Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

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

Evaluación de la condición del río Migüir mediante el desarrollo de un índice de calidad de agua

El río Migüir está ubicado en el Parque Nacional Cajas en la provincia del Azuay a 30 minutos de la ciudad de Cuenca, a lo largo de esta se encuentran diferentes comunidades como la de Molleturo y Migüir. La ejecución del estudio comenzó con la selección de diferentes profesionales con conocimientos en el tema de recursos hídricos y dispuestos a colaborar, de todos los postulantes se tomó en cuenta a 20 participantes. Se aplicó dos encuestas a los voluntarios, los resultados de dichas encuestas fueron útiles para el cálculo de los pesos y parámetros de calidad necesarios para el índice. De las encuestas se estimó los 16 parámetros que entran en la investigación de acuerdo a criterios de usos de agua que son: agrícola, pecuaria y recreativa. Una vez analizados los parámetros en el Laboratorio de Análisis de Agua y Suelos de la Universidad de Cuenca se procedió a desarrollar el Índice de Calidad del agua (ICA), posteriormente se validó con el ICA NSF mediante correlaciones de Pearson y por último se comparó con la normativa legal vigente, para ello se realizó cinco campañas de muestreo en tres puntos específicos tratando de abarcar los 7 km de la zona de estudio y además estaciones secas y lluviosas, durante los meses de octubre , noviembre y diciembre del 2020. Los resultados al aplicar los ICA’s demuestran que la calidad del agua del río Migüir está entre Buena a Excelente, por otra parte, se tuvo una correlación positiva y fuerte entre el ICA Desarrollado y el ICA NSF considerándolo válido, por último, ningún parámetro está por encima de los límites permisibles de la normativa.The Miguir River is located in the mountains of the Cajas National Park. This is 30 minutes from the Cuenca city belonging to the province of Azuay. Around this beautiful place are different communities; such as: Molleturo and Miguir. The study of my project began with the collection of information from different professionals who have knowledge on the subject of water resources and are willing to collaborate. Once the 20 participating experts were known, two surveys were carried out. These results will help to calculate the weights and quality subscripts necessary for the formulation of the aforementioned river index. From the surveys, the 16 parameters that enter the research were estimated according to criteria of water uses that are: agricultural, livestock and recreational. Once the parameters had been analyzed in the Soil and Water Analysis Laboratory of the University of Cuenca, the water quality index (ICA) was elaborated. Subsequently, it was validated with the ICA NSF using Pearsons correlations and finally it was compared with current legal regulations. For this, five sampling campaigns were carried out at three specific points. During the months of October, November and December 2020, we tried to cover the 7 km of the study area and with it also the dry and rainy seasons. The results show that the water quality of the Miguir River is between Good and Excellent. Furthermore, there is a positive and strong correlation between the ICA Developed and the ICA NSF and thus considering it valid. Finally, it should be mentioned that no parameter is above the permissible limits of the regulation.Ingeniero AmbientalCuenc

Combustion system model of a wet process clinker Kiln

En este trabajo se presenta el modelo del proceso de combustión de un horno rotatorio de clinker, el cual se obtiene a partir de un balance de energía representado en el calor que se genera por la combustión de carbón y la forma como se distribuye aquel en todo el proceso. Se utilizan datos de las variables reales del proceso, obtenidas del sistema de control mediante Ole Process Control, las cuales se operan con datos experimentales y variables que se asumen como constantes. El modelo obtenido se ajusta con dos herramientas: mínimos cuadrados y filtro Infinite Impulse Response de primer orden. Se valida y comprueba el modelo y sus ajustes utilizando dos herramientas estadísticas: diagrama de cajas y bigotes y un método de ocho métricas estadísticas relacionadas por una función difusa. La utilización de estas herramientas evidencia un desempeño satisfactorio del modelo planteado.This paper presents the model of the combustion process of a clinker kiln, which is obtained from an energy balance represented in the heat generated by burning coal and how this is distributed across the process. Data comes from the actual process variables, obtained from the control system using OLE Process Control, which operates using experimental data and variables that are assumed to be constant. The resulting model is fitted with two tools: least squares and Infinite Impulse Response filter of first order. It validates and verifies the model and its settings using two statistical tools: box and whisker diagram and method of eight statistical metrics related by a fuzzy function. The use of these tools evidence satisfactory performance of the proposed model

Combustion System Model of a Wet Process Clinker Kiln

This paper presents the model of the combustion process of a clinker kiln, which is obtained from an energy balance represented in the heat generated by burning coal and how this is distributed across the process. Data comes from the actual process variables, obtained from the control system using OLE for Process Control, which operates using experimental data and variables that are assumed to be constant. The resulting model is fitted with two tools: least squares and Infinite Impulse Response filter of first order. It validates and verifies the model and its settings using two statistical tools: box and whisker diagram and method of eight statistical metrics related by a fuzzy function. The use of these tools evidence satisfactory performance of the proposed model.En este trabajo se presenta el modelo del proceso de combustión de un horno rotatorio de Clinker, el cual se obtiene a partir de un balance de energía representado en el calor que se genera por la combustión de carbón y la forma como se distribuye aquel en todo el proceso. Se utilizan datos de las variables reales del proceso, obtenidas del sistema de control mediante OLE for Process Control, las cuales se operan con datos experimentales y variables que se asumen como constantes. El modelo obtenido se ajusta con dos herramientas: mínimos cuadrados y filtro Infinite Impulse Response de primer orden. Se valida y comprueba el modelo y sus ajustes utilizando dos herramientas estadísticas: diagrama de cajas y bigotes y un método de ocho métricas estadísticas relacionadas por una función difusa. La utilización de estas herramientas evidencia un desempeño satisfactorio del modelo planteado

Combustion system model of a wet process clinker Kiln

En este trabajo se presenta el modelo del proceso de combustión de un horno rotatorio de clinker, el cual se obtiene a partir de un balance de energía representado en el calor que se genera por la combustión de carbón y la forma como se distribuye aquel en todo el proceso. Se utilizan datos de las variables reales del proceso, obtenidas del sistema de control mediante Ole Process Control, las cuales se operan con datos experimentales y variables que se asumen como constantes. El modelo obtenido se ajusta con dos herramientas: mínimos cuadrados y filtro Infinite Impulse Response de primer orden. Se valida y comprueba el modelo y sus ajustes utilizando dos herramientas estadísticas: diagrama de cajas y bigotes y un método de ocho métricas estadísticas relacionadas por una función difusa. La utilización de estas herramientas evidencia un desempeño satisfactorio del modelo planteado.This paper presents the model of the combustion process of a clinker kiln, which is obtained from an energy balance represented in the heat generated by burning coal and how this is distributed across the process. Data comes from the actual process variables, obtained from the control system using OLE Process Control, which operates using experimental data and variables that are assumed to be constant. The resulting model is fitted with two tools: least squares and Infinite Impulse Response filter of first order. It validates and verifies the model and its settings using two statistical tools: box and whisker diagram and method of eight statistical metrics related by a fuzzy function. The use of these tools evidence satisfactory performance of the proposed model