Showing papers by "University of Arizona published in 2015"
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as discussed by the authors, the authors used the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data.
5,792 citations
Mohammad H. Forouzanfar1, Lily Alexander, H. Ross Anderson, Victoria F Bachman1 +733 more•Institutions (289)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as discussed by the authors provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
5,668 citations
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
4,510 citations
University of Washington1, Institute for Health Metrics and Evaluation2, Iran University of Medical Sciences3, King's College London4, Arabian Gulf University5, University of North Texas6, Auckland University of Technology7, Alaska Native Tribal Health Consortium8, Columbia University9, Wuhan University10, Imperial College London11, University of Alabama at Birmingham12, University at Albany, SUNY13, City University of New York14, University of California, San Francisco15, Griffith University16, Environment Agency17, New York University18, Southern University College19, Emory University20, University of Ottawa21, Kosin University22, University of Toronto23, University of British Columbia24, United Arab Emirates University25, Albert Einstein College of Medicine26, University of São Paulo27, Nova Southeastern University28, University of Sydney29, Heidelberg University30, Cancer Treatment Centers of America31, Case Western Reserve University32, University of Oxford33, George Mason University34, James Cook University35, University of Trieste36, University of Calgary37, Wageningen University and Research Centre38, University of Gothenburg39, University of the Witwatersrand40, Harvard University41, Jackson State University42, University of Arizona43, University of Hong Kong44, Tehran University of Medical Sciences45, University of Western Australia46, Aintree University Hospitals NHS Foundation Trust47, Veterans Health Administration48, University of Colorado Denver49, University of Melbourne50, Royal Children's Hospital51, Australian National University52, University of Marburg53, Charité54, Health Canada55, College of Health Sciences, Bahrain56, Karolinska Institutet57, Northumbria University58, University of Edinburgh59, National Research University – Higher School of Economics60, Queen Mary University of London61, Addis Ababa University62, Northwestern University63, Northeastern University64, Mario Negri Institute for Pharmacological Research65, Arak University of Medical Sciences66, University of Nottingham67, University of Tokyo68, Public Health Foundation of India69, University of Groningen70, University of the Philippines Manila71, University of Bologna72, Kyung Hee University73, Brighton and Sussex Medical School74, University of Bergen75, Stavanger University Hospital76, University of Queensland77, National Centre for Disease Control78, University of Sheffield79, Universidad Autónoma Metropolitana80, University College London81, Genentech82, Universiti Tunku Abdul Rahman83, Norwegian Institute of Public Health84
TL;DR: To estimate mortality, incidence, years lived with disability, years of life lost, and disability-adjusted life-years for 28 cancers in 188 countries by sex from 1990 to 2013, the general methodology of the Global Burden of Disease 2013 study was used.
Abstract: Importance Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and Relevance Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.
2,375 citations
TL;DR: This work identifies ocean microbial core functionality and reveals that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.
Abstract: Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with >40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing >35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.
1,934 citations
Huntsman Cancer Institute1, Rutgers University2, University of North Carolina at Chapel Hill3, University of Texas MD Anderson Cancer Center4, University of Louisville5, Emory University6, Lynn University7, University of California, San Diego8, Amgen9, Vanderbilt University10, Temple University11, University of Iowa Hospitals and Clinics12, University of Arizona13, University of Colorado Boulder14, Washington University in St. Louis15, The Royal Marsden NHS Foundation Trust16, National Institute for Health Research17, McGill University18
TL;DR: T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial and represents a novel potential therapy for patients with metastatic melanoma.
Abstract: Purpose Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1‐derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial. Patients and Methods Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate. Results Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in 2% of T-VEC‐treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred.
1,815 citations
TL;DR: In this article, the authors identify ten contrasting perspectives that shape the vulnerability debate but have not been discussed collectively and present a set of global vulnerability drivers that are known with high confidence: (1) droughts eventually occur everywhere; (2) warming produces hotter Droughts; (3) atmospheric moisture demand increases nonlinearly with temperature during drought; (4) mortality can occur faster in hotter Drought, consistent with fundamental physiology; (5) shorter Drought can become lethal under warming, increasing the frequency of lethal Drought; and (6) mortality happens rapidly
Abstract: Patterns, mechanisms, projections, and consequences of tree mortality and associated broad-scale forest die-off due to drought accompanied by warmer temperatures—“hotter drought”, an emerging characteristic of the Anthropocene—are the focus of rapidly expanding literature. Despite recent observational, experimental, and modeling studies suggesting increased vulnerability of trees to hotter drought and associated pests and pathogens, substantial debate remains among research, management and policy-making communities regarding future tree mortality risks. We summarize key mortality-relevant findings, differentiating between those implying lesser versus greater levels of vulnerability. Evidence suggesting lesser vulnerability includes forest benefits of elevated [CO2] and increased water-use efficiency; observed and modeled increases in forest growth and canopy greening; widespread increases in woody-plant biomass, density, and extent; compensatory physiological, morphological, and genetic mechanisms; dampening ecological feedbacks; and potential mitigation by forest management. In contrast, recent studies document more rapid mortality under hotter drought due to negative tree physiological responses and accelerated biotic attacks. Additional evidence suggesting greater vulnerability includes rising background mortality rates; projected increases in drought frequency, intensity, and duration; limitations of vegetation models such as inadequately represented mortality processes; warming feedbacks from die-off; and wildfire synergies. Grouping these findings we identify ten contrasting perspectives that shape the vulnerability debate but have not been discussed collectively. We also present a set of global vulnerability drivers that are known with high confidence: (1) droughts eventually occur everywhere; (2) warming produces hotter droughts; (3) atmospheric moisture demand increases nonlinearly with temperature during drought; (4) mortality can occur faster in hotter drought, consistent with fundamental physiology; (5) shorter droughts occur more frequently than longer droughts and can become lethal under warming, increasing the frequency of lethal drought nonlinearly; and (6) mortality happens rapidly relative to growth intervals needed for forest recovery. These high-confidence drivers, in concert with research supporting greater vulnerability perspectives, support an overall viewpoint of greater forest vulnerability globally. We surmise that mortality vulnerability is being discounted in part due to difficulties in predicting threshold responses to extreme climate events. Given the profound ecological and societal implications of underestimating global vulnerability to hotter drought, we highlight urgent challenges for research, management, and policy-making communities.
1,786 citations
Mohammad H. Forouzanfar1, Lily Alexander1, H. Ross Anderson2, Victoria F Bachman1 +718 more•Institutions (295)
TL;DR: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) as mentioned in this paper provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
1,656 citations
University of Texas Health Science Center at Houston1, Medical College of Wisconsin2, Oregon Health & Science University3, University of Washington4, University of California, San Francisco5, University of Tennessee Health Science Center6, University of Southern California7, University of Alabama at Birmingham8, University of Cincinnati9, University of Arizona10, University of Toronto11, University of Maryland, Baltimore12, Sunnybrook Health Sciences Centre13, American College of Surgeons14, National Institutes of Health15
TL;DR: In this article, the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1 :1:2 ratio was evaluated.
Abstract: Importance Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. Objective To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Design, Setting, and Participants Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Interventions Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Main Outcomes and Measures Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. Results No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, −4.2% [95% CI, −9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, −3.7% [95% CI, −10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, −5.4% [95% CI, −10.4% to −0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P P Conclusions and Relevance Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. Trial Registration clinicaltrials.gov Identifier:NCT01545232
1,643 citations
Christopher J L Murray1, Ryan M Barber, Kyle J Foreman2, Ayse Abbasoglu Ozgoren +608 more•Institutions (251)
TL;DR: Patterns of the epidemiological transition with a composite indicator of sociodemographic status, which was constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population, were quantified.
1,609 citations
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
University of Florida1, University of Bonn2, Institut national de la recherche agronomique3, Blaise Pascal University4, Stanford University5, Prince of Songkla University6, Agricultural Research Service7, University of Arizona8, International Maize and Wheat Improvement Center9, Kansas State University10, International Water Management Institute11, Washington State University12, Michigan State University13, University of Leeds14, CGIAR15, Counterintelligence Field Activity16, Spanish National Research Council17, University of Tübingen18, University of Guelph19, Texas A&M University20, University of Maryland, College Park21, Aarhus University22, Potsdam Institute for Climate Impact Research23, Indian Agricultural Research Institute24, Goddard Institute for Space Studies25, Rothamsted Research26, University of Hohenheim27, Wageningen University and Research Centre28, Chinese Academy of Sciences29, Commonwealth Scientific and Industrial Research Organisation30, China Agricultural University31, Nanjing Agricultural University32
TL;DR: The authors systematically tested 30 different wheat crop models of the Agricultural Model Intercomparison and Improvement Project against field experiments in which growing season mean temperatures ranged from 15 degrees C to 32 degrees C, including experiments with artificial heating.
Abstract: Crop models are essential tools for assessing the threat of climate change to local and global food production(1). Present models used to predict wheat grain yield are highly uncertain when simulating how crops respond to temperature(2). Here we systematically tested 30 different wheat crop models of the Agricultural Model Intercomparison and Improvement Project against field experiments in which growing season mean temperatures ranged from 15 degrees C to 32 degrees C, including experiments with artificial heating. Many models simulated yields well, but were less accurate at higher temperatures. The model ensemble median was consistently more accurate in simulating the crop temperature response than any single model, regardless of the input information used. Extrapolating the model ensemble temperature response indicates that warming is already slowing yield gains at a majority of wheat-growing locations. Global wheat production is estimated to fall by 6% for each degrees C of further temperature increase and become more variable over space and time.
TL;DR: A broadened view of service innovation is offered--one grounded in service-dominant logic--that transcends the tangible--intangible and producer--consumer divides that have plagued extant research in this area.
Abstract: In this article, we offer a broadened view of service innovation--one grounded in service-dominant logic--that transcends the tangible--intangible and producer--consumer divides that have plagued extant research in this area. Such a broadened conceptualization of service innovation emphasizes (1) innovation as a collaborative process occurring in an actor-to-actor (A2A) network, (2) service as the application of specialized competences for the benefit of another actor or the self and as the basis of all exchange, (3) the generativity unleashed by increasing resource liquefaction and resource density, and (4) resource integration as the fundamental way to innovate. Building on these core themes, we offer a tripartite framework of service innovation: (1) service ecosystems, as emergent A2A structures actors create and recreate through their effectual actions and which offer an organizing logic for the actors to exchange service and cocreate value; (2) service platforms, which enhance the efficiency and effectiveness of service exchange by liquefying resources and increasing resource density (facilitating easy access to appropriate resource bundles) and thereby serve as the venue for innovation; and (3) value cocreation, which views value as cocreated by the service offer(er) and the service beneficiary (e.g., customer) through resource integration and indicate the need for mechanisms to support the underlying roles and processes. In discussing these components, we consider the role of information technology--both as an operand resource and as an operant resource--and then examine the implications for research and practice in digitally enabled service innovation.
10 Aug 2015
TL;DR: This work links disparate impact to a measure of classification accuracy that while known, has received relatively little attention and proposes a test for disparate impact based on how well the protected class can be predicted from the other attributes.
Abstract: What does it mean for an algorithm to be biased? In U.S. law, unintentional bias is encoded via disparate impact, which occurs when a selection process has widely different outcomes for different groups, even as it appears to be neutral. This legal determination hinges on a definition of a protected class (ethnicity, gender) and an explicit description of the process.When computers are involved, determining disparate impact (and hence bias) is harder. It might not be possible to disclose the process. In addition, even if the process is open, it might be hard to elucidate in a legal setting how the algorithm makes its decisions. Instead of requiring access to the process, we propose making inferences based on the data it uses.We present four contributions. First, we link disparate impact to a measure of classification accuracy that while known, has received relatively little attention. Second, we propose a test for disparate impact based on how well the protected class can be predicted from the other attributes. Third, we describe methods by which data might be made unbiased. Finally, we present empirical evidence supporting the effectiveness of our test for disparate impact and our approach for both masking bias and preserving relevant information in the data. Interestingly, our approach resembles some actual selection practices that have recently received legal scrutiny.
University of California, Los Angeles1, Vanderbilt University2, University of Zurich3, University of Duisburg-Essen4, University of Paris-Sud5, Harvard University6, Sheba Medical Center7, New York University8, University of Colorado Denver9, University of Arizona10, Netherlands Cancer Institute11, Durham University12, Seattle Cancer Care Alliance13, University of Tübingen14, University of Pennsylvania15, Temple University16, University of North Carolina at Chapel Hill17, University of Pittsburgh18, Memorial Sloan Kettering Cancer Center19, Merck & Co.20, University of California, San Francisco21
TL;DR: In this article, the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma were compared.
Abstract: Summary Background Patients with melanoma that progresses on ipilimumab and, if BRAF V600 mutant-positive, a BRAF or MEK inhibitor or both, have few treatment options. We assessed the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma. Methods We carried out a randomised phase 2 trial of patients aged 18 years or older from 73 hospitals, clinics, and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF V600 mutant-positive, previous treatment with a BRAF or MEK inhibitor or both. Patients had to have resolution of all ipilimumab-related adverse events to grade 0–1 and prednisone 10 mg/day or less for at least 2 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and at least one measurable lesion to be eligible. Using a centralised interactive voice response system, we randomly assigned (1:1:1) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide). Randomisation was stratified by ECOG performance status, lactate dehydrogenase concentration, and BRAF V600 mutation status. Individual treatment assignment between pembrolizumab and chemotherapy was open label, but investigators and patients were masked to assignment of the dose of pembrolizumab. We present the primary endpoint at the prespecified second interim analysis of progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01704287. The study is closed to enrolment but continues to follow up and treat patients. Findings Between Nov 30, 2012, and Nov 13, 2013, we enrolled 540 patients: 180 patients were randomly assigned to receive pembrolizumab 2 mg/kg, 181 to receive pembrolizumab 10 mg/kg, and 179 to receive chemotherapy. Based on 410 progression-free survival events, progression-free survival was improved in patients assigned to pembrolizumab 2 mg/kg (HR 0·57, 95% CI 0·45–0·73; p Interpretation These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumab-refractory melanoma. Funding Merck Sharp & Dohme.
TL;DR: In this paper, a strong negative relationship between firm-level capital investment and the aggregate level of uncertainty associated with future policy and regulatory outcomes is found, and the relation between policy uncertainty and capital investment is not uniform in the cross section, being significantly stronger for firms with a higher degree of investment irreversibility and for firms more dependent on government spending.
Abstract: Using the policy uncertainty index of Baker, Bloom, and Davis (2013), we document a strong negative relationship between firm-level capital investment and the aggregate level of uncertainty associated with future policy and regulatory outcomes. More importantly, we find evidence that the relation between policy uncertainty and capital investment is not uniform in the cross section, being significantly stronger for firms with a higher degree of investment irreversibility and for firms which are more dependent on government spending. Our results lend empirical support to the notion that policy uncertainty can depress corporate investment by inducing precautionary delays due to investment irreversibility.
Research Institute for Fragrance Materials1, Columbia University Medical Center2, Malmö University3, University of Nebraska–Lincoln4, University of São Paulo5, University of Würzburg6, Oregon Health & Science University7, International Flavors & Fragrances, Inc.8, Symrise9, Vanderbilt University10, Kyoto University11, Takasago International Corporation12, University of Tennessee13, University of Arizona14
TL;DR: This publication is designed to update the RifM safety assessment process, which follows a series of decision trees, reflecting advances in approaches in risk assessment and new and classical toxicological methodologies employed by RIFM over the past ten years.
TL;DR: This first report of the whole genome sequence of A. cerana provides resources for comparative sociogenomics, especially in the field of social insect communication, to contribute to a better understanding of the complex behaviors and natural biology of the Asian honey bee and to anticipate its future evolutionary trajectory.
Abstract: The honey bee is an important model system for increasing understanding of molecular and neural mechanisms underlying social behaviors relevant to the agricultural industry and basic science. The western honey bee, Apis mellifera, has served as a model species, and its genome sequence has been published. In contrast, the genome of the Asian honey bee, Apis cerana, has not yet been sequenced. A. cerana has been raised in Asian countries for thousands of years and has brought considerable economic benefits to the apicultural industry. A cerana has divergent biological traits compared to A. mellifera and it has played a key role in maintaining biodiversity in eastern and southern Asia. Here we report the first whole genome sequence of A. cerana. Using de novo assembly methods, we produced a 238 Mbp draft of the A. cerana genome and generated 10,651 genes. A.cerana-specific genes were analyzed to better understand the novel characteristics of this honey bee species. Seventy-two percent of the A. cerana-specific genes had more than one GO term, and 1,696 enzymes were categorized into 125 pathways. Genes involved in chemoreception and immunity were carefully identified and compared to those from other sequenced insect models. These included 10 gustatory receptors, 119 odorant receptors, 10 ionotropic receptors, and 160 immune-related genes. This first report of the whole genome sequence of A. cerana provides resources for comparative sociogenomics, especially in the field of social insect communication. These important tools will contribute to a better understanding of the complex behaviors and natural biology of the Asian honey bee and to anticipate its future evolutionary trajectory.
TL;DR: VirSorter is a tool designed to detect viral signal in these different types of microbial sequence data in both a reference-dependent and reference-independent manner, leveraging probabilistic models and extensive virome data to maximize detection of novel viruses.
Abstract: Viruses of microbes impact all ecosystems where microbes drive key energy and substrate transformations including the oceans, humans and industrial fermenters. However, despite this recognized importance, our understanding of viral diversity and impacts remains limited by too few model systems and reference genomes. One way to fill these gaps in our knowledge of viral diversity is through the detection of viral signal in microbial genomic data. While multiple approaches have been developed and applied for the detection of prophages (viral genomes integrated in a microbial genome), new types of microbial genomic data are emerging that are more fragmented and larger scale, such as Single-cell Amplified Genomes (SAGs) of uncultivated organisms or genomic fragments assembled from metagenomic sequencing. Here, we present VirSorter, a tool designed to detect viral signal in these different types of microbial sequence data in both a reference-dependent and reference-independent manner, leveraging probabilistic models and extensive virome data to maximize detection of novel viruses. Performance testing shows that VirSorter's prophage prediction capability compares to that of available prophage predictors for complete genomes, but is superior in predicting viral sequences outside of a host genome (i.e., from extrachromosomal prophages, lytic infections, or partially assembled prophages). Furthermore, VirSorter outperforms existing tools for fragmented genomic and metagenomic datasets, and can identify viral signal in assembled sequence (contigs) as short as 3kb, while providing near-perfect identification (>95% Recall and 100% Precision) on contigs of at least 10kb. Because VirSorter scales to large datasets, it can also be used in "reverse" to more confidently identify viral sequence in viral metagenomes by sorting away cellular DNA whether derived from gene transfer agents, generalized transduction or contamination. Finally, VirSorter is made available through the iPlant Cyberinfrastructure that provides a web-based user interface interconnected with the required computing resources. VirSorter thus complements existing prophage prediction softwares to better leverage fragmented, SAG and metagenomic datasets in a way that will scale to modern sequencing. Given these features, VirSorter should enable the discovery of new viruses in microbial datasets, and further our understanding of uncultivated viral communities across diverse ecosystems.
Nevada System of Higher Education1, University of Washington2, University of California, Berkeley3, Queen's University Belfast4, Energy Institute5, Oeschger Centre for Climate Change Research6, Purdue University7, University of Copenhagen8, Alfred Wegener Institute for Polar and Marine Research9, University of Nottingham10, Lund University11, Natural Environment Research Council12, University of Arizona13
TL;DR: It is shown that large eruptions in the tropics and high latitudes were primary drivers of interannual-to-decadal temperature variability in the Northern Hemisphere during the past 2,500 years and cooling was proportional to the magnitude of volcanic forcing.
Abstract: Volcanic eruptions contribute to climate variability, but quantifying these contributions has been limited by inconsistencies in the timing of atmospheric volcanic aerosol loading determined from ice cores and subsequent cooling from climate proxies such as tree rings. Here we resolve these inconsistencies and show that large eruptions in the tropics and high latitudes were primary drivers of interannual-to-decadal temperature variability in the Northern Hemisphere during the past 2,500 years. Our results are based on new records of atmospheric aerosol loading developed from high-resolution, multi-parameter measurements from an array of Greenland and Antarctic ice cores as well as distinctive age markers to constrain chronologies. Overall, cooling was proportional to the magnitude of volcanic forcing and persisted for up to ten years after some of the largest eruptive episodes. Our revised timescale more firmly implicates volcanic eruptions as catalysts in the major sixth-century pandemics, famines, and socioeconomic disruptions in Eurasia and Mesoamerica while allowing multi-millennium quantification of climate response to volcanic forcing.
TL;DR: In this paper, the authors discuss new constraints on the epoch of cosmic reionization and test the assumption that most of the ionizing photons responsible arose from high-redshift star-forming galaxies.
Abstract: We discuss new constraints on the epoch of cosmic reionization and test the assumption that most of the ionizing photons responsible arose from high-redshift star-forming galaxies. Good progress has been made in charting the end of reionization through spectroscopic studies of z≃ 6–8 QSOs, gamma-ray bursts, and galaxies expected to host Lyα emission. However, the most stringent constraints on its duration have come from the integrated optical depth, τ, of Thomson scattering to the cosmic microwave background. Using the latest data on the abundance and luminosity distribution of distant galaxies from Hubble Space Telescope imaging, we simultaneously match the reduced value τ = 0.066 ± 0.012 recently reported by the Planck collaboration and the evolving neutrality of the intergalactic medium with a reionization history within 6 ≾ z ≾ 10, thereby reducing the requirement for a significant population of very high redshift (z ≫ 10) galaxies. Our analysis strengthens the conclusion that star-forming galaxies dominated the reionization process and has important implications for upcoming 21 cm experiments and searches for early galaxies with the James Webb Space Telescope.
TL;DR: The discovery of an ultraluminous quasar, SDSS J010013.02+280225.8, at redshift z = 6.30, which has an optical and near-infrared luminosity a few times greater than those of previously known z > 6 quasars.
Abstract: So far, roughly 40 quasars with redshifts greater than z = 6 have been discovered(1-8) Each quasar contains a black hole with a mass of about one billion solar masses (10(9) M-circle dot)(2,6,7,9-13) The existence of such black holes when the Universe was less than one billion years old presents substantial challenges to theories of the formation and growth of black holes and the coevolution of black holes and galaxies(14) Here we report the discovery of an ultraluminous quasar, SDSS J01001302+2802258, at redshift z = 630 It has an optical and near-infrared luminosity a few times greater than those of previously known z > 6 quasars On the basis of the deep absorption trough(15) on the blue side of the Lyman-alpha emission line in the spectrum, we estimate the proper size of the ionized proximity zone associated with the quasar to be about 26 million light years, larger than found with other z > 61 quasars with lower luminosities(16) We estimate (on the basis of a near-infrared spectrum) that the black hole has a mass of similar to 12 x 10(10) M-circle dot, which is consistent with the 13 x 10(10) M-circle dot derived by assuming an Eddington-limited accretion rate
Earth System Research Laboratory1, Geophysical Fluid Dynamics Laboratory2, Georgia Institute of Technology3, University of California, Irvine4, University of Arizona5, Texas A&M University6, University of Reading7, Woods Hole Oceanographic Institution8, University of Miami9, California Institute of Technology10, Hanyang University11
TL;DR: The authors surveys the current state of knowledge of ENSO diversity, identifies key gaps in understanding, and outlines some promising future research directions, as well as identifying key gaps and promising future directions.
