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Showing papers by "University of British Columbia published in 2018"


Journal ArticleDOI
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4  +414 moreInstitutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

5,988 citations


Journal ArticleDOI
TL;DR: In this paper, the authors assess the burden of 29 cancer groups over time to provide a framework for policy discussion, resource allocation, and research focus, and evaluate cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) for 195 countries and territories by age and sex using the Global Burden of Disease study estimation methods.
Abstract: Importance The increasing burden due to cancer and other noncommunicable diseases poses a threat to human development, which has resulted in global political commitments reflected in the Sustainable Development Goals as well as the World Health Organization (WHO) Global Action Plan on Non-Communicable Diseases. To determine if these commitments have resulted in improved cancer control, quantitative assessments of the cancer burden are required. Objective To assess the burden for 29 cancer groups over time to provide a framework for policy discussion, resource allocation, and research focus. Evidence Review Cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) were evaluated for 195 countries and territories by age and sex using the Global Burden of Disease study estimation methods. Levels and trends were analyzed over time, as well as by the Sociodemographic Index (SDI). Changes in incident cases were categorized by changes due to epidemiological vs demographic transition. Findings In 2016, there were 17.2 million cancer cases worldwide and 8.9 million deaths. Cancer cases increased by 28% between 2006 and 2016. The smallest increase was seen in high SDI countries. Globally, population aging contributed 17%; population growth, 12%; and changes in age-specific rates, −1% to this change. The most common incident cancer globally for men was prostate cancer (1.4 million cases). The leading cause of cancer deaths and DALYs was tracheal, bronchus, and lung cancer (1.2 million deaths and 25.4 million DALYs). For women, the most common incident cancer and the leading cause of cancer deaths and DALYs was breast cancer (1.7 million incident cases, 535 000 deaths, and 14.9 million DALYs). In 2016, cancer caused 213.2 million DALYs globally for both sexes combined. Between 2006 and 2016, the average annual age-standardized incidence rates for all cancers combined increased in 130 of 195 countries or territories, and the average annual age-standardized death rates decreased within that timeframe in 143 of 195 countries or territories. Conclusions and Relevance Large disparities exist between countries in cancer incidence, deaths, and associated disability. Scaling up cancer prevention and ensuring universal access to cancer care are required for health equity and to fulfill the global commitments for noncommunicable disease and cancer control.

4,621 citations


Journal ArticleDOI
Nabila Aghanim1, Yashar Akrami2, Yashar Akrami3, Yashar Akrami4  +229 moreInstitutions (70)
TL;DR: In this paper, the cosmological parameter results from the final full-mission Planck measurements of the CMB anisotropies were presented, with good consistency with the standard spatially-flat 6-parameter CDM cosmology having a power-law spectrum of adiabatic scalar perturbations from polarization, temperature, and lensing separately and in combination.
Abstract: We present cosmological parameter results from the final full-mission Planck measurements of the CMB anisotropies. We find good consistency with the standard spatially-flat 6-parameter $\Lambda$CDM cosmology having a power-law spectrum of adiabatic scalar perturbations (denoted "base $\Lambda$CDM" in this paper), from polarization, temperature, and lensing, separately and in combination. A combined analysis gives dark matter density $\Omega_c h^2 = 0.120\pm 0.001$, baryon density $\Omega_b h^2 = 0.0224\pm 0.0001$, scalar spectral index $n_s = 0.965\pm 0.004$, and optical depth $\tau = 0.054\pm 0.007$ (in this abstract we quote $68\,\%$ confidence regions on measured parameters and $95\,\%$ on upper limits). The angular acoustic scale is measured to $0.03\,\%$ precision, with $100\theta_*=1.0411\pm 0.0003$. These results are only weakly dependent on the cosmological model and remain stable, with somewhat increased errors, in many commonly considered extensions. Assuming the base-$\Lambda$CDM cosmology, the inferred late-Universe parameters are: Hubble constant $H_0 = (67.4\pm 0.5)$km/s/Mpc; matter density parameter $\Omega_m = 0.315\pm 0.007$; and matter fluctuation amplitude $\sigma_8 = 0.811\pm 0.006$. We find no compelling evidence for extensions to the base-$\Lambda$CDM model. Combining with BAO we constrain the effective extra relativistic degrees of freedom to be $N_{\rm eff} = 2.99\pm 0.17$, and the neutrino mass is tightly constrained to $\sum m_ u< 0.12$eV. The CMB spectra continue to prefer higher lensing amplitudes than predicted in base -$\Lambda$CDM at over $2\,\sigma$, which pulls some parameters that affect the lensing amplitude away from the base-$\Lambda$CDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAO data. (Abridged)

3,077 citations


Journal ArticleDOI
TL;DR: Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate‐ and poor‐risk patients with previously untreated advanced renal‐cell carcinoma.
Abstract: Background Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. Methods We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk. Results A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follo...

