Méthodologie pour l'évaluation des signaux émis par les technologies émergentes. : Applications à la compatibilité électromagnétique des systèmes et à l'exposition des personnes.

The knowledge of human exposure, either general public or occupational, to radiofrequency electromagnetic fields, is still incomplete. Two issues are yet to be addressed:•Knowledge of the uses of communicating objects that are ever changing,•The evaluation of the potential impact that these new technologies could have on the environment.This document provides a synthesis of studies conducted to address the issues of electromagnetic compatibility and human exposure. In this context, it was necessary to evaluate, to characterize and to define the most relevant parameters of the radiated signals or the levels of electromagnetic fields emitted by devices that implement these emerging technologies. We additionally examined related issues such as exposure to electromagnetic fields at very low frequencies induced by high-voltage lines or emissions from domestic equipment integrating potentially radiating electronic devices. It also includes a summary of all results obtained from actual case studies, in terms of the knowledge of both the detailed electromagnetic compatibility of new or emerging systems and human exposure. Finally, solutions have been proposed that can help to improve the knowledge of signals and potential impacts, through updates of either current standards by taking into account more relevant new parameters or modification of calibration procedures of the instrumentation employed to characterize the exposure.La connaissance de l’exposition des personnes aux champs électromagnétiques radiofréquences, pour le public ou pour les professionnels, est encore aujourd’hui très parcellaire. Deux problématiques sont encore mal connues:•La connaissance des usages des objets communicants, en évolution constante et rapide,•L'estimation de l'impact potentiel que pourraient avoir ces nouvelles technologies sur l'environnement.Ce document est une synthèse des travaux de recherche conduits pour affiner les questions de compatibilité électromagnétique et d’exposition des personnes. Dans ce contexte, il a fallu évaluer, caractériser et définir les paramètres les plus importants des signaux rayonnés ou des niveaux des champs électromagnétiques émis par les dispositifs mettant en œuvre les technologies émergentes. Dans cette étude, on s’est également intéressé à des problématiques connexes comme l’exposition des personnes aux champs électromagnétiques de très basses fréquences induits par des lignes à très haute tension ou aux émissions rayonnées par des équipements domestiques intégrant des dispositifs électroniques potentiellement rayonnants. Il comprend également, une synthèse de tous les résultats obtenus à partir d'études de cas concrets, tant sur le plan des connaissances détaillées de la compatibilité électromagnétique des systèmes nouveaux ou émergents que sur la problématique de l’exposition des personnes. Enfin, des solutions ont été proposées, pouvant permettre d’améliorer les connaissances des signaux et des impacts potentiels par des modifications de normes, par la prise en compte de nouveaux paramètres plus pertinents, ou par la modification de procédures d’étalonnage de systèmes utilisés pour caractériser l’exposition

Autisme : une médiation en-jouée

Ce mémoire s'interroge sur les apports de l'activité ludique dans la relation enseignant/enfant autiste. Le jeu y est analysé à travers sa fonction de médiation. Il propose un support réflexif de départ de ce que peut être la médiation en-jouée avec l'enfant autiste

Causal nonseparability and the structure of spacetime

Quantum nonseparability is central to most philosophical puzzles related to quantum mechanics. Yet, it is not an exclusive property of quantum mechanics, as it is also found in theoretical generalizations thereof. Investigating the implications of quantum nonseparability in a broader context could shed a new light on the conceptual problems in quantum physics. This work focuses on an operational theory called the process matrix formalism that generalizes quantum mechanics by relaxing the assumption of a well-defined causal structure. That broader theoretical context allows for the existence of quantum processes that are causally nonseparable, i.e. for which there is no definite global causal order among its interacting elements. Therefore, this notion of causal nonseparability somehow extends the notion of entanglement to the geometry of spacetime

Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice

The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4′,5′:4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial β-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial β-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system

Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice

The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4′,5′:4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial β-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial β-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system

Quantum Metaphysics and the Foundations of Spacetime

The main research programs in quantum gravity tend to suggest in one way or another that most (if not all) spacetime structures are not fundamental. At the same time, work in quantum foundations highlights fundamental features that are in tension with any straightforward space- time understanding. This paper aims to explore the little investigated but potentially fruitful links between these two fields

Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.Peer reviewedFinal Published versio

A comparison of collision cross section values obtained via travelling wave ion mobility-mass spectrometry and ultra high performance liquid chromatography-ion mobility-mass spectrometry : application to the characterisation of metabolites in rat urine

A comprehensive Collision Cross Section (CCS) library was obtained via Travelling Wave Ion Guide mobility measurements through direct infusion (DI). The library consists of CCS and Mass Spectral (MS) data in negative and positive ElectroSpray Ionisation (ESI) mode for 463 and 479 endogenous metabolites, respectively. For both ionisation modes combined, TWCCSN2 data were obtained for 542 non-redundant metabolites. These data were acquired on two different ion mobility enabled orthogonal acceleration QToF MS systems in two different laboratories, with the majority of the resulting TWCCSN2 values (from detected compounds) found to be within 1% of one another. Validation of these results against two independent, external TWCCSN2 data sources and predicted TWCCSN2 values indicated to be within 1-2% of these other values. The same metabolites were then analysed using a rapid reversed-phase ultra (high) performance liquid chromatographic (U(H)PLC) separation combined with IM and MS (IM-MS) thus providing retention time (tr), m/z and TWCCSN2 values (with the latter compared with the DI-IM-MS data). Analytes for which TWCCSN2 values were obtained by U(H)PLC-IM-MS showed good agreement with the results obtained from DI-IM-MS. The repeatability of the TWCCSN2 values obtained for these metabolites on the different ion mobility QToF systems, using either DI or LC, encouraged the further evaluation of the U(H)PLC-IM-MS approach via the analysis of samples of rat urine, from control and methotrexate-treated animals, in order to assess the potential of the approach for metabolite identification and profiling in metabolic phenotyping studies. Based on the database derived from the standards 63 metabolites were identified in rat urine, using positive ESI, based on the combination of tr, TWCCSN2 and MS data.</p