Showing papers by "York University published in 2017"

cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination

Abstract: Single-particle electron cryomicroscopy (cryo-EM) is a powerful method for determining the structures of biological macromolecules. With automated microscopes, cryo-EM data can often be obtained in a few days. However, processing cryo-EM image data to reveal heterogeneity in the protein structure and to refine 3D maps to high resolution frequently becomes a severe bottleneck, requiring expert intervention, prior structural knowledge, and weeks of calculations on expensive computer clusters. Here we show that stochastic gradient descent (SGD) and branch-and-bound maximum likelihood optimization algorithms permit the major steps in cryo-EM structure determination to be performed in hours or minutes on an inexpensive desktop computer. Furthermore, SGD with Bayesian marginalization allows ab initio 3D classification, enabling automated analysis and discovery of unexpected structures without bias from a reference map. These algorithms are combined in a user-friendly computer program named cryoSPARC (http://www.cryosparc.com).

The SAGE Handbook of Organizational Institutionalism

Abstract: Introduction - Royston Greenwood, Christine Oliver, Kerstin Sahlin and Roy Suddaby PART ONE: FOUNDATIONAL THEMES Legitimacy in Organizational Institutionalism - David L Deephouse and Marc Suchman Isomorphism, Diffusion and Decoupling - Eva Boxenbaum and Stefan Jonsson Institutional Logics - Patricia H Thornton and William Ocasio Organizational Fields - Melissa Wooten and Andrew J Hoffman Past, Present and Future PART TWO: INSTITUTIONAL DYNAMICS The Work of Meanings in Institutional Processes and Thinking - Tammar B Zilber Power, Institutions and Organizations - Thomas B Lawrence Institutional Entrepreneurship - Cynthia Hardy and Steve Maguire Circulating Ideas - Kerstin Sahlin and Linda Wedlin Imitation, Translation and Editing Organizational Implications of Institutional Pluralism - Matthew S Kraatz and Emily S. Block Microfoundations of Institutional Theory - Walter W Powell and Jeannette A. Colyvas Institutions and Transnationalization - Marie-Laure Djelic and Sigrid Quack PART THREE: APPLICATIONS Traditions as Institutionalized Practice - M Tina Dacin and Peter A Dacin Implications for de-institutionalization New Forms as Settlements - Hayagreeva Rao and Martin Kenney Social Movements and Failed Institutionalization - Gerald F Davis and Peter J J Anderson Corporate, (Non)Response to the AIDS Epidemic Institutions and Corporate Governance - Peer C Fiss PART FOUR: INTERFACES Beyond Constraint - Mary Ann Glynn How Institutions Enable Identities Institutionalism and the Professions - Kevin T Leicht and Mary L Fennell Institutionalism and Globalization Studies - Gili S Drori Organizational Institutionalism and Sociology - C R Hinings and Pamela S Tolbert A Reflection Coalface Institutionalism - Stephen R Barley New Sociology of Knowledge - Renate E Meyer Historical Legacy and Contributions Systems Theory, Societal Contexts and Organizational Heterogeneity - Raimund Hasse and Georg Kr cken Charting Progress at the Nexus of Institutional Theory and Economics - Peter W Roberts Ecologists and Institutionalists - Heather A Haveman and Robert J David Friends or Foes? Networks and Institutions - Jason Owen-Smith and Walter W Powell Institutional-Level Learning - Pamela Haunschild and David Chandler Learning as a Source of Institutional Change Social Movements and Institutional Analysis - Marc Schneiberg and Michael Lounsbury Examining 'Institutionalization' - David J Cooper, Mahmoud Ezzamel and Hugh Willmott A Critical Theoretic Perspective Taking Social Construction Seriously - Nelson Phillips and Namrata Malhotra Extending the Discursive Approach in Institutional Theory Institutional Leadership - Marvin Washington, Kimberly B Boal and John N Davis Past, Present and Future PART FIVE: REFLECTIONS Is the New Institutionalism a Theory? - Donald Palmer, Nicole Biggart and Brian Dick How to Misuse Institutions and Get Away with It - Barbara Czarniawska Some Reflections on Institutional Theory(ies) Been There, Done That, Moving on - Paul Hirsch Reflections on Institutional Theory's Continuing Evolution Reflections on Institutional Theories of Organizations - John W Meyer

