Is modelling complexity always needed?:Insights from modelling PrEP introduction in South Africa

BACKGROUND: Mathematical models can be powerful policymaking tools. Simple, static models are user-friendly for policymakers. More complex, dynamic models account for time-dependent changes but are complicated to understand and produce. Under which conditions are static models adequate? We compare static and dynamic model predictions of whether behavioural disinhibition could undermine the impact of HIV pre-exposure prophylaxis (PrEP) provision to female sex workers in South Africa. METHODS: A static model of HIV risk was developed and adapted into a dynamic model. Both models were used to estimate the possible reduction in condom use, following PrEP introduction, without increasing HIV risk. The results were compared over a 20-year time horizon, in two contexts: at epidemic equilibrium and during an increasing epidemic. RESULTS: Over time horizons of up to 5 years, the models are consistent. Over longer timeframes, the static model overstates the tolerated reduction in condom use where initial condom use is reasonably high ($\ge$50%) and/or PrEP effectiveness is low ($\le$45%), especially during an increasing epidemic. CONCLUSIONS: Static models can provide useful deductions to guide policymaking around the introduction of a new HIV intervention over short-medium time horizons of up to 5 years. Over longer timeframes, static models may not sufficiently emphasise situations of programmatic importance, especially where underlying epidemics are still increasing

An Assessment of Geophysical Survey Techniques for Characterising the Subsurface Around Glacier Margins, and Recommendations for Future Applications

Geophysical surveys provide an efficient and non-invasive means of studying subsurface conditions in numerous sedimentary settings. In this study, we explore the application of three geophysical methods to a proglacial environment, namely ground penetrating radar (GPR), seismic refraction and multi-channel analysis of surface waves (MASW). We apply these geophysical methods to three glacial landforms with contrasting morphologies and sedimentary characteristics, and we use the various responses to assess the applicability and limitations of each method for these proglacial targets. Our analysis shows that GPR and seismic (refraction and MASW) techniques can provide spatially extensive information on the internal architecture and composition of moraines, but careful survey designs are required to optimise data quality in these geologically complex environments. Based on our findings, we define a number of recommendations and a potential workflow to guide future geophysical investigations in analogous settings. We recommend the initial use of GPR in future studies of proglacial environments to inform (a) seismic survey design and (b) the selection of seismic interpretation techniques. We show the benefits of using multiple GPR antenna frequencies (e.g., 25 and 100 MHz) to provide decimetre scale imaging in the near surface (e.g., < 15 m) while also enabling signal penetration to targets at up to ∼40 m depth (e.g., bedrock). This strategy helps to circumvent changes in radar signal penetration resulting from variations in substrate conductivity or abundant scatterers. Our study also demonstrates the importance of combining multiple geophysical methods together with ground-truthing through sedimentological observations to reduce ambiguity in interpretations. Implementing our recommendations will improve geophysical survey practice in the field of glacial geology and allow geophysical methods to play an increasing role in the interpretation of glacial landforms and sediments.publishedVersio

INCREASING FOOD ACCESSIBILITY AND MENTAL HEALTH RESOURCES TO PROMOTE ADOLESCENT WELL-BEING IN A RURAL COMMUNITY

The Neighborhood and Built Environment is one of five Social Determinants of Health domains and is defined as where one lives, works, plays, and learns — all factors that affect one’s health. Cleveland County, North Carolina has a high percentage of school-age children who live in poverty, and face greater adversities including financial hardships, food insecurity, and adverse childhood experiences. The objective of this proposal is to increase the proportion of schools with policies and practices that promote health and safety. To address these issues, the nutrition-focused recommendation is to increase access to healthy foods by providing free meals to all participating County School students by expanding the Community Eligibility Provision of the National School Lunch Program. The policy-focused recommendation is to implement the “Require All Schools to Staff Mental Health Counselors” policy, encouraging a sustainable mental health support system in schools.Master of Public Healt

INCREASING FOOD ACCESSIBILITY AND MENTAL HEALTH RESOURCES TO PROMOTE ADOLESCENT WELL-BEING IN A RURAL COMMUNITY

The Neighborhood and Built Environment is one of five Social Determinants of Health domains and is defined as where one lives, works, plays, and learns - all factors that affect one’s health. Cleveland County, North Carolina has a high percentage of school-age children who live in poverty, and face greater adversities including financial hardships, food insecurity, and adverse childhood experiences. The objective of this proposal is to increase the proportion of schools with policies and practices that promote health and safety. To address these issues, the nutrition-focused recommendation is to increase access to healthy foods by providing free meals to all participating County School students by expanding the Community Eligibility Provision of the National School Lunch Program. The policy-focused recommendation is to implement the “Require All Schools to Staff Mental Health Counselors” policy, encouraging a sustainable mental health support system in schools.Master of Public Healt

INCREASING FOOD ACCESSIBILITY AND MENTAL HEALTH RESOURCES TO PROMOTE ADOLESCENT WELL-BEING IN A RURAL COMMUNITY

The Neighborhood and Built Environment is one of five Social Determinants of Health domains and is defined as where one lives, works, plays, and learns — all factors that affect one’s health. Cleveland County, North Carolina has a high percentage of school-age children who live in poverty, and face greater adversities including financial hardships, food insecurity, and adverse childhood experiences. The objective of this proposal is to increase the proportion of schools with policies and practices that promote health and safety. To address these issues, the nutrition-focused recommendation is to increase access to healthy foods by providing free meals to all participating County School students by expanding the Community Eligibility Provision of the National School Lunch Program. The policy-focused recommendation is to implement the “Require All Schools to Staff Mental Health Counselors” policy, encouraging a sustainable mental health support system in schools.Master of Public Healt

Eliminating Preventable HIV-Related Maternal Mortality in Sub-Saharan Africa: What Do We Need to Know?

