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1.  Risk of disclosure of participating in an internet-based HIV behavioral risk study of men who have sex with men (MSM) 
Journal of medical ethics  2011;37(12):768-769.
As the frequency of internet-based research has increased, it is important for researchers to consider how the conditions in which data are collected may influence the risks to participants. In particular, because internet-based data collection often occurs outside a clinical or research setting, there may be unintentional disclosures of a participant’s involvement in a research study of which the researcher is unaware. The current analysis examined the responses of men who have sex with men participating in an internet-based HIV behavioral risk study when queried about the possible disclosure of their participation in the study. Fewer than 2% of participants indicated that their participation in the research study was disclosed, and all but one indicated no negative outcomes associated with the disclosure. As the field of online research continues to expand, it is important to consider risks that are unique to internet-based research, and to monitor these risks to ensure that the confidentiality of research subjects is maintained.
doi:10.1136/jme.2011.043976
PMCID: PMC3593712  PMID: 21708832
2.  Prevalence of seroconversion symptoms and relationship to set point viral load: Findings from a subtype C epidemic, 1995–2009 
AIDS (London, England)  2012;26(2):175-184.
Objective
To describe symptoms, physical exam findings, and set point viral load associated with acute HIV seroconversion in a heterosexual cohort of discordant couples in Zambia.
Design
We followed HIV serodiscordant couples in Lusaka, Zambia from 1995–2009 with HIV testing of negative partners and symptom inventories 3-monthly, and physical examinations annually.
Methods
We compared prevalence of self-reported or treated symptoms (malaria syndrome, chronic diarrhea, asthenia, night sweats, and oral candidiasis) and annual physical exam [PE] findings (unilateral or bilateral neck, axillary, or inguinal adenopathy; and dermatosis) in seroconverting versus HIV-negative or HIV-positive intervals, controlling for repeated observations, age, and sex. A composite score comprised of significant symptoms and PE findings predictive of seroconversion versus HIV-negative intervals was constructed. We modeled the relationship between number of symptoms and PE findings at seroconversion and log set-point viral load [VL] using linear regression.
Results
2,388 HIV-negative partners were followed for a median of 18 months; 429 seroconversions occurred. Neither symptoms nor PE findings were reported for most seroconverters. Seroconversion was significantly associated with malaria syndrome among non-diarrheic patients (adjusted odds ratio [aOR]=4.0) night sweats (aOR=1.4), and bilateral axillary (aOR = 1.6), inguinal (aOR=2.2), and neck (aOR=2.2) adenopathy relative to HIV-negative intervals. Median number of symptoms was positively associated with set-point VL (p<0.001).
Conclusions
Though most acute and early infections were asymptomatic, malaria syndrome was more common and more severe during seroconversion compared with HIV-negative and HIV-positive intervals. When present, symptoms and physical exam findings were non-specific and associated with higher set point viremia.
doi:10.1097/QAD.0b013e32834ed8c8
PMCID: PMC3589587  PMID: 22089380
HIV; seroconversion syndrome; set point HIV viral load
3.  Birth Outcomes in Women with Eating Disorders in the Norwegian Mother and Child Cohort Study (MoBa) 
Background
We explored the impact of eating disorders on birth outcomes in the Norwegian Mother and Child Cohort Study (MoBa).
Method
35,929 pregnant women in the MoBa included women with broadly defined anorexia nervosa (AN; n=35), bulimia nervosa (BN; n=304), binge eating disorder (BED; n=1,812), and EDNOS-purging type (EDNOS-P; n=36) in the six months prior to or during pregnancy and the referent group--women who reported no eating disorders (no-ED; n=33,742).
Results
Pre-pregnancy BMI was significantly lower in mothers with AN and higher in mothers with BED than the referent. Mothers with AN, BN, and BED reported greater weight gain during pregnancy and more mothers with eating disorders reported smoking during pregnancy than the referent. Women with BED had higher birth weight babies, lower risk of small for gestational age babies, and higher risk for large for gestational age babies and cesarean section than the referent.
Conclusions
BED influences birth outcomes. The absence of differences in birth outcomes in women with AN and EDNOS-P may reflect small sample size and differential severity of illness in population versus clinical samples. The detection of eating disorders in pregnancy could help identify modifiable factors (e.g., binge eating, smoking) that could influence birth outcomes.
doi:10.1002/eat.20578
PMCID: PMC3586575  PMID: 18720472
5.  SNP-based analysis of neuroactive ligand-receptor interaction pathways implicates PGE2 as a novel mediator of antipsychotic treatment response: Data from the CATIE Study 
Schizophrenia research  2011;135(1-3):200-201.
doi:10.1016/j.schres.2011.11.002
PMCID: PMC3515657  PMID: 22099390
antipsychotics; genome-wide association; neurotransmitters; pathways; prostaglandin; schizophrenia
6.  Deep Resequencing and Association Analysis of Schizophrenia Candidate Genes 
Molecular psychiatry  2012;18(2):138-140.
doi:10.1038/mp.2012.28
PMCID: PMC3577417  PMID: 22472875
schizophrenia; sequencing; SNV; genetic; association; mutation; DISC1
7.  Genotype-Based Ancestral Background Consistently Predicts Efficacy and Side Effects across Treatments in CATIE and STAR*D 
PLoS ONE  2013;8(2):e55239.
Only a subset of patients will typically respond to any given prescribed drug. The time it takes clinicians to declare a treatment ineffective leaves the patient in an impaired state and at unnecessary risk for adverse drug effects. Thus, diagnostic tests robustly predicting the most effective and safe medication for each patient prior to starting pharmacotherapy would have tremendous clinical value. In this article, we evaluated the use of genetic markers to estimate ancestry as a predictive component of such diagnostic tests. We first estimated each patient’s unique mosaic of ancestral backgrounds using genome-wide SNP data collected in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) (n = 765) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) (n = 1892). Next, we performed multiple regression analyses to estimate the predictive power of these ancestral dimensions. For 136/89 treatment-outcome combinations tested in CATIE/STAR*D, results indicated 1.67/1.84 times higher median test statistics than expected under the null hypothesis assuming no predictive power (p<0.01, both samples). Thus, ancestry showed robust and pervasive correlations with drug efficacy and side effects in both CATIE and STAR*D. Comparison of the marginal predictive power of MDS ancestral dimensions and self-reported race indicated significant improvements to model fit with the inclusion of MDS dimensions, but mixed evidence for self-reported race. Knowledge of each patient’s unique mosaic of ancestral backgrounds provides a potent immediate starting point for developing algorithms identifying the most effective and safe medication for a wide variety of drug-treatment response combinations. As relatively few new psychiatric drugs are currently under development, such personalized medicine offers a promising approach toward optimizing pharmacotherapy for psychiatric conditions.
doi:10.1371/journal.pone.0055239
PMCID: PMC3566192  PMID: 23405125
8.  Associations between Perceived HIV Stigma and Quality of Life at the Dyadic Lvel: The Actor-Partner Interdependence Model 
PLoS ONE  2013;8(2):e55680.
Background
Few studies have investigated the relationship between HIV-related stigma and quality life at the dyadic level. The objective of this study was to examine the actor and partner effects of stigma that was perceived by people living with HIV/AIDS (PLWHAs) and caregivers on quality of life at the dyadic level.
Method
A survey was conducted among 148 dyads consisting of one PLWHA and one caregiver (296 participants) in Nanning, China. The interdependent relationship between a pair of dyadic members that influences the associations between stigma and quality of life was analyzed, using an innovative dyadic analysis technique: the Actor-Partner Interdependence Model (APIM).
Results
We found in this dyadic analysis that (1) PLWHAs compared to their caregivers exhibited a higher level of perceived HIV stigma and lower level of quality of life measured in four domains; (2) both PLWHAs' and caregivers' perceived HIV stigma influenced their own quality of life; (3) The quality of life was not substantially influenced by their partners' perceived stigma; and (4) Both actor and partner effects of stigma on quality of life were similar among PLWHAs and their caregivers.
Conclusion
As HIV stigma and quality of life are complex phenomena rooted in cultures, intervention programs should be carefully planned based on social or cognitive theories and should be culturally adopted.
doi:10.1371/journal.pone.0055680
PMCID: PMC3562178  PMID: 23383343
9.  Impact of HIV Comprehensive Care and Treatment on Serostatus Disclosure among Cameroonian Patients in Rural District Hospitals 
PLoS ONE  2013;8(1):e55225.
This work aimed to analyze the rate of disclosure to relatives and friends over time and to identify factors affecting disclosure among seropositive adults initiating antiretroviral therapy (ART) in rural district hospitals in the context of decentralized, integrated HIV care and task-shifting to nurses in Cameroon. Stratall was a 24-month, randomized, open-label trial comparing the effectiveness of clinical monitoring alone with laboratory plus clinical monitoring on treatment outcomes. It enrolled 459 HIV-infected ART-naive adults in 9 rural district hospitals in Cameroon. Participants in both groups were sometimes visited by nurses instead of physicians. Patients with complete data both at enrolment (M0) and at least at one follow-up visit were included in the present analysis. A mixed Poisson regression was used to estimate predictors of the evolution of disclosure index over 24 months (M24).The study population included 385 patients, accounting for 1733 face-to-face interviews at follow-up visits from M0 to M24. The median [IQR] number of categories of relatives and friends to whom patients had disclosed was 2 [1]–[3] and 3 [2]–[5] at M0 and M24 (p-trend<0.001), respectively. After multiple adjustments, factors associated with disclosure to a higher number of categories of relatives and friends were as follows: having revealed one’s status to one’s main partner, time on ART, HIV diagnosis during hospitalization, knowledge on ART and positive ratio of follow-up nurse-led to physician-led visits measuring task-shifting. ART delivered in the context of decentralized, integrated HIV care including task-shifting was associated with increased HIV serological status disclosure.
doi:10.1371/journal.pone.0055225
PMCID: PMC3561392  PMID: 23383117
10.  No Effect of Genome-Wide Copy Number Variation on Measures of Intelligence in a New Zealand Birth Cohort 
PLoS ONE  2013;8(1):e55208.
Variation in human intelligence is approximately 50% heritable, but understanding of the genes involved is limited. Several forms of genetic variation remain under-studied in relation to intelligence, one of which is copy number variation (CNV). Using single-nucleotide polymorphism (SNP) -based microarrays, we genotyped CNVs genome-wide in a birth cohort of 723 New Zealanders, and correlated them with four intelligence-related phenotypes. We found no significant association for any common CNV after false discovery correction, which is consistent with previous work. In contrast to a previous study, however, we found no effect on any cognitive measure of rare CNV burden, defined as total number of bases inserted or deleted in CNVs rarer than 5%. We discuss possible reasons for this failure to replicate, including interaction between CNV and aging in determining the effects of rare CNVs. While our results suggest that no CNV assayable by SNP chips contributes more than a very small amount to variation in human intelligence, it remains possible that common CNVs in segmental duplication arrays, which are not well covered by SNP chips, are important contributors.
doi:10.1371/journal.pone.0055208
PMCID: PMC3559383  PMID: 23383111
11.  Routine HIV Testing among Providers of HIV Care in the United States, 2009 
PLoS ONE  2013;8(1):e51231.
In 2006, CDC recommended HIV screening as part of routine medical care for all persons aged 13–64 years. We examined adherence to the recommendations among a sample of HIV care providers in the US to determine if known providers of HIV care are offering routine HIV testing in outpatient settings.
Data were from the CDC's Medical Monitoring Project Provider Survey, administered to physicians, nurse practitioners and physician assistants from June-September 2009. We assessed bivariate associations between testing behaviors and provider and practice characteristics and used multivariate regression to determine factors associated with offering HIV screening to all patients aged 13–64 years.
Sixty percent of providers reported offering HIV screening to all patients 13 to 64 years of age. Being a nurse practitioner (aOR = 5.6, 95% CI = 2.6–11.9) compared to physician, age<39 (aOR = 1.9, 95% CI = 1.0–3.5) or 39–49 (aOR = 2.1, 95% CI = 1.4–3.3) compared with ≥50 years, and black race (aOR = 2.6, 95% CI = 1.2–6.0) compared with white race was associated with offering testing to all patients. Providers with low (aOR = 0.2, 95% CI = 0.1–0.3) or medium (aOR = 0.4, 95% CI = 0.2–0.6) HIV-infected patient loads were less likely to offer HIV testing to all patients compared with providers with high patient loads.
Many providers of HIV care are still conducting risk-based rather than routine testing. We found that provider profession, age, race, and HIV-infected patient load were associated with offering HIV testing. Health care providers should use patient encounters as an opportunity to offer routine HIV testing to patients as outlined in CDC's revised recommendations for HIV testing in health care settings.
doi:10.1371/journal.pone.0051231
PMCID: PMC3544875  PMID: 23341880
12.  Penile Implants among Prisoners—A Cause for Concern? 
PLoS ONE  2013;8(1):e53065.
Background
We report the prevalence of penile implants among prisoners and determine the independent predictors for having penile implants. Questions on penile implants were included in the Sexual Health and Attitudes of Australian Prisoners (SHAAP) survey following concerns raised by prison health staff that increasing numbers of prisoners reported having penile implants while in prison.
Methods
Computer-Assisted Telephone Interviewing (CATI) of a random sample of prisoners was carried out in 41 prisons in New South Wales and Queensland (Australia). Men were asked, “Have you ever inserted or implanted an object under the skin of your penis?” If they responded Yes: “Have you ever done so while you were in prison?” Univariate logistic regression and logistic regression were used to determine the factors associated with penile implants.
Results
A total of 2,018 male prisoners were surveyed, aged between 18 and 65 years, and 118 (5.8%) reported that they had inserted or implanted an object under the skin of their penis. Of these men, 87 (73%) had this done while they were in prison. In the multivariate analysis, a younger age, birth in an Asian country, and prior incarceration were all significantly associated with penile implants (p<0.001). Men with penile implants were also more likely to report being paid for sex (p<0.001), to have had body piercings (p<0.001) or tattoos in prison (p<0.001), and to have taken non-prescription drugs while in prison (p<0.05).
Conclusions
Penile implants appear to be fairly common among prisoners and are associated with risky sexual and drug use practices. As most of these penile implants are inserted in prison, these men are at risk of blood borne viruses and wound infection. Harm reduction and infection control strategies need to be developed to address this potential risk.
doi:10.1371/journal.pone.0053065
PMCID: PMC3543437  PMID: 23326383
13.  Forced Sexual Experiences as Risk Factor for Self-Reported HIV Infection among Southern African Lesbian and Bisexual Women 
PLoS ONE  2013;8(1):e53552.
Even though women who have sex with women are usually understood to be at no or very low risk for HIV infection, we explored whether lesbian and bisexual women in a geographical area with high HIV prevalence (Southern Africa) get tested for HIV and whether, among those women who get tested, there are women who live with HIV/AIDS. The study was conducted in collaboration with community-based organizations in Botswana, Namibia, South Africa and Zimbabwe. Data were collected via written surveys of women who in the preceding year had had sex with a woman (18 years and older; N = 591). Most participating women identified as lesbian and black. Almost half of the women (47.2%) reported ever having had consensual heterosexual sex. Engagement in transactional sex (lifetime) was reported by 18.6% of all women. Forced sex by men or women was reported by 31.1% of all women. A large proportion of the women reported to ever have been tested for HIV (78.3%); number of lifetime female and male partners was independently associated with having been tested; women who had engaged in transactional sex with women only or with women and men were less likely to have been tested. Self-reported HIV prevalence among tested women who knew their serostatus was 9.6%. Besides age, the sole independent predictor of a positive serostatus was having experienced forced sex by men, by women, or by both men and women. Study findings indicate that despite the image of invulnerability, HIV/AIDS is a reality for lesbian and bisexual women in Southern Africa. Surprisingly, it is not sex with men per se, but rather forced sex that is the important risk factor for self-reported HIV infection among the participating women. HIV/AIDS policy should also address the needs of lesbian, bisexual and other women who have sex with women.
doi:10.1371/journal.pone.0053552
PMCID: PMC3541146  PMID: 23326452
14.  Trichloroethylene induces dopaminergic neurodegeneration in Fisher 344 rats 
Journal of neurochemistry  2009;112(3):773-783.
Trichloroethylene, a chlorinated solvent widely used as a degreasing agent, is a common environmental contaminant. Emerging evidence suggests that chronic exposure to tri-chloroethylene may contribute to the development of Parkinson’s disease. The purpose of this study was to determine if selective loss of nigrostriatal dopaminergic neurons could be reproduced by systemic exposure of adult Fisher 344 rats to trichloroethylene. In our experiments, oral administration of trichloroethylene induced a significant loss of dopaminergic neurons in the substantia nigra pars compacta in a dose-dependent manner, whereas the number of both cholinergic and GABAergic neurons were not decreased in the striatum. There was a robust decline in striatal levels of 3, 4-dihydroxyphenylacetic acid without a significant depletion of striatal dopamine. Rats treated with trichloroethylene showed defects in rotarod behavior test. We also found a significantly reduced mitochondrial complex I activity with elevated oxidative stress markers and activated microglia in the nigral area. In addition, we observed intracellular α-synuclein accumulation in the dorsal motor nucleus of the vagus nerve, with some in nigral neurons, but little in neurons of cerebral cortex. Overall, our animal model exhibits some important features of Parkinsonism, and further supports that trichloroethylene may be an environmental risk factors for Parkinson’s disease.
doi:10.1111/j.1471-4159.2009.06497.x
PMCID: PMC3535262  PMID: 19922440
neurodegeneration; Parkinson’s disease; substantia nigra; trichloroethylene; tyrosine hydroxylase; α-synuclein
15.  Analysis of regional brain mitochondrial bioenergetics and susceptibility to mitochondrial inhibition utilizing a microplate based system 
Journal of neuroscience methods  2011;198(1):36-43.