Industry sponsorship and research outcome

Abstract: Background Clinical research affecting how doctors practice medicine is increasingly sponsored by companies that make drugs and medical devices. Previous systematic reviews have found that pharmaceutical industry sponsored studies are more often favorable to the sponsor’s product compared with studies with other sources of sponsorship. This review is an update using more stringent methodology and also investigating sponsorship of device studies. Objectives To investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship. Search methods We searched MEDLINE (1948 to September 2010), EMBASE (1980 to September 2010), the Cochrane Methodology Register (Issue 4, 2010) and Web of Science (August 2011). In addition, we searched reference lists of included papers, previous systematic reviews and author files. Selection criteria Cross-sectional studies, cohort studies, systematic reviews and meta-analyses that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. We had no language restrictions. Data collection and analysis Two assessors identified potentially relevant papers, and a decision about final inclusion was made by all authors. Two assessors extracted data, and we contacted authors of included papers for additional unpublished data. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether the conclusions agreed with the study results. Two assessors assessed risk of bias of included papers. We calculated pooled risk ratios (RR) for dichotomous data (with 95% confidence intervals). Main results Forty-eight papers were included. Industry sponsored studies more often had favorable efficacy results, risk ratio (RR): 1.32 (95% confidence interval (CI): 1.21 to 1.44), harms results RR: 1.87 (95% CI: 1.54 to 2.27) and conclusions RR: 1.31 (95% CI: 1.20 to 1.44) compared with non-industry sponsored studies. Ten papers reported on sponsorship and effect size, but could not be pooled due to differences in their reporting of data. The results were heterogeneous; five papers found larger effect sizes in industry sponsored studies compared with non-industry sponsored studies and five papers did not find a difference in effect size. Only two papers (including 120 device studies) reported separate data for devices and we did not find a difference between drug and device studies on the association between sponsorship and conclusions (test for interaction, P = 0.23). Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment and follow-up. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.32 (95% CI: 1.05 to 1.65), compared with non-industry sponsored studies. In industry sponsored studies, there was less agreement between the results and the conclusions than in non-industry sponsored studies, RR: 0.84 (95% CI: 0.70 to 1.01). Authors' conclusions Sponsorship of drug and device studies by the manufacturing company leads to more favorable results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.

Enhanced LSTM for Natural Language Inference

Abstract: Reasoning and inference are central to human and artificial intelligence. Modeling inference in human language is very challenging. With the availability of large annotated data (Bowman et al., 2015), it has recently become feasible to train neural network based inference models, which have shown to be very effective. In this paper, we present a new state-of-the-art result, achieving the accuracy of 88.6% on the Stanford Natural Language Inference Dataset. Unlike the previous top models that use very complicated network architectures, we first demonstrate that carefully designing sequential inference models based on chain LSTMs can outperform all previous models. Based on this, we further show that by explicitly considering recursive architectures in both local inference modeling and inference composition, we achieve additional improvement. Particularly, incorporating syntactic parsing information contributes to our best result—it further improves the performance even when added to the already very strong model.

Optimal database combinations for literature searches in systematic reviews: a prospective exploratory study.

Abstract: Within systematic reviews, when searching for relevant references, it is advisable to use multiple databases. However, searching databases is laborious and time-consuming, as syntax of search strategies are database specific. We aimed to determine the optimal combination of databases needed to conduct efficient searches in systematic reviews and whether the current practice in published reviews is appropriate. While previous studies determined the coverage of databases, we analyzed the actual retrieval from the original searches for systematic reviews. Since May 2013, the first author prospectively recorded results from systematic review searches that he performed at his institution. PubMed was used to identify systematic reviews published using our search strategy results. For each published systematic review, we extracted the references of the included studies. Using the prospectively recorded results and the studies included in the publications, we calculated recall, precision, and number needed to read for single databases and databases in combination. We assessed the frequency at which databases and combinations would achieve varying levels of recall (i.e., 95%). For a sample of 200 recently published systematic reviews, we calculated how many had used enough databases to ensure 95% recall. A total of 58 published systematic reviews were included, totaling 1746 relevant references identified by our database searches, while 84 included references had been retrieved by other search methods. Sixteen percent of the included references (291 articles) were only found in a single database; Embase produced the most unique references (n = 132). The combination of Embase, MEDLINE, Web of Science Core Collection, and Google Scholar performed best, achieving an overall recall of 98.3 and 100% recall in 72% of systematic reviews. We estimate that 60% of published systematic reviews do not retrieve 95% of all available relevant references as many fail to search important databases. Other specialized databases, such as CINAHL or PsycINFO, add unique references to some reviews where the topic of the review is related to the focus of the database. Optimal searches in systematic reviews should search at least Embase, MEDLINE, Web of Science, and Google Scholar as a minimum requirement to guarantee adequate and efficient coverage.

