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

NHS CHECK: protocol for a cohort study investigating the psychosocial impact of the COVID-19 pandemic on healthcare workers

INTRODUCTION: The COVID-19 pandemic has had profound effects on the working lives of healthcare workers (HCWs), but the extent to which their well-being and mental health have been affected remains unclear. This longitudinal cohort study aims to recruit a cohort of National Health Service (NHS) HCWs, conducting surveys at regular intervals to provide evidence about the prevalence of symptoms of mental disorders, and investigate associated factors such as occupational contexts and support interventions available. METHODS AND ANALYSIS: All staff, students and volunteers working in the 18 participating NHS Trusts in England will be sent emails inviting them to complete a survey at baseline, with email invitations for the follow-up surveys sent 6 months and 12 months later. Opening in late April 2020, the baseline survey collects data on demographics, occupational/organisational factors, experiences of COVID-19, validated measures of symptoms of poor mental health (eg, depression, anxiety, post-traumatic stress disorder), and constructs such as resilience and moral injury. These surveys will be complemented by in-depth psychiatric interviews with a sample of HCWs. Qualitative interviews will also be conducted, to gain deeper understanding of the support programmes used or desired by staff, and facilitators and barriers to accessing such programmes. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the Health Research Authority (reference: 20/HRA/210, IRAS: 282686) and local Trust Research and Development approval. Cohort data are collected via Qualtrics online survey software, pseudonymised and held on secure university servers. Participants are aware that they can withdraw from the study at any time, and there is signposting to support services if participants feel they need it. Only those consenting to be contacted about further research will be invited to participate in further components. Findings will be rapidly shared with NHS Trusts, and via academic publications in due course

Reshaping the testing pyramid:Utilisation of data-rich NDT techniques as a means to develop a 'high fidelity' component and sub-structure testing methodology for composites

A key issue in the certification of composite structures is the heavy reliance on ‘coupon level’ tests that do not always translate well to the sub-structure, component and full scale structural behaviour within a ‘building block’ or ‘testing pyramid’ framework. This has a strong bearing on the certification process as many of the design allowables and failure predictions are determined from the behaviour of coupon specimens. The overarching aim of this work is to develop an understanding into the behaviour of composites at the larger sub-component scales, which better represent the in-service behaviour of these structures, reducing the reliance on extensive coupon level testing. This requires non-destructive testing (NDT) methods that are scalable to large components. This study investigates the feasibilities of Thermoelastic Stress Analysis (TSA) and Digital Image Correlation (DIC) as scalable strain based NDT methods that provide full-field information to study the effects of defects on structural composite components. Both techniques are successfully demonstrated showing their capability for detecting the detrimental effects of fibre waviness (wrinkles) on a thick non-generic composite component. X-ray computed tomography (CT) is used to validate the observations made with the two strain based NDT techniques

A comparison of single and intersectional social identities associated with discrimination and mental health service use: data from the 2014 Adult Psychiatric Morbidity Survey in England

Inequities in mental health service use (MHSU) and treatment are influenced by social stratification processes linked to socially contextualised interactions between individuals, organisations and institutions. These complex relations underpin observed inequities and their experience by people at the intersections of social statuses. Discrimination is one important mechanism influencing such differences. We compared inequities in MHSU/treatment through single and intersectional status analyses, accounting for need. We assessed whether past-year discrimination differentially influences MHSU/treatment across single and intersecting statuses. Data came from a population survey (collected 2014–2015) nationally representative of English households (N = 7546). We used a theory and datadriven approach (latent class analysis) which identified five intersectional groups in the population comprising common combinations of social statuses. Single status analyses identified characteristics associated with MHSU/treatment (being a sexual minority (adjusted odds ratio (AOR) 1.65 95% CI:1.09-2.50), female (AOR 1.71, 95% CI:1.45–2.02), economically inactive (AOR 2.02, 95% CI:1.05–3.90), in the most deprived quintile (AOR 1.33, 95% CI:1.02–1.74), and Black (AOR 0.36 95% CI:0.20–0.66)). Intersectional analyses detected patterns not apparent from single status analyses. Compared to the most privileged group (“White British, highly educated, employed, high social class”), “Retired WhiteBritish” had greater odds of MHSU/treatment (AOR 1.88, 95% CI:1.53-2.32) while “Employed migrants” had lower odds (AOR 0.39, 95% CI:0.27–0.55). Past-year discrimination was associated with certain disadvantaged social statuses and greater MHSU/treatment but—except for sexual minorities—adjusting for discrimination had little influence using either analytic approach. Observing patterns only by single social statuses masks potentially unanticipated and contextually varying inequities. The latent class approach offers policy-relevant insights into patterns and mechanisms of inequity but may mask other key intersectional patterns by statuses less common or under represented in surveys (e.g. UK-born ethnic minority groups). We propose multiple, context-relevant, theory-driven approaches to intersectional understanding of mental health inequalities

ENCODE whole-genome data in the UCSC Genome Browser

The Encyclopedia of DNA Elements (ENCODE) project is an international consortium of investigators funded to analyze the human genome with the goal of producing a comprehensive catalog of functional elements. The ENCODE Data Coordination Center at The University of California, Santa Cruz (UCSC) is the primary repository for experimental results generated by ENCODE investigators. These results are captured in the UCSC Genome Bioinformatics database and download server for visualization and data mining via the UCSC Genome Browser and companion tools (Rhead et al. The UCSC Genome Browser Database: update 2010, in this issue). The ENCODE web portal at UCSC (http://encodeproject.org or http://genome.ucsc.edu/ENCODE) provides information about the ENCODE data and convenient links for access

