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Showing papers by "University of Toronto published in 2020"


Journal ArticleDOI
16 Sep 2020-Nature
TL;DR: In this paper, the authors review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data, and their evolution into a flexible interoperability layer between increasingly specialized computational libraries is discussed.
Abstract: Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves1 and in the first imaging of a black hole2. Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis. NumPy is the primary array programming library for Python; here its fundamental concepts are reviewed and its evolution into a flexible interoperability layer between increasingly specialized computational libraries is discussed.

7,624 citations


Journal ArticleDOI
Theo Vos1, Theo Vos2, Theo Vos3, Stephen S Lim  +2416 moreInstitutions (246)
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


Journal ArticleDOI
Nabila Aghanim1, Yashar Akrami2, Yashar Akrami3, Yashar Akrami4  +229 moreInstitutions (70)
TL;DR: In this article, the authors present cosmological parameter results from the full-mission Planck measurements of the cosmic microwave background (CMB) anisotropies, combining information from the temperature and polarization maps and the lensing reconstruction.
Abstract: We present cosmological parameter results from the final full-mission Planck measurements of the cosmic microwave background (CMB) anisotropies, combining information from the temperature and polarization maps and the lensing reconstruction Compared to the 2015 results, improved measurements of large-scale polarization allow the reionization optical depth to be measured with higher precision, leading to significant gains in the precision of other correlated parameters Improved modelling of the small-scale polarization leads to more robust constraints on manyparameters,withresidualmodellinguncertaintiesestimatedtoaffectthemonlyatthe05σlevelWefindgoodconsistencywiththestandard spatially-flat6-parameter ΛCDMcosmologyhavingapower-lawspectrumofadiabaticscalarperturbations(denoted“base ΛCDM”inthispaper), from polarization, temperature, and lensing, separately and in combination A combined analysis gives dark matter density Ωch2 = 0120±0001, baryon density Ωbh2 = 00224±00001, scalar spectral index ns = 0965±0004, and optical depth τ = 0054±0007 (in this abstract we quote 68% confidence regions on measured parameters and 95% on upper limits) The angular acoustic scale is measured to 003% precision, with 100θ∗ = 10411±00003Theseresultsareonlyweaklydependentonthecosmologicalmodelandremainstable,withsomewhatincreasederrors, in many commonly considered extensions Assuming the base-ΛCDM cosmology, the inferred (model-dependent) late-Universe parameters are: HubbleconstantH0 = (674±05)kms−1Mpc−1;matterdensityparameterΩm = 0315±0007;andmatterfluctuationamplitudeσ8 = 0811±0006 We find no compelling evidence for extensions to the base-ΛCDM model Combining with baryon acoustic oscillation (BAO) measurements (and consideringsingle-parameterextensions)weconstraintheeffectiveextrarelativisticdegreesoffreedomtobe Neff = 299±017,inagreementwith the Standard Model prediction Neff = 3046, and find that the neutrino mass is tightly constrained toPmν < 012 eV The CMB spectra continue to prefer higher lensing amplitudesthan predicted in base ΛCDM at over 2σ, which pulls some parameters that affect thelensing amplitude away from the ΛCDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAOdataThejointconstraintwithBAOmeasurementsonspatialcurvatureisconsistentwithaflatuniverse, ΩK = 0001±0002Alsocombining with Type Ia supernovae (SNe), the dark-energy equation of state parameter is measured to be w0 = −103±003, consistent with a cosmological constant We find no evidence for deviations from a purely power-law primordial spectrum, and combining with data from BAO, BICEP2, and Keck Array data, we place a limit on the tensor-to-scalar ratio r0002 < 006 Standard big-bang nucleosynthesis predictions for the helium and deuterium abundances for the base-ΛCDM cosmology are in excellent agreement with observations The Planck base-ΛCDM results are in good agreement with BAO, SNe, and some galaxy lensing observations, but in slight tension with the Dark Energy Survey’s combined-probe results including galaxy clustering (which prefers lower fluctuation amplitudes or matter density parameters), and in significant, 36σ, tension with local measurements of the Hubble constant (which prefer a higher value) Simple model extensions that can partially resolve these tensions are not favoured by the Planck data

4,688 citations


Journal ArticleDOI
TL;DR: How a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data is reviewed.
Abstract: Array programming provides a powerful, compact, expressive syntax for accessing, manipulating, and operating on data in vectors, matrices, and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It plays an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, material science, engineering, finance, and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves and the first imaging of a black hole. Here we show how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring, and analyzing scientific data. NumPy is the foundation upon which the entire scientific Python universe is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Because of its central position in the ecosystem, NumPy increasingly plays the role of an interoperability layer between these new array computation libraries.

4,342 citations


Book
Georges Aad1, E. Abat2, Jalal Abdallah3, Jalal Abdallah4  +3029 moreInstitutions (164)
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


Journal ArticleDOI
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


Journal ArticleDOI
TL;DR: The COVID-19 pandemic is associated with highly significant levels of psychological distress that, in many cases, would meet the threshold for clinical relevance.

3,011 citations


Journal ArticleDOI
TL;DR: Allocating Scarce Medical Resources for Covid-19 The Covd-19 pandemic has already stressed health care systems throughout the world, requiring rationing of medical equipment and care.
Abstract: Allocating Scarce Medical Resources for Covid-19 The Covid-19 pandemic has already stressed health care systems throughout the world, requiring rationing of medical equipment and care. The authors ...

2,286 citations


Journal ArticleDOI
TL;DR: The rationale for angiotensin-converting enzyme 2 (ACE2) receptor as a specific target is reviewed, and a number of pharmaceuticals already being tested are tested but a better understanding of the underlying pathobiology is required.
Abstract: A novel infectious disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in Wuhan, China, in December 2019. The disease (COVID-19) spread rapidly, reaching epidemic proportions in China, and has been found in 27 other countries. As of February 27, 2020, over 82,000 cases of COVID-19 were reported, with > 2800 deaths. No specific therapeutics are available, and current management includes travel restrictions, patient isolation, and supportive medical care. There are a number of pharmaceuticals already being tested [1, 2], but a better understanding of the underlying pathobiology is required. In this context, this article will briefly review the rationale for angiotensin-converting enzyme 2 (ACE2) receptor as a specific target.

1,943 citations


Journal ArticleDOI
02 Sep 2020-JAMA
TL;DR: A prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19 found that low-dose dexamethasone reduced mortality in hospitalized patients with Cohen's disease who required respiratory support.
Abstract: Importance Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support. Objective To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality. Design, Setting, and Participants Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using theI2statistic. The primary analysis was an inverse variance–weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance–weighted fixed-effect analysis using risk ratios. Exposures Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients). Main Outcomes and Measures The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events. Results A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as “low” for 6 of the 7 mortality results and as “some concerns” in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82];P Conclusions and Relevance In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.

1,764 citations


Journal ArticleDOI
TL;DR: The Surviving Sepsis Campaign CO VID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19, and will provide new recommendations in further releases of these guidelines.
Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.

Journal ArticleDOI
Yashar Akrami1, Yashar Akrami2, M. Ashdown3, J. Aumont4  +180 moreInstitutions (59)
TL;DR: In this paper, a power-law fit to the angular power spectra of dust polarization at 353 GHz for six nested sky regions covering from 24 to 71 % of the sky is presented.
Abstract: The study of polarized dust emission has become entwined with the analysis of the cosmic microwave background (CMB) polarization. We use new Planck maps to characterize Galactic dust emission as a foreground to the CMB polarization. We present Planck EE, BB, and TE power spectra of dust polarization at 353 GHz for six nested sky regions covering from 24 to 71 % of the sky. We present power-law fits to the angular power spectra, yielding evidence for statistically significant variations of the exponents over sky regions and a difference between the values for the EE and BB spectra. The TE correlation and E/B power asymmetry extend to low multipoles that were not included in earlier Planck polarization papers. We also report evidence for a positive TB dust signal. Combining data from Planck and WMAP, we determine the amplitudes and spectral energy distributions (SEDs) of polarized foregrounds, including the correlation between dust and synchrotron polarized emission, for the six sky regions as a function of multipole. This quantifies the challenge of the component separation procedure required for detecting the reionization and recombination peaks of primordial CMB B modes. The SED of polarized dust emission is fit well by a single-temperature modified blackbody emission law from 353 GHz to below 70 GHz. For a dust temperature of 19.6 K, the mean spectral index for dust polarization is $\beta_{\rm d}^{P} = 1.53\pm0.02 $. By fitting multi-frequency cross-spectra, we examine the correlation of the dust polarization maps across frequency. We find no evidence for decorrelation. If the Planck limit for the largest sky region applies to the smaller sky regions observed by sub-orbital experiments, then decorrelation might not be a problem for CMB experiments aiming at a primordial B-mode detection limit on the tensor-to-scalar ratio $r\simeq0.01$ at the recombination peak.


Journal ArticleDOI
Peter J. Campbell1, Gad Getz2, Jan O. Korbel3, Joshua M. Stuart4  +1329 moreInstitutions (238)
06 Feb 2020-Nature
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.

Journal ArticleDOI
01 Sep 2020-Pain
TL;DR: This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period.
Abstract: The current International Association for the Study of Pain (IASP) definition of pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications. Therefore, in 2018, the IASP formed a 14-member, multinational Presidential Task Force comprising individuals with broad expertise in clinical and basic science related to pain, to evaluate the current definition and accompanying note and recommend whether they should be retained or changed. This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period. The task force ultimately recommended that the definition of pain be revised to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage," and that the accompanying notes be updated to a bulleted list that included the etymology. The revised definition and notes were unanimously accepted by the IASP Council early this year.

Journal ArticleDOI
TL;DR: Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those whoreceived a comparator EGFR-TKI.
Abstract: Background Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing ...

Journal ArticleDOI
30 Mar 2020-ACS Nano
TL;DR: Diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics are described and point-of-care diagnostics that are on the horizon are described to encourage academics to advance their technologies beyond conception.
Abstract: COVID-19 has spread globally since its discovery in Hubei province, China in December 2019. A combination of computed tomography imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiology of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.

Journal ArticleDOI
01 Oct 2020
TL;DR: The updated JBI guidance for scoping reviews includes additional guidance on several methodological issues, such as when a scoping review is (or is not) appropriate, and how to extract, analyze, and present results, and provides clarification for implications for practice and research.
Abstract: OBJECTIVE: The objective of this paper is to describe the updated methodological guidance for conducting a JBI scoping review, with a focus on new updates to the approach and development of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (the PRISMA-ScR). INTRODUCTION: Scoping reviews are an increasingly common approach to informing decision-making and research based on the identification and examination of the literature on a given topic or issue. Scoping reviews draw on evidence from any research methodology and may also include evidence from non-research sources, such as policy. In this manner, scoping reviews provide a comprehensive overview to address broader review questions than traditionally more specific systematic reviews of effectiveness or qualitative evidence. The increasing popularity of scoping reviews has been accompanied by the development of a reporting guideline: the PRISMA-ScR. In 2014, the JBI Scoping Review Methodology Group developed guidance for scoping reviews that received minor updates in 2017 and was most recently updated in 2020. The updates reflect ongoing and substantial developments in approaches to scoping review conduct and reporting. As such, the JBI Scoping Review Methodology Group recognized the need to revise the guidance to align with the current state of knowledge and reporting standards in evidence synthesis. METHODS: Between 2015 and 2020, the JBI Scoping Review Methodology Group expanded its membership; extensively reviewed the literature; engaged via annual face-to-face meetings, regular teleconferences, and email correspondence; sought advice from methodological experts; facilitated workshops; and presented at scientific conferences. This process led to updated guidance for scoping reviews published in the JBI Manual for Evidence Synthesis. The updated chapter was endorsed by JBI's International Scientific Committee in 2020. RESULTS: The updated JBI guidance for scoping reviews includes additional guidance on several methodological issues, such as when a scoping review is (or is not) appropriate, and how to extract, analyze, and present results, and provides clarification for implications for practice and research. Furthermore, it is aligned with the PRISMA-ScR to ensure consistent reporting. CONCLUSIONS: The latest JBI guidance for scoping reviews provides up-to-date guidance that can be used by authors when conducting a scoping review. Furthermore, it aligns with the PRISMA-ScR, which can be used to report the conduct of a scoping review. A series of ongoing and future methodological projects identified by the JBI Scoping Review Methodology Group to further refine the methodology are planned.

