case Western Reserve University15, Louisiana State University16, University of Washington17, Johns Hopkins University18, University of Texas Health Science Center at Houston19, University of Mississippi20, Tufts University21, Vanderbilt University22
TL;DR: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.
Abstract: Background Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19)...
1,887 citations
Francis Crick Institute1, Fox Chase Cancer Center2, Washington University in St. Louis3, Cold Spring Harbor Laboratory4, Howard Hughes Medical Institute5, Salk Institute for Biological Studies6, Cornell University7, Goethe University Frankfurt8, Fred Hutchinson Cancer Research Center9, Massachusetts Institute of Technology10, Harvard University11, University of Manchester12, New York University13, University of Texas Health Science Center at Houston14, University of Pennsylvania15, Stony Brook University16, Hofstra University17, Weizmann Institute of Science18, Oregon Health & Science University19, University of California, San Francisco20, King's College London21, Johns Hopkins University22
TL;DR: This Consensus Statement issues a call to action for all cancer researchers to standardize assays and report metadata in studies of cancer-associated fibroblasts to advance the understanding of this important cell type in the tumour microenvironment.
Abstract: Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.
1,616 citations
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
Stanford University1, New York University2, Duke University3, Boston University4, Saint Louis University5, Imperial College London6, Northwick Park Hospital7, Hospital Universitario La Paz8, Durham University9, NewYork–Presbyterian Hospital10, Albany Medical College11, St. Michael's Hospital12, Montreal Heart Institute13, Auckland City Hospital14, All India Institute of Medical Sciences15, University of British Columbia16, Cedars-Sinai Medical Center17, Harvard University18, Brigham and Women's Hospital19, Columbia University Medical Center20, Saint Francis University21, University of Missouri–Kansas City22, Government Medical College, Thiruvananthapuram23, Sri Jayadeva Institute of Cardiovascular Sciences and Research24, University of São Paulo25, Veterans Health Administration26, Emory University27, Mayo Clinic28, Semmelweis University29, Flinders Medical Centre30, Université Paris-Saclay31, Uppsala University Hospital32, Uppsala University33, Keio University34, National Institutes of Health35, Vanderbilt University36, East Carolina University37, Icahn School of Medicine at Mount Sinai38
TL;DR: Evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years is not found.
Abstract: Background Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical ther...
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.
Université Paris-Saclay1, Commonwealth Scientific and Industrial Research Organisation2, Goddard Space Flight Center3, Stanford University4, Yale University5, National Oceanic and Atmospheric Administration6, Netherlands Institute for Space Research7, VU University Amsterdam8, 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, National Institute of Geophysics and Volcanology20, Babeș-Bolyai University21, 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, Imperial College London45, Technical University of Crete46, 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.
TL;DR: In this paper, the authors proposed a method to solve the problem of the problem: this paper ] of "uniformity" of the distribution of data points in the data set.
Abstract: Abstract
University of Pennsylvania1, Boston University2, University of Maryland, Baltimore3, Arcadia University4, McMaster University5, Rush University Medical Center6, University of North Carolina at Chapel Hill7, University of Chicago8, University of Michigan9, Tufts Medical Center10, University of Toronto11, University of Arizona12, New York University13, University of Delaware14, University of California, Davis15, Ronald Reagan UCLA Medical Center16, Johns Hopkins University School of Medicine17, ECRI Institute18, Cedars-Sinai Medical Center19, American College of Rheumatology20, University of Minnesota21
TL;DR: An evidence‐based guideline for the comprehensive management of osteoarthritis (OA) is developed as a collaboration between the American College of Rheumatology and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA.
Abstract: Objective To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA. Methods We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations. Results Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol. Conclusion This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
TL;DR: There was no association between any single medication class and an increased likelihood of a positive test for Covid-19 or in the risk of severe Covd-19 among patients who tested positive in association with five common classes of antihypertensive medications.
Abstract: Background There is concern about the potential of an increased risk related to medications that act on the renin–angiotensin–aldosterone system in patients exposed to coronavirus disease ...
TL;DR: In this paper, the authors provide a full-stack, system-level perspective on 6G scenarios and requirements, and select 6G technologies that can satisfy them either by improving the 5G design or by introducing completely new communication paradigms.
Abstract: Reliable data connectivity is vital for the ever increasingly intelligent, automated, and ubiquitous digital world. Mobile networks are the data highways and, in a fully connected, intelligent digital world, will need to connect everything, including people to vehicles, sensors, data, cloud resources, and even robotic agents. Fifth generation (5G) wireless networks, which are currently being deployed, offer significant advances beyond LTE, but may be unable to meet the full connectivity demands of the future digital society. Therefore, this article discusses technologies that will evolve wireless networks toward a sixth generation (6G) and which we consider as enablers for several potential 6G use cases. We provide a fullstack, system-level perspective on 6G scenarios and requirements, and select 6G technologies that can satisfy them either by improving the 5G design or by introducing completely new communication paradigms.
TL;DR: Hidden in Plain Sight Diagnostic algorithms and practice guidelines that adjust or “correct” their outputs on the basis of a patient’s race or ethnicity guide decisions in ways that may direct more decisions about treatment.
Abstract: Hidden in Plain Sight Diagnostic algorithms and practice guidelines that adjust or “correct” their outputs on the basis of a patient’s race or ethnicity guide decisions in ways that may direct more...
Romina Ahumada1, Carlos Allende Prieto2, Carlos Allende Prieto3, Andres Almeida4 +342 more•Institutions (94)
TL;DR: The most recent data release from the Sloan Digital Sky Surveys (SDSS-IV) is DR16 as mentioned in this paper, which is the fourth and penultimate from the fourth phase of the survey.
Abstract: This paper documents the sixteenth data release (DR16) from the Sloan Digital Sky Surveys; the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the southern hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey (TDSS) and new data from the SPectroscopic IDentification of ERosita Survey (SPIDERS) programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).
University of Pennsylvania1, University of Texas Southwestern Medical Center2, Washington University in St. Louis3, University of Chicago4, Icahn School of Medicine at Mount Sinai5, University of California, San Francisco6, University of Wisconsin-Madison7, University of California, San Diego8, New York University9
TL;DR: The goal of this expert consensus is to help radiologists recognize findings of COVID-19 pneumonia and aid their communication with other healthcare providers, assisting management of patients during this pandemic.
Abstract: Routine screening CT for the identification of COVID-19 pneumonia is currently not recommended by most radiology societies. However, the number of CTs performed in persons under investigation (PUI) for COVID-19 has increased. We also anticipate that some patients will have incidentally detected findings that could be attributable to COVID-19 pneumonia, requiring radiologists to decide whether or not to mention COVID-19 specifically as a differential diagnostic possibility. We aim to provide guidance to radiologists in reporting CT findings potentially attributable to COVID-19 pneumonia, including standardized language to reduce reporting variability when addressing the possibility of COVID-19. When typical or indeterminate features of COVID-19 pneumonia are present in endemic areas as an incidental finding, we recommend contacting the referring providers to discuss the likelihood of viral infection. These incidental findings do not necessarily need to be reported as COVID-19 pneumonia. In this setting, using the term "viral pneumonia" can be a reasonable and inclusive alternative. However, if one opts to use the term "COVID-19" in the incidental setting, consider the provided standardized reporting language. In addition, practice patterns may vary, and this document is meant to serve as a guide. Consultation with clinical colleagues at each institution is suggested to establish a consensus reporting approach. The goal of this expert consensus is to help radiologists recognize findings of COVID-19 pneumonia and aid their communication with other healthcare providers, assisting management of patients during this pandemic.
Queen Mary University of London1, University of California, San Francisco2, New York University3, German Cancer Research Center4, Pontifícia Universidade Católica do Rio Grande do Sul5, Curie Institute6, Hoffmann-La Roche7, Genentech8, Harvard University9, Peter MacCallum Cancer Centre10, University of Pittsburgh11
TL;DR: The prespecified second interim overall survival analysis of the phase 3 IMpassion130 study assessing the efficacy and safety of atezolizumab plus nab-paclitaxel in patients with unresectable, locally advanced or metastatic triple-negative breast cancer occurred.
Abstract: Summary Background Immunotherapy in combination with chemotherapy has shown promising efficacy across many different tumour types. We report the prespecified second interim overall survival analysis of the phase 3 IMpassion130 study assessing the efficacy and safety of atezolizumab plus nab-paclitaxel in patients with unresectable, locally advanced or metastatic triple-negative breast cancer. Methods In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 246 academic centres and community oncology practices in 41 countries, patients aged 18 years or older, with previously untreated, histologically documented, locally advanced or metastatic triple-negative breast cancer, and Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) using a permuted block method (block size of four) and an interactive voice–web response system. Randomisation was stratified by previous taxane use, liver metastases, and PD-L1 expression on tumour-infiltrating immune cells. Patients received atezolizumab 840 mg or matching placebo intravenously on day 1 and day 15 of every 28-day cycle and nab-paclitaxel 100 mg/m2 of body surface area intravenously on days 1, 8, and 15 until progression or unacceptable toxicity. Investigators, patients, and the funder were masked to treatment assignment. Coprimary endpoints were investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival, assessed in the intention-to-treat population and in patients with PD-L1 immune cell-positive tumours (tumours with ≥1% PD-L1 expression). The final progression-free survival results were previously reported at the first interim overall survival analysis. The prespecified statistical testing hierarchy meant that overall survival in the subgroup of PD-L1 immune cell-positive patients could only be formally tested if overall survival was significantly different between the treatment groups in the intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT02425891 . Findings Between June 23, 2015, and May 24, 2017, 902 patients were enrolled, of whom 451 were randomly assigned to receive atezolizumab plus nab-paclitaxel and 451 were assigned to receive placebo plus nab-paclitaxel (the intention-to-treat population). Six patients from each group did not receive treatment. At the second interim analysis (data cutoff Jan 2, 2019), median follow-up was 18·5 months (IQR 9·6–22·8) in the atezolizumab group and 17·5 months (8·4–22·4) in the placebo group. Median overall survival in the intention-to-treat patients was 21·0 months (95% CI 19·0–22·6) with atezolizumab and 18·7 months (16·9–20·3) with placebo (stratified hazard ratio [HR] 0·86, 95% CI 0·72–1·02, p=0·078). In the exploratory overall survival analysis in patients with PD-L1 immune cell-positive tumours, median overall survival was 25·0 months (95% CI 19·6–30·7) with atezolizumab versus 18·0 months (13·6–20·1) with placebo (stratified HR 0·71, 0·54–0·94]). As of Sept 3, 2018 (the date up to which updated safety data were available), the most common grade 3–4 adverse events were neutropenia (38 [8%] of 453 patients in the atezolizumab group vs 36 [8%] of 437 patients in the placebo group), peripheral neuropathy (25 [6%] vs 12 [3%]), decreased neutrophil count (22 [5%] vs 16 [4%]), and fatigue (17 [4%] vs 15 [3%]). Treatment-related deaths occurred in two ( Interpretation Consistent with the first interim analysis, this second interim overall survival analysis of IMpassion130 indicates no significant difference in overall survival between the treatment groups in the intention-to-treat population but suggests a clinically meaningful overall survival benefit with atezolizumab plus nab-paclitaxel in patients with PD-L1 immune cell-positive disease. However, this positive result could not be formally tested due to the prespecified statistical testing hierarchy. For patients with PD-L1 immune cell-positive metastatic triple-negative breast cancer, atezolizumab plus nab-paclitaxel is an important therapeutic option in a disease with high unmet need. Funding F Hoffmann-La Roche and Genentech.
TL;DR: Eight patients with Covid-19 presented with ST-segment elevation on ECG or had it develop during hospitalization and eight patients received a diagnosis of acute my...
Abstract: ST-Segment Elevation in Covid-19 Eighteen patients with Covid-19 presented with ST-segment elevation on ECG or had it develop during hospitalization. Eight patients received a diagnosis of acute my...
TL;DR: This study examines the incidence of and risk factors for venous and arterial thrombosis in patients hospitalized with COVID-19 in 4 New York City hospitals.
Abstract: This study examines the incidence of and risk factors for venous and arterial thrombosis in patients hospitalized with COVID-19 in 4 New York City hospitals.
Posted Content•
TL;DR: A general-purpose fine-tuning recipe for retrieval-augmented generation (RAG) -- models which combine pre-trained parametric and non-parametric memory for language generation, and finds that RAG models generate more specific, diverse and factual language than a state-of-the-art parametric-only seq2seq baseline.
Abstract: Large pre-trained language models have been shown to store factual knowledge in their parameters, and achieve state-of-the-art results when fine-tuned on downstream NLP tasks. However, their ability to access and precisely manipulate knowledge is still limited, and hence on knowledge-intensive tasks, their performance lags behind task-specific architectures. Additionally, providing provenance for their decisions and updating their world knowledge remain open research problems. Pre-trained models with a differentiable access mechanism to explicit non-parametric memory can overcome this issue, but have so far been only investigated for extractive downstream tasks. We explore a general-purpose fine-tuning recipe for retrieval-augmented generation (RAG) -- models which combine pre-trained parametric and non-parametric memory for language generation. We introduce RAG models where the parametric memory is a pre-trained seq2seq model and the non-parametric memory is a dense vector index of Wikipedia, accessed with a pre-trained neural retriever. We compare two RAG formulations, one which conditions on the same retrieved passages across the whole generated sequence, the other can use different passages per token. We fine-tune and evaluate our models on a wide range of knowledge-intensive NLP tasks and set the state-of-the-art on three open domain QA tasks, outperforming parametric seq2seq models and task-specific retrieve-and-extract architectures. For language generation tasks, we find that RAG models generate more specific, diverse and factual language than a state-of-the-art parametric-only seq2seq baseline.
TL;DR: New survey evidence is presented of significant gaps at the individual level between Republicans and Democrats in self-reported social distancing, beliefs about personal COVID risk, and beliefs about the future severity of the pandemic.
Cornell University1, Tokyo Institute of Technology2, Yonsei University3, Linköping University4, Uppsala University5, National Institutes of Health6, Memorial Sloan Kettering Cancer Center7, University of Porto8, Rockefeller University9, École Polytechnique Fédérale de Lausanne10, Carlos III Health Institute11, University of Tokyo12, Ohio State University13, Princeton University14, University of Oviedo15, Icahn School of Medicine at Mount Sinai16, Weizmann Institute of Science17, Lucile Packard Children's Hospital18, New York University19, Champalimaud Foundation20, University of Nebraska Medical Center21, Fred Hutchinson Cancer Research Center22, University of Pennsylvania23, University of California, San Diego24, University of Vermont25, University of Southern California26, City of Hope National Medical Center27, Lawrence Berkeley National Laboratory28
TL;DR: EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type, and a panel of tumor-type-specific EVP proteins in TEs and plasma are defined, which can classify tumors of unknown primary origin.
TL;DR: This study describes demographic characteristics and hospital bed capacities of the 5 New York City boroughs, and evaluates whether differences in testing for coronavirus disease 2019 (COVID-19), hospitalizations, and deaths have emerged as a signal of racial, ethnic, and financial disparities.
Abstract: This study describes demographic characteristics and hospital bed capacities of the 5 New York City boroughs, and evaluates whether differences in testing for coronavirus disease 2019 (COVID-19), hospitalizations, and deaths have emerged as a signal of racial, ethnic, and financial disparities.
Children's Hospital of Philadelphia1, Great Ormond Street Hospital2, McMaster University3, Boston Children's Hospital4, St Mary's Hospital5, University of Queensland6, University of Cape Town7, University of Liverpool8, Durham University9, South University10, French Institute of Health and Medical Research11, University of Cambridge12, University Hospital Southampton NHS Foundation Trust13, Nationwide Children's Hospital14, Erasmus University Medical Center15, All India Institute of Medical Sciences16, Radboud University Nijmegen17, Royal Children's Hospital18, Children's Hospital Los Angeles19, New York University20, Stony Brook University21, Apollo Hospitals22, Johns Hopkins University23, University of the West of England24, University of Iowa25, St. Jude Children's Research Hospital26, Cincinnati Children's Hospital Medical Center27, Seattle Children's28, University of British Columbia29, Centre national de la recherche scientifique30
TL;DR: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations.
Abstract: OBJECTIVES: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified. CONCLUSIONS: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.
TL;DR: It is shown that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves theAutophagy cargo receptor NBR1 and leads to improved antigen presentation, enhanced anti-tumour T cell responses and reduced tumour growth in syngeneic host mice.
Abstract: Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy1-3. However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB4, mutations that cause loss of MHC-I are rarely found5 despite the frequent downregulation of MHC-I expression6-8. Here we show that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced expression of MHC-I at the cell surface and instead demonstrate predominant localization within autophagosomes and lysosomes. Notably, inhibition of autophagy restores surface levels of MHC-I and leads to improved antigen presentation, enhanced anti-tumour T cell responses and reduced tumour growth in syngeneic host mice. Accordingly, the anti-tumour effects of autophagy inhibition are reversed by depleting CD8+ T cells or reducing surface expression of MHC-I. Inhibition of autophagy, either genetically or pharmacologically with chloroquine, synergizes with dual ICB therapy (anti-PD1 and anti-CTLA4 antibodies), and leads to an enhanced anti-tumour immune response. Our findings demonstrate a role for enhanced autophagy or lysosome function in immune evasion by selective targeting of MHC-I molecules for degradation, and provide a rationale for the combination of autophagy inhibition and dual ICB therapy as a therapeutic strategy against PDAC.