A proposed new approach to light rail safety management in Spain and other countries

[Abstract:] The light rail transit (LRT) has experienced considerable growth in Spain since 1994; to date, this has led to the installation of more than 200 km of light rail lines and LRT operations in 11 metropolitan areas. Nevertheless, its institutional and regulatory framework have not been developed accordingly. Thus, in this paper, an approach for managing the LRT safety in Spain is proposed. The approach is based on the French model and could be applied to any other country that is interested in improving its LRT safety management. The paper explains the current situation of LRT safety management in Spain and provides a critical review. A comparison of the situations in several European countries is presented. Moreover, the paper presents details pertaining to the French framework and tool as the most adequate model for managing the LRT safety; a critical review is also included in order to propose ways for improving it. Finally, the main points of the proposed LRT safety management approach include the following: (1) development of a National Light Rail Safety Act, which would create the National Light Rail Safety Body; (2) implementation of a light rail safety database, which is created through the codification of light rail lines in homogenised sections from the safety point of view and the standardised light rail accident/incident reports, to be filled in by light rail operators directly; (3) management of the database by the National Light Rail Safety Body in order to improve safety based on the conclusions obtained

Spike-Threshold Adaptation Predicted by Membrane Potential Dynamics In Vivo

International audienceNeurons encode information in sequences of spikes, which are triggered when their membrane potential crosses a threshold. In vivo, the spiking threshold displays large variability suggesting that threshold dynamics have a profound influence on how the combined input of a neuron is encoded in the spiking. Threshold variability could be explained by adaptation to the membrane potential. However, it could also be the case that most threshold variability reflects noise and processes other than threshold adaptation. Here, we investigated threshold variation in auditory neurons responses recorded in vivo in barn owls. We found that spike threshold is quantitatively predicted by a model in which the threshold adapts, tracking the membrane potential at a short timescale. As a result, in these neurons, slow voltage fluctuations do not contribute to spiking because they are filtered by threshold adaptation. More importantly, these neurons can only respond to input spikes arriving together on a millisecond timescale. These results demonstrate that fast adaptation to the membrane potential captures spike threshold variability in vivo

Éditorial

Ce numéro thématique invite à une réflexion documentée sur le rapport entre les situations d’usage de la parole et leurs contextes sociaux (entendus dans un sens large). Il propose sept études fondées sur des enquêtes tout à la fois ethnographiques et historiques. Si les auteurs sont associés formellement à des disciplines différentes (anthropologie sociale et linguistique, littérature comparée, sociologie), leurs perspectives spécifiques n’en contribuent pas moins à mettre en évidence la dim..

In Vivo Detection of Succinate by Magnetic Resonance Spectroscopy as a Hallmark of SDHx Mutations in Paraganglioma

International audiencePurpose: Germline mutations in genes encoding mitochon-drial succinate dehydrogenase (SDH) are found in patients with paragangliomas, pheochromocytomas, gastrointestinal stromal tumors, and renal cancers. SDH inactivation leads to a massive accumulation of succinate, acting as an oncometabolite and which levels, assessed on surgically resected tissue are a highly specific biomarker of SDHx-mutated tumors. The aim of this study was to address the feasibility of detecting succinate in vivo by magnetic resonance spectroscopy. Experimental Design: A pulsed proton magnetic resonance spectroscopy (1 H-MRS) sequence was developed, optimized, and applied to image nude mice grafted with Sdhb À/À or wild-type chromaffin cells. The method was then applied to patients with paraganglioma carrying (n ¼ 5) or not (n ¼ 4) an SDHx gene mutation. Following surgery, succinate was measured using gas chromatography/mass spectrometry, and SDH protein expression was assessed by immunohistochemistry in resected tumors. Results: A succinate peak was observed at 2.44 ppm by 1 H-MRS in all Sdhb À/À-derived tumors in mice and in all paragangliomas of patients carrying an SDHx gene mutation, but neither in wild-type mouse tumors nor in patients exempt of SDHx mutation. In one patient, 1 H-MRS results led to the identification of an unsus-pected SDHA gene mutation. In another case, it helped define the pathogenicity of a variant of unknown significance in the SDHB gene. Conclusions: Detection of succinate by 1 H-MRS is a highly specific and sensitive hallmark of SDHx mutations. This non-invasive approach is a simple and robust method allowing in vivo detection of the major biomarker of SDHx-mutated tumors. Clin Cancer Res; 22(5); 1120–9. Ó2015 AACR

Mixing performance of viscoelastic fluids in a kenics km in-line static mixer

AbstractThe mixing of ideal viscoelastic (Boger) fluids within a Kenics KM static mixer has been assessed by the analysis of images obtained by Planar Laser Induced Fluorescence (PLIF). The effect of fluid elasticity and fluid superficial velocity has been investigated, with mixing performance quantified using the traditional measure of coefficient of variance CoV alongside the areal method developed by Alberini et al. (2013). As previously reported for non-Newtonian shear thinning fluids, trends in the coefficient of variance follow no set pattern, whilst areal analysis has shown that the >90% mixed fraction (i.e. portion of the flow that is within ±10% of the perfectly mixed concentration) decreases as fluid elasticity increases. Further, the >90% mixed fraction does not collapse onto a single curve with traditional dimensionless parameters such as Reynolds number Re and Weissenberg number Wi, and thus a generalised Reynolds number Reg=Re/(1+2Wi) has been implemented with data showing a good correlation to this parameter

The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis.

The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10-4). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ultimately affecting the SP cleavage site. We tested the effect of the p.Leu16Pro variant on the secretion of IL-22BPi1, IL-22BPi2 and IL-22BPi3 and observed that the Pro16 risk allele significantly lowers secretion levels of each of the isoforms to around 50%-60% in comparison to the Leu16 reference allele. Thus, our study suggests that genetically coded decreased levels of IL-22BP isoforms are associated with augmented risk for MS

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