An extended method for evaluating assumptions deviations in quantitative risk assessment and its application to external flooding risk assessment of a nuclear power plant

In quantitative risk assessment, assumptions are typically made, based on best judgement, conservative, or (sometimes) optimistic judgments. Best judgment and optimistic assumptions may result in failing to meet the quantitative safety objectives, whereas conservative assumptions may increase the margins which the objectives are met with but result in cost-ineffective design or operation. In the present paper, we develop an extended framework for the analysis of the criticality of assumptions in risk assessment by evaluating the risk that deviations from the assumptions lead to a reduction of the safety margins. The framework aims to support risk-informed decision making by identifying important assumptions and integrating the assessment of their criticality into the quantitative risk assessment (QRA). The framework is, finally applied within the quantitative risk assessment of a Nuclear Power Plant (NPP) exposed to external flooding. Compared to previous works on the subject, we consider also conservative assumptions and introduce decision flow diagrams to support the classification of the criticality of the assumptions. The framework provides a more comprehensive and transparent evaluation of the assumptions deviation risk through the decision flow diagrams that facilitate the standardization of the evaluation of the assumption deviation effects on the risk assessment.acceptedVersio

A Framework for Multi-Hazards Risk Aggregation Considering Risk Model Maturity Levels

International audienc

A HIERARCHICAL TREE-BASED DECISION MAKING APPROACH FOR ASSESSING THE TRUSTWORTHINESS OF RISK ASSESSMENT MODELS

International audienc

A proposal for a high performance γ\gamma-camera based on liquid Xenon converter and gaseous photomultiplier for PET

présenté par D. Ther

366 Combined exploratory immunophenotyping and transcriptomic tumor analysis in patients treated with OSE2101 vaccine in HLA-A2+ advanced non-small cell lung cancer (NSCLC) from the ATALANTE-1 trial

BackgroundOSE2101 (Tedopi®) is an anticancer vaccine with HLA-A2+ restricted modified epitopes targeting five tumor-associated antigens (TAAs) frequently expressed in lung cancer (CEA, HER2, MAGE2, MAGE3, P53). Step-1 results of the phase III, randomized, open-label ATALANTE-1 study comparing Tedopi® vs standard treatment (SoC) showed a favorable benefit/risk of Tedopi® over SoC (HR 0.71 for overall survival OS) in HLA-A2+ NSCLC patients in 2nd or 3rd line treatment after progression on immune checkpoint blockers (ICB).1 We analyze available tumor biopsies at initial diagnosis from some patients treated with Tedopi® to determine the expression of the 5 TAAs and to identify other tumor factors associated with long-term survival.MethodsTumor biopsies were available for 8 HLA-A2+ (blood test) stage IV NSCLC patients included in the trial. Primary (<12 weeks) and secondary (≥ 12 weeks) resistance to ICB were observed in 3 (38%) and 5 (62%) of patients. Best response to Tedopi® and OS were: 1 partial response (PR) (OS of 33 months), 3 stable disease (SD) (OS of 22, 26 and 41 mo.) and 4 disease progression (PD) (OS of 3, 4, 30 and 31 mo.). HLA-class I, PD-L1, CD8 T-cells, HER2, CEA and P53 tumor expression were evaluated by immunohistochemistry (IHC). NanoString gene expression profiling was performed using the Pan Cancer Immune gene set.ResultsHLA-class I was expressed in all tumor samples. IHC analysis revealed that P53, CEA and HER2 were expressed in 6/7, 5/7 and 0/7 patients, respectively. P53, CEA, HER2, MAGE2, and MAGE3 were detected at RNA level in 5/5 tested patients (table 1). IMMUNOSCORE® IC CD8/PDL1 analysis showed High/High, High/Low and Low/Low scores for 1/7, 1/7 and 5/7 patients, respectively. The High/High IMMUNOSCORE® with a pronounced CD8+ T-cell tumor infiltration was observed in the patient with PR. High percentage of tumor cells expressing P53 (69%–97%) and overexpression of genes associated with activated macrophages (TREM2, MARCO, SLC11A1, CHIT1, SERPINB2) were observed in the PR and SD patients. High IFN-gamma and Expanded Immune Gene Signature scores were observed in long-term survivor patients with secondary resistance to ICB, even after progressive disease.Abstract 366 Table 1Summary of clinical and translational dataCEACarcinoembryonic antigen; HER2: Human Epidermal Growth Factor Receptor-2; ICB: Immune checkpoint blocker; IHC: Immunohistochemistry; ND: Not determined; OS: Overall Survival; Patient ID: Patient identification; PDL1: Programmed death-ligand 1; PFS: Progression-free survival; ssGSEA: Single-sample Gene Set Enrichment Analysis. Blue bars = Length of overall survival; Green bars = Gene Signature upregulation; Red bars = Gene Signature downregulationConclusionsThis study shows that all HLA-A2+ patients (blood test), expressed HLA class I in the tumors at initial diagnosis. Transcriptomic data in the patients that benefited from Tedopi® showed activated macrophage pathway, high IFN-gamma and Expanded Immune Gene Signatures scores. These data will be validated on larger number of patients treated with Tedopi® after the step 2 analysis.AcknowledgementsWe thank Julie Le Boulicaut, François Montestruc and Constant Josse (eXYSTAT, Malakoff, France) for the statistical analysis, and HalioDx for the IHC and NanoString analysis.Trial RegistrationEudraCT number2015-003183-36; NCT number: NCT02654587ReferenceGiaccone, et al. Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (ICI): step 1 results of phase III ATALANTE-1 randomised trial. ESMO meeting 2020, abstract #1260MO.Ethics ApprovalThe study protocol and its related documents (including the patient information and informed consent form) received approval from the Institutional Review Board (IRB), and the Competent Authority prior to study initiation.ConsentEach patient gave his/her written informed consent prior to study enrolment