The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA):Data on mortality, by HIV status and stage on the HIV care continuum, among the general population in seven longitudinal studies between 1989 and 2014

Timely progression of people living with HIV (PLHIV) from the point of infection through the pathway from diagnosis to treatment is important in ensuring effective care and treatment of HIV and preventing HIV-related deaths and onwards transmission of infection. Reliable, population-based estimates of new infections are difficult to obtain for the generalised epidemics in sub-Saharan Africa. Mortality data indicate disease burden and, if disaggregated along the continuum from diagnosis to treatment, can also reflect the coverage and quality of different HIV services. Neither routine statistics nor observational clinical studies can estimate mortality prior to linkage to care nor following disengagement from care. For this, population-based data are required.The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa brings together studies in Kenya, Malawi, South Africa, Tanzania, Uganda, and Zimbabwe. Eight studies have the necessary data to estimate mortality by HIV status, and seven can estimate mortality at different stages of the HIV care continuum. This data note describes a harmonised dataset containing anonymised individual-level information on survival by HIV status for adults aged 15 and above. Among PLHIV, the dataset provides information on survival during different periods: prior to diagnosis of infection; following diagnosis but before linkage to care; in pre-antiretroviral treatment (ART) care; in the first six months after ART initiation; among people continuously on ART for 6+ months; and among people who have ever interrupted ART

The UCSC Genome Browser Database: 2008 update

The University of California, Santa Cruz, Genome Browser Database (GBD) provides integrated sequence and annotation data for a large collection of vertebrate and model organism genomes. Seventeen new assemblies have been added to the database in the past year, for a total coverage of 19 vertebrate and 21 invertebrate species as of September 2007. For each assembly, the GBD contains a collection of annotation data aligned to the genomic sequence. Highlights of this year's additions include a 28-species human-based vertebrate conservation annotation, an enhanced UCSC Genes set, and more human variation, MGC, and ENCODE data. The database is optimized for fast interactive performance with a set of web-based tools that may be used to view, manipulate, filter and download the annotation data. New toolset features include the Genome Graphs tool for displaying genome-wide data sets, session saving and sharing, better custom track management, expanded Genome Browser configuration options and a Genome Browser wiki site. The downloadable GBD data, the companion Genome Browser toolset and links to documentation and related information can be found at: http://genome.ucsc.ed

Ethnic inequalities during clinical placement: A qualitative study of student nurses' experiences within the London National Health Service

AIM: To understand how student nurse experiences on clinical placement, within National Health Service (NHS) hospitals, differ for ethnic minority and White British groups. DESIGN: A qualitative thematic analysis with an inductive approach. METHODS: Data from semi-structured interviews with 21 London (United Kingdom) hospital-based student nurses were examined using thematic analysis. Participants were interviewed as part of the Tackling Inequalities and Discrimination Experiences in Health Services (TIDES) study and asked about their experiences during clinical placement. RESULTS: Five main themes were identified: (1) Role of mentors, (2) Discrimination and unfair treatment, (3) Speaking up/out, (4) Career progression, and (5) Consequences of adverse experiences. All themes were linked, with the social dynamics and workplace environment (referred to as "ward culture") providing a context that normalizes mistreatment experienced by nursing students. Students from ethnic minority backgrounds reported racism as well as cultural and/or religious microaggressions. While being valued for their race and ethnicity, White British students also experienced discrimination and inequity due to their age, sex, gender, and sexual orientation. Students from both White British and ethnic minority groups acknowledged that being treated badly was a barrier to career progression. Ethnic minority students also noted the lack of diverse representation within senior nursing positions discouraged career progression within the UK NHS. CONCLUSION: These initial experiences of inequality and discrimination are liable to shape a student's perspective of their profession and ability to progress within nursing. The NHS is responsible for ensuring that student nurses' developmental opportunities are equal, irrespective of ethnicity. IMPACT: Ward culture is perpetuated by others who normalize mistreatment and concurrently disadvantage ethnic minority students, making them feel unvalued. This in turn impacts both staff retention and career progression within the NHS. Training assessors should be aware of the existing culture of discrimination within clinical placements and work to eradicate it

The UCSC Genome Browser database: update 2010

The University of California, Santa Cruz (UCSC) Genome Browser website (http://genome.ucsc.edu/) provides a large database of publicly available sequence and annotation data along with an integrated tool set for examining and comparing the genomes of organisms, aligning sequence to genomes, and displaying and sharing users’ own annotation data. As of September 2009, genomic sequence and a basic set of annotation ‘tracks’ are provided for 47 organisms, including 14 mammals, 10 non-mammal vertebrates, 3 invertebrate deuterostomes, 13 insects, 6 worms and a yeast. New data highlights this year include an updated human genome browser, a 44-species multiple sequence alignment track, improved variation and phenotype tracks and 16 new genome-wide ENCODE tracks. New features include drag-and-zoom navigation, a Wiki track for user-added annotations, new custom track formats for large datasets (bigBed and bigWig), a new multiple alignment output tool, links to variation and protein structure tools, in silico PCR utility enhancements, and improved track configuration tools