Examining the Factors Affecting PrEP Implementation Within Community-Based HIV Testing Sites in Florida: A Mixed Methods Study Applying the Consolidated Framework for Implementation Research.

HIV testing/counseling is a critical point during which non-clinical staff could intervene, discuss and/or refer clients for pre-exposure prophylaxis (PrEP). This analysis investigated the contextual factors affecting PrEP implementation within HIV testing sites. Two generalized linear mixed models were conducted to estimate PrEP implementation as a function of constructs from the Consolidated Framework for Implementation Research (CFIR). Qualitative interviews were analyzed thematically. Data integration occurred via joint analysis and triangulation. Constructs from the CFIR domain Characteristics of Individuals did not predict PrEP implementation when controlling for demographic characteristics; qualitative data signaled divergent findings in PrEP knowledge. Within the CFIR domains Inner and Outer Settings, relevant priority and available resources predicted PrEP implementation; qualitative data confirmed the importance of available resources and provided insight into the impact of cosmopolitanism and leadership. Addressing the contextual factors that affect PrEP implementation may help HIV testing staff to better implement PrEP programs.

The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts.

We recently reported the association of the PCSK6 gene with handedness through a quantitative genome-wide association study (GWAS; P < 0.5 × 10(-8)) for a relative hand skill measure in individuals with dyslexia. PCSK6 activates Nodal, a morphogen involved in regulating left-right body axis determination. Therefore, the GWAS data suggest that the biology underlying the patterning of structural asymmetries may also contribute to behavioural laterality, e.g. handedness. The association is further supported by an independent study reporting a variable number tandem repeat (VNTR) within the same PCSK6 locus to be associated with degree of handedness in a general population cohort. Here, we have conducted a functional analysis of the PCSK6 locus combining further genetic analysis, in silico predictions and molecular assays. We have shown that the previous GWAS signal was not tagging a VNTR effect, suggesting that the two markers have independent effects. We demonstrated experimentally that one of the top GWAS-associated markers, rs11855145, directly alters the binding site for a nuclear factor. Furthermore, we have shown that the predicted regulatory region adjacent to rs11855415 acts as a bidirectional promoter controlling the expression of novel RNA transcripts. These include both an antisense long non-coding RNA (lncRNA) and a short PCSK6 isoform predicted to be coding. This is the first molecular characterization of a handedness-associated locus that supports the role of common variants in non-coding sequences in influencing complex phenotypes through gene expression regulation.

Homogenization of three-dimensional metamaterial objects and validation by a fast surface-integral equation solver.

A homogenization model is applied to describe the wave interaction with finite three-dimensional metamaterial objects composed of periodic arrays of magnetodielectric spheres and is validated with full-wave numerical simulations. The homogenization is based on a dipolar model of the inclusions, which is shown to hold even in the case of densely packed arrays once weak forms of spatial dispersion and the full dynamic array coupling are taken into account. The numerical simulations are based on a fast surface-integral equation solver that enables the analysis of scattering from complex piecewise homogeneous objects. We validate the homogenization model by considering electrically large disk- and cube-shaped arrays and quantify the accuracy of the transition from an array of spheres to a homogeneous object as a function of the array size. Simulation results show that the fields scattered from large arrays with up to one thousand spheres and equivalent homogeneous objects agree well, not only far away from the arrays but also near them.

Meta-evaluation of a whole systems programme, ActEarly: A study protocol.

INTRODUCTION: Living in an area with high levels of child poverty predisposes children to poorer mental and physical health. ActEarly is a 5-year research programme that comprises a large number of interventions (>20) with citizen science and co-production embedded. It aims to improve the health and well-being of children and families living in two areas of the UK with high levels of deprivation; Bradford in West Yorkshire, and the London Borough of Tower Hamlets. This protocol outlines the meta-evaluation (an evaluation of evaluations) of the ActEarly programme from a systems perspective, where individual interventions are viewed as events in the wider policy system across the two geographical areas. It includes investigating the programme's impact on early life health and well-being outcomes, interdisciplinary prevention research collaboration and capacity building, and local and national decision making. METHODS: The ActEarly meta-evaluation will follow and adapt the five iterative stages of the 'Evaluation of Programmes in Complex Adaptive Systems' (ENCOMPASS) framework for evaluation of public health programmes in complex adaptive systems. Theory-based and mixed-methods approaches will be used to investigate the fidelity of the ActEarly research programme, and whether, why and how ActEarly contributes to changes in the policy system, and whether alternative explanations can be ruled out. Ripple effects and systems mapping will be used to explore the relationships between interventions and their outcomes, and the degree to which the ActEarly programme encouraged interdisciplinary and prevention research collaboration as intended. A computer simulation model ("LifeSim") will also be used to evaluate the scale of the potential long-term benefits of cross-sectoral action to tackle the financial, educational and health disadvantages faced by children in Bradford and Tower Hamlets. Together, these approaches will be used to evaluate ActEarly's dynamic programme outputs at different system levels and measure the programme's system changes on early life health and well-being. DISCUSSION: This meta-evaluation protocol presents our plans for using and adapting the ENCOMPASS framework to evaluate the system-wide impact of the early life health and well-being programme, ActEarly. Due to the collaborative and non-linear nature of the work, we reserve the option to change and query some of our evaluation choices based on the feedback we receive from stakeholders to ensure that our evaluation remains relevant and fit for purpose.

