Démonstrateurs pour l'analyse d'alternatives socio-techniques

At a time when politicians increasingly call on experts to decide on social issues, the French democratic crisis reflects in the citizens’ mistrust of scientists. In a context of absolute environmental emergency, several planetary boundaries already being overstepped by the Western world, it seems necessary to rebuild confidence between the people, scientists and politicians.To rethink our consumption and production patterns and to design desirable alternatives to our current way of life, the society as a whole must take part in the profound societal decisions that await us.With this in mind, scientific research develops new tools capable of modelling socio-technical organizations, thanks to which vulnerabilities of these systems are highlighted. The aim of this internship is to work on translating these phenomena and risks from a scientific language to a form accessible to all. This internship investigates a possible method, which combines three dimensions: playfulness, materiality and minimality.To do so, this report studies how knowledge transfer is explored in the practice of stakeholder participation. Serious games are studied as a relevant form to answer this need of transposition. Concept of lucidity and the way in which the ideas are represented in board games are used.This work leads to the design of two demonstrators based on the scientific work of STEEP’s team located in INRIA, Grenoble Rhônes-Alpes. The methodology of the creation process, the content of the game as well as the follow-up and evaluation of these demonstrators are presented.Alors que les politiques font de plus en plus appel aux experts pour trancher des questions de société, la crise démocratique que traverse la France se traduit aujourd’hui par une méfiance des citoyens à l’égard des scientifiques. Dans un contexte d’urgence environnementale absolue, où plusieurs limites planétaires ont déjà été franchies par la société occidentale moderne, il est fondamental de retisser le lien entre citoyens, scientifiques et politiques.L’ensemble de la société doit en effet participer aux décisions sociétales profondes qui nous attendent : repenser nos modes de production et de consommation et imaginer des alternatives désirables au fonctionnement actuel de la société occidentale.Dans cette perspective, la recherche scientifique se mobilise pour développer des outils à même de modéliser des organisations socio-techniques, grâce auxquels des vulnérabilités de ces systèmes sont mises en évidence. L’objectif de ce stage est d’œuvrer à traduire ces phénomènes et risques d’un langage scientifique vers une forme accessible à tous. Ce stage investigue une méthode possible, qui combine trois dimensions : la ludicité, le caractère haptique et la minimalité.Pour cela, ce rapport s’intéresse à des courants de pratique de la participation, pour situer le questionnement de la passation des savoirs. Le jeu sérieux est étudié comme une forme pertinente pour répondre à ce besoin de transposition. Le concept de ludicité et les représentations dans des jeux de société de plusieurs notions sont mis à profit.Ce travail aboutit à la conception de deux démonstrateurs, qui s’appuient sur les travaux scientifiques de l’équipe STEEP de l’INRIA Grenoble Rhône-Alpes. La méthodologie du processus de création, le contenu des dispositifs ludiques, ainsi que le suivi et évaluation de ces démonstrateurs sont présentés

The role of nominating committees and director reputation in shaping the labor market for directors: an empirical assessment

Research Question/Issue: Do the presence and independence of nominating committees within boards of directors affect the extent of rewards and sanctions provided by the labor market to directors with a reputation for being active in monitoring management? Research Findings/Insights: Results drawn from a longitudinal sample of directors sitting on the board of 200 public French firms suggest that the stronger a director's reputation for being active in increasing control over management, the larger the number of his/her subsequent appointments to (1) boards with a nominating committee, (2) to boards with a nominating committee which excludes the CEO and (3) to boards with a nominating committee dominated by non-executive directors. In contrast, we found that a director's reputation of being active in increasing control over management does not impact the number of his/her subsequent appointments (1) to boards without a nominating committee, (2) to boards with a nominating committee which includes the CEO and (3) to boards with a nominating committee dominated by executive directors. Theoretical/Academic Implications: This study shows that the outcome of the power struggle between the CEO and incumbent directors during the candidate selection process determines the profile of directors who will ultimately obtain the board appointment. On the one hand, independent nominating committees are likely to reduce the influence of CEOs over the process of a director's appointment, and therefore are likely to increase the recruitment of directors with reputations for being active in exercising control over managers. On the other hand, nonexistence of nominating committees or presence of weak nominating committees under the influence of the CEO decouple directors' reputations for being active in controlling management from the likelihood of obtaining new appointments. Practitioner/Policy Implications: This study offers insights to policy makers interested in increasing the efficiency of the labor market for directors. More specifically, it highlights the conditions under which directors with a reputation of being active in increasing control over management are likely to be rewarded by the labor market for directors. These conditions include (1) the creation of a nominating committee; (2) exclusion of the CEO from this committee and (3) domination of this committee by outside directors

