Modélisation du mouvement des chevreuils dans un paysage bocager simulé : premiers résultats, projets

Les tiques, dont Ixodes ricinus, espèce la plus répandue en Europe, sont vecteurs de nombreux agents pathogènes, protozoaires, bactéries ou virus, qui peuvent être responsables de maladies touchant l’Homme (Borreliose de Lyme) ou l’animal(babésiose bovine). En vue d’identifier les zones à risque vis-à-vis de ces maladies, il est important de connaître la distribution spatiale des tiques. Cette distribution dépend d’une part des conditions locales de température et d’humidité, d’autre part des mouvements des hôtes des tiques(Estrada-Peña, 2002). Les chevreuils sont notamment reconnus pour influencer fortement la densité de tiques(Ruiz-Fons et Gilbert 2010) et se déplacer sur de longues distances. Dans le cadre de l’estimation spatiale des risques, il est nécessaire de disposer d’un modèle de déplacement des hôtes en fonction des caractéristiques du paysage, dont le développement n’a pas été réalisé à ce jour. Dans un premier temps, une approche théorique a été privilégiée. Un modèle du paysage a été développé via une tesselation de Voronoï et un processus de marquage. Au sein de ce paysage modélisé, le mouvement du chevreuil est modélisé par des équations différentielles stochastiques. Ce mouvement se décompose donc en deux termes : un de dérive, qui dépend d’une fonction de potentiel reliée aux différents habitats qui composent le paysage, et un terme de diffusion. A partir d’une première fonction potentielle, il est donc possible de simuler le déplacement d’un individu dans un paysage modélisé. Les développements actuels visent dans un premier temps à tester différentes fonctions de potentiel en fonction de nos connaissances sur le comportement du chevreuil. L’étape suivante consistera à développer des méthodes d’inférence afin d’estimer les paramètres à partir de données simulées ou observées. Par la suite le prototype obtenu pourra être utilisé pour tester l’influence des caractéristiques du paysage sur le mouvement des chevreuils. Enfin, un couplage avec un modèle de dynamique de population de tiques (Hoch et al, 2010) fournira des aires de répartition simulées des vecteurs

A cluster-randomized trial to reduce caesarean delivery rates in Quebec: cost-effectiveness analysis.

BACKGROUND: Widespread increases in caesarean section (CS) rates have sparked concerns about risks to mothers and infants and rising healthcare costs. A multicentre, two-arm, cluster-randomized trial in Quebec, Canada assessed whether an audit and feedback intervention targeting health professionals would reduce CS rates for pregnant women compared to usual care, and concluded that it reduced CS rates without adverse effects on maternal or neonatal health. The effect was statistically significant but clinically small. We assessed cost-effectiveness to inform scale-up decisions. METHODS: A prospective economic evaluation was undertaken using individual patient data from the Quality of Care, Obstetrics Risk Management, and Mode of Delivery (QUARISMA) trial (April 2008 to October 2011). Analyses took a healthcare payer perspective. The time horizon captured hospital-based costs and clinical events for mothers and neonates from labour onset to 3 months postpartum. Resource use was identified and measured from patient charts and valued using standardized government sources. We estimated the changes in CS rates and costs for the intervention group (versus controls) between the baseline and post-intervention periods. We examined heterogeneity between clinical subgroups of high-risk versus low-risk pregnancies and estimated the joint uncertainty in cost-effectiveness over 20,000 trial simulations. We decomposed costs to identify drivers of change. RESULTS: The intervention group experienced per-patient reductions of 0.005 CS (95% confidence interval (CI): -0.015 to 0.004, P = 0.09) and $180 (95$277 to - $83, P < 0.001). Women with low-risk pregnancies experienced statistically significant reductions in CS rates and costs; changes for the high-risk subgroup were not significant. The intervention was "dominant" (effective in reducing CS and less costly than usual care) in 86.08$190, 95% CI: -$255 to -$125, P < 0.001). Given 88,000 annual provincial births, a similar intervention could save $15.8 million (range:$7.3 to $24.4 million) in Quebec annually. CONCLUSIONS: From a healthcare payer perspective, a multifaceted intervention involving audits and feedback resulted in a small reduction in caesarean deliveries and important cost savings. Cost reductions are consistent with improved quality of care in intervention group hospitals. TRIAL REGISTRATION: International Clinical Trials Registry Platform, ISRCTN95086407 . Registered on 23 October 2007

Why cave planthoppers study matters: are Cixiidae a subtroglophile lineage? (Hemiptera, Fulgoromorpha)

Planthoppers are an interesting and contrasting model among insects for studying the subterranean environments. Their morphological and ethological adaptations to the underground conditions (complete darkness, lower temperatures, high hygrometry, stability of environmental constants, rarefied food sources, etc.), and their worldwide distribution in both temperate and tropical areas make them an interesting model among invertebrates. In this review, we highlight why cave planthoppers study matters, with particular emphasis on the Cixiidae. The two hypotheses proposed, the ‘climatic relict hypothesis’ and the ‘adaptive shift’, are not sufficient enough to clearly understand and explain the drivers to cavernicoly. Phylogenetic analyses approaches might help to better document and increase our knowledge on such peculiar environments. The singularity of the distribution pattern of the adaptation to cavernicoly in planthoppers raises also interesting questions to investigate and suggest contrasting scenarios to explore further, particularly should the Cixiidae be defined as a subtroglophile lineage

Development of an In Vitro Model for the Multi-Parametric Quantification of the Cellular Interactions between Candida Yeasts and Phagocytes

We developed a new in vitro model for a multi-parameter characterization of the time course interaction of Candida fungal cells with J774 murine macrophages and human neutrophils, based on the use of combined microscopy, fluorometry, flow cytometry and viability assays. Using fluorochromes specific to phagocytes and yeasts, we could accurately quantify various parameters simultaneously in a single infection experiment: at the individual cell level, we measured the association of phagocytes to fungal cells and phagocyte survival, and monitored in parallel the overall phagocytosis process by measuring the part of ingested fungal cells among the total fungal biomass that changed over time. Candida albicans, C. glabrata, and C. lusitaniae were used as a proof of concept: they exhibited species-specific differences in their association rate with phagocytes. The fungal biomass uptaken by the phagocytes differed significantly according to the Candida species. The measure of the survival of fungal and immune cells during the interaction showed that C. albicans was the more aggressive yeast in vitro, destroying the vast majority of the phagocytes within five hours. All three species of Candida were able to survive and to escape macrophage phagocytosis either by the intraphagocytic yeast-to-hyphae transition (C. albicans) and the fungal cell multiplication until phagocytes burst (C. glabrata, C. lusitaniae), or by the avoidance of phagocytosis (C. lusitaniae). We demonstrated that our model was sensitive enough to quantify small variations of the parameters of the interaction. The method has been conceived to be amenable to the high-throughput screening of mutants in order to unravel the molecular mechanisms involved in the interaction between yeasts and host phagocytes

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival