Where surveillance has been done, it has shown that men (MSM) who have sex with men bear a disproportionate burden of HIV. Yet they continue to be excluded, sometimes systematically, from HIV services because of stigma, discrimination, and criminalisation. This situation must change if global control of the HIV epidemic is to be achieved. On both public health and human rights grounds, expansion of HIV prevention, treatment, and care to MSM is an urgent imperative. Effective combination prevention and treatment approaches are feasible, and culturally competent care can be developed, even in rights-challenged environments. Condom and lubricant access for MSM globally is highly cost effective. Antiretroviral-based prevention, and antiretroviral access for MSM globally, would also be cost effective, but would probably require substantial reductions in drug costs in high-income countries to be feasible. To address HIV in MSM will take continued research, political will, structural reform, community engagement, and strategic planning and programming, but it can and must be done.
Men who have sex with men (MSM) accounted for 61% of new HIV diagnoses in the United States in 2010. Recent analyses indicate that socio-structural factors are important correlates of HIV infection. NYCM2M was a cross-sectional study designed to identify neighborhood-level characteristics within the urban environment that influence sexual risk behaviors, substance use and depression among MSM living in New York City. The sample was recruited using a modified venue-based time-space sampling methodology and through select websites and mobile applications.
This paper describes novel methodological approaches used to improve the quality of data collected for analysis of the impact of neighborhoods on MSM health. Previous research has focused predominately on residential neighborhoods and used pre-determined administrative boundaries (e.g., census tracts) that often do not reflect authentic and meaningful neighborhoods. This study included the definition and assessment of multiple neighborhoods of influence including where men live (home neighborhood), socialize (social neighborhood) and have sex (sexual neighborhood). Furthermore, making use of technological advances in mapping, we collected geo-points of reference for each type of neighborhood and identified and constructed self-identified neighborhood boundary definitions. Finally, this study collected both perceived neighborhood characteristics and objective neighborhood conditions to create a comprehensive, flexible and rich neighborhood-level set of covariates. This research revealed that men perceived their home, social and sexual neighborhoods in different ways. Few men (15%) had the same home, social and sexual neighborhoods; for 31%, none of the neighborhoods was the same. Of the three types of neighborhoods, the number of unique social neighborhoods was the lowest; the size of sexual neighborhoods was the smallest. The resultant dataset offers the opportunity to conduct analyses that will yield context-specific and nuanced understandings of the relations among neighborhood space, and the well-being and health of urban MSM.
Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts.
The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort.
Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety.
The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.
Men who have sex with men (MSM) are the largest HIV risk-group in the United States. Sexual concurrency may contribute to high HIV incidence, or to racial/ethnic HIV disparities among MSM. Limited information is available on concurrency and racial/ethnic differences among MSM, or on the extent to which MSM engage in concurrent unprotected anal intercourse (UAI).
Data are from baseline responses in a prospective online study of MSM aged ≥ 18 years, having ≥ 1 male sex partner in the past 12 months, and recruited from social networking websites. Pair-wise sexual concurrency and UAI in the previous 6 months among up to 5 recent partners was measured, using an interactive questionnaire. Period prevalences of concurrency and concurrent UAI were computed and compared across racial/ethnic groups at the individual and triad (a respondent and 2 sex partners) levels.
2,940 MSM reported on 8,911 partnerships; 45% indicated concurrent partnerships and 16% indicated concurrent UAI in the previous 6 months. Respondents were more likely to have UAI with two partners when they were concurrent, compared to serially monogamous (OR [95% CI] = 1.93 [1.75, 2.14]). No significant differences in levels of individual concurrency or concurrency among triads were found between non-Hispanic white, non-Hispanic black, and Hispanic men.
Concurrency and concurrent UAI in the previous 6 months was common. Although there were no differences by race/ethnicity, the high levels of concurrency and concurrent UAI may be catalyzing the transmission of HIV among MSM in general.
Concurrency; MSM; sexual networks; UAI; racial disparities
Summary: zCall is a variant caller specifically designed for calling rare single-nucleotide polymorphisms from array-based technology. This caller is implemented as a post-processing step after a default calling algorithm has been applied. The algorithm uses the intensity profile of the common allele homozygote cluster to define the location of the other two genotype clusters. We demonstrate improved detection of rare alleles when applying zCall to samples that have both Illumina Infinium HumanExome BeadChip and exome sequencing data available.
Supplementary data are available at Bioinformatics online.
Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, “Advancing Drug Discovery for Schizophrenia” was held March 9–11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia.
schizophrenia; genetics; GWAS; neuronal function; small molecules; therapeutics
Personality can be thought of as a set of characteristics that influence people’s thoughts, feelings, and behaviour across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in ten discovery samples (17 375 adults) and five in-silico replication samples (3 294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data were available of ~2.4M Single Nucleotide Polymorphisms (SNPs; directly typed and imputed using HAPMAP data). In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P = 2.8 × 10−8 and 3.1 × 10−8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P = 4.9 × 10−8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In-silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.
Personality; Five-Factor Model; Genome-wide association; Meta-analysis; Genetic variants
Intermittent dosing of pre-exposure prophylaxis (iPrEP) has potential to decrease costs, improve adherence, and minimize toxicity. Practical event-based dosing of iPrEP requires men who have sex with men (MSM) to be sexually active on fewer than 3 days each week and plan for sexual activity. MSM who may be most suitable for event-based dosing were older, more educated, more frequently used sexual networking websites, and more often reported that their last sexual encounter was not with a committed partner. A substantial proportion of these MSM endorse high-risk sexual activity, and event-based iPrEP may best target this population.
intermittent pre-exposure prophylaxis (iPrEP); pre-exposure prophylaxis (PrEP); event-based dosing; men-who-have-sex-with-men (MSM); HIV; sexual frequency; sexual planning
Black and Hispanic men who have sex with men (MSM) are disproportionately affected by HIV in the United States. The Internet is a promising vehicle for delivery of HIV prevention interventions to these men, but retention of MSM of color in longitudinal Internet-based studies has been problematic. Text message follow-up may enhance retention in these studies.
To compare retention in a 12-month prospective Internet-based study of HIV-negative MSM randomized to receive bimonthly follow-up surveys either through an Internet browser online or through text messages.
Internet-using MSM were recruited through banner advertisements on social networking and Internet-dating sites. White, black, and Hispanic men who were ≥18, completed an online baseline survey, and returned an at-home HIV test kit, which tested HIV negative, were eligible. Men were randomized to receive follow-up surveys every 2 months on the Internet or by text message for 12 months (unblinded). We used time-to-event methods to compare the rate of loss-to-follow-up (defined as non-response to a follow-up survey after multiple systematically-delivered contact attempts) in the 2 follow-up groups, overall and by race/ethnicity. Results are reported as hazard ratios (HR) and 95% confidence intervals (CI) of the rate of loss-to-follow-up for men randomized to text message follow-up compared to online follow-up.
Of 1489 eligible and consenting men who started the online baseline survey, 895 (60%) completed the survey and were sent an at-home HIV test kit. Of these, 710 of the 895 (79%) returned the at-home HIV test kit, tested HIV-negative, and were followed prospectively. The study cohort comprised 66% white men (470/710), 15% (106/710) black men, and 19% (134/710) Hispanic men. At 12 months, 77% (282/366) of men randomized to online follow-up were retained in the study, compared to 70% (241/344) men randomized to text message follow-up (HR=1.30, 95% CI 0.97-1.73). The rate of loss-to-follow-up was non-significantly higher in the text message arm compared to the online arm for both white (HR=1.43, 95% CI 0.97-1.73) and Hispanic men (HR=1.71, 95% CI 0.91-3.23); however, loss-to-follow-up among black men was non-significantly lower among those who received text message follow-up compared to online follow-up (HR=0.78, 95% CI 0.41-1.50). In the online arm, black men were significantly more likely to be lost to follow-up compared to white men (HR=2.25, 95% CI 1.36-3.71), but this was not the case in the text message arm (HR=1.23, 95% CI 0.70-2.16).
We retained >70% of MSM enrolled in an online study for 12 months; thus, engaging men in online studies for a sufficient time to assess sustained outcomes is possible. Text message follow-up of an online cohort of MSM is feasible, and may result in higher retention among black MSM.
HIV infections/prevention and control; prospective studies; Internet/organization and administration; SMS text messaging; homosexuality; male/statistics and numerical data
Amyloid-β (Aβ) is causally implicated in Alzheimer’s disease and neuroplasticity failure has acquired validity as a possible mechanism of early AD pathogenesis. We have previously demonstrated that oligomeric Aβ 1–42 inhibits LTP in the dentate gyrus of rat hippocampal slices. We now show, using whole cell recordings in hippocampal granule cells, that oligomeric Aβ1–42 decreases neuronal excitability. In particular, Aβ1–42 application was associated with a decrease in the number of action potentials fired in response to current injection, and with an increase in the amplitude of the afterhyperpolarization. Reduced excitability may underlie the Aβ-mediated impairment in neuroplasticity, and ultimately may contribute to the memory loss in Alzheimer disease.
Whole cell recording; Hippocampal slices; Afterhyperpolarization; Alzheimer disease
Autosomal dominant mutations that increase amyloid-β(1–42) (Aβ42) cause familial Alzheimer’s disease (AD), and the most common genetic risk factor for AD is the presence of the ε4 allele of apolipoprotein E (apoE). Previously, we characterized stable preparations of Aβ42 oligomers and fibrils and reported that oligomers induced a 10-fold greater increase in neurotoxicity than fibrils in Neuro-2A cells. To determine the effects of apoE genotype on Aβ42 oligomer- and fibril-induced neurotoxicity in vitro, we co-cultured wild type (WT) neurons with glia from WT, apoE-knockout (apoE-KO), and human apoE2-, E3-, and E4-targeted replacement (TR) mice. Dose-dependent neurotoxicity was induced by oligomeric Aβ42 with a ranking order of apoE4-TR > KO = apoE2-TR = apoE3-TR > WT. Neurotoxicity induced by staurosporine or glutamate were not affected by apoE genotype, indicating specificity for oligomeric Aβ42-induced neurotoxicity. These in vitro data demonstrate a gain of negative function for apoE4, synergistic with oligomeric Aβ42, in mediating neurotoxicity.
ApoE; Alzheimer disease; Amyloid-β; Neurotoxicity; Co-cultures; ApoE transgenic mice
Large genomic copy number variations (CNVs) have been implicated as strong risk factors for schizophrenia. However, the rarity of these events has created challenges for the identification of further pathogenic loci, and extremely large samples are required to provide convincing replication.
To detect novel CNVs increasing susceptibility to schizophrenia, utilizing two ethnically homogeneous discovery cohorts and replication in large samples.
Genetic association study of microarray data.
DNA samples were collected at nine sites from different countries.
Two discovery cohorts were comprised of: a) 790 cases (schizophrenia and schizoaffective disorder) and 1347 controls of Ashkenazi Jewish descent; and b) 662 trios (offspring affected with schizophrenia or schizoaffective disorder) from Bulgaria. Replication datasets consisted of 12,398 cases and 17,945 controls.
Main outcome measure
Statistically increased rate of specific CNVs in cases versus controls.
One novel locus was implicated: a deletion at distal 16p11.2, which does not overlap the proximal 16p11.2 locus previously reported in schizophrenia and autism. Deletions at this locus were found in 13 out of 13,850 cases (0.094%) and in 3 out of 19,954 controls (0.015%), Fisher Exact p = 0.0014; OR = 6.25 (95%CI = 1.78 – 21.93).
Deletions at distal 16p11.2 have been previously implicated in developmental delay and obesity. The region contains nine genes, several of which are implicated in neurological diseases, regulation of body weight, and glucose homeostasis. A telomeric extension of the deletion, observed in about half the cases but no controls, potentially implicates an additional eight genes. Our findings add a new locus to the list of CNVs that increase risk to develop schizophrenia.
This cross-sectional study assessed the frequency of discrimination, harassment, and violence and the associated factors among a random sample of 1000 lesbian, gay men, and bisexual women and men recruited from randomly selected public venues in Italy.
A face-to-face interview sought information about: socio-demographics, frequency of discrimination, verbal harassment, and physical and sexual violence because of their sexual orientation, and their fear of suffering each types of victimization.