Journal ArticleDOI
TL;DR: The results showed that negative emotions and sensitivity to social risks increased, while the scores of positive emotions and life satisfaction decreased, and people were concerned more about their health and family, while less about leisure and friends.
Abstract: COVID-19 (Corona Virus Disease 2019) has significantly resulted in a large number of psychological consequences. The aim of this study is to explore the impacts of COVID-19 on people’s mental health, to assist policy makers to develop actionable policies, and help clinical practitioners (e.g., social workers, psychiatrists, and psychologists) provide timely services to affected populations. We sample and analyze the Weibo posts from 17,865 active Weibo users using the approach of Online Ecological Recognition (OER) based on several machine-learning predictive models. We calculated word frequency, scores of emotional indicators (e.g., anxiety, depression, indignation, and Oxford happiness) and cognitive indicators (e.g., social risk judgment and life satisfaction) from the collected data. The sentiment analysis and the paired sample t-test were performed to examine the differences in the same group before and after the declaration of COVID-19 on 20 January, 2020. The results showed that negative emotions (e.g., anxiety, depression and indignation) and sensitivity to social risks increased, while the scores of positive emotions (e.g., Oxford happiness) and life satisfaction decreased. People were concerned more about their health and family, while less about leisure and friends. The results contribute to the knowledge gaps of short-term individual changes in psychological conditions after the outbreak. It may provide references for policy makers to plan and fight against COVID-19 effectively by improving stability of popular feelings and urgently prepare clinical practitioners to deliver corresponding therapy foundations for the risk groups and affected people.

Journal ArticleDOI
B. P. Abbott1, R. Abbott1, T. D. Abbott2, Sheelu Abraham3  +1271 moreInstitutions (145)
TL;DR: In 2019, the LIGO Livingston detector observed a compact binary coalescence with signal-to-noise ratio 12.9 and the Virgo detector was also taking data that did not contribute to detection due to a low SINR but were used for subsequent parameter estimation as discussed by the authors.
Abstract: On 2019 April 25, the LIGO Livingston detector observed a compact binary coalescence with signal-to-noise ratio 12.9. The Virgo detector was also taking data that did not contribute to detection due to a low signal-to-noise ratio, but were used for subsequent parameter estimation. The 90% credible intervals for the component masses range from to if we restrict the dimensionless component spin magnitudes to be smaller than 0.05). These mass parameters are consistent with the individual binary components being neutron stars. However, both the source-frame chirp mass and the total mass of this system are significantly larger than those of any other known binary neutron star (BNS) system. The possibility that one or both binary components of the system are black holes cannot be ruled out from gravitational-wave data. We discuss possible origins of the system based on its inconsistency with the known Galactic BNS population. Under the assumption that the signal was produced by a BNS coalescence, the local rate of neutron star mergers is updated to 250-2810.

Journal ArticleDOI
06 Feb 2020-Cell
TL;DR: The largest exome sequencing study of autism spectrum disorder (ASD) to date, using an enhanced analytical framework to integrate de novo and case-control rare variation, identifies 102 risk genes at a false discovery rate of 0.1 or less, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.

Journal ArticleDOI
TL;DR: An updated evolutionary classification of CRISPR–Cas systems and cas genes is provided, with an emphasis on the major developments that have occurred since the publication of the latest classification, in 2015, which includes 2 classes, 6 types and 33 subtypes.
Abstract: The number and diversity of known CRISPR-Cas systems have substantially increased in recent years. Here, we provide an updated evolutionary classification of CRISPR-Cas systems and cas genes, with an emphasis on the major developments that have occurred since the publication of the latest classification, in 2015. The new classification includes 2 classes, 6 types and 33 subtypes, compared with 5 types and 16 subtypes in 2015. A key development is the ongoing discovery of multiple, novel class 2 CRISPR-Cas systems, which now include 3 types and 17 subtypes. A second major novelty is the discovery of numerous derived CRISPR-Cas variants, often associated with mobile genetic elements that lack the nucleases required for interference. Some of these variants are involved in RNA-guided transposition, whereas others are predicted to perform functions distinct from adaptive immunity that remain to be characterized experimentally. The third highlight is the discovery of numerous families of ancillary CRISPR-linked genes, often implicated in signal transduction. Together, these findings substantially clarify the functional diversity and evolutionary history of CRISPR-Cas.

