A Role for the Vacuolating Cytotoxin, VacA, in Colonization and Helicobacter pylori-Induced Metaplasia in the Stomach

Carriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gas-tric adenocarcinoma. To our knowledge, we are the first to determine effects of different polymorphic forms of VacA on inflammation and metaplasia in the mouse stomach. Bacteria producing the less active s2/i2 form of VacA colonized mice more efficiently than mutants null for VacA or producing more active forms of it, providing the first evidence of a positive role for the minimally active s2/i2 toxin. Strains producing more active toxin forms induced more severe and extensive metaplasia and in flammation in the mouse stomach than strains producing weakly active (s2/i2) toxin. We also examined the association in humans, controlling for cag PAI status. In human gastric biopsy specimens, the vacA i1 allele was strongly associated with precancerous intestinal metaplasia, with almost complete absence of intestinal metaplasia in subjects infected with i2-type strains, even in a vacA s1, cagA+ background

Effects of ply angle and blocking on open-hole tensile strength of composite laminates:A design and certification perspective

The failure strength of carbon-fibre reinforced plastic laminates under open-hole tension varies considerably with ply angle, ply blocking and loading direction. Here, laminates with various standard-angle and non-standard angle stacking sequences are subjected to both on- and off-axis loading in a comprehensive experimental and progressive damage finite element analysis testing campaign. It is found that interlaminar and intralaminar matrix damage can be beneficial when accumulated sub-critically in ply blocks aligned with loading direction, but can also lead to significant strength decreases owing to edge failure. In such cases, a numerical edge treatment is proposed for more accurate representation of open-hole tensile strength in large structures where holes are positioned away from free edges. The solution suppresses edge failure and results in up to 80% strength increases, challenging the validity of standard open-hole tension testing and current design rules for some applications.</p

Tensile strain mapping in flat germanium membranes

Under the terms of the Creative Commons Attribution (CC BY) license to their work.-- et al.Scanning X-ray micro-diffraction has been used as a non-destructive probe of the local crystalline quality of a thin suspended germanium (Ge) membrane. A series of reciprocal space maps were obtained with ~4 μm spatial resolution, from which detailed information on the strain distribution, thickness, and crystalline tilt of the membrane was obtained. We are able to detect a systematic strain variation across the membranes, but show that this is negligible in the context of using the membranes as platforms for further growth. In addition, we show evidence that the interface and surface quality is improved by suspending the Ge.This work was carried out under the RCUK Basic Technology Programme supported by research Grant Nos. EP/F040784/1, EP/J001074/1, EP/L007010/1, by the European Community's Seventh Framework Programme (FP7/2007-2013) under Grant Agreement NANOFUNCTION No. 257375, by TAPHOR (MAT2012–31392), and by FP7 project MERGING (Grant No. 309150). This research used equipment funded by AWM and ERDF through the Science City Energy Efficiency project.Peer Reviewe

Providing a conceptual framework for HIV prevention cascades and assessing feasibility of empirical measurement with data from east Zimbabwe: a case study

BACKGROUND: The HIV treatment cascade illustrates the steps required for successful treatment and is a powerful advocacy and monitoring tool. Similar cascades for people susceptible to infection could improve HIV prevention programming. We aim to show the feasibility of using cascade models to monitor prevention programmes. METHODS: Conceptual prevention cascades are described taking intervention-centric and client-centric perspectives to look at supply, demand, and efficacy of interventions. Data from two rounds of a population-based study in east Zimbabwe are used to derive the values of steps for cascades for voluntary medical male circumcision (VMMC) and for partner reduction or condom use driven by HIV testing and counselling (HTC). FINDINGS: In 2009 to 2011 the availability of circumcision services was negligible, but by 2012 to 2013 about a third of the population had access. However, where it was available only 12% of eligible men sought to be circumcised leading to an increase in circumcision prevalence from 3·1% to 6·9%. Of uninfected men, 85·3% did not perceive themselves to be at risk of acquiring HIV. The proportions of men and women tested for HIV increased from 27·5% to 56·6% and from 61·1% to 79·6%, respectively, with 30·4% of men tested self-reporting reduced sexual partner numbers and 12·8% reporting increased condom use. INTERPRETATION: Prevention cascades can be populated to inform HIV prevention programmes. In eastern Zimbabwe programmes need to provide greater access to circumcision services and the design and implementation of associated demand creation activities. Whereas, HTC services need to consider how to increase reductions in partner numbers or increased condom use or should not be considered as contributing to prevention services for the HIV-negative adults. FUNDING: Wellcome Trust and Bill & Melinda Gates Foundation

Do female sex workers have lower uptake of HIV treatment services than non-sex workers? A cross-sectional study from east Zimbabwe.

OBJECTIVE: Globally, HIV disproportionately affects female sex workers (FSWs) yet HIV treatment coverage is suboptimal. To improve uptake of HIV services by FSWs, it is important to identify potential inequalities in access and use of care and their determinants. Our aim is to investigate HIV treatment cascades for FSWs and non-sex workers (NSWs) in Manicaland province, Zimbabwe, and to examine the socio-demographic characteristics and intermediate determinants that might explain differences in service uptake. METHODS: Data from a household survey conducted in 2009-2011 and a parallel snowball sample survey of FSWs were matched using probability methods to reduce under-reporting of FSWs. HIV treatment cascades were constructed and compared for FSWs (n=174) and NSWs (n=2555). Determinants of service uptake were identified a priori in a theoretical framework and tested using logistic regression. RESULTS: HIV prevalence was higher in FSWs than in NSWs (52.6% vs 19.8%; age-adjusted OR (AOR) 4.0; 95% CI 2.9 to 5.5). In HIV-positive women, FSWs were more likely to have been diagnosed (58.2% vs 42.6%; AOR 1.62; 1.02-2.59) and HIV-diagnosed FSWs were more likely to initiate ART (84.9% vs 64.0%; AOR 2.33; 1.03-5.28). No difference was found for antiretroviral treatment (ART) adherence (91.1% vs 90.5%; P=0.9). FSWs' greater uptake of HIV treatment services became non-significant after adjusting for intermediate factors including HIV knowledge and risk perception, travel time to services, physical and mental health, and recent pregnancy. CONCLUSION: FSWs are more likely to take up testing and treatment services and were closer to achieving optimal outcomes along the cascade compared with NSWs. However, ART coverage was low in all women at the time of the survey. FSWs' need for, knowledge of and proximity to HIV testing and treatment facilities appear to increase uptake

Spatial patterns of HIV prevalence and Service Use in East Zimbabwe: implications for future targeting of interventions

Introduction: Focusing resources for HIV control on geographic areas of greatest need in countries with generalised epidemics has been recommended to increase cost-effectiveness. However, socio-economic inequalities between areas of high and low prevalence could raise equity concerns and have been largely overlooked. We describe spatial patterns in HIV prevalence in east Zimbabwe and test for inequalities in accessibility and uptake of HIV services prior to the introduction of spatially-targeted programmes. Methods: 8092 participants in an open-cohort study were geo-located to 110 locations. HIV prevalence and HIV testing and counselling (HTC) uptake were mapped with ordinary kriging. Clusters of high or low HIV prevalence were detected with Kulldorff statistics, and the socio-economic characteristics and sexual risk behaviours of their populations, and levels of local HIV service availability (measured in travel distance) and uptake were compared. Kulldorff statistics were also determined for HTC, antiretroviral therapy (ART), and voluntary medical male circumcision (VMMC) uptake. Results: One large and one small high HIV prevalence cluster (relative risk [RR]=1.78, 95% confidence interval [CI]=1.53–2.07; RR=2.50, 95% CI=2.08–3.01) and one low-prevalence cluster (RR=0.70, 95% CI=0.60–0.82) were detected. The larger high-prevalence cluster was urban with a wealthier population and more high-risk sexual behaviour than outside the cluster. Despite better access to HIV services, there was lower HTC uptake in the high-prevalence cluster (odds ratio [OR] of HTC in past 3 years: OR=0.80, 95% CI=0.66–0.97). The low-prevalence cluster was predominantly rural with a poorer population and longer travel distances to HIV services; however, uptake of HIV services was not reduced. Conclusions: High-prevalence clusters can be identified to which HIV control resources could be targeted. To date, poorer access to HIV services in the poorer low-prevalence areas has not resulted in lower service uptake, while there is significantly lower uptake of HTC in the high-prevalence cluster where health service access is better. Given the high levels of risky sexual behaviour and lower uptake of HTC services, targeting high-prevalence clusters may be cost-effective in this setting. If spatial targeting is introduced, inequalities in HIV service uptake may be avoided through mobile service provision for lower prevalence areas

Variation resources at UC Santa Cruz

The variation resources within the University of California Santa Cruz Genome Browser include polymorphism data drawn from public collections and analyses of these data, along with their display in the context of other genomic annotations. Primary data from dbSNP is included for many organisms, with added information including genomic alleles and orthologous alleles for closely related organisms. Display filtering and coloring is available by variant type, functional class or other annotations. Annotation of potential errors is highlighted and a genomic alignment of the variant's flanking sequence is displayed. HapMap allele frequencies and linkage disequilibrium (LD) are available for each HapMap population, along with non-human primate alleles. The browsing and analysis tools, downloadable data files and links to documentation and other information can be found at