Introduction: HIV makes a significant contribution to maternal mortality, and women living in sub-Saharan Africa are most affected. International commitments to eliminate preventable maternal mortality and reduce HIV-related deaths among pregnant and postpartum women by 50% will not be achieved without a better understanding of the links between HIV and poor maternal health outcomes and improved health services for the care of women living with HIV (WLWH) during pregnancy, childbirth, and postpartum. Methods: This article summarizes priorities for research and evaluation identified through consultation with 30 international researchers and policymakers with experience in maternal health and HIV in sub-Saharan Africa and a review of the published literature. Results: Priorities for improving the evidence about effective interventions to reduce maternal mortality and improve maternal health among WLWH include better quality data about causes of maternal death among WLWH, enhanced and harmonized program monitoring, and research and evaluation that contributes to improving: (1) clinical management of pregnant and postpartum WLWH, including assessment of the impact of expanded antiretroviral therapy on maternal mortality and morbidity, (2) integrated service delivery models, and (3) interventions to create an enabling social environment for women to begin and remain in care. Conclusions: As the global community evaluates progress and prepares for new maternal mortality and HIV targets, addressing the needs of WLWH must be a priority now and after 2015. Research and evaluation on maternal health and HIV can increase collaboration on these 2 global priorities, strengthen political constituencies and communities of practice, and accelerate progress toward achievement of goals in both areas

An Assessment of Geophysical Survey Techniques for Characterising the Subsurface Around Glacier Margins, and Recommendations for Future Applications

Geophysical surveys provide an efficient and non-invasive means of studying subsurface conditions in numerous sedimentary settings. In this study, we explore the application of three geophysical methods to a proglacial environment, namely ground penetrating radar (GPR), seismic refraction and multi-channel analysis of surface waves (MASW). We apply these geophysical methods to three glacial landforms with contrasting morphologies and sedimentary characteristics, and we use the various responses to assess the applicability and limitations of each method for these proglacial targets. Our analysis shows that GPR and seismic (refraction and MASW) techniques can provide spatially extensive information on the internal architecture and composition of moraines, but careful survey designs are required to optimise data quality in these geologically complex environments. Based on our findings, we define a number of recommendations and a potential workflow to guide future geophysical investigations in analogous settings. We recommend the initial use of GPR in future studies of proglacial environments to inform (a) seismic survey design and (b) the selection of seismic interpretation techniques. We show the benefits of using multiple GPR antenna frequencies (e.g., 25 and 100 MHz) to provide decimetre scale imaging in the near surface (e.g., < 15 m) while also enabling signal penetration to targets at up to ∼40 m depth (e.g., bedrock). This strategy helps to circumvent changes in radar signal penetration resulting from variations in substrate conductivity or abundant scatterers. Our study also demonstrates the importance of combining multiple geophysical methods together with ground-truthing through sedimentological observations to reduce ambiguity in interpretations. Implementing our recommendations will improve geophysical survey practice in the field of glacial geology and allow geophysical methods to play an increasing role in the interpretation of glacial landforms and sediments

Climate change and water in the UK: past changes and future prospects

Climate change is expected to modify rainfall, temperature and catchment hydrological responses across the world, and adapting to these water-related changes is a pressing challenge. This paper reviews the impact of anthropogenic climate change on water in the UK and looks at projections of future change. The natural variability of the UK climate makes change hard to detect; only historical increases in air temperature can be attributed to anthropogenic climate forcing, but over the last 50 years more winter rainfall has been falling in intense events. Future changes in rainfall and evapotranspiration could lead to changed flow regimes and impacts on water quality, aquatic ecosystems and water availability. Summer flows may decrease on average, but floods may become larger and more frequent. River and lake water quality may decline as a result of higher water temperatures, lower river flows and increased algal blooms in summer, and because of higher flows in the winter. In communicating this important work, researchers should pay particular attention to explaining confidence and uncertainty clearly. Much of the relevant research is either global or highly localized: decision-makers would benefit from more studies that address water and climate change at a spatial and temporal scale appropriate for the decisions they mak

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

Genotype-phenotype correlation at codon 1740 ofSETD2

The SET domain containing 2, histone lysine methyltransferase encoded by SETD2 is a dual-function methyltransferase for histones and microtubules and plays an important role for transcriptional regulation, genomic stability, and cytoskeletal functions. Specifically, SETD2 is associated with trimethylation of histone H3 at lysine 36 (H3K36me3) and methylation of α-tubulin at lysine 40. Heterozygous loss of function and missense variants have previously been described with Luscan-Lumish syndrome (LLS), which is characterized by overgrowth, neurodevelopmental features, and absence of overt congenital anomalies. We have identified 15 individuals with de novo variants in codon 1740 of SETD2 whose features differ from those with LLS. Group 1 consists of 12 individuals with heterozygous variant c.5218C>T p.(Arg1740Trp) and Group 2 consists of 3 individuals with heterozygous variant c.5219G>A p.(Arg1740Gln). The phenotype of Group 1 includes microcephaly, profound intellectual disability, congenital anomalies affecting several organ systems, and similar facial features. Individuals in Group 2 had moderate to severe intellectual disability, low normal head circumference, and absence of additional major congenital anomalies. While LLS is likely due to loss of function of SETD2, the clinical features seen in individuals with variants affecting codon 1740 are more severe suggesting an alternative mechanism, such as gain of function, effects on epigenetic regulation, or posttranslational modification of the cytoskeleton. Our report is a prime example of different mutations in the same gene causing diverging phenotypes and the features observed in Group 1 suggest a new clinically recognizable syndrome uniquely associated with the heterozygous variant c.5218C>T p.(Arg1740Trp) in SETD2