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Adolescents and young people globally are highly vulnerable to poor mental health especially depression, and they account for 36% of new HIV infections in Eastern and Southern Africa. HIV services remain inadequate for this population and their adherence to ART is low. The Friendship Bench (FB), an evidence-based model developed in Zimbabwe to bridge the mental health gap, is a brief psychological intervention delivered on benches in primary care facilities by lay health workers (\"grandmothers\") trained in problem-solving therapy. This study explored the experience of young people living with HIV attending FB, and their perception of how problem-solving therapy impacted their adherence to ART. Semi-structured interviews were conducted in July 2019 with 10 young people living with HIV aged 18-24 years, who had recently completed FB counselling in Harare. Participants were purposively sampled and recruited from three primary care facilities. Interviews were conducted in Shona, audio-recorded, transcribed verbatim and translated into English. Transcripts were analysed in NVivo12 using inductive thematic analysis. Study findings revealed a clear emotional denial towards HIV, particularly for young people infected perinatally, and a resulting low adherence to ART. The study also unpacked the issues of internal stigma and how young people living with perinatally acquired HIV are informed of their HIV status. Participants reported that FB had a critical role in helping them accept their HIV status. Grandmothers' empathic attitude was key during counselling on adherence to ART, to demystify the disease and treatment, normalize the reality of living with HIV, encourage young people to socialize with peers and free them of guilt. Interviewees unanimously reported improved ART adherence following FB counselling, and many described enhanced health and wellbeing. Participants saw FB as a strong contributor to their general well-being, evident in decreased symptoms of depression and improved adherence to ART. FB problem-solving therapy should be rolled out to further support young people after post-test counselling or HIV serostatus disclosure for perinatally acquired HIV, for acceptance of HIV status and adherence to ART.

Given the well-documented failings in mathematics education in many Western societies, there has been an increased interest in understanding the cognitive underpinnings of mathematical achievement. Recent research has proposed the existence of an Approximate Number System (ANS) which allows individuals to represent and manipulate non-verbal numerical information. Evidence has shown that performance on a measure of the ANS (a dot comparison task) is related to mathematics achievement, which has led researchers to suggest that the ANS plays a critical role in mathematics learning. Here we show that, rather than being driven by the nature of underlying numerical representations, this relationship may in fact be an artefact of the inhibitory control demands of some trials of the dot comparison task. This suggests that recent work basing mathematics assessments and interventions around dot comparison tasks may be inappropriate.

Adolescents living with HIV have poor virological suppression and high prevalence of common mental disorders (CMDs). In Zimbabwe, the Zvandiri adolescent peer support programme is effective at improving virological suppression. We assessed the effect of training Zvandiri peer counsellors known as Community Adolescent Treatment Supporters (CATS) in problem-solving therapy (PST) on virological suppression and mental health outcomes. Sixty clinics were randomised 1:1 to either normal Zvandiri peer counselling or a peer counsellor trained in PST. In January to March 2019, 842 adolescents aged 10 to 19 years and living with HIV who screened positive for CMDs were enrolled (375 (44.5%) male and 418 (49.6%) orphaned of at least one parent). The primary outcome was virological nonsuppression (viral load ≥1,000 copies/mL). Secondary outcomes were symptoms of CMDs measured with the Shona Symptom Questionnaire (SSQ ≥8) and depression measured with the Patient Health Questionnaire (PHQ-9 ≥10) and health utility score using the EQ-5D. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusting for clinic-level clustering. Case reviews and focus group discussions were used to determine feasibility of intervention delivery. At baseline, 35.1% of participants had virological nonsuppression and 70.3% had SSQ≥8. After 48 weeks, follow-up was 89.5% for viral load data and 90.9% for other outcomes. Virological nonsuppression decreased in both arms, but there was no evidence of an intervention effect (prevalence of nonsuppression 14.7% in the Zvandiri-PST arm versus 11.9% in the Zvandiri arm; AOR = 1.29; 95% CI 0.68, 2.48; p = 0.44). There was strong evidence of an apparent effect on common mental health outcomes (SSQ ≥8: 2.4% versus 10.3% [AOR = 0.19; 95% CI 0.08, 0.46; p < 0.001]; PHQ-9 ≥10: 2.9% versus 8.8% [AOR = 0.32; 95% CI 0.14, 0.78; p = 0.01]). Prevalence of EQ-5D index score <1 was 27.6% versus 38.9% (AOR = 0.56; 95% CI 0.31, 1.03; p = 0.06). Qualitative analyses found that CATS-observed participants had limited autonomy or ability to solve problems. In response, the CATS adapted the intervention to focus on empathic problem discussion to fit adolescents' age, capacity, and circumstances, which was beneficial. Limitations include that cost data were not available and that the mental health tools were validated in adult populations, not adolescents. PST training for CATS did not add to the benefit of peer support in reducing virological nonsuppression but led to improved symptoms of CMD and depression compared to standard Zvandiri care among adolescents living with HIV in Zimbabwe. Active involvement of caregivers and strengthened referral structures could increase feasibility and effectiveness. Pan African Clinical Trials Registry PACTR201810756862405.