Brain Struct Funct

Opioid receptors are G protein-coupled receptors (GPCRs) that modulate brain function at all levels of neural integration, including autonomic, sensory, emotional and cognitive processing. Mu (MOR) and delta (DOR) opioid receptors functionally interact in vivo, but whether interactions occur at circuitry, cellular or molecular levels remains unsolved. To challenge the hypothesis of MOR/DOR heteromerization in the brain, we generated redMOR/greenDOR double knock-in mice and report dual receptor mapping throughout the nervous system. Data are organized as an interactive database offering an opioid receptor atlas with concomitant MOR/DOR visualization at subcellular resolution, accessible online. We also provide co-immunoprecipitation-based evidence for receptor heteromerization in these mice. In the forebrain, MOR and DOR are mainly detected in separate neurons, suggesting system-level interactions in high-order processing. In contrast, neuronal co-localization is detected in subcortical networks essential for survival involved in eating and sexual behaviors or perception and response to aversive stimuli. In addition, potential MOR/DOR intracellular interactions within the nociceptive pathway offer novel therapeutic perspectives

Les parcours d'information dans un centre social

Abraham Moles avait promu « une psychologie de la vie quotidienne » et trouvé de grands enseignements dans des petites choses : les attentes de l'autobus, les queues devant un guichet, etc. Influencés plus directement par les travaux d'Eliseo Veron, les auteurs se sont intéressés ici aux comportements des personnes dans un lieu d'accueil et d'informations sociales. Ils ont étudié une centaine de consommateurs dans deux lieux différents. Une observation pleine de leçons pour l'amélioration du service, qui s'inscrit dans une « sémiotique de l'espace » au quotidien.Boullier Dominique, Vasseur Véronique. Les parcours d'information dans un centre social. In: Communication et langages, n°104, 2ème trimestre 1995. pp. 56-71

Estimation of common cause failure parameters with periodic tests

International audienceIn the specific case of safety systems, CCF parameters estimators for standby components depend on the periodic test schemes. Classically, the testing schemes are either staggered (alternation of tests on redundant components) or non-staggered (all components are tested at the same time). In reality, periodic tests schemes performed on safety components are more complex and combine staggered tests, when the plant is in operation, to non-staggered tests during maintenance and refueling outage periods of the installation. Moreover, the CCF parameters estimators described in the US literature are derived in a consistent way with US Technical Specifications constraints that do not apply on the French Nuclear Power Plants for staggered tests on standby components. Given these issues, the evaluation of CCF parameters from the operating feedback data available within EDF implies the development of methodologies that integrate the testing schemes specificities. This paper aims to formally propose a solution for the estimation of CCF parameters given two distinct difficulties respectively related to a mixed testing scheme and to the consistency with EDF’s specific practices inducing systematic non-simultaneity of the observed failures in a staggered testing scheme

Etudes de sensibilité, facteurs d'importance et défaillances de cause commune

International audienceIn this paper, we derive mathematical expressions to assess reliability importance measures for a component in a common cause failure group (CCF). The main originality of this work is that the existing information on the cause of the component unavailability (intrinsic, unknown, CCF-related, maintenance) can be explicitly taken into account in the importance factor computation.Cet article a pour objet de présenter des expressions permettant de calculer les facteurs d’importance fiabilistes d’un composant appartenant à un groupe de défaillance de cause commune (DCC). La possibilité de prendre en compte l’information sur la nature de la défaillance du composant considéré (intrinsèque, origine non identifiée, DCC, maintenance) lors du calcul des facteurs d’importance constitue la principale originalité de l’approche proposé

How to build an adequate set of minimal cut sets for PSA importance measures calculation

International audienceSome models using Boolean algebra like nuclear PSA models are very detailed and, when quantified, result in an enormous amount of Minimal Cut Sets (MCS). The negligible contributions (non-significative MCS) have to be suppressed by a cut off process to respect computing limitations and to have a reasonable quantification time. When an acceptable level of cutoff uncertainty for the baseline risk is obtained with common cutoff thresholds, the final cut set equation is only useable to study small changes in the occurrence probability of basic events. So this set of MCS may be inadequate to estimate importance measures like the Birnbaum indicator or RAW. The truncation process has to be adapted to obtain a baseline risk set of MCS adapted to any importance measure calculation. This paper summaries and comments existing truncation processes. Then we propose a new truncation process that enables us to generate a set of MCS as small as possible and adapted to estimate all importance measures with a good level of accuracy for any elementary event in the mode