Formats techniques, formats communautaires, formats d’engagement : le cas d’une communauté diasporique

A l'image des communautés virtuelles traitées par Howard Rheingold, la plupart des travaux sur cette thématique partent de l'offre technique pour analyser la communauté qui se développe autour de (sur, dans, avec, grâce à) cette infrastructure (l'incertitude sur la préposition qui va qualifier la relation est significative). A partir de cette approche, on débouche aisément sur une adéquation peu interrogée entre offre technique et communauté sans possibilité de comparer les différentes communautés entre elles. Il est en effet impossible à partir de ce point de départ de penser la diversité des supports techniques qui peuvent concourir à faire tenir la communauté en question et à redéfinir ses frontières pertinentes (...)

Climate Variability in Europe and Africa: a PAGES-PEP III Time Stream II Synthesis

The PEP III Europe-Africa transect extends from the arctic fringes of NW Eurasia to South Africa. It encompasses the presently temperate sector of mid-latitude Europe, the Mediterranean region, the arid and semi-arid lands of the Sahara, Sahel and the Arabian Peninsula, and the inter-tropical belt of Africa. The palaeoenvironmental evidence available from these regions, which has been summarised in earlier chapters of this volume and which collectively spans the last 250,000 years, clearly bears the stamp of long-term global climate forcing induced by variations in solar insolation. External forcing is ultimately the reason why the Eurasian continental ice sheets waxed and waned repeatedly during the late Quaternary, and why the southerly limit of permafrost migrated southwards across mid-latitude Europe, periodically becoming degraded during warmer episodes. At the same time, pronounced fluctuations in atmospheric and soil moisture have affected the Mediterranean, desert and Sahel regions, while there is abundant evidence from every sector of the PEP III transect for marked migrations of the principal vegetation belts, as well as for other major environmental changes, that are also considered to reflect long-term climate forcing. It is only in the last decade or so, however, that the full complexity of the history of climate changes during the last interglacial-glacial cycle, and their environmental impacts in continental Europe and Africa, have begun to be recognised. The discovery of evidence for the abrupt Dansgaard-Oeschger (D-O) and Heinrich (H) climatic oscillations in Greenland ice-core (Johnsen et al. 1992) and North Atlantic (Bond et al. 1993) records, have prompted a re-examination of the continental record. This, together with a number of technical improvements in field and laboratory equipment, greater access to sites in remote and difficult terrain, diversification in the range of available palaeoecological and geochronological tools, and closer inter-disciplinary collaboration, have led to a more penetrating examination of the field evidence, which has progressed the science considerably. We can now see that the stratigraphical record is much more complex than appreciated hitherto, and more detailed and refined models of past climatic and environmental models are beginning to emerge. There is, for example, a growing body of evidence which suggests that D-O and H events had significant impacts on the environment of Europe and Africa, as well as on the Mediterranean Sea

The safety of agomelatine in standard medical practice in depressed patients : a 26‐week international multicentre cohort study

© 2020 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Objective: The present observational cohort study documented the safety of agomelatine in current medical practice in out-patients suffering from major depressive disorder. Method: The 6-month evolution of agomelatine-treated patients was assessed with a focus on safety (emergent adverse events, liver acceptability), severity of depression using the Clinical Global Impression Severity (CGI-S) score, and functioning measured by the Sheehan Disability Scale (SDS). Results: A total of 8453 depressed patients from 761 centres in 6 countries were analysed (female: 67.7%; mean age: 49.1 ± 14.8 years). Adverse events reported were in accordance with the known safety profile of agomelatine. Cutaneous events were reported in 1.7% of the patients and increased hepatic transaminases values were reported in 0.9 % of the patients. The incidence of events related to suicide/self-injury was 1.0%. Two completed suicides, not related to the study drug, were reported. CGI-S total scores and SDS sub-scores improved and numbers of days lost or underproductive decreased over the treatment period. Conclusions: In standard medical practice, agomelatine treatment was associated with a low incidence of side effects. No unexpected events were reported. A decrease in the severity of the depressive episode and improved functioning were observed.info:eu-repo/semantics/publishedVersio

Earlier seasonal onset of intense Mesoscale Convective Systems in the Congo Basin since 1999

Mesoscale Convective Systems (MCSs) produce some of the most intense rainfall on the planet, and their response to climate variability and change is rather uncertain. Under global warming, increased water vapour is expected to intensify the most extreme rain events and enhance flood frequency. However, MCS dynamics are also sensitive to other atmospheric variables, most notably, wind shear. Here we build on a recent study showing strong MCS intensification in the African Sahel, and examine evidence of similar trends elsewhere in tropical Africa. Using satellite data, we find a remarkable increase post‐1999 in intense MCS frequency over the Congo Basin during the month of February. This earlier onset of the spring rainy season has been accompanied by strong increases in the February meridional temperature gradient and associated wind shear. This supports the hypothesis that contrasts in warming across the continent can drive important decadal‐scale trends in storm intensity

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation

End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive antiviral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to reinfect the liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants reinfecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pretransplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft

Ki-67 as a prognostic marker in mantle cell lymphoma—consensus guidelines of the pathology panel of the European MCL Network

Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 × 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value has been shown to predict survival in prospective randomized trials of the European MCL Network. Estimation by eyeballing and digital image analysis showed a poor concordance with the gold standard (concordance correlation coefficients [CCC] between 0.29 and 0.61 for eyeballing and CCC of 0.24 and 0.37 for two methods of digital image analysis, respectively). Counting a reduced number of lymphoma cells (2 × 100 cells) showed high interobserver agreement (CCC = 0.74). Pitfalls of the Ki-67 index are discussed and guidelines and recommendations for assessing the Ki-67 index in MCL are given

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe