ED Sciences Chimiques
Study of biogenic secondary organic aerosols: characterization of molecular markers and their heterogeneous reactivity of atmospheric interest
by Pauline POUYES (Environnements et Paléoenvironnements Océaniques et Continentaux)
The defense will take place at 14h00 - Salle de conférence de l'ISM Université de Bordeaux Campus Peixotto Bâtiment A12 - 3ème étage est 351 cours de la libération 33400 Talence
in front of the jury composed of
- Eric VILLENAVE - Professeur des universités - Université de Bordeaux - CoDirecteur de these
- Alexandre ALBINET - Cadre scientifique des EPIC - INERIS - Rapporteur
- Alexandre TOMAS - Professeur - IMT Nord Europe - Rapporteur
- Aline GRATIEN - Maîtresse de conférences - Université Paris Cité - Examinateur
- Karine SARTELET - Directrice de recherche - CEREA Ecole des Ponts - Examinateur
- Williams ESTEVE - Chargé de recherche - INRS - Examinateur
- Véronique DAELE - Directrice de recherche - CNRS-ICARE - Examinateur
- Emilie PERRAUDIN - Maîtresse de conférences - Université de Bordeaux - CoDirecteur de these
Among the main environmental issues, secondary atmospheric aerosols, whose emissions cannot be regulated, have been the focus of much attention for several years because of their impact on both climate change and air quality. The aim of this work was to study the main tracers of secondary organic aerosols (SOA) produced by the oxidation of terpenes emitted by vegetation. Two complementary aspects were studied experimentally both on the field and in laboratory. The first one focused on the chemical characterisation at the molecular scale of atmospheric particles collected during intensive field campaigns in the Landes and Rambouillet forests, using liquid chromatography coupled with time-of-flight mass spectrometry, to better understand biosphere-atmosphere interactions. The second part dealt with atmospheric markers in the particulate phase, and more specifically with the limitations of their use as tracers of aerosol sources as well as formation and fate processes, related to heterogeneous (photo-)chemical degradation, which has been very poorly documented to date. Thus, the reactivity at the gas-particle interface of 6 tracers (i.e. terebic, terpenylic, pinonic, pinic, β-caryophyllinic acids and MBTCA) generated from the oxidation of α- and β-pinene as well as β-caryophyllene, was investigated with hydroxyl radicals, ozone or by photodegradation, to determine their atmospheric lifetimes.
Studies of molecular monolayers by linear and non-linear optical spectroscopies
by Simon DUBUIS (Institut des Sciences Moléculaires)
The defense will take place at 14h30 - Salle Agora 43 Rue Pierre Noailles, Bâtiment Haut-Carré, 33400 Talence
in front of the jury composed of
- Vincent RODRIGUEZ - Professeur des universités - Université de Bordeaux - Directeur de these
- Hélène SERIER-BRAULT - Maîtresse de conférences - Institut des Matériaux de Nantes - Nantes Université - Rapporteur
- Koen CLAYS - Professeur des universités - Molecular Imaging and Photonics, KU Leuven - Rapporteur
- Marc DUSSAUZE - Directeur de recherche - Institut des Sciences Moléculaires - Université de Bordeaux - Examinateur
- Céline OLIVIER - Chargée de recherche - Institut des Sciences Moléculaires - Université de Bordeaux - Examinateur
- Philippe LEPROUX - Maître de conférences - XLim Université Limoges - Examinateur
Photocommutable molecules exhibiting different nonlinear optical responses (NLO) between two states are particularly promising for information encoding and storage applications at the molecular scale. This thesis focuses on two families of photocommutable molecules: azobenzenes and Donor-Acceptor Stenhouse adducts (DASA). We studied their linear optical properties using UV-Visible absorption spectroscopy in solution. The quadratic ONL responses of the molecules were characterized by hyper-Rayleigh scattering. We explored different molecular architectures of azobenzenes and DASA promoting photocommutation kinetics and strong ONL response, by varying the electron-acceptor and electron-donor moieties. An experimental setup was also developed to monitor photocommutation kinetics in real time. In the second part, devoted to the study of these molecules grafted onto glass slides in the form of self-assembled monolayers (SAM), only azobenzene SAMs in an ONL-active form were obtained and characterized. We investigated their anisotropic linear optical properties by UV-Visible polarized reflection-absorption spectroscopy (UV-Vis RAS). From these polarization studies, we were able to experimentally estimate the surface concentration of azobenzene (typically of the order of one molecule per nm²), from a simple model based on the average absorption in solution and in monolayer. The quadratic ONL responses of the SAMs were characterized by polarized second harmonic reflection (R-SHG). To carry out these studies, we developed and optimized a high-performance R-SHG reflectometer. We were able to demonstrate the high selectivity and sensitivity of this R-SHG setup dedicated to the study of interfaces between air and the probed medium. A wide range of incident and reflected polarization measurements, including surface imaging (spatial resolution ~5x20 µm²), were used to characterize the SHG response of SAMs and assess their homogeneity on a scale of a few micrometers. Using R-SHG measurements, we were able to evaluate the main ONL susceptibilities ratio. Finally, from the linear dichroism and the main ONL susceptibilities ratio obtained by UV-Vis RAS and R-SHG respectively, we determined the orientation distribution functions of the photochromes using an entropy-maximizing statistical approach. These novel approaches enable us to estimate the π-π and dipole-dipole interaction effects present in the different azobenzenes.
ED Droit
French and Mexican legal doctrine in the face of contemporary revolutions: conservative reactions to paradigm shifts (1789-2000)
by Juan Fernando ARGUIJO HOYO (INSTITUT DE RECHERCHE MONTESQUIEU)
The defense will take place at 14h00 - Salle des thèses Avenue Léon Duguit 33608 Pessac
in front of the jury composed of
- Nader HAKIM - Professeur des universités - Université de Bordeaux - Directeur de these
- Fabrice MELLERAY - Professeur des universités - École de droit de Sciences Po - Rapporteur
- Annamaria MONTI - Professeure des universités - Université de Milan - Rapporteur
- Oscar CRUZ BARNEY - Professeur - Instituto de Investigaciones Jurídicas, UNAM - CoDirecteur de these
- Laëtitia GUERLAIN - Professeure des universités - Université de Bordeaux - Examinateur
- Anna NEYRAT - Maîtresse de conférences - Sciences Po Bordeaux - Examinateur
- Florent GARNIER - Professeur des universités - Université de Toulouse - Examinateur
- Pierre BONIN - Professeur des universités - Université Panthéon-Sorbonne - Examinateur
The aim of this work is to show how the French Revolution of 1789 led in the 20th century, in Mexico and France, to a conservative paradigm that we call the “new tradition”. Indeed, following the Revolution of 1789, a “legalistic” paradigm emerged in France and Mexico. However, at the turn of the century, this old law-based model came up against a new “social” paradigm, which sought to adapt the law to social evolution. This period of struggle in French and Mexican legal doctrines resulted in a new paradigm synthesizing the two previous ones, that of the new tradition.
ED Entreprise Economie Société
The sustainability drivers of Henokien companies: construction of an explanatory conceptual model. The case of Henokian SMEs in the New Aquitaine region
by Meriem GHARBI (IRGO - Institut de Recherche en Gestion des Organisations)
The defense will take place at 9h00 - C107 Institut de Recherche en Gestion des Organisations - IRGO PUSG 35, avenue Abadie CS 51412 33072 Bordeaux cedex
in front of the jury composed of
- Christian PRAT DIT HAURET - Professeur des universités - Université de Bordeaux - Directeur de these
- Gérard HIRIGOYEN - Professeur émérite - Université de Bordeaux - CoDirecteur de these
- Martine HLADY RISPAL - Professeure des universités - Université de Limoges (IAE Limoges) - Rapporteur
- Thierry POULAIN-REHM - Professeur des universités - La Rochelle Université - Rapporteur
- Jean-Pierre MATHIEU - Professeur émérite - ISPI - Examinateur
- Amélie VILLéGER - Maître de conférences - Université de Bordeaux - Examinateur
In a current context marked by growing uncertainty, the survival of companies and their solidity in the face of the unexpected is more of a question than ever. The resilience and sustainability of companies are then at the heart of the concerns and speeches of decision-makers, leaders and managers. This craze for the survival and longevity of companies suggests that the vast majority of companies are doomed to disappear after a few decades of existence at most. It is surprising then to note the existence of companies that defy these statistics by accumulating more than a hundred years of longevity and by managing to preserve their family character since their creation. This sustainability then raises the questions and curiosity of any researcher who studies this very particular category of organizations. As a result, this doctoral work aims to understand how these companies were able to survive and remain sustainable for several decades or even centuries, through the study and identification of the factors of their sustainability. To do this, this research is based on the study of a sample of small and medium-sized French family businesses (SMEs) called "Hénokiennes", located in the Nouvelle Aquitaine region. Indeed, these century-old companies undoubtedly embody the best of entrepreneurship and would be carriers of a model of sustainability that could constitute an alternative to classic models. Adopting a constructivist posture, this research is based on a qualitative methodology based on a multiple case study. The abductive reasoning mode is retained for this purpose. This work is composed of two parts: - A theoretical part from which the theoretical framework of the research as well as the corpus of theoretical propositions will be identified: a review of the literature on the theme of the sustainability of EFs will be conducted first. Then, to refine and outline the empirical approach, theoretical axes of research relating to the governance of family businesses, their resilience and their strategic capabilities will be identified and analyzed. - An empirical part devoted to explaining the research methodology chosen, analyzing the cases and presenting the research results: the case analysis is carried out in two phases: a first step in which an individual analysis of each case is carried out: this is the intra-case analysis. This is followed by a comparative analysis aimed at identifying trends and results common to the individual case studies: this is the inter-case analysis. Finally, we close this study by proposing a conceptual model to explain the sustainability of Henokian SMEs, the latter constituting the ultimate objective of this research.
ED Sciences de la Vie et de la Santé
Activities of novel stilbenoids in breast cancer models: monolayer and spheroid cultures
by Ayoub JAA (Oenologie)
The defense will take place at 15h00 - Salla de grados Barrio Sarriena, s/n, Facultad de Medicina y Enfermería, 48940 Leioa, Vizcaya
in front of the jury composed of
- María Luisa HERNANDEZ FRIAS - Professeure - Universidad del País Vasco, Facultad de Medicina y Enfermería - Examinateur
- Consuelo BORRAS BLASCO - Professor - Universitat de València, Facultad de Medicina - Examinateur
- Víctor Manuel VICTOR GONZALEZ - Professeur - Universitat de València - Rapporteur
- Isabelle BESTEL - Professeure - Université de Bordeaux, UMR-CNRS 5248, Chemistry & Biology of membranes and nano-objects - Examinateur
- Djebbar ATMANI - Professeur - Université de Béjaïa, Faculté des Sciences de la Nature et de la vie - Rapporteur
Breast cancer is among the most frequently diagnosed malignancies worldwide and represents the most prevalent neoplasm in women. Despite significant advancements in therapeutic strategies, the treatment of breast cancer continues to encounter substantial challenges. Current research efforts are directed toward the identification of novel therapeutic targets and the exploration of natural compounds with potential anticancer properties. Stilbenes, a class of polyphenolic compounds, have been extensively documented for their diverse biological activities, including antifungal, anti-inflammatory, and anticancer effects. In this context, a three-dimensional (3D) model was developed to enhance the screening of the biological activities of stilbenes. Stilbenes are known to undergo various chemical transformations. In this thesis, we investigated the oligomerization of trans-resveratrol and trans-piceid, as well as their isomerization under ultraviolet (UV) irradiation. These chemical processes resulted in the formation of novel stilbene derivatives. The biological activities of these newly derived compounds were evaluated in the context of breast cancer. Initially, the compounds' effects were assessed in monolayer cell cultures, and the results were subsequently compared with those obtained in 3D models. Among the nine stilbenes tested, r2-viniferin exhibited the highest cytotoxicity, demonstrating potent anticancer activity in both monolayer and 3D models. Notably, r2-viniferin did not exhibit cytotoxic effects on non-tumorigenic mammary epithelial cells. The findings presented in this study confirm the anticancer potential of r2-viniferin and underscore its promising therapeutic potential as a candidate for breast cancer treatment.
Development and Evaluation of New MRI-guided Laser Therapy Techniques - Application to the Treatment of Prostate Cancer
by Clément MARCELIN (BoRdeaux Institute of onCology)
The defense will take place at 14h00 - salle broussin delorme CHU Bordeaux Pellegrin Service d'imagerie médicale
in front of the jury composed of
- Nicolas GRENIER - Professeure des universités - praticienne hospitalière - Université de Bordeaux - Directeur de these
- vania TACHER - Professeure des universités - praticienne hospitalière - Hôpital Henri-Mondor - Rapporteur
- hélène VERNHET-KOVACSIK - Professeur des universités - praticien hospitalier - Hôpital Arnaud de Villeneuve - Examinateur
- eva JAMBON - Praticien hospitalier - chu bordeaux - Examinateur
- julien FRANDON - Professeure des universités - praticienne hospitalière - CHU Nimes - Rapporteur
MRI (Magnetic Resonance Imaging) is the reference imaging examination for the prostate to detect tumor targets, using a multiparametric protocol that includes T2, diffusion, and T1 sequences with gadolinium injection. A prognostic PIRADS score is derived from the various sequences, and if lesions with a high probability of malignancy (PIRADS 4 and 5) are found, a targeted biopsy is performed. Minimally invasive ablations, known as focal treatments, are increasingly being developed: HIFU, cryotherapy, laser, etc. For the guidance of these therapies, ultrasound remains the most commonly used technique due to its availability, but with lower sensitivity than MRI. Therefore, ablations are now performed under ultrasound guidance with MRI image fusion. To better cover the lesion volume, measuring temperature variations throughout the treatment is necessary; MRI is capable of measuring these variations, allowing for the anticipation of ablation efficacy. Temperature mapping is possible, as demonstrated in cardiac MRI during radiofrequency ablation procedures at the IHU in Bordeaux. MRI thermometry is based on the principle of the change in magnetic resonance frequency of water protons depending on temperature. When tissues are subjected to an increase in temperature, the molecular movements of water protons intensify, leading to a broadening of nuclear magnetic resonance (NMR) lines. This results in a shift in the resonance frequency of water protons, which is measured by MRI. This MRI thermometry method offers high spatial resolution, allowing for precise real-time mapping of temperature changes within targeted tissues. We focused on the prostates of patients undergoing screening for prostate tumors or assessment of prostatic adenomas. This prospective study included 56 adults undergoing prostate MRI on 1.5-T and 3-T MR systems. The MR-thermometry sequence consisted of 2D-multislice segmented Echo Planar Imaging. The proportion and location of "outlier voxels" in the prostate (with a temporal standard deviation above 2°C) were assessed per patient and compared between 1.5-T and 3-T. Clinical and technical variables were documented and correlated with the proportion of noisy voxels. Temperature processing was checked by performing an ablation on an ex vivo muscle with the same sequence and comparing the temperature of two sensors to the corresponding voxels. Temperature processing was validated. Of the 51 patients analyzed, 24 had MRIs at 3-T. The overall proportion of noisy voxels was 12.1% at 1.5-T and 3.3% at 3-T, almost evenly distributed in the prostate. No clinical or technical variables were associated with the proportion of noisy voxels (P > 0.05). Additionally, we tested this thermometry sequence during hepatic Microwave ablations in pigs. The results show that the isodose at 120 CEM43 can be a useful method for estimating the size of the ablation lesion, but it has certain limitations in precision. The lesion measurements obtained by post-gadolinium T1 MRI imaging were on average slightly larger than those based on the isodose at 120 CEM43. This suggests that thermal dose estimation may underestimate the actual lesion size in some cases. In conclusion, the thermometry sequence allowed the generation of highly relevant temperature maps on the human prostate and temperature maps during ablations in pigs with reliable results.
Computational approaches for the analysis and modeling of atypical sensory experience in autism
by Théo GAUVRIT (Neurocentre Magendie)
The defense will take place at 14h00 - Amphithéatre ENSTBB 146 Rue Léo Saignat, 33000 Bordeaux Université Bordeaux campus Carrere Bâtiment ENSTBB
in front of the jury composed of
- Andréas FRICK - Directeur de recherche - Université de Bordeaux- INSERM - Directeur de these
- Elizabeth MILNE - Professeur - Université de Sheffield - Rapporteur
- Brice BATHELLIER - Directeur de recherche - Institut de l'audition, Institut Pasteur, INSERM, Université Paris-Cité - Rapporteur
- Ian DUGUID - Professeur - University of Edinburgh - Examinateur
- Susanna PIETROPAOLO - Chargée de recherche - Université de Bordeaux - CNRS - Examinateur
How does the brain encode the perception of sensory stimuli in our environment? This question, still not fully answered, becomes even more intriguing in the context of autism, a neurodevelopmental condition characterized by atypical sensory experience as one of its core symptoms. These sensory alterations, often manifesting as hyper- or hyporeactivity or variability in sensory responses, are present in the vast majority of autistic individuals, have a strong impact on their daily lives, and contribute to other core symptoms of the condition. Strong neurophysiological alterations in the brain are suspected to drive these symptoms, but limited research leaves the underlying mechanisms and potential therapeutic targets unclear. We adopted a preclinical translational approach to investigate the neurobiological underpinnings of atypical sensory experience in the tactile domain. This involved recording spontaneous and stimulus-evoked neuronal activity at the single-neuron level in the primary somatosensory cortex (S1) of anesthetized mice of the well-established Fmr-/y mouse model of autism. This was followed by characterization of the S1 population activity with single-cell resolution in behaving animals during a perceptual decision-making task in the same mouse model. Examining spontaneous and stimulus-evoked neuronal activity in single neurons within the S1, we identified significant trial-by-trial variability in the neuronal responses of Fmr1-/y mice, a hallmark of atypical sensory processing in autistic individuals. We traced the sources of this variability to increased endogenous neuronal noise, manifesting as random fluctuations in neuronal activity, and to network instability, characterized by rapid, inconsistent, and contrasting states. This elevated noise and instability impair the integration of sensory information in the cortex and may contribute to the sensory perception variability observed in clinical studies of autism. Furthermore, the local (within S1) application of a BkCa channel agonist reduced local neuronal hyperexcitability and corrected many synaptic response features and their variance, but had little effect on the trial-by-trial variability, suggesting that this variability and hyperexcitability are less closely coupled than previously thought. To evaluate the impact of these neuronal alterations on tactile detection, we combined a translational decision-making task (back-translated from human studies) with functional imaging in S1. Our results recapitulated the multifaceted tactile alterations seen in autistic individuals, with tactile hyposensitivity, interindividual variability, and unreliable behavioral responses in Fmr1-/y mice. By examining the evoked activity of pyramidal and GABAergic neurons, we found that this altered tactile perception could be explained by weak stimulus encoding in S1, rendering stimulus detection more vulnerable to ongoing network states and thus less reliable. By reducing local hyperexcitability in S1 using an agonist of BkCa channels, we were able to strengthen stimulus encoding and thus improve tactile detection in Fmr1-/y mice. Our results emphasize the critical role of neuronal noise and variability in sensory information processing and the role of hyperexcitability and network states in shaping sensory perception. This translational approach offers mechanistic insight into the neural foundations of atypical tactile perception in autism and underscores the therapeutic potential of targeting these neural mechanisms to enhance sensory sensitivity and reliability in autistic individuals.
Cloning, engineering and transfer of large genome fragments in Bacillus subtilis.
by Julien BARRET (BFP - Biologie du Fruit et Pathologie)
The defense will take place at 14h00 - Amphithéâtre de l'ISVV 210, chemin de leysotte 33882 Villenave d'Ornon
in front of the jury composed of
- Anne-Gaëlle PLANSON - Chargée de recherche - Université Paris-Saclay, INRAE, AgroParisTech - Examinateur
- Anaïs LE RHUN - Chargée de recherche - Université de Bordeaux - Examinateur
- Christophe DANELON - Professeur - TBI - INSA - Rapporteur
- Guillaume CAMBRAY - Chargé de recherche - Centre de Biologie Structurale (CBS) - Rapporteur
- François DOIGNON - Professeur - Université de Bordeaux - Examinateur
- Matthieu JULES - Professeur - Université Paris-Saclay, AgrosParisTech - Examinateur
Genome engineering of microorganisms has become a standard in microbial biotechnology. In 2010, promising synthetic biology technologies using yeast as a platform for the assembly and engineering of synthetic bacterial genomes followed by their transplantation into a recipient cell have emerged. These technologies have led to the creation of the first synthetic cells and opened new avenues towards the construction of cells with fully controlled biological properties. Transferring these tools to microorganisms of industrial interest such as the Gram+ bacterium Bacillus subtilis (Bsu), a model in the biotechnology sector, would be a major step forward. This is precisely the aim of the ANR "Bacillus 2.0" project, which brings together two INRAE teams and aims to adapt all these synthetic biology tools to Bsu so as to be able to go from computer-aided design of semi-synthetic Bsu genomes to the production of new industrial strains. However, initial work on this project showed that the entire Bsu genome could not be cloned and maintained in yeast in its current state. These results threatened to call into question the feasibility of the entire project and, in particular, the relevance of using yeast as a platform for assembling the semi-synthetic Bsu genome. The goal of my thesis was to demonstrate that yeast remained a relevant host for the Bacillus 2.0 project. It was divided into 3 parts. In the first part, a genome cloning method recently developed in the laboratory, called CReasPy-Fusion, was progressively adapted to Bsu. The results obtained showed (i) the possible transfer of plasmid DNA between bacterial protoplasts and yeast spheroplasts, (ii) the efficiency of a CRISPR-Cas9 system carried by yeast cells to capture/modify this plasmid DNA during Bsu/yeast fusion, and then (iii) the efficiency of the same system to capture genomic fragments of about a hundred kb from three different strains. Fluorescence microscopy observations were also carried out revealing two types of interaction that would enable the transition from protoplast/spheroplast contact to cloned bacterial DNA in yeast. In the second part of my thesis, the CReasPy-Fusion method was used in an attempt to clone large Bsu genome fragments in yeast. Genomic fragments of up to ~1 Mb could be cloned in yeast, but their capture required the prior addition of a large number of ARS to the Bsu genome to stabilize the genetic constructs. The final part was the adaptation of the RAGE method to Bsu. This method allow the transfer, not of a whole genome, but of portions of bacterial genomes from yeast to the bacteria to be edited. Proof of concept was achieved by exchanging a 155 kb genome fragment with a reduced 44 kb version. In conclusion, the work carried out during this thesis has shown the relevance of using yeast as an engineering platform for large-scale modifications of the Bsu genome. On the one hand, we have shown that fragments of around 100 kb can be cloned in yeast, modified and transferred into a recipient cell to generate Bsu mutants. This strategy offers a real alternative to genome transplantation. On the other hand, we have shown that large fragments of the Bsu genome (up to 1 Mb) can also be cloned in yeast, provided they contain numerous ARS in their sequences. Thanks to these results, cloning a reduced Bsu genome in yeast has once again become an achievable goal.
Effect of protein therapies on the gut-lung axis in cystic fibrosis
by Florian LUSSAC-SORTON (Centre de recherche Cardio-Thoracique de Bordeaux)
The defense will take place at 13h30 - Amphithéâtre de l'IHU IHU Liryc Hôpital Xavier Arnozan Avenue du Haut-Lévêque 33600 PESSAC
in front of the jury composed of
- Laurence DELHAES - Professeure des universités - praticienne hospitalière - Université de Bordeaux - Directeur de these
- Hélène YERA - Professeure des universités - praticienne hospitalière - Université de Limoges - Rapporteur
- Jean MENOTTI - Maître de conférences - praticien hospitalier - Université Claude Bernard Lyon 1 - Rapporteur
- Emmanuel RICHARD - Professeur des universités - praticien hospitalier - Université de Bordeaux - Examinateur
Cystic fibrosis is a multi-organ disease whose progression is mainly determined by respiratory and digestive damage. The advent of CFTR modulators has revolutionized its prognosis over the last decade. Alterations in microbiota and mycobiota have been well described in cystic fibrosis, as have, to a lesser extent, the inter-organ connections defining the gut-lung axis. Yet there is still a lack of data regarding the impact of protein therapies on the mycobiota-microbiota. The LUM-IVA-BIOTA protocol is a national multicentric study designed to decipher the evolution of mycobiota-microbiota and inflammation in patients receiving the lumacaftor-ivacaftor (LUM/IVA) combination, using targeted metagenomic approaches. The first part of this work, involving patients over 12 years of age, showed that the effect of LUM/IVA on lung microbiota depended on chronic colonization with Pseudomonas aeruginosa. The next stage of the project involved a cohort of children aged 2 to 11 and demonstrated improvements in lung and gut microbiotas on LUM/IVA with changes in the gut-lung axis, while confirming the key role of P. aeruginosa colonization in improving lung microbiota. These results highlight that protein therapies can improve the diversity of microbial florae within the gut-lung axis if initiated early on, before the turning point of P. aeruginosa colonization. These findings need to be further confirmed in patients receiving next-generation modulators such as the elexacaftor-tezacaftor-ivacaftor triple therapy.
Role of extracellular space in neurodegenerative diseases
by Juan ESTAUN PANZANO (Institut des Maladies Neurodégénératives)
The defense will take place at 12h00 - Amphithéâtre Centre Broca, 1 Rue Leo Saignat, 33000, Bordeaux
in front of the jury composed of
- Erwan BEZARD - Directeur de recherche - Université de Bordeaux - Directeur de these
- Federico SORIA - Directeur de recherche - Ikerbasque Research Fellow, Basque Center for Neuroscience - Rapporteur
- Rosaria MORATALLA - Professeure des universités - Cajal Institute - Rapporteur
- José A. OBESO - Professeur des universités - praticien hospitalier - CEU-San Pablo University - Examinateur
The ECS, comprising the narrow compartment between the cells filled with interstitial fluid and extracellular matrix it is key for communication between neurons and glial cells and is vital for maintaining brain homeostasis. In this work, we try to shed some light in the relation between proteinopathies, particularly synucleinopathies and amyloid pathologies, and the extracellular space (ECS) within the brain. Proteinopathies, a class of neurodegenerative diseases characterized by the abnormal accumulation of misfolded proteins, such as α-synuclein and amyloid-beta. These protein accumulations are known to disrupt normal brain functions, but their impact on the brain's ECS, which plays a critical role in molecular diffusion and waste clearance, has not been thoroughly examined. This introduction presents an overview of amyloid and a-synuclein pathology and ECS and its components, focusing on the extracellular matrix and diffusion processes within the ECS. Furthermore, the glymphatic system, a proposed waste-clearance mechanism linked to the ECS, is discussed. Understanding these mechanisms is crucial for interpreting how the ECS is altered in proteinopathies. Additionally, the study reviews current techniques used to investigate the ECS, including traditional methods as well as advanced imaging and single-particle tracking techniques. The study investigates the structural and rheological changes in the ECS in two different models of proteinopathies, focusing on the altered diffusion properties within this space and its implications for disease pathology. To address these questions, a variety of advanced techniques were employed. First, we repot ECS diffusivity changes in the striatum of a mouse synucleinopathy model. Using SWCNTs tracking in the ECS, the study demonstrates that intracellular α-synuclein assemblies can significantly alter nanoscale diffusion in the striatal ECS. We repeat the same approach in an amyloid mouse model (APP/PS1), with special focus on diffusion alterations around amyloid plaques and its fine relationship with matrix disruptions. We employed a complementary set of nanoscopic imaging techniques to investigate the ECS alterations in a mouse AD model. Two-photon shadow imaging in vivo revealed cortical amyloid plaques and their surroundings, highlighting a dense ring of cells and a central core. Quantum dot tracking unraveled the core of the plaque is not easily penetrable by ab-sized molecules. Furthermore, we report ECS rheological parameters are heterogeneous in and around plaques, with an increased diffusivity within plaques and low nanoparticle density in the core. Using another type of nanoparticle, single-walled carbon nanotube, we confirmed these altered local diffusion properties in the cortex of AD mice. We found an altered ECM, notably disrupted within the amyloid plaque but not only, providing a rationale for the altered molecular dynamics in AD brain tissue and shedding new light on strategies to develop effective Aβ plaques-penetrating therapies. Overall, the findings presented in this work contribute to a deeper understanding of the ECS's role in neurodegenerative diseases. The results suggest that targeting the altered diffusion properties of the ECS could offer new therapeutic approaches for mitigating the effects of proteinopathies. The study concludes with a discussion of its implications for future research and clinical interventions aimed at restoring ECS function in the diseased brain.
Self-Supervised Learning for Improved Classification and Characterization of Sharp Wave Ripples
by Saber GRAF (Neurocentre Magendie)
The defense will take place at 10h00 - Visioconférence Visioconférence
in front of the jury composed of
- Cyril HERRY - Directrice de recherche - Université de Bordeaux - Directeur de these
- Da-Chuan CHENG - Professeur - China Medical University - Examinateur
- Sarina Hui-Lin CHIEN - Professeur - China Medical University - Rapporteur
- François GEORGES - Directeur de recherche - Université de Bordeaux - Examinateur
- Yann HUMEAU - Directeur de recherche - Friedrich Miescher Institute for Biomedical Research - Rapporteur
Sharp wave ripples (SWRs) in the hippocampus are essential oscillatory events associated with memory consolidation and cognitive processing. This research explores the application of self-supervised learning (SSL) techniques to enhance the classification of SWRs, focusing on distinguishing between before and after learning events. Traditional methods often fail to capture the subtle nuances in SWR properties that emerge as a result of learning. By integrating SSL with a custom 1D convolutional neural network (CNN) architecture, this study introduces a novel approach to address these challenges, significantly improving the classification accuracy of SWRs. The 1D CNN demonstrated strong performance in classifying SWRs, with SSL-based data re-labeling further enhancing the model's robustness by mitigating the effects of label noise. This approach leverages critical features such as Fast Fourier Transform (FFT) coefficients and wavelet entropy, which were identified as key indicators of learning-induced changes in the spectral and temporal properties of SWRs. The findings revealed significant shifts in frequency content and power distribution of SWRs following learning, highlighting the dynamic nature of hippocampal activity in response to cognitive demands. Additionally, the application of Gradient-weighted Class Activation Mapping (Grad-CAM) combined with Morlet wavelet analysis validated the biological relevance of the model's classification decisions, providing insights into the underlying neural mechanisms. Extending the analysis to a transgenic mouse model of Alzheimer's disease uncovered distinct differences in SWR characteristics compared to wild-type animals, underscoring the potential of SWR classification as a biomarker for cognitive impairments and neurodegenerative conditions. This study demonstrates the efficacy of deep learning for the analysis of complex neural signals, offering a more nuanced understanding of learning-induced changes in SWRs.
