Showing papers by "University of Wisconsin-Madison 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
Centers for Disease Control and Prevention1, University of Arizona2, University of Arkansas for Medical Sciences3, Colorado Department of Public Health and Environment4, University of Colorado Denver5, Johns Hopkins University6, University of Minnesota7, Washington University in St. Louis8, Rutgers University9, University of North Carolina at Chapel Hill10, Vanderbilt University11, University of Wisconsin-Madison12
TL;DR: The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014, highlighting the variability in the evaluation and detection of ASD across communities and between sociodemographic groups.
Abstract: Problem/condition Autism spectrum disorder (ASD). Period covered 2016. Description of system The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Results For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (39% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively) [corrected]. Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). Interpretation The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. Public health action These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.
2,613 citations
Duke University1, University of British Columbia2, Albert Einstein College of Medicine3, University of Parma4, University of Wisconsin-Madison5, Lenox Hill Hospital6, Columbia University7, New Generation University College8, Medical College of Wisconsin9, Stanford University10, University of Missouri11, National Institutes of Health12, University of California, Los Angeles13, Université Paris-Saclay14, University Hospital Heidelberg15, Sichuan University16, Cleveland Clinic17, Radboud University Nijmegen18, university of lille19, Catholic University of the Sacred Heart20, Osaka University21
TL;DR: A multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing COVID-19 patients across a spectrum of healthcare environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of CXR and CT in the management of COIDs.
1,232 citations
University of Sydney1, University of Michigan2, Duke University3, University of Alabama at Birmingham4, University of Pittsburgh5, University of Florida6, Centers for Disease Control and Prevention7, University of Münster8, University of Udine9, Ankara University10, University of Wisconsin-Madison11, Paris Diderot University12, University of Arkansas for Medical Sciences13, University of Paris14, University of Lausanne15, Brown University16, Istituto Giannina Gaslini17, Carlos III Health Institute18, Uniformed Services University of the Health Sciences19, National Institutes of Health20, University of Pennsylvania21, St George's, University of London22, Heidelberg University23, University of Copenhagen24, University College London25, University of Texas MD Anderson Cancer Center26, Katholieke Universiteit Leuven27, Goethe University Frankfurt28, University of Würzburg29, Johns Hopkins University30, Monash University31, Federal University of Rio de Janeiro32, Catholic University of the Sacred Heart33, University of Texas Health Science Center at San Antonio34, Masaryk University35, RMIT University36, Radboud University Nijmegen37, University of Melbourne38, Stanford University39, University of California, Davis40, Georgia Regents University41, Cornell University42, University of Aberdeen43, University Hospital of Wales44
TL;DR: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.
Abstract: BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.
1,211 citations
Northwestern University1, Seattle Cancer Care Alliance2, Case Western Reserve University3, Washington University in St. Louis4, Ohio State University5, Stanford University6, University of California, San Diego7, Brigham and Women's Hospital8, Memorial Sloan Kettering Cancer Center9, University of Colorado Boulder10, University of Texas MD Anderson Cancer Center11, Mayo Clinic12, Fox Chase Cancer Center13, Harvard University14, Duke University15, University of Pennsylvania16, Vanderbilt University17, Yale University18, City of Hope National Medical Center19, University of Wisconsin-Madison20, University of Michigan21, University of California, San Francisco22, Johns Hopkins University23, University of South Florida24, University of Alabama at Birmingham25, University of Utah26, Roswell Park Cancer Institute27, National Comprehensive Cancer Network28
TL;DR: The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.
Abstract: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guerin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.
1,018 citations
TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements.
Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
882 citations
TL;DR: It is found that SARS-CoV-2 isolates replicate efficiently in the lungs of Syrian hamsters and cause severe pathological lesions in the lung of these animals similar to commonly reported imaging features of COVID-19 patients with pneumonia.
Abstract: At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy Here, we assessed the replicative ability and pathogenesis of SARS-CoV-2 isolates in Syrian hamsters SARS-CoV-2 isolates replicated efficiently in the lungs of hamsters, causing severe pathological lung lesions following intranasal infection In addition, microcomputed tomographic imaging revealed severe lung injury that shared characteristics with SARS-CoV-2-infected human lung, including severe, bilateral, peripherally distributed, multilobular ground glass opacity, and regions of lung consolidation SARS-CoV-2-infected hamsters mounted neutralizing antibody responses and were protected against subsequent rechallenge with SARS-CoV-2 Moreover, passive transfer of convalescent serum to naive hamsters efficiently suppressed the replication of the virus in the lungs even when the serum was administrated 2 d postinfection of the serum-treated hamsters Collectively, these findings demonstrate that this Syrian hamster model will be useful for understanding SARS-CoV-2 pathogenesis and testing vaccines and antiviral drugs
814 citations
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).
