Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy

Contains fulltext : 97006.pdf (publisher's version ) (Open Access)The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc

Le bien, la vie, la mort: art et art politique d’après le Gorgias de Platon

National audienceTaking Gorgias, a transitional dialogue, as a starting point, this paper highlights the fact that when knowledge of the good is placed by Plato at the heart of any real techne and politics is considered eminently a techne, this high level of requirement may result in a certain disregard for human lifeDescription de la conception platonicienne de la politique comme art principalement à partir du Gorgias, en vue de mettre en évidence comment la référence au bien, centrale dans la notion platonicienne d’art et a fortiori dans la notion platonicienne d’art politique, a pour contrepartie un certain mépris pour la vie

A study of pre- and post-recovery cores from Aberfeldy thermal recovery pilots, Lloydminster area, Saskatchewan

Bibliography: p. 158-167

Aristote : Rationalités

International audienceLes contributions réunies dans le présent recueil ont, pour la plupart, fait l’objet de communications à l’occasion de deux Journées d’étude organisées l’une à l’Université de Rouen Haute-Normandie par l’ « Équipe de recherche sur les aires culturelles » (ERIAC), l’autre à l’Université de Rennes I par « Philosophie des normes », respectivement les 23 et 25 janvier 2008.Leur ensemble ne donne pas une cartographie complète, même dans les grandes lignes, de la conception aristotélicienne de la rationalité sous ses divers visages : la pratique scientifique d’Aristote et sa conception de la physique, par exemple, ne sont pas considérées ici, pas plus que la contribution décisive du Stagirite à l’histoire de la philosophie première, ontologie ou théologie. La forme achevée du recueil reflète l’esprit dans lequel ont été envisagées les deux Journées dans le prolongement desquelles il s’inscrit et lors desquelles ont été privilégiés les aspects publics et éthiques de la rationalité telle qu’a pu la concevoir celui qui, comme auteur dudit Organon et héritier de la dialectique socratique et platonicienne, est tout d’abord le fondateur de ce que nous appelons « logique », dont il envisage aussi, dans les Seconds analytiques, les prolongements scientifiques (didactiques et démonstratifs).L’ouvrage, qui traite à plusieurs reprises de l’influence d’Aristote, comporte ainsi trois sections : « De la dialectique à la science », « Art oratoire et poésie », « La rationalité éthique ».Ont été réunies, dans la première section, des contributions de Jean-Baptiste Gourinat (« Dialogue et dialectique : la place de la dialectique dans l’organon d’Aristote »), Pierre Joray (« Principe de contradiction et ecthèse dans la syllogistique d’Aristote »), Franck Varenne (« Le rapport entre science et logique chez Aristote vu à travers la critique de Dewey ») ; d’Annie Hourcade (« Le conseil dans la Rhétorique d’Aristote »), Jean-Pierre Cléro (« La Rhétorique d’Aristote et les penseurs des passions du xviiie siècle »), Michele Corradi (« Aristote et la réflexion de Protagoras sur les noms »), Maddalena Vallozza (« Entre poésie et histoire. Aristote, Poétique 1451 a 36-b 11, et l’Évagoras d’Isocrate ») dans la seconde ; dans la troisième, de David Lefebvre (« Avoir un èthos et être philotoioutos. Sur le sens de la notion d’èthos dans les Éthiques d’Aristote »), Michel Narcy (« La phronèsis entre Platon et Aristote »), René Lefebvre (« Syllogisme de l’action et délibération : deux formes de l’alternative pratique chez Aristote ») Marco Zingano (« Décisions morales et interdictions absolues chez Aristote »)