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Background In 2019, the RTS,S/AS01 E malaria vaccine (RTS,S) was introduced into Ghana’s routine health system as part of the Malaria Vaccine Implementation Programme (MVIP). Household surveys were conducted prior to vaccine introduction and approximately 18 and 30 months post-introduction. We present a description of the area in Ghana based on the baseline household survey including malaria prevalence, malnutrition, wealth, insecticide-treated net (ITN) coverage, other health interventions (deworming, Vitamin A supplementation (VAS)), coverage of Expanded Programme on Immunization (EPI) vaccines, and health-seeking behaviour for febrile children. Methods The baseline household survey was conducted between 25 February and 18 March 2019 in a representative sample of 6778 households across 66 districts (33 in each of the implementing and comparator areas) in Ghana. Caregivers of children aged 5–48 months were interviewed. For each child, vaccination details were transcribed from the maternal and child health record book, and we measured the mid-upper arm circumference and obtained a malaria Rapid Diagnostic Test (RDT). Survey-weighted coverage estimates were obtained using standard survey methods. Survey Poisson regression was used to estimate prevalence ratios. Results Overall, 7768 children were included in the study, and 21% (95% CI 18–23) tested positive for malaria parasitemia by RDT. About 87%, 95%CI (85–89) of all households owned at least one ITN, and 62%, 95%CI (59–64) of children aged 5–48 months slept under an insecticide-treated net (ITN) the night before the survey. Additionally, 22%, 95%CI (21–24) of children reported having fever in the two weeks preceding the survey; among those with reported fever, 72%, 95%CI (69–74) sought advice or treatment, 40%, 95%CI (37–44) were tested for malaria, and 42%, 95%CI (39–46) of those with fever took an antimalarial drug. Additionally, 17%, 95%CI (16–19) had a mid-upper arm circumference (MUAC) ≤ 13.5 cm, and 1%, 95%CI (0–1) had a (MUAC) ≤ 11.5 cm. The uptake of vitamin A VAS in the 6 months prior to the survey was 36%, based on routine delivery through EPI, and deworming coverage was 29%. Coverage of EPI vaccines was > 90%. Indicators in comparison and implementation areas were comparable. Conclusions The pilot implementation and evaluation of the RTS,S malaria vaccine in Ghana was conducted in an area with substantial malaria transmission and illness, modest health-seeking behaviour and ITN use, and good EPI vaccine coverage. This study has established the baseline comparability between implementation and comparator areas, which serves as the foundation for future feasibility assessments.

In Ghana, few studies have focused on the link between risky sexual behaviours and contraceptive use among adolescents. Based on a survey of 260 randomly sampled unmarried adolescents, this study examined risky sexual behaviours and modern contraceptive use. Descriptive statistical analyses were performed in addition to bivariate and logistic regression models. Results show that 50.4% of respondents have had sex before, and many engaged in risky sexual behaviours: 48.8% have had two or more sexual partners in their lifetime; 21.4% have had sex while drunk; and 60.7% of those who reported having sex while drunk did not use a condom. Only 22.9% of sexually active adolescents ever used contraceptives. Factors that predicted use of contraceptives included being aged 17-19, knowing a place to get contraceptive, not having had drunk sex, and not feeling pressured to have unprotected sex. Public health education and self-efficacy interventions are needed to address risky sexual behaviours and improve contraceptive use.

BackgroundGSK3368715, a first-in-class, reversible inhibitor of type I protein methyltransferases (PRMTs) demonstrated anticancer activity in preclinical studies. This Phase 1 study (NCT03666988) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of GSK3368715 in adults with advanced-stage solid tumors.MethodsIn part 1, escalating doses of oral once-daily GSK3368715 (50, 100, and 200 mg) were evaluated. Enrollment was paused at 200 mg following a higher-than-expected incidence of thromboembolic events (TEEs) among the first 19 participants, resuming under a protocol amendment starting at 100 mg. Part 2 (to evaluate preliminary efficacy) was not initiated.ResultsDose-limiting toxicities were reported in 3/12 (25%) patients at 200 mg. Nine of 31 (29%) patients across dose groups experienced 12 TEEs (8 grade 3 events and 1 grade 5 pulmonary embolism). Best response achieved was stable disease, occurring in 9/31 (29%) patients. Following single and repeat dosing, GSK3368715 maximum plasma concentration was reached within 1 h post dosing. Target engagement was observed in the blood, but was modest and variable in tumor biopsies at 100 mg.ConclusionBased on higher-than-expected incidence of TEEs, limited target engagement at lower doses, and lack of observed clinical efficacy, a risk/benefit analysis led to early study termination.Trial registration numberNCT03666988.

Purpose Based on a sample of 1,872 firm-year observations for 573 global firms over the period 2013–2016, this study aims to provide empirical evidence on how environmental, social and governance (ESG) performance affects corporate creditworthiness as measured by credit default swap (CDS) spreads.Design/methodology/approach The authors use a regression model that accounts for country, industry and time-fixed effects as well as the instrumental-based Generalized Method of Moments (GMM) approach to dynamic panel modeling.Findings This study finds that improvements in ESG performance, especially in its governance pillar, reduce credit risk. Further, the authors uncover evidence suggesting the complementarity between ESG performance and country-level sustainability. The results indicate a stronger risk-mitigating impact of ESG performance in countries with higher sustainability scores.Practical implications In terms of practical implications, the findings suggest that corporations should strengthen governance frameworks and procedures to reduce credit risk, prior to embarking on environmental and social objectives. Further, the finding that country sustainability is an important determinant of CDS spreads suggests that country-level sustainability initiatives would not only help to preserve natural capital and promote social capital but also be beneficial to businesses and financial stability.Originality/value The study adds to the literature on the effects of ESG performance on credit risk by (1) utilizing a measure of ESG performance that considers the financial materiality of ESG issues across different industries; (2) utilizing a market-based measure of credit risk and CDS spreads; (3) examining the relative importance of ESG components to credit risk, rather than just the aggregate measure; and (4) assessing the influence of country sustainability on the relationship between ESG and credit risk.