Characterization of the different populations of granular neurons in the dentate gyrus of the hippocampus: from morphology to function
by Pierre MORTESSAGNE (Neurocentre Magendie)
The defense will take place at 14h00 - Salle de conférence Neurocentre Magendie, 146 Rue Léo Saignat 33076 Bordeaux
in front of the jury composed of
- Emilie PACARY - Chargée de recherche - INSERM U1215 - Neurocentre Magendie - Directeur de these
- Flavio DONATO - Assistant professor - Biozentrum - Université de Bale - Rapporteur
- Julien COURCHET - Directeur de recherche - INSERM U1315 - Institut NeuroMyoGene - Rapporteur
- Rosa COSSART - Directrice de recherche - INSERM U1249 - Institut de Neurobiologie de la Méditerranée - Examinateur
- Noelia URBAN AVELLANEDA - Principal Investigator - Group Leader - IMBA - Institute of Molecular Biotechnology of the Austrian Academy of Sciences - Examinateur
- François GEORGES - Directeur de recherche - IMN - UMR 5293 - Centre Broca - Examinateur
In most areas of the brain, neurons are generated during embryogenesis. In contrast, in the dentate gyrus (DG) of the hippocampus - a key region for memory and emotional state regulation - the majority of granular neurons (GNs) are born during the early postnatal period and this neuronal production continues throughout adulthood, highlighting the peculiarity of this brain structure. The adult DG is therefore composed of GNs of different ontogenic origins (embryonic, early postnatal and adult) constituting sub-populations of GNs that could play different roles in hippocampal physiology and contribute differently to DG functions. Surprisingly, this hypothesis has received little attention and although most GNs are produced during development, little is known about their properties compared to adult-born GNs. In this context, this thesis project aims at better characterizing developmentally-born GNs (born in the embryonic and early postnatal period) in order to compare them with GNs generated in the adult brain. Thus, we will characterize their morphology (dendritic spines, axons), their afferent and efferent connectivity, their electrophysiological properties and their functional contribution.
FUNCTIONAL CHARACTERIZATION OF A PROTEIN IN THE CROSSTALK BETWEEN LIPID METABOLISM AND AUTOPHAGY IN ARABIDOPSIS
by Julie CASTETS (Laboratoire de Biogenese Membranaire)
The defense will take place at 14h00 - Amphithéâtre Colette et Josy Bové 71 avenue Edouard Bourlaux, Campus INRAE 33400 VILLENAVE D'ORNON
in front of the jury composed of
- Morgane MICHAUD - Chargée de recherche - Laboratoire Physiologie Cellulaire et Végétale - Rapporteur
- Sebastien THOMINE - Directeur de recherche - Institut de Biologie Intégrative de la Cellule - Examinateur
- Céline MASCLAUX-DAUBRESSE - Directrice de recherche - Institut Jean-Pierre Bourgin - Rapporteur
- Hernould MICHEL - Professeur des universités - Université de Bordeaux - Examinateur
Autophagy is an intracellular degradation process conserved across eukaryotes and critical for plant development and physiology. Autophagy relies on the formation of specialized membrane vesicles, called autophagosome, that encapsulate and traffic cargo to the lytic vacuole. Upon fusion with the tonoplast, autophagic bodies are released inside the vacuolar lumen and rapidly hydrolyzed to guarantee cargo degradation. How plant vacuoles deal with the large influx of autophagic bodies upon autophagy induction and how the membrane of the autophagic body is specifically hydrolyzed remain completely unknown. Upstream of this project, immuno-isolation of autophagy compartments identified an atypical phospholipase, LCAT4, as a putative component of the autophagy machinery. Studying the subcellular localization of LCAT4 revealed its associatation with early and late autophagy compartments, including autophagic bodies. Upon starvation, LCAT4 massively relocates inside the vacuole lumen using autophagy as a transport system, suggesting that LCAT4 could be involved in the disruption of autophagic membrane and/or cargo in the vacuole. Seedlings knocked-out for LCAT4 do not show defects in physiology or autophagic flux, suggesting that the activity of LCAT4 could be compensated by additional phospholipases. Indeed, LCAT3, the closest homolog of LCAT4 co-localizes with autophagic bodies under starvation. Fluorescent and electronic microscopy analyses demonstrate an accumulation of autophagic bodies inside the vacuole in the double lcat3 lcat4 knock out mutant and this is correlated with a significant slowdown in the autophagic flux. Together, this work characterizes novel actors of the autophagy machinery thus shading light on the penultimate step of this critical process for plant tolerance to environmental stresses
ED Sciences Physiques et de l'Ingénieur
Integration of Industry 4.0 technologies and lean management techniques to optimize enterprise performance
by Ilse URQUIA ORTEGA (Laboratoire de l'Intégration du Matériau au Système)
The defense will take place at 10h00 - Jean-Paul Dom IMS, CNRS UMR 5218, Bât. A31 - 351 Cours de la Libération - 33400 Talence
in front of the jury composed of
- Bruno VALLESPIR - Professeur des universités - Université de Bordeaux - Directeur de these
- Lamia BERRAH - Professeure des universités - Université Savoie Mont Blanc - Rapporteur
- Franck FONTANILI - Associate Professor - IMT Mines Albi - Rapporteur
- Jérôme PAILHES - Professeur des universités - Arts et Métiers ParisTech - École Nationale Supérieure d'Arts et Métiers - Examinateur
- Anne ZOUGGAR AMRANI - Maîtresse de conférences - Université de Bordeaux - CoDirecteur de these
- Daryl POWELL - Professeur - SINTEF - Examinateur
For competitive positioning, manufacturing companies are leveraging two key paradigms: Lean for organizational efficiency in production and Industry 4.0 (I4.0) for technological transformation. The objective of this thesis is to explore potential synergies between Lean practices (LP) and the technologies of I4.0 through a comprehensive global model of interaction analysis. This conjoint model is developed based on an extensive literature review and empirical evidence gathered from a survey sent to 200 manufacturing industrialists. The model aims to analyze specific requirements, such as industrial objectives, to define the most effective pathways joining LP and I4.0 for achieving desired outcomes. The integrative model, formalized by a supporting algorithm called LeaTechRP (Lean Practices and Technologies of I4.0 Research Path), aligns with the company's goals and provides diverse combinations for implementation. To contextualize the model's application in industry and predict its impact to ease the implementation, conjoint critical success factors (CCSFs) have been identified. The overarching goal is to provide a decision-support approach that explores cohesive implementation model, able to analyze the effectiveness of LP, and assesses the relevance of I4.0 technologies. The model is applied within the automotive industry, specifically with a company pursuing a conjoint Lean and I4.0 implementation. For a deeper understanding of the conjoint implementation of LP and I4.0, a statistical validation is conducted on the possible correlations between the model's parameters.
Definition and implementation of a transformer-based receiver for 140 GHz automotive radar applications
by Léo LANCON (Laboratoire de l'Intégration du Matériau au Système)
The defense will take place at 10h00 - Amphithéâtre Jean-Paul DOM UMR 5218 - IMS - Laboratoire de l'Intégration du Matériau au Système, 351 Cours de la Libération, 33405 Talence
in front of the jury composed of
- Thierry TARIS - Professeur - Bordeaux INP - Directeur de these
- Domenico ZITO - Professeur - AGH University of Science and Technology - Rapporteur
- Sylvain BOURDEL - Professeur - Grenoble INP - Rapporteur
- Jean-Baptiste BEGUERET - Professeur - Université de Bordeaux - Examinateur
- Hugo VALLEE - Docteur - NXP Semiconductors - Examinateur
- Dominique MORCHE - Ingénieur de recherche - CEA Leti - Examinateur
The constant increase in the number of sensors in modern cars, fulfilling advanced driving assistance functions, place the automotive radar as an essential element in today's and tomorrow's vehicle. This tendency is motivated in the long term by the development of autonomous vehicles. The industry considers moving the automotive radar product from the current standard around 80 GHz to a new frequency band around 140 GHz. This increase in the operation frequency would enable more compact sensors while maintaining and even improving the sensor accuracy thanks to MIMO applications. This work aims to assess the feasibility of a radar receiver at 140 GHz. A first part of this work is dedicated to the development of design tools and models which facilitate the implementation of millimeter wave circuits. First, a design methodology for impedance matching networks based on integrated transformers is presented. Thanks to their numerous advantages in addition to their impedance matching capability, they will be used in all the following development of this work. Then, a complete model of the multi-harmonic behavior of passive N-path circuits and more particularly N-path mixers is proposed. Their benefits in term of noise, current consumption and linearity make them suitable for the implementation of 140 GHz automotive radars. A second part of this work is focused on the implementation of multiples RF front-ends for radar receivers, based on a mixer-first architecture. Two solutions are first proposed which fully exploit the advantages of the modeled mixers at the considered frequency. A fundamental solution is proposed which complies with the long-range radar applications. A sub-harmonic alternative with a slightly reduced range is then presented. It would enable significant savings on the chip area and the current consumption, answering to a market demand for low-cost radar products that can be embedded in large number inside one vehicle. Finally, a novel type of passive mixers, called bottom-plate mixer is studied to design two additional radar receivers front-ends. These mixers keep the advantages of the traditional N-path mixers while also presenting a high voltage gain. A fundamental receiver is proposed, based on an existing topology at RF frequencies only, that addresses the constraints for the 140 GHz radar application. A second sub-harmonic receiver is designed with a novel topology developed in this work, which complement the first receiver. These two front-ends allows a longer detection range for the radar module.
Understanding of degradation mechanisms involving moisture diffusion into BEOL integrated dielectric stacks
by Léo MISCHLER (Laboratoire de l'Intégration du Matériau au Système)
The defense will take place at 9h00 - Jean-Paul DOM 351 Cours de la Libération, 33405 Talence
in front of the jury composed of
- Geneviève DUCHAMP - Professeure des universités - Université de Bordeaux - Directeur de these
- Kaspar JANSEN - Professeur des universités - Faculty of Industrial Design Engineering - Rapporteur
- Gaël GAUTIER - Professeur des universités - INSA CVL - GREMAN UMR CNRS - Rapporteur
- Benoît COASNE - Directeur de recherche - CNRS Liphy - Examinateur
- Jean-Pierre LANDESMAN - Professeur des universités - Institut FOTON (UMR 6082) - équipe OHM - Examinateur
- Hélène FREMONT - Professeure des universités - Université de Bordeaux - CoDirecteur de these
The presence of moisture is particularly critical for microelectronic applications, leading to overall performance degradation, metal corrosion within the integrated circuit, and even delamination between different layers. To protect the chips from environmental aggressions, a continuous metal interconnection structure, known as the "seal ring," is placed around them. However, the integrity of this protective structure is sometimes compromised, often due to integration problems during manufacture, which can pose major reliability issues. Therefore, the aim of this thesis is to elucidate the interactions between moisture and these new types of integrated circuits to establish an acceleration model (temperature and humidity) for industrial reliability testing. To achieve this, a comprehensive approach from material to integrated circuit was adopted. Previous work leading up to this thesis established the absorption properties of the main dielectric materials used in the Back End of Line (BEOL). Then, in my work, integrated circuits were studied through physico-chemical and electrical characterizations. By cross-referencing these analyses, a failure criterion was defined for the development of an acceleration model based on Peck's model.
Evaluation of the robustness of ultrathin AlN barrier GaN HEMTs technologies for power amplification beyond the Ka band.
by Nasri SAID (Laboratoire de l'Intégration du Matériau au Système)
The defense will take place at 10h00 - Amphithéâtre Jean-Paul Dom Laboratoire IMS, bâtiment A31, Université de Bordeaux 351 cours de la libération, 33405 Talence, France
in front of the jury composed of
- Nathalie MALBERT SAYSSET - Professeure des universités - Université de Bordeaux - Directeur de these
- Jean-Guy TARTARIN - Professeur des universités - Université Paul Sabatier - CoDirecteur de these
- Labat LABAT - Professeure des universités - Université de Bordeaux - Examinateur
- Olivier LATRY - Professeur des universités - Université de Rouen Normandie - Rapporteur
- Denis BARATAUD - Professeur des universités - Université de Limoges - Rapporteur
- Farid MEDJDOUB - Chargé de recherche - IEMN, Université de Lille - Examinateur
- Fabio COCCETTI - Docteur - IRT Saint Exupéry - Examinateur
The GaN technology is strategically important for the European Union as it enhances the power and energy efficiency of radar and telecommunication systems, particularly in the S to Ka frequency bands (up to 30 GHz). To meet the requirements of future applications such as 5G and military systems, GaN technologies are being developed to increase operating frequencies into the millimeter-wave range. This advancement necessitates the optimization of epitaxy and the reduction of gate lengths below 150 nm, along with the use of ultra-thin barriers (<10 nm) to avoid short-channel effects. Replacing the AlGaN barrier with AlN provides a solution to maintain high performance while enabling further miniaturization of the devices. This thesis explores various technological structure with ultra-thin (3 nm) AlN barriers on undoped GaN channels of different thicknesses. The evaluation of the performance and robustness of these technologies is crucial for their qualification and long-term use in their critical mission profiles. Both DC and RF assessments were conducted to define the safe operating areas (SOA) and to identify potential degradation mechanisms. DC and pulsed characterizations revealed minimal dispersion in the similar devices after electrical stabilization, demonstrating a high level of technological control and good maturity of the process. The sensitivity study of the devices at temperatures up to 200°C showed strong thermal stability in diode and transistor modes, based on key performance indicators. The addition of an AlGaN back-barrier on a moderately C-doped buffer layer compromised electron confinement and trap density. Accelerated aging tests under DC at various DC bias points, as well as RF stress tests with increasing input power (Pin), indicated that the AlGaN back-barrier improves leakage current stability, reduces trapping and self-heating effects, and extends the operational SOA in DC mode. Dynamic aging tests at 10 GHz on HEMTs with different gate-to-drain distances showed that the RF SOA is more dependent on the gate's ability to handle high RF signals than on the gate-to-drain spacing. Using an original nonlinear modeling method that takes into account self-biasing, devices with an AlGaN barrier have proven to be more robust in RF operation as well, due to their delayed gain compression as a function of Pin, which can reach up to ~10 dB without any degradation observed through photoluminescence. Regardless of the AlN/GaN variant, the RF stress degradation mechanism corresponds to an abrupt breakdown of the Schottky gate. These results demonstrate that the devices are more sensitive to DC bias conditions than to the injected power level. In conclusion, this work provides a deeper understanding of the degradation mechanisms responsible for the decline in performance and reliability of AlN/GaN HEMTs, which could lead to improvement pathways for their advancement toward higher technological maturity levels (TRL). The addition of a back AlGaN barrier helps reduce and limit leakage currents, which pose a threat to the reliability of GaN HEMTs, thereby improving their robustness and reliability for high-power millimeter-wave applications.