2,984 citations


Journal ArticleDOI
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1  +1050 moreInstitutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.

2,910 citations


Journal ArticleDOI
Naomi R. Wray1, Stephan Ripke2, Stephan Ripke3, Stephan Ripke4  +259 moreInstitutions (79)
TL;DR: A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent and significant loci and finds important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia.
Abstract: Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

1,898 citations


Journal ArticleDOI
TL;DR: Patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis with polyneuropathy and showed an effect on gait speed and modified BMI.
Abstract: BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.METHODS: In this phase 3 trial, we randomly assigned patients ...

1,671 citations


Journal ArticleDOI
Daniel J. Benjamin1, James O. Berger2, Magnus Johannesson1, Magnus Johannesson3, Brian A. Nosek4, Brian A. Nosek5, Eric-Jan Wagenmakers6, Richard A. Berk7, Kenneth A. Bollen8, Björn Brembs9, Lawrence D. Brown7, Colin F. Camerer10, David Cesarini11, David Cesarini12, Christopher D. Chambers13, Merlise A. Clyde2, Thomas D. Cook14, Thomas D. Cook15, Paul De Boeck16, Zoltan Dienes17, Anna Dreber3, Kenny Easwaran18, Charles Efferson19, Ernst Fehr20, Fiona Fidler21, Andy P. Field17, Malcolm R. Forster22, Edward I. George7, Richard Gonzalez23, Steven N. Goodman24, Edwin J. Green25, Donald P. Green26, Anthony G. Greenwald27, Jarrod D. Hadfield28, Larry V. Hedges14, Leonhard Held20, Teck-Hua Ho29, Herbert Hoijtink30, Daniel J. Hruschka31, Kosuke Imai32, Guido W. Imbens24, John P. A. Ioannidis24, Minjeong Jeon33, James Holland Jones34, Michael Kirchler35, David Laibson36, John A. List37, Roderick J. A. Little23, Arthur Lupia23, Edouard Machery38, Scott E. Maxwell39, Michael A. McCarthy21, Don A. Moore40, Stephen L. Morgan41, Marcus R. Munafò42, Shinichi Nakagawa43, Brendan Nyhan44, Timothy H. Parker45, Luis R. Pericchi46, Marco Perugini47, Jeffrey N. Rouder48, Judith Rousseau49, Victoria Savalei50, Felix D. Schönbrodt51, Thomas Sellke52, Betsy Sinclair53, Dustin Tingley36, Trisha Van Zandt16, Simine Vazire54, Duncan J. Watts55, Christopher Winship36, Robert L. Wolpert2, Yu Xie32, Cristobal Young24, Jonathan Zinman44, Valen E. Johnson18, Valen E. Johnson1 
University of Southern California1, Duke University2, Stockholm School of Economics3, Center for Open Science4, University of Virginia5, University of Amsterdam6, University of Pennsylvania7, University of North Carolina at Chapel Hill8, University of Regensburg9, California Institute of Technology10, New York University11, Research Institute of Industrial Economics12, Cardiff University13, Northwestern University14, Mathematica Policy Research15, Ohio State University16, University of Sussex17, Texas A&M University18, Royal Holloway, University of London19, University of Zurich20, University of Melbourne21, University of Wisconsin-Madison22, University of Michigan23, Stanford University24, Rutgers University25, Columbia University26, University of Washington27, University of Edinburgh28, National University of Singapore29, Utrecht University30, Arizona State University31, Princeton University32, University of California, Los Angeles33, Imperial College London34, University of Innsbruck35, Harvard University36, University of Chicago37, University of Pittsburgh38, University of Notre Dame39, University of California, Berkeley40, Johns Hopkins University41, University of Bristol42, University of New South Wales43, Dartmouth College44, Whitman College45, University of Puerto Rico46, University of Milan47, University of California, Irvine48, Paris Dauphine University49, University of British Columbia50, Ludwig Maximilian University of Munich51, Purdue University52, Washington University in St. Louis53, University of California, Davis54, Microsoft55
TL;DR: The default P-value threshold for statistical significance is proposed to be changed from 0.05 to 0.005 for claims of new discoveries in order to reduce uncertainty in the number of discoveries.
Abstract: We propose to change the default P-value threshold for statistical significance from 0.05 to 0.005 for claims of new discoveries.

1,586 citations


Journal ArticleDOI
TL;DR: Ultra-long reads enabled assembly and phasing of the 4-Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length, and closure of gaps in the reference human genome assembly GRCh38.
Abstract: We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ∼30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ∼3 Mb). We developed a protocol to generate ultra-long reads (N50 > 100 kb, read lengths up to 882 kb). Incorporating an additional 5× coverage of these ultra-long reads more than doubled the assembly contiguity (NG50 ∼6.4 Mb). The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%. Ultra-long reads enabled assembly and phasing of the 4-Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length, and closure of gaps in the reference human genome assembly GRCh38.

1,425 citations


Journal ArticleDOI
22 Jun 2018-Science
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

1,357 citations


Journal ArticleDOI
TL;DR: PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.
Abstract: Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.

Journal ArticleDOI
TL;DR: The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome and this update comes with a new web framework with an interactive and responsive user-interface, along with new features.
Abstract: JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) and TF flexible models (TFFMs) for TFs across multiple species in six taxonomic groups. In the 2018 release of JASPAR, the CORE collection has been expanded with 322 new PFMs (60 for vertebrates and 262 for plants) and 33 PFMs were updated (24 for vertebrates, 8 for plants and 1 for insects). These new profiles represent a 30% expansion compared to the 2016 release. In addition, we have introduced 316 TFFMs (95 for vertebrates, 218 for plants and 3 for insects). This release incorporates clusters of similar PFMs in each taxon and each TF class per taxon. The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome. The predictions are made available to the scientific community through a UCSC Genome Browser track data hub. Finally, this update comes with a new web framework with an interactive and responsive user-interface, along with new features. All the underlying data can be retrieved programmatically using a RESTful API and through the JASPAR 2018 R/Bioconductor package.

Journal ArticleDOI
TL;DR: Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on “chronic active” B‐cell receptor signaling that is amenable to therapeutic inhibition, and an algorithm was developed and implemented to discover genetic subtypes based on the co‐occurrence of genetic alterations.
Abstract: Background Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell–like [ABC], germinal-center B-cell–like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. Methods We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. Results We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88L265P and CD79B muta...

Journal ArticleDOI
TL;DR: Two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences are presented, including the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum information about a Metagenome-Assembled Genomes (MIMAG), including estimates of genome completeness and contamination.
Abstract: We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a Metagenome-Assembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Gene Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.

Journal ArticleDOI
TL;DR: The findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults.
Abstract: Summary Background Lower respiratory infections are a leading cause of morbidity and mortality around the world The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date analysis of the burden of lower respiratory infections in 195 countries This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages Methods We used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus We calculated each modelled estimate for each age, sex, year, and location We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years We also did a decomposition analysis of the change in LRI deaths from 2000–16 using the risk factors associated with LRI in GBD 2016 Findings In 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval [UI] 586 475–720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749–1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584–2 512 809) in people of all ages, worldwide Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445–1 770 660) Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7–69·6) Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden Interpretation Our findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations Funding Bill & Melinda Gates Foundation


Journal ArticleDOI
TL;DR: Patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control.
Abstract: Background Dupilumab is a fully human anti–interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. Methods We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV1) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. Results The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among ...

Journal ArticleDOI
Ali H. Mokdad1, Katherine Ballestros1, Michelle Echko1, Scott D Glenn1, Helen E Olsen1, Erin C Mullany1, Alexander Lee1, Abdur Rahman Khan2, Alireza Ahmadi3, Alireza Ahmadi4, Alize J. Ferrari5, Alize J. Ferrari6, Alize J. Ferrari1, Amir Kasaeian7, Andrea Werdecker, Austin Carter1, Ben Zipkin1, Benn Sartorius8, Benn Sartorius9, Berrin Serdar10, Bryan L. Sykes11, Christopher Troeger1, Christina Fitzmaurice12, Christina Fitzmaurice1, Colin D. Rehm13, Damian Santomauro5, Damian Santomauro1, Damian Santomauro6, Daniel Kim14, Danny V. Colombara1, David C. Schwebel15, Derrick Tsoi1, Dhaval Kolte16, Elaine O. Nsoesie1, Emma Nichols1, Eyal Oren17, Fiona J Charlson5, Fiona J Charlson6, Fiona J Charlson1, George C Patton18, Gregory A. Roth1, H. Dean Hosgood19, Harvey Whiteford5, Harvey Whiteford6, Harvey Whiteford1, Hmwe H Kyu1, Holly E. Erskine6, Holly E. Erskine1, Holly E. Erskine5, Hsiang Huang20, Ira Martopullo1, Jasvinder A. Singh15, Jean B. Nachega21, Jean B. Nachega22, Jean B. Nachega23, Juan Sanabria24, Juan Sanabria25, Kaja Abbas26, Kanyin Ong1, Karen M. Tabb27, Kristopher J. Krohn1, Leslie Cornaby1, Louisa Degenhardt1, Louisa Degenhardt28, Mark Moses1, Maryam S. Farvid29, Max Griswold1, Michael H. Criqui30, Michelle L. Bell31, Minh Nguyen1, Mitch T Wallin32, Mitch T Wallin33, Mojde Mirarefin1, Mostafa Qorbani, Mustafa Z. Younis34, Nancy Fullman1, Patrick Liu1, Paul S Briant1, Philimon Gona35, Rasmus Havmoller4, Ricky Leung36, Ruth W Kimokoti37, Shahrzad Bazargan-Hejazi38, Shahrzad Bazargan-Hejazi39, Simon I. Hay1, Simon I. Hay40, Simon Yadgir1, Stan Biryukov1, Stein Emil Vollset41, Stein Emil Vollset1, Tahiya Alam1, Tahvi Frank1, Talha Farid2, Ted R. Miller42, Ted R. Miller43, Theo Vos1, Till Bärnighausen29, Till Bärnighausen44, Tsegaye Telwelde Gebrehiwot45, Yuichiro Yano46, Ziyad Al-Aly47, Alem Mehari48, Alexis J. Handal49, Amit Kandel50, Ben Anderson51, Brian J. Biroscak52, Brian J. Biroscak31, Dariush Mozaffarian53, E. Ray Dorsey54, Eric L. Ding29, Eun-Kee Park55, Gregory R. Wagner29, Guoqing Hu56, Honglei Chen57, Jacob E. Sunshine51, Jagdish Khubchandani58, Janet L Leasher59, Janni Leung6, Janni Leung51, Joshua A. Salomon29, Jürgen Unützer51, Leah E. Cahill29, Leah E. Cahill60, Leslie T. Cooper61, Masako Horino, Michael Brauer1, Michael Brauer62, Nicholas J K Breitborde63, Peter J. Hotez64, Roman Topor-Madry65, Roman Topor-Madry66, Samir Soneji67, Saverio Stranges68, Spencer L. James1, Stephen M. Amrock69, Sudha Jayaraman70, Tejas V. Patel, Tomi Akinyemiju15, Vegard Skirbekk41, Vegard Skirbekk71, Yohannes Kinfu72, Zulfiqar A Bhutta73, Jost B. Jonas44, Christopher J L Murray1 
Institute for Health Metrics and Evaluation1, University of Louisville2, Kermanshah University of Medical Sciences3, Karolinska Institutet4, Centre for Mental Health5, University of Queensland6, Tehran University of Medical Sciences7, University of KwaZulu-Natal8, South African Medical Research Council9, University of Colorado Boulder10, University of California, Irvine11, Fred Hutchinson Cancer Research Center12, Montefiore Medical Center13, Northeastern University14, University of Alabama at Birmingham15, Brown University16, San Diego State University17, University of Melbourne18, Albert Einstein College of Medicine19, Cambridge Health Alliance20, University of Pittsburgh21, University of Cape Town22, Johns Hopkins University23, Case Western Reserve University24, Marshall University25, University of London26, University of Illinois at Urbana–Champaign27, National Drug and Alcohol Research Centre28, Harvard University29, University of California, San Diego30, Yale University31, Veterans Health Administration32, Georgetown University33, Jackson State University34, University of Massachusetts Boston35, State University of New York System36, Simmons College37, University of California, Los Angeles38, Charles R. Drew University of Medicine and Science39, University of Oxford40, Norwegian Institute of Public Health41, Curtin University42, Pacific Institute43, Heidelberg University44, Jimma University45, Northwestern University46, Washington University in St. Louis47, Howard University48, University of New Mexico49, University at Buffalo50, University of Washington51, University of South Florida52, Tufts University53, University of Rochester Medical Center54, Kosin University55, Central South University56, Michigan State University57, Ball State University58, Nova Southeastern University59, Dalhousie University60, Mayo Clinic61, University of British Columbia62, Ohio State University63, Baylor University64, Wrocław Medical University65, Jagiellonian University Medical College66, Dartmouth College67, University of Western Ontario68, Oregon Health & Science University69, Virginia Commonwealth University70, Columbia University71, University of Canberra72, Aga Khan University73
10 Apr 2018-JAMA
TL;DR: There are wide differences in the burden of disease at the state level and specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention.
Abstract: Introduction Several studies have measured health outcomes in the United States, but none have provided a comprehensive assessment of patterns of health by state. Objective To use the results of the Global Burden of Disease Study (GBD) to report trends in the burden of diseases, injuries, and risk factors at the state level from 1990 to 2016. Design and Setting A systematic analysis of published studies and available data sources estimates the burden of disease by age, sex, geography, and year. Main Outcomes and Measures Prevalence, incidence, mortality, life expectancy, healthy life expectancy (HALE), years of life lost (YLLs) due to premature mortality, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 333 causes and 84 risk factors with 95% uncertainty intervals (UIs) were computed. Results Between 1990 and 2016, overall death rates in the United States declined from 745.2 (95% UI, 740.6 to 749.8) per 100 000 persons to 578.0 (95% UI, 569.4 to 587.1) per 100 000 persons. The probability of death among adults aged 20 to 55 years declined in 31 states and Washington, DC from 1990 to 2016. In 2016, Hawaii had the highest life expectancy at birth (81.3 years) and Mississippi had the lowest (74.7 years), a 6.6-year difference. Minnesota had the highest HALE at birth (70.3 years), and West Virginia had the lowest (63.8 years), a 6.5-year difference. The leading causes of DALYs in the United States for 1990 and 2016 were ischemic heart disease and lung cancer, while the third leading cause in 1990 was low back pain, and the third leading cause in 2016 was chronic obstructive pulmonary disease. Opioid use disorders moved from the 11th leading cause of DALYs in 1990 to the 7th leading cause in 2016, representing a 74.5% (95% UI, 42.8% to 93.9%) change. In 2016, each of the following 6 risks individually accounted for more than 5% of risk-attributable DALYs: tobacco consumption, high body mass index (BMI), poor diet, alcohol and drug use, high fasting plasma glucose, and high blood pressure. Across all US states, the top risk factors in terms of attributable DALYs were due to 1 of the 3 following causes: tobacco consumption (32 states), high BMI (10 states), or alcohol and drug use (8 states). Conclusions and Relevance There are wide differences in the burden of disease at the state level. Specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention. These data can be used to inform national health priorities for research, clinical care, and policy.

