A data-driven Bayesian optimisation framework for the design and stacking sequence selection of increased notched strength laminates

A novel Bayesian optimisation framework is proposed for the design of stronger stacking sequences in composite laminates. The framework is the first to incorporate high-fidelity progressive damage finite element modelling in a data-driven optimisation methodology. Gaussian process regression is used as a surrogate for the finite element model, minimising the number of computationally expensive objective function evaluations. The case of open-hole tensile strength is investigated and used as an example problem, considering typical aerospace design constraints, such as in-plane stiffness, balance of plies and laminate symmetry about the mid-plane. The framework includes a methodology that applies the design constraints without jeopardising surrogate model performance, ensuring that good feasible solutions are found. Three case studies are conducted, considering standard and non-standard angle laminates, and on-axis and misaligned loading, illustrating the benefits of the optimisation framework and its application as a general tool to efficiently establish aerospace design guidelines.</p

Parental obligations, care and HIV treatment: How care for others motivates self-care in Zimbabwe

This article examines how parental obligations of care intersect with HIV treatment-seeking behaviours and retention. It draws on qualitative data from eastern Zimbabwe, produced from 65 interviews. Drawing on theories of practice and care ethics, our analysis revealed that norms of parental obligation and care acted as key motivators for ongoing engagement with HIV services and treatment. Parents' attentiveness to the future needs of their children ( caring about), and sense of obligation ( taking care of) and improved ability to care ( caregiving) following treatment initiation, emerged as central to understanding their drive for self-care and engagement with HIV services

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

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

COMPRESSION TESTING OF LAMINATES OPTIMISED FOR DAMAGE TOLERANCE

SUMMARY Barely Visible Impact Damage (BVID) can occur when laminated composite material is subject to out-of-plane impact loads and can result in a significant reduction in compressive strength. This paper will report on compression testing of laminates optimised to maximise damage tolerance. Results show an increase of up to 29% in Compression After Impact (CAI) strength in comparison to a baseline configuration

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

Helicobacter pylori Membrane Vesicles Stimulate Innate Pro- and Anti-Inflammatory Responses and Induce Apoptosis in Jurkat T Cells

Persistent Helicobacter pylori infection induces chronic inflammation in the human gastric mucosa, which is associated with development of peptic ulceration, gastric atrophy, and gastric adenocarcinoma. It has been postulated that secretion of immunomodulatory molecules by H. pylori facilitates bacterial persistence, and membrane vesicles (MV), which have the potential to cross the gastric epithelial barrier, may mediate delivery of these molecules to host immune cells. However, bacterial MV effects on human immune cells remain largely uncharacterized to date. In the present study, we investigated the immunomodulatory effects of H. pylori MV with and without the vacuolating cytotoxin, VacA, which inhibits human T cell activity. We show a high degree of variability in the toxin content of vesicles between two H. pylori strains (SS1 and 60190). Vesicles from the more toxigenic 60190 strain contain more VacA (s1i1 type) than vesicles from the SS1 strain (s2i2 VacA), but engineering the SS1 strain to produce s1i1 VacA did not increase the toxin content of its vesicles. Vesicles from all strains tested, including a 60190 isogenic mutant null for VacA, strongly induced interleukin-10 (IL-10) and IL-6 production by human peripheral blood mononuclear cells independently of the infection status of the donor. Finally, we show that H. pylori MV induce T cell apoptosis and that this is enhanced by, but not completely dependent on, the carriage of VacA. Together, these findings suggest a role for H. pylori MV in the stimulation of innate pro- and anti-inflammatory responses and in the suppression of T cell immunity

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