Optima Nutrition: an allocative efficiency tool to reduce childhood stunting by better targeting of nutrition-related interventions.

BACKGROUND: Child stunting due to chronic malnutrition is a major problem in low- and middle-income countries due, in part, to inadequate nutrition-related practices and insufficient access to services. Limited budgets for nutritional interventions mean that available resources must be targeted in the most cost-effective manner to have the greatest impact. Quantitative tools can help guide budget allocation decisions. METHODS: The Optima approach is an established framework to conduct resource allocation optimization analyses. We applied this approach to develop a new tool, 'Optima Nutrition', for conducting allocative efficiency analyses that address childhood stunting. At the core of the Optima approach is an epidemiological model for assessing the burden of disease; we use an adapted version of the Lives Saved Tool (LiST). Six nutritional interventions have been included in the first release of the tool: antenatal micronutrient supplementation, balanced energy-protein supplementation, exclusive breastfeeding promotion, promotion of improved infant and young child feeding (IYCF) practices, public provision of complementary foods, and vitamin A supplementation. To demonstrate the use of this tool, we applied it to evaluate the optimal allocation of resources in 7 districts in Bangladesh, using both publicly available data (such as through DHS) and data from a complementary costing study. RESULTS: Optima Nutrition can be used to estimate how to target resources to improve nutrition outcomes. Specifically, for the Bangladesh example, despite only limited nutrition-related funding available (an estimated $0.75 per person in need per year), even without any extra resources, better targeting of investments in nutrition programming could increase the cumulative number of children living without stunting by 1.3 million (an extra 5%) by 2030 compared to the current resource allocation. To minimize stunting, priority interventions should include promotion of improved IYCF practices as well as vitamin A supplementation. Once these programs are adequately funded, the public provision of complementary foods should be funded as the next priority. Programmatic efforts should give greatest emphasis to the regions of Dhaka and Chittagong, which have the greatest number of stunted children. CONCLUSIONS: A resource optimization tool can provide important guidance for targeting nutrition investments to achieve greater impact

How should HIV resources be allocated? Lessons learnt from applying Optima HIV in 23 countries.

INTRODUCTION: With limited funds available, meeting global health targets requires countries to both mobilize and prioritize their health spending. Within this context, countries have recognized the importance of allocating funds for HIV as efficiently as possible to maximize impact. Over the past six years, the governments of 23 countries in Africa, Asia, Eastern Europe and Latin America have used the Optima HIV tool to estimate the optimal allocation of HIV resources. METHODS: Each study commenced with a request by the national government for technical assistance in conducting an HIV allocative efficiency study using Optima HIV. Each study team validated the required data, calibrated the Optima HIV epidemic model to produce HIV epidemic projections, agreed on cost functions for interventions, and used the model to calculate the optimal allocation of available funds to best address national strategic plan targets. From a review and analysis of these 23 country studies, we extract common themes around the optimal allocation of HIV funding in different epidemiological contexts. RESULTS AND DISCUSSION: The optimal distribution of HIV resources depends on the amount of funding available and the characteristics of each country's epidemic, response and targets. Universally, the modelling results indicated that scaling up treatment coverage is an efficient use of resources. There is scope for efficiency gains by targeting the HIV response towards the populations and geographical regions where HIV incidence is highest. Across a range of countries, the model results indicate that a more efficient allocation of HIV resources could reduce cumulative new HIV infections by an average of 18% over the years to 2020 and 25% over the years to 2030, along with an approximately 25% reduction in deaths for both timelines. However, in most countries this would still not be sufficient to meet the targets of the national strategic plan, with modelling results indicating that budget increases of up to 185% would be required. CONCLUSIONS: Greater epidemiological impact would be possible through better targeting of existing resources, but additional resources would still be required to meet targets. Allocative efficiency models have proven valuable in improving the HIV planning and budgeting process

Polarity Changes in the Transmembrane Domain Core of HIV-1 Vpu Inhibits Its Anti-Tetherin Activity

Tetherin (BST-2/CD317) is an interferon-inducible antiviral protein that restricts the release of enveloped viruses from infected cells. The HIV-1 accessory protein Vpu can efficiently antagonize this restriction. In this study, we analyzed mutations of the transmembrane (TM) domain of Vpu, including deletions and substitutions, to delineate amino acids important for HIV-1 viral particle release and in interactions with tetherin. The mutants had similar subcellular localization patterns with that of wild-type Vpu and were functional with respect to CD4 downregulation. We showed that the hydrophobic binding surface for tetherin lies in the core of the Vpu TM domain. Three consecutive hydrophobic isoleucine residues in the middle region of the Vpu TM domain, I15, I16 and I17, were important for stabilizing the tetherin binding interface and determining its sensitivity to tetherin. Changing the polarity of the amino acids at these positions resulted in severe impairment of Vpu-induced tetherin targeting and antagonism. Taken together, these data reveal a model of specific hydrophobic interactions between Vpu and tetherin, which can be potentially targeted in the development of novel anti-HIV-1 drugs

