HIV prevalence and undiagnosed infection among a community sample of gay and bisexual men in Scotland, 2005-2011: implications for HIV testing policy and prevention

<b>Objective</b><p></p> To examine HIV prevalence, HIV testing behaviour, undiagnosed infection and risk factors for HIV positivity among a community sample of gay men in Scotland.<p></p> <b>Methods</b><p></p> Cross-sectional survey of gay and bisexual men attending commercial gay venues in Glasgow and Edinburgh, Scotland with voluntary anonymous HIV testing of oral fluid samples in 2011. A response rate of 65.2% was achieved (1515 participants).<p></p> <b>Results</b><p></p> HIV prevalence (4.8%, 95% confidence interval, CI 3.8% to 6.2%) remained stable compared to previous survey years (2005 and 2008) and the proportion of undiagnosed infection among HIV-positive men (25.4%) remained similar to that recorded in 2008. Half of the participants who provided an oral fluid sample stated that they had had an HIV test in the previous 12 months; this proportion is significantly higher when compared to previous study years (50.7% versus 33.8% in 2005, p<0.001). Older age (>25 years) was associated with HIV positivity (1.8% in those <25 versus 6.4% in older ages group) as was a sexually transmitted infection (STI) diagnosis within the previous 12 months (adjusted odds ratio 2.13, 95% CI 1.09–4.14). There was no significant association between age and having an STI or age and any of the sexual behaviours recorded.<p></p> <b>Conclusion</b><p></p> HIV transmission continues to occur among gay and bisexual men in Scotland. Despite evidence of recent testing within the previous six months, suggesting a willingness to test, the current opt-out policy may have reached its limit with regards to maximising HIV test uptake. Novel strategies are required to improve regular testing opportunities and more frequent testing as there are implications for the use of other biomedical HIV interventions.<p></p&gt

Challenges and Opportunities: What Can We Learn from Patients Living with Chronic Musculoskeletal Conditions, Health Professionals and Carers about the Concept of Health Literacy Using Qualitative Methods of Inquiry?

The field of health literacy continues to evolve and concern public health researchers and yet remains a largely overlooked concept elsewhere in the healthcare system. We conducted focus group discussions in England UK, about the concept of health literacy with older patients with chronic musculoskeletal conditions (mean age = 73.4 years), carers and health professionals. Our research posed methodological, intellectual and practical challenges. Gaps in conceptualisation and expectations were revealed, reiterating deficiencies in predominant models for understanding health literacy and methodological shortcomings of using focus groups in qualitative research for this topic. Building on this unique insight into what the concept of health literacy meant to participants, we present analysis of our findings on factors perceived to foster and inhibit health literacy and on the issue of responsibility in health literacy. Patients saw health literacy as a result of an inconsistent interactive process and the implications as wide ranging; healthcare professionals had more heterogeneous views. All focus group discussants agreed that health literacy most benefited from good inter-personal communication and partnership. By proposing a needs-based approach to health literacy we offer an alternative way of conceptualising health literacy to help improve the health of older people with chronic conditions

Antitumour activity of a potent MEK inhibitor RDEA119/BAY 869766 combined with rapamycin in human orthotopic primary pancreatic cancer xenografts

<p>Abstract</p> <p>Background</p> <p>Combining MEK inhibitors with other signalling pathway inhibitors or conventional cytotoxic drugs represents a promising new strategy against cancer. RDEA119/BAY 869766 is a highly potent and selective MEK1/2 inhibitor undergoing phase I human clinical trials. The effects of RDEA119/BAY 869766 as a single agent and in combination with rapamycin were studied in 3 early passage primary pancreatic cancer xenografts, OCIP19, 21, and 23, grown orthotopically.</p> <p>Methods</p> <p>Anti-cancer effects were determined in separate groups following chronic drug exposure. Effects on cell cycle and downstream signalling were examined by flow cytometry and western blot, respectively. Plasma RDEA119 concentrations were measured to monitor the drug accumulation <it>in vivo</it>.</p> <p>Results</p> <p>RDEA119/BAY 869766 alone or in combination with rapamycin showed significant growth inhibition in all the 3 models, with a significant decrease in the percentage of cells in S-phase, accompanied by a large decrease in bromodeoxyuridine labelling and cell cycle arrest predominantly in G1. The S6 ribosomal protein was inhibited to a greater extent with combination treatment in all the three models. Blood plasma pharmacokinetic analyses indicated that RDEA119 levels achieved <it>in vivo </it>are similar to those that produce target inhibition and cell cycle arrest <it>in vitro</it>.</p> <p>Conclusions</p> <p>Agents targeting the ERK and mTOR pathway have anticancer activity in primary xenografts, and these results support testing this combination in pancreatic cancer patients.</p

Patterns of HIV testing practices among young gay and bisexual men living in Scotland: a qualitative study

