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Background Understanding of the transmission dynamics of tuberculosis (TB) in high TB and HIV prevalent settings is required in order to develop effective intervention strategies for TB control. However, there are little data assessing incidence of TB infection in adolescents in these settings. Methods We performed a tuberculin skin test (TST) and HIV survey among secondary school learners in a high HIV and TB prevalence community. TST responses to purified protein derivative RT23 were read after 3 days. HIV-infection was assessed using Orasure® collection device and ELISA testing. The results of the HIV-uninfected participants were combined with those from previous surveys among primary school learners in the same community, and force of TB infection was calculated by age. Results The age of 820 secondary school participants ranged from 13 to 22 years. 159 participants had participated in the primary school surveys. At a 10 mm cut-off, prevalence of TB infection among HIV-uninfected and first time participants, was 54% (n = 334/620). HIV prevalence was 5% (n = 40/816). HIV infection was not significantly associated with TST positivity (p = 0.07). In the combined survey dataset, TB prevalence was 45% (n = 645/1451), and was associated with increasing age and male gender. Force of infection increased with age, from 3% to 7.3% in adolescents ≥20 years of age. Conclusions We show a high force of infection among adolescents, positively associated with increasing age. We postulate this is due to increased social contact with infectious TB cases. Control of the TB epidemic in this setting will require reducing the force of infection.

To measure HIV prevalence and uptake of HIV counseling and testing (HCT) in a peri-urban South African community. To assess predictors for previous HIV testing and the association between the yield of previously undiagnosed HIV and time of last negative HIV test A random sample of 10% of the adult population (≥15 years) were invited to attend a mobile HCT service. Study procedures included a questionnaire, HIV testing and CD4 counts. Predictors for previous testing were determined using a binominal model. 1,144 (88.0%) of 1,300 randomly selected individuals participated in the study. 71.0% (68.3-73.6) had previously had an HIV test and 37.5% (34.6-40.5) had tested in the past 12 months. Men, migrants and older (>35 years) and younger (<20 years) individuals were less likely to have had a previous HIV test. Overall HIV prevalence was 22.7 (20.3-25.3) with peak prevalence of 41.8% (35.8-47.8) in women aged 25.1-35 years and 37.5% (26.7-48.3) in men aged 25.1-45 years. Prevalence of previously undiagnosed HIV was 10.3% (8.5-12.1) overall and 4.5% (2.3-6.6), 8.0% (CI 3.9-12.0) and 20.0% (13.2-26.8) in individuals who had their most recent HIV test within 1, 1-2 and more than 2 years prior to the survey. The high burden of undiagnosed HIV in individuals who had recently tested underscores the importance of frequent repeat testing at least annually. The high prevalence of previously undiagnosed HIV in individuals reporting a negative test in the 12 months preceding the survey indicates a very high incidence. Innovative prevention strategies are needed.

Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female) were screened at three sites in South Africa: Soweto (n = 70, 33%), Cape Town (n = 68, 32%) and Klerksdorp (n = 73, 35%). Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n = 149). Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03-0.25 p<0.001 and Klerksdorp OR 0.13 CI: 0.04-0.41 p = 0.001). In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13-5.08, p = 0.02). Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies. ClinicalTrials.gov: NCT02109354.

Placebo-controlled trials of pre-exposure prophylaxis (PrEP) have reported challenges with study-product uptake and use, with the greatest challenges reported in studies with young women in sub-Saharan Africa. We conducted a qualitative sub-study to explore experiences with open-label PrEP among young women in Cape Town, South Africa participating in HTPN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT). HPTN 067/ADAPT provided open label oral FTC/TDF PrEP to young women in Cape Town, South Africa who were randomized to daily and non-daily PrEP regimens. Following completion of study participation, women were invited into a qualitative sub-study including focus groups and in-depth interviews. Interviews and groups followed a semi-structured guide, were recorded, transcribed, and translated to English from isiXhosa, and coded using framework analysis. Sixty of the 179 women enrolled in HPTN 067/ADAPT participated in either a focus group (six groups for a total of 42 participants) or an in-depth interview (n = 18). This sample of mostly young, unmarried women identified facilitators of and barriers to PrEP use, as well as factors influencing study participation. Cross-cutting themes characterizing discourse suggested that women placed high value on contributing to the well-being of one’s community (Ubuntu), experienced a degree of skepticism towards PrEP and the study more generally, and reported a wide range of approaches towards PrEP (ranging from active avoidance to high levels of persistence and adherence). A Mutuality Framework is proposed that identifies four dynamics (distrust, uncertainty, alignment, and mutuality) that represent distinct interactions between self, community and study and serve to contextualize women’s experiences. Implications for better understanding PrEP use, and non-use, and intervention opportunities are discussed. In this sample of women, PrEP use in the context of an open-label research trial was heavily influenced by underlying beliefs about safety, reciprocity of contributions to community, and trust in transparency and integrity of the research. Greater attention to factors positioning women in the different dynamics of the proposed Mutuality Framework could direct intervention approaches in clinical trials, as well as open-label PrEP scale-up.

Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female) were screened at three sites in South Africa: Soweto (n = 70, 33%), Cape Town (n = 68, 32%) and Klerksdorp (n = 73, 35%). Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n = 149). Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03-0.25 p<0.001 and Klerksdorp OR 0.13 CI: 0.04-0.41 p = 0.001). In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13-5.08, p = 0.02). Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies. Trial Registration ClinicalTrials.gov: NCT02109354

What are the risks and benefits of non-parental care for young children? What are the short- and long-term effects of academically vs. play-focused environments for learning? How and when should we teach reading? What are the purposes of Education? What is the best way to teach mathematics to children, from preschool and beyond? Contemporary Debates in Childhood Education and Development is a unique resource and reference work that brings together leading international researchers and thinkers, with divergent points of view, to discuss contemporary problems and questions in childhood education and developmental psychology. Through an innovative format whereby leading scholars each offer their own constructive take on the issue in hand, this book aims to inform readers of both sides of a variety of topics and in the process encourage constructive communication and fresh approaches. Spanning a broad spectrum of issues, this book covers: Phonic and whole language reading approaches The developmental effect of non-parental childcare The value of pre-school academic skill acquisition The most effective methods of teaching mathematics Standardized assessment - does it work? The role of electronic media and technology The pedagogical value of homework The value of parents' reading to children. This book combines breadth of vision with cutting edge research and is a 'must have' resource for researchers, students and policy makers in the fields of education and child development.

Gonçalo Abecasis, Chaolong Wang and colleagues report a new statistical method, implemented in a publicly available software program LASER, to estimate an individual's genetic ancestry directly from off-target sequence reads from targeted sequencing experiments, making use of a reference panel. Their simulations and testing on real data sets show accurate inference of worldwide continental ancestry with whole-genome shotgun coverage as low as 0.001× and of fine-scale ancestry within Europe with coverage as low as 0.1×. Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysis of off-target sequence reads, and implement our method in the publicly available LASER software. We validate the method using simulated and empirical data and show that the method can accurately infer worldwide continental ancestry when used with sequencing data sets with whole-genome shotgun coverage as low as 0.001×. For estimates of fine-scale ancestry within Europe, the method performs well with coverage of 0.1×. On an even finer scale, the method improves discrimination between exome-sequenced study participants originating from different provinces within Finland. Finally, we show that our method can be used to improve case-control matching in genetic association studies and to reduce the risk of spurious findings due to population structure.

Abstract Endocrine disorders in survivors of childhood, adolescent, and young adult (CAYA) cancers are associated with substantial adverse physical and psychosocial effects. To improve appropriate and timely endocrine screening and referral to a specialist, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) aims to develop evidence and expert consensus-based guidelines for healthcare providers that harmonize recommendations for surveillance of endocrine disorders in CAYA cancer survivors. Existing IGHG surveillance recommendations for premature ovarian insufficiency, gonadotoxicity in males, fertility preservation, and thyroid cancer are summarized. For hypothalamic-pituitary (HP) dysfunction, new surveillance recommendations were formulated by a guideline panel consisting of 42 interdisciplinary international experts. A systematic literature search was performed in MEDLINE (through PubMed) for clinically relevant questions concerning HP dysfunction. Literature was screened for eligibility. Recommendations were formulated by drawing conclusions from quality assessment of all evidence, considering the potential benefits of early detection and appropriate management. Healthcare providers should be aware that CAYA cancer survivors have an increased risk for endocrine disorders, including HP dysfunction. Regular surveillance with clinical history, anthropomorphic measures, physical examination, and laboratory measurements is recommended in at-risk survivors. When endocrine disorders are suspected, healthcare providers should proceed with timely referrals to specialized services. These international evidence-based recommendations for surveillance of endocrine disorders in CAYA cancer survivors inform healthcare providers and highlight the need for long-term endocrine follow-up care in subgroups of survivors and elucidate opportunities for further research. Graphical Abstract

School principals can play an important role in promoting teacher leadership by delegating authority and empowering teachers in ways that allow them influence in key organizational decisions and processes. However, it is unclear whether instruction and student learning are enhanced by promoting teacher influence in all aspects of school organization or whether it is better for principals to directly work on certain processes while delegating influence on others. We compare pathways from principal leadership through school organizational processes to student outcomes that include teacher influence as a mediating factor to pathways that do not include teachers’ influence. Our results suggest that effective principals use teacher leadership to improve the school learning climate while they work directly on professional development and school program coherence.

AbstractThe CONSORT 2010 (Consolidated Standards of Reporting Trials) statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency when evaluating new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes.The CONSORT-AI extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI. Both guidelines were developed through a staged consensus process, involving a literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed on in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The CONSORT-AI extension includes 14 new items, which were considered sufficiently important for AI interventions, that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and providing analysis of error cases.CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.