Journal ArticleDOI
TL;DR: These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments.
Abstract: The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

01 Jan 2018
TL;DR: The International League Against Epilepsy Classification of the Epilepsies has been updated to reflect the gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989.
Abstract: The International League Against Epilepsy (ILAE) classification of the epilepsies has been updated to reflect the gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for the clinical diagnosis of patients but it is also critical for epilepsy research, development of antiepileptic treatment and communication around the world. The new classification is based on a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It consists of three levels starting with seizure type, where it is assumed that the epileptic seizures of the patient are defined by the new 2017 ILAE seizure classification. After diagnosis of the seizure type, the next step is the diagnosis of the epilepsy type, which includes focal epilepsy, generalized epilepsy, combined generalized and focal epilepsy and also an unclassified epilepsy group. At the third level the disease is assigned to a specific epilepsy syndrome. The new classification incorporates etiology at each stage, emphasizing the need to consider etiology at each step of the diagnosis, as it often carries significant treatment implications. The various etiologies can be assigned to six subgroups, defined with respect to the potential therapeutic consequences. New terminology is introduced, such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limiting and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the twenty-first century.


Journal ArticleDOI
24 Oct 2018-Nature
TL;DR: The Moral Machine, an online experimental platform designed to explore the moral dilemmas faced by autonomous vehicles, gathered 40 million decisions in ten languages from millions of people in 233 countries and territories to shed light on similarities and variations in ethical preferences among different populations.
Abstract: With the rapid development of artificial intelligence have come concerns about how machines will make moral decisions, and the major challenge of quantifying societal expectations about the ethical principles that should guide machine behaviour. To address this challenge, we deployed the Moral Machine, an online experimental platform designed to explore the moral dilemmas faced by autonomous vehicles. This platform gathered 40 million decisions in ten languages from millions of people in 233 countries and territories. Here we describe the results of this experiment. First, we summarize global moral preferences. Second, we document individual variations in preferences, based on respondents’ demographics. Third, we report cross-cultural ethical variation, and uncover three major clusters of countries. Fourth, we show that these differences correlate with modern institutions and deep cultural traits. We discuss how these preferences can contribute to developing global, socially acceptable principles for machine ethics. All data used in this article are publicly available.