The analysis of mitochondrial bioenergetic function typically has required 50–100 μg of protein per sample and at least 15 min per run when utilizing a Clark-type oxygen electrode. In the present work we describe a method utilizing the Seahorse Biosciences XF24 Flux Analyzer for measuring mitochondrial oxygen consumption simultaneously from multiple samples and utilizing only 5 μg of protein per sample. Utilizing this method we have investigated whether regionally based differences exist in mitochondria isolated from the cortex, striatum, hippocampus, and cerebellum. Analysis of basal mitochondrial bioenergetics revealed that minimal differences exist between the cortex, striatum, and hippocampus. However, the cerebellum exhibited significantly slower basal rates of Complex I and Complex II dependent oxygen consumption (p < 0.05). Mitochondrial inhibitors affected enzyme activity proportionally across all samples tested and only small differences existed in the effect of inhibitors on oxygen consumption. Investigation of the effect of rotenone administration on Complex I dependent oxygen consumption revealed that exposure to 10 pM rotenone led to a clear time dependent decrease in oxygen consumption beginning 12 min after administration (p < 0.05). These studies show that the utilization of this microplate based method for analysis of mitochondrial bioenergetics is effective at quantifying oxygen consumption simultaneously from multiple samples. Additionally, these studies indicate that minimal regional differences exist in mitochondria isolated from the cortex, striatum, or hippocampus. Furthermore, utilization of the mitochondrial inhibitors suggests that previous work indicating regionally specific deficits following systemic mitochondrial toxin exposure may not be the result of differences in the individual mitochondria from the affected regions.
doi:10.1016/j.jneumeth.2011.03.007
PMCID: PMC3535268  PMID: 21402103
Mitochondria; Seahorse; XF24; Brain; Regional differences; Bioenergetics; Rotenone; Malonate
16.  Conditions Comorbid with Chronic Fatigue in a Population-Based Sample 
Psychosomatics  2011;53(1):44-50.
Background
Chronic fatigue syndrome (CFS) has been found to be comorbid with various medical conditions in clinical samples, but little research has investigated CFS comorbidity in population-based samples.
Objective
This study investigated conditions concurrent with a CFS-like illness among twins in the population-based Mid-Atlantic Twin Registry (MATR), including chronic widespread pain (CWP), irritable bowel syndrome (IBS), and major depression (MD).
Method
A survey was mailed to participants in the MATR in 1999. Generalized estimating equations were used to estimate odds ratios to assess associations between CFS-like illness and each comorbid condition.
Results
A total of 4,590 completed surveys were collected. Most participants were female (86.3%); mean age was 44.7 years. Among participants with a CFS-like illness, lifetime prevalence of CWP was 41%, IBS was 16%, and MD was 57%. Participants reporting at least one of the three comorbid conditions were about 14 times more likely to have CFS-like illness than those without CWP, IBS, or MD (95% confidence interval 8.1–21.3%). Only MD showed a temporal pattern of presentation during the same year as diagnosis of CFS-like illness. Age, gender, body mass index, age at illness onset, exercise level, self-reported health status, fatigue symptoms, and personality measures did not differ between those reporting CFS-like illness with and without comorbidity.
Conclusion
These results support findings in clinically based samples that CFS-like illness is frequently cormorbid with CWP, IBS, and/or MD. We found no evidence that CFS-like illnesses with comorbidities are clinically distinct from those without comorbidities.
doi:10.1016/j.psym.2011.04.001
PMCID: PMC3254018  PMID: 22221720
17.  Measuring Population Transmission Risk for HIV: An Alternative Metric of Exposure Risk in Men Who Have Sex with Men (MSM) in the US 
PLoS ONE  2012;7(12):e53284.
Background
Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL), population viral load (PVL), percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities.
Methods and Findings
Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM), we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. MSM with plasma VL>400 copies/mL were defined as having ‘transmission risk’. We calculated HIV prevalence, CVL, PVL, percent of HIV-positive with undetectable viral loads, and prevalence of plasma VL>400 copies/ml (%VL400) for black and white MSM. We used Monte Carlo simulation incorporating data on sexual mixing by race to estimate exposure of black and white HIV-negative MSM to a partner with transmission risk via unprotected anal intercourse (UAI). Of 709 MSM recruited, 42% (168/399) black and 14% (44/310) white MSM tested HIV-positive (p<.0001). No significant differences were seen in CVL, PVL, or percent of HIV positive with undetectable viral loads. The %VL400 was 25% (98/393) for black vs. 8% (25/310) for white MSM (p<.0001). Black MSM with 2 UAI partners were estimated to have 40% probability (95% CI: 35%, 45%) of having ≥1 UAI partner with transmission risk vs. 20% for white MSM (CI: 15%, 24%).
