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ObjectiveIdentify system-level features in HIV migration within a host across body tissues. Evaluate heterogeneity in the presence and magnitude of these features across hosts.MethodUsing HIV DNA deep sequencing data generated across multiple tissues from 8 people with HIV, we represent the complex dependencies of HIV migration among tissues as a network and model these networks using the family of exponential random graph models (ERGMs). ERGMs allow for the statistical assessment of whether network features occur more (or less) frequently in viral migration than might be expected by chance. The analysis investigates five potential features of the viral migration network: (1) bi-directional flow between tissues; (2) preferential migration among tissues in the same biological system; (3) heterogeneity in the level of viral migration related to HIV reservoir size; (4) hierarchical structure of migration; and (5) cyclical migration among several tissues. We calculate the Cohran's Q statistic to assess heterogeneity in the magnitude of the presence of these features across hosts. The analysis adjusts for missing data on body tissues.ResultsWe observe strong evidence for bi-directional flow between tissues; migration among tissues in the same biological system; and hierarchical structure of the viral migration network. This analysis shows no evidence for differential level of viral migration with respect to the HIV reservoir size of a tissue. There is evidence that cyclical migration among three tissues occurs less frequent than expected given the amount of viral migration. The analysis also provides evidence for heterogeneity in the magnitude that these features are present across hosts. Adjusting for missing tissue data identifies system-level features within a host as well as heterogeneity in the presence of these features across hosts that are not detected when the analysis only considers the observed data.DiscussionIdentification of common features in viral migration may increase the efficiency of HIV cure efforts as it enables targeting specific processes.

We aimed to elucidate the characteristics of HIV molecular epidemiology and identify transmission hubs in eastern China using genetic transmission network and lineage analyses. HIV-TRACE was used to infer putative relationships. Across the range of epidemiologically-plausible genetic distance (GD) thresholds (0.1-2.0%), a sensitivity analysis was performed to determine the optimal threshold, generating the maximum number of transmission clusters and providing reliable resolution without merging different small clusters into a single large cluster. Characteristics of genetically linked individuals were analyzed using logistic regression. Assortativity (shared characteristics) analysis was performed to infer shared attributes between putative partners. 1,993 persons living with HIV-1 were enrolled. The determined GD thresholds within subtypes CRF07_BC, CRF01_AE, and B were 0.5%, 1.2%, and 1.7%, respectively, and 826 of 1,993 (41.4%) sequences were linked with at least one other sequence, forming 188 transmission clusters of 2-80 sequences. Clustering rates for the main subtypes CRF01_AE, CRF07_BC, and B were 50.9% (523/1027), 34.2% (256/749), and 32.1% (25/78), respectively. Median cluster sizes of these subtypes were 2 (2-52, n = 523), 2 (2-80, n = 256), and 3 (2-6, n = 25), respectively. Subtypes in individuals diagnosed and residing in Hangzhou city (OR = 1.423, 95% CI: 1.168-1.734) and men who have sex with men (MSM) were more likely to cluster. Assortativity analysis revealed individuals were more likely to be genetically linked to individuals from the same age group (AIage = 0.090, P

BackgroundIncreasing HIV testing and treatment coverage among people living with HIV (PLHIV) is essential for achieving global HIV epidemic control. However, compared to women, cis-gender heterosexual men living with HIV are significantly less likely to know their HIV status, initiate anti-retroviral therapy (ART) and achieve viral suppression. This is particularly true in South Africa, where men are also at increased risk of mortality resulting from AIDS-related illnesses. While there is growing knowledge of Treatment as Prevention or the concept Undetectable = Untransmittable (U = U) among PLHIV in Western and high-income countries, the reach and penetration of the U = U message in sub-Saharan Africa remains limited, and few studies have evaluated the impact of accessible and relatable U = U messages on ART initiation and adherence. To address these gaps, rigorous evaluations of interventions that incorporate U = U messages are needed, especially among men in high prevalence settings.MethodsBuilding on our U = U messages that we previously developed for men using behavioral economics insights and a human-centered design, we will conduct two sequential hybrid type 1 effectiveness-implementation trials to evaluate the impact of U = U messages on men's uptake of community-based HIV testing and ART initiation (Trial 1), and retention in care and achievement of viral suppression (Trial 2). For trial 1, a cluster randomized trial will be implemented with HIV testing service site-days (each day at one testing site) randomized to U = U or standard-of-care (SoC) messages inviting men to test for HIV. For trial 2, an individual-level randomized control trial will be implemented, with men initiating ART at six government clinics randomized to receive U = U counselling or SoC treatment adherence messaging. We will incorporate a multi-method evaluation to inform future implementation of U = U messaging interventions. The study will be conducted in the Buffalo City Metro Health District of the Eastern Cape Province and in the Cape Town Metro Health District in the Western Cape Province in South Africa.DiscussionThese trials are the first to rigorously evaluate the impact of U = U messaging on HIV testing uptake, ART initiation and achievement of viral suppression among African men. If effective, these messaging interventions can shape global HIV testing, treatment and adherence counselling guidelines and practices.

Older people in residential aged care are susceptible to acute illness or injury which may necessitate an ambulance call out, assessment/treatment by a paramedic and transfer to a hospital emergency department. Understanding the case mix of residential aged care ambulance attendances is important for prevention strategies and for planning services. A retrospective observational closed cohort study was designed to investigate the characteristics of emergency ambulance call outs to 15 residential aged care sites in the Australian Capital Territory over a 12-month period. Data were collected from the local ambulance service and the aged care sites. Case load data were analysed to determine rates, clinical characteristics, ambulance attendance outcomes and the temporal distribution of call outs. A Poisson regression model was developed to investigate demographic, morbidity and medication-related risk factors associated with the number of ambulance call outs per resident. Annual ambulance call out costs were estimated. There were 1,275 residents, with 396 (31.1%) requiring at least one ambulance call out over 12 months. Of 669 ambulance attendances, the majority (87.0%) were transported to emergency departments. Trauma (23.9%), pain (16.9%) and infections (9.4%) were the most common primary assessments by the ambulance attendees. Cases/day were similar throughout the year and on weekdays compared to weekends/public holidays. The main predictors of ambulance call out were multi-morbidity, taking regular anticholinergic medicines, being male and younger age. Estimated costs of ambulance call outs/year were $475/resident and $40,375/residential aged care site. The most frequent primary assessments (trauma, pain, infections) may constitute priorities for developing prevention strategies and for treatment initiatives within residential aged care. Strategies to reduce anticholinergic medication prescribing may also be a potential intervention to decrease ambulance call outs and hospital emergency department demand. The ambulance usage data from this study may be useful to compare with future datasets to measure the impact of the introduction of new services.

BackgroundPrompt access to evidence-based treatment for children and young people with eating disorders is important for outcomes, yet the gap in service provision remains pervasive. Record levels of young people are waiting for eating disorder treatment and access to care is limited. Guided self-help interventions that are brief and require minimal clinician support have the potential to meet the unprecedented demand for treatment quickly and effectively.ObjectiveTo examine the feasibility, acceptability and proof of concept of a novel, CBT guided self-help intervention for children and young people with threshold and subthreshold eating disorders.MethodsA single-arm, proof-of-concept pilot study of the CBT guided self-help intervention will be conducted. Children and young people (aged 11-19) with threshold and subthreshold eating disorders will receive a self-help intervention covering the core components of CBT, supported by 8 weekly guidance sessions delivered remotely. Clinical outcomes (eating-related psychopathology and associated impairment, changes in weight, depression, anxiety, and behavioural difficulties) will be assessed at baseline and post-intervention (12 weeks). Feasibility and acceptability of the intervention will be measured using various outcomes, including adherence to, and engagement with the intervention, rates of recruitment and retention, measure completion and treatment satisfaction. Qualitative data will also be collected for future intervention refinement.DiscussionIf the intervention is shown to produce clinical benefits in this pilot study, a fully powered randomised pilot study will be warranted with the ultimate goal of increasing access to psychological treatment for children and young people threshold and subthreshold eating disorders.Administrative informationThis study protocol (S1 File) adheres to the guidelines outlined in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist for trial protocols [1, 2] which can be found in S1 Checklist. The numbers in parentheses in this protocol correspond to the item numbers in the SPIRIT checklist. The order of items has been modified to group similar items.

BackgroundA unique window of opportunity currently exists to generate ethical and practical considerations presented by interventional HIV cure-related research at the end-of-life (EOL). Because participants would enroll in these studies for almost completely altruistic reasons, they are owed the highest ethical standards, safeguards, and protections. This qualitative empirical ethics study sought to identify ethical and practical considerations for interventional HIV cure-related research at the EOL.Methods and findingsWe conducted 20 in-depth interviews and three virtual focus groups (N = 36) with four key stakeholder groups in the United States: 1) bioethicists, 2) people with HIV, 3) HIV care providers, and 4) HIV cure researchers. This study produced six key themes to guide the ethical implementation of interventional HIV cure-related research at the EOL: 1) all stakeholder groups supported this research conditioned upon a clearly delineated respect for participant contribution and autonomy, participant understanding and comprehension of the risks associated with the specific intervention(s) to be tested, and broad community support for testing of the proposed intervention(s); 2) to ensure acceptable benefit-risk profiles, researchers should focus on limiting the risks of unintended effects and minimizing undue pain and suffering at the EOL; 3) only well-vetted interventions that are supported by solid pre-clinical data should be tested in the EOL translational research model; 4) the informed consent process must be robust and include process consent; 5) research protocols should be flexible and adopt a patient/participant centered approach to minimize burdens and ensure their overall comfort and safety; and 6) a participant's next-of-kin/loved ones should be a major focus of EOL research but only if the participant consents to such involvement.ConclusionsTo our knowledge, this empirical ethics study generated the first ethical and practical considerations for interventional HIV cure-related research at the EOL. The ethical complexities of such research must be considered now. We must navigate this ethical conundrum so that we are good stewards of the participants' extremely altruistic gifts by maximizing the impact and social value of this research. We hope that this study will serve as the foundation for future research and discussion on this topic.

As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants' next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals (n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones' altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK.

IntroductionLittle is known about the effects of HIV reservoir research at the end of life on staff members involved. Staff members' perceptions and experiences were assessed related to their involvement in the Last Gift, a rapid autopsy study at the University of California San Diego enrolling people living with HIV who are terminally ill and have a desire to contribute to HIV cure-related research.MethodsTwo focus group discussions consisting of clinical (n = 7) and rapid research autopsy (n = 8) staff members were conducted to understand the perspectives of staff members and the impact the Last Gift rapid autopsy study had on them. The total sample consisted of 66.7% females and 33.3% males and was ethnically diverse (66.7% Caucasian, 6.7% African American, 20.0% Asian descent, 6.7% Hispanic descent and American Indian) with a range of experience in the HIV field from 1 year to 30 years.ResultsQualitative focus group data revealed five major themes underlying study staff members' multilayered mental and practical involvement: 1) positive perceptions of the Last Gift study, with sub-themes including Last Gift study participants' altruism, fulfillment, and control at the end of life, 2) perceptions of staff members' close involvement in the Last Gift study, with sub-themes related to staff members' cognitive processing, self-actualization and fulfillment, stress management and resilience, coping mechanisms, and gratitude toward Last Gift participants and toward the study itself, 3) considerations for successful and sustainable study implementation, such as ethical awareness and sustained community and patient engagement, 4) collaborative learning and organizational processes and the value of interdependence between staff members, and 5) considerations for potential study scale-up at other clinical research sites.DiscussionUnderstanding staff members' nuanced emotional and procedural experiences is crucial to the Last Gift study's sustainability and will inform similar cure research studies conducted with people living with HIV at the end of life. The study's potential reproducibility depends on a robust research infrastructure with established, interdependent clinical and rapid autopsy teams, continuous community engagement, and an ethical and well-informed engagement process with people living with HIV.

BackgroundFibrinogen is an essential hemostatic factor and cardiovascular disease risk factor. Early attempts at evaluating the causal effect of fibrinogen on coronary heart disease (CHD) and myocardial infraction (MI) using Mendelian randomization (MR) used single variant approaches, and did not take advantage of recent genome-wide association studies (GWAS) or multi-variant, pleiotropy robust MR methodologies.Methods and findingsWe evaluated evidence for a causal effect of fibrinogen on both CHD and MI using MR. We used both an allele score approach and pleiotropy robust MR models. The allele score was composed of 38 fibrinogen-associated variants from recent GWAS. Initial analyses using the allele score used a meta-analysis of 11 European-ancestry prospective cohorts, free of CHD and MI at baseline, to examine incidence CHD and MI. We also applied 2 sample MR methods with data from a prevalent CHD and MI GWAS. Results are given in terms of the hazard ratio (HR) or odds ratio (OR), depending on the study design, and associated 95% confidence interval (CI). In single variant analyses no causal effect of fibrinogen on CHD or MI was observed. In multi-variant analyses using incidence CHD cases and the allele score approach, the estimated causal effect (HR) of a 1 g/L higher fibrinogen concentration was 1.62 (CI = 1.12, 2.36) when using incident cases and the allele score approach. In 2 sample MR analyses that accounted for pleiotropy, the causal estimate (OR) was reduced to 1.18 (CI = 0.98, 1.42) and 1.09 (CI = 0.89, 1.33) in the 2 most precise (smallest CI) models, out of 4 models evaluated. In the 2 sample MR analyses for MI, there was only very weak evidence of a causal effect in only 1 out of 4 models.ConclusionsA small causal effect of fibrinogen on CHD is observed using multi-variant MR approaches which account for pleiotropy, but not single variant MR approaches. Taken together, results indicate that even with large sample sizes and multi-variant approaches MR analyses still cannot exclude the null when estimating the causal effect of fibrinogen on CHD, but that any potential causal effect is likely to be much smaller than observed in epidemiological studies.

ObjectivesSexually transmitted infections (STIs) are associated with adverse outcomes in pregnancy, including mother-to-child HIV transmission. Yet there are limited data on the prevalence and correlates of STI in pregnant women by HIV status in low- and middle-income countries, where syndromic STI management is routine.MethodsBetween November 2017 and July 2018, we conducted a cross-sectional study of consecutive pregnant women making their first visit to a public sector antenatal clinic (ANC) in Cape Town. We interviewed women ≥18 years and tested them for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) and Trichomonas vaginalis (TV) using Xpert assays (Cepheid, USA); results of syphilis serology came from routine testing records. We used multivariable logistic regression to identify correlates of STI in pregnancy.ResultsIn 242 women (median age 29 years [IQR = 24-34], median gestation 19 weeks [IQR = 14-24]) 44% were HIV-infected. Almost all reported vaginal sex during pregnancy (93%). Prevalence of any STI was 32%: 39% in HIV-infected women vs. 28% in HIV-uninfected women (p = 0.036). The most common infection was CT (20%) followed by TV (15%), then NG (5.8%). Of the 78 women diagnosed with a STI, 7 (9%) were identified and treated syndromically in ANC. Adjusting for age and gestational age, HIV-infection (aOR = 1.89; 95% CI = 1.02-3.67), being unmarried or not cohabiting with the fetus' father (aOR = 2.19; 95% CI = 1.16-4.12), and having STI symptoms in the past three days (aOR = 6.60; 95% CI = 2.08-20.95) were associated with STI diagnosis.ConclusionWe found a high prevalence of treatable STIs in pregnancy among pregnant women, especially in HIV-infected women. Few women were identified and treated in pregnancy.

ObjectivesSexually transmitted infections (STIs) are associated with adverse outcomes in pregnancy, including mother-to-child HIV transmission. Yet there are limited data on the prevalence and correlates of STI in pregnant women by HIV status in low- and middle-income countries, where syndromic STI management is routine.MethodsBetween November 2017 and July 2018, we conducted a cross-sectional study of consecutive pregnant women making their first visit to a public sector antenatal clinic (ANC) in Cape Town. We interviewed women ≥18 years and tested them for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) and Trichomonas vaginalis (TV) using Xpert assays (Cepheid, USA); results of syphilis serology came from routine testing records. We used multivariable logistic regression to identify correlates of STI in pregnancy.ResultsIn 242 women (median age 29 years [IQR = 24-34], median gestation 19 weeks [IQR = 14-24]) 44% were HIV-infected. Almost all reported vaginal sex during pregnancy (93%). Prevalence of any STI was 32%: 39% in HIV-infected women vs. 28% in HIV-uninfected women (p = 0.036). The most common infection was CT (20%) followed by TV (15%), then NG (5.8%). Of the 78 women diagnosed with a STI, 7 (9%) were identified and treated syndromically in ANC. Adjusting for age and gestational age, HIV-infection (aOR = 1.89; 95% CI = 1.02-3.67), being unmarried or not cohabiting with the fetus' father (aOR = 2.19; 95% CI = 1.16-4.12), and having STI symptoms in the past three days (aOR = 6.60; 95% CI = 2.08-20.95) were associated with STI diagnosis.ConclusionWe found a high prevalence of treatable STIs in pregnancy among pregnant women, especially in HIV-infected women. Few women were identified and treated in pregnancy.

Background: Increasing HIV testing and treatment coverage among people living with HIV (PLHIV) is essential for achieving global HIV epidemic control. However, compared to women, cis-gender heterosexual men living with HIV are significantly less likely to know their HIV status, initiate anti-retroviral therapy (ART) and achieve viral suppression. This is particularly true in South Africa, where men are also at increased risk of mortality resulting from AIDS-related illnesses. While there is growing knowledge of Treatment as Prevention or the concept Undetectable = Untransmittable (U = U) among PLHIV in Western and high-income countries, the reach and penetration of the U = U message in sub-Saharan Africa remains limited, and few studies have evaluated the impact of accessible and relatable U = U messages on ART initiation and adherence. To address these gaps, rigorous evaluations of interventions that incorporate U = U messages are needed, especially among men in high prevalence settings. Methods: Building on our U = U messages that we previously developed for men using behavioral economics insights and a human-centered design, we will conduct two sequential hybrid type 1 effectiveness-implementation trials to evaluate the impact of U = U messages on men's uptake of community-based HIV testing and ART initiation (Trial 1), and retention in care and achievement of viral suppression (Trial 2). For trial 1, a cluster randomized trial will be implemented with HIV testing service site-days (each day at one testing site) randomized to U = U or standard-of-care (SoC) messages inviting men to test for HIV. For trial 2, an individual-level randomized control trial will be implemented, with men initiating ART at six government clinics randomized to receive U = U counselling or SoC treatment adherence messaging. We will incorporate a multi-method evaluation to inform future implementation of U = U messaging interventions. The study will be conducted in the Buffalo City Metro Health District of the Eastern Cape Province and in the Cape Town Metro Health District in the Western Cape Province in South Africa. Discussion: These trials are the first to rigorously evaluate the impact of U = U messaging on HIV testing uptake, ART initiation and achievement of viral suppression among African men. If effective, these messaging interventions can shape global HIV testing, treatment and adherence counselling guidelines and practices. [ABSTRACT FROM AUTHOR]

Community-based chronic care intervention is important in the control and prevention of lifelong conditions such as podoconiosis and similar 'intensive disease management' neglected tropical diseases (NTDs). Despite a call for such interventions, few efforts have been made to identify opportunities and challenges related to their implementation. Employing a qualitative approach, this study explored the possibility of engaging community actors, physical places and networks to promote chronic care management in rural Ethiopia. We gathered data from affected individuals, community members, local leaders, health professionals and community health workers between April and May 2022. The study revealed that affected individuals, family members, religious leaders, traditional leaders, and health professionals have the potential to extend chronic care management in rural areas. Houses, churches, schools, and healthcare facilities are suitable venues at which to perform interventions. Strong community solidarity and political will are vital to chronic care interventions, while lack of understanding about chronic conditions, financial constraints, and limited resources at healthcare facilities could pose challenges. Using community assets has great promise for expanding chronic care management with minimal costs and efforts in under resourced areas. Achieving this will require a successful plan to coordinate the collaboration among the agents and settings. [ABSTRACT FROM AUTHOR]

Weight and skin-fold measurements were made at five-day intervals during a 47-day expedition by six men and three women from the edge of the sea ice to the South Pole. From these, together with detailed manual records of the nutrition for individual participants, the average daily energy expenditure was determined before and after a resupply at approximately mid-point of the expedition. For all participants body weight fell during the expedition with the overall loss being much smaller for the three female participants (-4.0, -4.0, -4.4kg) than for the male participants, (mean±sd) -8.6±2.0kg. Fat weight fell approximately linearly during the expedition with a total loss of (-4.1, -6.5 and -2.5kg) for the three female participants and -6.8±1.7kg for the male participants. Individual fat-free weight changed by a smaller amount overall: (0.13, 2.5 and -1.8kg) for the three female participants; -1.8±2.0kg for the male participants who, with one exception, lost fat-free tissue All participants showed a substantial variation in fat-free tissue weight during the expedition. Analysis of the daily energy expenditure showed adequate nutrition but the intake fell for the second part of the expedition although the reasons for this are unclear, but adaptation to the cold, altitude and workload are possible explanations. The validity of this time-averaged measurement for individual participants was determined from analysing moments about the mean of time-series actigraphy data from wrist worn devices. The mean and autocorrelation function of the actigraphy data across subjects were analysed to determine whether measures could be compared between participants. The first, second and third moment about the mean of the day-to-day activity was found to be time-invariant for individual subjects (χ2, p>0.05) and the normalized mean and autocorrelation measured over a day for each participant indistinguishable from the mean of the group (χ2, p>0.05) allowing both longitudinal and cross-sectional analysis. [ABSTRACT FROM AUTHOR]

ObjectiveIdentify system-level features in HIV migration within a host across body tissues. Evaluate heterogeneity in the presence and magnitude of these features across hosts.MethodUsing HIV DNA deep sequencing data generated across multiple tissues from 8 people with HIV, we represent the complex dependencies of HIV migration among tissues as a network and model these networks using the family of exponential random graph models (ERGMs). ERGMs allow for the statistical assessment of whether network features occur more (or less) frequently in viral migration than might be expected by chance. The analysis investigates five potential features of the viral migration network: (1) bi-directional flow between tissues; (2) preferential migration among tissues in the same biological system; (3) heterogeneity in the level of viral migration related to HIV reservoir size; (4) hierarchical structure of migration; and (5) cyclical migration among several tissues. We calculate the Cohran's Q statistic to assess heterogeneity in the magnitude of the presence of these features across hosts. The analysis adjusts for missing data on body tissues.ResultsWe observe strong evidence for bi-directional flow between tissues; migration among tissues in the same biological system; and hierarchical structure of the viral migration network. This analysis shows no evidence for differential level of viral migration with respect to the HIV reservoir size of a tissue. There is evidence that cyclical migration among three tissues occurs less frequent than expected given the amount of viral migration. The analysis also provides evidence for heterogeneity in the magnitude that these features are present across hosts. Adjusting for missing tissue data identifies system-level features within a host as well as heterogeneity in the presence of these features across hosts that are not detected when the analysis only considers the observed data.DiscussionIdentification of common features in viral migration may increase the efficiency of HIV cure efforts as it enables targeting specific processes.

To observe trends of diabetes and its associated risk factors from health surveys 2002-2017 in rural areas of Baluchistan-Pakistan and a secondary analysis based on community based health surveys of Baluchistan conducted between 2001-02, 2009-10, and 2016-17. A total of 4250 participants were included in this combined analysis, 2515 from 2001-2002, 1377 from 2009-2010 and 358 from 2016-2017 survey year. In each survey, detailed information of baseline parameters were noted on a predesigned questionnaire. Fasting plasma glucose (FPG) was used for diagnosis of diabetes for comparative purposes in this analysis. Cardiovascular (CVD) risk factors including hypertension, obesity, dyslipidaemia, tobacco use, alcohol consumption, and physical activity were compared. Most subjects were aged 30-50 years and males were found higher in 2016-17 compared to 2001-02 and 2009-10. Pronounced increases in BMI, waist circumference, blood pressure, and family history of diabetes were observed in 2016-17. Diabetes prevalence was 4.2 (3.4-4.9), 7.8 (6.6-9.2) and 31.9 (26.9-37.4), whilst pre-diabetes was 1.7 (1.3-2.2), 3.6 (2.8-4.6) and 10.7 (7.6-14.9) in years 2001-02, 2009-10, and 2016-17, respectively. Among those aged 20-39years, prevalence of diabetes was stable from 2001-10 yet increased considerably between the ages of 30-39years in 2016-17. Throughout the observed period, rapid increases were observed in hypertension, obesity, and dyslipidaemia, however, addiction to tobacco use and alcohol intake decreased. Adjusted odd ratios showed age, marital status, education, hypertension, and family history of diabetes as associated risk factors for glycaemic dysregulation. The rural Baluchistan population is confronted with increasing trends of early onset diabetes due to highly associated CVD risk factors, especially central obesity and dyslipidaemia, raising a major public health challenge.

