Comparison of CD63 Upregulation Induced by NSAIDs on Basophils and Monocytes in Patients with NSAID Hypersensitivity

Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial. Objectives. In patients with a history of nonallergic NSAID hypersensitivity, stratified according to the severity of the symptoms, to assess with NSAIDs the predictive value of basophil (BAT) and monocyte (MAT) activation tests. Patients/Methods. Sixty patients who had NSAIDs-induced or exacerbated urticaria/angiooedema and 20 controls was included. After incubation with NSAIDs or acetaminophen, leukocytes were analysed for CD63 upregulation. Results. With aspirin, the sensitivity (37%) and specificity (90%) of BAT agree with already published results. In contrast, when patients had had cutaneous and visceral reactions, the frequency of positive BAT 14/22 (64%, P < 0.001) or MAT 10/22 (46%, P < 0.01) were increased. Conclusions. Positive tests were more frequent among patients having a severe hypersensitivity contrasting with the other patients who had results similar to controls

The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver

PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal 3-keto-acyl-CoA thiolase B (Thb) is under the dependence of these two transcription factors. Transactivation and gel shift experiments identified a novel PPAR response element within intron 3 of the Thb gene, by which PPARα but not HNF4α transactivates. Intriguingly, we found that HNF4α enhanced PPARα/RXRα transactivation from TB PPRE3 in a DNA-binding independent manner. Coimmunoprecipitation assays supported the hypothesis that HNF4α was physically interacting with RXRα. RT-PCR performed with RNA from liver-specific HNF4α-null mice confirmed the involvement of HNF4α in the PPARα-regulated induction of Thb by Wy14,643. Overall, we conclude that HNF4α enhances the PPARα-mediated activation of Thb gene expression in part through interaction with the obligate PPARα partner, RXRα

Comparing post-event and pre-event damage assessment: Information gaps and lessons learnt

Abstract. Post event damage and needs assessment can supply fundamental information to feed risk models, i.e. data to define, calibrate and validate risk models. The lack or low quality of information regarding damage and losses collected in the aftermath of events conditions the quality of pre-event scenarios, thus affecting also the significance and the relevance of cost benefit analyses on mitigation measures to reduce the severity and magnitude of damage that are expected. Data collected in the aftermath of disasters are usually not suitable to this aim. Mostly, data on damage explicative variables (i.e. hazard, exposure, vulnerability and mitigation actions) are missing; damage data themselves can be also unsuitable as they refer to different spatial or temporal scales than those at which damage models work. In such a context, this paper presents results from the European Project IDEA (Improving Damage assessments to Enhance cost-benefit Analyses). The project is a response to the very limited reliability of data currently used to support cost-benefit analyses for natural hazards mitigation. The main objective of IDEA is an improvement of both damage data quality and procedures to collect and manage them. The paper focus in detail on the investigation of how improved damage data can better support the risk-modelling process. To this aim, the flood hitting the Umbria Region (Italy) in 2012 and the earthquake event that stuck the municipality of Lorca (Spain) in 2011 were investigated. Observed damages and damage predictions based on data that were available before the disaster have been compared. The comparison had several objectives: - to verify the reliability of damage models that are currently used for damage estimation and that are proposed in literature; - to identify data gaps in pre-event assessment that could be narrowed by better damage data. This is relevant for showing what data are currently missing in risk modelling but could be obtained at reasonable costs; - to identify sectors for which pre-event damage assessment cannot be carried out or is carried out at the expense of large uncertainties and/or roughness; - to show how improved risk modelling could better feed cost benefit analyses of pre-event mitigation measure

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I2 measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I2 measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI≥32.5, 35.0, 37.5, 40.0 kg/m2 versus BMI<25 kg/m2) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I2 measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I2 measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI≥32.5, 35.0, 37.5, 40.0 kg/m2 versus BMI<25 kg/m2) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

Cathodoluminescence : an imaging technique for the search of extraterrestrial life

International audienceSolids irradiated by a 10-20 keV electron beam emit ligth in the UV-visible range, which is called cathodoluminescence (CL). CL imagery is a powerful tool for visualizing minerals and their internal structures (lattice defects, zoning). For example, terrestrial calcite, either of sedimentary or biogenic origin, often display a bright orange CL, as a result of the incorporation of trace Mn2+ in its lattice. Aragonite can also be discriminated from calcite by its green CL. Carbonates are a major target for the search of life on Mars, and CL imagery could contribute to reveal carbonates in situ. Thomas et al. [1] have validated the concept of an electron lamp to make CL imagery of a rock surface placed in a martian CO2 atmosphere. We present 2 examples of terrestrial bacterial microstructures that are revealed by CL. (1) In Sinemurian sediments from the Montmiral borehole (Valence Basin, France), banded wavy calcite in contact with pyrite represents fossilized biofilms of sulfato-reducing bacteria, as confirmed by the sulfur isotopic composition of pyrite ~+36 %0 PDB. (2) At l'Ile Crémieux, north of the Valence basin, a dense filamentous microbial/fungal community with a bright orange CL signature is embedded in vuggy calcite from a tectonic vein. The mat is anchored 1-2 mm deep in the oolitic veinwall and emerges at right angle in the 'open' fracture space. Finally, carbonate vesicles and exhalite crusts from the Svalbard basalt in Groendland, with orange CL, are shown as analogues to carbonates from the martian ALH84001 igneous meteorite. [1]Thomas et al. (2009) in A. Gucsik (Ed.) "Cathodoluminescence and Its Application in the Planetary Sciences