Genomic duplication and translocation of reactivation transactivator and bZIP-homolog genes is a conserved event in alcelaphine herpesvirus 1.

Alcelaphine herpesvirus 1 (AlHV-1) is a gammaherpesvirus carried asymptomatically by wildebeest. Upon cross-species transmission, AlHV-1 induces malignant catarrhal fever (MCF), a fatal lymphoproliferative disease of ruminants, including cattle. The strain C500 has been cloned as an infectious, pathogenic bacterial artificial chromosome (BAC) that is used to study MCF. Although AlHV-1 infection can be established in cell culture, multiple passages in vitro cause a loss of virulence associated with rearrangements of the viral genome. Here, sequencing of the BAC clone showed that the long unique region (LUR) of the genome is nearly identical to that of the previously sequenced strain from which the BAC was derived, and identified the duplication and translocation of a region from within LUR, containing the entire coding sequences of ORF50-encoding reactivation transactivator Rta and A6-encoding bZIP protein genes. The duplicated region was further located to a position within the terminal repeat (TR) and its deletion resulted in lower ORF50 expression levels and reduced viral fitness. Finally, the presence of a similar but not identical duplication and translocation containing both genes was found in AlHV-1 strain WC11. These results indicate that selection pressure for enhanced viral fitness may drive the duplication of ORF50 and A6 in AlHV-1.Peer reviewe

Para a noção de transformação curricular

Neste artigo é evidenciada a relação entre currículo e conhecimento, abordando-se o conhecimento escolar na sua seleção, organização e transformação, a partir de uma revisão do conceito de transposição didática e da proposição dos conceitos de transformação curricular e transformação didática. Qualquer debate sobre o currículo exige a dilucidação do conhecimento e uma reflexão sobre os seus diversos significados, sobretudo quando a educação se torna num projeto amplo de questionamento da realidade social. Para além de várias questões colocadas acerca do conhecimento escolar e do modo como a sua organização pode ser realizada, procura-se centrar o debate numa reflexão sobre as fronteiras entre conhecimentos e esclarecer que, sobre essa temática, jamais poderão existir respostas fechadas.This article highlights the link between curriculum and knowledge, the approach of school knowledge’s selection, organization and transformation is based on a revision of the concept of didactic transposition and on the proposal of the concepts of curriculum and didactic transformation. Debates on curriculum demand an explanation and a reflection on the multiple meanings of knowledge mainly when education aims to be a broad project to contest social reality. It aims to focus the discussion on a reflection regarding the borders between knowledges and to show that in this subject there are never closed answers.Dans cet article est mis en évidence le rapport entre le curriculum et la connaissance, en abordant la connaissance scolaire dans sa sélection, son organisation et sa transformation à partir d’une révision du concept de transposition didactique et de la proposition des concepts de transformation du curriculum et de transformation didactique. Toute discussion sur le curriculum exige la dilucidation de la connaissance et une réflexion sur ses plusieurs signifiés, surtout quand l’éducation devient un projet plus large de mise en question de la réalité sociale. Au delà des plusieurs questions posées autour de la connaissance scolaire et de la manière comme son organisation peut être réalisée, on cherche á fixer le débat dans une réflexion sur les frontières entre connaissances et éclaircir que, sur cette thématique jamais ne pourront exister des réponses absolues.En este trabajo se pone en evidencia la relación entre el currículum y el conocimiento, abordándose el conocimiento escolar en su selección, organización y transformación desde una revisión del concepto de transposición didáctica y de la proposición de los conceptos de transformación curricular y transformación didáctica. Cualquier discusión sobre el currículum requiere la aclaración del conocimiento y una reflexión sobre sus diversos significados, especialmente cuando la educación se convierte en un proyecto más amplio de cuestionamiento de la realidad social. Además de varias preguntas sobre el conocimiento escolar y el modo en el que su organización puede tener lugar, se intenta centrar el debate en una reflexión sobre las fronteras entre conocimientos y aclarar que en esta temática jamás podrán existir respuestas cerradas.(undefined

Meat, eggs, dairy products, and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Background: A Western diet is associated with breast cancer risk. Objective: We investigated the relation of meat, egg, and dairy product consumption with breast cancer risk by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: Between 1992 and 2003, information on diet was collected from 319,826 women. Disease hazard ratios were estimated with multivariate Cox proportional hazard models. Results: Breast cancer cases (n = 7119) were observed during 8.8 y (median) of follow-up. No consistent association was found between breast cancer risk and the consumption of any of the food groups under study, when analyzed by both categorical and continuous exposure variable models. High processed meat consumption was associated with a modest increase in breast cancer risk in the categorical model (hazard ratio: 1.10; 95% CI: 1.00, 1.20; highest compared with lowest quintile: P for trend = 0.07). Subgroup analyses suggested an association with butter consumption, limited to premenopausal women (hazard ratio: 1.28; 95% CI: 1.06, 1.53; highest compared with lowest quintile: P for trend = 0.21). Between-country heterogeneity was found for red meat (Q statistic = 18.03; P = 0.05) and was significantly explained (P = 0.023) by the proportion of meat cooked at high temperature. Conclusions: We have not consistently identified intakes of meat, eggs, or dairy products as risk factors for breast cancer. Future studies should investigate the possible role of high-temperature cooking in the relation of red meat intake with breast cancer risk. Am J Clin Nutr 2009;90:602-12

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

La psicología histórica de Ignace Meyerson

Ce travail présente la psychologie historique de Ignace Meyerson (1888-1983); c'est une approche qui est restée presque inconnue, y compris dans l'histoire de la psychologie française, où elle a pourtant été conçue et développée. Venu de la médecine et bietôt nommé co-directeur du laboratoire de psychologie physiologique de la Sorbonne (de H. Piéron), Meyerson formule son projet pour une psychologie historique après plus de trente ans de recherches, dans un texte bref mais d'une grande densité théorique: "Les fonctions psychologiques et les oeuvres" (1948). Meyerson y met en question le cadre conceptuel sur lequel la psychologie est assise- héritier de la métaphysique et son dogmatisme de la permanence - et revendique non seulement l'historicité de l'esprit mais son inachèvement essentiel. Dans le but d'éclairicir les abses théoriques et méthodologiques sur lesquelles ce projet est fondé, les rapports qu'il garde avec d'autres approches génétiques et socio-historiques de l'esprit, ainsi que les difficultés qu'il pose et ses possibles apports dans les débats contemporains, nous avons entamé une exploration de ses archives personnelles, où il a conservé toute sa correspondance, les notes de ses cours, de ses conférences et toute la documentation concernant sa thèse. A partir de ces écrits, nous avons suivi la trajectoire intellectuelle de Meyerson depuis ses débuts dans la neuropsychiatrie et la psychophysiologie jusqu'à la formulation du projet pour une psychologie historique et comparée. Ensuite, nous nous concentrons sur ce projet: sur les conditions dans lesquelles il a été rédigé, sur la forme sous laquelle il réunit les nombreux aspects dont il avait traité depuis des années, et sur les réactions qu'il suscite. Enfin, nous parcourons le devenir de Meyerson et de sa psychologie historique, aussi bien sur le plan institutionnel que sur le plan théorique et méthodologique, où à la différence d'une psychologie génétique qui cherche une architecture cognitive, stabilisée au long de la phylogénèse, vise à dévoiler les incessantes transformations auxquelles l'activité psychologique est toujours soumise.This paper introduces the historical psychology of Ignace Meyerson (1888-1983), an approach that has remained marginal, even in the history of French psychology, where it was conceived and developed. Soon after finishing his medical studies Meyerson is named co-director of the laboratory of physiological psychology at the Sorbone.His research work during the next thirty years will bring him to the formulation of his historical psychology. He does that in a brief but extremely dense text, entitled "Les fonctions psychologiques et les oeuvres" (1948). Here he questions the conceptual framework that psychology has been based upon, which he considers to be inherited from metaphysics and its dogmatism of permanence. Meyerson invokes not only the mind's historicity but also the mind's essentiel incompletion. This PhD work attempts to clarify: a) the theoretical and methodological based Meyerson's project has been funded upon, b) its relations with other genetic and socio-historical approaches to the mind, and c) the difficulties it raises and its possible contributions. In order to achieve this, we have analyzed his personal archives, where he has kept all his correspondance, his courses, conferences and documentation related to his thesis. Based on these writings, we have followed Meyerson's intellectual path from his beginnings in the field of psychophysiology and neuropsychiatry until the formulation of this historical psychology's project. Next, we focus on the project itself: on the conditions under which it has been written, the form it was adopted by putting together various issues he had worked on for a long time, and the reactions it provoked. Finally, we follow Meyerson and the latest development of his historical psychology, at the institutional, theoretical and methodological level. Contrary to a genetic psychology which looks for a cognitive architecture, stabilised through the phylogenesis, Meyerson's historical psychology aims at unveiling the incessant transformation psychological activity is always subjected to.BOULOGNE-BU Psych. Henri Pieron (920125201) / SudocSudocFranceF

