Genetic association analysis of coronary heart disease by profiling gene-environment interaction based on latent components in longitudinal endophenotypes

Studies of complex diseases collect panels of disease-related traits, also known as secondary phenotypes or endophenotypes. They reflect intermediate responses to environment exposures, and as such, are likely to contain hidden information of gene-environment (G × E) interactions. The information can be extracted and used in genetic association studies via latent-components analysis. We present such a method that extracts G × E information in longitudinal data of endophenotypes, and apply the method to repeated measures of multiple phenotypes related to coronary heart disease in Genetic Analysis Workshop 16 Problem 2. The new method identified many genes, including SCNN1B (sodium channel nonvoltage-gated 1 beta) and PKP2 (plakophilin 2), with potential time-dependent G × E interactions; and several others including a novel cardiac-specific kinase gene (TNNI3K), with potential G × E interactions independent of time and marginal effects

Relación de los centros educativos de enseñanza secundaria con el entorno en Iberoamérica

La presente aportación recoge la visión de 46 especialistas de trece países iberoamericanos sobre las formas de entender y promover la relación de los centros educativos con el entorno. Situados en la enseñanza secundaria (y en la franja de edad de 15 a 18 años), se trata de delimitar la manera cómo se conecta la vida interna y la vida externa del centro educativo, presentando los modelos que se utilizan, las estrategias de intervención y las experiencias más significativas en cada uno de los países. Las aportaciones no buscan tanto revisar la vinculación de los centros educativos entre sí como de analizar fundamentalmente las vinculaciones con la comunidad y las organizaciones que acoge (asociaciones, empresas, organizaciones gubernamentales o no gubernamentales significativas,…). Al respecto, una parte de los escritos recogen experiencias y estrategias que concretan la relación que estudiamos. Esperamos sea así un apoyo para los estudiosos de la temática, pero también aporte contenidos que ayuden a los directivos a mejorar su gestión de las relaciones externas. La orientación de los escritos al análisis organizativo y a la función de los directivos como promotores de las relación con la comunidad tiene que ver con las finalidades y objetivos de la RedAGE; también con el convencimiento por parte de los que escriben que la ordenación que se haga del contexto de intervención y la actuación de los directivos es fundamental para obtener y mantener las respuestas más idóneas a las exigencias del medio socio-cultural-económico. Su realización se vincula al encuentro de especialistas de la RedAGE realizado en el mes de marzo de 2013 en La Paz. Allí, los representantes de las organizaciones miembro presentaron y debatieron, durante el mismo, documentos sobre la temática de la vinculación escuela y entorno, en sus respectivos países, que constituyen la base sobre la que se han realizado las aportaciones definitivas que recoge el presente texto. Se cubre así y de nuevo un propósito fundamental de la Red AGE, como es el de fomentar el intercambio de experiencias, la promoción del conocimiento sobre administración y gestión educativa y la reflexión sobre la práctica de la gestión. La finalidad última es la de mejorar el funcionamiento de los centros educativos (y, a través de ellos, de los sistemas educativos), procurando sean de calidad y un instrumento para el cambio profesional y social

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030