Protein tandem repeats (TRs) are motifs comprised of near-identical contiguous sequence duplications. They are found in approximately 14% of all proteins and are implicated in diverse biological functions facilitating both structured and disordered protein-protein and protein-DNA interactions. These functionalities make protein TR domains an attractive component for the modular design of protein constructs. However, the repetitive nature of DNA sequences encoding TR motifs complicates their synthesis and mutagenesis by traditional molecular biology workflows commonly employed by protein engineers and synthetic biologists. To address this challenge, we developed a computational protocol to significantly reduce the complementarity of DNA sequences encoding TRs called TReSR (for Tandem Repeat DNA Sequence Redesign). The utility of TReSR was demonstrated by constructing a novel constitutive repressor synthesized by duplicating the LacI DNA binding domain into a single-chain TR construct by assembly PCR. Repressor function was evaluated by expression of a fluorescent reporter delivered on a single plasmid encoding a three-component genetic circuit. The successful application of TReSR to construct a novel TR-containing repressor with a DNA sequence that is amenable to PCR-based construction and manipulation will enable the incorporation of a wide range of TR-containing proteins for protein engineering and synthetic biology applications.

IntroductionSecond-line pharmacotherapy for Type 2 Diabetes Mellitus ('diabetes') is necessary for optimal glycaemic control and preventing longer-term complications. We aimed to describe temporal trends in, and associations of, Australian general practitioner (GP) registrars' prescription, and initiation, of 'new' second-line oral agents (dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists) compared to sulphonylureas.Materials and methodsA longitudinal analysis (2010-2018) of data from the Registrar Clinical Encounters in Training project. Analysis included any diabetes problem/diagnosis that involved prescription of sulphonylureas or 'new' oral agents. Simple and multiple logistic regression models were fitted within the generalised estimating equations framework.Results2333 registrars recorded 6064 diabetes problems/diagnoses (1.4%). 835 problems/diagnoses involved sulphonylurea or 'new' medication prescription. Of these, 61.0% [95% CI:57.4-64.4] involved 'new' medication prescription. 230 problems/diagnoses involved sulphonylurea or 'new' medication initiation, with 77% [95%CI:70.8-82.1] involving a 'new' medication. There was a significant 52% per year increase in prescribing (OR = 1.52[95% CI:1.38-1.68],pConclusionRegistrar uptake of 'new' oral agents compared to sulphonylureas has increased rapidly.

IntroductionAttempts to conceive and pregnancy may increase HIV transmission to sex partners and infants. Our study evaluated the association between fertility intentions and HIV acquisition among Zambian HIV-serodiscordant couples.MethodsWe collected demographic, behavioral, clinical exposures, and data on fertility intentions in a cohort of HIV-serodiscordant couples in Lusaka, Zambia from 2005 to 2012. We evaluated factors associated with fertility intentions stratified by gender using multivariable logistic regression. Multivariable Cox proportional hazard models were used to evaluate the associations between fertility intentions and HIV acquisition controlling for a priori confounders and covariates that substantially (>10%) changed the effect estimates in univariate analyses.ResultsAmong 1,029 serodiscordant couples, 311 agreed that they wanted children in the future (30%), 368 agreed they did not want children (36%), and 344 couples disagreed about having children (34%), with men more likely than women to want children. Women wanting child(ren) was associated with increased odds of baseline pregnancy (adjusted odds ratio [aOR] = 4.80 (95% confidence interval [CI] = 2.93, 7.85)), fewer previous pregnancies (aOR = 0.85 per additional pregnancy (95% CI = 0.78, 0.93)), and partner fertility intention (aOR = 2.89 (95% CI = 2.14, 3.91)) adjusting for woman's age, literacy, years cohabiting and HIV status. Men wanting child(ren) was associated with younger age (aOR = 0.96 per year (95% CI = 0.93, 0.99)), fewer years cohabiting (aOR = 0.95 (95% CI = 0.92, 0.98)), number of previous partners' pregnancies (aOR = 0.90 (95% CI = 0.82, 0.98)), and partner fertility intention (aOR = 3.00 (95% CI = 2.21, 4.07)) adjusting for partner's age, literacy, HIV status and partner's baseline pregnancy. In adjusted survival analyses, HIV-negative women were more likely to seroconvert if they themselves wanted children (aHR = 2.36 (95% CI = 1.41, 3.96)) vs. did not want children, or if their partner wanted children (aHR = 2.34 (95% CI = 1.33, 4.11)) vs. did not want children, or if the couple agreed that they wanted children (aHR = 2.08 (95% CI = 1.01, 4.30)), adjusting for women's age, women's literacy, previous pregnancies and time in study. HIV-negative men were more likely to seroconvert if their female partner wanted a child in the next 12-months (aHR = 1.94 (95% CI = 1.02, 3.68)) vs. did not want children, and when both partners wanted children (aHR = 2.02 (CI = 1.09, 3.73)) vs. they did not want children, adjusting for men's age and literacy, couple income, number of live children, male circumcision status and time in study.ConclusionWomen had increased risk of HIV acquisition if they and/or their partner wanted a child, while men had increased risk of HIV acquisition when their partner or if both partners agreed that they wanted children. Safer-conception interventions are needed to protect HIV uninfected women and men from HIV acquisition in HIV-serodiscordant couples who want children.

HIV acquisition during pregnancy and breastfeeding significantly contributes toward paediatric HIV infection; however, little is known about risk behaviours in HIV-uninfected pregnant and postpartum women. We conducted twenty-six in-depth-interviews between July and December 2016 using a semi-structured interview guide among HIV-uninfected pregnant and recently postpartum women at-risk of HIV acquisition (defined as reporting ≥1 of the following: partner's serostatus unknown or HIV-infected, recent condomless sex in pregnancy, and/or alcohol use during pregnancy) who attended primary healthcare services. Our study contextualizes factors related to risky sexual behaviours during pregnancy and postpartum periods and assesses knowledge and hypothetical acceptability of pre-exposure prophylaxis (PrEP) in pregnancy. Translated and transcribed data were coded and analysed by three researchers using a thematic analysis approach. In interviews with HIV-uninfected pregnant/postpartum women at-risk of HIV acquisition, we identified common themes associated with sexual risk behaviours during pregnancy, including: lack of control over decisions in sex and condom use in pregnancy, low perceived risk (e.g. beliefs that their partner has the same HIV-negative serostatus), and socio-cultural beliefs around condom use during pregnancy (e.g. contact with sperm is essential for baby's development). PrEP knowledge was low among HIV-uninfected pregnant and breastfeeding women, and potential acceptability was good, though primary concerns were around the potential impact on the infant. While mothers presented a clear desire to protect themselves from HIV acquisition once pregnant, they also reported lack of control, and socio-cultural beliefs, like sex is good for the baby, that increased their risk of seroconversion. Mothers had limited PrEP awareness but reported hypothetical willingness to use PrEP because of concerns over HIV acquisition and onward mother to child transmission.

BackgroundHIV acquisition in pregnancy and breastfeeding contributes significantly toward pediatric HIV infection. However, little is known about how sexual behavior changes during pregnancy and postpartum periods which will help develop targeted HIV prevention and transmission interventions, including pre-exposure prophylaxis (PrEP).MethodsCross-sectional study in HIV-infected and uninfected pregnant and postpartum women in Cape Town, South Africa. Interviewers collected survey data on demographic, sexual behaviors, and alcohol use among pregnant and post-partum women. We report descriptive results of sexual behavior by trimester and postpartum period, and results of multivariable logistic regression stratified by pregnancy status.ResultsWe enrolled 377 pregnant and postpartum women (56% pregnant, 40% HIV-infected). During pregnancy, 98% of women reported vaginal sex (8% anal sex, 44% oral sex) vs. 35% and 88% during the periods 0-6 and 7-12 months postpartum, respectively (p1 partner in the past 12-months compared to postpartum women (18% vs. 13%, respectively, p6-months postpartum (13 mean sex acts in first trimester; 17 mean sex acts >6-months postpartum). Pregnant women had increased odds of reporting condomless sex at last sex (aOR = 2.96;95%CI = 1.84-4.78) and ever having condomless sex in past 3-months (aOR = 2.65;95%CI = 1.30-5.44) adjusting for age, HIV status, and sex frequency compared to postpartum women.ConclusionWe identified that sexual behaviors and risk behaviors were high and changing during pregnancy and postpartum periods, presenting challenges to primary and secondary HIV prevention efforts, including PrEP delivery to pregnant and breastfeeding women.

BackgroundHIV acquisition in pregnancy and breastfeeding contributes significantly toward pediatric HIV infection. However, little is known about how sexual behavior changes during pregnancy and postpartum periods which will help develop targeted HIV prevention and transmission interventions, including pre-exposure prophylaxis (PrEP).MethodsCross-sectional study in HIV-infected and uninfected pregnant and postpartum women in Cape Town, South Africa. Interviewers collected survey data on demographic, sexual behaviors, and alcohol use among pregnant and post-partum women. We report descriptive results of sexual behavior by trimester and postpartum period, and results of multivariable logistic regression stratified by pregnancy status.ResultsWe enrolled 377 pregnant and postpartum women (56% pregnant, 40% HIV-infected). During pregnancy, 98% of women reported vaginal sex (8% anal sex, 44% oral sex) vs. 35% and 88% during the periods 0-6 and 7-12 months postpartum, respectively (p1 partner in the past 12-months compared to postpartum women (18% vs. 13%, respectively, p6-months postpartum (13 mean sex acts in first trimester; 17 mean sex acts >6-months postpartum). Pregnant women had increased odds of reporting condomless sex at last sex (aOR = 2.96;95%CI = 1.84-4.78) and ever having condomless sex in past 3-months (aOR = 2.65;95%CI = 1.30-5.44) adjusting for age, HIV status, and sex frequency compared to postpartum women.ConclusionWe identified that sexual behaviors and risk behaviors were high and changing during pregnancy and postpartum periods, presenting challenges to primary and secondary HIV prevention efforts, including PrEP delivery to pregnant and breastfeeding women.

HIV acquisition during pregnancy and breastfeeding significantly contributes toward paediatric HIV infection; however, little is known about risk behaviours in HIV-uninfected pregnant and postpartum women. We conducted twenty-six in-depth-interviews between July and December 2016 using a semi-structured interview guide among HIV-uninfected pregnant and recently postpartum women at-risk of HIV acquisition (defined as reporting ≥1 of the following: partner's serostatus unknown or HIV-infected, recent condomless sex in pregnancy, and/or alcohol use during pregnancy) who attended primary healthcare services. Our study contextualizes factors related to risky sexual behaviours during pregnancy and postpartum periods and assesses knowledge and hypothetical acceptability of pre-exposure prophylaxis (PrEP) in pregnancy. Translated and transcribed data were coded and analysed by three researchers using a thematic analysis approach. In interviews with HIV-uninfected pregnant/postpartum women at-risk of HIV acquisition, we identified common themes associated with sexual risk behaviours during pregnancy, including: lack of control over decisions in sex and condom use in pregnancy, low perceived risk (e.g. beliefs that their partner has the same HIV-negative serostatus), and socio-cultural beliefs around condom use during pregnancy (e.g. contact with sperm is essential for baby's development). PrEP knowledge was low among HIV-uninfected pregnant and breastfeeding women, and potential acceptability was good, though primary concerns were around the potential impact on the infant. While mothers presented a clear desire to protect themselves from HIV acquisition once pregnant, they also reported lack of control, and socio-cultural beliefs, like sex is good for the baby, that increased their risk of seroconversion. Mothers had limited PrEP awareness but reported hypothetical willingness to use PrEP because of concerns over HIV acquisition and onward mother to child transmission.

IntroductionAnimal models have been vital for scientific discovery but have limitations, especially in infectious disease research. It is essential to develop a means to study these diseases in human models. We hypothesized that altruistic people would willingly participate in research near the end-of-life (EOL), for the benefit of science and to provide one last gift to society.MethodologyTwo surveys were administered to 377 self-reported HIV-negative and 96 HIV-positive individuals. Hypothetical questions assessed their willingness to participate in altruistic research in the last 6 months of life, which might result in a shortened lifespan or physical discomforts. The self-reported HIV-negative group was also asked about willingness to be exposed to infectious pathogens for the sake of research.ResultsAlmost all responders expressed willingness to participate in research at the EOL, regardless of HIV-status. The majority of participants were willing to endure physical discomfort for the sake of research. 'Blood draws' was identified as the most tolerable physical discomfort (>70% in both groups). In both groups, >60% were willing to shorten their lifespans for the sake of research. A third of the self-reported HIV-negative group expressed willingness to be exposed to at least one infectious agent to participate in EOL research.ConclusionsOur exploratory study demonstrates that people would welcome the opportunity to participate in altruistic research near the EOL. Such research could greatly impact the way infectious disease research is conducted. This study is limited however by its hypothetical nature. Further research is necessary to confirm this interest in those with terminal illness before any further clinical research effort at the EOL can be performed.

BackgroundAssessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.Methods and findingsWe identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results.ConclusionsOur results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.

Older people in residential aged care are susceptible to acute illness or injury which may necessitate an ambulance call out, assessment/treatment by a paramedic and transfer to a hospital emergency department. Understanding the case mix of residential aged care ambulance attendances is important for prevention strategies and for planning services. A retrospective observational closed cohort study was designed to investigate the characteristics of emergency ambulance call outs to 15 residential aged care sites in the Australian Capital Territory over a 12-month period. Data were collected from the local ambulance service and the aged care sites. Case load data were analysed to determine rates, clinical characteristics, ambulance attendance outcomes and the temporal distribution of call outs. A Poisson regression model was developed to investigate demographic, morbidity and medication-related risk factors associated with the number of ambulance call outs per resident. Annual ambulance call out costs were estimated. There were 1,275 residents, with 396 (31.1%) requiring at least one ambulance call out over 12 months. Of 669 ambulance attendances, the majority (87.0%) were transported to emergency departments. Trauma (23.9%), pain (16.9%) and infections (9.4%) were the most common primary assessments by the ambulance attendees. Cases/day were similar throughout the year and on weekdays compared to weekends/public holidays. The main predictors of ambulance call out were multi-morbidity, taking regular anticholinergic medicines, being male and younger age. Estimated costs of ambulance call outs/year were $475/resident and $40,375/residential aged care site. The most frequent primary assessments (trauma, pain, infections) may constitute priorities for developing prevention strategies and for treatment initiatives within residential aged care. Strategies to reduce anticholinergic medication prescribing may also be a potential intervention to decrease ambulance call outs and hospital emergency department demand. The ambulance usage data from this study may be useful to compare with future datasets to measure the impact of the introduction of new services. [ABSTRACT FROM AUTHOR]

Background: Indigenous populations globally have significantly high rates of type 2 diabetes compared to their non-Indigenous counterparts. This study aims to implement and evaluate the effectiveness of a culturally and contextually informed Aboriginal Diabetes Workforce Training Program on Aboriginal primary health care workforce knowledge, attitude, confidence, skill and practice relating to diabetes care. Methods: A Cluster Randomised Crossover Control Trial with two arms (Group A and Group B) will be conducted with Aboriginal primary health care services in South Australia. These services primarily provide primary health care to Aboriginal and Torres Strait Islander people. All healthcare service sites will be randomised into groups A and B to receive the training program. The training program consists of three components: 1) Peer support network, 2) E-Learning modules and 3) onsite support. Aboriginal Health Workers of participating sites will be invited to participate in the monthly online peer support network and all chronic disease staff are eligible to participate in the E-Learning modules and onsite support. The Peer Support Network runs for the entirety of the study, 17 months. Training components 2 and 3 occur simultaneously and are 2.5 months in length, with a six-month washout period between the two randomised groups undertaking the training. All primary outcomes of the study relate to diabetes management in a primary health care settings and measure participants' knowledge, attitude, confidence, practice and skills. These will be collected at seven time points across the entire study. Secondary outcomes measure satisfaction of the peer support network using a survey, interviews to understand enablers and barriers to participation, health service systems characteristics through focus groups, and medical record review to ascertain diabetes patients' care received and their clinical outcomes up to 12 months post training intervention. Discussion: The findings will explore the effectiveness of the training program on Aboriginal primary health care provider knowledge, attitude, confidence, skill and practice relating to diabetes care. The final findings will be published in 2027. Trial registration: The study was prospectively registered in The Australian New Zealand Clinical Trials Registry (ANZCTR), with registration number ACTRN12623000749606 at ANZCTR - Registration. Universal Trial Number (UTN) U1111-1283-5257. [ABSTRACT FROM AUTHOR]

Studies leveraging gene-environment (GxE) interactions within Mendelian randomization (MR) analyses have prompted the emergence of two similar methodologies: MR-GxE and MR-GENIUS. Such methods are attractive in allowing for pleiotropic bias to be corrected when using individual instruments. Specifically, MR-GxE requires an interaction to be explicitly identified, while MR-GENIUS does not. We critically examine the assumptions of MR-GxE and MR-GENIUS in the absence of a pre-defined covariate, and propose sensitivity analyses to evaluate their performance. Finally, we explore the effect of body mass index (BMI) upon systolic blood pressure (SBP) using data from the UK Biobank, finding evidence of a positive effect of BMI on SBP. We find both approaches share similar assumptions, though differences between the approaches lend themselves to differing research settings. Where a suitable gene-by-covariate interaction is observed MR-GxE can produce unbiased causal effect estimates. MR-GENIUS can circumvent the need to identify interactions, but as a consequence relies on either the MR-GxE assumptions holding globally, or additional information with respect to the distribution of pleiotropic effects in the absence of an explicitly defined interaction covariate.

IntroductionYoung female sex workers (FSW) are disproportionately vulnerable to HIV. Zimbabwe data show higher HIV incidence and lower engagement in services compared to older FSW. Utilizing data from a combination HIV prevention and treatment intervention, we describe engagement in the HIV services over time among FSW 18-24 years, compared to those ≥25 years of age.Materials and methodsData were collected via respondent-driven sampling (RDS) surveys in 14 communities in 2013 and 2016, with >2500 FSW per survey. They included blood samples for HIV and viral load testing. As the intervention had no significant impact on HIV care cascade outcomes, data were aggregated across study arms. Analyses used RDS-II estimation.ResultsMean age in 2013 and 2016 was 31 and 33 years, with 27% and 17% aged 18-24 years. Overall HIV prevalence was 59% at each timepoint, and 35% and 36% among younger FSW. From 2013 to 2016 there was an increase in young HIV-positive FSW knowing their status (38% vs 60%, OR = 2.51, pDiscussionYoung FSW had improvements in care cascade outcomes, and proportionate improvements similar to older FSW, yet they remain less engaged in services overall. This implies that the dedicated FSW services in Zimbabwe are having a comparably positive impact across age groups, however more is likely required to address young FSW's unique vulnerabilities and needs.

Background/objectivesWith the increasing popularity and saliency of social media, there is a pressing need to identify whether exposure to such content can affect road rule compliance, especially given that social media has been found to influence other risky behaviours. This systematic review (conducted in accordance with the PRISMA guidelines) summarised existing evidence concerning: (a) the nature of driving-related content on social media and (b) whether such content can influence attitudes and subsequent driving behaviour.MethodsPeer-reviewed articles written in English, that explored social media content in relation to road safety or driving behaviours (e.g., speeding, tailgating, distraction, impaired driving, and seatbelt use), were eligible for review. Searches were conducted via SCOPUS, PUBMED, ProQuest and TRID in June 2021.Results/discussionA total of 8 studies met the requirements for this study, resulting in three key findings. First, it was found that very few studies have explored the type and extent of driving-related content on social media, and the small collection of existing research has focused solely on YouTube and Twitter. Second, whilst the nature of driving-related content on social media varies substantially across studies, a body of content exists that promotes or encourages risky driving behaviour or road rule violations. Third, and despite the array of available online content, there is a paucity of research illuminating the impact of social media messages on attitudes towards, and behaviours linked to road safety. This review highlights the need for research to keep pace with the rapidly changing nature of social media (not least the impacts upon human behaviour) and outlines pathways to increase current scientific understanding.

ObjectiveSexually transmitted infections (STI) are common among HIV-infected men who have sex with men (MSM). While behavioral factors are important in STI acquisition, other biological factors such as immune modulation due to chronic viral infection may further predispose to STI acquisition.DesignPost Hoc analysis including data collected over 12 months of follow-up from 131 HIV-infected MSM receiving antiretroviral therapy and screened for incident bacterial STI every 3 months.MethodsGenital secretions collected at baseline were used to measure herpesvirus replication and inflammatory cytokines. Baseline predictors of STI were determined using survival analysis of time to incident STI.ResultsAll participants were seropositive for cytomegalovirus (CMV), and 52% had detectable genital CMV at baseline. Thirty-five individuals acquired STI during follow-up, sometimes with multiple pathogen (17 syphilis, 21 gonorrhea, 14 chlamydia). Syphilis acquisition was associated with genital CMV replication at baseline (19.1% CMV-shedders versus 4.8% non-shedders, p=0.03) and younger age (p=0.02). Lower seminal MCP-1 was associated with higher seminal CMV levels and with syphilis acquisition (p

BackgroundMeasurement of HIV DNA-bearing cells in cerebrospinal fluid (CSF) is challenging because few cells are present. We present a novel application of the sensitive droplet digital (dd)PCR in this context.MethodsWe analyzed CSF cell pellets and paired peripheral blood mononuclear cells (PBMC) from 28 subjects, 19 of whom had undetectable HIV RNA (

BackgroundIt is assumed that the oxytocin receptor gene (OXTR) is associated with factors that are related to features of reproduction as well as the currently emerging fields of mood and emotional response.MethodsWe analysed data from over 8000 mothers who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC). We determined reproductive, emotional and personality differences related to the two SNPs rs53576 and rs2254298 of the oxytocin receptor gene to determine whether there was evidence in this population for: (i) associations with emotional and personality differences, and (ii) behavioural or environmental links with these SNPs using a hypothesis free approach with over 1000 types of exposure.ResultsOur analyses of 7723 women showed that there were no differences in 11 mood, social or relationship characteristics associated with the rs2254298, and just one with rs53576 (with emotional loneliness)--one statistically significant out of 22 tests is no more than would be expected by chance. There were no interactions with childhood abuse. Using a hypothesis-free approach we found few indicators of environmental or behavioural differences associated with rs2254298, but there was an excess of associations with eating habits with rs53576. The findings included an association with dieting to lose weight, and habits typical of bulimia for the women with GG. The nutrition of the women also showed negative associations of the GG genotype with 13 nutrients, including vitamins D, B12 and retinol, and intake of calcium, potassium and iodine.ConclusionsWe conclude that this large database of pregnant women was unable to provide confirmation of the types of personality associated with these two OXTR SNPs, but we have shown some evidence of eating differences in those with GG on rs53576. Confirmation of our hypothesis free associations using other data sets is important.

BackgroundMultiple prevention measures have the possibility of impacting HIV incidence in South Korea, including early diagnosis, early treatment, and pre-exposure prophylaxis (PrEP). We investigated how each of these interventions could impact the local HIV epidemic, especially among men who have sex with men (MSM), who have become the major risk group in South Korea. A mathematical model was used to estimate the effects of each these interventions on the HIV epidemic in South Korea over the next 40 years, as compared to the current situation.MethodsWe constructed a mathematical model of HIV infection among MSM in South Korea, dividing the MSM population into seven groups, and simulated the effects of early antiretroviral therapy (ART), early diagnosis, PrEP, and combination interventions on the incidence and prevalence of HIV infection, as compared to the current situation that would be expected without any new prevention measures.ResultsOverall, the model suggested that the most effective prevention measure would be PrEP. Even though PrEP effectiveness could be lessened by increased unsafe sex behavior, PrEP use was still more beneficial than the current situation. In the model, early diagnosis of HIV infection was also effectively decreased HIV incidence. However, early ART did not show considerable effectiveness. As expected, it would be most effective if all interventions (PrEP, early diagnosis and early treatment) were implemented together.ConclusionsThis model suggests that PrEP and early diagnosis could be a very effective way to reduce HIV incidence in South Korea among MSM.

ObjectiveTo reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission.DesignHIV-1 pol sequence data were analyzed to infer the local transmission network.MethodsWe analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions.ResultsHIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p

BackgroundFatal opioid overdose is a pressing public health concern in the United States. Addressing barriers and augmenting facilitators to take-home naloxone (THN) access and administration could expand program reach in preventing fatal overdoses.MethodsTHN access (i.e., being prescribed or receiving THN) was assessed in a Baltimore, Maryland-based sample of 577 people who use opioids (PWUO) and had a history of injecting drugs. A sub-analysis examined correlates of THN administration among those with THN access and who witnessed an overdose (N = 345). Logistic generalized estimating equations with robust standard errors were used to identify facilitators and barriers to accessing and using THN.ResultsThe majority of PWUO (66%) reported THN access. In the multivariable model, decreased THN access was associated with the fear that a person may become aggressive after being revived with THN (aOR: 0.55, 95% CI: 0.35-0.85), police threaten people at an overdose event (aOR: 0.68, 95% CI: 0.36-1.00), and insufficient overdose training (aOR: 0.43, 95% CI: 0.28-0.68). Enrollment in medication-assisted treatment, personally experiencing an overdose, and graduating from high school were associated with higher access. About half (49%) of PWUO with THN access and who had witnessed an overdose reported having administered THN. THN use was positively associated with "often" or "always" carrying THN (aOR: 3.47, 95% CI: 1.99-6.06), witnessing more overdoses (aOR:5.18, 95% CI: 2.22-12.07), experiencing recent homelessness, and injecting in the past year. THN use was reduced among participants who did not feel that they had sufficient overdose training (aOR: 0.56, 95% CI: 0.32-0.96).ConclusionTHN programs must bolster confidence in administering THN and address barriers to use, such as fear of a THN recipient becoming aggressive. Normative change around carrying THN is an important component in an overdose prevention strategy.