Discussion
Despite similarities in other metrics, black MSM in our cohort are three times as likely as white MSM to have HIV transmission risk. With comparable risk behaviors, HIV-negative black MSM have a substantially higher likelihood of encountering a UAI partner at risk of transmitting HIV. Our results support increasing HIV testing, linkage to care, and antiretroviral treatment of HIV-positive MSM to reduce prevalence of those with transmission risk, particularly for black MSM.
doi:10.1371/journal.pone.0053284
PMCID: PMC3532405  PMID: 23285274
18.  Improving detection of copy-number variation by simultaneous bias correction and read-depth segmentation 
Nucleic Acids Research  2012;41(3):1519-1532.
Structural variation is an important class of genetic variation in mammals. High-throughput sequencing (HTS) technologies promise to revolutionize copy-number variation (CNV) detection but present substantial analytic challenges. Converging evidence suggests that multiple types of CNV-informative data (e.g. read-depth, read-pair, split-read) need be considered, and that sophisticated methods are needed for more accurate CNV detection. We observed that various sources of experimental biases in HTS confound read-depth estimation, and note that bias correction has not been adequately addressed by existing methods. We present a novel read-depth–based method, GENSENG, which uses a hidden Markov model and negative binomial regression framework to identify regions of discrete copy-number changes while simultaneously accounting for the effects of multiple confounders. Based on extensive calibration using multiple HTS data sets, we conclude that our method outperforms existing read-depth–based CNV detection algorithms. The concept of simultaneous bias correction and CNV detection can serve as a basis for combining read-depth with other types of information such as read-pair or split-read in a single analysis. A user-friendly and computationally efficient implementation of our method is freely available.
doi:10.1093/nar/gks1363
PMCID: PMC3561969  PMID: 23275535
19.  Extremely low-coverage sequencing and imputation increases power for genome-wide association studies 
Nature genetics  2012;44(6):631-635.
Genome wide association studies (GWAS) have proven a powerful method to identify common genetic variants contributing to susceptibility to common diseases. Here we show that extremely low-coverage sequencing (0.1–0.5x) captures almost as much of the common (>5%) and low-frequency (1–5%) variation across the genome as SNP arrays. As an empirical demonstration, we show that genome-wide SNP genotypes can be inferred at a mean r2 of 0.71 using off-target data (0.24x average coverage) in a whole-exome study of 909 samples. Using both simulated and real exome sequencing datasets we show that association statistics obtained using ultra low-coverage sequencing data attain similar P-values at known associated variants as genotyping arrays, without an excess of false positives. Within the context of reductions in sample preparation and sequencing costs, funds invested in ultra low-coverage sequencing can yield several times the effective sample size of SNP-array GWAS, and a commensurate increase in statistical power.
doi:10.1038/ng.2283
PMCID: PMC3400344  PMID: 22610117
20.  What Drives the US and Peruvian HIV Epidemics in Men Who Have Sex with Men (MSM)? 
PLoS ONE  2012;7(11):e50522.
In this work, we estimate the proportions of transmissions occurring in main vs. casual partnerships, and by the sexual role, infection stage, and testing and treatment history of the infected partner, for men who have sex with men (MSM) in the US and Peru. We use dynamic, stochastic models based in exponential random graph models (ERGMs), obtaining inputs from multiple large-scale MSM surveys. Parallel main partnership and casual sexual networks are simulated. Each man is characterized by age, race, circumcision status, sexual role behavior, and propensity for unprotected anal intercourse (UAI); his history is modeled from entry into the adult population, with potential transitions including HIV infection, detection, treatment, AIDS diagnosis, and death. We implemented two model variants differing in assumptions about acute infectiousness, and assessed sensitivity to other key inputs. Our two models suggested that only 4–5% (Model 1) or 22–29% (Model 2) of HIV transmission results from contacts with acute-stage partners; the plurality (80–81% and 49%, respectively) stem from chronic-stage partners and the remainder (14–16% and 27–35%, respectively) from AIDS-stage partners. Similar proportions of infections stem from partners whose infection is undiagnosed (24–31%), diagnosed but untreated (36–46%), and currently being treated (30–36%). Roughly one-third of infections (32–39%) occur within main partnerships. Results by country were qualitatively similar, despite key behavioral differences; one exception was that transmission from the receptive to insertive partner appears more important in Peru (34%) than the US (21%). The broad balance in transmission contexts suggests that education about risk, careful assessment, pre-exposure prophylaxis, more frequent testing, earlier treatment, and risk-reduction, disclosure, and adherence counseling may all contribute substantially to reducing the HIV incidence among MSM in the US and Peru.
doi:10.1371/journal.pone.0050522
PMCID: PMC3510067  PMID: 23209768
21.  Attitudes Towards Couples-Based HIV Testing Among MSM in Three US Cities 
AIDS and behavior  2011;15(Suppl 1):S80-S87.
Couples-based voluntary HIV counseling and testing (CVCT)—in which couples receive counseling and their HIV test results together—has been shown to be an effective strategy among heterosexual sero-discordant couples in Africa for reducing HIV transmission by initiating behavioral change. This study examined attitudes towards CVCT among men who have sex with men (MSM) in three US cities. Four focus group discussions (FGD) were held with MSM in Atlanta, Chicago, and Seattle. Although initially hesitant, participants reported an overwhelming acceptance of CVCT. CVCT was seen as a sign of commitment within a relationship and was reported to be more appropriate for men in longer-term relationships. CVCT was also seen as providing a forum for the discussion of risk-taking within the relationship. Our results suggest that there may be a demand for CVCT among MSM in the United States, but some modifications to the existing African CVCT protocol may be needed.
doi:10.1007/s10461-011-9893-2
PMCID: PMC3505763  PMID: 21336607
MSM; Couples; HIV testing
22.  Oral Human Papillomavirus in Men Having Sex with Men: Risk-Factors and Sampling 
PLoS ONE  2012;7(11):e49324.
Background
Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is becoming more common. We examined prevalence and risk factors for oral HPV among men who have sex with men (MSM) and compared sampling and transport methods.
Methods
In 2010, 500 MSM (249 HIV-positive) attending Melbourne Sexual Health Centre answered a questionnaire, swabbed their mouth and throat and collected a gargled oral rinse sample. Half the oral rinse was transported absorbed in a tampon (to enable postage). HPV was detected by polymerase chain reaction, and genotyped by Roche Linear Array®. Men with HPV 16 or 18 were retested after six months.
Results
Any HPV genotype was detected in 19% (95% confidence intervals (CI) 15–25%) of HIV-infected men and 7% (95% CI 4–11%) of HIV-negative men (p<0.001), and HPV 16 was detected in 4.4% (95% CI 2–8%) of HIV-infected men and 0.8% (0.1–2.8%) of HIV-negative men. Oral HPV was associated with: current smoking (adjusted odds ratio (aOR) 2.2 (95%CI: 1.2–3.9)), time since tooth-brushing (aOR per hour 0.87, 95%CI: 0.8–0.96) and number of lifetime tongue-kissing partners aOR 3.2 95%CI: (1.2–8.4) for 26–100 partners and 4.9 95%CI: (1.9–12.5) for>100 partners. Lifetime oral-penile sex partner numbers were significantly associated in a separate model: aOR 2.8(1.2–6.3) for 26–100 partners and 3.2(1.4–7.2) for>100 partners. HPV 16 and 18 persisted in 10 of 12 men after a median six months. Sensitivities of sampling methods compared to all methods combined were: oral rinse 97%, tampon-absorbed oral rinse 69%, swab 32%.
Conclusions
Oral HPV was associated with HIV infection, smoking, recent tooth-brushing, and more lifetime tongue-kissing and oral sex partners. The liquid oral rinse sample was more sensitive than a tampon-absorbed oral rinse or a self-collected swab.
doi:10.1371/journal.pone.0049324
PMCID: PMC3500282  PMID: 23173054
23.  Use of Web 2.0 to Recruit Australian Gay Men to an Online HIV/AIDS Survey 
Background
Continuous prevention efforts for human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) are recommended among those men who have sex with men (MSM). Creative use of e-technologies coupled with a better understanding of social networks could lead to improved health interventions among this risk population.
Objective
The aims of the study were to (1) compare the impact of various advertising strategies on recruiting MSM participants to an online HIV/AIDS survey, and (2) explore the feasibility of using a social network service (SNS) for study advertising.
Methods
A cross-sectional online survey was conducted in 2009. South Australian men over 18 years were invited to participate if they had had sexual intercourse with men in the previous year. A short questionnaire was used to collect demographics and information on sexual behavior, HIV history, use of the Internet for dating purposes, and sources of health information. The survey was promoted in community settings and online, including advertisements through social networks.
Results
A total of 243 men completed the online survey during the 8-week data collection period. Online advertisements recruited 91.7% (220/240) of the sample. Conversely, traditional advertisements in the community recruited only 5.8% (14/240) of the sample. Ten volunteers were asked to advertise on their personal SNS application, but only 2 effectively did so. Only 18/240 (7.5%) of the respondents reported having learned of our study through the SNS application. In this sample, 19.3% (47/243) of participants had never been tested for HIV. Among the participants who had been tested, 12.8% (25/196) reported being HIV-positive. Regarding Internet use, 82.3% (200/243) of participants had dated online in the previous 6 months. Among the participants who had dated online, most (175/200, 87.5%) had found an Internet sexual partner and two-thirds (132/200, 66.0%) had had anal sex with these partner(s). Among men who had anal sex with an Internet partner, 68.2% (90/132) used a condom during sex.
Conclusions
The MSM participants in this study had high-risk profiles for HIV and other sexually transmitted diseases (STDs), which highlights the need for ongoing health interventions among this group. In this study, the SNS marketing strategy did not appear to create a viral effect and it had a relatively poor yield.
doi:10.2196/jmir.1819
PMCID: PMC3510723  PMID: 23128646
Internet; advertising; HIV; Australia; homosexuality; male
24.  Sexual agreements in the partnerships of Internet-using men who have sex with men 
AIDS care  2012;24(10):1255-1263.
Recent studies among men who have sex with men (MSM) have found that the majority of HIV transmission results from sex with a main partner. One factor likely to affect the risk of transmission is the type of agreements the couple has regarding sexual behaviour within and outside the relationship. This study recruited 732 Internet-using MSM through Facebook banner ads. Participants completed an online questionnaire regarding demographic characteristics of the respondent and their main partner, the sexual behaviour of the couple, the existence of a sexual agreement, and the strength of investment in that agreement. The Pearson chi-square test was used to assess the association between sexual agreements (categorized as open, closed, or none) and the predictive variables. Respondents’ investment in their sexual agreement was measured using the sexual agreement investment scale (a composite score ranging from 0 to 52). Ninety-one percent of respondents had some form of sexual agreement in place with their main partner. The presence and type of sexual agreement was found to be strongly associated with many characteristics of the individual and couple, including the respondent’s HIV status, length of time with the main partner, having unprotected anal intercourse with a man other than their main partner, and happiness in the relationship. Increases in the strength of respondents’ investment in their sexual agreement were found to be associated with newness of the relationship, relationship happiness, having a closed relationship, and decreases in risky sexual behaviour. This study offers further evidence of the important role that sexual agreements play in male couples. The overwhelming prevalence of sexual agreements and their association with relationship happiness and risky sexual behaviours has important implications for future HIV prevention and control strategies, including the implementation of couples voluntary counseling and testing.
doi:10.1080/09540121.2012.656571
PMCID: PMC3483634  PMID: 22375729
sexual agreements; MSM couples; agreement investment; HIV; CVCT
25.  Comparative Performance of Electrochemiluminescence Immunoassay and EIA for HIV Screening in a Multiethnic Region of China 
PLoS ONE  2012;7(10):e48162.
Background
The recent approval of 4th generation HIV tests has forced many laboratories to decide whether to shift from 3rd to these tests. There are limited published studies on the comparative evaluation of these two different assays. We compare the performance of fourth-generation electrochemiluminescence immunoassay (ChIA) and third-generation enzyme linked immunosorbent assay (EIA) for human immunodeficiency virus (HIV) screening and gauge whether the shift from EIA to ChIA could be better in a multiethnic region of China.
Methodology/Principal Findings
We identified a large number of routine specimens (345,492) using two different assays from Jan 2008 to Aug 2011 in a teaching hospital with high sample throughput. Of the 344,596 specimens with interpretable HIV test results, 526(0.23%) of 228,761 using EIA and 303(0.26%) of 115,835 using ChIA were HIV-1 positive. The false-positive rate of EIA was lower than that of ChIA [0.03% vs. 0.08%, odds ratio 0.33 (95% confidence interval 0.24, 0.45)]. The positive predictive value (PPV) of EIA (89.6%) was significantly higher than that of ChIA (76.1%) (<0.001), reflecting the difference between the two assays. The clinical sensitivities of two assays in this study were 99.64% for EIA and 99.88% for ChIA.
Conclusion
Caution is needed before shifting from 3rd to 4th generation HIV tests. Since none of these tests are perfect, different geographic and ethnic area probably require different considerations with regard to HIV testing methods, taking into account the local conditions.
doi:10.1371/journal.pone.0048162
PMCID: PMC3483174  PMID: 23144740

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