Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 08/11/2023
• Auteurs : Jean-Philippe ChippauxRodrigue NtoneDavid BenhammouYoann MadecGaëlle NoëlAnais PerilhouFai KarlPierre AmtaMarie SanchezLucrece MatchimPedro ClauteauxLucrèce EtekiMark NdifonYap BoumArmand NkwescheuFabien Taieb
• Organismes : BioTop Institut Pasteur
• Publié dans PLoS Neglected Tropical Diseases le 23/10/2020

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Résumé : Background Snakebites is a serious public health issue but remains a neglected tropical disease. Data on antivenom effectiveness are urgently needed in Africa. We assessed effectiveness of Inoserp PAN-AFRICA (IPA), the recommended antivenom available in Cameroon. Methodology/Principal findings We enrolled 447 patients presenting with snakebite in 14 health facilities across Cameroon. At presentation, cytotoxicity, coagulation troubles and neurotoxicity were graded. We administered two to four vials of antivenom to patients based on hemotoxic or neurotoxic signs. We renewed antivenom administration to patients with persistence of bleedings or neurotoxicity 2 hours after each injection. We defined early improvement as a reduction of the grade of envenomation symptoms 2 hours after first injection. Medium-term effectiveness was investigated looking at disappearance of symptoms during hospitalization. After hospital discharge, a home visit was planned to assess long-term outcomes. Between October 2019 and May 2021, we enrolled 447 (93.7%), including 72% from the savannah regions. The median [IQR] age was 25 [14–40]. Envenomation was diagnosed in 369 (82.6%) participants. The antivenom was administered to 356 patients (96.5%) of whom 256 (71.9%) received one administration. Among these patients, cytotoxic symptoms were observed in 336 (94.4%) participants, coagulation disorders in 234 (65.7%) participants and neurotoxicity in 23 (6.5%) participants. Two hours after the first administration of antivenom, we observed a decrease in coagulation disorders or neurotoxicity in 75.2% and 39.1% of patients, respectively. Complete cessation of bleedings and neurotoxicity occurred in 96% and 93% of patients within 24 hours, respectively. Sequelae have been observed in 9 (3%) patients at the home visit 15 days after hospital admission and 11 (3%) died including one before antivenom injection. Conclusions/Significance We confirmed good effectiveness of the IPA and highlighted the rapid improvement in bleeding or neurotoxicity after the first administration. Sequential administrations of low doses of antivenom, rigorously assessed at short intervals for an eventual renewal, can preserve patient safety and save antivenom. Trial registration NCT03326492 .

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Fichiers liés : main.pdf

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• Type de publi. : Communication dans un congrès
• Date de publi. : 08/11/2023
• Auteurs : Maryam KhaliliPierre-François BertJean-Pascal GoutoulyArmelle MaraisThierry CandresseMaria LafargueChristel RenaudPhilippe DarrietGhislaine HilbertPhilippe GallusciPierre PétriacqSabine GuillaumieNathalie OllatJosep Valls FonayetCécile ThibonEric Gomès
• Organismes : Biologie du fruit et pathologie Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Biologie du fruit et pathologie Biologie du fruit et pathologie Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Unité de Recherche Œnologie [Villenave d'Ornon] Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Biologie du fruit et pathologie Plateforme Bordeaux Metabolome Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Unité de Recherche Œnologie [Villenave d'Ornon] Plateforme Bordeaux Metabolome Unité de Recherche Œnologie [Villenave d'Ornon] Plateforme Bordeaux Metabolome Ecophysiologie et Génomique Fonctionnelle de la Vigne

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Résumé : Sémillon is a cultivated grape variety known for contributing to dry and sweet white wine production. However, only seven approved clones have been officially recognized in France[1]. In this study, we aimed to characterize the genetic diversity and metabolomic profiles of a Sémillon clonal population, shedding light on the potential variations within this important grape variety. Through Illumina whole genome sequencing of 53 Sémillon clones, we observed various genetic variations, including single nucleotide polymorphisms (SNPs), providing comprehensive insights into their diversity and genomic variations. Additionally, metabolic profiling of berries was established with a combination of chemical and Gas Chromatography-Mass Spectrometry (GC-MS) analysis, allowing to quantify key quality-related parameters such as pH, acidity, sugar content and volatile thiol precursor compounds. Remarkably, our findings revealed significant variations among Sémillon clones, leading to their placing in three distinct clusters. Moreover, phenotypic evaluations highlighted variations in mid-veraison dates, cluster yield, and berry weight. These findings have practical implications for winemakers and vineyard managers, enabling informed decisions in selecting specific clones with desirable traits to achieve desired wine styles and adapt to specific environments and market demands. To unravel the underlying mechanisms behind the observed metabolomic and phenotypic variation within this Sémillon clonal population, comprehensive investigations of global metabolome profiles, epigenetic variations, and virome of the Sémillon clones will be conducted. Through the implementation of multi-omics approaches, we aim to obtain a comprehensive understanding of the Sémillon clonal population, unraveling complex regulatory networks and identifying factors that drive the unique characteristics of clones. This integrative approach will expand our knowledge beyond individual components and provides valuable insights into the intricate interplay among key players at various biological levels.

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• Type de publi. : Communication dans un congrès
• Date de publi. : 08/11/2023
• Auteurs : Marina de MiguelEtienne R. PatinElsa ChedidEnrique Saez-LagunaAnder del Sol IturraldeUsue Pérez-LopezJean-Pascal TandonnetPierre-François BertPhilippe VivinElisa MargueritSarah J. CooksonNathalie Ollat
• Organismes : Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Biodiversité, Gènes & Communautés Universidad del País Vasco [Espainia] / Euskal Herriko Unibertsitatea [España] = University of the Basque Country [Spain] = Université du pays basque [Espagne] Distributed Systems Group [UPV/EHU] Universidad del País Vasco [Espainia] / Euskal Herriko Unibertsitatea [España] = University of the Basque Country [Spain] = Université du pays basque [Espagne] Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne

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Résumé : Drought is one of the main challenges for viticulture in the context of global change. The choice of rootstock could be leveraged for vineyard adaptation to drought as we can improve plant performance without modifying the scion variety. However, most of the existing rootstocks, selected over a century ago, have a narrow genetic background which could compromise their adaptive potential. Thus, there is a scope for innovation in grapevine rootstock varieties by exploiting a wider range of wild Vitis species. The aim of this study was to investigate the drought adaptation potential of a wide range of previously unexplored wild Vitis species, integrating information at different biological scales: from genomics, transcriptomics and metabolomics to developmental and functional root traits. Our hypothesis is that metabolites can be considered as intermediate phenotypes in roots because they are expected to be mechanistically related to more complex root phenotypes. For these purposes, we investigated genetic differentiation between species and variability within species using SNPs obtained from Illumina paired-end whole genome sequencing (4k project)[1]. In addition, we characterized the response of cuttings from 12 American, Asian and Eurasian wild Vitis species (50 accessions in total) to moderate drought, during 1 month in a greenhouse experiment, with a focus on root morphological, functional and molecular responses (transcriptomics and metabolomics). We identified variability among species in root osmotic adjustment, an important mechanism of drought tolerance[2]. The link between root osmotic potential and metabolites differentially accumulated in response to drought was analyzed. The results obtained in this work will help to identify new genetic resources to be used in rootstocks breeding programs to improve drought adaptation. In addition, we will provide tools to accelerate the screening of desirable traits in rootstocks using intermediate molecular phenotypes as proxies of complex root responses. Acknowledgements: We received funding from INRAE, University of Bordeaux (project PurVitis), Nouvelle-Aquitaine region (project VitiScope) and CNIV. We acknowledge Maria Lafargue, Cyril Hevin, Nicolas Hocquard and Jean-Pierre Petit for their help with the plant material preparation. 1) Dong, Y.,et al. (2023). Dual domestications and origin of traits in grapevine evolution. Science, 379(6635), 892‑901. 2) Blum, A. (2017). Osmotic adjustment is a prime drought stress adaptive engine in support of plant production. Plant, Cell & Environment, 40(1), 4‑10.

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• Type de publi. :
• Date de publi. : 08/11/2023
• Auteurs : Elsa ChedidPierre GastouJean-Pascal TandonnetPhilippe VivinSarah CooksonPierre-François BertNathalie OllatElisa MargueritMarina De Miguel
• Organismes : Ecophysiologie et Génomique Fonctionnelle de la Vigne Santé et agroécologie du vignoble Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne Ecophysiologie et Génomique Fonctionnelle de la Vigne

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Résumé : In the context of global change, the environmental conditions are expected to be more stressful for viticulture. The choice of the rootstock may play a crucial role to improve the adaptation of viticulture to new biotic and abiotic threats (Ollat et al., 2016). However, the selection of interesting traits in rootstock breeding programs is complex because of the combination of multiple targets in a same ideotype. In this sense, the integration of studies about the genetic architecture for desired biotic and abiotic response traits allow us to identify genomic regions to combine and those with interesting pleiotropic effects. In this work we aimed to study the genetic determinism of several traits related to disease resistance and tolerance to abiotic stresses in Vitis sp. with a potential interest to be used as grapevine rootstocks. For this purpose, 30 genetic maps and QTL mapping data, available in the literature, were collected and combined with unpublished QTL for root traits obtained at EGFV lab. This information was used to construct a dense consensus genetic map of Vitis sp.. Then, a QTL meta-analysis was conducted using the software Biomercator. The obtained consensus genetic map, comprising information from different Vitis sp. is a useful genetic resource for translational genetics. In addition, the identified meta-QTLs, that combined information from independent studies, allowed to reduce QTL confidence intervals, notably for tolerance to abiotic stress traits. These results, highlight the interest of QTL meta-analysis to narrow-down the position of loci controlling desired traits for rootstock breeding programs, as previously proved for scions (Delfino et al., 2019).

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• Type de publi. : Article dans une revue
• Date de publi. : 06/11/2023
• Auteurs : Sylvain GoutelleVincent JullienJean-Pierre BruVincent CattoirRémy GauzitPhilippe LespritGérard LinaFrédéric SchrammEtienne CanouiOlivier Chosidow
• Organismes : Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 Hospices Civils de Lyon Université Sorbonne Paris Nord Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] ARN bactériens et médecine AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris] Centre International de Recherche en Infectiologie Fédération de Médecine Translationnelle de Strasbourg CHU Henri Mondor [Créteil]
• Publié dans Journal of Antimicrobial Chemotherapy le 31/10/2020

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Résumé : Background: The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable β-lactams, standard and high dosages have been proposed for short-infusion regimens only.Objectives: To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).Methods: Monte Carlo simulations were performed for seven injectable β-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable.Results: Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam.Conclusions: These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary.

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Fichiers liés : GOUTELLE et al-2023-Defining standard and high dosages for beta-lactam agents administered .pdf

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• Type de publi. : Rapport
• Date de publi. : 06/11/2023
• Auteurs : Nicolas Danel-BuhlAlain BoissonnasPatricia BoltzPascal CrennLouise GaboriauLaetitia Jacquesson-FournolsRaymond JianGisèle KannyLaetitia Koppe-GuichardMartine MorissetRuddy RichardFanny RocherPhilippe SchererJean-Fabien ZazzoClara Benzi-SchmidKarine Adel-PatientCharlotte BeaudartAnnabelle BedardCécile BetryPatrick BorelBlandine de Lauzon-GuillainChristine Feillet-CoudrayJerome Gay-QueheillardAurélie GoncalvesTao JiangEmmanuelle Kesse-GuyotNathanaël LapidusCorinne Malpuech BrugèreChristine MorandThomas MouillotRuddy RichardAnne-Sophie RousseauOlivier SteichenStéphane WalrandVincent BitaneAymeric DopterClaire MathiotAurélien Mondier CasiniPerrine Nadaud
• Organismes : GHT de l'Artois Université Paris-Sud - Paris 11 - Faculté de médecine Centre Hospitalier Régional Universitaire de Nancy AP-HP. Université Paris Saclay Centre Régional de PharmacoVigilance Nord-Pas-de-Calais [CHU Lille] Clinique de la Muette Hôpital Européen Georges Pompidou [APHP] Centre Hospitalier Universitaire de Nancy Hospices Civils de Lyon Centre Hospitalier Universitaire d'Angers Université Clermont Auvergne CHU Nice [Cimiez] Retraité AP-HP - Hôpital Antoine Béclère [Clamart] Office fédéral de la sécurité alimentaire et des affaires vétérinaires Université Paris-Saclay CEA- Saclay Université de Liège = University of Liège = Universiteit van Luik = Universität Lüttich Centre de recherche en épidémiologie et santé des populations Institut cellule souche et cerveau / Stem Cell and Brain Research Institute Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research Université Paris Cité Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques Dynamique du Muscle et Métabolisme Périnatalité et Risques Toxiques - UMR INERIS_I 1 UPJV Nîmes Université Laboratoire Activités Physiques et Sportives et processus PSYchologiques : recherches sur les Vulnérabilités - Nîmes Université Université de Bourgogne Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle Institut Pierre Louis d'Epidémiologie et de Santé Publique Université Clermont Auvergne Département Alimentation Humaine - INRAE Unité de Nutrition Humaine Unité de Nutrition Humaine Université Clermont Auvergne Université Bourgogne Franche-Comté [COMUE] Centre des Sciences du Goût et de l'Alimentation [Dijon] Université Clermont Auvergne Institut de Biologie Valrose Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Tenon [AP-HP] Unité de Nutrition Humaine Université Clermont Auvergne Direction de l'Evaluation des Risques Direction de l'Evaluation des Risques Direction de l'Evaluation des Risques Direction de l'Evaluation des Risques Direction de l'Evaluation des Risques

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Résumé : Dans le cadre de son dispositif de nutrivigilance créé en 2009, l’Anses a reçu 9 signalements d’effets indésirables susceptibles d’être liés à la consommation des produits de nutrition entérale (NE) Fresubin 2kcal HP Fibre® ou de Fresubin 2 kcal HP® commercialisés en France par la société Fresenius Kabi. Parmi ceux-ci, 8 rapportaient des effets ayant une sévérité de niveau 3 (dont 2 avec menace du pronostic vital) et 1 rapportait un effet ayant une sévérité de niveau 41. Ces cas, enregistrés dans la base de données de nutrivigilance sous les numéros 2022-250, 023-013,2023-014, 2023-15, 2023-066, 2023-102, 2023-103 et 2023-105 ont été jugés d’imputabilité très vraisemblable et le cas 2023-104 a été jugé d’imputabilité vraisemblable. Etant donné la sévérité des effets indésirables rapportés, l’Anses a estimé nécessaire de porter ces cas à la connaissance des professionnels de santé et du public, dans un but d’amélioration de la sécurité de leur utilisation et s’est autosaisie le 17 octobre 2022.

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• Type de publi. : Pré-publication, Document de travail
• Date de publi. : 03/11/2023
• Auteurs : Chloé BeaulieuCyril LibourelDuchesse Lacourt Mbadinga ZamarKarima El MahboubiDavid HoeyJean KellerCamille GirouHélène San ClementeIssa DiopEmilie AmblardAnthony ThéronStephane CauetNathalie RoddeSabine ZachgoWiebke HalpapeAnja MeierhenrichBianca LakerAndrea BräutigamGeorge Rl GreiffPeter SzovenyiShifeng ChengYasuhiro TanizawaJames Leebens-MackJeremy SchmutzJenel WebberJane GrimwoodChristophe JacquetChristophe DunandJessica NelsonFabrice RouxHervé PhilippeSebastian SchornackMaxime BonhommePierre-Marc Delaux
• Organismes : Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Sainsbury Laboratory Cambridge University Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Laboratoire de Recherche en Sciences Végétales Universität Zürich [Zürich] = University of Zurich Zurich Basel Plant Science Center LRSV-Evolution des Interactions Plantes-Microorganismes Centre National de Ressources Génomiques Végétales Centre National de Ressources Génomiques Végétales Centre National de Ressources Génomiques Végétales University of Osnabrueck = Osnabrueck Universität Universität Bielefeld = Bielefeld University Universität Bielefeld = Bielefeld University Universität Bielefeld = Bielefeld University Universität Bielefeld = Bielefeld University Sainsbury Laboratory Cambridge University Universität Zürich [Zürich] = University of Zurich Zurich Basel Plant Science Center Chinese Academy of Agricultural Sciences National Institute of Genetics [Shizuoka, Japan] University of Georgia [USA] HudsonAlpha Institute for Biotechnology [Huntsville, AL] Lawrence Berkeley National Laboratory [Berkeley] HudsonAlpha Institute for Biotechnology [Huntsville, AL] HudsonAlpha Institute for Biotechnology [Huntsville, AL] LRSV-Evolution des Interactions Plantes-Microorganismes LRSV-Dynamique et Evolution des Parois cellulaires végétales Maastricht University [Maastricht] Laboratoire des Interactions Plantes Microbes Environnement Station d'Ecologie Théorique et Expérimentale National Institute of Genetics [Shizuoka, Japan] Sainsbury Laboratory Cambridge University LRSV-Evolution des Interactions Plantes-Microorganismes LRSV-Evolution des Interactions Plantes-Microorganismes

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Résumé : Plant adaptation to a terrestrial life 450 million years ago played a major role in the evolution of life on Earth. This shift from an aquatic environment has been mostly studied by focusing on flowering plants. Here, we gathered a collection of 133 accessions of the non-vascular plants Marchantia polymorpha and studied its intraspecific diversity using selection signature analyses, genome-environment association study and a gene-centered pangenome. We identified adaptive features shared with flowering plants, such as peroxidases or nucleotide-binding and leucine-rich repeat (NLR), which likely played a role in the adaptation of the first land plants to the terrestrial habitat. The M. polymorpha pangenome also harbored lineage-specific accessory genes absent from seed plants. We conclude that different land plants lineages still share many elements from the genetic toolkit evolved by their most recent common ancestor to adapt to the terrestrial habitat, refined by lineage specific polymorphisms and gene family evolutions.

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• Type de publi. : Article dans une revue
• Date de publi. : 02/11/2023
• Auteurs : Martin SchwartzPhilippe CiaisAurelien de TruchisJérôme ChaveCatherine OttleCedric VegaWigneron J.-P.Manuel NicolasSami JouaberSiyu LiuMartin BrandtIbrahim Fayad
• Organismes : Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Kayrros Evolution et Diversité Biologique Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Modélisation des Surfaces et Interfaces Continentales IGN-France International Interactions Sol Plante Atmosphère Réseau national de suivi à long terme des écosytèmes forestiers Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] IT University of Copenhagen IT University of Copenhagen Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Kayrros
• Publié dans Earth System Science Data le 23/10/2020

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Résumé : The contribution of forests to carbon storage and biodiversity conservation highlights the need for accurate forest height and biomass mapping and monitoring. In France, forests are managed mainly by private owners and divided into small stands, requiring 10 to 50 m spatial resolution data to be correctly separated. Further, 35 % of the French forest territory is covered by mountains and Mediterranean forests which are managed very extensively. In this work, we used a deep-learning model based on multi-stream remote-sensing measurements (NASA's Global Ecosystem Dynamics Investigation (GEDI) lidar mission and ESA's Copernicus Sentinel-1 and Sentinel-2 satellites) to create a 10 m resolution canopy height map of France for 2020 (FORMS-H). In a second step, with allometric equations fitted to the French National Forest Inventory (NFI) plot data, we created a 30 m resolution above-ground biomass density (AGBD) map (Mg ha−1) of France (FORMS-B). Extensive validation was conducted. First, independent datasets from airborne laser scanning (ALS) and NFI data from thousands of plots reveal a mean absolute error (MAE) of 2.94 m for FORMS-H, which outperforms existing canopy height models. Second, FORMS-B was validated using two independent forest inventory datasets from the Renecofor permanent forest plot network and from the GLORIE forest inventory with MAE of 59.6 and 19.6 Mg ha−1, respectively, providing greater performance than other AGBD products sampled over France. Finally, we compared FORMS-V (for volume) with wood volume estimations at the ecological region scale and obtained an R2 of 0.63 with an MAE of 30 m3 ha−1. These results highlight the importance of coupling remote-sensing technologies with recent advances in computer science to bring material insights to climate-efficient forest management policies. Additionally, our approach is based on open-access data having global coverage and a high spatial and temporal resolution, making the maps reproducible and easily scalable. FORMS products can be accessed from https://doi.org/10.5281/zenodo.7840108 (Schwartz et al., 2023).

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Fichiers liés : essd-15-4927-2023.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/11/2023
• Auteurs : Sébastien BourdinPhilippe Jean-PierreDavid Perrain
• Organismes : Métis Lab EM Normandie Centre d'Économie et de Management de l'Océan Indien Institut d'Administration des Entreprises - La Réunion Centre d'Économie et de Management de l'Océan Indien Institut d'Administration des Entreprises - La Réunion
• Publié dans Eastern Journal of European Studies le 02/11/2020

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Résumé : This article examines the issue of innovation in the tourism sector, emphasising its crucial role in the transformation of the tourist offer within European regions. Faced with territorial disparities in terms of tourism innovations, we examine the impact of Regional Innovation and Smart Specialization Strategies (RIS3) on the deployment of tourism innovation. By analysing the 2014-2020 program through a three-step action research study, we identify a positive correlation between RIS3 initiatives and innovation in the tourism industry. However, RIS3 seem to be a necessary but not sufficient condition to stimulate innovation.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/11/2023
• Auteurs : Tae Won KimPhilippe BedardPatricia LorussoMichael GordonJohanna BendellDo-Youn OhMyung-Ju AhnElena GarraldaSandra D’angeloJayesh DesaiF. Stephen HodiZev WainbergJean-Pierre DelordPhillippe CassierAndrés CervantesMarta Gil-MartinBenjamin WuNamrata PatilYanling JinTien HoangDiana MendusXiaohui WenRaymond MengByoung Chul Cho
• Organismes : Centre de Recherches en Cancérologie de Toulouse Oncopole Claudius Regaud Institut Universitaire du Cancer de Toulouse - Oncopole
• Publié dans JAMA oncology le 27/10/2020

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Résumé : Importance Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of atezolizumab in programmed death ligand 1–selected tumors. Objective To evaluate the safety and antitumor activity of the anti-TIGIT antibody tiragolumab and its combination with atezolizumab in patients with advanced solid tumors. Design, Setting, and Participants The GO30103 open-label, first-in-human phase 1a/1b dose-escalation and dose-expansion nonrandomized controlled trial was conducted at 13 sites in 6 countries (Australia, Canada, France, Korea, Spain, and the US). The start dates were May 23, 2016, for phase 1a and October 11, 2016, for phase 1b. Patients were aged 18 years or older with measurable disease at baseline. The clinical cutoff date was October 1, 2021. Data analysis was performed on January 24, 2022. Interventions Patients received fixed-dose intravenous tiragolumab on day 1 of each 21-day cycle (2 mg escalating to 1200 mg) in phase 1a, plus fixed-dose intravenous atezolizumab (1200 mg every 3 weeks) in phase 1b. Patients were treated until disease progression, loss of clinical benefit, or development of unacceptable toxicity. Main Outcomes and Measures The primary end points included the safety, tolerability, and recommended phase 2 dose (RP2D) of tiragolumab or combination tiragolumab plus atezolizumab. The secondary end point included the investigator-assessed objective response rate (ORR). Counts and percentages are used for categorical variables, and medians and ranges are used for continuous variables. Results Among the phase 1a (n = 24) and 1b (n = 49) dose-escalation cohorts, the median age was 60 (range, 40-77) and 54 (range, 25-81) years, respectively. More than half of patients were women (14 of 24 [58%] and 25 of 49 [51%]), and more than a third (10 [42%] and 18 [37%]) had received 4 or more prior cancer therapies. No dose-limiting toxicities occurred, and the maximum tolerated dose of tiragolumab was not reached (NR). The most frequent treatment-related adverse events (AEs) were fatigue (5 of 24 [21%]) in phase 1a and pruritus (5 of 49 [10%]) in phase 1b; the majority of AEs were grade 1 or 2. Immune-mediated AEs occurred in 4 of 24 (17%) and 29 of 49 (59%) patients during phases 1a and 1b, respectively (primarily grade 1 or 2). The RP2D of tiragolumab was 600 mg intravenously every 3 weeks, which was tested in phase 1b dose expansion. The confirmed ORR was 0% during phase 1a, with evidence of antitumor activity in 6% of patients (n = 3) during phase 1b. The safety profile of combination tiragolumab plus atezolizumab in phase 1b was similar in the dose-escalation and dose-expansion cohorts. The confirmed ORR was 46% (6 of 13) in the non–small cell lung cancer (NSCLC) cohort (median duration of response [DOR], NR) and 28% (5 of 18) in the esophageal cancer (EC) cohort (median DOR, 15.2 [95% CI, 7.0 to NR] months). Conclusions and Relevance In this nonrandomized controlled trial, tiragolumab was well tolerated with or without atezolizumab; no new safety signals were observed. Preliminary antitumor activity was demonstrated for the combination regimen in patients with cancer immunotherapy–naive metastatic NSCLC or EC. Trial Registration ClinicalTrials.gov Identifier: NCT02794571

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