Ability of verbal autopsy data to detect deaths due to uncontrolled hyperglycaemia:testing existing methods and development and validation of a novel weighted score

Objectives: Verbal autopsy (VA) is a useful tool to ascertain cause of death where no other mechanisms exist. We aimed to assess the utility of VA data to ascertain deaths due to uncontrolled hyperglycaemia and to develop a weighted score (WS) to specifically identify cases. Cases were identified by a study or site physician with training in diabetes. These diagnoses were also compared with diagnoses produced by a standard computer algorithm (InterVA-4). Setting: This study was done using VA data from the Health and Demographic Survey sites in Agincourt in rural South Africa. Validation of the WS was done using VA data from Karonga in Malawi. Participants: All deaths from ages 1 to 49 years between 1992 and 2015 and between 2002 and 2016 from Agincourt and Karonga, respectively. There were 8699 relevant deaths in Agincourt and 1663 in Karonga. Results: Of the Agincourt deaths, there were 77 study physician classified cases and 58 computer algorithm classified cases. Agreement between study physician classified cases and computer algorithm classified cases was poor (Cohen’s kappa 0.14). Our WS produced a receiver operator curve with area under the curve of 0.952 (95% CI 0.920 to 0.985). However, positive predictive value (PPV) was below 50% when the WS was applied to the development set and the score was dominated by the necessity for a premortem diagnosis of diabetes. Independent validation showed the WS performed reasonably against site physician classified cases with sensitivity of 86%, specificity of 99%, PPV of 60% and negative predictive value of 99%. Conclusion: Our results suggest that widely used VA methodologies may be missing deaths due to uncontrolled hyperglycaemia. Our WS may offer improved ability to detect deaths due to uncontrolled hyperglycaemia in large populations studies where no other means exist

Diabetes in sub-Saharan Africa: from clinical care to health policy.

Rapid demographic, sociocultural, and economic transitions are driving increases in the risk and prevalence of diabetes and other non-communicable diseases (NCDs) in sub-Saharan Africa. The impacts of these transitions and their health and economic consequences are evident. Whereas, in 1990, the leading causes of death in sub-Saharan Africa were HIV/AIDS, lower respiratory infections, diarrhoeal diseases, malaria, and vaccine-preventable diseases in children, in more recent years, cardiovascular diseases and their risk factors are replacing infectious diseases as the leading causes of death in this region, and rates of increase of cardiovascular risk factors are predicted to be greater in sub-Saharan Africa than in other parts of the world. Thus, sub-Saharan Africa—which contains a high proportion of the world\u27s least developed countries—will face the multifaceted challenge of dealing with a high burden of infectious diseases and diseases of poverty, while also addressing the increasing burden of cardiovascular disease and its risk factors. At present, many of the health systems in sub-Saharan Africa struggle to cope with infectious diseases. Meeting the goals of the UN high-level meeting on NCDs (to reduce premature mortality from NCDs by 25% by 2025) and Sustainable Development Goals (SDGs; to reduce premature mortality from NCDs by a third by 2030) requires a coordinated approach within countries, which starts with a firm consideration of disease burden, needs, and priorities

Endocrine Activity of Extraembryonic Membranes Extends beyond Placental Amniotes

BACKGROUND. During development, all amniotes (mammals, reptiles, and birds) form extraembryonic membranes, which regulate gas and water exchange, remove metabolic wastes, provide shock absorption, and transfer maternally derived nutrients. In viviparous (live-bearing) amniotes, both extraembryonic membranes and maternal uterine tissues contribute to the placenta, an endocrine organ that synthesizes, transports, and metabolizes hormones essential for development. Historically, endocrine properties of the placenta have been viewed as an innovation of placental amniotes. However, an endocrine role of extraembryonic membranes has not been investigated in oviparous (egg-laying) amniotes despite similarities in their basic structure, function, and shared evolutionary ancestry. In this study, we ask whether the oviparous chorioallantoic membrane (CAM) of chicken (Gallus gallus) has the capability to synthesize and receive signaling of progesterone, a major placental steroid hormone. METHODOLOGY/PRINCIPAL FINDINGS. We quantified mRNA expression of key steroidogenic enzymes involved in progesterone synthesis and found that 3β-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone exhibited a 464 fold increase in the CAM from day 8 to day 18 of embryonic development (F5, 68=89.282, p<0.0001). To further investigate progesterone synthesis, we performed explant culture and found that the CAM synthesizes progesterone in vitro in the presence of a steroid precursor. Finally, we quantified mRNA expression and performed protein immunolocalization of the progesterone receptor in the CAM. CONCLUSIONS/SIGNIFICANCE. Collectively, our data indicate that the chick CAM is steroidogenic and has the capability to both synthesize progesterone and receive progesterone signaling. These findings represent a paradigm shift in evolutionary reproductive biology by suggesting that endocrine activity of extraembryonic membranes is not a novel characteristic of placental amniotes. Rather, we hypothesize that these membranes may share an additional unifying characteristic, steroidogenesis, across amniotes at large.Sigma Xi (G20073141634396861); National Science Foundation (2008059161); UF-Howard Hughes G.A.T.O.R. Program; Howard Hughes Medical Institute Professorshi

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Characteristics of insulin registry patients with Type 1 diabetes in Sri Lanka

Background: There is a paucity of literature on epidemiology of type 1 diabetes (T1D) in Sri Lanka. This study reviews the characteristics of patients registered in an insulin bank programme in Sri Lanka. Materials and Methods: Data were collected and analysed from records of all 672 patients diagnosed with T1D registered in the insulin bank with dates of the diagnosis ranging from 1971 to 2016. Results: Of the 672 patients, age at the diagnosis ranged from the day of birth to 44 years. The majority of patients, 526 (78.3%) were diagnosed before 15 years of age, with 7 (1.0%) cases diagnosed before 6 months. Females accounted for 56.8% of cases. The ethnic distribution of T1D in the study population was consistent with the overall population. Conclusion: This study gives some insight into the epidemiological features of T1D in young people in Sri Lanka. The peak age at the diagnosis is similar to studies in the western countries. This study also demonstrated a slight female predominance and a small but significant number of cases diagnosed in infancy. Further epidemiological and clinical research would help guide organisation of care and distribution of resources in the management of T1D in Sri Lanka