L'incubation d'entreprises : la nouvelle frontière européenne

Le soutien à la création d'entreprise est une préoccupation commune à de nombreux pays de l'Union Européenne et la communauté fait de l'esprit d'entreprise un défi pour l'Europe tout en soulignant le moindre dynamisme entrepreneurial des européens, pour lesquels le processus de création d'entreprise demeure un processus à hauts risques. Dans un tel contexte, les pays membres sont encouragés à mettre en œuvre des politiques publiques coordonnées permettant d'augmenter le nombre d'entrepreneurs et de stimuler la croissance des entreprises. Les incubateurs (et pépinières) d'entreprises s'inscrivent dans cette perspective. Les études déjà menées sur les incubateurs européens montrent qu'il existe des différences significatives en matière de stratégies et de pratiques d'incubation, que ce soit entre états membres ou au sein de chaque pays. Dans de telles conditions quel peut-être l'apport d'une politique européenne ? L'objectif de cette communication est donc de proposer, à la lumière des approches institutionnaliste et culturaliste, une analyse des incubateurs européens et des politiques nationales et communautaires en faveur de l'incubation. Après avoir souligné la diversité du paysage de l'incubation en Europe, tant sur le plan du dynamisme entrepreneurial que sur celui des formes d'incubateurs ou des modes d'accompagnement proposés par ces structures, nous analyserons plus précisément les dimensions institutionnelles et culturelles de cette diversité et nous nous interrogerons enfin sur la possibilité d'élaboration d'un modèle d'incubation européen, à travers la mise en œuvre d'un contexte permissif et d'un modèle interculturel d'incubation.Incubateurs ; pépinières ; entrepreneuriat ; culturalisme ; institutionnalisme ; management interculturel ; benchmarking

Les incubateurs d'entreprises innovantes : un réseau entrepreneurial reconfiguré ?

Les travaux sur l'entrepreneuriat se sont multipliés ces dernières années, mettant l'accent sur les traits de l'entrepreneur mais aussi sur les réseaux d'aide à la création d'entreprise. Cependant, ces travaux se sont peu intéressés aux incubateurs et pépinières d'entreprises, alors que ces acteurs se sont multipliés, en particulier dans le domaine de la création d'entreprises innovantes. Notre objectif sera donc dans un premier temps d'éclairer le rôle des réseaux dans la dynamique de développement des jeunes entreprises. Pour cela, nous mobiliserons la théorie des réseaux sociaux, dans la lignée de Granovetter et de Burt. Puis en nous appuyant sur une étude exploratoire menée auprès de 4 incubateurs /pépinières, nous tenterons de reconstituer les réseaux mobilisés par ces structures d'accompagnement particulières et de déterminer leurs caractéristiques.création d'entreprise ; entrepreneuriat ; pépinières ; incubateurs ; réseaux sociaux

Pôles de compétitivité : enjeux et interrogations tirés des expériences des districts industriels et des clusters

L'impulsion par le gouvernement français de la création de pôles de compétitivité s'inscrit dans une tradition de recherche ancienne et féconde, initiée par les travaux de Marshall, et qui s'est développée et enrichie autour des notions de « districts industriels » et de « clusters ». Encouragées par les travaux plus récents de Porter (1998), un peu partout dans le monde, des politiques volontaristes visant à créer des avantages compétitifs nationaux ont été initiées. Il nous a semblé important d'interroger les éléments et hypothèses sur lesquels repose cette politique volontariste, les fondements de la performance des clusters et les conditions de transposition des démarches mises en œuvre. Ainsi, après une revue de la littérature ciblée où nous avons mis en évidence les éléments rattachés à la performance des districts industriels et clusters (et plus largement aux phénomènes d'agglomération économique), nous nous sommes interrogés sur la proximité entre ces analyses et la conception des pôles de compétitivité français. A travers les diverses stratégies de zonage, de partenariat autour de projets de R&D et de mise en place de dispositif de gouvernance, nous avons pu dégager les principales caractéristiques fondatrices des pôles labellisés dont il conviendra par la suite d'observer la mise en œuvre sur le terrain.pôles de compétitivité ; districts ; clusters ; innovation ; gouvernance

Quelle gouvernance pour les réseaux territorialisés d'organisations ?

Pour de nombreux spécialistes des réseaux territorialisés, la question de leur gouvernance se pose de façon critique. Cependant, peu de travaux se sont focalisés sur le sujet. Dans un contexte de multiplication de ce type de réseaux et devant les résultats mitigés des diverses expériences menées jusqu'à ce jour, cet article propose une synthèse des connaissances et des pistes de formalisation d'une structure de gouvernance territoriale.Gouvernance ; Réseaux interorganisationnels ; Gouvernance territoriale ; Gouvernance collective ; Territoire.

The dynamics of gene expression changes in a mouse model of oral tumorigenesis may help refine prevention and treatment strategies in patients with oral cancer.

