Methodology and baseline results from the evaluation of a sexuality education activity in Mpumalanga and KwaZulu-Natal, South Africa

In South Africa, adolescents and young adults (ages 15–24) are at risk of HIV, sexually transmitted infections, and unintended pregnancies. Recently, the Department of Basic Education has revised its sexuality education content and teaching strategies (using scripted lessons plans) as part of its life orientation curriculum. This paper presents the methodology and baseline results from the evaluation of the scripted lesson plans and supporting activities. A rigorous cluster-level randomized design with random assignment of schools as clusters is used for the evaluation. Baseline results from grade 8 female and male learners and grade 10 female learners demonstrate that learners are at risk of HIV and early and unintended pregnancies. Multivariable analyses demonstrate that household-level food insecurity and living with an HIV-positive person are associated with sexual experience and pregnancy experience. Implications are discussed for strengthening the current life orientation program for future scale-up by the government of South Africa.The U.S. Agency for International Development (USAID) under the terms of MEASURE Evaluation cooperative agreement AID-OAA-L-14-00004.http://www.guilford.com/journals/AIDS-Education-and-Prevention/Francisco-Sy/089995462019-10-01hj2018School of Health Systems and Public Health (SHSPH

Perceptions about data-informed decisions: an assessment of information-use in high HIV-prevalence settings in South Africa

BACKGROUND: Information-use is an integral component of a routine health information system and essential to influence policy-making, program actions and research. Despite an increased amount of routine data collected, planning and resource-allocation decisions made by health managers for managing HIV programs are often not based on data. This study investigated the use of information, and barriers to using routine data for monitoring the prevention of mother-to-child transmission of HIV (PMTCT) programs in two high HIV-prevalence districts in South Africa. METHODS: We undertook an observational study using a multi-method approach, including an inventory of facility records and reports. The performance of routine information systems management (PRISM) diagnostic ‘Use of Information’ tool was used to assess the PMTCT information system for evidence of data use in 57 health facilities in two districts. Twenty-two in-depth interviews were conducted with key informants to investigate barriers to information use in decision-making. Participants were purposively selected based on their positions and experience with either producing PMTCT data and/or using data for management purposes. We computed descriptive statistics and used a general inductive approach to analyze the qualitative data. RESULTS: Despite the availability of mechanisms and processes to facilitate information-use in about two-thirds of the facilities, evidence of information-use (i.e., indication of some form of information-use in available RHIS reports) was demonstrated in 53% of the facilities. Information was inadequately used at district and facility levels to inform decisions and planning, but was selectively used for reporting and monitoring program outputs at the provincial level. The inadequate use of information stemmed from organizational issues such as the lack of a culture of information-use, lack of trust in the data, and the inability of program and facility managers to analyze, interpret and use information. CONCLCUSIONS: Managers’ inability to use information implied that decisions for program implementation and improving service delivery were not always based on data. This lack of data use could influence the delivery of health care services negatively. Facility and program managers should be provided with opportunities for capacity development as well as practice-based, in-service training, and be supported to use information for planning, management and decision-making

Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: conformational analysis and binding mode of multisite inhibitors

The critical role of BACE-1 in the formation of neurotoxic ß-amyloid peptides in the brain makes it an attractive target for an efficacious treatment of Alzheimer’s disease. However, the development of clinically useful BACE-1 inhibitors has proven to be extremely challeng- ing. In this study we examine the binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed by synergistic combination of two fragments—huprine and rhein— that individually are endowed with very low activity against BACE-1. Examination of crystal structures reveals no appropriate binding site large enough to accommodate 1. Therefore we have examined the conformational flexibility of BACE-1 through extended molecular dynamics simulations, paying attention to the highly flexible region shaped by loops 8–14, 154–169 and 307–318. The analysis of the protein dynamics, together with studies of pocket druggability, has allowed us to detect the transient formation of a secondary binding site, which contains Arg307 as a key residue for the interaction with small molecules, at the edge of the catalytic cleft. The formation of this druggable “floppy” pocket would enable the bind- ing of multisite inhibitors targeting both catalytic and secondary sites. Molecular dynamics simulations of BACE-1 bound to huprine-rhein hybrid compounds support the feasibility of this hypothesis. The results provide a basis to explain the high inhibitory potency of the two enantiomeric forms of 1, together with the large dependence on the length of the oligo- methylenic linker. Furthermore, the multisite hypothesis has allowed us to rationalize the inhibitory potency of a series of tacrine-chromene hybrid compounds, specifically regarding the apparent lack of sensitivity of the inhibition constant to the chemical modifications intro- duced in the chromene unit. Overall, these findings pave the way for the exploration of novel functionalities in the design of optimized BACE-1 multisite inhibitors

Assessing the Effectiveness of the UN Mission in South Sudan (UNMISS)

The report focuses on the most recent period of UNMISS’ mandate (2014-18), aiming to provide a “snapshot” of the mission’s work across its four main mandate areas: the protection of civilians (PoC), facilitation of humanitarian delivery, promotion of human rights, and support to the peace process. As a large, multidimensional peacekeeping operation – with 17,000 troops, 2,000 police and 2,000 civilians – UNMISS has been provided with significant resources and an extraordinarily ambitious mandate. Assessing the match between resources and mandate, and the ways the Mission has adapted its approaches to be effective in extremely challenging circumstances is a key objective of this report. Throughout its existence, UNMISS has been part of a much broader regional and international constellation of actors working to stabilise the country and encourage conflict parties to enter into a meaningful peace process. In many cases, UNMISS has played a limited supportive, coordinating, or otherwise indirect role in the overall trajectory of the country; in others, it is a central actor in the eyes of the people of South Sudan. This presents a challenge to any assessment of the Mission because, at most, UNMISS can be considered one contributor among many working together to end the civil war and lay the foundations for durable peace. Causality in these settings is difficult to establish. Nevertheless, drawing on the substantial data and analyses available, and interviews with more than 260 people in South Sudan and the region over several weeks, this study presents a set of evidence-based findings about the impact of the Mission and the factors that have enabled and inhibited the fulfilment of its mandate