Will I? won't I? Why do men who have sex with men present for post-exposure prophylaxis for sexual exposures?

Background: Failures of post-exposure prophylaxis following sexual exposure (PEPSE) to prevent seroconversion have been reported and are often associated with ongoing risk exposure. Understanding why men who have sex with men (MSM) access PEPSE on some occasions and not others may lead to more effective health promotion and disease prevention strategies Methods: A qualitative study design using semi-structured interviews of 15 MSM within 6 months of them initiating PEPSE treatment at an HIV outpatient service in Brighton, UK. Results: PEPSE seeking was motivated by a number of factors: an episode that related to a particular sexual partner and their behaviour; the characteristics of the venue where the risk occurred; the respondent’s state of mind and influences of alcohol and recreational drug use; and their perceived beliefs on the effectiveness of PEPSE. Help was sought in the light of a “one-off” or “unusual” event. Many respondents felt they were less likely to behave in a risky manner following PEPSE. Conclusion: If PEPSE is to be effective as a public health measure, at risk individuals need to be empowered to make improved risk calculations from an increased perception that they could be exposed to HIV if they continue their current behaviour patterns. The concern is that PEPSE was sought by a low number of MSM implying that a greater number are not using the service based on failure to make accurate risk calculations or recognise high-risk scenario

Relativistic effects in neutrino-Fermi gas interactions

We study neutrino interactions in a hadron gas within a relativistic framework. The hadron matter is described by a non-interacting Fermi gas in beta equilibrium. We show that the introduction of relativistic effects causes a sizable enhancement of the neutrino-scattering cross sections.Comment: To appear in the proceedings of International School of Nuclear Physics: 27th Course: "Neutrinos in Cosmology, in Astro, Particle and Nuclear Physics". Erice, Sicily, Italy, 16-2

The Predatory Bird Monitoring Scheme (PBMS) Report 2006-7

The Predatory Bird Monitoring Scheme (PBMS) examines the levels of certain pollutants in selected wildlife species in Britain. It started in the 1960s to assess the impact of organochlorine pesticides on raptor populations, and the scheme is now the longest-running of its kind in the world. The aims of the PBMS are to monitor the levels of contaminants to determine how and why they vary between species and regions, how they are changing over time, and the risks they may have on individual birds and on their populations. Dead predatory birds are submitted to the PBMS by the public and by wildlife hospitals, veterinarian and zoological organisations. Eggs are collected, under licence, from a range of nests. The majority of these eggs are addled or deserted, although for some species, e.g. northern gannets, fresh egg are sampled. Second generation anticoagulant rodenticides (SGARs) are potentially toxic to all mammals and birds, and predators that feed upon rodents are particularly likely to be exposed to these compounds. Since 1983 the PBMS has monitored SGAR residues in barn owls, while kestrels have been monitored since 2001. The proportion of barn owls which have one or more SGARs in their liver increased from less than 10% in the 1980s to approximately 40% in the early 2000s. However, there has been a small decrease in this percentage in the last few years. A higher proportion of kestrels have detectable residues of SGARs in their liver than barn owls with 60% of birds received in the years 2001 to 2006 having one or more SGAR in their liver. There is no evidence of a change over time in the proportion ok kestrels with detectable liver SGAR residues. Overall, the high incidence of exposure amongst monitored species remains of concern. Sparrowhawk livers are analysed for a range of persistent organic pollutants (POPs) and heavy metals. Sparrowhawks are studied because they have a wide distribution across the Britain and can be used as a sentinel species for the terrestrial environment. Following restrictions on its use as an agricultural pesticide, mercury concentrations have declined in sparrowhawks. However, despite PCBs being banned in 1981, there has not been any long-term change in polychlorinated biphenyl (PCB) liver concentrations in sparrowhawks during the period 1968-2006. In herons, used as a sentinel species for freshwater habitats, both PCB and mercury concentrations have declined. In 2006, mean PCB and mercury concentrations in both species were below those thought to have an adverse effect on individual birds. Pollutants, such as mercury and PCBs, can affect development and hatchability.. Therefore, the PBMS monitors the levels of contaminants in the eggs of a range of species including those of conservation concern such as golden eagle and the re-introduced white-tailed sea eagle. Other species that are monitored are the northern gannet, which are used as a monitor of the marine environment, and merlin that hunt in upland habitats. In general, and specifically in 2006, the residues measured in the eggs of golden eagle and gannets are below those thought to have an adverse effect on bird eggs, but some residues in individual merlin eggs were at concentrations associated with effects in other species. Few white-tailed see eagle eggs are received for analysis by the PBMS but a large proportion of those eggs that have been analysed, including the egg collected in 2006, have DDE, PCB and mercury concentrations above levels associated with adverse effects on bird embryos and the hatching success of eggs. Despite the withdrawal of PCBs from manufacturing over 20 years ago, the evidence for declining PCB concentrations in predatory birds is equivocal, with declines in liver or egg residues in some species but not in others. Mercury concentrations in most species have not significantly changed during the monitoring period