Journal ArticleDOI
TL;DR: The presented conceptual framework is based on systemic models of human development and family functioning and links social disruption due to COVID-19 to child adjustment through a cascading process involving caregiver well-being and family processes (i.e., organization, communication, and beliefs).
Abstract: The COVID-19 pandemic poses an acute threat to the well-being of children and families due to challenges related to social disruption such as financial insecurity, caregiving burden, and confinement-related stress (e.g., crowding, changes to structure, and routine). The consequences of these difficulties are likely to be longstanding, in part because of the ways in which contextual risk permeates the structures and processes of family systems. The current article draws from pertinent literature across topic areas of acute crises and long-term, cumulative risk to illustrate the multitude of ways in which the well-being of children and families may be at risk during COVID-19. The presented conceptual framework is based on systemic models of human development and family functioning and links social disruption due to COVID-19 to child adjustment through a cascading process involving caregiver well-being and family processes (i.e., organization, communication, and beliefs). An illustration of the centrality of family processes in buffering against risk in the context of COVID-19, as well as promoting resilience through shared family beliefs and close relationships, is provided. Finally, clinical and research implications are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Journal ArticleDOI
Marielle Saunois1, Ann R. Stavert2, Ben Poulter3, Philippe Bousquet1, Josep G. Canadell2, Robert B. Jackson4, Peter A. Raymond5, Edward J. Dlugokencky6, Sander Houweling7, Sander Houweling8, Prabir K. Patra9, Prabir K. Patra10, Philippe Ciais1, Vivek K. Arora, David Bastviken11, Peter Bergamaschi, Donald R. Blake12, Gordon Brailsford13, Lori Bruhwiler6, Kimberly M. Carlson14, Mark Carrol3, Simona Castaldi15, Naveen Chandra9, Cyril Crevoisier16, Patrick M. Crill17, Kristofer R. Covey18, Charles L. Curry19, Giuseppe Etiope20, Giuseppe Etiope21, Christian Frankenberg22, Nicola Gedney23, Michaela I. Hegglin24, Lena Höglund-Isaksson25, Gustaf Hugelius17, Misa Ishizawa26, Akihiko Ito26, Greet Janssens-Maenhout, Katherine M. Jensen27, Fortunat Joos28, Thomas Kleinen29, Paul B. Krummel2, Ray L. Langenfelds2, Goulven Gildas Laruelle, Licheng Liu30, Toshinobu Machida26, Shamil Maksyutov26, Kyle C. McDonald27, Joe McNorton31, Paul A. Miller32, Joe R. Melton, Isamu Morino26, Jurek Müller28, Fabiola Murguia-Flores33, Vaishali Naik34, Yosuke Niwa26, Sergio Noce, Simon O'Doherty33, Robert J. Parker35, Changhui Peng36, Shushi Peng37, Glen P. Peters, Catherine Prigent, Ronald G. Prinn38, Michel Ramonet1, Pierre Regnier, William J. Riley39, Judith A. Rosentreter40, Arjo Segers, Isobel J. Simpson12, Hao Shi41, Steven J. Smith42, L. Paul Steele2, Brett F. Thornton17, Hanqin Tian41, Yasunori Tohjima26, Francesco N. Tubiello43, Aki Tsuruta44, Nicolas Viovy1, Apostolos Voulgarakis45, Apostolos Voulgarakis46, Thomas Weber47, Michiel van Weele48, Guido R. van der Werf7, Ray F. Weiss49, Doug Worthy, Debra Wunch50, Yi Yin22, Yi Yin1, Yukio Yoshida26, Weiya Zhang32, Zhen Zhang51, Yuanhong Zhao1, Bo Zheng1, Qing Zhu39, Qiuan Zhu52, Qianlai Zhuang30 
Université Paris-Saclay1, Commonwealth Scientific and Industrial Research Organisation2, Goddard Space Flight Center3, Stanford University4, Yale University5, National Oceanic and Atmospheric Administration6, VU University Amsterdam7, Netherlands Institute for Space Research8, Japan Agency for Marine-Earth Science and Technology9, Chiba University10, Linköping University11, University of California, Irvine12, National Institute of Water and Atmospheric Research13, New York University14, Seconda Università degli Studi di Napoli15, École Polytechnique16, Stockholm University17, Skidmore College18, University of Victoria19, Babeș-Bolyai University20, National Institute of Geophysics and Volcanology21, California Institute of Technology22, Met Office23, University of Reading24, International Institute for Applied Systems Analysis25, National Institute for Environmental Studies26, City University of New York27, University of Bern28, Max Planck Society29, Purdue University30, European Centre for Medium-Range Weather Forecasts31, Lund University32, University of Bristol33, Geophysical Fluid Dynamics Laboratory34, University of Leicester35, Université du Québec à Montréal36, Peking University37, Massachusetts Institute of Technology38, Lawrence Berkeley National Laboratory39, Southern Cross University40, Auburn University41, Joint Global Change Research Institute42, Food and Agriculture Organization43, Finnish Meteorological Institute44, Technical University of Crete45, Imperial College London46, University of Rochester47, Royal Netherlands Meteorological Institute48, Scripps Institution of Oceanography49, University of Toronto50, University of Maryland, College Park51, Hohai University52
