Multiple factors affecting Ixodes ricinus ticks and associated pathogens in European temperate ecosystems (northeastern France).

In Europe, the main vector of tick-borne zoonoses is Ixodes ricinus, which has three life stages. During their development cycle, ticks take three separate blood meals from a wide variety of vertebrate hosts, during which they can acquire and transmit human pathogens such as Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis. In this study conducted in Northeastern France, we studied the importance of soil type, land use, forest stand type, and temporal dynamics on the abundance of ticks and their associated pathogens. Negative binomial regression modeling of the results indicated that limestone-based soils were more favorable to ticks than sandstone-based soils. The highest tick abundance was observed in forests, particularly among coniferous and mixed stands. We identified an effect of habitat time dynamics in forests and in wetlands: recent forests and current wetlands supported more ticks than stable forests and former wetlands, respectively. We observed a close association between tick abundance and the abundance of Cervidae, Leporidae, and birds. The tick-borne pathogens responsible for Lyme borreliosis, anaplasmosis, and hard tick relapsing fever showed specific habitat preferences and associations with specific animal families. Machine learning algorithms identified soil related variables as the best predictors of tick and pathogen abundance.

Computation of the conditions for anti-angiogenesis and gene therapy synergistic effects: Sensitivity analysis and robustness of target solutions.

Both anti-angiogenesis and gene therapy involve complex processes depending on non-point parameters belonging to a space of values. To successfully overcome the challenges involved in their therapeutic approaches, there is a need to analyze the sensitivity of these parameters. In this paper, a new mathematical model that combines immune system stimulations, inflammatory processes associated with tumor development, and gene therapy aimed at enhancing the efficacy of both treatments are explored. Using the global sensitivity methods of Sobol and Morris, the most important parameters are estimated. Estimation of the sensitivity variance revealed a strong interdependence between the parameters. Also, determinations of the conditions for effective therapy lead to a target of reducing the cancer cell numbers by at least 50%. This opened the way for delimiting the parameter spaces making it possible to reach the treatment target in addition to enhancing the estimation of the minimum time of remission. The combination of therapies and sensitivity analysis have demonstrated the robustness of therapy success.

Microplastics enhance Daphnia magna sensitivity to the pyrethroid insecticide deltamethrin: Effects on life history traits.

The aim of the study was to investigate the influence of microplastics (MPs) on the ecotoxicity of common contaminants of aquatic ecosystems. As a model contaminant, the hydrophobic pesticide deltamethrin (DM) was chosen, and its effects on life history traits of Daphnia magna were studied in the presence or absence of polyethylene MPs. Commercialized DM and MPs obtained as dry powder were used in the experiment. According the manufacturer (Cospheric, Santa Barbara, CA, USA) MPs were spherical (1-4 µm in diameter), had a density of 0.96 g/cm-3 and were without any solvent. Three concentrations of polyethylene MPs were tested (0, 1, 10 mg/L) with two realistic concentrations of DM (0 and 40 ng/L) and a solvent control (acetone). During the 21 d experiment, D. magna neonates were individually exposed to the treatments, and the effects of MPs and DM alone and together were evaluated by assessing survival, number of cumulative molts, days to first brood, number of broods, number of neonates per surviving adult, and body length. Significant detrimental effects on survival were only observed for the two mixture treatments. DM alone (40 ng/L) delayed the days to first brood and reduced the number of neonates per surviving adult, whereas MPs alone (10 mg/L) induced significant reduction in the number of juveniles by surviving adults. The combined exposure to DM and MPs clearly had a synergistic effect on survival, brood number, and number of neonates per surviving female. For example, compared to exposure to 40 ng/L of DM alone, the addition of 1 mg/L of MPs resulted in a 51.1% reduction in number of neonates per surviving female and a 46% reduction in brood number. These results suggest the potential drastic effects of this kind of mixed exposure on daphnid populations, which are key components of freshwater food webs.

Combined acute ecotoxicity of malathion and deltamethrin to Daphnia magna (Crustacea, Cladocera): comparison of different data analysis approaches.

We studied the combined acute effect (i.e., after 48 h) of deltamethrin (a pyrethroid insecticide) and malathion (an organophosphate insecticide) on Daphnia magna. Two approaches were used to examine the potential interaction effects of eight mixtures of deltamethrin and malathion: (i) calculation of mixture toxicity index (MTI) and safety factor index (SFI) and (ii) response surface methodology coupled with isobole-based statistical model (using generalized linear model). According to the calculation of MTI and SFI, one tested mixture was found additive while the two other tested mixtures were found no additive (MTI) or antagonistic (SFI), but these differences between index responses are only due to differences in terminology related to these two indexes. Through the surface response approach and isobologram analysis, we concluded that there was a significant antagonistic effect of the binary mixtures of deltamethrin and malathion that occurs on D. magna immobilization, after 48 h of exposure. Index approaches and surface response approach with isobologram analysis are complementary. Calculation of mixture toxicity index and safety factor index allows identifying punctually the type of interaction for several tested mixtures, while the surface response approach with isobologram analysis integrates all the data providing a global outcome about the type of interactive effect. Only the surface response approach and isobologram analysis allowed the statistical assessment of the ecotoxicological interaction. Nevertheless, we recommend the use of both approaches (i) to identify the combined effects of contaminants and (ii) to improve risk assessment and environmental management.

Mathematical modeling of glioma therapy using oncolytic viruses.

Diffuse infiltrative gliomas are adjudged to be the most common primary brain tumors in adults and they tend to blend in extensively in the brain micro-environment. This makes it difficult for medical practitioners to successfully plan effective treatments. In attempts to prolong the lengths of survival times for patients with malignant brain tumors, novel therapeutic alternatives such as gene therapy with oncolytic viruses are currently being explored. Based on such approaches and existing work, a spatio-temporal model that describes interaction between tumor cells and oncolytic viruses is developed. Conditions that lead to optimal therapy in minimizing cancer cell proliferation and otherwise are analytically demonstrated. Numerical simulations are conducted with the aim of showing the impact of virotherapy on proliferation or invasion of cancer cells and of estimating survival times.