332 research outputs found

    Structural Topic Models for Open-Ended Survey Responses

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    Collection and especially analysis of open-ended survey responses are relatively rare in the discipline and when conducted are almost exclusively done through human coding. We present an alternative, semiautomated approach, the structural topic model (STM) (Roberts, Stewart, and Airoldi 2013; Roberts et al. 2013), that draws on recent developments in machine learning based analysis of textual data. A crucial contribution of the method is that it incorporates information about the document, such as the author's gender, political affiliation, and treatment assignment (if an experimental study). This article focuses on how the STM is helpful for survey researchers and experimentalists. The STM makes analyzing open-ended responses easier, more revealing, and capable of being used to estimate treatment effects. We illustrate these innovations with analysis of text from surveys and experiments

    Bayesian optimization for materials design

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    We introduce Bayesian optimization, a technique developed for optimizing time-consuming engineering simulations and for fitting machine learning models on large datasets. Bayesian optimization guides the choice of experiments during materials design and discovery to find good material designs in as few experiments as possible. We focus on the case when materials designs are parameterized by a low-dimensional vector. Bayesian optimization is built on a statistical technique called Gaussian process regression, which allows predicting the performance of a new design based on previously tested designs. After providing a detailed introduction to Gaussian process regression, we introduce two Bayesian optimization methods: expected improvement, for design problems with noise-free evaluations; and the knowledge-gradient method, which generalizes expected improvement and may be used in design problems with noisy evaluations. Both methods are derived using a value-of-information analysis, and enjoy one-step Bayes-optimality

    Estimates of volcanic mercury emissions from Redoubt Volcano, Augustine Volcano, and Mount Spurr eruption ash

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    Ash is a potential sink of volcanically sourced atmospheric mercury (Hg), and the concentration of particle-bound Hg may provide constraints on Hg emissions during eruptions. We analyze Hg concentrations in 227 bulk ash samples from the Mount Spurr (1992), Redoubt Volcano (2009), and Augustine Volcano (2006) volcanic eruptions to investigate large-scale spatial, temporal, and volcanic-source trends. We find no significant difference in Hg concentrations in bulk ash by distance or discrete eruptive events at each volcano, suggesting that in-plume reactions converting gaseous Hg0 to adsorbed Hg2+ are happening on shorter timescales than considered in this study (minutes) and any additional in-plume controls are not discernable within intra-volcanic sample variability. However, we do find a significant difference in Hg concentration of ash among volcanic sources, which indicates that volcanoes may emit comparatively high or low quantities of Hg. We combine our Hg findings with total mass estimates of ashfall deposits to calculate minimum, first-order Hg emissions of 8.23 t Hg for Mount Spurr (1992), 1.25 t Hg for Redoubt Volcano (2009), and 0.16 t Hg for Augustine Volcano (2006). In particular, we find that Mount Spurr is a high Hg emitting volcano, and that its 1992 particulate Hg emissions likely contributed substantially to the global eruptive volcanic Hg budget for that year. Based on our findings, previous approaches that use long-term Hg/SO2 mass ratios to estimate eruptive total Hg under-account for Hg emitted in explosive events, and global volcanogenic Total Hg estimates need revisiting

    Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6

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    Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFÎČ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature. Here we show that BMP6 and BMP2 ligands are pro-angiogenic in vitro and in vivo, and that lateral vessel branching requires threshold levels of R-SMAD phosphorylation. Endothelial cell responsiveness to these pro-angiogenic BMP ligands is regulated by Notch status and Notch sets responsiveness by regulating a cell-intrinsic BMP inhibitor, SMAD6, which affects BMP responses upstream of target gene expression. Thus, we reveal a paradigm for Notch-dependent regulation of angiogenesis: Notch regulates SMAD6 expression to affect BMP responsiveness of endothelial cells and new vessel branch formation

    D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

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    Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

    Sequential design of computer experiments for the estimation of a probability of failure

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    This paper deals with the problem of estimating the volume of the excursion set of a function f:Rd→Rf:\mathbb{R}^d \to \mathbb{R} above a given threshold, under a probability measure on Rd\mathbb{R}^d that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of ff and aim at performing evaluations of ff as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

    Characterization of Sulfolobus islandicus rod-shaped virus 2 gp19, a single-strand specific endonuclease

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    The hyperthermophilic Sulfolobus islandicus rod-shaped virus 2 (SIRV2) encodes a 25-kDa protein (SIRV2gp19) annotated as a hypothetical protein with sequence homology to the RecB nuclease superfamily. Even though SIRV2gp19 homologs are conserved throughout the rudivirus family and presumably play a role in the viral life cycle, SIRV2gp19 has not been functionally characterized. To define the minimal requirements for activity, SIRV2gp19 was purified and tested under varying conditions. SIRV2gp19 is a single-strand specific endonuclease that requires Mg2+ for activity and is inactive on double-stranded DNA. A conserved aspartic acid in RecB nuclease superfamily Motif II (D89) is also essential for SIRV2gp19 activity and mutation to alanine (D89A) abolishes activity. Therefore, the SIRV2gp19 cleavage mechanism is similar to previously described RecB nucleases. Finally, SIRV2gp19 single-stranded DNA endonuclease activity could play a role in host chromosome degradation during SIRV2 lytic infection

    ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction—Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)

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    Although considerable improvement has occurred in the process of care for patients with ST-elevation myocardial infarction (STEMI), room for improvement exists (1–3). The purpose of the present guideline is to focus on the numerous advances in the diagnosis and management of patients with STEMI since 1999. This is reflected in the changed name of the guideline: “ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction.” The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in patients with STEMI summarize both clinical evidence and expert opinion (Table 1).To provide clinicians with a set of recommendations that can easily be translated into the practice of caring for patients with STEMI, this guideline is organized around the chronology of the interface between the patient and the clinician. The full guideline is available at http://www.acc.org/clinical/guidelines/stemi/index.htm
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