Posted ContentDOI
Evan Bolyen1, Jai Ram Rideout1, Matthew R. Dillon1, Nicholas A. Bokulich1, Christian C. Abnet, Gabriel A. Al-Ghalith2, Harriet Alexander3, Harriet Alexander4, Eric J. Alm5, Manimozhiyan Arumugam6, Francesco Asnicar7, Yang Bai8, Jordan E. Bisanz9, Kyle Bittinger10, Asker Daniel Brejnrod6, Colin J. Brislawn11, C. Titus Brown4, Benjamin J. Callahan12, Andrés Mauricio Caraballo-Rodríguez13, John Chase1, Emily K. Cope1, Ricardo Silva13, Pieter C. Dorrestein13, Gavin M. Douglas14, Daniel M. Durall15, Claire Duvallet5, Christian F. Edwardson16, Madeleine Ernst13, Mehrbod Estaki15, Jennifer Fouquier17, Julia M. Gauglitz13, Deanna L. Gibson15, Antonio Gonzalez18, Kestrel Gorlick1, Jiarong Guo19, Benjamin Hillmann2, Susan Holmes20, Hannes Holste18, Curtis Huttenhower21, Curtis Huttenhower22, Gavin A. Huttley23, Stefan Janssen24, Alan K. Jarmusch13, Lingjing Jiang18, Benjamin D. Kaehler23, Kyo Bin Kang13, Kyo Bin Kang25, Christopher R. Keefe1, Paul Keim1, Scott T. Kelley26, Dan Knights2, Irina Koester18, Irina Koester13, Tomasz Kosciolek18, Jorden Kreps1, Morgan G. I. Langille14, Joslynn S. Lee27, Ruth E. Ley28, Ruth E. Ley29, Yong-Xin Liu8, Erikka Loftfield, Catherine A. Lozupone17, Massoud Maher18, Clarisse Marotz18, Bryan D Martin30, Daniel McDonald18, Lauren J. McIver21, Lauren J. McIver22, Alexey V. Melnik13, Jessica L. Metcalf31, Sydney C. Morgan15, Jamie Morton18, Ahmad Turan Naimey1, Jose A. Navas-Molina32, Jose A. Navas-Molina18, Louis-Félix Nothias13, Stephanie B. Orchanian18, Talima Pearson1, Samuel L. Peoples33, Samuel L. Peoples30, Daniel Petras13, Mary L. Preuss34, Elmar Pruesse17, Lasse Buur Rasmussen6, Adam R. Rivers35, Ii Michael S Robeson36, Patrick Rosenthal34, Nicola Segata7, Michael Shaffer17, Arron Shiffer1, Rashmi Sinha, Se Jin Song18, John R. Spear37, Austin D. Swafford18, Luke R. Thompson38, Luke R. Thompson39, Pedro J. Torres26, Pauline Trinh30, Anupriya Tripathi13, Anupriya Tripathi18, Peter J. Turnbaugh9, Sabah Ul-Hasan40, Justin J. J. van der Hooft41, Fernando Vargas18, Yoshiki Vázquez-Baeza18, Emily Vogtmann, Max von Hippel42, William A. Walters28, Yunhu Wan, Mingxun Wang13, Jonathan Warren43, Kyle C. Weber35, Kyle C. Weber44, Chase Hd Williamson1, Amy D. Willis30, Zhenjiang Zech Xu18, Jesse R. Zaneveld30, Yilong Zhang45, Rob Knight18, J. Gregory Caporaso1 
24 Oct 2018-PeerJ
TL;DR: QIIME 2 provides new features that will drive the next generation of microbiome research, including interactive spatial and temporal analysis and visualization tools, support for metabolomics and shotgun metagenomics analysis, and automated data provenance tracking to ensure reproducible, transparent microbiome data science.
Abstract: We present QIIME 2, an open-source microbiome data science platform accessible to users spanning the microbiome research ecosystem, from scientists and engineers to clinicians and policy makers. QIIME 2 provides new features that will drive the next generation of microbiome research. These include interactive spatial and temporal analysis and visualization tools, support for metabolomics and shotgun metagenomics analysis, and automated data provenance tracking to ensure reproducible, transparent microbiome data science.

Journal ArticleDOI
TL;DR: Both patterns are unlikely to be the result of ecological drift, but are inevitable emergent properties of open microbial systems resulting mainly from biotic interactions and environmental and spatial processes.
Abstract: Microbial communities often exhibit incredible taxonomic diversity, raising questions regarding the mechanisms enabling species coexistence and the role of this diversity in community functioning. On the one hand, many coexisting but taxonomically distinct microorganisms can encode the same energy-yielding metabolic functions, and this functional redundancy contrasts with the expectation that species should occupy distinct metabolic niches. On the other hand, the identity of taxa encoding each function can vary substantially across space or time with little effect on the function, and this taxonomic variability is frequently thought to result from ecological drift between equivalent organisms. Here, we synthesize the powerful paradigm emerging from these two patterns, connecting the roles of function, functional redundancy and taxonomy in microbial systems. We conclude that both patterns are unlikely to be the result of ecological drift, but are inevitable emergent properties of open microbial systems resulting mainly from biotic interactions and environmental and spatial processes.

Proceedings ArticleDOI
29 May 2018
TL;DR: This paper collects the most prominent definitions of fairness for the algorithmic classification problem, explains the rationale behind these definitions, and demonstrates each of them on a single unifying case-study.
Abstract: Algorithm fairness has started to attract the attention of researchers in AI, Software Engineering and Law communities, with more than twenty different notions of fairness proposed in the last few years. Yet, there is no clear agreement on which definition to apply in each situation. Moreover, the detailed differences between multiple definitions are difficult to grasp. To address this issue, this paper collects the most prominent definitions of fairness for the algorithmic classification problem, explains the rationale behind these definitions, and demonstrates each of them on a single unifying case-study. Our analysis intuitively explains why the same case can be considered fair according to some definitions and unfair according to others.

Proceedings Article
15 Feb 2018
TL;DR: The exact equivalence between infinitely wide deep networks and GPs is derived and it is found that test performance increases as finite-width trained networks are made wider and more similar to a GP, and thus that GP predictions typically outperform those of finite- width networks.
Abstract: It has long been known that a single-layer fully-connected neural network with an i.i.d. prior over its parameters is equivalent to a Gaussian process (GP), in the limit of infinite network width. This correspondence enables exact Bayesian inference for infinite width neural networks on regression tasks by means of evaluating the corresponding GP. Recently, kernel functions which mimic multi-layer random neural networks have been developed, but only outside of a Bayesian framework. As such, previous work has not identified that these kernels can be used as covariance functions for GPs and allow fully Bayesian prediction with a deep neural network. In this work, we derive the exact equivalence between infinitely wide deep networks and GPs. We further develop a computationally efficient pipeline to compute the covariance function for these GPs. We then use the resulting GPs to perform Bayesian inference for wide deep neural networks on MNIST and CIFAR-10. We observe that trained neural network accuracy approaches that of the corresponding GP with increasing layer width, and that the GP uncertainty is strongly correlated with trained network prediction error. We further find that test performance increases as finite-width trained networks are made wider and more similar to a GP, and thus that GP predictions typically outperform those of finite-width networks. Finally we connect the performance of these GPs to the recent theory of signal propagation in random neural networks.

Journal ArticleDOI
Marlee A. Tucker1, Katrin Böhning-Gaese1, William F. Fagan2, John M. Fryxell3, Bram Van Moorter, Susan C. Alberts4, Abdullahi H. Ali, Andrew M. Allen5, Andrew M. Allen6, Nina Attias7, Tal Avgar8, Hattie L. A. Bartlam-Brooks9, Buuveibaatar Bayarbaatar10, Jerrold L. Belant11, Alessandra Bertassoni12, Dean E. Beyer13, Laura R. Bidner14, Floris M. van Beest15, Stephen Blake16, Stephen Blake10, Niels Blaum17, Chloe Bracis1, Danielle D. Brown18, P J Nico de Bruyn19, Francesca Cagnacci20, Francesca Cagnacci21, Justin M. Calabrese22, Justin M. Calabrese2, Constança Camilo-Alves23, Simon Chamaillé-Jammes24, André Chiaradia25, André Chiaradia26, Sarah C. Davidson27, Sarah C. Davidson16, Todd E. Dennis28, Stephen DeStefano29, Duane R. Diefenbach30, Iain Douglas-Hamilton31, Iain Douglas-Hamilton32, Julian Fennessy, Claudia Fichtel33, Wolfgang Fiedler16, Christina Fischer34, Ilya R. Fischhoff35, Christen H. Fleming2, Christen H. Fleming22, Adam T. Ford36, Susanne A. Fritz1, Benedikt Gehr37, Jacob R. Goheen38, Eliezer Gurarie39, Eliezer Gurarie2, Mark Hebblewhite40, Marco Heurich41, Marco Heurich42, A. J. Mark Hewison43, Christian Hof, Edward Hurme2, Lynne A. Isbell14, René Janssen, Florian Jeltsch17, Petra Kaczensky44, Adam Kane45, Peter M. Kappeler33, Matthew J. Kauffman38, Roland Kays46, Roland Kays47, Duncan M. Kimuyu48, Flávia Koch33, Flávia Koch49, Bart Kranstauber37, Scott D. LaPoint50, Scott D. LaPoint16, Peter Leimgruber22, John D. C. Linnell, Pascual López-López51, A. Catherine Markham52, Jenny Mattisson, Emília Patrícia Medici53, Ugo Mellone54, Evelyn H. Merrill8, Guilherme Miranda de Mourão55, Ronaldo Gonçalves Morato, Nicolas Morellet43, Thomas A. Morrison56, Samuel L. Díaz-Muñoz57, Samuel L. Díaz-Muñoz14, Atle Mysterud58, Dejid Nandintsetseg1, Ran Nathan59, Aidin Niamir, John Odden, Robert B. O'Hara60, Luiz Gustavo R. Oliveira-Santos7, Kirk A. Olson10, Bruce D. Patterson61, Rogério Cunha de Paula, Luca Pedrotti, Björn Reineking62, Björn Reineking63, Martin Rimmler, Tracey L. Rogers64, Christer Moe Rolandsen, Christopher S. Rosenberry65, Daniel I. Rubenstein66, Kamran Safi67, Kamran Safi16, Sonia Saïd, Nir Sapir68, Hall Sawyer, Niels Martin Schmidt15, Nuria Selva69, Agnieszka Sergiel69, Enkhtuvshin Shiilegdamba10, João P. Silva70, João P. Silva71, João P. Silva72, Navinder J. Singh6, Erling Johan Solberg, Orr Spiegel14, Olav Strand, Siva R. Sundaresan, Wiebke Ullmann17, Ulrich Voigt44, Jake Wall32, David W. Wattles29, Martin Wikelski67, Martin Wikelski16, Christopher C. Wilmers73, John W. Wilson74, George Wittemyer32, George Wittemyer75, Filip Zięba, Tomasz Zwijacz-Kozica, Thomas Mueller1, Thomas Mueller22 
Goethe University Frankfurt1, University of Maryland, College Park2, University of Guelph3, Duke University4, Radboud University Nijmegen5, Swedish University of Agricultural Sciences6, Federal University of Mato Grosso do Sul7, University of Alberta8, Royal Veterinary College9, Wildlife Conservation Society10, Mississippi State University11, Sao Paulo State University12, Michigan Department of Natural Resources13, University of California, Davis14, Aarhus University15, Max Planck Society16, University of Potsdam17, Middle Tennessee State University18, Mammal Research Institute19, Edmund Mach Foundation20, Harvard University21, Smithsonian Conservation Biology Institute22, University of Évora23, University of Montpellier24, Parks Victoria25, Monash University26, Ohio State University27, Fiji National University28, University of Massachusetts Amherst29, United States Geological Survey30, University of Oxford31, Save the Elephants32, German Primate Center33, Technische Universität München34, Institute of Ecosystem Studies35, University of British Columbia36, University of Zurich37, University of Wyoming38, University of Washington39, University of Montana40, Bavarian Forest National Park41, University of Freiburg42, University of Toulouse43, University of Veterinary Medicine Vienna44, University College Cork45, North Carolina State University46, North Carolina Museum of Natural Sciences47, Karatina University48, University of Lethbridge49, Lamont–Doherty Earth Observatory50, University of Valencia51, Stony Brook University52, International Union for Conservation of Nature and Natural Resources53, University of Alicante54, Empresa Brasileira de Pesquisa Agropecuária55, University of Glasgow56, New York University57, University of Oslo58, Hebrew University of Jerusalem59, Norwegian University of Science and Technology60, Field Museum of Natural History61, University of Grenoble62, University of Bayreuth63, University of New South Wales64, Pennsylvania Game Commission65, Princeton University66, University of Konstanz67, University of Haifa68, Polish Academy of Sciences69, Instituto Superior de Agronomia70, University of Porto71, University of Lisbon72, University of California, Santa Cruz73, University of Pretoria74, Colorado State University75
26 Jan 2018-Science
TL;DR: Using a unique GPS-tracking database of 803 individuals across 57 species, it is found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in area with a low human footprint.
Abstract: Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission.