Amid growing concern over sustainability issues, there is increasing demand to incorporate environmental and social issues into assessments of credit risk, the possibility of loss resulting from a borrower's failure to meet their financial obligations. In this paper, we sought to identify empirical evidence of a relationship between sustainability measures and credit risk. We contribute to this literature in three main ways: firstly, by using a measure that considers the financial materiality of sustainability issues across different industries; secondly, by using corporate default swap (CDS) spreads as a market-based measure of credit risk; and thirdly, by exploring the context-dependent nature of the relationship. Though the extent differs across industries, our results suggest risk-reducing effects across several corporate sustainability dimensions: climate change; natural resource use; human capital and corporate governance. Furthermore, we found that country sustainability plays a moderating role in the nexus between corporate sustainability and credit risk. Hence, a one-size-fits-all policy may not be suitable in developing the credit-relevant standardization of sustainability factors. Nevertheless, the robustness of corporate governance throughout our findings suggests that corporations should strengthen governance frameworks and procedures prior to embarking on environmental and social objectives to mitigate credit risk.

Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyze 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlight the very early origins of LMS. We uncover three specific subtypes of LMS that likely develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynecological origin harbor genomic dystrophin deletions and/or loss of dystrophin expression, acquire the highest burden of genomic mutation, and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP trappers and other DNA damage response inhibitors, suggesting a promising therapeutic strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis. Heterogeneity in leiomyosarcomas (LMS) makes treatment of the disease challenging. Here the authors analyze LMS heterogeneity and molecular LMS subtypes using genomics and transcriptomics, finding origins in distinct lineages and associations with survival, in addition to the early emergence of metastatic clones.

The use of nanoparticle-infused blended refrigerants is essential for achieving an effective sustainable system. This investigation analyses the efficiency of three nano-refrigerants (CuO-R152a, TiO2-R152a and TiO2-R113a) on the basis of the thermal performance and energy usage of the compressor using MATLAB-Simulink in the vapour compression refrigeration cycle with a two-phase flow domain. Also, nanoparticle volume concentrations of 0.1%–0.5% in the basic refrigerants are investigated. In the Simulink model, the outcomes are calculated mathematically. Using the NIST chemistry webbook, the thermo-physical characteristics of base refrigerants were calculated, and different numerical models were used to compute the characteristics of nano-enhanced refrigerants. MS Excel was used to perform the liquid–vapour interpolation. It was discovered that refrigerants with nanoparticles have superior heat-transfer properties and operate most excellently at an optimal volume fraction of 0.1% for TiO2-R152a and CuO-R152a with a coefficient of performance (COP) as 10.8. However, the other blended nano-refrigerant TiO2-R113a performed the best at 0.5% of nano-particle volume fraction with a COP value of 5.27.

Background The chronic care model was proven effective in improving clinical outcomes of diabetes in developed countries. However, evidence in developing countries is scarce. The objective of this study was to evaluate the effectiveness of EMPOWER-PAR intervention (based on the chronic care model) in improving clinical outcomes for type 2 diabetes mellitus using readily available resources in the Malaysian public primary care setting. Methods This was a pragmatic, cluster-randomised, parallel, matched pair, controlled trial using participatory action research approach, conducted in 10 public primary care clinics in Malaysia. Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care. Patients who fulfilled the criteria were recruited over a 2-week period by each clinic. The obligatory intervention components were designed based on four elements of the chronic care model i.e. healthcare organisation, delivery system design, self-management support and decision support. The primary outcome was the change in the proportion of patients achieving HbA1c < 6.5%. Secondary outcomes were the change in proportion of patients achieving targets for blood pressure, lipid profile, body mass index and waist circumference. Intention to treat analysis was performed for all outcome measures. A generalised estimating equation method was used to account for baseline differences and clustering effect. Results A total of 888 type 2 diabetes mellitus patients were recruited at baseline (intervention: 471 vs. control: 417). At 1-year, 96.6 and 97.8% of patients in the intervention and control groups completed the study, respectively. The baseline demographic and clinical characteristics of both groups were comparable. The change in the proportion of patients achieving HbA1c target was significantly higher in the intervention compared to the control group (intervention: 3.0% vs. control: -4.1%, P < 0.002). Patients who received the EMPOWER-PAR intervention were twice more likely to achieve HbA1c target compared to those in the control group (adjusted OR 2.16, 95% CI 1.34-3.50, P < 0.002). However, there was no significant improvement found in the secondary outcomes. Conclusions This study demonstrates that the EMPOWER-PAR intervention was effective in improving the primary outcome for type 2 diabetes in the Malaysian public primary care setting.

Identification of diagnostic markers for early detection and development of novel and therapeutic agents for effective patient management are the main motivation for cancer research. Biological specimens from large cohort and case-control studies which are crucial in providing successful research outcomes are often the limiting factor that hinders research efforts, especially in developing countries. Therefore, the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS) were established to systematically collect large number of samples with comprehensive sociodemographic, clinicopathological, management strategies, quality of life and associated patient follow-up data to facilitate oral cancer research in Malaysia. The MOCDTBS also promotes sharing among researchers and the development of a multidisciplinary research team. The following article aims to describe the process of setting-up and managing the MOCDTBS.