Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

BACKGROUND: Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. FINDINGS: Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. INTERPRETATION: Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. FUNDING: Bill & Melinda Gates Foundation

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The effect of experimental infection of trypanosoma vivax upon production of testosterone as a response to administration with GnRH, in Crossbred Bulls. Thecnical note

En el presente trabajo se evaluaron los cambios de la concentración de testosterona en suero sanguíneo en respuesta a la estimulación con GnRH en toros mestizos (5/8 Bos taurus 3/8 Bos indicus), infectados experimentalmente con Trypanosoma vivax. La determinación de testosterona fue llevada a cabo mediante el ensayo inmunofluorométrico estandarizado (DELFIA). Tres (3) toros (cuyas edades oscilaban entre 24 y 30 meses) fueron evaluados clínica y parasito lógicamente, además se realizó el seguimiento de la calidad espermática durante el proceso de experimentación. La determinación de la concentración de testosterona durante el período de post-infección se realizó en la fase crónica de la enfermedad (65 días posteriores a la inoculación). Los resultados indican que los animales infectados responden más lentamente al estímulo con GnRH, y la concentración de testosterona producida es menor. Este resultado es consistente con la hipótesis que la tripanosomiasis puede interferir en la modulación del eje hipotálamo-hipófisisgónada, afectando la esteroidogénesis testicular.503 - 507BimestralPresent work deals with the evaluation of changes in testosterone concentration as a response to treatment with GnRH in crossbred bulls (5/8 Bos taurus 3/8 Bos índicus) infected experimentally with Trypanosoma vivax. The determination of testosterone was carried out by means of standarized inmunofluorometric essay (DELFIA). Three bulls (whose ages range between 24 and 30 months old) were evaluated clinical and parasitologically, also for spermatic quality during experimental period. Determination of concentration of testosterone postinoculation was carried out during chronic phase of the illness (65 after inoculation). Results indicate that infected animals have a slower response to the stimulus with GnRH, also they have a smaller concentration of testosterone. These results are consistent with the hypothesis that trypanososmiasis may interfere in the modulation of the hypothalamic-hypophisis-gonadal axis by tripanosomiasis afecting testicular steroidogenesis

Scanning electron microscopy of sperm alterations of siboney crossbred bulls

Los espermatozoides poseen un alto grado de polimorfismo. Se considera normal que hasta un 20% de ellos estén alterados en el eyaculado, mientras que un semen cuyo porcentaje de atiplas sea superior al 20%, se tiene como de baja calidad. La mayoría de tales alteraciones pueden ocurrir durante el tránsito y maduración a lo largo del epidídimo. Esas malformaciones pueden ser debido a factores genéticos, parasitarios, etarios, alimenticios, ecológicos, etc., que alteran el normal desarrollo de las diferentes etapas de la morfogénesis del esperma. El propósito del presente trabajo fue describir a través de microscopía electrónica de barrido, las alteraciones presentes en los espermatozoides de toros mestizos Siboney (5/8 Bos taurus, 3/8 Bos indicus), que no son detectadas por las pruebas convencionales. Para ello, a un grupo de cuatro toros tomados al azar, se les extrajo semen por electroeyaculación en dos ocasiones, en un intervalo de quince días, el cual se procesó para microscopía electrónica de barrido. Se observaron, además de las atipias detectables por microscopía óptica como: flagelos enrollados sobre si mismos, gotas citoplasmáticas y cabezas sin flagelos, otras alteraciones no detectables a ese nivel, tales como: desprendimiento de la membrana plasmática, pliegues de la misma membrana en la zona del acrosoma, restos vesiculares en la membrana que recubre la cabeza, desprendimiento de la misma con exposición del acrosoma. La observación, por microscopía electrónica de barrido de las alteraciones presentes en espermatozoides de toros, incrementó el número de atipias detectadas con respecto a lo reportado por los métodos convencionales. Al poder mostrar alteraciones que escapan del poder resolutivo del microscopio óptico, permite un diagnóstico de viabilidad más confiable, de manera que se puedan seleccionar los sementales adecuados para la inseminación natural y artificial, y así incrementar significativamente el porcentaje de fertilidad.235 - 242BimestralThe sperms posses a high polymorphism degree. It is considered normal that until 20% of them are altered in the ejaculated semen, while a semen whose atypical percentage is superior to 20%, has low quality. Most of such alterations could be happen during the traffic and maturation along the epididymis. Those malformations can be due to genetic, parasitic, age, nutritional and ecological factors, that alter the normal development of the different stages in the morphogenesis of the sperm. The purpose of the present work was to describe by scanning electron microscopy, the present alterations in the sperm of siboney crossbred bull (5/8 Bos taurus, 3/8 Bos indicus) that are no detected by the conventional tests. From four bulls taken at random, semen was extracted by electroejaculation in two times in an interval of fifteen days, and were processed for scanning electron microscopy. In addition to sperm cells alterations observed in light microscopy, such as: self coiled flagellum, in scanning electron microscopy were observed bovine spermatozoon with detachment of the plasmatic membrane, folds of the same membrane in acrosome area, vesicular structure and detachment of the head membrane with exposure of acrosome. These observations increased the number of malformations detected and reported by light microscopy. Therefore, scanning electron microscopy allows a more reliable diagnosis of viability of sperm cells, so that, the appropriate bull can be selected for natural and artificial in semination, and, in this way, to increase significantly the percentage of fertility

Effect of Trypanosoma vivax infection on semen quality of siboney Bull

Existen evidencias en las que toros africanos infectados experimentalmente con Trypanosoma vivax manifiestan un descenso en la calidad espermática, traduciéndose éste hecho en una posible disminución en la capacidad de fertilización. En el presente trabajo se determinan algunas de las alteraciones que causa sobre la calidad del esperma, la infección experimental con Trypanosoma vivax en toros tropicales tipo Siboney (5/8 Bos taurus, 3/8 Bos indicus). Para ello, un grupo de seis toros mestizos fueron tomados al azar, cuatro (4) de estos fueron inoculados con 106 trypanosomas/ml; los dos (2) toros restantes permanecieron como control. Los parámetros utilizados, pre y post-infección, para la evaluación espermática fueron: motilidad individual, concentración espermática, porcentaje de atípias y viabilidad celular. Paralelamente se recopilaron datos sobre el peso corporal, circunferencia escrotal, hematocrito, parasitemia y temperatura corporal. El experimento se llevo a cabo en un período de dieciocho semanas, durante las cuales los animales infectados presentaron parasitemias recurrentes, anemia, anorexia, aletargamiento, pérdida de equilibrio, debilidad, fiebre, Además, se observó un deterioro en la calidad del semen, que se manifestó como un aumento de las atípias, disminución de la viabilidad y concentración espermática. Es probable que esto afecte la capacidad de fertilización y por ende la productividad de cualquier rebaño expuesto a este parásito, con sus implicaciones negativas en el desarrollo socioeconómico de la actividad ganadera.411 - 417BimestralThere are evidences that African bulls infected experimentally with Trypanosoma vivax show lower spermatic quality, this fact can imply a possible decrease in the fertilization capacity. In the present work, we study, the effect of the experimental infection with Trypanosoma vivax in the quality of the semen of tropical bulls (Siboney: 3/8 Bos taurus, 5/8 Bos indicus), and some alterations of the sperm are determinated. A group of six crossbred bulls was taken at random, four of them, were inoculated intravenously with 106 trypanosomes/ml, and two bulls remained as control. The used parameters (obtained pre and post-infection) for the spermatic evaluation were: individual motility, spermatic concentration, percentage of atipias and cellular viability. At the same time, data were gathered on the corporal weight, scrotal circumference, hematocrit level, parasitemia and corporal temperature. The assay was carried out in a period of eighteen weeks, during which the infected animals presented recurrent parasitemias, anemia, anorexia, lethargy, balance loos, weakness and fever. Also, deterioration was observed in the quality of the semen, which showed as an increase of the atipias, decrease of the viability and spermatic concentration. This probably affects, the fertilization capacity, and therefore, the productivity of any exposed flock to T vivax with negative implications in the economic development of the cattle activity

Lectin-binding pattern in the kidney of mice experimentally infected with a venezuelan strain of Trypanosoma evansi

El Trypanosoma evansi es un hemoparásito que ocasiona la tripanosomosis equina en Venezuela. Esta enfermedad cursa con un incremento en la temperatura corporal, anemia, debilidad, parálisis y en algunos casos la muerte. Los mecanismos celulares del proceso infeccioso no se conocen con exactitud y pueden involucrar a los glicoconjugados de superficie del parásito y del hospedador. El propósito del presente estudio fue determinar las diferencias en el patrón de enlazamiento de las lectinas: sCon A, sWGA, PNA, SBA, UEA-I, LFA, SNA, y MAL-II en el riñón de ratones sanos e infectados con T. evansi. Para ello se realizó el marcaje sobre cortes en parafina de riñón utilizando el método del Complejo Avidina-Biotina (ABC). En controles se observó una reacción de moderada a intensa del endotelio glomerular con LFA, SNA y MAL-II mientras que en los animales infectados la reacción fue intensa. Los controles no experimentaron marcaje con sConA, sWGA, PNA y SBA a la vez que los infectados mostraron reacción mínima. El endotelio glomerular de los animales infectados no experimentó cambios en el enlazamiento de UEA-I con respecto a los controles. En los animales infectados, los eritrocitos y los túbulos contorneados proximales incrementaron su reactividad con SNA, y los componentes de la matriz extracelular con UEA-I. El marcaje con sWGA en la cápsula Bowmann de los riñones de animales infectados disminuyó con respecto a los controles. Estos resultados sugieren que en ratones infectados, los tripanosomas vivos o muertos pueden liberar componentes que alteran el patrón de glicoconjugados en las membranas celulares del riñón.431 - [email protected]@yahoo.comBimestralTrypanosoma evansi is the aethiological agent of equine trypanosomosis in Venezuela. This disease causes an increment in body temperature, anaemia, weakness and paralysis, finally causing the death of the host. The cellular mechanisms involved in the infectious process are not known and may involve the growth of superficial glycoconjugates with characteristic sugar residuals on the surfaces of both host and trypanosomes. The aim of the present study was to determine possible differences in the binding patterns of lectins: sCon A, sWGA, PNA, SBA, UEA-I, LFA, SNA, and MAL-II in kidneys of healthy mice and and mice infected with T. evansi. Sections of infected and control mice kidneys were labelled according to the Avidine-Biotine Complex (ABC) method. In controls and infected animals an intense reaction in the glomerular endothelium was observed with: LFA, SNA and MAL-II, and a low to moderate reaction with sCon A, sWGA, PNA, SBA, and UEA-I. In infected animals, the red blood cells and the Henle loop showed increased reactivity with SNA, and the components of the extracellular matrix with UEA-I. In infected animals the binding with SNA in the proximal convolute tubules and with PNA and sWGA in the renal capsule was reduced. These results suggest that in infected mice, living or dead trypanosomes might liberate biologically active products that alter the pattern of the glycoconjugates in the cell membranes of the kidney

Informe de Análisis de Necesidades de Formación del Profesorado Activo de Educación Primaria y Secundaria mediante la Opinión de Docentes Universitarios de América Latina y el Caribe

Analisi, tramite indagine empirica a campione presso professori universitari, dei bisogni formativi dei docenti in servizio della scuola primaria e della scuola secondaria negli istituti latinoamericani e dei Caraib