Fluropyrimidine single agent or doublet chemotherapy as second line treatment in advanced biliary tract cancer

Fluoropyrimidine (FP) plus platinum chemotherapy has been recently established as a second-line (L2) preferred option in advanced biliary tract cancer (aBTC) (ABC-06 phase III trial). However, the overall survival (OS) benefit was limited and comparison with FP monotherapy was not available. Our aim was to assess the OS of patients treated with a FP monotherapy compared to a doublet with irinotecan or platinum in L2. We performed a retrospective analysis of two large multicenter prospective cohorts: a French cohort (28 centers) and an Italian cohort (9 centers). All consecutive patients with aBTC receiving FP-based L2 after gemcitabine plus cisplatin/gemcitabine plus oxaliplatin L1 between 2003 and 2016 were included. A subgroup analysis according to performance status (PS) and an exploratory analysis according to platinum sensitivity in L1 were planned. In the French cohort (n = 351), no significant OS difference was observed between the FP monotherapy and doublet groups (median OS: 5.6 vs 6.8 months, P =.65). Stratification on Eastern Cooperative Oncology Group (ECOG) PS showed similar results in PS 0-1 and 2. Median OS was not different between FP monotherapy, platinum- and irinotecan-based doublets (5.6 vs 7.1 vs 6.7 months, P =.68). Similar findings were observed in the Italian cohort (n = 174) and in the sensitivity analysis in pooled cohorts (n = 525). No L2 regimen seemed superior over others in the platinum resistant/refractory or sensitive subgroups. Our results suggest that FP monotherapy is as active as FP doublets in aBTC in L2, regardless of the patient PS and country, and could be a therapeutic option in this setting

prediction of overall survival with 2nd line l2os chemotherapy ct in patients with advanced biliary tract cancer abtc ageo ct2bil cohort update and international multicenter external validations

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The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age

PurposeCancer patients are at risk of severe COVID-19 infection, and vaccination is recommended. Nevertheless, we observe a failure of COVID-19 vaccines in this vulnerable population. We hypothesize that senescent peripheral T-cells alter COVID-19 vaccine-induced immunity.MethodsWe performed a monocentric prospective study and enrolled cancer patients and healthy donors before the COVID-19 vaccination. The primary objective was to assess the association of peripheral senescent T-cells (CD28-CD57+KLRG1+) with COVID-19 vaccine-induced immunity.ResultsEighty cancer patients have been included, with serological and specific T-cell responses evaluated before and at 3 months post-vaccination. Age ≥ 70 years was the principal clinical factor negatively influencing the serological (p=0.035) and specific SARS-CoV-2 T-cell responses (p=0.047). The presence of senescent T-cells was correlated to lower serological (p=0.049) and specific T-cell responses (p=0.009). Our results sustained the definition of a specific cut-off for senescence immune phenotype (SIP) (≥ 5% of CD4 and ≥ 39.5% of CD8 T-cells), which was correlated to a lower serological response induced by COVID-19 vaccination for CD4 and CD8 SIPhigh (p=0.039 and p=0.049 respectively). While CD4 SIP level had no impact on COVID-19 vaccine efficacy in elderly patients, our results unraveled a possible predictive role for CD4 SIPhigh T-cell levels in younger cancer patients.ConclusionsElderly cancer patients have a poor serological response to vaccination; specific strategies are needed in this population. Also, the presence of a CD4 SIPhigh affects the serological response in younger patients and seems to be a potential biomarker of no vaccinal response

Prognostic role of HPV integration status and molecular profile in advanced anal carcinoma: An ancillary study to the epitopes-HPV02 trial.

peer reviewedSquamous Cell Carcinoma of the Anal canal (SCCA) is a rare disease associated with a Human Papillomavirus (HPV) infection in most cases, predominantly the HPV16 genotype. About 15% of SCCA are diagnosed in metastatic stage and some will relapse after initial chemoradiotherapy (CRT). Treatment of patients by Docetaxel, Cisplatin and 5-fluorouracil (DCF) has been recently shown to improve their complete remission and progression-free survival. The aim of this retrospective study was to explore the impact of HPV infection, HPV DNA integration, TERT promoter mutational status and somatic mutations of oncogenes on both progression-free (PFS) and overall survivals (OS) of patients treated by DCF. Samples obtained from 49 patients included in the Epitopes-HPV02 clinical trial, diagnosed with metastatic or non-resectable local recurrent SCCA treated by DCF, were used for analyses. Median PFS and OS were not associated with HPV status. Patients with episomal HPV had an improved PFS compared with SCCA patients with integrated HPV genome (p=0.07). TERT promoter mutations were rarely observed and did not specifically distribute in a subset of SCCA and did not impact DCF efficacy. Among the 42 genes investigated, few gene alterations were observed, and were in majority amplifications (68.4%), but none were significantly correlated to PFS. As no biomarker is significantly associated with patients' survival, it prompts us to include every patient failing CRT or with metastatic disease in DCF strategy

Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations

BACKGROUND: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. METHODS: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. RESULTS: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). CONCLUSION: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design

EMC modeling methods for power electronics applied to the automotive field

La réduction des émissions polluantes est un élément clé pour le futur du transport automobile. Pour cela, des systèmes électriques peuvent être utilisés en complément du moteur à combustion interne afin de rendre les véhicules hybrides. La solution étudiée est le système alternateur, qui peut devenir réversible grâce à de nouvelles structures d’électronique de puissance. Dans ce contexte, les travaux de thèse portent sur la compatibilité électromagnétique permettant de garantir l’intégration de ces systèmes dans l’environnement électrique complexe du véhicule.L’objectif des travaux est de développer des outils de modélisation prédictifs permettant de déterminer les niveaux des perturbations électromagnétiques générés par les systèmes d’électronique de puissance. Ces modèles permettent de décrire les sources de perturbations et les mécanismes de couplages à l’origine des émissions conduites. Cela permet d’étudier puis de proposer des solutions afin de respecter les contraintes normatives de compatibilité électromagnétique.Les travaux réalisés portent sur le développement d’outils et de méthodes pour la modélisation des couplages parasites, la caractérisation des composants actifs et passifs ainsi que la prise en compte de la chaine d’acquisition. Les modèles obtenus sont ensuite appliqués à la simulation des émissions conduites d’un alternateur automobile. Afin de réduire les durées de simulation, nous avons travaillé sur des simulations dans le domaine fréquentiel avec la méthode MTES (Multi-Topology Equivalent Sources) développée au L2EP. L’objectif est d’améliorer la représentativité des sources de perturbations et des impédances des convertisseurs statiques de types hacheurs et onduleurs.The reduction of polluting emissions is a key element for the future of automobile transport. For that purpose, electrical systems can be used in addition to the internal combustion engine to make vehicles hybrid. The solution studied is the alternator system, which can become reversible thanks to new structures of power electronics. In this context, the thesis work focuses on electromagnetic compatibility to ensure the integration of these systems in the complex electrical environment of the vehicle.The objective of this work is to develop predictive modeling tools to determine the levels of electromagnetic disturbances generated by power electronic systems. These models make it possible to describe the sources of disturbances and the coupling mechanisms underlying the overall conducted emissions. This makes it possible to study and then propose solutions in order to comply with the normative constraints of electromagnetic compatibility.The work carried out relates to the development of tools and methods for the modeling of parasitic couplings, the characterization of active and passive components as well as the inclusion of the acquisition chain properties. The models are then applied to the simulation of conducted emissions from an automotive alternator. In order to reduce the simulation times, we worked on simulations in the frequency domain with the MTES (Multi-Topology Equivalent Sources) method which is developed at L2EP. The objective is to improve the representativeness of the sources of disturbances and the impedances of static converters such as DC to DC and inverters

Traumatismes fermés du rein : épidémiologie, traitement conservateur et prise en charge du saignement : à propos de 500 cas entre 2010 et 2019 dans un trauma center de niveau 1

