The growing challenge: a strategic review of HIV social care, support and information services across the UK.

This report appears 10 years after the widespread introduction of anti-retroviral therapies. Availability of effective HIV treatment has transformed the UK epidemic, producing a dramatic reduction in mortality and, for many people living with HIV, an increase in health and well-being. Yet, in spite of medical advances, many services seem to continue to follow a historical pattern. Against this background we commissioned Sigma Research to review service commissioning in the HIV sector in order to inform members’ future grant making strategies. Results in the report indicate that commissioners and providers of services believe that people from ethnic minority backgrounds, migrants, children, carers and people from different age groups have unmet needs. Other findings in this research indicate that many more services have been commissioned recently for Africans, on the basis that Africans make up a significant part of the current UK epidemic. We believe this is a valid focus but are discouraged by the approach to these varied communities as one homogenous population. It seems timely to ask whether configuring services to follow broad epidemiological categories without any further refinement is sufficient. The report further suggests that commissioners and providers believe the needs of gay men are well met. This is a surprise and does not accord with the views and experiences of many gay men living with the virus. A significant minority of HIV positive people are neither gay men nor Africans. Even within these two groups the experience of living with HIV varies by age, geographical location and length of infection. HIV positive individuals may look at their needs from another starting point – for example, as a woman or an injecting drug user. The picture appears to be, increasingly, one of fragmentation and isolation. This poses the question: do we have the service models to meet the needs of HIV positive people in the third decade of the epidemic? The report further shows that many of the problems with access to services – including housing and welfare rights – are structural problems, present across health and social care, and are not unique to HIV. HIV support services are funded from budgets which must also contain the increasing costs of anti-retroviral drugs and other medical interventions, and which are therefore subject to continuous attrition and dissaggregation. Also highlighted is the lack of needs-based planning, the diminishing levels of knowledge and expertise among commissioners and the lack of a national strategic vision. In view of the fact that the Government has established a cross-departmental task force to address the epidemic in developing countries this lack of a national strategic vision is lamentable and has the effect of keeping the issue off the political agenda and almost invisible within local funding priorities. This is a concern both to us as funders and to agencies working within the HIV voluntary sector

A Relook at Canada’s Western Canada Sedimentary Basin for Power Generation and Direct-Use Energy Production

The Alberta No. 1 Project, under the terms of Canada’s Federal government’s Emerging Renewable Power Program (ERPP), must produce 5MWe net. The goal of this study was to identify areas where three essential constraining conditions overlap; (1) the temperature gradient is sufficiently high that 120°C brines at depths of 4,500m or less are potentially available, (2) there are formations at the depths targeted with known high fluid flows, and (3) there is adequate existing infrastructure that supports low-cost power grid connection as well as a direct use application. A fluid temperature of at least 120oC is needed to profitably operate the plant. Temperatures below this require increasingly greater amount of fluids to be pumped and injected making them uneconomic. Three hundred liters per second (l/sec) of 120oC water is required to generate 5 MW net of electrical power with an Organic Rankin Cycle (ORC) binary plant. A depth cut off from a project economics perspective is about 4,500m for large diameter geothermal wells. Fortunately, these formations don’t need to be thick to supply these volumes of water to the well bore and thin permeable formations are expected to be laterally extensive in the regional layer cake (Western Canada Sedimentary Basin, WCSB) geology of Alberta. Thus, targeting known high fluid producing geologic units, rather than narrow faults is an important aspect of developing a geothermal project in the WCSB. Alberta No. 1 identified nine study areas to assess for geothermal potential. Of these, the Tri-Municipal Industrial Park (south of Grande Prairie) was determined to be the most suitable for both power production and development, followed by Edson (west-central Alberta). Other areas were identified as being most suitable for basement EGS to produce power, as well as direct use from shallower formations

Analytical frameworks and outcome measures in economic evaluations of digital health interventions: a methodological systematic review

Background Digital health interventions (DHIs) can improve the provision of healthcare services. To fully account for their effects in economic evaluations, traditional methods based on measuring health-related quality of life may not be appropriate, as non-health and process outcomes are likely to be relevant too. Purpose This systematic review identifies, assesses and synthesises the arguments on the analytical frameworks and outcome measures used in the economic evaluations of DHIs. The results informed recommendations for future economic evaluations. Data Sources We ran searches on multiple databases, complemented by grey literature, backward and forward citation searches. Study Selection We included records containing theoretical and empirical arguments associated with the use of analytical frameworks and outcome measures for economic evaluations of DHIs. Following title/abstract and full-text screening, our final analysis included 15 studies. Data extraction The arguments we extracted related to analytical frameworks (14 studies), generic outcome measures (5 studies), techniques used to elicit utility values (3 studies), disease-specific outcome measures and instruments to collect health states data (both from 2 studies). Data synthesis Rather than assessing the quality of the studies, we critically assessed and synthesised the extracted arguments. Building on this synthesis, we developed a three-stage set of recommendations where we encourage the use of impact matrices and analyses of equity impacts to integrate traditional economic evaluation methods. Limitations Our review and recommendations explored but not fully covered other potentially important aspects of economic evaluations which were outside our scope. Conclusions This is the first systematic review that summarises the arguments on how the effects of DHIs could be measured in economic evaluations. Our recommendations will help design future economic evaluations

Help-seeking for genitourinary symptoms: a mixed methods study from Britain’s Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Objectives: Quantify non-attendance at sexual health clinics and explore help-seeking strategies for genitourinary symptoms. Design: Sequential mixed methods using survey data and semistructured interviews. Setting: General population in Britain. Participants: 1403 participants (1182 women) from Britain’s Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3; undertaken 2010–2012), aged 16–44 years who experienced specific genitourinary symptoms (past 4 weeks), of whom 27 (16 women) who reported they had never attended a sexual health clinic also participated in semistructured interviews, conducted May 2014–March 2015. Primary and secondary outcome measures: From survey data, non-attendance at sexual health clinic (past year) and preferred service for STI care; semistructured interview domains were STI social representations, symptom experiences, help-seeking responses and STI stigma. Results: Most women (85.9% (95% CI 83.7 to 87.9)) and men (87.6% (95% CI 82.3 to 91.5)) who reported genitourinary symptoms in Natsal-3 had not attended a sexual health clinic in the past year. Around half of these participants cited general practice (GP) as their preferred hypothetical service for STI care (women: 58.5% (95% CI 55.2% to 61.6%); men: 54.3% (95% CI 47.1% to 61.3%)). Semistructured interviews elucidated four main responses to symptoms: not seeking healthcare, seeking information to self-diagnose and self-treat, seeking care at non-specialist services and seeking care at sexual health clinics. Collectively, responses suggested individuals sought to gain control over their symptoms, and they prioritised emotional reassurance over accessing medical expertise. Integrating survey and interview data strengthened the evidence that participants preferred their general practitioner for STI care and extended understanding of help-seeking strategies. Conclusions: Help-seeking is important to access appropriate healthcare for genitourinary symptoms. Most participants did not attend a sexual health clinic but sought help from other sources. This study supports current service provision options in Britain, facilitating individual autonomy about where to seek help

Men who have sex with men in Great Britain: comparing methods and estimates from probability and convenience sample surveys.

OBJECTIVE: To examine sociodemographic and behavioural differences between men who have sex with men (MSM) participating in recent UK convenience surveys and a national probability sample survey. METHODS: We compared 148 MSM aged 18-64 years interviewed for Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) undertaken in 2010-2012, with men in the same age range participating in contemporaneous convenience surveys of MSM: 15 500 British resident men in the European MSM Internet Survey (EMIS); 797 in the London Gay Men's Sexual Health Survey; and 1234 in Scotland's Gay Men's Sexual Health Survey. Analyses compared men reporting at least one male sexual partner (past year) on similarly worded questions and multivariable analyses accounted for sociodemographic differences between the surveys. RESULTS: MSM in convenience surveys were younger and better educated than MSM in Natsal-3, and a larger proportion identified as gay (85%-95% vs 62%). Partner numbers were higher and same-sex anal sex more common in convenience surveys. Unprotected anal intercourse was more commonly reported in EMIS. Compared with Natsal-3, MSM in convenience surveys were more likely to report gonorrhoea diagnoses and HIV testing (both past year). Differences between the samples were reduced when restricting analysis to gay-identifying MSM. CONCLUSIONS: National probability surveys better reflect the population of MSM but are limited by their smaller samples of MSM. Convenience surveys recruit larger samples of MSM but tend to over-represent MSM identifying as gay and reporting more sexual risk behaviours. Because both sampling strategies have strengths and weaknesses, methods are needed to triangulate data from probability and convenience surveys

Central and East European migrant men who have sex with men in London: a comparison of recruitment methods

Background: Following the expansion of the European Union, there has been a large influx of Central and East European (CEE) migrants to the UK. CEE men who have sex with men (MSM) represent a small minority within this population that are none-the-less important to capture in sexual health research among the CEE migrant community. This paper examines the feasibility of recruiting CEE MSM for a survey of sexual behaviour in London using respondent driven sampling (RDS), via gay websites and in GUM clinics.Methods: We sought CEE MSM to start RDS chain referral among GUM clinic attendees, our personal contacts and at gay events and venues in central London. We recruited CEE MSM (n = 485) via two popular websites for gay men in Britain (March-May 2009) and at two central London GUM clinics (n = 51) (July 2008-March 2009).Results: We found seventeen men who knew other CEE MSM in London and agreed to recruit contacts into the study. These men recruited only three men into the study, none of whom recruited any further respondents, and RDS was abandoned after 7 months (July 2008-January 2009). Half of the men that we approached to participate in RDS did not know any other CEE MSM in London. Men who agreed to recruit contacts for RDS were rather more likely to have been in the UK for more than one year (94.1% vs 70.0%, p = 0.052). Men recruited through gay websites and from GUM clinics were similar.Conclusions: The Internet was the most successful method for collecting data on sexual risk behaviour among CEE MSM in London. CEE MSM in London were not well networked. RDS may also have failed because they did not fully understand the procedure and/or the financial incentive was not sufficient motivation to take part

Checkpoint Signaling, Base Excision Repair, and PARP Promote Survival of Colon Cancer Cells Treated with 5-Fluorodeoxyuridine but Not 5-Fluorouracil

The fluoropyrimidines 5-fluorouracil (5-FU) and FdUrd (5-fluorodeoxyuridine; floxuridine) are the backbone of chemotherapy regimens for colon cancer and other tumors. Despite their widespread use, it remains unclear how these agents kill tumor cells. Here, we have analyzed the checkpoint and DNA repair pathways that affect colon tumor responses to 5-FU and FdUrd. These studies demonstrate that both FdUrd and 5-FU activate the ATR and ATM checkpoint signaling pathways, indicating that they cause genotoxic damage. Notably, however, depletion of ATM or ATR does not sensitize colon cancer cells to 5-FU, whereas these checkpoint pathways promote the survival of cells treated with FdUrd, suggesting that FdUrd exerts cytotoxicity by disrupting DNA replication and/or inducing DNA damage, whereas 5-FU does not. We also found that disabling the base excision (BER) repair pathway by depleting XRCC1 or APE1 sensitized colon cancer cells to FdUrd but not 5-FU. Consistent with a role for the BER pathway, we show that small molecule poly(ADP-ribose) polymerase 1/2 (PARP) inhibitors, AZD2281 and ABT-888, remarkably sensitized both mismatch repair (MMR)-proficient and -deficient colon cancer cell lines to FdUrd but not to 5-FU. Taken together, these studies demonstrate that the roles of genotoxin-induced checkpoint signaling and DNA repair differ significantly for these agents and also suggest a novel approach to colon cancer therapy in which FdUrd is combined with a small molecule PARP inhibitor

Quaternary volcanism in the Wells Gray-Clearwater area, east central British Columbia

Basaltic volcanism in the form of small-volume, subaerial and subaqueous eruptions have occurred in the Wells Cray—Clearwater area of east central British Columbia. These eruptions have been dated by the K-Ar method and by relationships to dated glaciations. The oldest known eruption may be as old as 3.2 Ma, but is more likely 2 Ma or less. The youngest eruptions are less than 7560 ± 110 radiocarbon years. The most extensive basalts are valley-filling and plateau-capping flows of the Clearwater unit, which are Pleistocene in age and greater than 25 km³ in volume. The deposition of flows of the Clearwater unit has overlapped at least three periods of glaciation. The interaction of glacial ice and basaltic magma has been recorded in the form of tuyas, ice ponded valley deposits and subglacial mounds (SUGM). In a few place glacial till has been preserved beneath basalt flows. Flows of Wells Gray—Clearwater suite appear to have erupted from vents that are both spatially and temporally separated. The individual eruptions were of low volume (<1km³) and chemically distinct from one another. Major element composition is variable but the lavas are predominantly alkalic. Olivine is the predominant phenocryst phase. Plagioclase and augitic clinopyroxene rarely occur as phenocrysts, but both minerals are ubiquitous in the groundmass. Orthopyroxene was not seen in any of the samples. Flows appear to have erupted with minimal crystal fractionation or crustal contamination. The range of compositions seen in the suite is best explained by a process of partial melting and the progressive depletion of the mantle source by earlier melts. Progressive depletion of the mantle source was coupled with enrichment of parts of the mantle in K as well as some lithophile and siderophile elements. Increasing alkali content may have triggered the highly enriched eruptions of Holocene age that, despite very low degrees of partial melting, were capable of reaching the surface. Overprinting the effects of partial melting are inherited heterogeneities in the source zone of the magmas. Based on whole-rock chemistry the magma source appears to be a highly depleted region similar to that which produces the most depleted mid-ocean ridge basalts (MORB). The zone is, however, capable of producing large volume (≃ 15%) partial melts and has not been isotopically depleted to the same extent as MORB source regions. Isotope analyses of ⁸⁷Sr/⁸⁶Sr, ¹⁴³Nd/¹⁴⁴Nd and whole-rock Pb indicate that the magmas may be derived from a remnant of subducted oceanic lithosphere which has been variously depleted by the prior generation of basaltic melts. Isotopic enrichment above the level seen in MORB's is due in part to crustal contamination. The isotopic results are very different than those obtained from samples erupted through thin, allochthonous crust in the Intermontane Belt and may be explained in part by generation of the magmas in oceanic material which was subducted when allochthonous crust lay against the parautochthonous rocks underlying the Wells Cray—Clearwater area. The alkali olivine basalts of the Wells Cray—Clearwater area have erupted onto a tectonically active surface. A peneplain (erosion surface), formed in Eocene-Miocene time has been uplifted since the Miocene and uplift may be continuing. This uplift is in response to an elevated geothermal gradient which may be due to crustal extension. This crustal extension may be similar to that which occurred in the Eocene. The elevated geothermal gradient and reduced pressures attendant with recent uplift and erosion may have initiated basaltic volcanism in the region, rather than a fixed mantle hot spot as proposed in earlier work.Science, Faculty ofEarth, Ocean and Atmospheric Sciences, Department ofGraduat