La réponse d'une direction des achats pour intégrer et suivre les projets tout au long d'un cycle de développement

The global subject of the thesis is in line with the continuous improvement method withinindustrial company. Our target is to analyse what would be the answer coming from thepurchasing organization to interface with New Project Development (NPD). Basically, toinsure their future industrial company must integrate their supplier base in NPD phases.Our study is based around six main axes : the context and the target of NPD, NPD globalorganization, human resources (project buyer tasks and competences), the relationshipbetween purchasing and suppliers inside Early Supplier Involvement (ESI) processesincluding a special focus on innovation and responsible approach, purchasing process tomanage NPD and finally future evolution (continuous improvement). Those axes are includedin four parts. The first part describes current issues in industrial industry in terms of quality,production capacity, permanent structure evolution, customer expectation and their impacton the purchasing organization. The second part shows the bibliographical research aboutthe state of the art and makes a deeper analysis of the first part topics. The third partpresents the research method chosen (DELPHI), how the questionnaire has been createdand the data collection and analysis processes (date code). Finally, the fourth part is fullydedicated to the 14 expert interview analysis. We introduce 13 recommendations to improvethe purchasing performance within the NPD. In order to implement those recommendationswe suggest to follow rules describe in a special guide. This guide is made to present a biggroup « best practice », also to give some guideline to the tier 2 suppliers in order to changetheir own organization and to better understand how their customers work in NPD. At theend, our thesis intends to enlarge the purchasing view within industry above the basic visionon company productivity support.Le cadre général de la thèse porte sur une démarche d’amélioration des suivis de projets dans les entreprises industrielles. Notre questionnement de recherche s’intéresse à la réponse que peut apporter une direction des Achats au cours de la phase de développement des produits nouveaux (DPN). La problématique s’inscrit dans l’obligation des entreprises à intégrer leurs fournisseurs dans les phases amont des DPN pour assurer leur pérennité. Nous avons orienté notre recherche suivant six axes principaux : le contexte et les enjeux des DPN, l’organisation en phase DPN, les ressources humaines (rôles et compétences d’un acheteur projets), la relation Achats/fournisseurs (problématiques de mise en oeuvre d’une démarche ESI (Early Supplier Involvement)) avec un focus particulier sur l’innovation et l’achat responsable, le processus des Achats pour suivre les DPN et l’axe prospectif (amélioration continue). L’ensemble de ces axes sont développés au cours des quatre parties du mémoire. La première partie aborde les problématiques contemporaines de l’industrie en termes de qualité, de capacité de production, de remise en cause permanente des organisations et, d’attentes des clients. Les impacts pour une direction des Achats sont alors étudiés. La deuxième partie présente la recherche bibliographique de l’état de l’art relatif à chacun des axes analysés. La troisième partie décrit la méthode de recherche retenue (DELPHI), la création d’un questionnaire d’entretien et la méthode d’analyse des données (le codage). Enfin la quatrième partie est exclusivement consacrée à l’analyse des entretiens réalisés auprès de 14 experts. Nous proposons alors 13 préconisations pour améliorer la performance d’une direction des Achats lors de la phase de développement des produits nouveaux. La mise en oeuvre de ces préconisations est détaillée au travers d’un guide pratique. La finalité de ce guide pratique est d’échanger sur les « best practice » des grands groupes, d’accompagner les PME dans ce changement et d’éclairer les fournisseurs sur la manière d’intégrer les cycles de développement de leurs clients. Au final, notre démarche cherche à contribuer à l’élargissement du cadre du métier des Achats bien au delà du stéréotype de la négociation commerciale pour permettre ainsi, l’amélioration de la compétitivité des entreprises

Cytotoxic dendritic cells generated from cancer patients.

International audienceKnown for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies

Review of current Severe Accident Management (SAM) approaches for Nuclear Power Plants in Europe

The Fukushima accidents highlighted that both the in-depth understanding of such sequences and the development or improvement of adequate Severe Accident Management (SAM) measures are essential in order to further increase the safety of the nuclear power plants operated in Europe. To support this effort, the CESAM (Code for European Severe Accident Management) R&D project, coordinated by GRS, started in April 2013 for 4 years in the 7th EC Framework Programme of research and development of the European Commission. It gathers 18 partners from 12 countries: IRSN, AREVA NP SAS and EDF (France), GRS, KIT, USTUTT and RUB (Germany), CIEMAT (Spain), ENEA (Italy), VUJE and IVS (Slovakia), LEI (Lithuania), NUBIKI (Hungary), INRNE (Bulgaria), JSI (Slovenia), VTT (Finland), PSI (Switzerland), BARC (India) plus the European Commission Joint Research Center (JRC). The CESAM project focuses on the improvement of the ASTEC (Accident Source Term Evaluation Code) computer code. ASTEC,, jointly developed by IRSN and GRS, is considered as the European reference code since it capitalizes knowledge from the European R&D on the domain. The project aims at its enhancement and extension for use in severe accident management (SAM) analysis of the nuclear power plants (NPP) of Generation II-III presently under operation or foreseen in near future in Europe, spent fuel pools included. In the frame of the CESAM project one of the tasks consisted in the preparation of a report providing an overview of the Severe Accident Management (SAM) approaches in European Nuclear Power Plants to serve as a basis for further ASTEC improvements. This report draws on the experience in several countries from introducing SAMGs and on substantial information that has become available within the EU “stress test”. To disseminate this information to a broader audience, the initial CESAM report has been revised to include only public available information. This work has been done with the agreement and in collaboration with all the CESAM project partners. The result of this work is presented here.JRC.F.5-Nuclear Reactor Safety Assessmen

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Incidence of Sarcoma Histotypes and Molecular Subtypes in a Prospective Epidemiological Study with Central Pathology Review and Molecular Testing

International audienceBACKGROUND: The exact overall incidence of sarcoma and sarcoma subtypes is not known. The objective of the present population-based study was to determine this incidence in a European region (Rhone-Alpes) of six million inhabitants, based on a central pathological review of the cases. METHODOLOGY/PRINCIPAL FINDINGS: From March 2005 to February 2007, pathology reports and tumor blocks were prospectively collected from the 158 pathologists of the Rhone-Alpes region. All diagnosed or suspected cases of sarcoma were collected, reviewed centrally, examined for molecular alterations and classified according to the 2002 World Health Organization classification. Of the 1287 patients screened during the study period, 748 met the criteria for inclusion in the study. The overall crude and world age-standardized incidence rates were respectively 6.2 and 4.8 per 100,000/year. Incidence rates for soft tissue, visceral and bone sarcomas were respectively 3.6, 2.0 and 0.6 per 100,000. The most frequent histological subtypes were gastrointestinal stromal tumor (18%; 1.1/100,000), unclassified sarcoma (16%; 1/100,000), liposarcoma (15%; 0.9/100,000) and leiomyosarcoma (11%; 0.7/100,000). CONCLUSIONS/SIGNIFICANCE: The observed incidence of sarcomas was higher than expected. This study is the first detailed investigation of the crude incidence of histological and molecular subtypes of sarcomas

The Fukushima Daiichi Accident

The Fukushima Daiichi Accident consists of a Report by the IAEA Director General and five technical volumes. It is the result of an extensive international collaborative effort involving five working groups with about 180 experts from 42 Member States with and without nuclear power programmes and several international bodies. It provides a description of the accident and its causes, evolution and consequences, based on the evaluation of data and information from a large number of sources available at the time of writing. The set contains six printed parts and five supplementary CD-ROMs. Contents: Report by the Director General; Technical Volume 1/5, Description and Context of the Accident; Technical Volume 2/5, Safety Assessment; Technical Volume 3/5, Emergency Preparedness and Response; Technical Volume 4/5, Radiological Consequences; Technical Volume 5/5, Post-accident Recovery; Annexes. The JRC contributed to volumes 1,2 and 3, which are attached.JRC.F.5-Nuclear Reactor Safety Assessmen