In the whole sample, 28.3% and 11.9% self-reported at least one episode of victimization because of the sexual orientation in their lifetime and in the last year. Those unmarried, compared to the others, and with a college degree or higher, compared to less educated respondents, were more likely to have experienced an episode of victimization in their lifetime. Lesbians, compared to bisexual, had almost twice the odds of experiencing an episode of victimization. The most commonly reported experiences across the lifetime were verbal harassment, discrimination, and physical or sexual violence. Among those who had experienced one episode of victimization in their lifetime, 42.1% self-reported one episode in the last year. Perceived fear of suffering violence because of their sexual orientation, measured on a 10-point Likert scale with a higher score indicative of greater fear, ranges from 5.7 for verbal harassment to 6.4 for discrimination. Participants were more likely to have fear of suffering victimization because of their sexual orientation if they were female (compared to male), lesbian and gay men (compared to bisexual women and men), unmarried (compared to the others), and if they have already suffered an episode of victimization (compared to those who have not suffered an episode).
The study provides important insights into the violence experiences of lesbian, gay men, and bisexual women and men and the results may serve for improving policy initiatives to reduce such episodes.
Numerous clinical trials in stroke have failed, most probably partially due to preclinical studies using young, healthy male rodents with little relevance to the heterogenic conditions of human stroke. Co-morbid conditions such as atherosclerosis and infections coupled with advanced age are known to contribute to increased risk of cerebrovascular diseases. Clinical and preclinical studies have shown that the E4 allele of human apolipoprotein (ApoE4) is linked to poorer outcome in various conditions of brain injury and neurodegeneration, including cerebral ischemia. Since ApoE is a known regulator of lipid homeostasis, we studied the impact of a high-cholesterol diet in aged mice in the context of relevant human ApoE isoforms on the outcome of focal brain ischemia.
Aged mice expressing human E3 and E4 isoforms of ApoE in C57BL/6J background and C57BL/6J mice fed on either a high-fat diet or a normal diet underwent permanent middle cerebral artery occlusion. The impact of a high-cholesterol diet was assessed by measuring the serum cholesterol level and the infarction volume was determined by magnetic resonance imaging. Sensorimotor deficits were assessed using an adhesive removal test and the findings were correlated with inflammatory markers.
We show that expression of human ApoE4 renders aged mice fed with a western-type diet more susceptible to sensorimotor deficits upon stroke. These deficits are not associated with atherosclerosis but are accompanied with altered astroglial activation, neurogenesis, cyclooxygenase-2 immunoreactivity and increased plasma IL-6.
Our results support the hypothesis that ApoE alleles modify the inflammatory responses in the brain and the periphery, thus contributing to altered functional outcome following stroke.
Brain ischemia; Inflammation; Apolipoprotein E; Atherosclerosis; Western diet; Aging
In Vietnam, men who have sex with men (MSM) are highly affected by HIV and need new targeted HIV prevention strategies.
To assess the willingness to use the Internet to seek information on HIV prevention and care and associated factors among MSM in Ho Chi Minh City.
A descriptive cross-sectional study was conducted in 2012. Participants were recruited using a convenience sampling method in venues most frequented by MSM and completed a self-administered questionnaire. Logistic regression models were performed to estimate factors associated with the willingness to use the Internet to seek information on HIV prevention and care.
A total of 358 MSM were approached for the survey and 222 questionnaires (62.0%) were eligible for analyses. Overall, 76.1% of the respondents reported that they were willing to use the Internet to seek information on HIV prevention and care. A number of male partners in last year less than or equal to 3 (Adjusted Odds Ratio: 3.07, 95% Confidence interval: 1.40–6.73), a history of STI screening (4.10, 1.02–16.48) and HIV testing (3.23, 1.20–8.64) and having ever sought a male sexual partner through the Internet (3.56, 1.55–8.18) were significantly positively associated with the willingness to use the Internet to seek information on HIV prevention and care.
The MSM interviewed in Ho Chi Minh City reported a high willingness to use the Internet to seek information on HIV prevention and care. In a context where new media are increasingly considered as promising options for reaching this HIV risk group, further research should be conducted on developing and testing tailored online tools adapted to the needs of Vietnamese MSM.
Research on gay and other men who have sex with men's (G/MSM) preferences for sexual healthcare services focuses largely on HIV testing and to some extent on sexually transmitted infections (STI). This research illustrates the frequency and location of where G/MSM interface with the healthcare system, but it does not speak to why men seek care in those locations. As HIV and STI prevention strategies evolve, evidence about G/MSM's motivations and decision-making can inform future plans to optimize models of HIV/STI prevention and primary care.
We conducted a phenomenological study of gay men's sexual health seeking experiences, which included 32 in-depth interviews with gay and bisexual men. Interviews were transcribed verbatim and entered into Atlas.ti. We conducted a Framework Analysis.
We identified a continuum of sexual healthcare seeking practices and their associated drivers. Men differed in their preferences for separating sexual healthcare from other forms of healthcare (“fragmentation”) versus combining all care into one location (“consolidation”). Fragmentation drivers included: fear of being monitored by insurance companies, a desire to seek non-judgmental providers with expertise in sexual health, a desire for rapid HIV testing, perceiving sexual health services as more convenient than primary care services, and a lack of healthcare coverage. Consolidation drivers included: a comfortable and trusting relationship with a provider, a desire for one provider to oversee overall health and those with access to public or private health insurance.
Men in this study were likely to separate sexual healthcare from primary care. Based on this finding, we recommend placing new combination HIV/STI prevention interventions within sexual health clinics. Furthermore, given the evolution of the financing and delivery of healthcare services and in HIV prevention, policymakers and clinicians should consider including more primary care services within sexual healthcare settings.
Men who have sex with men (MSM), particularly black MSM, are disproportionally infected with HIV. Little is known about how discussion of HIV status between partners varies among MSM by race/ethnicity, and by HIV transmission risk. Among a national survey of 2,031 MSM reporting 5,410 partnerships, black MSM, especially black HIV-positive MSM, serodiscussed with UAI partners less than did white MSM. Although non-black HIV-positive, non-black HIV-negative MSM, and black HIV-negative MSM were more likely to report serodiscussion with UAI partners, black HIV-positive MSM were not. Differential serodiscussion may play a role in explaining the racial/ethnic disparity in HIV incidence.
Health inequities in developing countries are difficult to eradicate because of limited resources. The neglect of adult mortality in Sub-Saharan Africa (SSA) is a particular concern. Advances in data availability, software and analytic methods have created opportunities to address this challenge and tailor interventions to small areas. This study demonstrates how a generic framework can be applied to guide policy interventions to reduce adult mortality in high risk areas. The framework, therefore, incorporates the spatial clustering of adult mortality, estimates the impact of a range of determinants and quantifies the impact of their removal to ensure optimal returns on scarce resources.
Data from a national cross-sectional survey in 2007 were used to illustrate the use of the generic framework for SSA and elsewhere. Adult mortality proportions were analyzed at four administrative levels and spatial analyses were used to identify areas with significant excess mortality. An ecological approach was then used to assess the relationship between mortality “hotspots” and various determinants. Population attributable fractions were calculated to quantify the reduction in mortality as a result of targeted removal of high-impact determinants.
Overall adult mortality rate was 145 per 10,000. Spatial disaggregation identified a highly non-random pattern and 67 significant high risk local municipalities were identified. The most prominent determinants of adult mortality included HIV antenatal sero-prevalence, low SES and lack of formal marital union status. The removal of the most attributable factors, based on local area prevalence, suggest that overall adult mortality could be potentially reduced by ∼90 deaths per 10,000.
The innovative use of secondary data and advanced epidemiological techniques can be combined in a generic framework to identify and map mortality to the lowest administration level. The identification of high risk mortality determinants allows health authorities to tailor interventions at local level. This approach can be replicated elsewhere.
Emerging evidence suggests sex and apolipoprotein E (APOE) genotype separately modify outcomes after intracerebral hemorrhage (ICH). We test the hypothesis that an interaction exists between sex and APOE polymorphism in modifying outcomes after ICH and is altered by administration of exogenous apoE-mimetic peptide. To define the effects of sex and APOE polymorphism in ICH, we created collagenase-induced ICH in male and female APOETR mice (targeted replacement mice homozygous for APOE3 or APOE4 alleles; n=12/group) and assessed performance on Rotarod (RR) and Morris water maze (MWM). To evaluate hematoma formation, we used hematoxylin and eosin staining at 24 h after injury (n=8/group). Using separate cohorts (n=12/group), apoE-mimetic peptide (COG1410 at 2 mg/kg) was administered after ICH, and mice were assessed by RR and MWM. Female mice outperformed male mice via RR and MWM by over 190% improvement through 7 days (RR) and 32 days (MWM) of testing after ICH (p<0.01). Female APOE3TR mice demonstrated improved function compared with all other groups (p<0.05) without any difference in hematoma volume at 24 h after injury in any group. Administration of a therapeutic apoE-mimetic peptide improved RR latencies through 7 days after ICH in male and female APOE4TR mice and MWM latencies over days 28–32 after ICH in male APOE4TR mice (p<0.05). Sex and APOE polymorphism influence functional outcomes in our murine model of ICH. Moreover, administration of exogenous apoE-mimetic peptide after injury differentially modifies the interaction between sex and APOE polymorphism.
Apolipoprotein E; Sex differences; Murine; Intracerebral hemorrhage; Female
Exome sequencing is emerging as a popular approach to study the effect of rare coding variants on complex phenotypes. The promise of exome sequencing is grounded in theoretical population genetics and in empirical successes of candidate gene sequencing studies. Many projects aimed at common diseases are underway, and their results are eagerly anticipated. In this Perspective, using exome sequencing data from 438 individuals, we discuss several aspects of exome sequencing studies that we view as particularly important. We review processing and quality control of raw sequence data, evaluate the statistical properties of exome sequencing studies, discuss rare variant burden tests to detect association to phenotypes, and demonstrate the importance of accounting for population stratification in the analysis of rare variants. We conclude that enthusiasm for exome sequencing studies of complex traits should be combined with the caution that thousands of samples may be required to reach sufficient statistical power.
To assess whether the relationship between using the Internet to meet sex partners and unprotected anal intercourse (UAI) differs for men who have sex with men (MSM) living in rural and urban areas.
Data on Internet use, residence and UAI were collected from MSM attending Gay Pride events in 12 U.S. cities.
Rural MSM who used the Internet to meet sex partners were more likely to report any UAI (aOR: 1.89 (1.12-3.19)) and insertive UAI (aOR: 2.16 (1.13- 4.10)) with the last sex partner than those who did not use the Internet. For urban MSM, UAI was not more commonly reported by men who used the Internet to meet sex partners.
The association between using the Internet to meet sex partners and UAI depended on whether MSM resided in rural or urban areas. Rural MSM may have different patterns of risk behavior from urban MSM. The Internet may offer new prevention opportunities for rural MSM.
MSM; Internet; UAI; residence; rural; urban
To evaluate systematically in real clinical settings whether functional genetic variations in drug metabolizing enzymes influence optimized doses, efficacy, and safety of antipsychotic medications.
DNA was collected from 750 patients with chronic schizophrenia treated with five antipsychotic drugs (olanzapine, quetiapine, risperidone, ziprasidone and perphenazine) as part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. Doses for each of the medicines were optimized to 1, 2, 3, or 4x units in identically-appearing capsules in a double blind design. We analyzed 25 known functional genetic variants in the major and minor metabolizing enzymes for each medication. These variants were tested for association with optimized dose and other relevant clinical outcomes.
None of the tested variants showed a nominally significant main effect in association with any of the tested phenotypes in European-Americans, African-Americans or all patients. Even after accounting for potential covariates no genetic variant was found to be associated with dosing, efficacy, overall tolerability, or tardive dyskinesia.
There are no strong associations between common functional genetic variants in drug metabolizing enzymes and dosing, safety or efficacy of leading antipsychotics, strongly suggesting merely modest effects on the use of these medicines in most patients in typical clinical settings.
Pharmacogenetics; CYP 450; Drug Metabolizing Enzymes; Antipsychotics; Personalized Medicine
We assessed HIV/AIDS expenditures in Dehong Prefecture, Yunnan Province, one of the highest prevalence regions in China, and describe funding sources and spending for different categories of HIV-related interventions and at-risk populations.
2010 HIV/AIDS expenditures in Dehong Prefecture were evaluated based on UNAIDS’ National AIDS Spending Assessment methodology.
Nearly 93% of total expenditures for HIV/AIDS was contributed by public sources. Of total expenditures, 52.7% was allocated to treatment and care, 24.5% to program management and administration and 19.8% to prevention. Spending on treatment and care was primarily allocated to the treatment of opportunistic infections. Most (40.4%) prevention spending was concentrated on most-at-risk populations, injection drug users (IDUs), sex workers, and men who have sex with men (MSM), with 5.5% allocated to voluntary counseling and testing. Prevention funding allocated for MSM, partners of people living with HIV and prisoners and other confined populations was low compared to the disproportionate burden of HIV/AIDS in these populations. Overall, people living with HIV accounted for 57.57% of total expenditures, while most-at-risk populations accounted for only 7.99%.
Our study demonstrated the applicability of NASA for tracking and assessing HIV expenditure in the context of China, it proved to be a useful tool in understanding national HIV/AIDS response from financial aspect, and to assess the extent to which HIV expenditure matches epidemic patterns. Limited funding for primary prevention and prevention for MSM, prisoners and partners of people living with HIV, signal that resource allocation to these key areas must be strengthened. Comprehensive analyses of regional and national funding strategies are needed to inform more equitable, effective and cost-effective HIV/AIDS resource allocation.
Differences in the prevalence of undiagnosed HIV between different types of emergency departments (EDs) are not well understood. We seek to define missed opportunities for HIV diagnosis within 3 geographically proximate EDs serving different patient populations in a single metropolitan area.
For an urban academic, an urban community, and a suburban community ED located within 10 miles of one another, we reviewed visit records for a cohort of patients who received a new diagnosis of HIV between July 1999 and June 2003. Missed opportunities for earlier HIV diagnosis were defined as ED visits in the year before diagnosis, during which there was no documented ED HIV testing offer or test. Outcomes were the number of missed opportunity visits and the number of patients with a missed opportunity for each ED. We secondarily reviewed medical records for missed opportunity encounters, using an extensive list of indications that might conceivably trigger testing.
Among 276 patients with a new HIV diagnosis, 123 (44.5%) visited an ED in the year before diagnosis or received a diagnosis in the ED. The urban academic ED HIV testing program diagnosed 23 (8.3%) cases and offered testing to 24 (8.7%) patients who declined. Missed opportunities occurred during 187 visits made by 76 (27.5%) patients. These included 70 patients with 157 visits at the urban academic ED, 9 patients with 24 visits at the urban community ED, and 4 patients with 6 visits at the suburban community ED. Medical records were available for 172 of the 187 missed opportunity visits. Visits were characterized by the following potential testing indicators: HIV risk factors (58; 34%), related diagnosis indicating risk (7; 4%), AIDS-defining illness (8; 5%), physician suspicion of HIV (29; 17%), and nonspecific signs or symptoms of illness potentially consistent with HIV (126; 73%).
Geographically proximate EDs differ in their opportunities for earlier HIV diagnosis, but all 3 sites had missed opportunities. Many ED patients with undiagnosed HIV have potential indications for testing documented even in the absence of a dedicated risk assessment, although most of these are nonspecific signs or symptoms of illness that may not be clinically useful selection criteria.
Young people are at high risk of HIV and developing appropriate prevention programmes requires an understanding of the risk factors for HIV in this age group. We investigated factors associated with HIV among participants aged 15–30 years in a 2007–8 cross-sectional survey nested within a community-randomised trial of the MEMA kwa Vijana intervention in 20 rural communities in northwest Tanzania.
We analysed data for 7259(53%) males and 6476(47%) females. Using a proximate-determinant conceptual framework and conditional logistic regression, we obtained sex-specific Odds Ratios (ORs) for the association of HIV infection with socio-demographic, knowledge, behavioural and biological factors.
HSV-2 infection was strongly associated with HIV infection (females: adjOR 4.4, 95%CI 3.2–6.1; males: adjOR 4.2, 95%CI 2.8–6.2). Several socio-demographic factors (such as age, marital status and mobility), behavioural factors (condom use, number and type of sexual partnerships) and biological factors (blood transfusion, lifetime pregnancies, genital ulcers, Neisseria gonorrhoeae) were also associated with HIV infection. Among females, lifetime sexual partners (linear trend, p<0.001), ≥2 partners in the past year (adjOR 2.0, 95%CI 1.4–2.8), ≥2 new partners in the past year (adjOR 1.9 95%CI 1.2, 3.3) and concurrent partners in the past year (adjOR 1.6 95%CI 1.1, 2.4) were all associated with HIV infection.
Efforts must be intensified to find effective interventions to reduce HSV-2. Effective behavioural interventions focusing on reducing the number of sexual partnerships and risk behaviour within partnerships are also needed. An increase in risky sexual behaviour may occur following marriage dissolution or when a young woman travels outside of her community and interventions addressing the needs of these subgroups of vulnerable women may be important.