Abstract Background Increasing overall rates, and frequency, of HIV testing in populations at risk is a key public health objective and a critical dimension of HIV prevention efforts. In the UK, men who have sex with men (MSM) remain one of the communities most at risk of HIV and, within this, young gay men are a key risk group. Understanding HIV testing practices is important in the development of interventions to promote testing among young gay and bisexual men. Methods Qualitative interviews were conducted with thirty young gay and bisexual men (aged 18–29) in Scotland. Thematic analysis of men’s accounts of their approach to HIV testing identified three overarching patterns of testing: ‘habitual’, ‘reactive’ and ‘ ad hoc’. Results This qualitative study, the first to explore patterns of HIV testing practices among young gay and bisexual men in the UK, contributes novel findings around the role of social support and ‘community’ in shaping young men’s approaches to HIV testing. The findings suggest that social support can play an important role in encouraging and facilitating HIV testing among young gay men, however, social norms of non-testing also have the potential to act as a barrier to development of a regular routine. Men with habitual testing practices framed HIV testing as both a personal and ‘community’ responsibility, and more effective than testing in response to risk events or emergent symptoms. Men who reported reactive testing practices described testing for HIV primarily in response to perceived exposure to sexual risk, along with ‘transitional moments’ such as starting, ending or changes to a relationship. Among young men who reported testing on an ad hoc basis, inconvenience and disruptions to HIV testing practices, particularly where men lacked social support, acted as a barrier to developing a routine of regular testing. Conclusions Our findings suggest that interventions which seek to increase rates of HIV testing and testing frequency among young gay and bisexual men should include a specific focus on promoting and supporting positive testing practices within young men’s friendship groups and wider gay communities

Issues in the incorporation of economic perspectives and evidence into Cochrane reviews

Methods for systematic reviews of the effects of health interventions have focused mainly on addressing the question of 'What works?' or 'Is this intervention effective in achieving one or more specific outcomes?' Addressing the question 'Is it worth it given the resources available?' has received less attention. This latter question can be addressed by applying an economic lens to the systematic review process.This paper reflects on the value and desire for the consideration by end users for coverage of an economic perspective in a Cochrane review and outlines two potential approaches and future directions

The Origin and Evolutionary History of HIV-1 Subtype C in Senegal

Background: The classification of HIV-1 strains in subtypes and Circulating Recombinant Forms (CRFs) has helped in tracking the course of the HIV pandemic. In Senegal, which is located at the tip of West Africa, CRF02_AG predominates in the general population and Female Sex Workers (FSWs). In contrast, 40% of Men having Sex with Men (MSM) in Senegal are infected with subtype C. In this study we analyzed the geographical origins and introduction dates of HIV-1 C in Senegal in order to better understand the evolutionary history of this subtype, which predominates today in the MSM population Methodology/Principal Findings: We used a combination of phylogenetic analyses and a Bayesian coalescent-based approach, to study the phylogenetic relationships in pol of 56 subtype C isolates from Senegal with 3,025 subtype C strains that were sampled worldwide. Our analysis shows a significantly well supported cluster which contains all subtype C strains that circulate among MSM in Senegal. The MSM cluster and other strains from Senegal are widely dispersed among the different subclusters of African HIV-1 C strains, suggesting multiple introductions of subtype C in Senegal from many different southern and east African countries. More detailed analyses show that HIV-1 C strains from MSM are more closely related to those from southern Africa. The estimated date of the MRCA of subtype C in the MSM population in Senegal is estimated to be in the early 80's. Conclusions/Significance: Our evolutionary reconstructions suggest that multiple subtype C viruses with a common ancestor originating in the early 1970s entered Senegal. There was only one efficient spread in the MSM population, which most likely resulted from a single introduction, underlining the importance of high-risk behavior in spread of viruses

Pragmatists versus dogmatists: Explaining the failure of power-sharing in Northern Ireland during the 1970s

This article argues that the failure of Northern Ireland’s first power-sharing executive, and subsequent attempts to restore power-sharing during the 1970s, was the result of conflicting attitudes towards devolution among Northern Ireland’s politicians. Traditional ideological divisions between nationalists and unionists were not the primary barrier to creating and sustaining cross-community institutions, as stressed in accounts of this period premised on consociational theory. Drawing extensively from archival sources, it argues that the split between the pragmatists from both communities, who were prepared to compromise their core principles and accept power-sharing devolution within a UK framework, and the dogmatists (both nationalists and unionists) who refused to contemplate any compromise to their core position, prevented a consensual political settlement emerging during the 1970s

Contact with HIV prevention services highest in gay and bisexual men at greatest risk: cross-sectional survey in Scotland

Background: Men who have sex with men (MSM) remain the group most at risk of acquiring HIV in the UK and new HIV prevention strategies are needed. In this paper, we examine what contact MSM currently have with HIV prevention activities and assess the extent to which these could be utilised further.Methods: Anonymous, self-complete questionnaires and Orasure (TM) oral fluid collection kits were distributed to men visiting the commercial gay scenes in Glasgow and Edinburgh in April/May 2008. 1508 men completed questionnaires (70.5% response rate) and 1277 provided oral fluid samples (59.7% response rate); 1318 men were eligible for inclusion in the analyses.Results: 82.5% reported some contact with HIV prevention activities in the past 12 months, 73.1% obtained free condoms from a gay venue or the Internet, 51.1% reported accessing sexual health information (from either leaflets in gay venues or via the Internet), 13.5% reported talking to an outreach worker and 8.0% reported participating in counselling on sexual health or HIV prevention. Contact with HIV prevention activities was associated with frequency of gay scene use and either HIV or other STI testing in the past 12 months, but not with sexual risk behaviours. Utilising counselling was also more likely among men who reported having had an STI in the past 12 months and HIV-positive men.Conclusions: Men at highest risk, and those likely to be in contact with sexual health services, are those who report most contact with a range of current HIV prevention activities. Offering combination prevention, including outreach by peer health workers, increased uptake of sexual health services delivering behavioural and biomedical interventions, and supported by social marketing to ensure continued community engagement and support, could be the way forward. Focused investment in the needs of those at highest risk, including those diagnosed HIV-positive, may generate a prevention dividend in the long term

Bidirectional Coupling between Astrocytes and Neurons Mediates Learning and Dynamic Coordination in the Brain: A Multiple Modeling Approach

In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model) which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a “learning signal” to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity), and the modeling strategy may be extended to coordination among remote neuron clusters