ED Sciences et environnements
Genomic bases of downy mildew adaptation to grapevine resistances: towards the identification of avirulence genes by a quantitative genetics approach
by Etienne DVORAK (SAVE - Santé et Agroécologie du VignoblE)
The defense will take place at 9h00 - Amphithéâtre Colette et Josy Bové INRAE Bordeaux Nouvelle-Aquitaine 71 Av. Edouard Bourlaux - Bâtiment D2 33140 VILLENAVE D'ORNON
in front of the jury composed of
- Sylvain RAFFAELE - Directeur de recherche - CNRS-INRAE - Rapporteur
- Didier THARREAU - Chargé de recherche - CIRAD - Rapporteur
- Véronique DECROOCQ - Directrice de recherche - INRAE-Université de Bordeaux - Examinateur
- Véronique JORGE - Chargée de recherche - INRAE - Examinateur
- Marie FOULONGNE-ORIOL - Chargée de recherche - INRAE - Directeur de these
- Thierry CANDRESSE - Directeur de recherche - INRAE - Université de Bordeaux - Examinateur
Breeding for resistant varieties is one of the most efficient approach to control plant diseases, but the adaptation of pathogen populations limits their durability. The causal agent of grapevine downy mildew, the oomycete Plasmopara viticola, has demonstrated the ability to rapidly overcome several resistance factors recently deployed in Europe. Grapevine resistances to downy mildew are strong but partial, which raises the question of the mechanisms of pathogen virulence in this phenotypically quantitative interaction. A QTL mapping approach was used to identify the genetic determinants of P. viticola adaptation to three grapevine resistance factors: Rpv3.1, Rpv10 and Rpv12. Two crosses were made between downy mildew strains with contrasting virulence profiles. These progenies were genotyped by targeted sequencing of 5263 SNPs. The construction of high-density linkage maps enabled a pseudo-assembly of the genome at the chromosome level (2n=34). Some offspring carry karyotypic abnormalities (aneuploidies, triploidies) that originate almost exclusively from the male gamete, via several mechanisms (diploid gametes, dispermy). By phenotyping the interaction between these progenies and different grapevine cultivars (sporulation, necrosis), a major QTL was detected for each virulence. A candidate locus for AvrRpv12 was identified, containing several putative RXLR effector genes absent or non-functional in the virulent alleles. This resistance breakdown is consistent with a gene-for-gene relationship in which virulence is recessive. In the case of Rpv10, an atypical genetic determinism was observed. Resistance breakdown is partial and dominant, which strongly suggests an avirulence suppressor mechanism. The QTL detected corresponds to a 537 kb interval that is poorly recombinant and highly enriched in secreted protein genes. An haplotype-aware assembly of the parent strain revealed major structural rearrangements and variation in the repertoire of putative effectors in the virulent haplotype. Study of a backcross population confirms the dominance of this avirulence suppressor allele. Analysis of the genetic structure of a panel of isolates suggests several independent events with regard to Rpv12 breakdown. In contrast, virulence against Rpv10 probably has a unique origin linked to the recent introduction of a non-European genetic background. The position of the AvrRpv3.1 locus, previously identified by GWAS, was confirmed. The sequencing of around a hundred P. viticola isolates revealed a wide diversity of Rpv3.1 bypass alleles in Europe. This diversity may be linked to the long-standing distribution of hybrid grape varieties carrying Rpv3.1, before their areas were drastically reduced in the mid-twentieth century. A molecular tool has been developed to monitor the presence-absence of AvrRpv3.1 effectors by qPCR. This tool makes high-throughput monitoring of mildew populations possible. Taken together, these results improve our understanding of the mechanisms by which P. viticola adapts to grapevine resistances. They also pave the way for the functional characterization of new oomycete effectors. Finally, monitoring the evolutionary dynamics of the genes involved will inform the design of better deployment strategies for resistant grapevines.
ED Sociétés, Politique, Santé Publique
pharmacoepidemiologic evaluation of drugs for the secondary prevention of stroke
by Julia PERRIER (Bordeaux Population Health Research Center)
The defense will take place at 9h30 - Amphithéâtre Pierre-Alexandre Louis Amphithéâtre Pierre-Alexandre Louis ISPED - Institut de Santé Publique, d'Epidémiologie et de Développement Université de Bordeaux, Campus Carreire 146 rue Léo Saignat 33076 Bordeaux cedex, France
in front of the jury composed of
- Julien BEZIN - Maître de conférences - praticien hospitalier - Université de Bordeaux, CHU de Bordeaux - Directeur de these
- Yannick BEJOT - Professeur des universités - praticien hospitalier - Université de Bourgogne, CHU Dijon Bourgogne - Rapporteur
- Emmanuel OGER - Professeur des universités - praticien hospitalier - Université de Rennes 1, CHU de Rennes - Rapporteur
- Karen LEFFONDRE - Professeure des universités - Université de Bordeaux - Examinateur
- Philippe TUPPIN - Docteur - CNAM - Examinateur
With more than 6 million deaths in 2019, stroke is the second leading cause of death worldwide. In France, stroke is the leading cause of death in women and the third leading cause of death in men. Controlling risk factors is a key issue in secondary prevention. The guidelines recommend as first-line treatment a combination of antihypertensive drugs (a renin-angiotensin-aldosterone system drug and a calcium channel blocker or a thiazide diuretic), a statin, and an antithrombotic drug depending on the nature of the stroke (cardioembolic: antiplatelet agent; non-cardioembolic: anticoagulant). These guidelines are mainly based on the results of clinical trials. However, these studies are not devoid of limitations. The populations studied are often selected (few elderly people, few co-morbidities) and therefore not representative of the population finally treated for post-stroke. In addition, the efficacy of treatments is often assessed individually and in optimal conditions, so the overall benefit of combining them in real-life settings remains incompletely studied. Preliminary work in real healthcare situations had already shown sub-optimal use of lipid-lowering and antihypertensive drugs in France after a first stroke. Thereby, real-life effectiveness may differ from that found in clinical trials. In this context, the aim of this work was to describe the use of secondary stroke prevention treatments in France, and to assess the effectiveness of these treatments in the population and in real-life settings. In the first part, we described firstly the use of different combinations of antihypertensive drugs. Although the number of combinations found in practice was large, the most frequent drugs were those recommended, and the delay in first post-stroke delivery was reassuring. In a second study, we conducted a systematic review on sex differences in post-stroke drug patterns. Women were less likely to receive lipid-lowering and antithrombotic drugs than men, and more likely to receive antihypertensive drugs. Given the lack of data in France, we conducted a study assessing the differences in drug utilization between the sexes, which showed that women received fewer lipid-lowering drugs than men. To explore ways of improving this situation, we undertook a qualitative study of general practitioners and neurologists in the Nouvelle-Aquitaine region (south western France). In the second part, we assessed the effectiveness of the recommended drugs in real-life settings. While the effectiveness of statins and antithrombotics in post-stroke treatment is clear, all antihypertensive drugs were associated with a reduction in cardiovascular morbidity and mortality, but only diuretics and calcium channel blockers were associated with a reduction of stroke recurrence. The effectiveness of some antihypertensive drugs was sex-dependent: beta-blockers were associated with an increased risk of stroke in women, and angiotensin receptor blockers were associated with an increased risk of stroke in men with atrial fibrillation. Conversely, there was no difference in the effectiveness of lipid-lowering and antithrombotics according to sex. These results highlight the need to improve secondary prevention after stroke by reinforcing the personalisation of guidelines concerning the choice of antihypertensive drug and the implementation of guidelines concerning the initiation of lipid-lowering and antithrombotic drugs in women. Finally, therapeutic education for secondary prevention treatments seems essential to maximise their effectiveness.
From perception to regulation of bodily signals in eating behavior: the role of interoceptive awareness and mindfulness
by Léa MARINELLI (Laboratoire de Psychologie)
The defense will take place at 14h00 - Denucé Faculté de la victoire, 3 ter place de la Victoire, 33000 Bordeaux
in front of the jury composed of
- Greg DECAMPS - Professeur des universités - Université de Bordeaux - Directeur de these
- Rebecca SHANKLAND - Professeur des universités - Université Lyon 2 - Rapporteur
- Jean-Louis NANDRINO - Professeur des universités - Université de lille - Rapporteur
- Cécile DANTZER - Maître de conférences - Université de Bordeaux - CoDirecteur de these
- Michael DAMBRUN - Professeur des universités - Université de Clermont-Ferrand - Examinateur
- Sylvie BERTHOZ - Docteur - Université de Bordeaux - Inserm - Examinateur
The ability to perceive and interpret internal bodily signals, as know as interoceptive awareness, is with other bodily factors one of the determinants of the regulation of eating behaviors. The influence of interoceptive awareness may concern normal eating behaviors such as intuitive eating, but also disturbed eating behaviors and Eating Disorders (EDs). While mindfulness skills are a potential resource for enhancing interoceptive awareness, studies in both general and clinical populations exploring simultaneously these two processes remain scarce. Objectives: Through studies employing both variable-centered and person-centered approaches, this thesis aims to (1) test the nature of the relationships between intuitive eating and bodily factors such as self-evaluation and BMI, (2) identify profiles of interoception and mindfulness and examine their links with eating behaviors, and (3) determine which dimensions of interoceptive awareness and mindfulness are substantively involved in ED symptomatology. Results: The results provide insights into the personalization of interventions for patients suffering from EDs by adapting them to their BMI, identifying interoceptive profiles at risk for disturbed eating behaviors, and targeting the interoceptive and emotional processes involved in eating disturbances. The results are discussed to support the development of a conceptual model of mindful interoceptive functioning as well as a treatment protocol based on mindfulness.
Air pollution exposure and age-related eye diseases : an epidemiological approach
by Laure GAYRAUD (Bordeaux Population Health Research Center)
The defense will take place at 14h00 - Amphithéâtre Pierre-Alexandre Louis Inserm "Bordeaux Population Health Research Center" (BPH) UMR1219 Université de Bordeaux 146 rue Léo Saignat 33076 Bordeaux Cedex
in front of the jury composed of
- Cécile DELCOURT - Directrice de recherche - Université de Bordeaux - Directeur de these
- Jean-François KOROBELNIK - Professeur des universités - praticien hospitalier - Université de Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, - Examinateur
- Benedicte JACQUEMIN - Chargée de recherche - IRSET (Institut de Recherche en Santé Environnement et Travail- INSERM U1085) - Rapporteur
- Alain BRON - Professeur des universités - praticien hospitalier - UMR 1324 INRA, 6265 CNRS, Université de Bourgogne-Franche-Comté - Rapporteur
Age-related eye diseases, such as cataract, age-related macular degeneration (AMD) and glaucoma, are the three leading causes of blindness worldwide. Oxidative stress is a key factor in their development, and exposure to air pollution, which is known to exacerbate oxidative stress, may contribute to the progression of these conditions. This thesis aims at investigating the association between air pollution exposure and retinal nerve fiber layer (RNFL) degeneration, as well as the incidence of cataracts and AMD, using data from three large French cohorts comprising over 36,000 participants followed for more than 10 years. Cases of cataracts and AMD were identified from the French National Health Data System (SNDS) in the national Constances and Gazel cohorts, or verified by an ophthalmologist in the 3C-Alienor cohort. Additionally, in the 3C-Alienor cohort, repeated measurements using optical coherence tomography (OCT) allowed for precise assessment of RNFL thickness, a biomarker of neurodegeneration in glaucoma. Exposure to air pollution, including nitrogen dioxide (NO₂) and fine particulate matter (PM2.5 and Black Carbon (BC)), was estimated using land use regression (LUR) models, providing a precise estimation of pollutant concentrations with a 100-meter resolution based on the geocoding of participants' residential addresses. The findings revealed an accelerated thinning of the RNFL among participants of the 3C-Alienor cohort who were most exposed to fine particulate matter (PM2.5 and BC). This observation suggests a potentially neurotoxic effect of fine particulate matter on the optic nerve. Furthermore, across the Constances and Gazel cohorts, and the 3C-Alienor cohort, participants exposed to NO₂ concentrations exceeding 38.5 and 40 µg/m³, respectively (with the current European regulatory limit set at 40 µg/m³), presented an increased risk of cataract surgery, particularly among those living in urban areas. Lastly, participants with the highest exposure to black carbon (BC), a component of fine particulate matter derived from combustion activities, had an 88% higher risk of developing AMD in the Constances cohort, although this association was not observed in the Gazel cohort. These findings suggest that NO₂ has a significant effect on cataract development, while fine particulate matter (PM2.5 and BC) contribute to retinal degeneration, even at pollution levels below current European regulatory limits. The results from this thesis strengthen the evidence of the harmful effects of air pollution on eye health and support the need to lower European regulatory thresholds, in line with WHO recommendations.
Innovation in active pedagogy, crossed views learning by Design Thinking for an inclusive university
by Raoudha BRINI (Laboratoire Cultures, Education, Sociétés)
The defense will take place at 16h00 - Visioconférence
in front of the jury composed of
- Magdalena KOHOUT-DIAZ - Professeure des universités - Université de Bordeaux - Directeur de these
- Pierre Johan LAFFITTE - Professeur des universités - Université de Paris 8 Vincennes-Saint-Denis - Rapporteur
- Martin STROUHAL - Maître de conférences - Université Charles, Faculté de philosophie, Département de l'éducation - Rapporteur
- Franc MORANDI - Professeur émérite - Université de Bordeaux - Examinateur
With a view to improving learner engagement and motivation, the renewal of educational practices is constantly evolving by proposing the implementation, within a framework of pedagogical innovation, of new learning strategies using new information and communication technologies for ICT learning and collective intelligence methods that place collaborative work and group dynamics at the centre of reflection on the evolution of learning environments. The thesis focuses on the challenge of the declining engagement and motivation of generation Z learners in a learning environment that they feel is poorly structured and does not meet their aspirations. It aims to explore innovative learning methods by testing an active method inspired by the Design Thinking model. This model, based on a socio-cognitive approach, aims to create a more collaborative and stimulating learning environment. The study seeks to identify the factors that promote the well-being of learners in a learning environment based on collective intelligence (socioconstructivist approach) and motivation, within the framework of a multimodal digital affordance (connectivism). To assess the effectiveness of the model and its impact on the motivation and engagement of Generation Z learners, we adopted a methodology based on design experimentation, supplemented by mixed quantitative and qualitative methods. This included non-participant observation, which highlighted the correlation and interdependence of variables such as interactivity and autonomy, and the need for affiliation encouraged and promoted by our model, and the level of satisfaction, and shedding light on the posture of teachers. The results obtained provide contributions and proposals for a new approach to active teaching through our model, which other teachers can adopt and personalise according to their course themes. We have established a set of pedagogical recommendations that can be useful with a strong impact on the learner experience and highlight the role and importance of the teacher's posture in the learning experience. We reveal a significant correlation between interactivity, autonomy time, social bonding, well-being and learner motivation and engagement in learning.