Journal ArticleDOI
TL;DR: The fundamental properties of TEs and their complex interactions with their cellular environment are introduced, which are crucial to understanding their impact and manifold consequences for organismal biology.
Abstract: Transposable elements (TEs) are major components of eukaryotic genomes. However, the extent of their impact on genome evolution, function, and disease remain a matter of intense interrogation. The rise of genomics and large-scale functional assays has shed new light on the multi-faceted activities of TEs and implies that they should no longer be marginalized. Here, we introduce the fundamental properties of TEs and their complex interactions with their cellular environment, which are crucial to understanding their impact and manifold consequences for organismal biology. While we draw examples primarily from mammalian systems, the core concepts outlined here are relevant to a broad range of organisms.

Journal ArticleDOI
TL;DR: A computational tool, demuxlet, that harnesses natural genetic variation to determine the sample identity of each droplet containing a single cell (singlet) and detect droplets containing two cells (doublets), which enable multiplexed dscRNA-seq experiments in which cells from unrelated individuals are pooled and captured at higher throughput than in standard workflows.
Abstract: Droplet single-cell RNA-sequencing (dscRNA-seq) has enabled rapid, massively parallel profiling of transcriptomes. However, assessing differential expression across multiple individuals has been hampered by inefficient sample processing and technical batch effects. Here we describe a computational tool, demuxlet, that harnesses natural genetic variation to determine the sample identity of each droplet containing a single cell (singlet) and detect droplets containing two cells (doublets). These capabilities enable multiplexed dscRNA-seq experiments in which cells from unrelated individuals are pooled and captured at higher throughput than in standard workflows. Using simulated data, we show that 50 single-nucleotide polymorphisms (SNPs) per cell are sufficient to assign 97% of singlets and identify 92% of doublets in pools of up to 64 individuals. Given genotyping data for each of eight pooled samples, demuxlet correctly recovers the sample identity of >99% of singlets and identifies doublets at rates consistent with previous estimates. We apply demuxlet to assess cell-type-specific changes in gene expression in 8 pooled lupus patient samples treated with interferon (IFN)-β and perform eQTL analysis on 23 pooled samples.

Journal ArticleDOI
TL;DR: Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding.
Abstract: Background Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. Methods We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. Results A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the ...