Introduction: Traumatic kidney injuries are the most frequent among urogenital injuries. The management used to be surgical witch nephrectomy, it has become conservative since the early 2000s with the development of medical imaging, interventional radiology and trauma center organization. Our retrospective series studied epidemiological data and predictive factors of arterial embolization in a level 1 trauma center. Methods: We carried out a single-center retrospective study, including all patients admitted between january 2010 and december 2019 with a kidney injury. There were 500 patients with a kidney trauma, including 307 grades III, IV and V. The inclusion criteria was a grade III, IV or V trauma. Traumas after surgery, after biopsy or after extracorporeal shock wave lithotripsy were excluded. Our primary outcome for univariate analysis was the use of arterial embolization in renal trauma. We adjusted for multivariate analysis with statistically significant factors in univariate analysis. Results: The mean age was 33 years (SD: 18y/o). Management was conservative for 293/307 (95.5%) of grade III, IV and V traumas. Interventional radiology management was performed in 55 (18%) patients, including 23 (16%) grades III, 26 (18%) grades IV and 6 (26%) grades V. There were 44 (80%) selective embolizations, allowing renal preservation in 41 cases (93%). There were 5 (9%) proximal embolizations followed in 3 cases (60%) by nephrectomy afterwards. Finally, 6 patients had an arteriography without embolization. In total, 49/55 (89%) patients treated in interventional radiology were treated conservatively. The nephrectomy rate was 14/307 (4.5%) including 2/141 (1.4%) for grades III, 9/143 (6.3%) for grades IV and 3/23 (13%) for grades V. In univariate analysis, the factors significantly associated with the use of embolization were, hematoma rim distance (p <0.001), hemoglobin (p = 0.031), surgical procedure (p = 0.039) and hematuria (p = 0.032). Predictors of arterial embolization significant on multivariate analysis were hematoma rim distance (p <0.01) and trauma grade V (p = 0.031). Conclusion: Management was conservative for 293/307 trauma (95.5%). The rate of nephrectomy has decreased since 2014, from 10/144 (6.9%) to 4/163 (2.5%) after 2014. Arterial embolization was selective for 41 patients (80%), the rate of renal conservation after embolization management was 49/55 (89%). The structuring of a "trauma center" associated with the development of interventional radiology and standardization of the management of abdominal trauma have enabled the extension of a conservative strategy in, the management of renal trauma. These results allowed us to establish a diagnostic tree allowing a calculation of arterial embolization probability according to the initial characteristics of trauma. A project in the continuity of our study would be to validate these results prospectively.Les traumatismes du rein sont les plus fréquents de la sphère uro-génitale. La prise en charge qui était anciennement la néphrectomie est devenue conservatrice depuis une vingtaine d’années. Cela a été permis par le développement de l’imagerie, de la radiologie interventionnelle et de la structuration de trauma center permettant une prise en charge optimale des traumatisés rénaux. Notre étude rétrospective, visait à étudier les données épidémiologiques des traumatisés rénaux et les facteurs prédictifs de recours à l’embolisation artérielle au CHU de Grenoble Alpes, « trauma center » de niveau 1. Méthodes : Nous avons réalisé, une étude rétrospective monocentrique, incluant tous les patients, admis au CHU de GRENOBLE entre janvier 2010 et décembre 2019 avec un traumatisme du rein, identifiés grâce à l’utilisation du PMSI. Il y a eu 500 patients inclus dont 307 grades III, IV et V. Le critère d’inclusion était le grade : III, IV, V. Étaient exclus les traumatismes post chirurgie, post biopsie rénale ou post LEC. Le critère de jugement principal pour l’analyse univariée était le recours à l’embolisation artérielle chez le traumatisé rénal. Nous avons ajusté pour l’analyse multivariée avec les facteurs significatifs de l’analyse univariée. Résultats : La moyenne d’âge était de 33 ans (SD : 18). La prise en charge était conservatrice pour 293/307 (95,5%) traumatismes de grades III, IV et V. Une prise en charge en radiologie interventionnelle a été nécessaire chez 55 (18%) patients dont 23 (16%) grades III, 26 (18%) grades IV et 6 (26%) grades V. Il y a eu 44 (80%) embolisations sélectives permettant dans 41 cas (93%) la conservation rénale. Il y a eu 5 (9%) embolisations proximales suivies dans 3 cas (60%) d’une néphrectomie dans les suites. Enfin, 6 patients ont eu une artériographie sans embolisation. Au total, 49/55 (89%) patients pris en charge en radiologie interventionnelle ont pu être traités de manière conservatrice. Le taux de néphrectomie était de 14/307 (4,5%) dont 17 2/141 (1,4%) pour les grades III, 9/143 (6,3%) pour les grades IV et 3/23 (13%) pour les grades V. En analyse univariée, les facteurs qui étaient associées, de façon significative, au recours à l’embolisation étaient, la distance du bord de l’hématome (p<0,001), l’hémoglobine à l’entrée (p=0,031), la prise en charge au bloc opératoire (p=0,039) et l’hématurie (p=0,032). Les facteurs prédictifs de recours à l’embolisation artérielle qui étaient significatifs en analyse multivariée étaient la distance du bord de l’hématome (p<0,01) et le grade V (p=0,031). Conclusion : La prise en charge était conservatrice pour 293/307 traumatismes (95.5%). Le taux de néphrectomie par traumatisme a diminué depuis 2014, de 10/144 (6.9%) à 4/163 (2.5%). L’embolisation artérielle était sélective pour 41 patients (80%), le taux de conservation rénale après prise en charge en radiologie interventionnelle était de 49/55 (89%). La structuration d’un « trauma center » associée au développement de la radiologie interventionnelle avec une standardisation de la prise en charge en cas de traumatisme abdominal ont permis l’évolution de la prise en charge du traumatisé rénal vers une stratégie conservatrice. Ces résultats nous ont permis d’établir un arbre diagnostique permettant un calcul de probabilité de recours à l’embolisation artérielle en fonction des caractéristiques initiales du traumatisme rénal. La continuité de notre étude serait de valider cet arbre décisionnel de manière prospective