HIV-1 infection of microglial cells in a reconstituted humanized mouse model and identification of compounds that selectively reverse HIV latency.

Most studies of HIV latency focus on the peripheral population of resting memory T cells, but the brain also contains a distinct reservoir of HIV-infected cells in microglia, perivascular macrophages, and astrocytes. Studying HIV in the brain has been challenging, since live cells are difficult to recover from autopsy samples and primate models of SIV infection utilize viruses that are more myeloid-tropic than HIV due to the expression of Vpx. Development of a realistic small animal model would greatly advance studies of this important reservoir and permit definitive studies of HIV latency. When radiation or busulfan-conditioned, immune-deficient NSG mice are transplanted with human hematopoietic stem cells, human cells from the bone marrow enter the brain and differentiate to express microglia-specific markers. After infection with replication competent HIV, virus was detected in these bone marrow-derived human microglia. Studies of HIV latency in this model would be greatly enhanced by the development of compounds that can selectively reverse HIV latency in microglial cells. Our studies have identified members of the CoREST repression complex as key regulators of HIV latency in microglia in both rat and human microglial cell lines. The monoamine oxidase (MAO) and potential CoREST inhibitor, phenelzine, which is brain penetrant, was able to stimulate HIV production in human microglial cell lines and human glial cells recovered from the brains of HIV-infected humanized mice. The humanized mice we have developed therefore show great promise as a model system for the development of strategies aimed at defining and reducing the CNS reservoir

Recent, independent and anthropogenic origins of Trypanosoma cruzi hybrids.

The single celled eukaryote Trypanosoma cruzi, a parasite transmitted by numerous species of triatomine bug in the Americas, causes Chagas disease in humans. T. cruzi generally reproduces asexually and appears to have a clonal population structure. However, two of the six major circulating genetic lineages, TcV and TcVI, are TcII-TcIII inter-lineage hybrids that are frequently isolated from humans in regions where chronic Chagas disease is particularly severe. Nevertheless, a prevalent view is that hybridisation events in T. cruzi were evolutionarily ancient and that active recombination is of little epidemiological importance. We analysed genotypes of hybrid and non-hybrid T. cruzi strains for markers representing three distinct evolutionary rates: nuclear GPI sequences (n = 88), mitochondrial COII-ND1 sequences (n = 107) and 28 polymorphic microsatellite loci (n = 35). Using Maximum Likelihood and Bayesian phylogenetic approaches we dated key evolutionary events in the T. cruzi clade including the emergence of hybrid lineages TcV and TcVI, which we estimated to have occurred within the last 60,000 years. We also found evidence for recent genetic exchange between TcIII and TcIV and between TcI and TcIV. These findings show that evolution of novel recombinants remains a potential epidemiological risk. The clearly distinguishable microsatellite genotypes of TcV and TcVI were highly heterozygous and displayed minimal intra-lineage diversity indicative of even earlier origins than sequence-based estimates. Natural hybrid genotypes resembled typical meiotic F1 progeny, however, evidence for mitochondrial introgression, absence of haploid forms and previous experimental crosses indicate that sexual reproduction in T. cruzi may involve alternatives to canonical meiosis. Overall, the data support two independent hybridisation events between TcII and TcIII and a recent, rapid spread of the hybrid progeny in domestic transmission cycles concomitant with, or as a result of, disruption of natural transmission cycles by human activities

NHS commissioning practice and health system governance: a mixed-methods realistic evaluation

Background By 2010 English health policy-makers had concluded that the main NHS commissioners [primary care trusts (PCTs)] did not sufficiently control provider costs and performance. After the 2010 general election, they decided to replace PCTs with general practitioner (GP)-controlled Clinical Commissioning Groups (CCGs). Health-care commissioners have six main media of power for exercising control over providers, which can be used in different combinations (‘modes of commissioning’). Objectives To: elicit the programme theory of NHS commissioning policy and empirically test its assumptions; explain what shaped NHS commissioning structures; examine how far current commissioning practice allowed commissioners to exercise governance over providers; examine how commissioning practices differ in different types of commissioning organisation and for specific care groups; and explain what factors influenced commissioning practice and the relationships between commissioners and providers. Design Mixed-methods realistic evaluation, comprising: Leximancer and cognitive frame analyses of policy statements to elicit the programme theory of NHS commissioning policy; exploratory cross-sectional analysis of publicly available managerial data about PCTs; systematic comparison of case studies of commissioning in four English sites – including commissioning for older people at risk of unplanned hospital admission; mental health; public health; and planned orthopaedic surgery – and of English NHS commissioning practice with that of a German sick-fund and an Italian region (Lombardy); action learning sets, to validate the findings and draw out practical implications; and two framework analyses synthesising the findings and testing the programme theory empirically. Results In the four English case study sites, CCGs were formed by recycling former commissioning structures, relying on and maintaining the existing GP commissioning leaderships. The stability of distributed commissioning depended on the convergence of commissioners’ interests. Joint NHS and local government commissioning was more co-ordinated at strategic than operational level. NHS providers’ responsiveness to commissioners reflected how far their interests converged, but also providers’ own internal ability to implement agreements. Commissioning for mental health services and to prevent recurrent unplanned hospital readmissions relied more on local ‘micro-commissioning’ (collaborative care pathway design) than on competition. Service commissioning was irrelevant to intersectoral health promotion, but not clinical prevention work. On balance, the possibility of competition did not affect service outcomes in the ways that English NHS commissioning policies assumed. ‘Commodified’ planned orthopaedic surgery most lent itself to provider competition. In all three countries, tariff payments increased provider activity and commissioners’ costs. To contain costs, commissioners bundled tariff payments into blocks, agreed prospective case loads with providers and paid below-tariff rates for additional cases. Managerial performance, negotiated order and discursive control were the predominant media of power used by English, German and Italian commissioners. Conclusions Commissioning practice worked in certain respects differently from what NHS commissioning policy assumed. It was often laborious and uncertain. In the four English case study sites financial and ‘real-side’ contract negotiations were partly decoupled, clinician involvement being least on the financial side. Tariff systems weakened commissioners’ capacity to choose providers and control costs. Commissioners adapted the systems to solve this problem. Our findings suggest a need for further research into whether or not differently owned providers (corporate, third sector, public, professional partnership, etc.) respond differently to health-care commissioners and, if so, what specific implications for commissioning practice follow. They also suggest that further work is needed to assess how commissioning practices impact on health system integration when care pathways have to be constructed across multiple providers that must tender competitively for work, perhaps against each other. Funding The National Institute for Health Research Health Services and Delivery Research programme

Secure Proximity-Based Identity Pairing using an Untrusted Signalling Service

New protocols such as WebRTC promise seamless in-browser peer-to-peer communications that in theory remove the need for third-party services. In practice, widespread use of Firewalls, NATS and dynamic IP addresses mean that overlay addressing or use of some fixed rendezvous point is still needed. In this paper we describe a proximity-based pairing scheme that uses a signalling service to minimise the trust requirements on the third party, achieving anonymity and avoiding the need for PKI, while still requiring only a simple asymmetric pairing protocol