ARAMIS : an integrated risk assessment methodology for SEVESO plants

International audienceThis paper intends to give a very general description of the ARAMIS Methodology and to show how it answers the needs of various stakeholders concerned by the safety of industrial plants. ARAMIS is divided into six major steps, which will be described shortly in this paper. The potential end users of ARAMIS are mainly the industry, the competent authorities and the local authorities. If all of them have an interest in the same risk management process, their needs are slightly different. Their expectations are detailed and the way ARAMIS brings an answer is explained in this paper

Knowledge management and major industrial hazards : an integrated approach

International audienceThe reflection that followed the Toulouse 2001 accident has stressed the fact that there was an urgent need for a coherent and trustable information about industrial hazards. This is true for the public who needs to be informed about the surrounding risks but it is also, and all the more, true for the industrial operators who have the responsibility to assess the risk and take the necessary provisions to reduce it, the workers who face the risk everyday and the competent authorities, in charge of the control. With this context in mind, INERIS is developing a series of tools for the knowledge management in the context of industrial major hazards. The aim is to make accessible the right information to the right person at the right moment. For this purpose, it is necessary to clearly analyze the needs of the different actors of industrial risks management and then to propose the structure of the system that will support and make the knowledge available. This paper presents the results of this preliminary analysis. It describes the first features of the system developed in the framework of this project, PRIMARSIK , and illustrates how it was built in a fully integrated approach of knowledge management. PRIMARSIK is not only a way to make different models and data available but it is also a way to provide the structure for future capitalization of the knowledge

Participative design of participation structures: a general approach and some risk management case studies

Organising participation of multiple stakeholders is nowadays a widespread request in decision processes, especially for organisations managing environmental risks. Therefore, analysts delivering decision support are expected to provide decision makers with scientifically sound andpractically realisable approaches regarding this issue. One of the main challenges in dealing with participation is the definition of the organisation, the so called participative structure, through which stakeholders will contribute and interact during the decision process. Who should participate when and according to which rules are the main questions to be answered. Stakes associated to this challenge are of extreme importance for decision makers since decision legitimacy and acceptance strongly relies on the ability to demonstrate a real transparency and information disclosure during the whole decision process.This paper proposes the iterative comparison approach as a new and original frame to be used by an analyst supporting a client dealing with such questions. Through an unambiguous definition of cognitive artefacts to be constructed when designing participative structures, this paper providesa clear framework that organises an analyst intervention in participative contexts. Furthermore, it offers the opportunity to design tailored participative structures that integrate context specificities in one hand, and satisfies quality criteria being fairness, competence and efficiency on the other hand

COBRA : Une plate-forme de RàPC basée sur des ontologies

International audienceCet article présente un projet en cours qui a pour objectif de développer une plate-forme de RàPC pour le diagnostic basée sur des ontologies, appelée COBRA. Cette plate-forme est constituée de deux parties principales : les modèles de connaissances décrits par des ontologies, et les processus de raisonnement. Nous travaillons actuellement sur la défaillance des barrières de sécurité installées sur des sites industriels. Cependant, notre objectif est de rendre la plate-forme générique et indépendante du domaine d'application. Nous affirmons que, pour mieux exploiter les avantages des ontologies dans les systèmes de RàPC, il est important de pouvoir utiliser n'importe quel concept dans la description des cas. Ainsi, COBRA permet de définir les attributs de chaque cas dynamiquement au moment de l'exécution, ce qui conduit à une base de cas hétérogène. Dans cet article, nous présentons l'architecture de la plate-forme, les modèles de connaissances, les processus principaux, ainsi que les problèmes rencontrés en travaillant avec des cas hétérogènes

Conductance fluctuations in the presence of spin scattering

Electron transport through disordered systems that include spin scatterers is studied numerically. We consider three kinds of magnetic impurities: the Ising, the XY and the Heisenberg. By extending the transfer matrix method to include the spin degree of freedom, the two terminal conductance is calculated. The variance of conductance is halved as the number of spin components of the magnetic impurities increases. Application of the Zeeman field in the lead causes a further halving of the variance under certain conditions.Comment: to be published in Phys. Rev.

<i>RPA3-UMAD1</i> rs12702634 and rheumatoid arthritis-associated interstitial lung disease in European ancestry

Objective Recently, a genome-wide association study identified an association between RA-associated interstitial lung disease (ILD) and RPA3-UMAD1 rs12702634 in the Japanese population, especially for patients with a usual interstitial pneumonia (UIP) pattern. We aimed to replicate this association in a European population and test for interaction with MUC5B rs35705950.Methods In this genetic case-control association study, patients with RA and ILD and controls with RA and no ILD were included from France, the USA and the Netherlands. Only cases and controls from European genetic ancestries determined by principal components analysis were included in the analyses. RA was defined by the 1987 ACR or 2010 ACR/EULAR criteria and ILD by chest high-resolution CT scan, except in the control dataset from the Netherlands, where the absence of ILD was determined by chart review. Patients were genotyped for RPA3-UMAD1 rs12702634 and MUC5B rs35705950. Associations were tested using logistic regression adjusted for sex, age at RA onset, age at ILD onset or at certified absence of ILD, tobacco smoking status and country of origin.Results Among the 883 patients included, 322 were RA-ILD cases (36.5%). MUC5B rs35705950 was strongly associated with RA-ILD in all datasets {combined adjusted odds ratio [OR] 2.9 [95% CI 2.1, 3.9], P = 1.1 x 10-11. No association between RPA3-UMAD1 rs12702634 and RA-ILD was observed [combined OR 1.2 (95% CI 0.8, 1.6), P = 0.31. No interaction was found between RPA3-UMAD1 rs12702634 and MUC5B rs35705950 (P = 0.70).Conclusion Our findings did not support a contribution of RPA3-UMAD1 rs12702634 to the overall RA-ILD susceptibility in the European population.What does this mean for patients?Interstitial lung disease (ILD) can develop in 10-60% of patients with rheumatoid arthritis (RA) and is associated with an increased risk of death. We do not yet fully understand why RA-ILD occurs, but risk factors include genetics and environmental factors such as tobacco smoking. Identifying new genetic risk factors for RA-ILD may improve our understanding of how this disease occurs, help us categorize patients in terms of their risk level and help us to potentially identify new drug targets. A previous Japanese genetic study identified the RPA3-UMAD1 rs12702634 common genetic variant as a risk factor for RA-ILD. However, a second Japanese study failed to replicate these findings. In this international study including patients with European ancestry, we did not find that RPA3-UMAD1 rs12702634 contributed to the overall risk of RA-ILD. Our findings highlight the importance of conducting analyses that try to replicate the results of a study. We also emphasize that genetic associations-even those already reported-require rigorous testing in different groups of people before we can conclude that they contribute to disease risk. Ongoing collaboration and multi-ancestry genetic studies are essential in order to advance our understanding of the complex genetics underlying RA-ILD

Incentivizing the Dynamic Workforce: Learning Contracts in the Gig-Economy

In principal-agent models, a principal offers a contract to an agent to perform a certain task. The agent exerts a level of effort that maximizes her utility. The principal is oblivious to the agent's chosen level of effort, and conditions her wage only on possible outcomes. In this work, we consider a model in which the principal is unaware of the agent's utility and action space. She sequentially offers contracts to identical agents, and observes the resulting outcomes. We present an algorithm for learning the optimal contract under mild assumptions. We bound the number of samples needed for the principal obtain a contract that is within $\epsilon$ of her optimal net profit for every $\epsilon>0$

RPA3-UMAD1 rs12702634 and rheumatoid arthritis–associated interstitial lung disease in European ancestry

Objective: Recently, a genome-wide association study identified an association between RA-associated interstitial lung disease (ILD) and RPA3-UMAD1 rs12702634 in the Japanese population, especially for patients with a usual interstitial pneumonia (UIP) pattern. We aimed to replicate this association in a European population and test for interaction with MUC5B rs35705950. Methods: In this genetic case–control association study, patients with RA and ILD and controls with RA and no ILD were included from France, the USA and the Netherlands. Only cases and controls from European genetic ancestries determined by principal components analysis were included in the analyses. RA was defined by the 1987 ACR or 2010 ACR/EULAR criteria and ILD by chest high-resolution CT scan, except in the control dataset from the Netherlands, where the absence of ILD was determined by chart review. Patients were genotyped for RPA3-UMAD1 rs12702634 and MUC5B rs35705950. Associations were tested using logistic regression adjusted for sex, age at RA onset, age at ILD onset or at certified absence of ILD, tobacco smoking status and country of origin. Results: Among the 883 patients included, 322 were RA-ILD cases (36.5%). MUC5B rs35705950 was strongly associated with RA-ILD in all datasets fcombined adjusted odds ratio [OR] 2.9 [95% CI 2.1, 3.9], P¼ 1.1 × 10−11. No association between RPA3-UMAD1 rs12702634 and RA-ILD was observed [combined OR 1.2 (95% CI 0.8, 1.6), P¼ 0.31. No interaction was found between RPA3-UMAD1 rs12702634 and MUC5B rs35705950 (P¼ 0.70). Conclusion: Our findings did not support a contribution of RPA3-UMAD1 rs12702634 to the overall RA-ILD susceptibility in the European population

Structural basis for both pro- and anti-inflammatory response induced by mannose-specific legume lectin from Cymbosema roseum

Legume lectins, despite high sequence homology, express diverse biological activities that vary in potency and efficacy. In studies reported here, the mannose-specific lectin from Cymbosema roseum (CRLI), which binds N-glycoproteins, shows both pro-inflammatory effects when administered by local injection and anti-inflammatory effects when by systemic injection. Protein sequencing was obtained by Tandem Mass Spectrometry and the crystal structure was solved by X-ray crystallography using a Synchrotron radiation source. Molecular replacement and refinement were performed using CCP4 and the carbohydrate binding properties were described by affinity assays and computational docking. Biological assays were performed in order to evaluate the lectin edematogenic activity. The crystal structure of CRLI was established to a 1.8 Å resolution in order to determine a structural basis for these differing activities. The structure of CRLI is closely homologous to those of other legume lectins at the monomer level and assembles into tetramers as do many of its homologues. The CRLI carbohydrate binding site was predicted by docking with a specific inhibitory trisaccharide. CRLI possesses a hydrophobic pocket for the binding of α-aminobutyric acid and that pocket is occupied in this structure as are the binding sites for calcium and manganese cations characteristic of legume lectins. CRLI route-dependent effects for acute inflammation are related to its carbohydrate binding domain (due to inhibition caused by the presence of α-methyl-mannoside), and are based on comparative analysis with ConA crystal structure. This may be due to carbohydrate binding site design, which differs at Tyr12 and Glu205 position. © 2011 Elsevier Masson SAS. All rights reserved

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population