174 research outputs found

    Factors related to knowledge creation and career outcomes in French academia: The case of the human resource management field

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    In response to the increasing discourse on academic careers and knowledge creation, we develop and test a model predicting research performance in the field of management outside the Anglo-Saxon countries. Based on comprehensive data of French academics, we examine various factors – career-related and demographic factors like gender – that play a role in determining academic research performance in an increasingly global academia. The role of the English language is positively related to citations but not to the volume of papers or their global/national recognition. Higher institutional reputations were positively associated to number of papers, citations, and national recognition. Strikingly, there was no relationship with global recognition, suggesting that the reputation of institutions plays a role, but only insofar as the national context and without spillover into the global academic scene. Finally, men were over-performing in both publications’ quality and quantity. Career experience had a positive effect, although this reduced gradually over time. Our findings can help individuals’ career decision-making and institutional investment in human-capital. We offer an original contribution to facilitate the understanding of factors that may influence research performance outside the Anglo-Saxon academia by opening of the black box of knowledge development, exposing the role of academic publications and recognition

    IMPACT 2002+: A new life cycle impact assessment methodology

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    The new IMPACT 2002+ life cycle impact assessment methodology proposes a feasible implementation of a combined midpoint/damage approach, linking all types of life cycle inventory results (elementary flows and other interventions) via 14 midpoint categories to four damage categories. For IMPACT 2002+, new concepts and methods have been developed, especially for the comparative assessment of human toxicity and ecotoxicity. Human Damage Factors are calculated for carcinogens and non-carcinogens, employing intake fractions, best estimates of dose-response slope factors, as well as severities. The transfer of contaminants into the human food is no more based on consumption surveys, but accounts for agricultural and livestock production levels. Indoor and outdoor air emissions can be compared and the intermittent character of rainfall is considered. Both human toxicity and ecotoxicity effect factors are based on mean responses rather than on conservative assumptions. Other midpoint categories are adapted from existing characterizing methods (Eco-indicator 99 and CML 2002). All midpoint scores are expressed in units of a reference substance and related to the four damage categories human health, ecosystem quality, climate change, and resources. Normalization can be performed either at midpoint or at damage level. The IMPACT 2002+ method presently provides characterization factors for almost 1500 different LCI-results, which can be downloaded at http://www.epfl.ch/impac

    Estimating pesticide emission fractions for use in LCA: a global consensus-building effort

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    A practical challenge in LCA for comparing pesticide application in different agricultural practices is the agreement on how to quantify the amount emitted, while only the amount applied to the field is known. Main goal of this paper is to present an international effort carried out to reach agreement on recommended default agricultural pesticide emission fractions to environmental media. Consensual decisions on the assessment framework are (a) primary distributions are used as inputs for LCIA, while further investigating how to assess secondary emissions, (b) framework and LCA application guidelines and documentation will be compiled, (c) the emission framework will be based on modifying PestLCI 2.0, (d) drift values will be provided by German, Dutch and other drift modelers, (e) pesticide application methods will be complemented to develop scenarios for tropical regions, (f) climate, soil and application method scenarios will be based on sensitivity analysis, (g) default emission estimates for LCA will be derived from production-weighted averages, and (h) emission fractions will be reported spatially disaggregated. Recommendations for LCA practitioners and database developers are (a) LCA studies should state whether the agricultural field belongs to technosphere or ecosphere, (b) additional information needs to be reported in LCI (e.g. pesticide mass applied), (c) emissions after primary distribution and secondary fate processes should be reported, (d) LCIA methods should allow for treating the field as part of technosphere and ecosphere, (e) fate and exposure processes should be included in LCIA (e.g. crop uptake), (f) default emission estimates should be used in absence of detailed scenario data, (g) and all assumptions should be reported. The recommended pesticide emission fractions results and recommendations are presented and disseminated to strive for broad acceptance at a dedicated stakeholder workshop back-to-back with the current LCA Food 2016 conference in Dublin

    Masitinib Combined with Standard Gemcitabine Chemotherapy: In Vitro and In Vivo Studies in Human Pancreatic Tumour Cell Lines and Ectopic Mouse Model

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    International audienceBackground: Tyrosine kinases are attractive targets for pancreatic cancer therapy because several are over-expressed, including PDGFRα/β, FAK, Src and Lyn. A critical role of mast cells in the development of pancreatic cancer has also been reported. Masitinib is a tyrosine kinase inhibitor that selectively targets c-Kit, PDGFRα/β, Lyn, and to a lesser extent the FAK pathway, without inhibiting kinases of known toxicities. Masitinib is particularly efficient in controlling the proliferation, differentiation and degranulation of mast cells. This study evaluates the therapeutic potential of masitinib in pancreatic cancer, as a single agent and in combination with gemcitabine.Methodology/Findings: Proof-of-concept studies were performed in vitro on human pancreatic tumour cell lines and then in vivo using a mouse model of human pancreatic cancer. Molecular mechanisms were investigated via gene expression profiling. Masitinib as a single agent had no significant antiproliferative activity while the masitinib/gemcitabine combination showed synergy in vitro on proliferation of gemcitabine-refractory cell lines Mia Paca2 and Panc1, and to a lesser extent in vivo on Mia Paca2 cell tumour growth. Specifically, masitinib at 10 µM strongly sensitised Mia Paca2 cells to gemcitabine (>400-fold reduction in IC50); and moderately sensitised Panc1 cells (10-fold reduction). Transcriptional analysis identified the Wnt/β-catenin signalling pathway as down-regulated in the cell lines resensitised by the masitinib/gemcitabine combination.Conclusions: These data establish proof-of-concept that masitinib can sensitise gemcitabine-refractory pancreatic cancer cell lines and warrant further in vivo investigation. Indeed, such an effect has been recently observed in a phase 2 clinical study of patients with pancreatic cancer who received a masitinib/gemcitabine combination

    Dialogues artistiques avec les passés de l'Égypte

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    De l’architecture aux arts décoratifs et de la peinture au théâtre, ce recueil de textes traite d’œuvres dialoguant avec le patrimoine égyptien dans toutes ses composantes. La notion « d’égyptianisme » se trouve ainsi examinée dans la plus large variété de ses acceptions artistiques, architecturales et critiques, dans le monde occidental comme en Égypte. Les textes révèlent un historicisme artistique de veine égyptienne qui ne se cantonnerait ni à la référence antique, ni au monde occidental : nombreux sont les peintres, les sculpteurs, les cinéastes, les architectes… d’Égypte à avoir intégré des représentations du passé national – pharaonique, copte, médiéval, ottoman, et désormais khédivial ou nassérien – dans leur pratique artistique. À l’encontre de l’image habituelle de l’Égyptomanie, c’est un panorama plus riche et plus diversifié qui prend corps ici à travers divers médias et contextes nationaux. Le présent recueil trouve sa source dans un colloque international organisé à la faveur de la venue à Paris de l’exposition « Le théorème de Néfertiti : itinéraire de l’œuvre d’art, la création des icônes » présentée à l’Institut du monde arabe en 2013. Ce colloque s’est tenu les 26 et 27 juin 2013 en partenariat avec Mathaf : Arab Museum of Modern Art (Doha) sous l’intitulé « L’Égypte en ses miroirs ; art, architecture et critique, à demeure et au-delà (XIXe-XXe siècles) »

    Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT

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    International audienceBackground: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. Methodology/Principal Findings: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC50) of 200 ± 40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC50 of 150 ± 80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain. In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. Conclusions: Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicit

    Genetic counselling and testing in pulmonary arterial hypertension:a consensus statement on behalf of the International Consortium for Genetic Studies in PAH

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    Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.</p
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