HIV testing history and preferences for future tests among gay men, bisexual men and other MSM in England: results from a cross-sectional study.

OBJECTIVES: The British HIV Association's (BHIVA) testing guidelines recommend men who have sex with men (MSM) test annually or more frequently if ongoing risk is present. We identify which groups of MSM in England are less likely to have tested for HIV and their preferences for future tests by testing model, in order to inform health promotion programmes. METHODS: Data come from the Gay Men's Sex Survey 2014, a cross-sectional survey of MSM, aged 16 years or older and living in the UK. Only men who did not have diagnosed HIV and were living in England were included in this analysis. We used logistic regression models to understand how social determinants of health were associated with not testing for HIV in the past 12 months, and never having tested. We then cross-tabulated preferred testing location by demographic characteristics. RESULTS: Younger men, older men and men who were not gay identified were least likely to have tested for HIV. Higher educational attainment, migrancy, Black ethnicity and being at higher of risk were associated with greater levels of HIV testing. Men who were less likely to have tested for HIV preferred a wider range of options for future HIV testing. CONCLUSIONS: If the BHIVA's HIV testing policy of 2008 was used to guide testing priorities among MSM focus would be on increasing the rate of annual testing among MSM at less risk of HIV (ie, younger men, older men and non-gay identified MSM). Instead the promotion of more frequent testing among the groups most at risk of infection should be prioritised in order to reduce the time between infection and diagnosis

Predictors of crystal methamphetamine use in a community-based sample of UK men who have sex with men.

Background Crystal methamphetamine (‘crystal meth’) use by men who have sex with men is an ongoing public health issue in the UK. We conducted a descriptive epidemiological study to characterise demographic and socio-sexual risk factors for crystal meth use in a national sample of UK MSM recruited in late 2014. Methods We used data from the 2014 Gay Men's Sex Survey (n = 16,565), an online community-based survey in the UK. We used logistic regression to relate risk factors to last-year use of crystal meth. Results In univariate models, crystal meth use was significantly associated with being between the ages of 30 and 49 (30–39, OR 2.24; 40–49, OR 2.21), living in London, having received a positive HIV test result (OR 7.37, 95% CI [6.28, 8.65]), and with higher education qualifications (1.40, [1.13, 1.75]), as well as with having multiple steady (2.15, [1.73, 2.68]) and non-steady (13.83, [10.30, 18.58]) partners with condomless anal intercourse. Relationships were similar in multivariate models, but education was no longer associated with last-year crystal meth use and lack of full-time employment was. Conclusions This analysis confirms and updates previous findings from the UK. Crystal meth use may now be more concentrated in London since previous surveys. This analysis presents novel findings regarding the association between number and sexual risk with partners and last-year meth use

Functional characterisation of substrate-binding proteins to address nutrient uptake in marine picocyanobacteria.

Marine cyanobacteria are key primary producers, contributing significantly to the microbial food web and biogeochemical cycles by releasing and importing many essential nutrients cycled through the environment. A subgroup of these, the picocyanobacteria (Synechococcus and Prochlorococcus), have colonised almost all marine ecosystems, covering a range of distinct light and temperature conditions, and nutrient profiles. The intra-clade diversities displayed by this monophyletic branch of cyanobacteria is indicative of their success across a broad range of environments. Part of this diversity is due to nutrient acquisition mechanisms, such as the use of high-affinity ATP-binding cassette (ABC) transporters to competitively acquire nutrients, particularly in oligotrophic (nutrient scarce) marine environments. The specificity of nutrient uptake in ABC transporters is primarily determined by the peripheral substrate-binding protein (SBP), a receptor protein that mediates ligand recognition and initiates translocation into the cell. The recent availability of large numbers of sequenced picocyanobacterial genomes indicates both Synechococcus and Prochlorococcus apportion >50% of their transport capacity to ABC transport systems. However, the low degree of sequence homology among the SBP family limits the reliability of functional assignments using sequence annotation and prediction tools. This review highlights the use of known SBP structural representatives for the uptake of key nutrient classes by cyanobacteria to compare with predicted SBP functionalities within sequenced marine picocyanobacteria genomes. This review shows the broad range of conserved biochemical functions of picocyanobacteria and the range of novel and hypothetical ABC transport systems that require further functional characterisation

Parental domestic violence and abuse, mental ill-health, and substance misuse and the impact on child mental health: a secondary data analysis using the UK Millennium Cohort Study

This is the final version. Available from BMC via the DOI in this record. Data availability. This study uses data from the MCS. MCS data can be found and accessed via the UK Data Service: https://ukdataservice.ac.uk/.Background - Parental domestic violence and abuse (DVA), mental ill-health (MH), and substance misuse (SU) can have a negative impact on both parents and children. However, it remains unclear if and how parental DVA, MH, and SU cluster and the impacts this clustering might have. We examined how parental DVA, MH, and SU cluster during early childhood, the demographic/contextual profiles of these clusters, and how these clusters relate to child MH trajectories. Methods - We examined data from 15,377 families in the UK Millennium Cohort Study. We used: (1) latent class analysis to create groups differentially exposed to parental DVA, MH, and SU at age three; (2) latent growth curve modelling to create latent trajectories of child MH from ages 3–17; and (3) a case-weight approach to relate latent classes to child MH trajectories. Results - We identified three latent classes: high-frequency alcohol use (11.9%), elevated adversity (3.5%), and low-level adversity (84.6%). Children in the elevated adversity class had higher probabilities of being from low-socioeconomic backgrounds and having White, younger parents. Children exposed to elevated adversity displayed worse MH at age three (intercept=2.274; p<0.001) compared the low-level adversity (intercept=2.228; p<0.001) and high-frequency alcohol use class (intercept=2.068; p<0.001). However, latent growth factors (linear and quadratic terms) of child MH did not differ by latent class. Conclusions - Parental DVA, MH, and SU cluster during early childhood and this has a negative impact on children’s MH at age three, leading to similar levels of poor MH across time. Intervening early to prevent the initial deterioration, using a syndemic-approach is essential.National Institute for Health and Care ResearchUK Economic and Social Research Counci

Experiences of current UK service provision for co-occurring parental domestic violence and abuse, mental ill-health, and substance misuse: a reflexive thematic analysis

This is the author accepted manuscript.Domestic violence and abuse (DVA), mental ill-health (MH), and substance misuse (SU) are inter-related public health problems negatively impacting families. Improved support requires an understanding of key stakeholders’ perspectives and experiences of current UK service provision. We conducted a qualitative research study to explore service users’, service providers’, and senior leadership/commissioners’ experiences of service provision for responding to parental DVA, MH, and SU in one locality. Six service users participated in individual, semi-structured interviews and ten service providers and senior leadership/commissioners attended two separate focus groups. We analysed data using reflexive thematic analysis. Five themes captured participants’ experiences: ‘it’s hard to get the support I need, when I need it’; ‘almost all services come together around a family’; ‘it’s all about the right relationships’; ‘addressing upstream drivers’; and ‘it’s difficult providing support for multiple needs’. These highlighted the importance of: early support; a relational response; and addressing needs beyond parental DVA, MH, and SU. They also emphasised the barriers presented by siloed specialisms and overwhelmed practitioners. Our study is one of the first to consider multiple stakeholders’ perspectives on current UK service provision for co-occurring parental DVA, MH, and SU. It highlights key challenges for working at the intersection of these problems and suggests system-level change is needed to create the conditions to support families with multiple needs.National Institute for Health and Care Research (NIHR

Correlates and subgroups of injecting drug use in UK gay and bisexual men: Findings from the 2014 Gay Men's Sex Survey.

BACKGROUND: Evidence to understand which gay and bisexual men (GBM) inject drugs remains scant, especially in the UK. We describe correlates of last-year injecting in UK GBM, and characterise subgroups of GBM who inject drugs by types of drugs used. METHODS: Using data from the 2014 Gay Men's Sex Survey, an opportunistic internet-based survey conducted of GBM living in the UK, we examined via logistic regression correlates with any injecting of six drugs (amphetamine/speed, crystal methamphetamine, heroin, mephedrone, GHB/GBL, and ketamine) in the last year. We estimated latent class models to understand underlying subgroups of injecting drug use among GBM reporting injecting drug use in the last year. RESULTS: Injecting was most common in GBM who were of middle age, who were HIV seropositive, and who lived in London, and was significantly associated with sexual risk with multiple partners in the last year, whether steady or non-steady. Most GBM who engaged in injecting either injected crystal methamphetamine, mephedrone or both (class 1, chemsex, 88.6% of injectors), whereas a smaller group had a focus on opiates (class 2, opiate, 7.9%). A small but identifiable subgroup (class 3, eclectic, 3.5%) engaged in injecting across the range of drugs examined. CONCLUSIONS: This is the first epidemiological analysis to describe subgroups of injecting, and to describe correlates of injecting drug use, in UK GBM. Implications for design of harm reduction services include a need to focus on injecting drug use beyond opiates, currently the focus of most harm reduction services

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two

The Herschel Exploitation of Local Galaxy Andromeda (HELGA) II: Dust and Gas in Andromeda

We present an analysis of the dust and gas in Andromeda, using Herschel images sampling the entire far-infrared peak. We fit a modified-blackbody model to ~4000 quasi-independent pixels with spatial resolution of ~140pc and find that a variable dust-emissivity index (beta) is required to fit the data. We find no significant long-wavelength excess above this model suggesting there is no cold dust component. We show that the gas-to-dust ratio varies radially, increasing from ~20 in the center to ~70 in the star-forming ring at 10kpc, consistent with the metallicity gradient. In the 10kpc ring the average beta is ~1.9, in good agreement with values determined for the Milky Way (MW). However, in contrast to the MW, we find significant radial variations in beta, which increases from 1.9 at 10kpc to ~2.5 at a radius of 3.1kpc and then decreases to 1.7 in the center. The dust temperature is fairly constant in the 10kpc ring (ranging from 17-20K), but increases strongly in the bulge to ~30K. Within 3.1kpc we find the dust temperature is highly correlated with the 3.6 micron flux, suggesting the general stellar population in the bulge is the dominant source of dust heating there. At larger radii, there is a weak correlation between the star formation rate and dust temperature. We find no evidence for 'dark gas' in M31 in contrast to recent results for the MW. Finally, we obtained an estimate of the CO X-factor by minimising the dispersion in the gas-to-dust ratio, obtaining a value of (1.9+/-0.4)x10^20 cm^-2 [K kms^-1]^-1.Comment: 19 pages, 18 figures. Submitted to ApJ April 2012; Accepted July 201

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.&lt;/p&gt