Indicateurs de santé, mesure de la qualité de vie et évaluation médico-économique

Health indicators, quality of life measures and economic evaluation The objectives of this research are the comparison between health status and quality of life measures, between quantitative measures and the perception of the patients on their quality of life, a discussion of the results in decision making. The data corne from a survey which included elderly persons in a rehabilitation unit after hip fracture and patients in palliative care. The following tools were used: the Karnofsky Index, the EORTC- QLQ30, Euroqol, the STAS. Three measures were realised along a period of 45 days. Interviews were done at the same time to get the patient' s perception on his (her) quality of life. The results show some convergence but also differences according to the indicators and between the quantitative measures and the patient' s perception. The discussion indicates advocate for a plurality and a complementarity of measures, not for a single one.Résumé. L'objectif de ce travail exploratoire est de comparer plusieurs mesures d'état de santé et de qualité de vie sur deux populations, pour analyser leurs convergences et divergences, comparer les résultats des indicateurs quantitatifs avec l'expression libre des patients sur leur qualité de vie, recueillie par entretien, discuter les résultats du point de vue de leurs implications en terme d'aide à la décision. Les populations qui ont servi de support à ce travail sont des personnes âgées en rééducation après fracture du col du fémur et des patients en soins palliatifs en hospitalisation à domicile. Les outils utilisés sont l'Index de Karnofsky, l'EORTC-QLQ30, Euroqol, le STAS. Ils ont été passés à trois reprises dans un intervalle de 45 jours. Aux mêmes moments ont été réalisés des entretiens non-directifs. Les résultats montrent des convergences mais aussi des divergences entre les indicateurs, en niveau comme en variation. Un écart important existe entre le contenu des indicateurs et la perception des malades sur la qualité de vie. La discussion porte sur la nécessité d'un pluralisme de la mesure.Indicadores de salud, medición de la calidad de vida y evaluación médico-económica Este trabajo exploratorio compara varias mediciones de estado de salud y de calidad de vida en dos tipos de población. Su objetivo es analizar sus convergencias y divergencias, comparar los resultados de los indicadores cuantitativos con lo que han expresado libremente los pacientes en las entrevistas sobre su calidad de vida y debatir los resultados desde el punto de vista de las implicaciones que estos pueden tener en términos de ayuda a la décision. La población que sirve de soporte a este trabajo esta compuesta por personas de edad que se encuentran en reeducacion a consecuencia de la fractura del cuello del fémur y por pacientes que estan bajo cuidados médicos paliativos en hospitalización a domicilio. Los instrumentos utilizados très veces en el intervalo de 45 días, al mismo tiempo que se realizaban las entrevistas no-directivas, han sido : el Index de Karnofsky, el EORTC-QLQ30, El Euroqol y el STAS. Los resultados muestran convergencias así como también divergencias entre los indicadores, tanto en nivel como en variación. Existe una diferencia importante entre el contenido de los indicadores y la percepción de los enfermos en cuanto a su calidad de vida. El debate trata sobre la necesidad de un pluralismo de la medición.Frossard Michel, Jasso Mosqueda Guillermo, Suarez Cathy, Couturier Pascal, Guyot Françoise, Franco Alain. Indicateurs de santé, mesure de la qualité de vie et évaluation médico-économique. In: Sciences sociales et santé. Volume 17, n°4, 1999. pp. 45-64