New susceptibility Loci associated with kidney disease in type 1 diabetes

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P?=?1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P?=?2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-ß1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P?=?2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Composer in Interview: Pierre Boulez

Interview with composer Pierre Boulez

Le Comte de Monte Cristo: da literatura ao cinema

A presente dissertação discute o diálogo estabelecido entre literatura e cinema no tratamento da personagem principal – um homem traído que se vinga de forma cruel dos seus inimigos – na obra literária Le Comte de Monte-Cristo, de Alexandre Dumas, e nas três adaptações fílmicas escolhidas: Le Comte de Monte-Cristo de Robert Vernay (1943); The count of Monte Cristo de David Greene (1975) e The count of Monte Cristo de Kevin Reynolds (2002). O projecto centra-se na análise da personagem Edmond Dantès/Monte-Cristo na obra literária e na sua transposição para a obra fílmica, nos graus de adaptação e contaminação entre os diferentes textos em momentos temporais diferentes. Para isso, foram estudadas em pormenor cada uma das obras referidas, tendo sempre em vista o percurso do herói. A adaptação cinematográfica de uma obra literária é uma operação de criação de um novo texto com dinamismo e autonomia próprios, resultante de escolhas nem sempre fáceis de realizar. A grande extensão da obra literária dificultou essa tarefa, no entanto, os realizadores procuraram constituir um fluir de personagens e de situações enquadráveis num tempo ideal de visualização confortável. Todas as narrativas combinam romance e desilusão, acção e aventura, mas os temas da vingança e da traição são explorados numa perspectiva diferente. As conclusões apuradas constatam que, independentemente da época, a personagem descrita nos filmes manteve-se fiel à caracterização feita pelo seu criador Alexandre Dumas, apesar de algumas nuances necessárias para criar um objecto que garantisse reconhecimento da crítica mas, também, o sucesso comercial.

Changing patterns of first injection across key periods of the French Harm Reduction Policy: PrimInject, a cross sectional analysis

Background: Monitoring of emerging modes of drug consumption in France has identified new patterns of injection among youths with diverse social backgrounds, which may explain the persistence of high rates of hepatitis C virus infection. The circumstances surrounding the first injection have been poorly documented in the group of heavy drug users and in the context of the French opioid substitution treatment (OST) policy that provides expanded access to high-dosage buprenorphine (BHD). Methods: An Internet survey (Priminject) was conducted from October 2010 to March 2011 with French drug users. Four time periods were compared based on critical dates throughout the implementation of the Harm Reduction Policy in France. Results: Compared with drug users who injected for the first time prior to 1995, the aspects of drug use for users who recently injected for the first time were as follows: (1) experimentation with miscellaneous drugs before the first injection; (2) an older age at the time of first injection; (3) heroin as the drug of choice for an individual’s first injection, notwithstanding the increased usage of stimulant drugs; (4) BHD did not appear to be a pathway to injection; and (5) an increased number of users who injected their first time alone, without the help or presence of another individual. Conclusion: The PrimInject study showed that there is a group of injection drug users that is larger than the group of injection drug users observed in previous studies; therefore, it is necessary to diversify programs to reach the entire spectrum of high-risk users.

Letter, to Oliver Hawes Spencer, Cheraw, SC, 1824 March 25

This letter is from Henry D. to O. H. Spencer.

Évaluation du potentiel de croissance et de rendement d’une culture de tomates biologiques cultivées dans une serre climatisée à l’aide d’un système géothermique

Ce projet visait à comparer les effets agronomiques d’une serre de tomates biologiques semi-fermée utilisant un système de climatisation par géothermie comparativement à une serre ouverte. Deux serres de 228 et 230 m2 ont été équipées d’un système d’échangeur d’air avec géothermie qui refroidissait et déshumidifiait l’air (serre semi-fermée) et d’un système de ventilation naturelle (serre témoin). Ces dernières ont été comparées au cours des années 2012 et 2013 entre lesquels les traitements ont été permutés. Les variables mesurées étaient les paramètres de croissance des plants ainsi que le rendement, le calibre des fruits et les propriétés physico-chimiques des tomates. Les résultats ont démontré que le système de climatisation n’a pas eu d’effets significatifs sur la croissance des plants, la qualité des fruits ainsi que le rendement. Les deux serres avaient des cibles de concentration en CO2 comprises entre 450 µL L-1 et 1000 µL L-1 selon l’ensoleillement. Les quantités de CO2 injectées ont été de 11 kg/m2 et 15 kg/m2 respectivement en 2012 et 2013 dans la serre semi-fermée alors qu’elles ont été de 24 kg/m2 et 25 kg/m2 dans la serre témoin. Bien qu’ayant nécessité moins d’injection, la serre semi-fermée a permis de conserver des concentrations en CO2 de 638 µL L-1 en 2012 et de 593 µL L-1 en 2013. Ces concentrations sont plus élevées que celles obtenues dans la serre témoin qui étaient respectivement de 385 µL L-1 et 486 µL L-1 en 2012 et 2013. De ce fait, le coût monétaire associé à l’enrichissement carboné a été de 1,6 à 2,0 fois plus élevé dans la serre témoin que dans la serre semi-fermée.