bak deletion stimulates gastric epithelial proliferation and enhances Helicobacter felis-induced gastric atrophy and dysplasia in mice

Helicobacter infection causes a chronic superficial gastritis that in some cases progresses via atrophic gastritis to adenocarcinoma. Proapoptotic bak has been shown to regulate radiation-induced apoptosis in the stomach and colon and also susceptibility to colorectal carcinogenesis in vivo. Therefore we investigated the gastric mucosal pathology following H. felis infection in bak-null mice at 6 or 48 wk postinfection. Primary gastric gland culture from bak-null mice was also used to assess the effects of bak deletion on IFN-γ-, TNF-α-, or IL-1β-induced apoptosis. bak-null gastric corpus glands were longer, had increased epithelial Ki-67 expression, and contained fewer parietal and enteroendocrine cells compared with the wild type (wt). In wt mice, bak was expressed at the luminal surface of gastric corpus glands, and this increased 2 wk post-H. felis infection. Apoptotic cell numbers were decreased in bak-null corpus 6 and 48 wk following infection and in primary gland cultures following cytokine administration. Increased gastric epithelial Ki-67 labeling index was observed in C57BL/6 mice after H. felis infection, whereas no such increase was detected in bak-null mice. More severe gastric atrophy was observed in bak-null compared with C57BL/6 mice 6 and 48 wk postinfection, and 76% of bak-null compared with 25% of C57BL/6 mice showed evidence of gastric dysplasia following long-term infection. Collectively, bak therefore regulates gastric epithelial cell apoptosis, proliferation, differentiation, mucosal thickness, and susceptibility to gastric atrophy and dysplasia following H. felis infection

A serological investigation of caseous lymphadenitis in four flocks of sheep

A double antibody sandwich ELISA developed by ID-DLO, Lelystad to detect Corynebocterium pseudotuberculosis infection was used on 329 sheep from four pedigree Suffolk flocks in which clinical cases of caseous lymphadenitis (CLA) had occurred. At subsequent necropsy, typical CLA lesions were seen in 133 sheep, and the diagnosis was confirmed on culture. Lesions were most commonly seen in lungs (n = 46), parotid lymph nodes (n = 44), prescapular lymph nodes (n = 38) and mediastinal lymph nodes (n = 31). The sensitivity of the ELISA test for detecting culture-positive sheep was 0.88, while the specificity of the test was 0.55. The antibody ELISA detected 87.5 per cent of sheep that had CLA lesions restricted to internal organs only. It was concluded that the ELISA test has a valuable role in detecting sheep with both clinical and subclinical CLA

A circle-based method for detection of neural fibre cross-sections in classically stained 2D electron micrographs

Recent developments in electron microscopy now permit the unambiguous reconstruction of even the smallest neural fibres by human experts. However, manual reconstruction of an interesting volume of neural tissue would take thousands of person-years. Techniques to automate such reconstruction are therefore highly desirable and currently under active development. Here we present a novel circle-based technique and assess its performance on classically stained electron micrographs of the molecular layer of mouse cerebellar cortex. We compare its performance to a recently published pixel-based classifier (ilastik), selected because a similar random forest classifier from the same group has shown promising results on images of neural tissue. The performance of our algorithm and that of ilastik are similar, achieving approximately 50% on an overlap-based f-measure

Distinguishing personal use of drugs from drug supply: Approaches and challenges

The ability to fairly and justly distinguish between drug possession for personal use and drug possession for supply is a central feature of drug laws across the globe. Whether such distinctions pertain to decriminalisation of simple possession, or to the penalties associated with drug offences, such differentiation remains a core problem for policymakers. In this commentary, taking 91 different jurisdictions into consideration, we identify five different approaches to distinguishing personal use from supply: four of these involved quantification of an amount of drug (whether in weight or number of doses). The other approach relied on case-by-case judgement. Drawing upon survey data of drug use from nine countries, we provide an example of how the quantity bears little resemblance to drug use patterns, and does not take heterogeneity of drug use into account. While the non-quantified approach can lead to discriminatory and racialised policing, all of the quantification approaches also pose problems, largely concerned with arbitrary amounts. There appears to be no perfect way to differentiate possession for personal use from intentions to supply. This commentary opens up a number of important policy-relevant research questions given this central feature of drug policy design

Effectiveness and safety of oral HIV preexposure prophylaxis for all populations.

ObjectivePreexposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. This systematic review and meta-analysis evaluated the evidence for use of oral PrEP containing tenofovir disoproxil fumarate as an additional HIV prevention strategy in populations at substantial risk for HIV based on HIV acquisition, adverse events, drug resistance, sexual behavior, and reproductive health outcomes.DesignRigorous systematic review and meta-analysis.MethodsA comprehensive search strategy reviewed three electronic databases and conference abstracts through April 2015. Pooled effect estimates were calculated using random-effects meta-analysis.ResultsEighteen studies were included, comprising data from 39 articles and six conference abstracts. Across populations and PrEP regimens, PrEP significantly reduced the risk of HIV acquisition compared with placebo. Trials with PrEP use more than 70% demonstrated the highest PrEP effectiveness (risk ratio = 0.30, 95% confidence interval: 0.21-0.45, P < 0.001) compared with placebo. Trials with low PrEP use did not show a significantly protective effect. Adverse events were similar between PrEP and placebo groups. More cases of drug-resistant HIV infection were found among PrEP users who initiated PrEP while acutely HIV-infected, but incidence of acquiring drug-resistant HIV during PrEP use was low. Studies consistently found no association between PrEP use and changes in sexual risk behavior. PrEP was not associated with increased pregnancy-related adverse events or hormonal contraception effectiveness.ConclusionPrEP is protective against HIV infection across populations, presents few significant safety risks, and there is no evidence of behavioral risk compensation. The effective and cost-effective use of PrEP will require development of best practices for fostering uptake and adherence among people at substantial HIV risk

GravEn: Software for the simulation of gravitational wave detector network response

Physically motivated gravitational wave signals are needed in order to study the behaviour and efficacy of different data analysis methods seeking their detection. GravEn, short for Gravitational-wave Engine, is a MATLAB software package that simulates the sampled response of a gravitational wave detector to incident gravitational waves. Incident waves can be specified in a data file or chosen from among a group of pre-programmed types commonly used for establishing the detection efficiency of analysis methods used for LIGO data analysis. Every aspect of a desired signal can be specified, such as start time of the simulation (including inter-sample start times), wave amplitude, source orientation to line of sight, location of the source in the sky, etc. Supported interferometric detectors include LIGO, GEO, Virgo and TAMA.Comment: 10 Pages, 3 Figures, Presented at the 10th Gravitational Wave Data Analysis Workshop (GWDAW-10), 14-17 December 2005 at the University of Texas, Brownsvill

Inverse scattering approach to multiwavelength Fabry-Pérot laser design

A class of multiwavelength Fabry-Pérot lasers is introduced where the spectrum is tailored through a patterning of the cavity effective index. The cavity geometry is obtained using an inverse scattering approach and can be designed such that the spacing of discrete Fabry-Pérot lasing modes is limited only by the bandwidth of the inverted gain medium. A specific two-color semiconductor laser with a mode spacing in the THz region is designed, and measurements are presented demonstrating the simultaneous oscillation of the two wavelengths. The nonperiodic effective index profile of the particular two-color device considered is shown to be related to a Moiré or superstructure grating

Communication in cross-cultural consultations in primary care in Europe: the case for improvement. The rationale for the RESTORE FP 7 project

The purpose of this paper is to substantiate the importance of research about barriers and levers to the implementation of supports for cross-cultural communication in primary care settings in Europe. After an overview of migrant health issues, with the focus on communication in cross-cultural consultations in primary care and the importance of language barriers, we highlight the fact that there are serious problems in routine practice that persist over time and across different European settings. Language and cultural barriers hamper communication in consultations between doctors and migrants, with a range of negative effects including poorer compliance and a greater propensity to access emergency services. It is well established that there is a need for skilled interpreters and for professionals who are culturally competent to address this problem. A range of professional guidelines and training initiatives exist that support the communication in cross-cultural consultations in primary care. However, these are commonly not implemented in daily practice. It is as yet unknown why professionals do not accept or implement these guidelines and interventions, or under what circumstances they would do so. A new study involving six European countries, RESTORE (REsearch into implementation STrategies to support patients of different ORigins and language background in a variety of European primary care settings), aims to address these gaps in knowledge. It uses a unique combination of a contemporary social theory, normalisation process theory (NPT) and participatory learning and action (PLA) research. This should enhance understanding of the levers and barriers to implementation, as well as providing stakeholders, with the opportunity to generate creative solutions to problems experienced with the implementation of such interventions

Wing Defects in Drosophila xenicid Mutant Clones Are Caused by C-Terminal Deletion of Additional Sex Combs (Asx)

Background: The coordinated action of genes that control patterning, cell fate determination, cell size, and cell adhesion is required for proper wing formation in Drosophila. Defects in any of these basic processes can lead to wing aberrations, including blisters. The xenicid mutation was originally identified in a screen designed to uncover regulators of adhesion between wing surfaces [1]. Principal Findings: Here, we demonstrate that expression of the bPS integrin or the patterning protein Engrailed are not affected in developing wing imaginal discs in xenicid mutants. Instead, expression of the homeotic protein Ultrabithorax (Ubx) is strongly increased in xenicid mutant cells. Conclusion: Our results suggest that upregulation of Ubx transforms cells from a wing blade fate to a haltere fate, and that the presence of haltere cells within the wing blade is the primary defect leading to the adult wing phenotypes observed