TL;DR: The second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modeling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations) as discussed by the authors.
Abstract: Understanding and quantifying the global methane (CH4) budget is important for assessing realistic pathways to mitigate climate change. Atmospheric emissions and concentrations of CH4 continue to increase, making CH4 the second most important human-influenced greenhouse gas in terms of climate forcing, after carbon dioxide (CO2). The relative importance of CH4 compared to CO2 depends on its shorter atmospheric lifetime, stronger warming potential, and variations in atmospheric growth rate over the past decade, the causes of which are still debated. Two major challenges in reducing uncertainties in the atmospheric growth rate arise from the variety of geographically overlapping CH4 sources and from the destruction of CH4 by short-lived hydroxyl radicals (OH). To address these challenges, we have established a consortium of multidisciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate new research aimed at improving and regularly updating the global methane budget. Following Saunois et al. (2016), we present here the second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations). For the 2008–2017 decade, global methane emissions are estimated by atmospheric inversions (a top-down approach) to be 576 Tg CH4 yr−1 (range 550–594, corresponding to the minimum and maximum estimates of the model ensemble). Of this total, 359 Tg CH4 yr−1 or ∼ 60 % is attributed to anthropogenic sources, that is emissions caused by direct human activity (i.e. anthropogenic emissions; range 336–376 Tg CH4 yr−1 or 50 %–65 %). The mean annual total emission for the new decade (2008–2017) is 29 Tg CH4 yr−1 larger than our estimate for the previous decade (2000–2009), and 24 Tg CH4 yr−1 larger than the one reported in the previous budget for 2003–2012 (Saunois et al., 2016). Since 2012, global CH4 emissions have been tracking the warmest scenarios assessed by the Intergovernmental Panel on Climate Change. Bottom-up methods suggest almost 30 % larger global emissions (737 Tg CH4 yr−1, range 594–881) than top-down inversion methods. Indeed, bottom-up estimates for natural sources such as natural wetlands, other inland water systems, and geological sources are higher than top-down estimates. The atmospheric constraints on the top-down budget suggest that at least some of these bottom-up emissions are overestimated. The latitudinal distribution of atmospheric observation-based emissions indicates a predominance of tropical emissions (∼ 65 % of the global budget, < 30∘ N) compared to mid-latitudes (∼ 30 %, 30–60∘ N) and high northern latitudes (∼ 4 %, 60–90∘ N). The most important source of uncertainty in the methane budget is attributable to natural emissions, especially those from wetlands and other inland waters. Some of our global source estimates are smaller than those in previously published budgets (Saunois et al., 2016; Kirschke et al., 2013). In particular wetland emissions are about 35 Tg CH4 yr−1 lower due to improved partition wetlands and other inland waters. Emissions from geological sources and wild animals are also found to be smaller by 7 Tg CH4 yr−1 by 8 Tg CH4 yr−1, respectively. However, the overall discrepancy between bottom-up and top-down estimates has been reduced by only 5 % compared to Saunois et al. (2016), due to a higher estimate of emissions from inland waters, highlighting the need for more detailed research on emissions factors. Priorities for improving the methane budget include (i) a global, high-resolution map of water-saturated soils and inundated areas emitting methane based on a robust classification of different types of emitting habitats; (ii) further development of process-based models for inland-water emissions; (iii) intensification of methane observations at local scales (e.g., FLUXNET-CH4 measurements) and urban-scale monitoring to constrain bottom-up land surface models, and at regional scales (surface networks and satellites) to constrain atmospheric inversions; (iv) improvements of transport models and the representation of photochemical sinks in top-down inversions; and (v) development of a 3D variational inversion system using isotopic and/or co-emitted species such as ethane to improve source partitioning.

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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.

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TL;DR: The promise of targeting the inflammation pathway in the management of this challenging condition is today somewhat weaker, but this might not be the last word on the potential role of anti-inflammatory drugs in the treatment of bipolar depression.

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TL;DR: To determine the prevalence of bacterial co-infection and secondary infection in patients with confirmed COVID-19, a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020 was performed.

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TL;DR: A set of recommendations for model interpretation and benchmarking is developed, highlighting recent advances in machine learning to improve robustness and transferability from the lab to real-world applications.
Abstract: Deep learning has triggered the current rise of artificial intelligence and is the workhorse of today’s machine intelligence. Numerous success stories have rapidly spread all over science, industry and society, but its limitations have only recently come into focus. In this Perspective we seek to distil how many of deep learning’s failures can be seen as different symptoms of the same underlying problem: shortcut learning. Shortcuts are decision rules that perform well on standard benchmarks but fail to transfer to more challenging testing conditions, such as real-world scenarios. Related issues are known in comparative psychology, education and linguistics, suggesting that shortcut learning may be a common characteristic of learning systems, biological and artificial alike. Based on these observations, we develop a set of recommendations for model interpretation and benchmarking, highlighting recent advances in machine learning to improve robustness and transferability from the lab to real-world applications. Deep learning has resulted in impressive achievements, but under what circumstances does it fail, and why? The authors propose that its failures are a consequence of shortcut learning, a common characteristic across biological and artificial systems in which strategies that appear to have solved a problem fail unexpectedly under different circumstances.

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TL;DR: The Community Earth System Model Version 2 (CESM2) as discussed by the authors is the most recent version of the Coupled Model Intercomparison Project (CMEI) coupled model.
Abstract: An overview of the Community Earth System Model Version 2 (CESM2) is provided, including a discussion of the challenges encountered during its development and how they were addressed. In addition, an evaluation of a pair of CESM2 long preindustrial control and historical ensemble simulations is presented. These simulations were performed using the nominal 1° horizontal resolution configuration of the coupled model with both the “low-top” (40 km, with limited chemistry) and “high-top” (130 km, with comprehensive chemistry) versions of the atmospheric component. CESM2 contains many substantial science and infrastructure improvements and new capabilities since its previous major release, CESM1, resulting in improved historical simulations in comparison to CESM1 and available observations. These include major reductions in low-latitude precipitation and shortwave cloud forcing biases; better representation of the Madden-Julian Oscillation; better El Nino-Southern Oscillation-related teleconnections; and a global land carbon accumulation trend that agrees well with observationally based estimates. Most tropospheric and surface features of the low- and high-top simulations are very similar to each other, so these improvements are present in both configurations. CESM2 has an equilibrium climate sensitivity of 5.1–5.3 °C, larger than in CESM1, primarily due to a combination of relatively small changes to cloud microphysics and boundary layer parameters. In contrast, CESM2's transient climate response of 1.9–2.0 °C is comparable to that of CESM1. The model outputs from these and many other simulations are available to the research community, and they represent CESM2's contributions to the Coupled Model Intercomparison Project Phase 6.

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Jens Kattge1, Gerhard Bönisch2, Sandra Díaz3, Sandra Lavorel  +751 moreInstitutions (314)
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.