rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to $3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. INTERPRETATION Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. FUNDING UNITAID. https://www.selleckchem.com/products/golvatinib-e7050.html BACKGROUND In armed conflict, injuries among civilians are usually complex and commonly affect the extremities. Negative pressure wound therapy (NPWT) is an alternative to standard treatment of acute conflict-related extremity wounds. We aimed to compare the safety and effectiveness of NPWT with that of standard treatment. METHODS In this pragmatic, randomised, controlled superiority trial done at two civilian hospitals in Jordan and Iraq, we recruited patients aged 18 years or older, presenting with a conflict-related extremity wound within 72 h after injury. Participants were assigned (11) to receive either NPWT or standard treatment. We used a predefined, computer-generated randomisation list with three block sizes. Participants and their treating physicians were not masked to treatment allocation. The primary endpoint was wound closure by day 5. The coprimary endpoint was net clinical benefit, defined as a composite of wound closure by day 5 and freedom from any bleeding, wound infection, sepsis, or amputne in the NPWT group. The proportion of participants with sepsis, bleeding leading to blood transfusion, and limb amputation did not differ between groups. INTERPRETATION NPWT did not yield superior clinical outcomes compared with standard treatment for acute conflict-related extremity wounds. The results of this study not only question the use of NPWT, but also question the tendency for new and costly treatments to be introduced into resource-limited conflict settings without supporting evidence for their effectiveness. This study shows that high-quality, randomised trials in challenging settings are possible, and our findings support the call for further research that will generate context-specific evidence. FUNDING The Stockholm County Council, the Swedish National Board of Health and Welfare, and Médecins Sans Frontières. BACKGROUND Heart failure is a global public health problem, affecting a large number of individuals from low-income and middle-income countries. REPORT-HF is, to our knowledge, the first prospective global registry collecting information on patient characteristics, management, and prognosis of acute heart failure using a single protocol. The aim of this study was to investigate differences in 1-year post-discharge mortality according to region, country income, and income inequality. METHODS Patients were enrolled during hospitalisation for acute heart failure from 358 centres in 44 countries on six continents. We stratified countries according to a modified WHO regional classification (Latin America, North America, western Europe, eastern Europe, eastern Mediterranean and Africa, southeast Asia, and western Pacific), country income (low, middle, high) and income inequality (according to tertiles of Gini index). Risk factors were identified on the basis of expert opinion and knowledge of the literature. FINDINd prescribing of GDMT. FUNDING Novartis Pharma. BACKGROUND In resource-limited settings, pneumonia diagnosis and management are based on thresholds for respiratory rate (RR) and oxyhaemoglobin saturation (SpO2) recommended by WHO. However, as RR increases and SpO2 decreases with elevation, these thresholds might not be applicable at all altitudes. We sought to determine upper thresholds for RR and lower thresholds for SpO2 by age and altitude at four sites, with altitudes ranging from sea level to 4348 m. METHODS In this cross-sectional study, we enrolled healthy children aged 0-23 months who lived within the study areas in India, Guatemala, Rwanda, and Peru. Participants were excluded if they had been born prematurely ( less then 37 weeks gestation); had a congenital heart defect; had history in the past 2 weeks of overnight admission to a health facility, diagnosis of pneumonia, antibiotic use, or respiratory or gastrointestinal signs; history in the past 24 h of difficulty breathing, fast breathing, runny nose, or nasal congestion; and current runny nosarch in sick children is still needed. FUNDING US National Institutes of Health, Bill & Melinda Gates Foundation. BACKGROUND The UN Sustainable Development Goals (SDGs) call for stratification of social indicators by ethnic groups; however, no recent multicountry analyses on ethnicity and child survival have been done in low-income and middle-income countries (LMICs). METHODS We used data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys collected between 2010 and 2016, from LMICs that provided birth histories and information on ethnicity or a proxy variable. We calculated neonatal (age 0-27 days), post-neonatal (age 28-364 days), child (age 1-4 years), and under-5 mortality rates (U5MRs) for each ethnic group within each country. We assessed differences in mortality between ethnic groups using a likelihood ratio test, Theil's index, and between-group variance. We used multivariable analyses of U5MR by ethnicity to adjust for household wealth, maternal education, and urban-rural residence. FINDINGS We included data from 36 LMICs, which included 2 812 381 livebirths among 415 ethnic groups. In 25 to the effort towards leaving no one behind, which is at the centre of the SDGs. FUNDING Bill & Melinda Gates Foundation, UNICEF, Wellcome Trust, Associação Brasileira de Saúde Coletiva. BACKGROUND Peer-reviewed literature on health is almost exclusively published in English, limiting the uptake of research for decision making in francophone African countries. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to assess the burden of disease in francophone Africa and inform health professionals and their partners in the region. METHODS We assessed the burden of disease in the 21 francophone African countries and compared the results with those for their non-francophone counterparts in three economic communities the Economic Community of West African States, the Economic Community of Central African States, and the Southern African Development Community. GBD 2017 employed a variety of statistical models to determine the number of deaths from each cause, through the Cause of Death Ensemble model algorithm, using CoDCorrect to ensure that the number of deaths per cause did not exceed the total number of estimated deaths. After producing estimates for he quality and quantity of health-care services, especially in rural and remote areas. The region could also be prioritised in terms of technical and financial assistance focused on achieving these goals, as much as on demographic investments including education and family planning. FUNDING Bill & Melinda Gates Foundation. BACKGROUND Optimal strategies for pre-exposure prophylaxis (PrEP) engagement in generalised HIV epidemics are unknown. We aimed to assess PrEP uptake and engagement after population-level HIV testing and universal PrEP access to characterise gaps in the PrEP cascade in rural Kenya and Uganda. METHODS We did a 72-week interim analysis of observational data from the ongoing SEARCH (Sustainable East Africa Research in Community Health) study. Following community sensitisation and PrEP education, we did HIV testing and offered PrEP at health fairs and facilities in 16 rural communities in western Kenya, eastern Uganda, and western Uganda. We provided enhanced PrEP counselling to individuals 15 years and older who were assessed as having an elevated HIV risk on the basis of serodifferent partnership or empirical risk score, or who otherwise self-identified as being at high risk but were not in serodifferent partnerships or identified by the risk score. PrEP follow-up visits were done at facilities, homes, or commude 3) were assessed as being possibly related to the study drug. INTERPRETATION During population-level HIV testing, inclusive risk assessment (combining serodifferent partnership, an empirical risk score, and self-identification of HIV risk) was feasible and identified individuals who could benefit from PrEP. The biggest gap in the PrEP cascade was PrEP uptake, particularly for young and mobile individuals. Participants who initiated PrEP and had perceived HIV risk during follow-up reported taking PrEP, but one-third had drug concentrations consistent with poor adherence, highlighting the need for novel approaches and long-acting formulations as PrEP roll-out expands. FUNDING National Institutes of Health, President's Emergency Plan for AIDS Relief, Bill & Melinda Gates Foundation, and Gilead Sciences. The mechanism of tumor-selective replication of oncolytic measles virus (MV) is poorly understood. Using a stepwise model of cellular transformation, in which oncogenic hits were additively expressed in human bone marrow-derived mesenchymal stromal cells, we show that MV-induced oncolysis increased progressively with transformation. The type 1 interferon (IFN) response to MV infection was significantly reduced and delayed, in accordance with the level of transformation. Consistently, we observed delayed and reduced signal transducer and activator of transcription (STAT1) phosphorylation in the fully transformed cells. Pre-treatment with IFNβ restored resistance to MV-mediated oncolysis. Gene expression profiling to identify the genetic correlates of susceptibility to MV oncolysis revealed a dampened basal level of immune-related genes in the fully transformed cells compared to their normal counterparts. IFN-induced transmembrane protein 1 (IFITM1) was the foremost basally downregulated immune gene. Stable IFITM1 overexpression in MV-susceptible cells resulted in a 50% increase in cell viability and a significant reduction in viral replication at 24 h after MV infection. Overall, our data indicate that the basal reduction in functions of the type 1 IFN pathway is a major contributor to the oncolytic selectivity of MV. In particular, we have identified IFITM1 as a restriction factor for oncolytic MV, acting at early stages of infection. Mesenchymal stem cells (MSCs) have shown great promise in inflammatory bowel disease (IBD) treatment, owing to their immunosuppressive capabilities, but their therapeutic effectiveness is sometimes thwarted by their low efficiency in entering the inflamed colon and variable immunomodulatory ability in vivo. Here, we demonstrated a new methodology to manipulate MSCs to express CX3C chemokine receptor 1 (CX3CR1) and interleukin-25 (IL-25) to promote their delivery to the inflamed colon and enhance their immunosuppressive capability. Compared to MSCs without treatment, MSCs infected with a lentivirus (LV) encoding CX3CR1 and IL-25 (CX3CR1&IL-25-LV-MSCs) exhibited enhanced targeting to the inflamed colon and could further move into extravascular space of the colon tissues via trans-endothelial migration in dextran sodium sulfate (DSS)-challenged mice after MSC intravenous injection. The administration of the CX3CR1&IL-25-LV-MSCs achieved a better therapeutic effect than that of the untreated MSCs, as indicated by pathological indices and inflammatory markers.