803 citations
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.
748 citations
TL;DR: The current dominant structural variant of SARS-CoV-2 appears to have evolved from the ancestral form and enhances transmissibility, and the mutation renders the new virus variant more susceptible to neutralizing antisera without altering the efficacy of vaccine candidates currently under development.
Abstract: The spike aspartic acid–614 to glycine (D614G) substitution is prevalent in global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.
742 citations
Columbia University1, Mayo Clinic2, University of Barcelona3, Université de Montréal4, University of Caen Lower Normandy5, Ludwig Maximilian University of Munich6, German Center for Neurodegenerative Diseases7, University of California, San Diego8, University of Wisconsin-Madison9, National and Kapodistrian University of Athens10, Johns Hopkins University School of Medicine11, Imperial College London12, University of Sydney13, University of Helsinki14
TL;DR: The reserve, resilience, and protective factors professional interest area established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance and evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts.
Abstract: Several concepts, which in the aggregate get might be used to account for "resilience" against age- and disease-related changes, have been the subject of much research. These include brain reserve, cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research. Therefore the reserve, resilience, and protective factors professional interest area, established under the auspices of the Alzheimer's Association, established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance. The workgroup also evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts. The workgroup hopes that this whitepaper will form a reference point for researchers in this area and facilitate research by supplying a common language.
TL;DR: The FLUXNET2015 dataset provides ecosystem-scale data on CO 2 , water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe, and is detailed in this paper.
Abstract: The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.
Stockholm Resilience Centre1, University of Tasmania2, Australian National University3, Stockholm University4, Charles Darwin University5, University of Montana6, International Union for Conservation of Nature and Natural Resources7, National Autonomous University of Mexico8, The Pew Charitable Trusts9, McGill University10, Stellenbosch University11, University of Bern12, University of Maryland, College Park13, International Center for Tropical Agriculture14, Commonwealth Scientific and Industrial Research Organisation15, University of Wisconsin-Madison16, Royal Swedish Academy of Sciences17, Hobart Corporation18, Potsdam Institute for Climate Impact Research19, Pontifical Catholic University of Chile20, University of Sussex21, University College Cork22, Lüneburg University23, University of Arizona24, Azim Premji University25, University of the Witwatersrand26, Radboud University Nijmegen27, Utrecht University28
TL;DR: In this article, the authors propose a set of four general principles that underlie high-quality knowledge co-production for sustainability research, and offer practical guidance on how to engage in meaningful co-productive practices, and how to evaluate their quality and success.
Abstract: Research practice, funding agencies and global science organizations suggest that research aimed at addressing sustainability challenges is most effective when ‘co-produced’ by academics and non-academics. Co-production promises to address the complex nature of contemporary sustainability challenges better than more traditional scientific approaches. But definitions of knowledge co-production are diverse and often contradictory. We propose a set of four general principles that underlie high-quality knowledge co-production for sustainability research. Using these principles, we offer practical guidance on how to engage in meaningful co-productive practices, and how to evaluate their quality and success.
Memorial Sloan Kettering Cancer Center1, University Hospitals of Cleveland2, Washington University in St. Louis3, University of Utah4, Duke University5, University of Wisconsin-Madison6, Harvard University7, Moffitt Cancer Center8, Vanderbilt University9, Stanford University10, Johns Hopkins University11, University of Tennessee Health Science Center12, Mayo Clinic13, Fox Chase Cancer Center14, University of Texas MD Anderson Cancer Center15, Brigham and Women's Hospital16, Roswell Park Cancer Institute17, University of Colorado Boulder18, City of Hope National Medical Center19, University of California, San Diego20, Northwestern University21, Ohio State University22, Fred Hutchinson Cancer Research Center23, University of Pennsylvania24, University of Michigan25, University of California, San Francisco26, National Comprehensive Cancer Network27
TL;DR: The NCCN Guidelines for Head and Neck Cancers as mentioned in this paper describe supportive care recommendations for patients with H&N cancers and the rationale supporting a new section on imaging recommendations for head and neck cancers.
Abstract: Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
Rotem Botvinik-Nezer1, Rotem Botvinik-Nezer2, Felix Holzmeister3, Colin F. Camerer4 +217 more•Institutions (78)
TL;DR: The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
Abstract: Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.
TL;DR: This docking study is further complemented by the MD/MMGBSA study br and identified 9 compounds that can potentially inhibit SARS-CoV-2 3CLpro.
Abstract: We have performed vitual screening of 1000 ligands and identified 9 compounds that can potentially inhibit SARS-CoV-2 3CLpro This docking study is further complemented by the MD/MMGBSA study br
TL;DR: Single-nucleus RNA sequencing in a mouse model of Aβ accumulation and postmortem brain tissue from people with Alzheimer’s disease reveals substantial species-specific differences in transcriptional signatures, but both point to the contribution of glia and the importance of TREM2.
Abstract: Glia have been implicated in Alzheimer's disease (AD) pathogenesis. Variants of the microglia receptor triggering receptor expressed on myeloid cells 2 (TREM2) increase AD risk, and activation of disease-associated microglia (DAM) is dependent on TREM2 in mouse models of AD. We surveyed gene-expression changes associated with AD pathology and TREM2 in 5XFAD mice and in human AD by single-nucleus RNA sequencing. We confirmed the presence of Trem2-dependent DAM and identified a previously undiscovered Serpina3n+C4b+ reactive oligodendrocyte population in mice. Interestingly, remarkably different glial phenotypes were evident in human AD. Microglia signature was reminiscent of IRF8-driven reactive microglia in peripheral-nerve injury. Oligodendrocyte signatures suggested impaired axonal myelination and metabolic adaptation to neuronal degeneration. Astrocyte profiles indicated weakened metabolic coordination with neurons. Notably, the reactive phenotype of microglia was less evident in TREM2-R47H and TREM2-R62H carriers than in non-carriers, demonstrating a TREM2 requirement in both mouse and human AD, despite the marked species-specific differences.
Memorial Sloan Kettering Cancer Center1, Cornell University2, Hebron University3, University of Texas MD Anderson Cancer Center4, University of California, San Francisco5, University of Wisconsin-Madison6, Harvard University7, University of Chicago8, Mayo Clinic9, University of Washington10, Johns Hopkins University11, Seoul National University Hospital12, Trinity College, Dublin13, University of Arizona14, University of Southern California15, Agios Pharmaceuticals16, University of Manchester17, Fudan University18
TL;DR: Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivOSidenib was well tolerated, and this study shows the clinical benefit of targeting IDH1 mutations in advanced,IDH1-mutant cholangiocarcinoma.
Abstract: Summary Background Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)—a small-molecule targeted inhibitor of mutated IDH1—in patients with previously treated IDH1-mutant cholangiocarcinoma. Methods This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov , NCT02989857 . Findings Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8–10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6–4·2] vs 1·4 months [1·4–1·6]; hazard ratio 0·37; 95% CI 0·25–0·54; one-sided p Interpretation Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. Funding Agios Pharmaceuticals.
Pacific Northwest National Laboratory1, United States Geological Survey2, Smithsonian Conservation Biology Institute3, Smithsonian Tropical Research Institute4, University of Minnesota5, Joint Global Change Research Institute6, University of Maryland, College Park7, Duke University8, Boston University9, Swiss Federal Institute for Forest, Snow and Landscape Research10, University of California, Berkeley11, Stanford University12, University of Florida13, Lawrence Berkeley National Laboratory14, Northern Arizona University15, Goddard Space Flight Center16, University of Birmingham17, University of Natural Resources and Life Sciences, Vienna18, Technische Universität München19, University of Wisconsin-Madison20, Columbia University21, Oak Ridge National Laboratory22, Los Alamos National Laboratory23
TL;DR: The authors show that shifts in forest dynamics are already occurring, and the emerging pattern is that global forests are tending toward younger stands with faster turnover as old-growth forest with stable dynamics are dwindling.
Abstract: Forest dynamics arise from the interplay of environmental drivers and disturbances with the demographic processes of recruitment, growth, and mortality, subsequently driving biomass and species composition. However, forest disturbances and subsequent recovery are shifting with global changes in climate and land use, altering these dynamics. Changes in environmental drivers, land use, and disturbance regimes are forcing forests toward younger, shorter stands. Rising carbon dioxide, acclimation, adaptation, and migration can influence these impacts. Recent developments in Earth system models support increasingly realistic simulations of vegetation dynamics. In parallel, emerging remote sensing datasets promise qualitatively new and more abundant data on the underlying processes and consequences for vegetation structure. When combined, these advances hold promise for improving the scientific understanding of changes in vegetation demographics and disturbances.
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: In this article, the authors 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 COVID19.
Abstract: Routine screening CT for the identification of coronavirus disease 19 (COVID-19) pneumonia is currently not recommended by most radiology societies. However, the number of CT examinations performed in persons under investigation 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 health care providers, assisting management of patients during this pandemic. Published under a CC BY 4.0 license.
Emory University1, University of Texas MD Anderson Cancer Center2, University of Maryland, Baltimore3, Princess Margaret Cancer Centre4, Icahn School of Medicine at Mount Sinai5, University of Kansas6, University of Wisconsin-Madison7, Memorial Sloan Kettering Cancer Center8, Huntsman Cancer Institute9, Indiana University10, University of Lyon11, University of Washington12, University of Navarra13, Medical College of Wisconsin14, St. Vincent's Health System15, GlaxoSmithKline16, Research Triangle Park17, University College London Hospitals NHS Foundation Trust18, UCL Institute of Ophthalmology19, Harvard University20
TL;DR: Single-agent belantamab mafodotin shows anti-myeloma activity with a manageable safety profile in patients with relapsed or refractory multiple myeloma.
Abstract: Summary Background Belantamab mafodotin (GSK2857916), an immunoconjugate targeting B-cell maturation antigen, showed single-agent activity in the phase 1 DREAMM-1 study in heavily pre-treated patients with relapsed or refractory multiple myeloma. We further investigated the safety and activity of belantamab mafodotin in the DREAMM-2 study. Methods DREAMM-2 is an open-label, two-arm, phase 2 study done at 58 multiple myeloma specialty centres in eight countries. Patients (aged ≥18 years) with relapsed or refractory multiple myeloma with disease progression after three or more lines of therapy and who were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant (or both) to an anti-CD38 monoclonal antibody with an Eastern Cooperative Oncology Group performance status of 0–2 were recruited, centrally randomly assigned (1:1) with permuted blocks (block size 4), and stratified by previous lines of therapy (≤4 vs >4) and cytogenetic features to receive 2·5 mg/kg or 3·4 mg/kg belantamab mafodotin via intravenous infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity. The intention-to-treat population comprised all randomised patients, regardless of treatment administration. The safety population comprised all patients who received at least one dose of belantamab mafodotin. The primary outcome was the proportion of randomly assigned patients in the intention-to-treat population who achieved an overall response, as assessed by an independent review committee. This study is registered with ClinicalTrials.gov , NCT03525678 , and is ongoing. Findings Between June 18, 2018, and Jan 2, 2019, 293 patients were screened and 196 were included in the intention-to-treat population (97 in the 2·5 mg/kg cohort and 99 in the 3·4 mg/kg cohort). As of June 21, 2019 (the primary analysis data cutoff date), 30 (31%; 97·5% CI 20·8–42·6) of 97 patients in the 2·5 mg/kg cohort and 34 (34%; 23·9–46·0) of 99 patients in the 3·4 mg/kg cohort achieved an overall response. The most common grade 3–4 adverse events in the safety population were keratopathy (in 26 [27%] of 95 patients in the 2·5 mg/kg cohort and 21 [21%] of 99 patients in the 3·4 mg/kg cohort), thrombocytopenia (19 [20%] and 33 [33%]), and anaemia (19 [20%] and 25 [25%]); 38 (40%) of 95 patients in the 2·5 mg/kg cohort and 47 (47%) of 99 in the 3·4 mg/kg cohort reported serious adverse events. Two deaths were potentially treatment related (one case of sepsis in the 2·5 mg/kg cohort and one case of haemophagocytic lymphohistiocytosis in the 3·4 mg/kg cohort). Interpretation Single-agent belantamab mafodotin shows anti-myeloma activity with a manageable safety profile in patients with relapsed or refractory multiple myeloma. Funding GlaxoSmithKline.
TL;DR: Alcohol-related liver disease, alcohol-related steatohepatitis, and alcohol- related cirrhosis are suggested, retaining the familiar abbreviations (ALD, ASH, and AC, respectively), due to longstanding usage, the term alcoholic hepatitis will likely persist.
University of Wisconsin-Madison1, Washington University in St. Louis2, Columbia University3, Boston University4, Johns Hopkins University School of Medicine5, Durham University6, Imperial College London7, University of Chicago8, National Institutes of Health9, Benaroya Research Institute10, University of Washington11
TL;DR: Underlying respiratory allergy and experimental allergen exposure reduce the expression of the SARS-CoV-2 receptor, ACE2, which could lead to reduced COVID-19 susceptibility.
Abstract: Underlying respiratory allergy and experimental allergen exposure reduce the expression of the SARS-CoV-2 receptor, ACE2, which could lead to reduced COVID-19 susceptibility.
QIMR Berghofer Medical Research Institute1, Charité2, University of Alabama at Birmingham3, Charles University in Prague4, National Institutes of Health5, Paris Descartes University6, St. Michael's Hospital7, Istituto Giannina Gaslini8, University of Auckland9, Nanyang Technological University10, Cystic Fibrosis Trust11, European Medicines Agency12, University of Washington13, University of Wisconsin-Madison14, University of British Columbia15, Katholieke Universiteit Leuven16, Seattle Children's Research Institute17, Post Graduate Institute of Medical Education and Research18, University College Dublin19, University of Giessen20, University of Michigan21, Queen's University Belfast22, Johns Hopkins University23, University of Liverpool24, Woolcock Institute of Medical Research25, University of Toronto26, University of Cape Town27
TL;DR: Advances in clinical care have been multifaceted and include earlier diagnosis through the implementation of newborn screening programmes, formalised airway clearance therapy, and reduced malnutrition through the use of effective pancreatic enzyme replacement and a high-energy, high-protein diet.
Massachusetts Institute of Technology1, University of Alaska Fairbanks2, Woods Hole Oceanographic Institution3, Alfred Wegener Institute for Polar and Marine Research4, University of Bremen5, California Institute of Technology6, National Oceanic and Atmospheric Administration7, Texas State University8, Lund University9, Pennsylvania State University10, VU University Amsterdam11, Potsdam Institute for Climate Impact Research12, Utah State University13, United States Naval Academy14, Environment Canada15, University of Cambridge16, University of Gothenburg17, Naval Postgraduate School18, University of California, Irvine19, University of Washington20, University College London21, Langley Research Center22, University of Wisconsin-Madison23, Finnish Meteorological Institute24, Leipzig University25, Columbia University26, Gwangju Institute of Science and Technology27
TL;DR: The Arctic has warmed more than twice as fast as the global average since the late twentieth century, a phenomenon known as Arctic amplification (AA), and progress has been made in understanding the mechanisms that link it to midlatitude weather variability as discussed by the authors.
Abstract: The Arctic has warmed more than twice as fast as the global average since the late twentieth century, a phenomenon known as Arctic amplification (AA). Recently, there have been considerable advances in understanding the physical contributions to AA, and progress has been made in understanding the mechanisms that link it to midlatitude weather variability. Observational studies overwhelmingly support that AA is contributing to winter continental cooling. Although some model experiments support the observational evidence, most modelling results show little connection between AA and severe midlatitude weather or suggest the export of excess heating from the Arctic to lower latitudes. Divergent conclusions between model and observational studies, and even intramodel studies, continue to obfuscate a clear understanding of how AA is influencing midlatitude weather.
TL;DR: The results of these reviews can know how developmental and environmental factors qualitatively and quantitatively influence SMs of medicinal plants and how these can be integrated as tools to quality control, as well as on the improvement of clinical curative effects by altering their genomes, and/or growth conditions.
14 Jul 2020
TL;DR: A review of physical lake variables and their responses to climate change is presented in this paper, where the authors discuss recent and expected lake responses and look towards future research opportunities in lake monitoring and modelling.
Abstract: Climate change is one of the most severe threats to global lake ecosystems. Lake surface conditions, such as ice cover, surface temperature, evaporation and water level, respond dramatically to this threat, as observed in recent decades. In this Review, we discuss physical lake variables and their responses to climate change. Decreases in winter ice cover and increases in lake surface temperature modify lake mixing regimes and accelerate lake evaporation. Where not balanced by increased mean precipitation or inflow, higher evaporation rates will favour a decrease in lake level and surface water extent. Together with increases in extreme-precipitation events, these lake responses will impact lake ecosystems, changing water quantity and quality, food provisioning, recreational opportunities and transportation. Future research opportunities, including enhanced observation of lake variables from space (particularly for small water bodies), improved in situ lake monitoring and the development of advanced modelling techniques to predict lake processes, will improve our global understanding of lake responses to a changing climate. Climate change affects lakes worldwide and is predicted to continue to alter lake ice cover, surface temperature, evaporation rates, water levels and mixing regimes. This Review discusses recent and expected lake responses to climate change and looks towards future research opportunities in lake monitoring and modelling.
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...
TL;DR: Coronavirus in Cats SARS-CoV-2 was detected in three cats after they were cohoused with cats that had been experimentally inoculated with the virus.
Abstract: Coronavirus in Cats SARS-CoV-2 was detected in three cats after they were cohoused with cats that had been experimentally inoculated with the virus. Cats may be a silent intermediate host of SARS-C...