A better understanding of the dynamics of molecular changes occurring during the early stages of oral tumorigenesis may help refine prevention and treatment strategies. We generated genome-wide expression profiles of microdissected normal mucosa, hyperplasia, dysplasia and tumors derived from the 4-NQO mouse model of oral tumorigenesis. Genes differentially expressed between tumor and normal mucosa defined the "tumor gene set" (TGS), including 4 non-overlapping gene subsets that characterize the dynamics of gene expression changes through different stages of disease progression. The majority of gene expression changes occurred early or progressively. The relevance of these mouse gene sets to human disease was tested in multiple datasets including the TCGA and the Genomics of Drug Sensitivity in Cancer project. The TGS was able to discriminate oral squamous cell carcinoma (OSCC) from normal oral mucosa in 3 independent datasets. The OSCC samples enriched in the mouse TGS displayed high frequency of CASP8 mutations, 11q13.3 amplifications and low frequency of PIK3CA mutations. Early changes observed in the 4-NQO model were associated with a trend toward a shorter oral cancer-free survival in patients with oral preneoplasia that was not seen in multivariate analysis. Progressive changes observed in the 4-NQO model were associated with an increased sensitivity to 4 different MEK inhibitors in a panel of 51 squamous cell carcinoma cell lines of the areodigestive tract. In conclusion, the dynamics of molecular changes in the 4-NQO model reveal that MEK inhibition may be relevant to prevention and treatment of a specific molecularly-defined subgroup of OSCC

Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes

Background: Nucleolin (NCL) is a multifunctional protein with oncogenic properties. Anti-NCL drugs show strong cytotoxic effects, including in triple-negative breast cancer (TNBC) models, and are currently being evaluated in phase II clinical trials. However, few studies have investigated the clinical value of NCL and whether NCL stratified cancer patients. Here, we have investigated for the first time the association of NCL with clinical characteristics in breast cancers independently of the different subtypes. Methods: Using two independent series (n = 216; n = 661), we evaluated the prognostic value of NCL in non-metastatic breast cancers using univariate and/or multivariate Cox-regression analyses. Results: We reported that NCL mRNA expression levels are markers of poor survivals independently of tumour size and lymph node invasion status (n = 216). In addition, an association of NCL expression levels with poor survival was observed in TNBC (n = 40, overall survival (OS) p = 0.0287, disease-free survival (DFS) p = 0.0194). Transcriptomic analyses issued from The Cancer Genome Atlas (TCGA) database (n = 661) revealed that breast tumours expressing either low or high NCL mRNA expression levels exhibit different gene expression profiles. These data suggest that tumours expressing high NCL mRNA levels are different from those expressing low NCL mRNA levels. Conclusions: NCL is an independent marker of prognosis in breast cancers. We anticipated that anti-NCL is a promising therapeutic strategy that could rapidly be evaluated in high NCL-expressing tumours to improve breast cancer management

Coastal zone management in the fisheries sector program

International audienceThis paper presents an analysis of censored survival data for breast cancer specific mortality and disease-free survival. There are three stages to the process, namely time-to-event modelling, risk stratification by predicted outcome and model interpretation using rule extraction. Model selection was carried out using the benchmark linear model, Cox regression but risk staging was derived with Cox regression and with Partial Logistic Regression Artificial Neural Networks regularised with Automatic Relevance Determination (PLANN-ARD). This analysis compares the two approaches showing the benefit of using the neural network framework especially for patients at high risk. The neural network model also has results in a smooth model of the hazard without the need for limiting assumptions of proportionality. The model predictions were verified using out-of-sample testing with the mortality model also compared with two other prognostic models called TNG and the NPI rule model. Further verification was carried out by comparing marginal estimates of the predicted and actual cumulative hazards. It was also observed that doctors seem to treat mortality and disease-free models as equivalent, so a further analysis was performed to observe if this was the case. The analysis was extended with automatic rule generation using Orthogonal Search Rule Extraction (OSRE). This methodology translates analytical risk scores into the language of the clinical domain, enabling direct validation of the operation of the Cox or neural network model. This paper extends the existing OSRE methodology to data sets that include continuous-valued variables

Experimental designs for small randomised clinical trials: An algorithm for choice

Background: Small clinical trials are necessary when there are difficulties in recruiting enough patients for conventional frequentist statistical analyses to provide an appropriate answer. These trials are often necessary for the study of rare diseases as well as specific study populations e.g. children. It has been estimated that there are between 6,000 and 8,000 rare diseases that cover a broad range of diseases and patients. In the European Union these diseases affect up to 30 million people, with about 50% of those affected being children. Therapies for treating these rare diseases need their efficacy and safety evaluated but due to the small number of potential trial participants, a standard randomised controlled trial is ofte

Lymphopenia combined with low TCR diversity (divpenia) predicts poor overall survival in metastatic breast cancer patients

Lymphopenia (< 1Giga/L) detected before initiation of chemotherapy is a predictive factor for death in metastatic solid tumors. Combinatorial T cell repertoire (TCR) diversity was investigated and tested either alone or in combination with lymphopenia as a prognostic factor at diagnosis for overall survival (OS) in metastatic breast cancer (MBC) patients. The combinatorial TCR diversity was measured by semi quantitative multi-N-plex PCR on blood samples before the initiation of the first line chemotherapy in a development (n = 66) and validation (n = 67) MBC patient cohorts. A prognostic score, combining lymphocyte count and TCR diversity was evaluated. Univariate and multivariate analyses of prognostic factors for OS were performed in both cohorts. Lymphopenia and severe restriction of TCR diversity called “divpenia” (diversity ≤ 33%) were independently associated with shorter OS. Lympho-divpenia combining lymphopenia and severe divpenia accurately identified patients with poor OS in both cohorts (7.6 and 10.6 vs 24.5 and 22.9 mo). In multivariate analysis including other prognostic clinical factors, lympho-divpenia was found to be an independent prognostic factor in the pooled cohort (p = 0.005) along with lack of HER2 and hormonal receptors expression (p = 0.011) and anemia (p = 0.009). Lympho-divpenia is a novel prognostic factor that will be used to improve quality of MBC patients’ medical care

A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients

Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. Trial registration: The study was registered on the NCT01469975 ( https://clinicaltrials.gov/ct2/show/NCT01469975 ) website with a registration code NCT01469975 on November the third, 2011