Étude des mécanismes de démocratie directe applicables à la ville de Grenoble

Ce rapport vise à fournir des pistes juridiques et techniques pour promouvoir la diffusion des référendums d’initiative populaire à Grenoble. Il y a deux difficultés principales qui expliquent en partie les échecs de ce type d’initiative en France, par rapport à d’autres pays comme l’Allemagne ou l’Autriche, les deux liées à la centralisation qui caractérise notre pays. Premièrement, les règles qui régissent les procédures de décision (c’est à dire qui décide comment les décisions vont être prises) sont fixées au niveau national, et les municipalités n’ont aucune compétence pour produire du droit en la matière. Deuxièmement, les compétences des mairies sont très faibles, ce qui offre moins d’opportunités aux citoyens de prendre desinitiatives. En dépit de ces deux contraintes, nous fournissons ici un ensemble de préconisations pour fournir une procédure qui garantisse à la fois sa légalité, un coût limité et son succès. Par « succès » nous entendons le fait que le dispositif soit réellement utilisé par les citoyens. Pour avoir une idée plus précise des procédures qui fonctionnent, nous avons collecté les informations clefs sur sept systèmes métropolitains où les dispositifs de démocratie directe sont couramment utilisés par les citoyens : des villes Suisses, Los Angeles, San Francisco, le Lichtenstein, etplusieurs villes en Allemagne et en Autriche. Nous avons également analysé la procédure mise en place dans la Ville de Paris qui, à ce jour, n’a jamais réussi à obtenir le moindre succès

Étude des mécanismes de démocratie directe applicables à la ville de Grenoble

Ce rapport vise à fournir des pistes juridiques et techniques pour promouvoir la diffusion des référendums d’initiative populaire à Grenoble. Il y a deux difficultés principales qui expliquent en partie les échecs de ce type d’initiative en France, par rapport à d’autres pays comme l’Allemagne ou l’Autriche, les deux liées à la centralisation qui caractérise notre pays. Premièrement, les règles qui régissent les procédures de décision (c’est à dire qui décide comment les décisions vont être prises) sont fixées au niveau national, et les municipalités n’ont aucune compétence pour produire du droit en la matière. Deuxièmement, les compétences des mairies sont très faibles, ce qui offre moins d’opportunités aux citoyens de prendre desinitiatives. En dépit de ces deux contraintes, nous fournissons ici un ensemble de préconisations pour fournir une procédure qui garantisse à la fois sa légalité, un coût limité et son succès. Par « succès » nous entendons le fait que le dispositif soit réellement utilisé par les citoyens. Pour avoir une idée plus précise des procédures qui fonctionnent, nous avons collecté les informations clefs sur sept systèmes métropolitains où les dispositifs de démocratie directe sont couramment utilisés par les citoyens : des villes Suisses, Los Angeles, San Francisco, le Lichtenstein, etplusieurs villes en Allemagne et en Autriche. Nous avons également analysé la procédure mise en place dans la Ville de Paris qui, à ce jour, n’a jamais réussi à obtenir le moindre succès

Cell type-specific differences in β-glucan recognition and signalling in porcine innate immune cells

β-glucans exert receptor-mediated immunomodulating activities, including oxidative burst activity and cytokine secretion. The role of the β-glucan receptors dectin-1 and complement receptor 3 (CR3) in the response of immune cells towards β-glucans is still unresolved. Dectin-1 is considered as the main β-glucan receptor in mice, while recent studies in man show that CR3 is more important in β-glucan-mediated responses. This incited us to elucidate which receptor contributes to the response of innate immune cells towards particulate β-glucans in pigs as the latter might serve as a better model for man. Our results show an important role of CR3 in β-glucan recognition, as blocking this receptor strongly reduced the phagocytosis of β-glucans and the β-glucan-induced ROS production by porcine neutrophils. Conversely, dectin-1 does not seem to play a major role in β-glucan recognition in neutrophils. However, recognition of β-glucans appeared cell type-specific as both dectin-1 and CR3 are involved in the β-glucan-mediated responses in pig macrophages. Moreover, CR3 signalling through focal adhesion kinase (FAK) was indispensable for β-glucan-mediated ROS production and cytokine (TNFα, IL-1β, IL-8) production in neutrophils and macrophages, while the Syk-dependent pathway was only partly involved in these responses. We may conclude that as for man, CR3 plays a cardinal role in β-glucan signalling in porcine neutrophils, while macrophages use a more diverse receptor array to detect and respond towards β-glucans. Nonetheless, FAK acts as a master switch that regulates β-glucan-mediated responses in neutrophils as well as macrophages

Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer

Introduction: The PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes. Patients and methods: Eligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression. Results: At database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms. Discussion: Consistent with the primary results, adding pertuzumab to chemotherapy for low tumor HER3 mRNA-expressing platinum-resistant ovarian cancer did not improve overall survival, but showed trends in some cohorts. Except for increased diarrhea symptoms, pertuzumab had no impact on patient-reported outcomes. ClinicalTrials.gov: ClinicalTrials.gov: NCT01684878

Air pollution trends in the EMEP region between 1990 and 2012

The present report synthesises the main features of the evolution over the 1990-2012 time period of the concentration and deposition of air pollutants relevant in the context of the Convention on Long-range Transboundary Air Pollution: (i) ozone, (ii) sulfur and nitrogen compounds and particulate matter, (iii) heavy metals and persistent organic pollutants. It is based on observations gathered in State Parties to the Convention within the EMEP monitoring network of regional background stations, as well as relevant modelling initiatives. Joint Report of: EMEP Task Force on Measurements and Modelling (TFMM), Chemical Co-ordinating Centre (CCC), Meteorological Synthesizing Centre-East (MSC-E), Meteorological Synthesizing Centre-West (MSC-W)

Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer

Introduction: The PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes. Patients and methods: Eligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression. Results: At database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms. Discussion: Consistent with the primary results, adding pertuzumab to chemotherapy for low tumor HER3 mRNA-expressing platinum-resistant ovarian cancer did not improve overall survival, but showed trends in some cohorts. Except for increased diarrhea symptoms, pertuzumab had no impact on patient-reported outcomes. ClinicalTrials.gov: ClinicalTrials.gov: NCT01684878