Semiparametric posterior corrections

We present a new approach to semiparametric inference using corrected posterior distributions. The method allows us to leverage the adaptivity, regularization and predictive power of nonparametric Bayesian procedures to estimate low-dimensional functionals of interest without being restricted by the holistic Bayesian formalism. Starting from a conventional nonparametric posterior, we target the functional of interest by transforming the entire distribution with a Bayesian bootstrap correction. We provide conditions for the resulting $\textit{one-step posterior}$ to possess calibrated frequentist properties and specialize the results for several canonical examples: the integrated squared density, the mean of a missing-at-random outcome, and the average causal treatment effect on the treated. The procedure is computationally attractive, requiring only a simple, efficient post-processing step that can be attached onto any arbitrary posterior sampling algorithm. Using the ACIC 2016 causal data analysis competition, we illustrate that our approach can outperform the existing state-of-the-art through the propagation of Bayesian uncertainty.Comment: 53 page

Edge guards on a fortress

Includes bibliographical references (p. 16).Cover title.At head of title: Computer science publication.published_or_final_versio

Tubulin nucleotide status controls Sas-4-dependent pericentriolar material recruitment

Regulated centrosome biogenesis is required for accurate cell division and for maintaining genome integrity1. Centrosomes consist of a centriole pair surrounded by a protein network known as pericentriolar material (PCM)1. PCM assembly is a tightly regulated, critical step that determines a centrosome’s size and capability2–4. Here, we report a role for tubulin in regulating PCM recruitment via the conserved centrosomal protein Sas-4. Tubulin directly binds to Sas-4; together they are components of cytoplasmic complexes of centrosomal proteins5,6. A Sas-4 mutant, which cannot bind tubulin, enhances centrosomal protein complex formation and has abnormally large centrosomes with excessive activity. These suggest that tubulin negatively regulates PCM recruitment. Whereas tubulin-GTP prevents Sas-4 from forming protein complexes, tubulin-GDP promotes it. Thus, tubulin’s regulation of PCM recruitment depends on its GTP/GDP-bound state. These results identify a role for tubulin in regulating PCM recruitment independent of its well-known role as a building block of microtubules7. Based on its guanine bound state, tubulin can act as a molecular switch in PCM recruitment

Poverty alleviation policies and action in Hong Kong : an analysis of public engagement strategies

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Comparing Artificial Neural Networks, General Linear Models and Support Vector Machines in Building Predictive Models for Small Interfering RNAs

Exogenous short interfering RNAs (siRNAs) induce a gene knockdown effect in cells by interacting with naturally occurring RNA processing machinery. However not all siRNAs induce this effect equally. Several heterogeneous kinds of machine learning techniques and feature sets have been applied to modeling siRNAs and their abilities to induce knockdown. There is some growing agreement to which techniques produce maximally predictive models and yet there is little consensus for methods to compare among predictive models. Also, there are few comparative studies that address what the effect of choosing learning technique, feature set or cross validation approach has on finding and discriminating among predictive models.Three learning techniques were used to develop predictive models for effective siRNA sequences including Artificial Neural Networks (ANNs), General Linear Models (GLMs) and Support Vector Machines (SVMs). Five feature mapping methods were also used to generate models of siRNA activities. The 2 factors of learning technique and feature mapping were evaluated by complete 3x5 factorial ANOVA. Overall, both learning techniques and feature mapping contributed significantly to the observed variance in predictive models, but to differing degrees for precision and accuracy as well as across different kinds and levels of model cross-validation.The methods presented here provide a robust statistical framework to compare among models developed under distinct learning techniques and feature sets for siRNAs. Further comparisons among current or future modeling approaches should apply these or other suitable statistically equivalent methods to critically evaluate the performance of proposed models. ANN and GLM techniques tend to be more sensitive to the inclusion of noisy features, but the SVM technique is more robust under large numbers of features for measures of model precision and accuracy. Features found to result in maximally predictive models are not consistent across learning techniques, suggesting care should be taken in the interpretation of feature relevance. In the models developed here, there are statistically differentiable combinations of learning techniques and feature mapping methods where the SVM technique under a specific combination of features significantly outperforms all the best combinations of features within the ANN and GLM techniques

Astrocytic αVβ3 Integrin Inhibits Neurite Outgrowth and Promotes Retraction of Neuronal Processes by Clustering Thy-1

Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to αVβ3 integrin in trans eliciting responses in astrocytes. Nonetheless, whether αVβ3 integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of αVβ3 integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous αVβ3 integrin restricted neurite outgrowth. Likewise, αVβ3-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(−) CAD cells. In differentiating primary neurons exposed to αVβ3-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, αVβ3-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by αVβ3 integrin. Binding of αVβ3-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, αVβ3-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that αVβ3 integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage