The Influence of the Electric Supply Industry on Economic Growth in Less Developed Countries

This study measures the impact that electrical outages have on manufacturing production in 135 less developed countries using stochastic frontier analysis and data from World Bank’s Investment Climate surveys. Outages of electricity, for firms with and without backup power sources, are the most frequently cited constraint on manufacturing growth in these surveys. Outages are shown to reduce output below the production frontier by almost five percent in Africa and by a lower percentage in South Asia, Southeast Asia and the Middle East and North Africa. Production response to outages is quadratic in form. Outages also increase labor cost, reduce exports of manufacturing product and slightly increase imports of intermediate materials. The rate of inefficiency in manufacturing, however, is not higher in countries with state ownership of the transmission and distribution grids. This research has implications for economic theory. The output elasticity of electricity is nearly triple its share of inputs in production. The marginal revenue product of electricity is nearly triple the marginal revenue products of labor and capital inputs at equilibrium. Electric supply, akin to R&D, has a much larger role in economic output than postulated in production theory. Differences in the output elasticities between firm-level and worker-level production functions raise additional questions about the adequacy of the human capital theory of wage differentials. This research has several implications for development policy. First, unlike investments in human capital, stable electric supplies can deliver short-term improvements in living standards. Second, policies focused on small business development can inadvertently raise the level of inefficiency in manufacturing

Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

Teachers’ and Parents’ Perspectives on the Feasibility of a Preschool-Based Behavioral Intervention to Prevent Obesity: An Embedded Qualitative Study within ToyBox Study Malaysia

The aim of this qualitative study, an embedded component of ToyBox Study Malaysia (TSM), was to elicit the perspectives of teachers and parents regarding the implementation of TSM. TSM is a preschool-based behavioral intervention program aimed at improving healthy energy balance-related behaviors among young children attending preschools. The qualitative study adopted a descriptive-interpretive methodology, and triangulated data collected through semi-structured focus groups with artifacts collected. The setting involved rural and metropolitan preschools in Sarawak and Peninsular Malaysia, respectively. In Sarawak, 11 teachers and 20 parents from six intervention preschools participated in this study. In Peninsular Malaysia, 14 preschool teachers and seven assistant teachers representing all 15 intervention preschools participated in the study. Data were analyzed thematically and four overarching themes were identifed: impact of TSM on the children’s knowledge and practices of healthy energy balance-related behaviors; spheres of infuence upon the children’s energy balance-related behaviors; constraints and afordances related to the implementation of TSM; and prospective sustainability of TSM. The triangulation of data from teachers, parents, and the artifacts related to TSM enabled the corroboration of evidence to support the themes identifed. This study provides evidence on the reciprocal interactions between the teachers and parents who played key roles in facilitating behavioral change in the children, and the children who, in turn, served as change agents beyond the preschool. Furthermore, the mediational tools such as the TSM crockery and availability of healthy food and water led to the reported behavioral changes at both rural and metropolitan settings

From ToyBox Study to eToyBox : Advancing Childhood Obesity Reduction in Malaysian Kindergartens

Prevention and treatment of childhood obesity is a global concern, and in Malaysia, it is considered a national public health priority. Determinants of childhood obesity are multifactorial and include factors that directly and indirectly influence energy balance-related behaviours, including energy intake and energy expenditure. Interventions to address childhood obesity that have multiple components at different levels have been shown to be the most influential. The ToyBox-study is a childhood obesity intervention aimed at preschool-aged children and their families that had been shown to be effective in several European countries and so was chosen for adaption for the Malaysian setting. Materials were translated and adjusted for the Malaysian context and audience and implemented in kindergartens in Peninsular Malaysia and Sarawak. However, during the COVID-19 pandemic and lockdown, teaching transitioned to being online. This brought an opportunity to reach a wider audience and consider the long-term sustainability of the intervention, and thus eToybox was born. eToybox aims to bring support for healthy energy balance behaviours directly to the teachers, into kindergartens and homes, to encourage families to be active and eat healthily, and prevent or reduce obesity. Through online innovation, the Toybox Study Malaysia programme has been expanded to enhance its potential to impact the promotion of healthy lifestyles among preschoolers and their families, highlighting the importance of a holistic approach to preventing and treating childhood obesity in Malaysia