Abstract: El Nino–Southern Oscillation (ENSO) is a naturally occurring mode of tropical Pacific variability, with global impacts on society and natural ecosystems. While it has long been known that El Nino events display a diverse range of amplitudes, triggers, spatial patterns, and life cycles, the realization that ENSO’s impacts can be highly sensitive to this event-to-event diversity is driving a renewed interest in the subject. This paper surveys our current state of knowledge of ENSO diversity, identifies key gaps in understanding, and outlines some promising future research directions.
TL;DR: In this article, a news-based index of policy uncertainty was used to find a negative relationship between firm-level capital investment and the aggregate level of uncertainty associated with future policy and regulatory outcomes.
Abstract: Using a news-based index of policy uncertainty, we document a strong negative relationship between firm-level capital investment and the aggregate level of uncertainty associated with future policy and regulatory outcomes. More importantly, we find evidence that the relation between policy uncertainty and capital investment is not uniform in the cross-section, being significantly stronger for firms with a higher degree of investment irreversibility and for firms that are more dependent on government spending. Our results lend empirical support to the notion that policy uncertainty can depress corporate investment by inducing precautionary delays due to investment irreversibility.
Vrije Universiteit Brussel1, Pierre-and-Marie-Curie University2, Université libre de Bruxelles3, University of Arizona4, Université catholique de Louvain5, École Normale Supérieure6, Katholieke Universiteit Leuven7, Spanish National Research Council8, University of Paris9, University of Bremen10, Centre national de la recherche scientifique11, Kyoto University12, University of Western Brittany13, French Alternative Energies and Atomic Energy Commission14
TL;DR: It is found that environmental factors are incomplete predictors of community structure and associations across plankton functional types and phylogenetic groups to be nonrandomly distributed on the network and driven by both local and global patterns.
Abstract: Species interaction networks are shaped by abiotic and biotic factors. Here, as part of the Tara Oceans project, we studied the photic zone interactome using environmental factors and organismal abundance profiles and found that environmental factors are incomplete predictors of community structure. We found associations across plankton functional types and phylogenetic groups to be nonrandomly distributed on the network and driven by both local and global patterns. We identified interactions among grazers, primary producers, viruses, and (mainly parasitic) symbionts and validated network-generated hypotheses using microscopy to confirm symbiotic relationships. We have thus provided a resource to support further research on ocean food webs and integrating biological components into ocean models.
University of Southern Denmark1, Brigham and Women's Hospital2, University of Barcelona3, Autonomous University of Madrid4, University of Arizona5, University of Colorado Denver6, Manchester Academic Health Science Centre7, Autonomous University of Chile8, Harvard University9, Lovelace Respiratory Research Institute10, University of New Mexico11
TL;DR: It is suggested that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline inFEV1 is not an obligate feature of COPd.
Abstract: BackgroundChronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms. MethodsWe stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. ResultsAmong 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseli...
TL;DR: This project reached consensus of ophthalmology experts from around the world regarding keratoconus and ectatic diseases, focusing on their definition, concepts, clinical management, and surgical treatments, and provides an insight into the current worldwide treatment of these conditions.
Abstract: Background Despite extensive knowledge regarding the diagnosis and management of keratoconus and ectatic corneal diseases, many controversies still exist. For that reason, there is a need for current guidelines for the diagnosis and management of these conditions. Purpose This project aimed to reach consensus of ophthalmology experts from around the world regarding keratoconus and ectatic diseases, focusing on their definition, concepts, clinical management, and surgical treatments. Methods The Delphi method was followed with 3 questionnaire rounds and was complemented with a face-to-face meeting. Thirty-six panelists were involved and allocated to 1 of 3 panels: definition/diagnosis, nonsurgical management, or surgical treatment. The level of agreement considered for consensus was two thirds. Results Numerous agreements were generated in definitions, methods of diagnosing, and management of keratoconus and other ectatic diseases. Nonsurgical and surgical treatments for these conditions, including the use of corneal cross-linking and corneal transplantations, were presented in a stepwise approach. A flowchart describing a logical management sequence for keratoconus was created. Conclusions This project resulted in definitions, statements, and recommendations for the diagnosis and management of keratoconus and other ectatic diseases. It also provides an insight into the current worldwide treatment of these conditions.
TL;DR: In such nonstationary environments, where the probabilistic properties of the data change over time, a non-adaptive model trained under the false stationarity assumption is bound to become obsolete in time, and perform sub-optimally at best, or fail catastrophically at worst.
Abstract: The prevalence of mobile phones, the internet-of-things technology, and networks of sensors has led to an enormous and ever increasing amount of data that are now more commonly available in a streaming fashion [1]-[5]. Often, it is assumed - either implicitly or explicitly - that the process generating such a stream of data is stationary, that is, the data are drawn from a fixed, albeit unknown probability distribution. In many real-world scenarios, however, such an assumption is simply not true, and the underlying process generating the data stream is characterized by an intrinsic nonstationary (or evolving or drifting) phenomenon. The nonstationarity can be due, for example, to seasonality or periodicity effects, changes in the users' habits or preferences, hardware or software faults affecting a cyber-physical system, thermal drifts or aging effects in sensors. In such nonstationary environments, where the probabilistic properties of the data change over time, a non-adaptive model trained under the false stationarity assumption is bound to become obsolete in time, and perform sub-optimally at best, or fail catastrophically at worst.
Max Planck Society1, University College London2, University of Bonn3, Centre national de la recherche scientifique4, University of Maryland, College Park5, University of Toulouse6, ETH Zurich7, Spanish National Research Council8, University of California, Irvine9, Tel Aviv University10, University of Arizona11
TL;DR: In this paper, the scaling relations of molecular gas depletion timescale (t depl) and gas to stellar mass ratio (M mol gas/M* ) of 500 star-forming galaxies near the star formation "main-sequence" with redshift, specific star-formation rate (sSFR), and stellar mass (M* ).
Abstract: We combine molecular gas masses inferred from CO emission in 500 star-forming galaxies (SFGs) between z = 0 and 3, from the IRAM-COLDGASS, PHIBSS1/2, and other surveys, with gas masses derived from Herschel far-IR dust measurements in 512 galaxy stacks over the same stellar mass/redshift range. We constrain the scaling relations of molecular gas depletion timescale (t depl) and gas to stellar mass ratio (M mol gas/M* ) of SFGs near the star formation "main-sequence" with redshift, specific star-formation rate (sSFR), and stellar mass (M* ). The CO- and dust-based scaling relations agree remarkably well. This suggests that the CO → H2 mass conversion factor varies little within ±0.6 dex of the main sequence (sSFR(ms, z, M *)), and less than 0.3 dex throughout this redshift range. This study builds on and strengthens the results of earlier work. We find that t depl scales as (1 + z)–0.3 × (sSFR/sSFR(ms, z, M *))–0.5, with little dependence on M *. The resulting steep redshift dependence of M mol gas/M * ≈ (1 + z)3 mirrors that of the sSFR and probably reflects the gas supply rate. The decreasing gas fractions at high M* are driven by the flattening of the SFR-M * relation. Throughout the probed redshift range a combination of an increasing gas fraction and a decreasing depletion timescale causes a larger sSFR at constant M *. As a result, galaxy integrated samples of the M mol gas-SFR rate relation exhibit a super-linear slope, which increases with the range of sSFR. With these new relations it is now possible to determine M mol gas with an accuracy of ±0.1 dex in relative terms, and ±0.2 dex including systematic uncertainties.