297 research outputs found

    Bethe Projections for Non-Local Inference

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    Many inference problems in structured prediction are naturally solved by augmenting a tractable dependency structure with complex, non-local auxiliary objectives. This includes the mean field family of variational inference algorithms, soft- or hard-constrained inference using Lagrangian relaxation or linear programming, collective graphical models, and forms of semi-supervised learning such as posterior regularization. We present a method to discriminatively learn broad families of inference objectives, capturing powerful non-local statistics of the latent variables, while maintaining tractable and provably fast inference using non-Euclidean projected gradient descent with a distance-generating function given by the Bethe entropy. We demonstrate the performance and flexibility of our method by (1) extracting structured citations from research papers by learning soft global constraints, (2) achieving state-of-the-art results on a widely-used handwriting recognition task using a novel learned non-convex inference procedure, and (3) providing a fast and highly scalable algorithm for the challenging problem of inference in a collective graphical model applied to bird migration.Comment: minor bug fix to appendix. appeared in UAI 201

    The role of deep moist convective processes in western boundary currents - troposphere coupling

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    Previous studies have suggested that atmospheric deep convection is occurring above the oceans western boundary currents. To investigate the occurrence of deep (ocean surface to troposphere) convection in mid-latitudes, diagnostics of upright and slantwise convective instability are created and used in the ERA-interim re-analysis dataset. These diagnostics find that deep convection is restricted to the western boundary currents in winter. However, over the ocean currents deep convection can occur up to 50% of the winter. As these ocean currents, including the Gulf Stream and Kuroshio, are warm and carry large quantities of heat polewards they could influence the frequency of deep convection. A simple calculation demonstrates that decadal ocean variability can change the atmospheric stability by 80% in the core of the Kuroshio and Gulf Stream. The deep convective instability occurs in synoptic systems that pass over the ocean currents. Specifically, instability occurs on the atmospheric fronts in the extra-tropical cyclones. To investigate the convective instability and related circulation at atmospheric fronts a composite of all atmospheric fronts in the Gulf Stream region is produced. The front composites show that where slantwise instability occurred at a front an associated increase in frontal ascent throughout the troposphere and precipitation is also found. An investigation into the possible mechanisms that produced the increased ascent at slantwise unstable fronts concludes that a possible cause is a coarse resolution of slantwise circulations in the ERA-interim dataset. This increase in deep ascent associated with slantwise instability could explain, at least partially, the deep ascent found by previous studies over the Gulf Stream. This is consistent with the finding that the deep ascent in the Gulf Stream annual mean is a product of extreme events. The occurrence of deep slantwise instability and the associated circulations are also resolution dependent. A comparison between 25 km, 60 km and 135 km grid-spacing atmospheric model runs are made using the UPSCALE project dataset. The 25 km model runs indicate greater deep slantwise and upright convective instability. The 25-km set-up is also the only one where increased deep ascent at slantwise unstable fronts is observed.Open Acces

    Primary care and health inequality : Difference-in-difference study comparing England and Ontario

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    BACKGROUND: It is not known whether equity-oriented primary care investment that seeks to scale up the delivery of effective care in disadvantaged communities can reduce health inequality within high-income settings that have pre-existing universal primary care systems. We provide some non-randomised controlled evidence by comparing health inequality trends between two similar jurisdictions-one of which implemented equity-oriented primary care investment in the mid-to-late 2000s as part of a cross-government strategy for reducing health inequality (England), and one which invested in primary care without any explicit equity objective (Ontario, Canada). METHODS: We analysed whole-population data on 32,482 neighbourhoods (with mean population size of approximately 1,500 people) in England, and 18,961 neighbourhoods (with mean population size of approximately 700 people) in Ontario. We examined trends in mortality amenable to healthcare by decile groups of neighbourhood deprivation within each jurisdiction. We used linear models to estimate absolute and relative gaps in amenable mortality between most and least deprived groups, considering the gradient between these extremes, and evaluated difference-in-difference comparisons between the two jurisdictions. RESULTS: Inequality trends were comparable in both jurisdictions from 2004-6 but diverged from 2007-11. Compared with Ontario, the absolute gap in amenable mortality in England fell between 2004-6 and 2007-11 by 19.8 per 100,000 population (95% CI: 4.8 to 34.9); and the relative gap in amenable mortality fell by 10 percentage points (95% CI: 1 to 19). The biggest divergence occurred in the most deprived decile group of neighbourhoods. DISCUSSION: In comparison to Ontario, England succeeded in reducing absolute socioeconomic gaps in mortality amenable to healthcare from 2007 to 2011, and preventing them from growing in relative terms. Equity-oriented primary care reform in England in the mid-to-late 2000s may have helped to reduce socioeconomic inequality in health, though other explanations for this divergence are possible and further research is needed on the specific causal mechanisms

    The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

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    The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

    Autism associated with tetrasomy 15: A further report

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    Association of autism with tetrasomy of chromosome 15 has recently been described in six males. In this report, we describe the occurrence of autism in a girl with tetrasomy of chromosome 15. The patient showed hyperactivity, hand-flapping, short-stature, eye abnormalities, and hypotonia, which have been reported in males with tetrasomy of chromosome 15. This suggests that autism may be associated in both sexes with a distinct syndrome characterized by tetrasomy of chromosome 15, mental retardation and characteristic physical features. L'association d'autisme avec une tétrasomie du chromosome 15 a été décrite récemment chez six garçons. Dans cet article, nous décrivons la survenue d'un autisme chez une fille avec une tétrasomie du chromosome 15. La patiente présentait une hyperactivité, un battement des mains, une petite taille, des anormalités des yeux et une hypotonie qui ont été rapportées chez des garçons avec tétrasomie du chromosome 15. Ceci suggère que l'autisme peut être associé dans les deux sexes avec un syndrome distinct caractérisé par une tétrasomie du chromosome 15, un retard mental et des traits physiques caractéristiques. Kürzlich wurde eine Assoziation einer Tetrasomie des Chromosoms 15 mit Autismus bei 6 männlichen Individuen beschrieben. In dem vorliegenden Fallbericht wird das Vorkommen eines Autismus bei einem Mädchen mit einer Tetrasomie des Chromosoms 15 dargestellt. Die Patientin zeigte Hyperaktivität, Handstereotypien, ophthalmologische Auffälligkeiten und Hypotonie. Diese Auffälligkeiten sind auch bei den männlichen Individuen mit einer Tetrasomie 15 beschrieben worden. Diese Befunde legen nahe, daß bei beiden Geschlechtern Autismus mit einem eigenständigen Syndrom im Falle des Vorliegens einer Tetrasomie 15 einhergeht, dessen wesentliche Merkmale geistige Behinderung und charakteristische Auffälligkeiten sind.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41756/1/787_2005_Article_BF02098582.pd

    Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

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    Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

    Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

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    Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

    Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

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    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
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