Démonstrateurs pour l'analyse d'alternatives socio-techniques

At a time when politicians increasingly call on experts to decide on social issues, the French democratic crisis reflects in the citizens’ mistrust of scientists. In a context of absolute environmental emergency, several planetary boundaries already being overstepped by the Western world, it seems necessary to rebuild confidence between the people, scientists and politicians.To rethink our consumption and production patterns and to design desirable alternatives to our current way of life, the society as a whole must take part in the profound societal decisions that await us.With this in mind, scientific research develops new tools capable of modelling socio-technical organizations, thanks to which vulnerabilities of these systems are highlighted. The aim of this internship is to work on translating these phenomena and risks from a scientific language to a form accessible to all. This internship investigates a possible method, which combines three dimensions: playfulness, materiality and minimality.To do so, this report studies how knowledge transfer is explored in the practice of stakeholder participation. Serious games are studied as a relevant form to answer this need of transposition. Concept of lucidity and the way in which the ideas are represented in board games are used.This work leads to the design of two demonstrators based on the scientific work of STEEP’s team located in INRIA, Grenoble Rhônes-Alpes. The methodology of the creation process, the content of the game as well as the follow-up and evaluation of these demonstrators are presented.Alors que les politiques font de plus en plus appel aux experts pour trancher des questions de société, la crise démocratique que traverse la France se traduit aujourd’hui par une méfiance des citoyens à l’égard des scientifiques. Dans un contexte d’urgence environnementale absolue, où plusieurs limites planétaires ont déjà été franchies par la société occidentale moderne, il est fondamental de retisser le lien entre citoyens, scientifiques et politiques.L’ensemble de la société doit en effet participer aux décisions sociétales profondes qui nous attendent : repenser nos modes de production et de consommation et imaginer des alternatives désirables au fonctionnement actuel de la société occidentale.Dans cette perspective, la recherche scientifique se mobilise pour développer des outils à même de modéliser des organisations socio-techniques, grâce auxquels des vulnérabilités de ces systèmes sont mises en évidence. L’objectif de ce stage est d’œuvrer à traduire ces phénomènes et risques d’un langage scientifique vers une forme accessible à tous. Ce stage investigue une méthode possible, qui combine trois dimensions : la ludicité, le caractère haptique et la minimalité.Pour cela, ce rapport s’intéresse à des courants de pratique de la participation, pour situer le questionnement de la passation des savoirs. Le jeu sérieux est étudié comme une forme pertinente pour répondre à ce besoin de transposition. Le concept de ludicité et les représentations dans des jeux de société de plusieurs notions sont mis à profit.Ce travail aboutit à la conception de deux démonstrateurs, qui s’appuient sur les travaux scientifiques de l’équipe STEEP de l’INRIA Grenoble Rhône-Alpes. La méthodologie du processus de création, le contenu des dispositifs ludiques, ainsi que le suivi et évaluation de ces démonstrateurs sont présentés