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BackgroundCommunity mobilisation, engaging communities in a process to collectively enact change, could improve HIV testing and care engagement. In South Africa, current rates fall below those needed for epidemic control. We assessed whether community mobilisation increased HIV testing, linkage to care, and retention in care over time in intervention relative to control communities.MethodsWe conducted a cluster-randomised controlled trial in villages in the Agincourt sub-district of the rural Mpumalanga Province in South Africa. 15 villages were randomly assigned to either a community mobilisation intervention engaging residents to address social barriers to HIV testing and treatment (intervention arm) or to a control arm using balanced randomisation. Villages were eligible if they had been fully enumerated in 2014, had not been included in previous mobilisation activities, and included over 500 permanent adult residents aged 18-49 years. Primary outcomes included quarterly rates of HIV testing, linkage to care, and retention in care documented from health facility records among residents of the intervention and control communities over the 3-year study period. Intention-to-treat analyses employed generalised estimating equations stratified by sex. This trial is registered with ClinicalTrials.gov, NCT02197793.FindingsBetween Aug 1, 2015, and July 31, 2018, residents in eight intervention communities (n=20 544 residents) and seven control communities (n=17 848) contributed data; 92 residents contributed to both arms. Among men, HIV testing increased quarterly by 12·1% (relative change [RC] 1·121, 95% CI 1·099 to 1·143, p

The human immunodeficiency virus (HIV) epidemic among adolescent girls and young women (AGYW) in sub-Saharan Africa is a critical public health problem. We assessed whether depressive symptoms in AGYW were longitudinally associated with incident HIV, and identified potential social and behavioral mediators. Data came from a randomized trial of a cash transfer conditional on school attendance among AGYW (ages 13-21 years) in rural Mpumalanga Province, South Africa, during 2011-2017. We estimated the relationship between depressive symptoms and cumulative HIV incidence using a linear probability model, and we assessed mediation using inverse odds ratio weighting. Inference was calculated using the nonparametric bootstrap. AGYW with depressive symptoms had higher cumulative incidence of HIV compared with those without (risk difference = 3.5, 95% confidence interval (CI): 0.1, 7.0). The strongest individual mediators of this association were parental monitoring and involvement (indirect effect = 1.6, 95% CI: 0.0, 3.3) and reporting a partner would hit her if she asked him to wear a condom (indirect effect = 1.5, 95% CI: -0.3, 3.3). All mediators jointly explained two-thirds (indirect effect = 2.4, 95% CI: 0.2, 4.5) of the association between depressive symptoms and HIV incidence. Interventions addressing mental health might reduce risk of acquiring HIV among AGYW.

Ultrathin ferroelectric materials could potentially enable low-power perovskite ferroelectric tetragonality logic and nonvolatile memories1,2. As ferroelectric materials are made thinner, however, the ferroelectricity is usually suppressed. Size effects in ferroelectrics have been thoroughly investigated in perovskite oxides-the archetypal ferroelectric system3. Perovskites, however, have so far proved unsuitable for thickness scaling and integration with modern semiconductor processes4. Here we report ferroelectricity in ultrathin doped hafnium oxide (HfO2), a fluorite-structure oxide grown by atomic layer deposition on silicon. We demonstrate the persistence of inversion symmetry breaking and spontaneous, switchable polarization down to a thickness of one nanometre. Our results indicate not only the absence of a ferroelectric critical thickness but also enhanced polar distortions as film thickness is reduced, unlike in perovskite ferroelectrics. This approach to enhancing ferroelectricity in ultrathin layers could provide a route towards polarization-driven memories and ferroelectric-based advanced transistors. This work shifts the search for the fundamental limits of ferroelectricity to simpler transition-metal oxide systems-that is, from perovskite-derived complex oxides to fluorite-structure binary oxides-in which 'reverse' size effects counterintuitively stabilize polar symmetry in the ultrathin regime.

BackgroundHIV testing rates in many hyper-endemic areas are lower than needed to curtail the HIV epidemic. New HIV testing strategies are needed to overcome barriers to traditional clinic based testing; HIV self-testing is one modality that offers promise in reaching individuals who experience barriers to clinic-based testing.MethodsWe conducted a randomized control trial among young women ages 18-26 living in rural Mpumalanga, South Africa where they were randomized in a 1:1 allocation to either the: (1) HIV Counseling and Testing (HCT) arm: an invitation to test at one of the 9 local government clinics where free HCT is provided and is standard of care (SOC), or (2) choice arm: choice of either a clinic-based HCT invitation or oral HIV Self-Testing (HIVST) kits. Depending on the arm, participants were also provided either: (1) 4 HCT invitations to provide to peers/partners for HIV testing at one of the 9 local clinics, or (2) 4 HIV self-test kits to provide to peers/partners (thus 5 total HIVST kits or HCT invitations). Young women were asked to return 3 months and 9 months after enrollment to assess testing uptake and invitation or kit distribution to peers and partners and experiences with testing. Peers and partners who were reported by index participants to have received kits/invitations during follow-up visits were also invited to attend a study visit to assess their testing experiences. The trial is registered at clinical trials.gov NCT03162965.Findings287 young women were enrolled and randomized, with 146 randomized to the HCT arm and 141 to the choice (HCT or HIVST) arm. Of those randomized to the choice arm, over 95% (n=135) chose the HIV self-testing kit and only 6 individuals chose HCT. At the 3-month follow-up visit, 92% of index participants in the choice arm reported having tested for HIV compared to 43% of participants in the HCT arm, resulting in a significant risk difference of 49% (95% CI 40%, 58%). By 9 months, this difference decreased to a risk difference of 25% (95% CI 17%, 33%) between arms (96% in the choice arm and 72% in the HCT arm). Participants in the choice arm were also more likely to invite peers and partners to test compared to the HCT arm (94% vs. 76% or an average of 4.97 vs 2.79 tests). Few male partners were invited to test by index participants; however, index participants in the choice arm were more likely to have their male partners test than index participants in the HCT arm (RR 2.99, 95% CI 1.45, 6.16).InterpretationWhen given a choice between clinic-based HIV testing and HIV oral self-testing, the overwhelming majority of young women chose HIVST. In addition, those offered a choice of HIV testing modality were much more likely to test, distribute test kits to peers and partners, and to have peers and partners who reported testing compared to the HCT arm. Self-testing offers an important opportunity to significantly increase testing rates among young women and their peers and partners compared to clinic-based HCT. Other strategies to reach men with testing are needed.FundingUS National Institutes of Health.

BackgroundThe uptake of HIV self-testing (HIVST) could address socio-structural barriers that prevent South African youth from utilizing the testing resources available in their communities. However, to facilitate this, we must tailor components of the HIVST kit and process to ensure that we reach and encourage youth to test. The purpose of this study to elucidate concerns and issues regarding HIVST rollout among South African youth.MethodsThis study was conducted in two phases: 1) focus group discussions with rural, South African youth aged 18-24 and 2) direct observations of participants completing with an oral HIVST kit and/or a blood based HIVST kit. In phase 2a participants were invited to try both an oral and blood-based HIVST kit. In phase 2b, participants selected the HIVST kit of their choice.ResultsWe enrolled 35 unique participants in phase 1, 20 participants in phase 2a, and 40 participants in phase 2b. While the focus group discussions highlighted hypothetical HIVST use only, participants appreciated the privacy that the HIVST could afford them. However, they expressed concerns about whether HIVST could be trusted due to false positives and negatives, as well as whether a person would be able to emotionally handle the results if they tested alone. They suggested that the kits be used alongside someone who could provide support. In phases 2a and 2b, participants were overwhelmingly positive about both kits regarding ease of use and whether their results could be trusted. The participants, however, experienced more challenges with the blood-based versus oral test. When given the choice in phase 2b, most participants (80%) chose the oral HIVST over the blood-based HIVST.ConclusionsDuring the focus group discussions, participants raised concerns about the validity of HIVST, lack of emotional support when testing alone, and the cost of HIVST kits, all of which could be addressed through current testing campaigns. Most of those who actually tested had positive experiences with HIVST and would recommend it to their friends. When offered a choice, most preferred the oral test.Trial registrationNCT03162965 , registered 19th May 2017.

IntroductionAdolescent girls and young women (AGYW) in South Africa bear a disproportionate burden of HIV. Community mobilization (CM), defined as community members taking collective action to achieve a common goal related to health, equity and rights, has been associated with increased HIV testing and condom use and has been called a 'critical enabler' for addressing the HIV epidemic. However, limited research has examined whether CM is associated with HIV incidence among AGYW.MethodsWe examine the association of CM with incident HIV among AGYW (ages 13 to 21) enrolled in the HPTN 068 cohort in the Agincourt Health and socio-Demographic Surveillance System, South Africa. This analysis includes 2292 participants residing in 26 villages where cross-sectional, population-based surveys were conducted to measure CM among 18- to 35-year-old residents in 2012 and 2014. HPTN 068 participants completed up to five annual visits that included an HIV test (2011 to 2016). Household-level data were collected from AGYW parents/guardians and census data is updated annually. Mean village-level CM scores were created using a validated community mobilization measure with seven components (social cohesion, social control, critical consciousness, shared concerns, organizations and networks, leadership and collective action). We used pooled generalized estimating equation regression with a Poisson distribution to estimate risk ratios (RR) for the association of village-level CM score and CM components with incident HIV infection, accounting for village-level clustering and adjusting for key covariates.ResultsThere were 194 incident infections over the follow-up period. For every additional standard deviation of village-level CM there was 12% lower HIV incidence (RR: 0.88, 95% CI: 0.79, 0.98) after adjusting for individual, household and community characteristics. CM components associated with lower HIV incidence included critical consciousness (RR: 0.88; CI: 0.79, 0.97) and leadership (RR: 0.87; CI: 0.79, 0.95); while not statistically significant, social cohesion (RR: 0.91; CI: 0.81, 1.01), shared concerns (RR: 0.90; CI: 0.81, 1.00), and organizations and networks (RR: 0.91; CI: 0.79, 1.03) may also play a protective role.ConclusionsThese results suggest that having strong community social resources will reduce AGYW's risk of HIV acquisition. Work to mobilize communities, focusing on building social cohesion, shared concerns, critical consciousness, and effective and accountable leadership, can fortify prevention programming for AGYW.

Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair. Based on the results from over 100,000 perturbed gene pairs, we reconstruct a directional dependency network for human K562 leukemia cells and demonstrate how our approach allows the determination of directionality in activating genetic interactions. Our interaction network connects previously uncharacterized genes to well-studied pathways and identifies targets relevant for therapeutic intervention.

RationaleLittle research has evaluated the life course drivers of cognitive aging in South Africa.ObjectivesWe investigated the relationships of self-rated childhood health and father's occupation during childhood with later-life cognitive function score and whether educational attainment mediated these relationships among older South Africans living in a former region of Apartheid-era racial segregation.MethodsData were from baseline assessments of "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community" (HAALSI), a population-based study of 5059 men and women aged ≥40 years in 2015 in rural Agincourt sub-district, South Africa. Childhood health, father's occupation during childhood, and years of education were self-reported in study interviews. Cognitive measures assessed time orientation, numeracy, and word recall, which were included in a z-standardized latent cognitive function score variable. Linear regression models adjusted for age, sex, and country of birth were used to estimate the total and direct effects of each childhood risk factor, and the indirect effects mediated by years of education.ResultsPoor childhood health predicted lower cognitive scores (total effect = -0.28; 95% CI = -0.35, -0.21, versus good); this effect was not mediated by educational attainment. Having a father in a professional job during childhood, while rare (3% of sample), predicted better cognitive scores (total effect = 0.25; 95% CI = 0.10, 0.40, versus unskilled manual labor, 29% of sample). Half of this effect was mediated by educational attainment. Education was linearly associated with later-life cognitive function score (0.09; 95% CI = 0.09, 0.10 per year achieved).ConclusionIn this post-Apartheid, rural South African context, older adults with poor self-reported childhood health or whose father worked in unskilled manual labor had relatively poor cognitive outcomes. Educational attainment strongly predicted cognitive outcomes, and appeared to be, in part, a mechanism of social stratification in later-life cognitive health in this context.

Photothermal excitation at frequencies below the mechanical resonance of the atomic force microscopy (AFM) microcantilever can be utilized in force modulation microscopy, fast force displacement curve acquisition, and tip-based mass spectroscopy. To understand the microcantilever bending response in these modes, accurate models of the thermoelastic response of the AFM microcantilever are needed. We study the sub-resonance photothermal vibrational response of coated and uncoated AFM microcantilevers as a function of laser modulation frequency and spot location. The sub-resonance microcantilever response shows distinct thermoelastic regimes. Below the microcantilever's thermal roll-off frequency, the vibration amplitude is mostly constant. Past this frequency, the vibration amplitude decreases with increasing frequency. At modulation frequencies below the thermal roll-off frequency, the most efficient photothermal laser spot to excite harmonic motion is near the free end of both coated and uncoated microcantilevers. For the tested coated microcantilevers, the most efficient photothermal laser location migrates from near the free end of the microcantilever to near the fixed end as modulation frequency increases. For the tested uncoated microcantilever, the most efficient photothermal laser location remains unchanged at the tested frequencies. To predict the bending response of the coated microcantilever, a bilayer bending model is implemented. At low frequencies, this model underpredicts the bending response compared to experiments by up to 90%. This may be due to neglecting microcantilever bending contributed by a through-thickness temperature gradient. Our results illustrate different aspects of the frequency-dependent photothermal laser spot optimization that can guide users to maximizing microcantilever response to a given input power. [ABSTRACT FROM AUTHOR]

The Winam Gulf (Kenya) is frequently impaired by cyanobacterial harmful algal blooms (cHABs) due to inadequate wastewater treatment and excess agricultural nutrient input. While phytoplankton in Lake Victoria have been characterized using morphological criteria, our aim is to identify potential toxin‐producing cyanobacteria using molecular approaches. The Gulf was sampled over two successive summer seasons, and 16S and 18S ribosomal RNA gene sequencing was performed. Additionally, key genes involved in production of cyanotoxins were examined by quantitative PCR. Bacterial communities were spatially variable, forming distinct clusters in line with regions of the Gulf. Taxa associated with diazotrophy were dominant near Homa Bay. On the eastern side, samples exhibited elevated cyrA abundances, indicating genetic capability of cylindrospermopsin synthesis. Indeed, near the Nyando River mouth in 2022, cyrA exceeded 10 million copies L−1 where there were more than 6000 Cylindrospermopsis spp. cells mL−1. In contrast, the southwestern region had elevated mcyE gene (microcystin synthesis) detections near Homa Bay where Microcystis and Dolichospermum spp. were observed. These findings show that within a relatively small embayment, composition and toxin synthesis potential of cHABs can vary dramatically. This underscores the need for multifaceted management approaches and frequent cyanotoxin monitoring to reduce human health impacts. [ABSTRACT FROM AUTHOR]

Background and Purpose: Brain arterial diameters are markers of cerebrovascular disease. Demographic and anatomical factors may influence arterial diameters. We hypothesize that age, sex, height, total cranial volume (TCV), and persistent fetal posterior cerebral artery (fPCA) correlate with brain arterial diameters across populations. Methods: Participants had a time-of-flight MRA from nine international cohorts. Arterial diameters of the cavernous internal carotid arteries (ICA), middle cerebral arteries (MCA), and basilar artery (BA) were measured using LAVA software. Regression models assessed the association between exposures and brain arterial diameters. Results: We included 6,518 participants (mean age: 70 ± 9 years; 41% men). Unilateral fPCA was present in 13.2% and bilateral in 3.2%. Larger ICA, MCA, and BA diameters correlated with older age (Weighted average [WA] per 10 years: 0.18 mm, 0.11 mm, and 0.12 mm), male sex (WA: 0.24 mm, 0.13 mm, and 0.21 mm), and TCV (WA: for one TCV standard deviation: 0.24 mm, 0.29 mm, and 0.18 mm). Unilateral and bilateral fPCAs showed a positive correlation with ICA diameters (WA: 0.39 mm and 0.73 mm) and negative correlation with BA diameters (WA: −0.88 mm and −1.73 mm). Regression models including age, sex, TCV, and fPCA explained on average 15%, 13%, and 25% of the ICA, MCA, and BA diameter interindividual variation, respectively. Using height instead of TCV as a surrogate of head size decreased the R-squared by 3% on average. Conclusion: Brain arterial diameters correlated with age, sex, TCV, and fPCA. These factors should be considered when defining abnormal diameter cutoffs across populations. [ABSTRACT FROM AUTHOR]

Aim To investigate mid-life employment trajectories in relation to later-life memory function and rate of decline in rural South Africa. Methods Data from the Agincourt Health and Socio-Demographic Surveillance System were linked to the 'Health and Ageing in Africa: A Longitudinal Study of an INDEPTH Community in South Africa' (HAALSI) in rural Agincourt, South Africa (N  =   3133). Employment was assessed every 4 years over 2000–12 as being employed (0, 1, 2 and ≥3 time points), being employed in a higher-skill occupation (0, 1, 2 and ≥3 time points) and dynamic employment trajectories identified using sequence analysis. Latent memory z-scores were assessed over 2014–22. Mixed-effects linear regression models were fitted to examine the associations of interest. Results Sustained mid-life employment from 2000–12 (β = 0.052, 95% CI: -0.028 to 0.132, 1 vs 0 time points; β = 0.163, 95% CI: 0.077 to 0.250, 2 vs 0 time points; β = 0.212, 95% CI: 0.128 to 0.296, ≥3 vs 0 time points) and greater time spent in a higher-skill occupation (β = 0.077, 95% CI: -0.020 to 0.175, 1 vs 0 time points; β = 0.241, 95% CI: 0.070 to 0.412, 2 vs 0 time points; β = 0.361, 95% CI: 0.201 to 0.520, ≥3 vs 0 time points) were associated with higher memory scores in 2014/15, but not subsequent rate of memory decline. Moving from a lower-skill to higher-skill occupation was associated with higher memory function, but a faster rate of decline over 2014–22. Conclusions Sustained mid-life employment, particularly in higher-skill occupations, may contribute to later-life memory function in this post-Apartheid South African setting. [ABSTRACT FROM AUTHOR]