Clinical management of Ebola virus disease remains challenging. Routine laboratory analytics are often unavailable in the outbreak setting, and few data exist for the associated haematological and biochemical abnormalities. We aimed to assess laboratory and clinical data from patients with Ebola virus disease to better inform clinical management algorithms, improve understanding of key variables associated with outcome, and provide insight into the pathophysiology of Ebola virus disease. We recruited all patients, alive on arrival, with confirmed Ebola virus disease who were admitted to the Kerry Town Ebola treatment centre in Sierra Leone. At admission, all patients had clinical presentation recorded and blood taken for Ebola confirmation using reverse-transcriptase-PCR (RT-PCR) and for haematological and biochemical analysis. We studied the association between these and clinical outcome. The primary outcome was discharge from the Ebola treatment centre. 150 patients were admitted to the treatment centre between Dec 8, 2014, and Jan 9, 2015. The mean age of patients was 26 years (SD 14·7). Case fatality rate was 37% (55/150). Most patients presented with stage 2 (gastrointestinal involvement, 72/118 [61%]) and stage 3 (severe or complicated, 12/118 [10%]) disease. Acute kidney injury was common (52/104 [50%]), as were abnormal serum potassium (32/97 [33%]), severe hepatitis (54/92 [59%]), and raised C-reactive protein (21/100 [21%]). Haematological abnormalities were common, including raised haematocrit (15/100 [15%]), thrombocytopenia (47/104 [45%]), and granulocytosis (44/104 [42%]). Severe acute kidney injury, low RT-PCR cycle threshold (<20 cycles), and severe hepatitis were independently associated with mortality. Ebola virus disease is associated with a high prevalence of haematological and biochemical abnormalities, even in mild disease and in the absence of gastrointestinal symptoms. Clinical care that targets hypovolaemia, electrolyte disturbance, and acute kidney injury is likely to reduce historically high case fatality rates. None.

Mortality in people in Africa with HIV infection starting antiretroviral therapy (ART) is high, particularly in those with advanced disease. We assessed the effect of a short period of community support to supplement clinic-based services combined with serum cryptococcal antigen screening. We did an open-label, randomised controlled trial in six urban clinics in Dar es Salaam, Tanzania, and Lusaka, Zambia. From February, 2012, we enrolled eligible individuals with HIV infection (age ≥18 years, CD4 count of <200 cells per μL, ART naive) and randomly assigned them to either the standard clinic-based care supplemented with community support or standard clinic-based care alone, stratified by country and clinic, in permuted block sizes of ten. Clinic plus community support consisted of screening for serum cryptococcal antigen combined with antifungal therapy for patients testing antigen positive, weekly home visits for the first 4 weeks on ART by lay workers to provide support, and in Tanzania alone, re-screening for tuberculosis at 6–8 weeks after ART initiation. The primary endpoint was all-cause mortality at 12 months, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISCRTN 20410413. Between Feb 9, 2012, and Sept 30, 2013, 1001 patients were randomly assigned to clinic plus community support and 998 to standard care. 89 (9%) of 1001 participants in the clinic plus community support group did not receive their assigned intervention, and 11 (1%) of 998 participants in the standard care group received a home visit or a cryptococcal antigen screen rather than only standard care. At 12 months, 25 (2%) of 1001 participants in the clinic plus community support group and 24 (2%) of 998 participants in the standard care group had been lost to follow-up, and were censored at their last visit for the primary analysis. At 12 months, 134 (13%) of 1001 participants in the clinic plus community support group had died compared with 180 (18%) of 998 in the standard care group. Mortality was 28% (95% CI 10–43) lower in the clinic plus community support group than in standard care group (p=0·004). Screening and pre-emptive treatment for cryptococcal infection combined with a short initial period of adherence support after initiation of ART could substantially reduce mortality in HIV programmes in Africa. European and Developing Countries Clinical Trials Partnership.

PurposeMental disorders are a major contributor to the global burden of disease and disability, and can be extremely costly at both individual and community level. Social capital, (SC) defined as an individual’s social relationships and participation in community networks, may lower the risk of mental disorders while increasing resilience capacity, adaptation and recovery. SC interventions may be a cost-effective way of preventing and ameliorating these conditions. However, the impact of these SC interventions on mental health still needs research.MethodsWe conducted a systematic review of SC-based interventions to investigate their effect on mental health outcomes from controlled, quasi-experimental studies or pilot trials. We searched twelve academic databases, three clinical trials registries, hand-searched references and contacted field experts. Studies’ quality was assessed with the Cochrane Risk of Bias tools for randomized and non-randomized studies.ResultsSeven studies were included in the review, published between 2006 and 2016. There was substantial heterogeneity in the definitions of both SC and mental disorders among the studies, preventing us from calculating pooled effect sizes. The interventions included community engagement and educative programs, cognitive processing therapy and sociotherapy for trauma survivors, and neighbourhood projects.ConclusionsThere are paucity of SC interventions investigating the effect on mental health outcomes. This study showed that both SC scores and mental health outcomes improved over time but there was little evidence of benefit compared to control groups in the long term. Further high-quality trials are needed, especially among adverse populations to assess sustainability of effect.

The lives of adolescents and young people living with HIV (LHIV) are dominated by complex psychological and social stressors. These may be more pronounced among those perinatally infected. This longitudinal mixed-methods study describes the clinical and psychosocial challenges faced by HIV perinatally infected young mothers in Harare, Zimbabwe to inform tailored support. HIV perinatally infected young mothers were recruited in 2013 and followed up in 2019. In 2013, they completed a structured interview, clinical examination, psychological screening and had viral load and drug resistance testing. A subset completed in-depth interviews (n = 10). In 2019, they were re-interviewed and had viral load testing. Data were analyzed using STATA 15.0. and thematic analysis. Nineteen mothers aged 17-24 years were recruited in 2013. Eleven (57.9%) were successfully recontacted in 2019; 3 had died, 2 had relocated and 3 were untraceable. In 2013, all 19 mothers were taking antiretroviral therapy (median duration 8 years, range 2-11 years) and median CD4 count was 524 (IQR 272). In 2013, eight mothers (42.1%) had virological failure (≥1000 copies/ml) (3 of whom subsequently died) and 7 (36.8%) had evidence of drug resistance. In 2019, the proportion with virological failure was 2/11 (18.1%). Six of 11 (54.5%) had switched to second line therapy. In 2013, 64.3% were at risk of common mental disorder and this risk was higher at follow-up (72.7%). Qualitative data highlighted three pertinent themes: HIV status disclosure, adherence experiences and, social and emotional support. Findings from this study underscore the significant clinical, social and psychological challenges faced by perinatally infected young mothers. The high rates of virological failure, drug resistant mutations, mental health issues and mortality observed in this population indicate the need for tailored and comprehensive health and support services to assist these young mothers.

A large body of research has identified cognitive skills associated with overall mathematics achievement, focusing primarily on identifying associates of procedural skills. Conceptual understanding, however, has received less attention, despite its importance for the development of mathematics proficiency. Consequently, we know little about the quantitative and domain-general skills associated with conceptual understanding. Here we investigated 8-10-year-old children's conceptual understanding of arithmetic, as well as a wide range of basic quantitative skills, numerical representations and domain-general skills. We found that conceptual understanding was most strongly associated with performance on a number line task. This relationship was not explained by the use of particular strategies on the number line task, and may instead reflect children's knowledge of the structure of the number system. Understanding the skills involved in conceptual learning is important to support efforts by educators to improve children's conceptual understanding of mathematics.

Single molecule imaging approaches like dSTORM and PALM resolve structures at 10–20 nm, and allow for unique insights into protein stoichiometry and spatial relationships. However, key obstacles remain in developing highly accurate quantitative single molecule approaches. The genomic tagging of PALM fluorophores through CRISPR-Cas9 offers an excellent opportunity for generating stable cell lines expressing a defined single molecule probe at endogenous levels, without the biological disruption and variability inherent to transfection. A fundamental question is whether these comparatively low levels of expression can successfully satisfy the stringent labelling demands of super-resolution SMLM. Here we apply CRISPR-Cas9 gene editing to tag a cytoskeletal protein (α-tubulin) and demonstrate a relationship between expression level and the subsequent quality of PALM imaging, and that spatial resolutions comparable to dSTORM can be achieved with CRISPR-PALM. Our approach shows a relationship between choice of tag and the total expression of labelled protein, which has important implications for the development of future PALM tags. CRISPR-PALM allows for nanoscopic spatial resolution and the unique quantitative benefits of single molecule localization microscopy through endogenous expression, as well as the capacity for super-resolved live cell imaging.