IFITM proteins inhibit HIV-1 protein synthesis

Interferon induced transmembrane proteins (IFITMs) inhibit the cellular entry of a broad range of viruses, but it has been suspected that for HIV-1 IFITMs may also inhibit a post-integration replicative step. We show that IFITM expression reduces HIV-1 viral protein synthesis by preferentially excluding viral mRNA transcripts from translation and thereby restricts viral production. Codon-optimization of proviral DNA rescues viral translation, implying that IFITM-mediated restriction requires recognition of viral RNA elements. In addition, we find that expression of the viral accessory protein Nef can help overcome the IFITM-mediated inhibition of virus production. Our studies identify a novel role for IFITMs in inhibiting HIV replication at the level of translation, but show that the effects can be overcome by the lentiviral protein Nef.Wellcome Trust-University of Edinburgh Institutional Strategic Support Fun

Completeness of reporting and risks of overstating impact in cluster randomised trials : a systematic review

Acknowledgments We received no funding specifically for this systematic review. ELT is funded in part by awards R01-AI141444 from the National Institute of Allergy and Infectious Diseases and R01-MH120649 from the US National Institute of Mental Health; both Institutes are part of the National Institutes of Health (NIH). JAG and ACP's support of this project was made possible (in part) by grant number UL1TR002553 from the National Center for Advancing Translational Sciences of the NIH, and the NIH Roadmap for Medical Research. JEM is supported by an Australian National Health and Medical Research Council Career Development Fellowship (APP1143429). SN was supported by an award that is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, and part of the EDCTP2 programme supported by the European Union (grant reference MR/R010161/1). ABF acknowledges funding support from the National Health and Medical Research Council of Australia (grant ID 1183303). KH is funded by a National Institute for Health Research Senior Research Fellowship SRF-2017-10-002. The contents of the research included in this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of any of the funders. The research contributed by all authors of this manuscript are independent of their funders. Specifically, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We wish to thank the three reviewers for their insightful comments and constructive feedback.Peer reviewedPublisher PD

Global challenges for seagrass conservation

Seagrasses, flowering marine plants that form underwater meadows, play a significant global role in supporting food security, mitigating climate change and supporting biodiversity. Although progress is being made to conserve seagrass meadows in select areas, most meadows remain under significant pressure resulting in a decline in meadow condition and loss of function. Effective management strategies need to be implemented to reverse seagrass loss and enhance their fundamental role in coastal ocean habitats. Here we propose that seagrass meadows globally face a series of significant common challenges that must be addressed from a multifaceted and interdisciplinary perspective in order to achieve global conservation of seagrass meadows. The six main global challenges to seagrass conservation are (1) a lack of awareness of what seagrasses are and a limited societal recognition of the importance of seagrasses in coastal systems; (2) the status of many seagrass meadows are unknown, and up-to-date information on status and condition is essential; (3) understanding threatening activities at local scales is required to target management actions accordingly; (4) expanding our understanding of interactions between the socio-economic and ecological elements of seagrass systems is essential to balance the needs of people and the planet; (5) seagrass research should be expanded to generate scientific inquiries that support conservation actions; (6) increased understanding of the linkages between seagrass and climate change is required to adapt conservation accordingly. We also explicitly outline a series of proposed policy actions that will enable the scientific and conservation community to rise to these challenges. We urge the seagrass conservation community to engage stakeholders from local resource users to international policy-makers to address the challenges outlined here, in order to secure the future of the world’s seagrass ecosystems and maintain the vital services which they supply

The staircase cluster randomised trial design: A pragmatic alternative to the stepped wedge.

This article introduces the 'staircase' design, derived from the zigzag pattern of steps along the diagonal of a stepped wedge design schematic where clusters switch from control to intervention conditions. Unlike a complete stepped wedge design where all participating clusters must collect and provide data for the entire trial duration, clusters in a staircase design are only required to be involved and collect data for a limited number of pre- and post-switch periods. This could alleviate some of the burden on participating clusters, encouraging involvement in the trial and reducing the likelihood of attrition. Staircase designs are already being implemented, although in the absence of a dedicated methodology, approaches to sample size and power calculations have been inconsistent. We provide expressions for the variance of the treatment effect estimator when a linear mixed model for an outcome is assumed for the analysis of staircase designs in order to enable appropriate sample size and power calculations. These include explicit variance expressions for basic staircase designs with one pre- and one post-switch measurement period. We show how the variance of the treatment effect estimator is related to key design parameters and demonstrate power calculations for examples based on a real trial