Vehicle Routing Problems for Drone Delivery

Abstract: Unmanned aerial vehicles, or drones, have the potential to significantly reduce the cost and time of making last-mile deliveries and responding to emergencies. Despite this potential, little work has gone into developing vehicle routing problems (VRPs) specifically for drone delivery scenarios. Existing VRPs are insufficient for planning drone deliveries: either multiple trips to the depot are not permitted, leading to solutions with excess drones, or the effect of battery and payload weight on energy consumption is not considered, leading to costly or infeasible routes. We propose two multitrip VRPs for drone delivery that address both issues. One minimizes costs subject to a delivery time limit, while the other minimizes the overall delivery time subject to a budget constraint. We mathematically derive and experimentally validate an energy consumption model for multirotor drones, demonstrating that energy consumption varies approximately linearly with payload and battery weight. We use this approximation to derive mixed integer linear programs for our VRPs. We propose a cost function that considers our energy consumption model and drone reuse, and apply it in a simulated annealing (SA) heuristic for finding suboptimal solutions to practical scenarios. To assist drone delivery practitioners with balancing cost and delivery time, the SA heuristic is used to show that the minimum cost has an inverse exponential relationship with the delivery time limit, and the minimum overall delivery time has an inverse exponential relationship with the budget. Numerical results confirm the importance of reusing drones and optimizing battery size in drone delivery VRPs.

Spatiotemporal Multiplier Networks for Video Action Recognition

Abstract: This paper presents a general ConvNet architecture for video action recognition based on multiplicative interactions of spacetime features. Our model combines the appearance and motion pathways of a two-stream architecture by motion gating and is trained end-to-end. We theoretically motivate multiplicative gating functions for residual networks and empirically study their effect on classification accuracy. To capture long-term dependencies we inject identity mapping kernels for learning temporal relationships. Our architecture is fully convolutional in spacetime and able to evaluate a video in a single forward pass. Empirical investigation reveals that our model produces state-of-the-art results on two standard action recognition datasets.

Practical recommendations for reporting Fine-Gray model analyses for competing risk data

Abstract: In survival analysis, a competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. Outcomes in medical research are frequently subject to competing risks. In survival analysis, there are 2 key questions that can be addressed using competing risk regression models: first, which covariates affect the rate at which events occur, and second, which covariates affect the probability of an event occurring over time. The cause-specific hazard model estimates the effect of covariates on the rate at which events occur in subjects who are currently event-free. Subdistribution hazard ratios obtained from the Fine-Gray model describe the relative effect of covariates on the subdistribution hazard function. Hence, the covariates in this model can also be interpreted as having an effect on the cumulative incidence function or on the probability of events occurring over time. We conducted a review of the use and interpretation of the Fine-Gray subdistribution hazard model in articles published in the medical literature in 2015. We found that many authors provided an unclear or incorrect interpretation of the regression coefficients associated with this model. An incorrect and inconsistent interpretation of regression coefficients may lead to confusion when comparing results across different studies. Furthermore, an incorrect interpretation of estimated regression coefficients can result in an incorrect understanding about the magnitude of the association between exposure and the incidence of the outcome. The objective of this article is to clarify how these regression coefficients should be reported and to propose suggestions for interpreting these coefficients.

The Bilingual Adaptation: How Minds Accommodate Experience

Abstract: According to some estimates, more than half of the world's population is multilingual to some extent. Because of the centrality of language use to human experience and the deep connections between linguistic and nonlinguistic processing, it would not be surprising to find that there are interactions between bilingualism and cognitive and brain processes. The present review uses the framework of experience-dependent plasticity to evaluate the evidence for systematic modifications of brain and cognitive systems that can be attributed to bilingualism. The review describes studies investigating the relation between bilingualism and cognition in infants and children, younger and older adults, and patients, using both behavioral and neuroimaging methods. Excluded are studies whose outcomes focus primarily on linguistic abilities because of their more peripheral contribution to the central question regarding experience-dependent changes to cognition. Although most of the research discussed in the review reports some relation between bilingualism and cognitive or brain outcomes, several areas of research, notably behavioral studies with young adults, largely fail to show these effects. These discrepancies are discussed and considered in terms of methodological and conceptual issues. The final section proposes an account based on "executive attention" to explain the range of research findings and to set out an agenda for the next steps in this field. (PsycINFO Database Record

Performance of the ATLAS trigger system in 2015

Abstract: During 2015 the ATLAS experiment recorded 3.8 fb(-1) of proton-proton collision data at a centre-of-mass energy of 13 TeV. The ATLAS trigger system is a crucial component of the experiment, respons ...

The Sloan Digital Sky Survey Quasar Catalog: Twelfth data release

Abstract: PRIN INAF; "Investissements d'Avenir" French Government [ANR-11-IDEX-0001-02]; Agence Nationale de la Recherche [ANR-08-BLAN-0222, ANR-12-BS05-0015]; NASA ADAP [NNX12AE38G]; NSF [1211112, 1515404, AST-1516784]; Alfred P. Sloan Foundation; National Science Foundation; US Department of Energy Office of Science; University of Arizona; Brazilian Participation Group; Brookhaven National Laboratory; Carnegie Mellon University; University of Florida; French Participation Group; German Participation Group; Harvard University; Instituto de Astrofisica de Canarias; Michigan State/Notre Dame/JINA Participation Group; Johns Hopkins University; Lawrence Berkeley National Laboratory; Max Planck Institute for Astrophysics; Max Planck Institute for Extraterrestrial Physics; New Mexico State University; New York University; Ohio State University; Pennsylvania State University; University of Portsmouth; Princeton University; Spanish Participation Group; University of Tokyo; University of Utah; Vanderbilt University; University of Virginia; University of Washington; Yale University; National Aeronautics and Space Administration; Office of Science of the US Department of Energy [DE-AC02-05CH11231]

Dark Matter Self-interactions and Small Scale Structure

Abstract: We review theories of dark matter (DM) beyond the collisionless paradigm, known as self-interacting dark matter (SIDM), and their observable implications for astrophysical structure in the Universe. Self-interactions are motivated, in part, due to the potential to explain long-standing (and more recent) small scale structure observations that are in tension with collisionless cold DM (CDM) predictions. Simple particle physics models for SIDM can provide a universal explanation for these observations across a wide range of mass scales spanning dwarf galaxies, low and high surface brightness spiral galaxies, and clusters of galaxies. At the same time, SIDM leaves intact the success of $\Lambda$CDM cosmology on large scales. This report covers the following topics: (1) small scale structure issues, including the core-cusp problem, the diversity problem for rotation curves, the missing satellites problem, and the too-big-to-fail problem, as well as recent progress in hydrodynamical simulations of galaxy formation; (2) N-body simulations for SIDM, including implications for density profiles, halo shapes, substructure, and the interplay between baryons and self-interactions; (3) semi-analytic Jeans-based methods that provide a complementary approach for connecting particle models with observations; (4) merging systems, such as cluster mergers (e.g., the Bullet Cluster) and minor infalls, along with recent simulation results for mergers; (5) particle physics models, including light mediator models and composite DM models; and (6) complementary probes for SIDM, including indirect and direct detection experiments, particle collider searches, and cosmological observations. We provide a summary and critical look for all current constraints on DM self-interactions and an outline for future directions.

A radio counterpart to a neutron star merger

Abstract: Gravitational waves have been detected from a binary neutron star merger event, GW170817. The detection of electromagnetic radiation from the same source has shown that the merger occurred in the outskirts of the galaxy NGC 4993, at a distance of 40 megaparsecs from Earth. We report the detection of a counterpart radio source that appears 16 days after the event, allowing us to diagnose the energetics and environment of the merger. The observed radio emission can be explained by either a collimated ultrarelativistic jet, viewed off-axis, or a cocoon of mildly relativistic ejecta. Within 100 days of the merger, the radio light curves will enable observers to distinguish between these models, and the angular velocity and geometry of the debris will be directly measurable by very long baseline interferometry.

OSIRIS-REx: Sample Return from Asteroid (101955) Bennu

Abstract: In May of 2011, NASA selected the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS-REx) asteroid sample return mission as the third mission in the New Frontiers program. The other two New Frontiers missions are New Horizons, which explored Pluto during a flyby in July 2015 and is on its way for a flyby of Kuiper Belt object 2014 MU69 on January 1, 2019, and Juno, an orbiting mission that is studying the origin, evolution, and internal structure of Jupiter. The spacecraft departed for near-Earth asteroid (101955) Bennu aboard an United Launch Alliance Atlas V 411 evolved expendable launch vehicle at 7:05 p.m. EDT on September 8, 2016, on a seven-year journey to return samples from Bennu. The spacecraft is on an outbound-cruise trajectory that will result in a rendezvous with Bennu in November 2018. The science instruments on the spacecraft will survey Bennu to measure its physical, geological, and chemical properties, and the team will use these data to select a site on the surface to collect at least 60 g of asteroid regolith. The team will also analyze the remote-sensing data to perform a detailed study of the sample site for context, assess Bennu’s resource potential, refine estimates of its impact probability with Earth, and provide ground-truth data for the extensive astronomical data set collected on this asteroid. The spacecraft will leave Bennu in 2021 and return the sample to the Utah Test and Training Range (UTTR) on September 24, 2023.

Topological cell clustering in the ATLAS calorimeters and its performance in LHC Run 1

Abstract: The reconstruction of the signal from hadrons and jets emerging from the proton–proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals. The resulting topological cell clusters have shape and location information, which is exploited to apply a local energy calibration and corrections depending on the nature of the cluster. Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS.

Association Between Wait Time and 30-Day Mortality in Adults Undergoing Hip Fracture Surgery.

Abstract: Importance Although wait times for hip fracture surgery have been linked to mortality and are being used as quality-of-care indicators worldwide, controversy exists about the duration of the wait that leads to complications. Objective To use population-based wait-time data to identify the optimal time window in which to conduct hip fracture surgery before the risk of complications increases. Design, Setting, and Participants Population-based, retrospective cohort study of adults undergoing hip fracture surgery between April 1, 2009, and March 31, 2014, at 72 hospitals in Ontario, Canada. Risk-adjusted restricted cubic splines modeled the probability of each complication according to wait time. The inflection point (in hours) when complications began to increase was used to define early and delayed surgery. To evaluate the robustness of this definition, outcomes among propensity-score matched early and delayed surgical patients were compared using percent absolute risk differences (RDs, with 95% CIs). Exposure Time elapsed from hospital arrival to surgery (in hours). Main Outcomes and Measures Mortality within 30 days. Secondary outcomes included a composite of mortality or other medical complications (myocardial infarction, deep vein thrombosis, pulmonary embolism, and pneumonia). Results Among 42 230 patients with hip fracture (mean [SD] age, 80.1 years [10.7], 70.5% women) who met study entry criteria, overall mortality at 30 days was 7.0%. The risk of complications increased when wait times were greater than 24 hours, irrespective of the complication considered. Compared with 13 731 propensity-score matched patients who received surgery earlier, 13 731 patients who received surgery after 24 hours had a significantly higher risk of 30-day mortality (898 [6.5%] vs 790 [5.8%]; % absolute RD, 0.79; 95% CI, 0.23-1.35) and the composite outcome (1680 [12.2%]) vs 1383 [10.1%]; % absolute RD, 2.16; 95% CI, 1.43-2.89). Conclusions and Relevance Among adults undergoing hip fracture surgery, increased wait time was associated with a greater risk of 30-day mortality and other complications. A wait time of 24 hours may represent a threshold defining higher risk.

A grounded theory of positive youth development through sport based on results from a qualitative meta-study.

Abstract: The overall purpose of this study was to create a model of positive youth development (PYD) through sport grounded in the extant qualitative literature. More specifically, the first objective was to review and evaluate qualitative studies of PYD in sport. The second objective was to analyze and synthesize findings from these studies. Following record identification and screening, 63 articles were retained for analysis. Meta-method analysis revealed strengths of studies were the use of multiple data collection and validity techniques, which produced high-quality data. Weaknesses were limited use of ‘named’ methodologies and inadequate reporting of sampling procedures. Philosophical perspectives were rarely reported, and theory was used sparingly. Results of an inductive meta-data analysis produced three categories: PYD climate (adult relationships, peer relationships, and parental involvement), life skills program focus (life skill building activities and transfer activities), and PYD outcomes (in ...

The basic reproduction number (R0) of measles: a systematic review.

Abstract: Summary The basic reproduction number, R nought (R 0 ), is defined as the average number of secondary cases of an infectious disease arising from a typical case in a totally susceptible population, and can be estimated in populations if pre-existing immunity can be accounted for in the calculation. R 0 determines the herd immunity threshold and therefore the immunisation coverage required to achieve elimination of an infectious disease. As R 0 increases, higher immunisation coverage is required to achieve herd immunity. In July, 2010, a panel of experts convened by WHO concluded that measles can and should be eradicated. Despite the existence of an effective vaccine, regions have had varying success in measles control, in part because measles is one of the most contagious infections. For measles, R 0 is often cited to be 12–18, which means that each person with measles would, on average, infect 12–18 other people in a totally susceptible population. We did a systematic review to find studies reporting rigorous estimates and determinants of measles R 0 . Studies were included if they were a primary source of R 0 , addressed pre-existing immunity, and accounted for pre-existing immunity in their calculation of R 0 . A search of key databases was done in January, 2015, and repeated in November, 2016, and yielded 10 883 unique citations. After screening for relevancy and quality, 18 studies met inclusion criteria, providing 58 R 0 estimates. We calculated median measles R 0 values stratified by key covariates. We found that R 0 estimates vary more than the often cited range of 12–18. Our results highlight the importance of countries calculating R 0 using locally derived data or, if this is not possible, using parameter estimates from similar settings. Additional data and agreed review methods are needed to strengthen the evidence base for measles elimination modelling.

A deep ALMA image of the Hubble Ultra Deep Field

Abstract: European Research Council via the award of an Advanced Grant; EC [312725]; European Research Council via the award of a Consolidator Grant; UK Science and Technology Facilities Council; FWO Pegasus Marie Curie Fellowship; European Research Council through the Advanced Grant [321302, 669253, 670193]; JSPS KAKENHI [JP15K17604]; Chulalongkorn University's CUniverse (CUAASC); Royal Society

A computational psychiatry approach identifies how alpha-2A noradrenergic agonist Guanfacine affects feature-based reinforcement learning in the macaque.

Abstract: Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves specific attention and learning mechanisms beyond working memory, and whether the drug effects can be formalized computationally to allow single subject predictions. We tested and confirmed these suggestions in a case study with a healthy nonhuman primate performing a feature-based reversal learning task evaluating performance using Bayesian and Reinforcement learning models. In an initial dose-testing phase we found a Guanfacine dose that increased performance accuracy, decreased distractibility and improved learning. In a second experimental phase using only that dose we examined the faster feature-based reversal learning with Guanfacine with single-subject computational modeling. Parameter estimation suggested that improved learning is not accounted for by varying a single reinforcement learning mechanism, but by changing the set of parameter values to higher learning rates and stronger suppression of non-chosen over chosen feature information. These findings provide an important starting point for developing nonhuman primate models to discern the synaptic mechanisms of attention and learning functions within the context of a computational neuropsychiatry framework.

Intermediate and advanced topics in multilevel logistic regression analysis

Abstract: Multilevel data occur frequently in health services, population and public health, and epidemiologic research. In such research, binary outcomes are common. Multilevel logistic regression models allow one to account for the clustering of subjects within clusters of higher-level units when estimating the effect of subject and cluster characteristics on subject outcomes. A search of the PubMed database demonstrated that the use of multilevel or hierarchical regression models is increasing rapidly. However, our impression is that many analysts simply use multilevel regression models to account for the nuisance of within-cluster homogeneity that is induced by clustering. In this article, we describe a suite of analyses that can complement the fitting of multilevel logistic regression models. These ancillary analyses permit analysts to estimate the marginal or population-average effect of covariates measured at the subject and cluster level, in contrast to the within-cluster or cluster-specific effects arising from the original multilevel logistic regression model. We describe the interval odds ratio and the proportion of opposed odds ratios, which are summary measures of effect for cluster-level covariates. We describe the variance partition coefficient and the median odds ratio which are measures of components of variance and heterogeneity in outcomes. These measures allow one to quantify the magnitude of the general contextual effect. We describe an R2 measure that allows analysts to quantify the proportion of variation explained by different multilevel logistic regression models. We illustrate the application and interpretation of these measures by analyzing mortality in patients hospitalized with a diagnosis of acute myocardial infarction. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study.

Abstract: Background Prescription opioid use is highly associated with risk of opioid-related death, with 1 of every 550 chronic opioid users dying within approximately 2.5 years of their first opioid prescription. Although gabapentin is widely perceived as safe, drug-induced respiratory depression has been described when gabapentin is used alone or in combination with other medications. Because gabapentin and opioids are both commonly prescribed for pain, the likelihood of co-prescription is high. However, no published studies have examined whether concomitant gabapentin therapy is associated with an increased risk of accidental opioid-related death in patients receiving opioids. The objective of this study was to investigate whether co-prescription of opioids and gabapentin is associated with an increased risk of accidental opioid-related mortality. Methods and findings We conducted a population-based nested case–control study among opioid users who were residents of Ontario, Canada, between August 1, 1997, and December 31, 2013, using administrative databases. Cases, defined as opioid users who died of an opioid-related cause, were matched with up to 4 controls who also used opioids on age, sex, year of index date, history of chronic kidney disease, and a disease risk index. After matching, we included 1,256 cases and 4,619 controls. The primary exposure was concomitant gabapentin use in the 120 days preceding the index date. A secondary analysis characterized gabapentin dose as low (<900 mg daily), moderate (900 to 1,799 mg daily), or high (≥1,800 mg daily). A sensitivity analysis examined the effect of concomitant nonsteroidal anti-inflammatory drug (NSAID) use in the preceding 120 days. Overall, 12.3% of cases (155 of 1,256) and 6.8% of controls (313 of 4,619) were prescribed gabapentin in the prior 120 days. After multivariable adjustment, co-prescription of opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI 1.61 to 2.47, p < 0.001; adjusted OR [aOR] 1.49, 95% CI 1.18 to 1.88, p < 0.001) compared to opioid prescription alone. In the dose–response analysis, moderate-dose (OR 2.05, 95% CI 1.46 to 2.87, p < 0.001; aOR 1.56, 95% CI 1.06 to 2.28, p = 0.024) and high-dose (OR 2.20, 95% CI 1.58 to 3.08, p < 0.001; aOR 1.58, 95% CI 1.09 to 2.27, p = 0.015) gabapentin use was associated with a nearly 60% increase in the odds of opioid-related death relative to no concomitant gabapentin use. As expected, we found no significant association between co-prescription of opioids and NSAIDs and opioid-related death (OR 1.11, 95% CI 0.98 to 1.27, p = 0.113; aOR 1.14, 95% CI 0.98 to 1.32, p = 0.083). In an exploratory analysis of patients at risk of combined opioid and gabapentin use, we found that 46.0% (45,173 of 98,288) of gabapentin users in calendar year 2013 received at least 1 concomitant prescription for an opioid. This study was limited to individuals eligible for public drug coverage in Ontario, we were only able to identify prescriptions reimbursed by the government and dispensed from retail pharmacies, and information on indication for gabapentin use was not available. Furthermore, as with all observational studies, confounding due to unmeasured variables is a potential source of bias. Conclusions In this study we found that among patients receiving prescription opioids, concomitant treatment with gabapentin was associated with a substantial increase in the risk of opioid-related death. Clinicians should consider carefully whether to continue prescribing this combination of products and, when the combination is deemed necessary, should closely monitor their patients and adjust opioid dose accordingly. Future research should investigate whether a similar interaction exists between pregabalin and opioids.

Construct Validation in Social and Personality Research: Current Practice and Recommendations

Abstract: The verity of results about a psychological construct hinges on the validity of its measurement, making construct validation a fundamental methodology to the scientific process. We reviewed a representative sample of articles published in the Journal of Personality and Social Psychology for construct validity evidence. We report that latent variable measurement, in which responses to items are used to represent a construct, is pervasive in social and personality research. However, the field does not appear to be engaged in best practices for ongoing construct validation. We found that validity evidence of existing and author-developed scales was lacking, with coefficient α often being the only psychometric evidence reported. We provide a discussion of why the construct validation framework is important for social and personality researchers and recommendations for improving practice.

Search for new high-mass phenomena in the dilepton final state using 36 fb−1 of proton-proton collision data at √s=13 TeV with the ATLAS detector

Abstract: A search is conducted for new resonant and non-resonant high-mass phenomena in dielectron and dimuon fi nal states. The search uses 36 : 1 fb(-1) of proton-proton collision data, collected at root ...

Synthesis of Black TiOx Nanoparticles by Mg Reduction of TiO2 Nanocrystals and their Application for Solar Water Evaporation

Abstract: TiOx (x < 2) nanoparticles with tunable colors from white to gray to blue–gray to black are synthesized by magnesium (Mg) reduction of white P25 TiO2 nanocrystals followed by removal of excess Mg with aqueous HCl and distilled water Increasing amounts of Mg smoothly decrease the oxygen content in TiOx which is responsible for the gradual increase in light absorption and concomitant darkening of its color from white to black with decreasing values of x The as-synthesized TiOx nanoparticles are spin-coated onto the surface of a stainless steel mesh followed by surface superhydrophobization in order to test their performance as a solar water evaporator Results from the tests show that the black TiOx efficiently generates water vapor with a solar thermal conversion efficiency as high as 50% under solar-simulated light irradiance at an intensity of 1000 W m–2 (1 Sun) Moreover, TiOx nanoparticles have inherent advantages over other materials used for solar water desalination, such as their tunable light absorption, low-cost, low-toxicity, superhydrophobicity, and chemical stability

The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy : an evidence review

Abstract: Duchenne Muscular Dystrophy (DMD) is a rapidly progressive, lethal neuromuscular disorder, present from birth, which occurs almost exclusively in males. We have reviewed contemporary evidence of burden, epidemiology, illness costs and treatment patterns of DMD. This systematic review adhered to published methods with information also sought from the web and contacting registries. Searches were carried out from 2005 to June 2015. The population of interest was individuals with clearly defined DMD or their carers. Nine thousand eight hundred fifty titles were retrieved from searches. Fifty-eight studies were reviewed with three assessed as high, 33 as medium and 22 as low quality. We found two studies reporting birth and four reporting point prevalence, three reporting mortality, 41 reporting severity and/or progression, 18 reporting treatment patterns, 12 reporting quality of life, two reporting utility measures, three reporting costs of illness and three treatment guidelines. Birth prevalence ranged from 15.9 to 19.5 per 100,000 live births. Point prevalence per 100,000 males was for France, USA, UK and Canada, 10.9, 1.9, 2.2 and 6.1 respectively. A study of adult DMD patients at a centre in France found median survival for those born between 1970 and 1994 was 40.95 years compared to 25.77 years for those born between 1955 and 1969. Loss of ambulation occurred at a median age of 12 and ventilation starts at about 20 years. There was international variation in use of corticosteroids, scoliosis surgery, ventilation and physiotherapy. The economic cost of DMD climbs dramatically with disease progression – rising as much as 5.7 fold from the early ambulatory phase to the non-ambulatory phase in Germany. This is the first systematic review of treatment, progression, severity and quality of life in DMD. It also provides the most recent description of the burden, epidemiology, illness costs and treatment patterns in DMD. There are evidence gaps, particularly in prevalence and mortality. People with DMD seem to be living longer, possibly due to corticosteroid use, cardiac medical management and ventilation. Future research should incorporate registry data to improve comparability across time and between countries and to investigate the quality of life impact as the condition progresses.

Ecology under lake ice

Abstract: Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer ‘growing seasons’. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.

Teen dating violence: a meta-analytic review of prevalence rates

Abstract: Objective: The goals of the present review were to determine the prevalence of physical and sexual TDV among adolescents, obtain the rates of teen dating violence (TDV) separately by gender, and examine the potential moderation effects of age, demographics, and measurement. Method: A systematic literature search elicited 101 studies reporting rates for youth aged 13 to 18. Results: Meta-analytic combination produced an overall prevalence of 20% for physical TDV and 9% for sexual TDV. Significant variability in rates was found, with physical TDV ranging from 1% to 61% and sexual TDV ranging from <1% to 54%. Gender differences in physical TDV were significant for perpetration (boys 13% vs. girls 25%) but not for victimization (21% boys and girls). A different pattern was observed for sexual TDV with girls reporting lower rates of perpetration compared with boys (3% vs. 10%) and higher rates of victimization (14% vs. 8%). Moderator analyses revealed higher rates in samples representing higher proportions of older teens (sexual TDV), cultural minority girls (physical TDV), and disadvantaged neighborhoods (physical TDV). Studies using broad measurement tools yielded higher rates of both forms of TDV across gender. Conclusions: Basing the meta-analysis on a large pool of studies with comparable samples, 1 in 5 adolescents reported physical TDV and roughly 1 in 10 reported sexual TDV. Systematic bias in boys’ and girls’ self-reports was evident along with high variability in TDV rates across studies and significant moderator influences. These findings are suggestive of substantive methodological challenges in extant studies. The obtained rates should be cautiously interpreted and future research should address the methodological limitations of self-reported TDV, taking into consideration the potential influences of gender, demographics, age, and measurement issues when designing TDV research.

A Circular RNA Binds To and Activates AKT Phosphorylation and Nuclear Localization Reducing Apoptosis and Enhancing Cardiac Repair.

Abstract: As central nodes in cardiomyocyte signaling, nuclear AKT appears to play a cardio-protective role in cardiovascular disease. Here we describe a circular RNA, circ-Amotl1 that is highly expressed in neonatal human cardiac tissue, and potentiates AKT-enhanced cardiomyocyte survival. We hypothesize that circ-Amotl1 binds to PDK1 and AKT1, leading to AKT1 phosphorylation and nuclear translocation. In primary cardiomyocytes, epithelial cells, and endothelial cells, we found that forced circ-Amotl1 expression increased the nuclear fraction of pAKT. We further detected increased nuclear pAKT in circ-Amotl1-treated hearts. In vivo, circ-Amotl1 expression was also found to be protective against Doxorubicin (Dox)-induced cardiomyopathy. Putative PDK1- and AKT1-binding sites were then identified in silico. Blocking oligonucleotides could reverse the effects of exogenous circ-Amotl1. We conclude that circ-Amotl1 physically binds to both PDK1 and AKT1, facilitating the cardio-protective nuclear translocation of pAKT.