Developing a model for health determinants research within local government: lessons from a large, urban local authority.

Background: Socio-economic, cultural and environmental conditions strongly affect health across the life course. Local government plays a key role in influencing these wider determinants of health and levels of inequality within their communities. However, they lack the research infrastructure and culture that would enable them to develop an evidence-based approach to tackling the complex drivers of those conditions. Methods: We undertook a scoping project to explore the potential for, and what would be needed to develop a local authority research system for the City of Bradford, UK. This included identifying the current research landscape and any barriers and enablers to research activity within the local authority using qualitative individual and focus group interviews, a rapid review of existing local research system models, scoping of the use of evidence in decision making and training opportunities and existing support for local government research. Results: We identified four key themes important to developing and sustaining a research system: leadership, resource and capacity, culture, partnerships. Some use of research in decision making was evident but research training opportunities within the local authority were limited. Health research funders are slowly adapting to the local government environment, but this remains limited and more work is needed to shift the centre of gravity towards public health, local government and the community more generally.  Conclusions: We propose a model for a local authority research system that can guide the development of an exemplar whole system research framework that includes research infrastructure, data sharing, research training and skills, and co-production with local partners, to choose, use, generate, and deliver research in local government.

PrEP Implementation Behaviors of Community-Based HIV Testing Staff: A Mixed-Methods Approach Using Latent Class Analysis.

BACKGROUND: Pre-exposure Prophylaxis (PrEP) is an important option for HIV prevention, but the approach has reached a limited number of people at risk of HIV infection. METHODS: A mixed-methods concurrent triangulation design was used to investigate unobserved subgroups of staff who provide community-based, publicly funded HIV testing in Florida (USA). PrEP implementation groups, or classes, were determined using latent class analysis. Generalized linear mixed models were used to estimate PrEP implementation as a function of staff characteristics. In-depth interviews based on the Consolidated Framework for Implementation Research were analyzed thematically. RESULTS: Based on fit statistics and theoretical relevance, a 3-class latent class analysis was selected. Class 1 ("Universal") staff were highly likely to talk about PrEP with their clients, regardless of client eligibility. Class 2 ("Eligibility dependent") staff were most likely to discuss PrEP if they believed their client was eligible. Class 3 ("Limited") staff sometimes spoke to clients about PrEP, but not systematically. In multivariate analyses, only race and sexual orientation remained significant predictors of the PrEP implementation group. Staff who identified as a racial or sexual minority were less likely to be in the Limited group than their heterosexual or white counterparts. Age, gender, ever having taken PrEP, and HIV status did not impact the odds of being in a specific PrEP implementation group. CONCLUSIONS: A subset of HIV testing staff differentially discuss PrEP based on perceived client eligibility; others inconsistently talk to clients about PrEP. Targeted training based on PrEP implementation groups may be beneficial.

A Randomised Controlled Trial of a Brief Online Mindfulness-Based Intervention on Paranoia in a Non-Clinical Sample.

Paranoia is common and distressing in the general population and can impact on health, emotional well-being and social functioning, such that effective interventions are needed. Brief online mindfulness-based interventions (MBIs) have been shown to reduce symptoms of anxiety and depression in non-clinical samples; however, at present, there is no research investigating whether they can reduce paranoia. The current study explored whether a brief online MBI increased levels of mindfulness and reduced levels of paranoia in a non-clinical population. The mediating effect of mindfulness on any changes in paranoia was also investigated. One hundred and ten participants were randomly allocated to either a 2-week online MBI including 10 min of daily guided mindfulness practice or to a waitlist control condition. Measures of mindfulness and paranoia were administered at baseline, post-intervention and 1-week follow-up. Participants in the MBI group displayed significantly greater reductions in paranoia compared to the waitlist control group. Mediation analysis demonstrated that change in mindfulness skills (specifically the observe, describe and non-react facets of the FFMQ) mediated the relationship between intervention type and change in levels of paranoia. This study provides evidence that a brief online MBI can significantly reduce levels of paranoia in a non-clinical population. Furthermore, increases in mindfulness skills from this brief online MBI can mediate reductions in non-clinical paranoia. The limitations of the study are discussed.