Arsenic exposure and outcomes of antimonial treatment in visceral leishmaniasis patients in bihar, India:a retrospective cohort study

Funding: This work was supported by a Clinical PhD Fellowship to MRP (090665) and a Principal Research Fellowship to AHF (079838) from the Wellcome Trust (http://www.wellcome.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Adaptation of a Couple-Based HIV Intervention for Methamphetamine-Involved African American Men who have Sex with Men

In the U.S., incidence of HIV infection among men who have sex with men (MSM) has steadily increased since the 1990s. This points to a need for innovation to address both emerging trends as well as longer-standing disparities in HIV risk and transmission among MSM, such as the elevated rates of HIV/STIs among African American MSM and methamphetamine users. While couple-based sexual risk reduction interventions are a promising avenue to reduce HIV/STI transmission, prior research has been almost exclusively with heterosexual couples. We sought to adapt an existing, evidence-based intervention—originally developed and tested with heterosexual couples—for a new target population consisting of African American MSM in a longer-term same-sex relationship where at least one partner uses methamphetamine. The adaptation process primarily drew from data obtained from a series of focus groups with 8 couples from the target population. Attention is given to the methods used to overcome challenges faced in this adaptation process: limited time, a lead investigator who is phenotypically different from the target population, a dearth of descriptive information on the experiences and worldviews among the target population, and a concomitant lack of topical experts. We also describe a visualization tool used to ensure that the adaptation process promotes and maintains adherence to the theory that guides the intervention and behavior change. The process culminated with an intervention adapted for the new target population as well as preliminary indications that a couple-based sexual-risk reduction intervention for African American, methamphetamine-involved male couples is feasible and attractive

Spin Caloritronics

This is a brief overview of the state of the art of spin caloritronics, the science and technology of controlling heat currents by the electron spin degree of freedom (and vice versa).Comment: To be published in "Spin Current", edited by S. Maekawa, E. Saitoh, S. Valenzuela and Y. Kimura, Oxford University Pres

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

A genome-wide association study of corneal astigmatism: The CREAM Consortium

PURPOSE: To identify genes and genetic markers associated with corneal astigmatism. METHODS: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. RESULTS: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08–1.16), p=5.55×10−9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans—claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). CONCLUSIONS: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism

A genome-wide association study for corneal astigmatism: The CREAM Consortium

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis was performed of genome-wide association studies (GWAS) of corneal astigmatism undertaken for 14 European ancestry (N = 22,250) and 8 Asian ancestry (N = 9,120) cohorts by the CREAM Consortium. Cases were defined as having >0.75 D of corneal astigmatism. For the meta-analysed results of European ancestry cohorts, subsequent gene-based and gene-set analyses were performed using VEGAS2 and MAGMA software. Additionally, estimates of SNP-based heritability for corneal and refractive astigmatism and spherical equivalent were calculated for Europeans using LD score regression. Results: Meta-analysis of all cohorts identified a genome-wide significant locus near the gene PDGFRA (platelet derived growth factor receptor alpha): top SNP: rs7673984, odds ratio = 1.12 (95% CI: 1.08-1.16), P = 5.55 x 10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified 3 novel candidate genes for corneal astigmatism in Europeans: CLDN7 (claudin-7), ACP2 (acid phosphatase 2, lysosomal) and TNFAIP8L3 (TNF alpha induced protein 8 like 3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified 3 novel candidate genes CLDN7, ACP2 and TNFAIP8L3 that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors to the development of astigmatism

A Case Study for Large-Scale Human Microbiome Analysis Using JCVI’s Metagenomics Reports (METAREP)

As metagenomic studies continue to increase in their number, sequence volume and complexity, the scalability of biological analysis frameworks has become a rate-limiting factor to meaningful data interpretation. To address this issue, we have developed JCVI Metagenomics Reports (METAREP) as an open source tool to query, browse, and compare extremely large volumes of metagenomic annotations. Here we present improvements to this software including the implementation of a dynamic weighting of taxonomic and functional annotation, support for distributed searches, advanced clustering routines, and integration of additional annotation input formats. The utility of these improvements to data interpretation are demonstrated through the application of multiple comparative analysis strategies to shotgun metagenomic data produced by the National Institutes of Health Roadmap for Biomedical Research Human Microbiome Project (HMP) (http://nihroadmap.nih.gov). Specifically, the scalability of the dynamic weighting feature is evaluated and established by its application to the analysis of over 400 million weighted gene annotations derived from 14 billion short reads as predicted by the HMP Unified Metabolic Analysis Network (HUMAnN) pipeline. Further, the capacity of METAREP to facilitate the identification and simultaneous comparison of taxonomic and functional annotations including biological pathway and individual enzyme abundances from hundreds of community samples is demonstrated by providing scenarios that describe how these data can be mined to answer biological questions related to the human microbiome. These strategies provide users with a reference of how to conduct similar large-scale metagenomic analyses using METAREP with their own sequence data, while in this study they reveal insights into the nature and extent of variation in taxonomic and functional profiles across body habitats and individuals. Over one thousand HMP WGS datasets and the latest open source code are available at http://www.jcvi.org/hmp-metarep

MSOAR 2.0: Incorporating tandem duplications into ortholog assignment based on genome rearrangement

<p>Abstract</p> <p>Background</p> <p>Ortholog assignment is a critical and fundamental problem in comparative genomics, since orthologs are considered to be functional counterparts in different species and can be used to infer molecular functions of one species from those of other species. MSOAR is a recently developed high-throughput system for assigning one-to-one orthologs between closely related species on a genome scale. It attempts to reconstruct the evolutionary history of input genomes in terms of genome rearrangement and gene duplication events. It assumes that a gene duplication event inserts a duplicated gene into the genome of interest at a random location (<it>i.e.</it>, the random duplication model). However, in practice, biologists believe that genes are often duplicated by tandem duplications, where a duplicated gene is located next to the original copy (<it>i.e.</it>, the tandem duplication model).</p> <p>Results</p> <p>In this paper, we develop MSOAR 2.0, an improved system for one-to-one ortholog assignment. For a pair of input genomes, the system first focuses on the tandemly duplicated genes of each genome and tries to identify among them those that were duplicated after the speciation (<it>i.e.</it>, the so-called inparalogs), using a simple phylogenetic tree reconciliation method. For each such set of tandemly duplicated inparalogs, all but one gene will be deleted from the concerned genome (because they cannot possibly appear in any one-to-one ortholog pairs), and MSOAR is invoked. Using both simulated and real data experiments, we show that MSOAR 2.0 is able to achieve a better sensitivity and specificity than MSOAR. In comparison with the well-known genome-scale ortholog assignment tool InParanoid, Ensembl ortholog database, and the orthology information extracted from the well-known whole-genome multiple alignment program MultiZ, MSOAR 2.0 shows the highest sensitivity. Although the specificity of MSOAR 2.0 is slightly worse than that of InParanoid in the real data experiments, it is actually better than that of InParanoid in the simulation tests.</p> <p>Conclusions</p> <p>Our preliminary experimental results demonstrate that MSOAR 2.0 is a highly accurate tool for one-to-one ortholog assignment between closely related genomes. The software is available to the public for free and included as online supplementary material.</p

The effect of a manual instrumentation technique on five types of premolar root canal geometry assessed by microcomputed tomography and three-dimensional reconstruction

<p>Abstract</p> <p>Background</p> <p>Together with diagnosis and treatment planning, a good knowledge of the root canal system and its frequent variations is a necessity for successful root canal therapy. The selection of instrumentation techniques for variants in internal anatomy of teeth has significant effects on the shaping ability and cleaning effectiveness. The aim of this study was to reveal the differences made by including variations in the internal anatomy of premolars into the study protocol for investigation of a single instrumentation technique (hand ProTaper instruments) assessed by microcomputed tomography and three-dimensional reconstruction.</p> <p>Methods</p> <p>Five single-root premolars, whose root canal systems were classified into one of five types, were scanned with micro-CT before and after preparation with a hand ProTaper instrument. Instrumentation characteristics were measured quantitatively in 3-D using a customized application framework based on MeVisLab. Numeric values were obtained for canal surface area, volume, volume changes, percentage of untouched surface, dentin wall thickness, and the thickness of dentin removed. Preparation errors were also evaluated using a color-coded reconstruction.</p> <p>Results</p> <p>Canal volumes and surface areas were increased after instrumentation. Prepared canals of all five types were straightened, with transportation toward the inner aspects of S-shaped or multiple curves. However, a ledge was formed at the apical third curve of the type II canal system and a wide range in the percentage of unchanged canal surfaces (27.4-83.0%) was recorded. The dentin walls were more than 0.3 mm thick except in a 1 mm zone from the apical surface and the hazardous area of the type II canal system after preparation with an F3 instrument.</p> <p>Conclusions</p> <p>The 3-D color-coded images showed different morphological changes in the five types of root canal systems shaped with the same hand instrumentation technique. Premolars are among the most complex teeth for root canal treatment and instrumentation techniques for the root canal systems of premolars should be selected individually depending on the 3-D canal configuration of each tooth. Further study is needed to demonstrate the differences made by including variations in the internal anatomy of teeth into the study protocol of clinical RCT for identifying the best preparation technique.</p