Validity and Reliability of a Food Frequency Questionnaire (FFQ) to Assess Dietary Intake of Preschool Children

As there are few food frequency questionnaires (FFQ) to assess the dietary intake of preschool children, this study examined the validity and reliability of an FFQ for this purpose. A total of 210 preschoolers aged 4 to 6 years participated in the validation study, while a subsample of 66 participants joined the reliability study. The FFQ is modified from the ToyBox-study and South East Asian Nutrition Surveys (SEANUTS), and comprised 108 food items from 13 food groups. A three-day estimated dietary record (3DR) was used as reference and reliability was assessed through a second administration of the FFQ (FFQ2), four weeks after the first administration (FFQ1). For the validation study, Spearman’s correlation coefficients showed moderate to high correlations (p < 0.001) between FFQ and 3DR. Cross-classification of quartile analysis showed moderate agreement between the two methods. As for reliability, Spearman’s correlation coefficients showed moderate to high correlations (p < 0.001) between FFQ1 and FFQ2. Cronbach’s alpha values (0.708 to 0.824) and intraclass correlation coefficients (0.710 to 0.826) showed good agreement between repeated FFQs. The results suggest that the FFQ has acceptable validity and good reliability. Hence, the FFQ can be used to assess preschool children’s food intake

Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis

BackgroundCascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective.ObjectivesThe objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers.Design and methodsThis study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)–Hospital Episode Statistics (HES) linked primary–secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals.ResultSystematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing (p < 0.01); the CPRD–HES data set indicated that 70% did not achieve target treatment levels, and demonstrated increased cardiovascular disease risk among these individuals, compared with controls (hazard ratio 9.14, 95% CI 8.55 to 9.76). The specialist familial hypercholesterolaemia register confirmed excessive cardiovascular morbidity (standardised morbidity ratio 7.17, 95% CI 6.79 to 7.56). Cost-effectiveness modelling found a net health gain from diagnosis of –0.27 to 2.51 quality-adjusted life-years at the willingness-to-pay threshold of £15,000 per quality-adjusted life-year gained. The cost-effective protocols cascaded from genetically confirmed index cases by contacting first- and second-degree relatives simultaneously and directly. Interviews found a service-led direct-contact approach was more reliable, but combining direct and indirect approaches, guided by index patients and family relationships, may be more acceptable.LimitationsSystematic reviews were not used in the economic analysis, as relevant studies were lacking or of poor quality. As only a proportion of those with primary care-coded familial hypercholesterolaemia are likely to actually have familial hypercholesterolaemia, CPRD analyses are likely to underestimate the true effect. The cost-effectiveness analysis required assumptions related to the long-term cardiovascular disease risk, the effect of treatment on cholesterol and the generalisability of estimates from the data sets. Interview recruitment was limited to white English-speaking participants.ConclusionsBased on limited evidence, most cost-effective cascade-testing protocols, diagnosing most relatives, select index cases by genetic testing, with services directly contacting relatives, and contacting second-degree relatives even if first-degree relatives have not been tested. Combined approaches to contact relatives may be more suitable for some families.Future workEstablish a long-term familial hypercholesterolaemia cohort, measuring cholesterol levels, treatment and cardiovascular outcomes. Conduct a randomised study comparing different approaches to contact relatives.Study registrationThis study is registered as PROSPERO CRD42018117445 and CRD42019125775.FundingThis project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 16. See the NIHR Journals Library website for further project information

Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study.

Background Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease. Methods/Design A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also. Discussion The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and the first 2 years of life) on the development of vaccine immunity and allergy. The data will inform an ongoing debate of potential effects of geohelminths on child health and will contribute to policy decisions on new interventions designed to improve vaccine immunogenicity and protect against the development of allergic diseases

Study of ordered hadron chains with the ATLAS detector

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Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease

Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases