ED Mathématiques et Informatique
DEEP LEARNING METHODS FOR FINE-GRAINED PARCELLISATION OF THE BRAIN FROM FLAIR MRIs
by Edern LE BOT (LaBRI - Laboratoire Bordelais de Recherche en Informatique)
The defense will take place at 9h30 - AMPHI (050) AMPHI (050) - Bat. A30 Université de Bordeaux 351 Cours de la Libération
in front of the jury composed of
- Pierrick COUPE - Directeur de recherche - Université de Bordeaux - Directeur de these
- Victoria BOURGEAIS - Maîtresse de conférences - Université de Bordeaux - Examinateur
- Caroline PETITJEAN - Professeure des universités - Université de Rouen Normandie - Examinateur
- Jean-Philippe DOMENGER - Professeur des universités - Université de Bordeaux - Examinateur
- Pierre-Henri CONZE - Maître de conférences - IMT Atlantique - Rapporteur
- Marc-Emmanuel BELLEMARE - Maître de conférences - Université d'Aix-Marseille - Polytech' Marseille - Rapporteur
Magnetic Resonance Imaging is a key tool for studying the brain and diagnosing numerous neurological diseases. It enables non-invasive observation of brain structure and abnormalities. Among MRI sequences, the Fluid-Attenuated Inversion Recovery (FLAIR) sequence plays a crucial role in detecting brain lesions and is widely used in clinical practice, particularly for disorders such as multiple sclerosis, brain tumors, and stroke. However, automatic analysis of FLAIR images remains challenging due to low tissue contrast, reduced signal-to-noise ratio, and variations between scanners and acquisition protocols. In neuroimaging, quantitative brain analysis increasingly relies on automated segmentation tools that can identify anatomical structures and pathological regions. Most existing segmentation methods have been developed for T1w MRI, which is considered the standard reference for anatomical segmentation. However, T1w images are not always acquired in clinical protocols, which limits the applicability of existing tools. In many cases, FLAIR is the only available sequence, but conventional T1w-based approaches fail to produce reliable segmentations under such conditions. This thesis addresses this limitation by investigating the feasibility of performing fine-grained brain segmentation using FLAIR MRI alone. The goal is to design robust methods capable of extracting meaningful anatomical and pathological information from FLAIR data, while remaining resilient to acquisition variability and the presence of lesions. The proposed work led to the development of tools specifically adapted to FLAIR imaging, improving the robustness of both preprocessing and segmentation steps in realistic clinical settings. The results demonstrate that fine-grained and reliable brain segmentations can be obtained from FLAIR MRI alone, enabling the use of large clinical datasets that are often underexploited. These findings also highlight the advantages of modality-specific approaches over generic, modality-agnostic methods. In the long term, the tools developed in this work could be integrated into the volBrain online platform (https://volbrain.net) to facilitate their dissemination to the scientific and clinical communities.
Statistical learning for Boolean network ensembles and scRNA-seq data
by Gustavo MAGAÑA LOPEZ (LaBRI - Laboratoire Bordelais de Recherche en Informatique)
The defense will take place at 14h00 - 050-AMPHI (198) 351, cours de la Libération F-33405 Talence cedex
in front of the jury composed of
- Loïc PAULEVE - Directeur de recherche - Université de Bordeaux - Directeur de these
- Nacho MOLINA - Directeur de recherche - CNRS - Rapporteur
- David SAFRANEK - Maître de conférences - Faculty of Informatics, Masaryk University - Rapporteur
- Clémence REDA - Chargée de recherche - CNRS - Examinateur
- Patricia THEBAULT - Professeure des universités - Université de Bordeaux - Examinateur
- Ulysse HERBACH - Chargé de recherche - Inria - Examinateur
Systems Biology is the study of the interactions and behaviour of the components of biological entities, including molecules, cells, organs, and organisms. It is a holistic approach, which emphasises the central role of complex interactions within biological systems in opposition to the study of their isolated parts. A subject of great interest within this discipline with high stakes both for fundamental biology and numerous biomedical applications is the regulation of gene expression. Research in this area is conducted by the mathematical and computational modelling of experimental data. The latter has significantly advanced over the last decade with the advent of single-cell RNA sequencing (scRNA-seq) which enables measuring gene expression with unprecedented resolution. A first step to model and understand gene expression is detecting interactions by which genes may influence one another. Currently, statistical and deep learning methods are used alongside bioinformatic analyses to infer plausible interactions from scRNA-seq and other data sources. The set of inferred interactions constitutes then a gene regulatory network (GRN) which is an static model of influences amongst genes. GRNs are valuable information but provide a description that is too coarse to explain the regulatory mechanisms that give rise to observed biological phenomena. Dynamical models aim to fill this explanatory gap by providing a mechanistic view that can account for and reproduce the observed changes in data. Boolean networks (BNs) are a particular class of dynamical system commonly used to model the regulation of gene expression. In these models, the activity of biological entities is represented as either active or inactive. The binary representation allows reasoning on the causal relationships between entities without having to estimate kinetic parameters or regulation thresholds. In spite of recent advances in the fields, numerous questions on modelling scRNA-data with BNs remain open. In my thesis, I work on two principal axes regarding BNs and scRNA-seq data. The first axis is linking scRNA-seq data which is quantitative in nature with the qualitative view of BNs. To this end, my first contribution is novel method scBoolSeq which provides a qualitative interpretation of experimental scRNA-seq data and is also capable of generating synthetic scRNA-seq data taking into account Boolean gene activation states. scBoolSeq has already been used to benchmark inference methods using the aforementioned synthetic scRNA-seq data reflecting Boolean dynamics. The second axis takes inspiration from the data splitting approach used to build and assess statistical learning models. Boolean network inference is often performed manually, aims to account for isolated experiments, and lacks subsequent testing on held out data. My proposal is to leverage multiple experimental conditions as follows: By inferring BNs on “training” experimental conditions and assessing their fitness on previously unseen “testing” data, it is possible to assess and subsequently optimise their predictive power. Thus, my research constitutes a new direction that combines formal methods with statistical learning in order to streamline Boolean network modelling of scRNA-seq data.
An arbitrary order finite volume scheme for Helmholtz equation - Application to laser energy deposition in dielectric materials
by Nicolas BOURDINEAUD (IMB - Institut de Mathématiques de Bordeaux)
The defense will take place at 13h00 - Salle de conférence Université de Bordeaux, Institut mathématique de Bordeaux. 351, cours de la Libération, CS 10004 - Bâtiment A33, 33405 Talence CEDEX, France
in front of the jury composed of
- Rodolphe TURPAULT - Professeur des universités - Université de Bordeaux, Institut de Mathématiques de Bordeaux - Directeur de these
- Guillaume DUCHATEAU - Ingénieur Chercheur du CEA - CEA CESTA - CoDirecteur de these
- Claire CHAINAIS - Professeure des universités - Université de Lille - Examinateur
- Raphaël LOUBERE - Directeur de recherche - Université de Bordeaux, Institut de Mathématiques de Bordeaux - Examinateur
- Stéphane CLAIN - Professeur des universités - Université de Coimbra, Portugal - Rapporteur
- Emmanuel LABOURASSE - Ingénieur Chercheur du CEA - CEA Bruyères Le Châtel - Rapporteur
- Jean Philippe COLOMBIER - Professeur des universités - Université de Saint-Etienne - Examinateur
To understand the resistance of a ceramic medium subjected to a hydrodynamic shock, it can be irradiated with a laser pulse. This induces energy deposition in the medium, forming the shock. The energy deposition results from the microscopic excitation of electrons coupled to the propagation of the laser pulse. Media considered are porous. They give rise to multiple scattering of laser radiation, which modifies laser propagation and hence energy deposition. In this manuscript, a model of laser energy deposition in porous ceramics is proposed. This model involves coupling the electronic dynamics, described by a highly nonlinear ordinary differential equation, with the evolution of the laser electric field, described by the elliptic Helmholtz equation in one and two spatial dimensions. Solving the Helmholtz equation is costly in terms of computation time, as large computational domains (hundreds of wavelengths) have to be considered, while guaranteeing a sufficiently fine pore meshing. Increasing the order of the numerical scheme to solve this coupled problem is therefore a solution for obtaining a computationally efficient approach. A high-order finite volume scheme, achieved by polynomial reconstruction, is proposed. In addition, since porosity generates non-regular behavior at medium-pore interfaces, a special treatment for reconstructing accurate numerical fluxes, based on a partitioned formulation of the Helmholtz equation, is proposed. The arbitrary curvature of the medium-pore interface is taken into account without recourse to curved cells. This finite volume scheme was coupled to a numerical scheme solving the electronic dynamics equation using an adaptive time-step Dormand Prince-type scheme. The time step adaptation criterion has been modified to guarantee stability and convergence in the context of non-linearities in the differential system. The convergence of the numerical schemes and their efficiency in terms of computation time are studied through various test cases. Simulations of laser energy deposition in porous media are also presented.
MATHEMATICAL MODELING IN ONCOLOGY TO IMPROVE THE ASSESSMENT OF LESIONAL HETEROGENEITY IN MEDICAL IMAGING
by Khaoula CHAHDI (IMB - Institut de Mathématiques de Bordeaux)
The defense will take place at 10h00 - Salle de conférences Institut de Mathématiques de Bordeaux 351 Cours de la libération, A33, 33400, Talence
in front of the jury composed of
- Olivier SAUT - Directeur de recherche - Université de Bordeaux - Directeur de these
- Fabien CRAUSTE - Directeur de recherche - Université de Paris Cité - Rapporteur
- Laurent RISSER - Ingénieur de recherche - Université de Toulouse - Rapporteur
- Christèle ETCHEGARAY - Chargée de recherche - INRIA de l'Université de Bordeaux - Examinateur
- Nicolas PAPADAKIS - Directeur de recherche - Université de Bordeaux - Examinateur
- Nadège ANIZAN - Physicienne médicale - Institut de Bergonié - Examinateur
Machine learning applied to medical imaging is reshaping analytical strategies and opening new opportunities for prognostic stratification and cancer diagnosis. This thesis investigates the contribution of radiomics and multiple instance learning (MIL) methods in two highly heterogeneous clinical settings: diffuse large B-cell lymphoma (DLBCL) and hepatocellular adenomas (HCA). In DLBCL, conventional analyses focusing on the dominant lesion or SUVmax proved insufficient to capture disease complexity (AUC = 0.56). Integrating all lesions led to improved predictive performance: simple MinMax aggregation (AUC = 0.70) provided a robust compromise, while post-processed KMeans clustering (AUC = 0.73, recall = 0.85) achieved the best results, with survival stratification significantly more discriminant than reference clinical models. These findings demonstrate that tumor heterogeneity, rather than being noise, contains valuable prognostic signals. For HCA, digital whole-slide histopathology images (WSI) were divided into thousands of tiles, each treated as an instance. Models based on ResNet34 and ConCH combined with classical classifiers (Random Forest, MLP) yielded competitive performances. However, the MIL model with an attention mechanism reached an AUC of 0.97 while offering intrinsic interpretability by explicitly identifying the most relevant tiles. This explainability aligns the models more closely with pathologists' reasoning and enhances their clinical applicability. In conclusion, this work highlights the value of MIL approaches for modeling heterogeneity in multifocal or multisite diseases. Future directions include multicenter validation, multimodal integration (imaging, clinical and biological data), and the design of hybrid models combining statistical robustness with interpretability.
ED Sciences Chimiques
Development of bioenergetic artificial cells based on mitochondria encapsulated in microcompartments
by Léonie BEAUPERE (Institut de Chimie & de Biologie des Membranes & des Nano-objets)
The defense will take place at 10h00 - Amphithéâtre Institut européen de chimie et biologie (IECB) 2 Rue Robert Escarpit, 33600 Pessac
in front of the jury composed of
- Stéphane ARBAULT - Directeur de recherche - CNRS - Université de Bordeaux - Directeur de these
- Anne DEVIN - Directrice de recherche - CNRS - Université de Bordeaux - CoDirecteur de these
- Laura BACIOU - Directrice de recherche - CNRS - Université Paris-Saclay - Examinateur
- Jean-Christophe BARET - Professeur - Université de Bordeaux - Examinateur
- Manon GUILLE - Professeure - Sorbonne Université - Rapporteur
- Christophe DANELON - Professeur - Toulouse Biotechnology Institute (TBI) - Rapporteur
There is growing interest in artificial cells designed to mimic the biological functions of living cells. They facilitate the study of complex biological processes and advance research into the origins of life. One of the essential functions of cells, necessary for most biological processes, is the conversion of cellular energy into ATP. Since mitochondria are the main producers of cellular ATP, at least in aerobic processes, we present the encapsulation of mitochondria isolated from the yeast Saccharomyces cerevisiae in synthetic microcompartments to form bioenergetic artificial cells. Two types of compartments were used throughout our studies: giant liposomes or GUVs (giant unilamellar vesicles), consisting of unilamellar phospholipid membranes that can mimic natural cell membranes, and coacervates, which are droplets produced by liquid-liquid phase separation of biocompatible polymers, forming membrane-less compartments that provide a crowded cytosol-like chassis. These two types of microcompartments provide controlled structures and environments for biological and biochemical reactions to take place. Mitochondrial bioenergetic activities in the compartments were studied using spectrophotometric and electrochemical methods. Epifluorescence microscopy is used to evaluate membrane potential, NADH content and reactive oxygen species (ROS) production in mitochondria, while oxygen consumption and ATP synthesis were measured by electrochemistry and bioluminescence, respectively. The activity of the oxidative phosphorylation system was modulated by the addition of substrates and inhibitors. Finally, enzymes were also added to complexify the biomimetic system and produce autonomous artificial cells, using the ATP synthesised in situ to fuel other enzymatic reactions.
Evolution of ceramic matrix composites in a geological storage environment
by Guillaume GERMAN (Laboratoire des Composites ThermoStructuraux)
The defense will take place at 14h00 - Amphithéâtre du LCTS Laboratoire des Composites ThermoStructuraux 3 allée de la Boétie, 33600 Pessac
in front of the jury composed of
- Francis REBILLAT - Professeur des universités - Université de Bordeaux - CoDirecteur de these
- Jocelyne BRENDLE - Professeure des universités - Université de Haute-Alsace - Rapporteur
- Sylvie FOUCAUD - Professeure des universités - Université de Limoges - Rapporteur
- Aurélien DEBELLE - Ingénieur de recherche - Agence nationale pour la gestion des déchets radioactifs - Examinateur
- Fernando PEDRAZA - Professeur des universités - Université de La Rochelle - Examinateur
- Jérôme ROGER - Maître de conférences - Université de Bordeaux - Directeur de these
- Emilie PERRET - Ingénieure de recherche - IRT Saint Exupéry - CoDirecteur de these
The Cigéo project is the French project for a deep geological repository for radioactive waste led by ANDRA (Agence nationale pour la gestion des déchets radioactifs). It aims to store highly radioactive and long-lived waste produced by current nuclear facilities and by the processing of spent fuel used in nuclear power plants. The concept for the disposal of high-level waste (HLW) provides for the installation of a liner, i.e., a hollow cylinder inserted into a small-diameter tunnel dug into the geological environment of the Callovo-Oxfordian (clay). The primary function of this liner is mechanical: it allows the emplacement and eventual retrieval of the HLW storage packages during the entire period of reversible operation of the repository. Among the potential areas of development for the repository, ANDRA is studying the development of alternative materials to metallic materials for the HL cell. Ceramic Matrix Composites (CMC) combine the thermal resistance and chemical stability of ceramics and have a tenacious mechanical behavior due to their composite structure (incorporation of reinforcements). Developed for high-temperature technical applications, including aeronautics, they are now being considered for lower-temperature applications with longer operating times through the development of less expensive CMC materials. In this context, ANDRA is studying the possibility of using oxide/oxide composites for the lining of HA waste storage cells. Different pairs of materials are currently being considered (oxide or geopolymer matrices, oxide or carbon fibers). An experimental approach allowing to identify the mechanisms of ageing of the microstructures under leaching and the evolution of the mechanical properties under storage conditions (water representative of the environment of the storage, temperature) will be necessary in order to determine the properties of the composites envisaged in storage situation. The acquired data will be able to feed the most relevant damage models to evaluate the long-term behavior of the liner. They will also allow to advance on the final choices of the most relevant matrix/fibre pairs for the envisaged application.
Study of yield stress fluids based on emulsions and microgels: The role of interactions and architecture at the colloidal scale
by Magdalena PRZERADZKA (Institut des Sciences Moléculaires)
The defense will take place at 14h00 - Amphitheater 2 16 Avenue Pey-Berland ENSMAC Institut des Sciences Moléculaires - UMR 5255 CNRS Université de Bordeaux 33600 Pessac
in front of the jury composed of
- Valérie RAVAINE - Professeure - Bordeaux INP - Directeur de these
- Véronique SCHMITT - Directrice de recherche - CNRS, Bordeaux - CoDirecteur de these
- Céline PICARD - Professeure - Université Le Havre Normandie - Rapporteur
- Pascal PANIZZA - Professeur - Université de Rennes - Rapporteur
- Michel CLOITRE - Directeur de recherche émérite - CNRS, ESPCI Paris - Examinateur
Yield-stress fluids are materials that resist deformation until a critical stress is exceeded, after which they flow like liquids. They are widely used in areas such as food processing, construction, and additive manufacturing, where control over flow and stability is essential. This thesis aims at investigating how the mesoscopic structure and interactions of soft colloidal systems determine their rheological response. Soft colloids, such as emulsions and microgels, serve as model systems for studying these phenomena because they combine deformability, tunable interactions, and well-defined particle-scale structure. Concentrated emulsions stabilized by a nonionic surfactant were prepared with controlled droplet size and interfacial properties to examine how droplet packing and interfacial energy influence elasticity and flow. The observed rheological behaviour followed the one expected for soft glassy materials, with yield stress and elastic modulus increasing with concentration. By varying the surfactant concentration above the critical micellar concentration, depletion-induced attractions were introduced, enabling a controlled transition from repulsive, jammed emulsions to weakly attractive networks. These emulsions served as reference systems for comparison with soft colloids of greater internal complexity. The study then focused on suspensions of poly(N-isopropylacrylamide) (pNIPAM) microgels—cross-linked polymer particles that swell in water and collapse above their volume phase transition temperature. By adjusting the internal cross-linking density, we examined how microgel softness and structure influence the transition between fluid-like and solid-like states. Rheological measurements showed a continuous evolution of elasticity with increasing concentration, resulting from progressive particle deformation and interpenetration. At high effective volume fractions, the suspensions formed continuous elastic networks whose modulus increased linearly with concentration, consistent with rubber-like behaviour of compressed polymer systems. Start-up flow experiments revealed a two-step yielding response in the most concentrated suspensions, corresponding to the sequential breakdown of local cages and interpenetrated polymer regions under deformation. This system was further modified by introducing phenylboronic acid (PBA) groups onto the microgels and adding poly(vinyl alcohol) (PVA), allowing the formation of multivalent dynamic covalent bonds between boronate groups and diols. Rheological measurements revealed pronounced shear-thickening behaviour—an increase in viscosity and elasticity with shear rate—arising from the stress-induced formation of PBA–PVA bridges between microgels and the resulting transient network. This process was reversible and could be suppressed by adding competing monodiols such as fructose, confirming the role of dynamic bonding in controlling the flow behaviour. These results highlight the importance of transient interparticle connections in defining the non-linear response of microgel suspensions. Overall, this work provides a coherent understanding of how mesoscopic structure, deformability, and reversible interactions govern the rheology of soft colloidal materials. The comparison between emulsions, microgels, and dynamically bonded networks establishes a unified experimental framework for analysing flow and yielding transitions in systems that bridge colloidal and polymeric behaviour.
ED Droit
Articulation of international instruments for the protection of children's rights in Africa
by Robin LECHEKS (CENTRE DE RECHERCHES ET DE DOCUMENTATION EUROPÉENNES ET INTERNATIONALES)
The defense will take place at 14h30 - Salle des Thèses Université de Bordeaux,16 Av. Léon Duguit, 33600 Pessac, France
in front of the jury composed of
- Baptiste TRANCHANT - Professeur des universités - Université de Bordeaux - Directeur de these
- Abdou-Khadre DIOP - Professeur agrégé - Université numérique Cheikh Hamidou Kane - Rapporteur
- François ROCH - Professeur agrégé - UQAM - Rapporteur
- Hélène RASPAIL - Professeure des universités - Le Mans Université - Examinateur
- Mulry MONDELICE - Professeur agrégé - Collège militaire royal de Saint-Jean - Examinateur
- Olivier DELAS - Professeur agrégé - Université Laval - CoDirecteur de these
Africa is distinguished by the existence of a dual binding instrument specifically dedicated to children's rights, a singularity on a continental scale, which finds its concretization in the United Nations Convention on the Rights of the Child (1989) and the African Charter on the Rights and Welfare of the Child (1990). This normative duality raises complex challenges of articulation. This research examines how the articulation between these two instruments influences the effectiveness of child rights protection in Africa. The central hypothesis posits that this coexistence offers potential for enhanced protection, provided that coherent articulation is developed between the two systems. The methodology combines comparative legal analysis, empirical documentary research covering the practice of both Committees, and an interdisciplinary approach. The results demonstrate that normative divergences reflect complementary rather than contradictory conceptions of child protection. The research develops the concept of « contextual universalism » which recognizes the validity of regional adaptations while maintaining the requirement of effectiveness. Concrete proposals include notably the creation of a permanent coordination mechanism between the two Committees and the harmonization of reporting procedures.
ED Sciences de la Vie et de la Santé
Radiopharmaceuticals for precision medecine
by Lina ALI (Institut de neurosciences cognitives et intégratives d'Aquitaine)
The defense will take place at 10h00 - Salle S2040 2 rue du Docteur Hoffmann Martinot, Batiment BBS, Campus Carreire, INCIA, 2ème étage, 33076, Bordeaux
in front of the jury composed of
- Clément MORGAT - Professeur des universités - praticien hospitalier - Université de Bordeaux - Directeur de these
- Jonathan VIGNE - Professeur des universités - praticien hospitalier - Université de Caen - Rapporteur
- Johnny VERCOUILLIE - Maître de conférences - Université de Tours - Rapporteur
- Suzan SAMRA - Assistant professor - Université de Tishreen - Examinateur
In the realm of oncological treatment, radiotherapy, specially targeted radionuclide therapy (TRT), holds significant potential for both diagnosis and therapy. TRT is a novel and advanced therapeutic approach that involves the use of radioactive substances (radionuclides) to deliver targeted radiation to cancer cells while minimising exposure to surrounding healthy tissues. The underlying mechanism of TRT involves arming a radioactive element to a biological molecule, such as peptides, antibodies or other compounds with high affinity for cancer cell markers, to specifically target tumour-associated receptors or antigens. The resulting drugs are called radiopharmaceuticals. These drugs could be used for either diagnostic or therapeutic purposes in what is termed "radiotheranostic." These radionuclides can be β+ emitters such as 68Ga for imaging, or β- emitters such as 177Lu or α-emitters such as 225Ac for therapy). Nowadays, TRT is evolving quickly. Several radiopharmaceuticals are already in use to treat specific tumours, for example, 177Lu-labeled radiopharmaceuticals targeting somatostatin receptors in metastatic neuroendocrine tumours ([177Lu]Lu-DOTATATE) and the Prostate-Specific Membrane Antigen (PSMA) in castration-resistant metastatic prostate cancer ([177Lu]Lu-PSMA-617). However, the potential of personalised TRT can only be achieved if patient/cancer-specific markers are identified and related radiopharmaceuticals are developed and validated. In this work, we decided to focus our investigations on neuropeptides-based radiopharmaceuticals targeting neurotensin receptors (mainly NTS1), the Gastrin-Releasing Peptide Receptor (GRPR) and neuropeptide-Y (NPY) receptors (mainly Y5) for radiotheranostic purposes. In the first part of this thesis, our aim was to develop optimised neurotensin radiopharmaceuticals for better patients' selection eligible to TRT. The impact of changing the radionuclide and/or the chelate on the binding properties of a series of novel peptide-based NTS1 radiopharmaceuticals was evaluated. Radiolabelling of these compounds were performed and optimised with 68Ga, 18F and 64Cu. In vitro assessments, to define their affinity towards NTS1, their internalisation and excretion out of the cells were conducted, followed by in-vivo translation of the most promising compounds in mice. In a separate work, we highlighted a novel mechanism by which NTS1-radiopharmaceuticals are uptaken (patent pending). For TRT applications, we aimed at using a pure Auger electron emitter “103Pd” linked to an innovated chelate conjugated with a neurotensin analogue, and in vitro and in vivo assessment were conducted. Finally, to expand the use of NTS1-based radiotheranostic, the expression of NTS1 was investigated in primary kidney cancer and compared to PSMA and other neuropeptide receptors (Y5). In the second section, we decided to focus on GRPR and its analogues. RM2 is a previously designed GRPR antagonist, which opened new possibilities for cancer imaging and therapy. However, 18F-GRPR radiopharmaceuticals are not yet available. Thus, we assessed the impact of structural modifications on RM2 to introduce 18F through the [18F]AlF-RESCA strategy. The resulting compound has been evaluated only in-vitro and compared with different radionuclides (68Ga and 177Lu), to observe the influence of substituting the radionuclide on the binding characteristics of the peptide. Finally, the last chapter is dedicated to NPY analogues, specifically those targeting the Y5 receptor. Various generations of NPY analogues were developed and the binding properties of these compounds has also been examined in-vitro, as well as in vivo . The engagement of Y5 in cancer, precisely tumour imaging and therapy using TRT, was the most complicated to be evaluated due to the absence of literature. In summary, this research aims at advancing TRT for personalised cancer treatment.
Therapeutic targeting of the metabolic vulnerability of cutaneous squamous cell carcinomas
by Ferial KHALIFE (BoRdeaux Institute of onCology)
The defense will take place at 14h00 - Module 1.1 Université de Bordeaux, campus Carreire, bâtiment CROUS, 1er étage 146 Rue Léo Saignat, 33000 Bordeaux
in front of the jury composed of
- Hamid-Reza REZVANI - Directeur de recherche - Université de Bordeaux - Directeur de these
- Walid RACHIDI - Professeur des universités - Université Grenoble Alpes - Rapporteur
- Pierre SONVEAUX - Professor - Université catholique de Louvain (UCLouvain), FNRS - Rapporteur
- Anne-Karine BOUZIER-SORE - Directrice de recherche - Université de Bordeaux – UMR 5536 CRMSB - Examinateur
- Alice CARRIER - Directrice de recherche - Centre de Recherche en Cancérologie de Marseille (CRCM) - Examinateur
Alteration in metabolic activities is a critical step in cancer progression, and several metabolic-based therapy options are increasingly being proposed for human tumors. However, emerging evidence highlights interpatient metabolic heterogeneity and underscores the importance of metabolic phenotyping in cancer treatment. In this study, we profiled the metabolism of human cSCC samples across stages of carcinogenesis and identified three subgroups with low, medium, and high metabolic scores—even at the precancerous stage. We then investigate the impact of this metabolic heterogeneity on cSCC responses to inhibitors of dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine biosynthesis. Using patient-derived xenograft (PDX) models, we showed that DHODH inhibitor efficacy correlates with metabolic score, highlighting its potential for predicting treatment response. To further assess the therapeutic potential of DHODH inhibition, we evaluated the efficacy of two DHODH inhibitors, leflunomide and PTC299, in immunocompromised mice xenografted with A431 and SCC13 cell lines. Our results demonstrate that leflunomide significantly inhibited tumor growth only in the A431-derived xenografts, whereas PTC299 suppressed tumor growth in both SCC13 and A431 models. These findings highlight the relevance of metabolic profiling in the design of therapeutic strategies that target the bioenergetic vulnerabilities of tumors. They also suggest DHODH may be a promising therapeutic target, at least in a subset of cSCC. Moreover, our data suggest that PTC299 could offer broader therapeutic benefits by potentially overcoming resistance mechanisms associated with metabolic plasticity.
STUDY AND IN VITRO MODELING OF INTERFACES DURING TUMOR PROGRESSION
by Lucile ROUYER (BoRdeaux Institute of onCology)
The defense will take place at 14h00 - Amphithéâtre BBS Batiment Bordeaux Biologie Santé (BBS) 2 rue du docteur Hoffmann Martinot 33000 Bordeaux
in front of the jury composed of
- Frédéric SALTEL - Directeur de recherche - Université de Bordeaux - Directeur de these
- Audrey FERRAND - Chargée de recherche - Université de Toulouse - Rapporteur
- Frédéric BARD - Directeur de recherche - Université Aix Marseille - Rapporteur
- Danijela VIGNJEVIC - Directrice de recherche - Université Paris Sciences et Lettres - Examinateur
- Morgan DELARUE - Chargé de recherche - Université de Toulouse - Examinateur
- Fatima MECHTA-GRIGORIOU - Directrice de recherche - Université Paris Sciences et Lettres - Examinateur
- Grégory GIANNONE - Directeur de recherche - Université de Bordeaux - Examinateur
The tumor microenvironment plays a central role in cancer progression, particularly through the interfaces between cancer cells and their surrounding elements. These interfaces directly influence tumor cell behavior, especially migration and invasion. In my thesis, I investigated two types of interfaces: collagen/cancer cells and normal epithelial cells/cancer cells. The first part focused on the collagen/cancer cell interface in triple-negative breast cancer (TNBC), through the study of structures named “collagen-tracks”. During migration, cancer cells deposit vesicles enriched in adhesion receptors and microRNAs onto type I collagen fibers. Collagen-tracks can be internalized by less aggressive cells and acquire invasive properties from highly invasive cancer cells. This work uncovers a novel local mechanism of intercellular communication at the collagen/cancer cell interface that promotes tumor invasion, a critical step in cancer progression. The second part of this thesis investigate the normal epithelial/cancer cell interface in hepatocellular carcinoma (HCC). We developed a dynamic 3D model that recreates the interface between normal hepatic cells and cancer cells. This system enables the analysis of how interactions between normal and tumor cells evolve during proliferation and invasion, providing a powerful tool to better understand the mechanisms driving tumor progression.
DECIPHERING WHOLE GENOME TRANSPLANTATION MECHANISMS IN MOLLICUTES
by Jitra-Marie JITTASEVI (BFP - Biologie du Fruit et Pathologie)
The defense will take place at 14h00 - Amphithéâtre de l'Institut des Sciences de la Vigne et du Vin Institut des Sciences de la Vigne et du Vin 210 Chemin de Leysotte 33140 Villenave-d'Ornon
in front of the jury composed of
- Carole LARTIGUE - Chargée de recherche - INRAE Nouvelle Aquitaine-Bordeaux - Directeur de these
- Sébastien RODRIGUE - Professor - Université de Sherbrooke - Rapporteur
- Christophe DANELON - Professeur des universités - Institut National des Sciences Appliquées (INSA) Toulouse - Rapporteur
- Sabine PEREYRE - Professeure des universités - praticienne hospitalière - Centre Hospitalier Universitaire de l'Université de Bordeaux - Examinateur
- Patrice GAURIVAUD - Ingénieur de recherche - Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail - Laboratoire de Lyon - Examinateur
- Grégory BOËL - Directeur de recherche - Institut de Biologie Physico-Chimique - Examinateur
One of the goals of synthetic biology is to determine the functions that are essential for life, and to use that knowledge to assemble an artificial cell. To that purpose, the members of the bacterial class Mollicutes are a good study model. With their reduced genomes, they are the smallest living organisms capable of self-replication outside of a host, earning them the title of natural minimal cells. Whole genome transplantation (GT) is a technique in which a donor genome from Species A is isolated and genetically modified through an intermediate host, the yeast Saccharomyces cerevisae. The genome is then transferred into the cytoplasm of Species B, the recipient cell. After a selection process, the cell compartment (B) acquires the genetic and phenotypic identity of the donor genome (A). This method is revolutionary for the production of synthetic cells. It delivers a framework to determine the molecular interactions that are essential for genetic information processing. However, GT is limited to a handful of Mollicutes donor genomes in the recipient cell Mycoplasma capricolum subsp. capricolum (Mcap). Its expansion to other species is held back by an insufficient comprehension of its mechanisms. It has been shown that GT efficiency decreases when the phylogenetic distance between donor genome and recipient cell increases, suggesting that there are genetic and biochemical parameters that govern their compatibility. This PhD project aimed to identify such compatibility factors and to better describe GT mechanisms. First, we attempted to describe the behaviour of the molecular machineries that enable the boot-up of a genome in a cell compartment. We hypothesised that the ability of the recipient to transcribe the donor genome is an early and essential factor in cell boot-up. We designed two complementary strategies to study the role of transcription during GT of Mesoplasma florum in Mcap. To characterize the interactions between two transcription machineries within the same cellular environment, we expressed five recombinant M. florum RNA polymerase (RNAP) protein subunits in Mcap. When the RNAPs of both species are expressed simultaneously, we observed mutations in the coding sequences of the catalytic subunits RpoBMfl and RpoCMfl of M. florum. In parallel with this strategy, we aimed to evaluate the compatibility between a genome and the RNAP expressing it by replacing all the coding sequences of Mcap's RNAP by Mflorum's. We discovered that Mcap is functional when it expresses only the M. florum RNAP, as well as several hybrid combinations, but it doesn't significantly increase the transplantation efficiency of M. florum in Mcap. We also confirmed that the RpoB/RpoCMfl subunits are incompatible with the remaining Mcap RNAP subunits. We conclude that the formation of hybrid transcription machineries is toxic for the cell and decreases the probability of selecting a viable donor genome. In a second part of the project, our purpose was to identify specific factors that enable GT in a new species (Mbovis), which was established for the first time during the course of the PhD. We characterised the genome and proteome of the clone yielding the best GT results and discovered multiple distinctive genetic features which could be involved in GT. In particular, inactivating a surface nuclease (MnuA) and deregulating the cell division cluster through the inactivation of FtsZ were shown to favour GT. In summary, this PhD work allowed us to add new elements to the GT model and will orient further studies of its mechanisms. It reported the possibility of interferences within the multiple cellular processes expressed simultaneously by both genomes during the boot-up process, and emphasized the importance of the manner in which the donor genome enters the recipient cell.
Impacts of immune ageing on vaccine cellular responses
by Pauline SAINT-CHARLES (Immunologie Conceptuelle, Expérimentale et Translationnelle)
The defense will take place at 14h00 - Amphithéâtre ENSTBB ENSTBB-Bordeaux INP 146 Rue Léo Saignat, 33000 Bordeaux
in front of the jury composed of
- Victor APPAY - Directeur de recherche - Université de Bordeaux - Directeur de these
- Stéphanie GRAFF-DUBOIS - Professeure - Centre d'Immunologie et des Maladies Infectieuses (CIMI) - Rapporteur
- Delphine SAUCE - Directrice de recherche - Centre d'Immunologie et des Maladies Infectieuses - Rapporteur
- Arnaud MARCHANT - Professeur - Université libre de Bruxelles - Examinateur
- Bruno SALAUN - Docteur - GlaxoSmithKline - Examinateur
The increase in life expectancy in the general population, driven by medical and technological advances, is accompanied by demographic aging. At the same time, the introduction of effective antiretroviral therapies (ART) since 1996 has transformed HIV infection into a chronic disease, allowing people living with HIV (PLWH) to achieve a life expectancy similar to the general population. This dual phenomenon raises major public health issues regarding the management of aging and protection against infectious diseases. Older people, and particularly PLWH, constitute a population at increased risk of infectious complications. In this context, the adaptation of vaccination strategies and vaccination schedules is necessary. However, vaccine efficacy is limited by immunosenescence, a biological process characterized by progressive age-related alterations of the immune system. Understanding the cellular dynamics involved in this immune aging is therefore essential to optimize vaccination and strengthen the protection of aging populations, whether they are living with HIV or not. In this context, the analyses focused on two cohorts in order to characterize the vaccine cellular response and particularly the Th1 response, which is involved in the initiation of the cytotoxic response, necessary for the control of viral replication. We also studied the circulating component of follicular helper T lymphocytes in order to associate it with the vaccine-specific antibody response. Finally, we carried out ex vivo functional tests and the study of senescence markers by flow cytometry in order to link a potential alteration of the cellular vaccine response with the state of senescence. First, we carried out these analyses on the Vaccines and Infectious Diseases in the Ageing Population (VITAL) cohort, composed of people aged 25 to 98 years, vaccinated against influenza. This work is part of a European consortium in which several teams in France, the Netherlands, Denmark, Austria, Italy, and Spain are involved. Second, the SHINGR'HIV cohort consists of older PLWH vaccinated against shingles (using the recombinant vaccine Shingrix [GSK] which has not been studied in this population).
Study of the mechanism of interaction between red varietal wines anthocyanins and proteins rich in proline and sensory consequences
by Katarina DELIC (Oenologie)
The defense will take place at 9h00 - Amphitheâtre de l'Institut des Sciences de la Vigne et du Vin ISVV, 210 chemin de Leysotte 33882 Villenave d'Ornon, France
in front of the jury composed of
- Pierre-Louis TEISSEDRE - Full professor - Université de Bordeaux - Directeur de these
- Fernando ZAMORA - Full professor - Universitat Rovira i Virgili Departamento de Bioquímica y Biotechnología Campus Sescelades - Rapporteur
- Danijel MILINCIC - Senior Research Associate - Faculty of Agriculture University of Belgrade - Examinateur
- Stamatina KALLITHRAKA - Full professor - Agricultural University Athens Food Science and Human Nutrition Dept. Laboratory of Oenology - Examinateur
- Aleksandar KOSTIC - Associate Professor - Faculty of Agriculture University of Belgrade - Examinateur
- Ivana KARABEGOVIC - Full professor - Food Technology and Food Safety, Faculty of Technology, University of Niš - Rapporteur
In this study, the reactivity of procyanidins and anthocyanins in young and aged ‘Prokupac', ‘Merlot' and ‘Cabernet Sauvignon' wines toward salivary proteins is investigated via SDS-PAGE and UHPLC-QTOF-MS to determine the differences between the phenolic compounds of red wine in relation to the aging process of wine. SDS-PAGE analysis revealed that procyanidins, flavanol-anthocyanin polymers, and ellagitannins in aged wine have strong affinities for salivary proteins, leading to the formation of insoluble complexes. By contrast, young wine contained predominantly procyanidins with high salivary protein affinity, as well as monomeric flavan-3-ols and anthocyanins, which mainly form soluble aggregates, while polymeric phenolics were less represented. Electrophoretic patterns further showed that seed-derived procyanidins mainly formed insoluble complexes with salivary proteins, whereas skin-derived anthocyanins tended to form soluble ones. The total content of all phenolic compounds quantified by UHPLC-QTOF-MS was 2.5 times higher in young wine than in aged wine, primarily due to the significantly greater abundance of malvidine-3-O-glucoside in young wine (eightfold higher level in young wine). Targeted UHPLC-QTOF-MS analysis of selected phenolics confirmed the electrophoretic results and showed a higher binding affinity of procyanidins in aged wine compared to young wine, as well as a higher percentage of procyanidin binding compared to anthocyanins, independent of the age of the wine. Sensory evaluation showed that aged wine had higher tannin quality scores, whereas young wine exhibited greater acidity and astringency, with bitterness being comparable between them. These results highlight the influence of wine aging on the interaction between phenolic compounds and salivary proteins and emphasize the dominant role of procyanidins in protein binding and the potential synergistic contribution of anthocyanins to mouthfeel perception.
Effect of rootstock genetic variability on the aroma of Vitis vinifera cv. Cabernet-Sauvignon wines. Compositional and sensory approaches
by Laura FARRIS (Oenologie)
The defense will take place at 9h00 - Amphi Lescouzères Bordeaux Sciences Agro 1 Cour du Général de Gaulle 33170 Gradignan
in front of the jury composed of
- Jean-Christophe BARBE - Professeur - Université de Bordeaux, INRAE, Bordeaux INP, Bordeaux Sciences Agro, UMR 1366, OENO, ISVV, F-33140 - Directeur de these
- Aurélie ROLAND - Maîtresse de conférences - SPO, Université Montpellier, INRAE, Institut Agro Montpellier Supagro - Rapporteur
- Christian CHERVIN - Professeur - AgroToulouse, Université de Toulouse, INP-ENSAT, BP 32607 - Rapporteur
- Cécile COULON-LEROY - Maîtresse de conférences - ESA, USC 1422 INRA-GRAPPE, Ecole Supérieure d'Agricultures - Examinateur
- Luigi MOIO - Professeur - Department of Agricultural Sciences, Section of Vine and Wine Sciences, University of Napoli ″Federico II″ - Examinateur
The aromatic profile of wine is a crucial element for its quality and consumer acceptance. While factors such as climate, grape variety, and winemaking conditions are well known for their decisive influence on this profile, the role of the rootstock remains a fragmented area of research. Initially selected for its resistance to phylloxera, the rootstock has become an essential tool for adapting to pedoclimatic conditions and achieving production objectives. Despite this importance, its impact on wine aromatic compounds is still poorly studied. In this context, this thesis aims to address this gap by investigating how rootstocks influence aromatic compounds and the sensory expression of wines. The study particularly examines how this impact is related to the modulation of grape ripening, itself dependent on the vine's water and mineral status, as well as key agronomic parameters such as phenological stage, vegetative expression, and yield. The research was carried out within the GreffAdapt experimental design, which includes 55 rootstocks grafted with five different scion varieties. The study focused on 20 rootstocks grafted with Cabernet-Sauvignon across three vintages. To evaluate the influence of rootstocks, an extensive phenotyping was performed on the vines, including mid-veraison date, vegetative growth and yield measurements, as well as assessments of water and nitrogen status. Once harvested, the grapes were analyzed for their chemical composition before standardized microvinifications were conducted. The resulting wines were subjected to targeted analyses to quantify a wide range of aromatic compounds. Finally, a two-step sensory methodology was employed, combining a Napping task to assess perceived diversity and a descriptive sensory profile to characterize the same wines. The results showed that rootstocks had a significant impact on ripening parameters, particularly organic acids. However, their effect on most quantified aromatic compounds was limited. Notable effects were observed only for β-damascenone, IBMP, and linalool, with concentrations varying across vintages. The Napping task confirmed sensory diversity among wines, with some interannual variability, although certain rootstocks formed stable groups over multiple vintages. The descriptive profile further characterized these differences, identifying aromas such as blackcurrant and jammy red fruits as being significantly influenced by the rootstock.
ED Sciences Physiques et de l'Ingénieur
Development of an ultrasonic method for active microrheology with acoustical tweezers.
by Antoine PENNERON (I2M - Institut de Mécanique et d'Ingénierie de Bordeaux)
The defense will take place at 14h00 - Amphi A Bâtiment A29, 351 Cr de la Libération, 33400 Talence
in front of the jury composed of
- Diego BARESCH - Chargé de recherche - Université de Bordeaux - Directeur de these
- Régis MARCHIANO - Professeur des universités - Sorbonne Université - Rapporteur
- Valentin LEROY - Directeur de recherche - Université Paris Cité - Rapporteur
- Stefan CATHELINE - Directeur de recherche - Université Lyon 1 - Examinateur
- Émilie FRANCESCHINI - Directrice de recherche - Université Aix-Marseille - Examinateur
- Thomas BRUNET - Maître de conférences - Université de Bordeaux - CoDirecteur de these
Non-invasive mechanical characterization of soft and fragile materials is a major challenge for mechanobiology and rheology of complex media. Existing active microrheology techniques (optical, magnetic) face intrinsic limitations. Among these are the weak forces developed by optical tweezers (pN), the opacity of biological media, or the necessity of ferromagnetic probes. In this work, we demonstrate that an acoustic tweezer with a single focused beam with helical wavefront (vortex) enables local probing of soft media elasticity (20--100~Pa). This approach generates forces on the order of $mu$N with low beam intensities (<~1~W/cm$^2$). The scientific contribution of this thesis concerns the experimental validation of a recent theoretical formalism for calculating acoustic radiation force in elastic media. The approximation of very soft aqueous media leads to major simplifications of the radiation stress tensor. These assumptions allow us to show that forces in very soft aqueous media and in water are equivalent, a result verified both numerically and experimentally. Our approach exploits microbubbles as probes manipulated by an acoustic vortex (2.25 MHz). Their high impedance contrast between the gas and aqueous phases generates significant forces for low beam amplitudes. The induced displacement of bubbles in the vortex focal plane results from two contributions. The first is a restoring component called the gradient force. The second, called the scattering force, arises from the transfer of angular momentum flux. By combining a simple elastic model for hydrogel deformation induced by bubble displacement with radiation force calculations, we extract local values of the medium's shear modulus. The results demonstrate excellent agreement with standard rheometry. These measurements simultaneously validate the theoretical model and establish the first functional acoustic tweezer for active microrheology. Unlike usual approaches based on empirical calibration, our method relies on rigorous theoretical prediction of radiation force. This technique opens perspectives for three-dimensional and local characterization of complex, heterogeneous, anisotropic, and light-opaque media. A methodological extension allowing bubble tracking by localized ultrasound imaging is conceivable. Miniaturization of the device by working with high-frequency beams (< 10 MHz) is also possible. This work presents the foundations of an all-acoustic active microrheology method for complex media rheology and mechanobiology.
ED Sociétés, Politique, Santé Publique
Children's participation in decision-making in child protection. An ecosystemic and psycho-developmental approach of the representations and practices of children in foster care and professionals
by Alizée DELHOSTE (Laboratoire de Psychologie)
The defense will take place at 14h00 - Amphithéâtre Pitres Université de Bordeaux, Campus Victoire 3ter Place de la Victoire, 33076 Bordeaux Cedex
in front of the jury composed of
- Véronique ROUYER - Professeure des universités - Université de Bordeaux - Directeur de these
- Fabien BACRO - Maître de conférences - Laboratoire de Psychologie des Pays de la Loire (LPPL, UR 4638), Université de Nantes - Rapporteur
- Benoît SCHNEIDER - Professeur des universités - Laboratoire Lorrain de Psychologie et Neurosciences de la Dynamique des Comportements(2LPN) / EA 7489, Université de Lorraine - Examinateur
- Séverine EUILLET - Maîtresse de conférences - CREF, Université Paris Nanterre - Rapporteur
Abstract. The adoption of the CRC in 1989 recognises the right of all children, under the age of 18, to freely express their opinions in decisions that affect them and to have those opinions duly taken into account, in accordance with their age and degree of maturity. However, this legal recognition alone does not guarantee effective participation, particularly in the field of child protection. Several national reports (Cerisuela et al., 2023; Hédon, 2020) and international research (Euillet & Faisca, 2019; Toros, 2021; van Bijleveld et al., 2015) highlight the existence of multiple obstacles that hinder its implementation and limit the recognition of children as actors in decision-making processes. Yet, participation is not only a fundamental right: it also determines the effectiveness of other rights recognised by the CRC (Hédon, 2020), contributes to the development and well-being of children in care, and to the quality of their placement (Lansdown, 2001; Rafeedie et al., 2019; Toros, 2021). Furthermore, multidisciplinary research still frequently associates children with the legal term ‘minor' and mainly documents the participatory experiences of adolescents, and more rarely those of school-age children. In this context, this doctoral thesis in developmental psychology examines the participation of children aged between 6 and 12, who are in foster placement, in decisions concerning them. This research is based on a dual approach: ecosystemic (Bronfenbrenner, 2005) to understand the influence of several ecological contexts on the effectiveness of participation, conceived as a psycho-social process, and psycho-developmental (Malrieu, 1973, 1977, 2003), considering the active role of children in their own development through their interactions with their living environments. This study is structured around four objectives: to study the representations and practices of a variety of child protection professionals (1), as well as the obstacles, levers and adjustments to participation that they identify (2); to examine the influence of the representations of fostered children's (6-12 years old) concerning their participation in institutional decisions on their subjective experience of placement (3); to understand how they perceive and make sense of their participation in daily and institutional decision-making (4). To this end, semi-structured interviews were conducted with 21 professionals (11 foster carers, 6 caseworkers, 2 heads of child welfare services, 2 juvenile court judges) and 6 children (aged 8-12) in the form of activities designed to facilitate access to their views. Findings from the thematic analysis indicate that, in professional practice, children's participation remains mainly consultative. Its implementation appears to be conditioned by certain levers and obstacles situated at different levels: ontosystemic (children's individual characteristics and lived experiences), microsystemic (child-professional relationships), mesosystemic (relationships between professionals), exosystemic (organisation of child welfare services, legal framework for placement) and macrosystemic (child-adult power relations). The results of the analytical questioning analysis show that participation has an influence on the subjective experiences of children (aged 8-12) throughout the placement process. Furthermore, participation also acts as a lever for socialization, through the way in which children position themselves and make sense of the relationships they build with adults, as well as to the educational rules and institutional functioning with which they are confronted.
Understanding the fate and related risk factors in European children on kidney replacement therapy through epidemiological studies and registry data
by Evgenia PREKA (Bordeaux Population Health Research Center)
The defense will take place at 14h00 - Module 1.4 Campus Carreire 146 rue Leo Saignat 33000 Bordeaux
in front of the jury composed of
- Jérôme HARAMBAT - Professeur des universités - praticien hospitalier - Université de Bordeaux - Directeur de these
- Marjolein BONTHUIS - Docteure - ERA Registry, University of Amsterdam, UMC - CoDirecteur de these
- Kitty JAGER - Full professor - ERA Registry - Examinateur
- Karen LEFFONDRE - Professeure des universités - ISPED Université de Bordeaux - Examinateur
- Thomas JOUVE - Professeur des universités - praticien hospitalier - Universite Grenoble Alpes - Rapporteur
- Cecile COUCHOUD - Docteure - Agence de Biomedecine - Rapporteur
End-stage kidney disease (ESKD) in children is rare yet serious, requiring kidney replacement therapy (KRT) by dialysis or kidney transplantation (KT). This thesis investigates determinants of care and outcomes for pediatric KRT in Europe using population-based studies from the ESPN/ERA Registry. We addressed three questions: (1) whether earlier dialysis initiation improves outcomes, (2) which factors shape access to first and repeat transplantation, and (3) long-term patient and graft survival after one or more KTs. We included European patients who initiated renal replacement therapy (RRT) before adulthood from the ESPN/ERA Registry. Study 1 drew data from 21 national registries, analysing 2,963 children starting chronic dialysis across a range of kidney function (early vs. late by estimated glomerular filtration rate, eGFR) to evaluate survival, access to transplant, growth, and cardiovascular risk. Studies 2 and 3 used data from 11 national registries: Study 2 examined 12,623 patients who began RRT before age 20 (1978–2019) to quantify access to first, second, and third KTs and identify demographic and disease-related disparities; Study 3 assessed survival in 11,078 first, 2,962 second, and 718 third KT recipients. Survival was evaluated with Kaplan–Meier and Cox models with adjustment for confounding. Early dialysis initiation (higher eGFR at start) did not improve short-term survival or transplant access compared with later initiation; mortality and transplant rates at 1, 2, and 5 years were similar. Hypertension was more prevalent among late starters (64% vs. 51%). These findings suggest no general benefit to early dialysis in asymptomatic children and support clinical, rather than eGFR-only, triggers for starting dialysis. Transplant access was high overall—88% received a first KT, 73% a second, and 60% a third over long-term follow-up—but inequities were evident. Very young children (<5 years) and adolescents (15–19 were less likely to receive timely transplants than 10–14-year-olds. female patients had slightly reduced access (hr 0.94). diseases prone recurrence (e.g., glomerulonephritis) associated with delayed first kt. pre-emptive transplantation prior graft survival>5 years favoured retransplant access. Patient survival after transplantation was excellent: 5-year survival after first KT was 97% and remained >90% at 10 years; after second and third KTs, 10-year patient survival exceeded 94%. Graft survival declined with each successive KT (5-year: 79% first, 69% second, 67% third; 10-year: 63%, 52%, 51%). Adolescents, females, and recipients with focal segmental glomerulosclerosis or other recurrent/metabolic diseases had higher graft loss risk. Living donor and pre-emptive KTs were associated with superior outcomes across first and repeat transplants. In summary, European registry evidence indicates dialysis can often be deferred until conventional thresholds (≈8 mL/min/1.73 m²) without compromising early survival or transplant access, reinforcing guideline recommendations to base dialysis start on clinical need. While patient survival after pediatric KT is outstanding—even through multiple transplants—graft longevity remains a key limitation influenced by age, sex, and primary disease. Policies to ensure equitable, timely transplantation (especially for very young children, adolescents, and females), strengthen adolescent transition to adult care, mitigate immunologic risks in recurrent diseases, and expand preemptive and living donation are likely to further improve lifelong outcomes for children with ESKD.
Changes in mathematical frameworks and the conversions between representation registers within both the teaching and learning processes of elementary algebra.
by Maria GEITANI (Laboratoire d'épistémologie et didactiques disciplinaires, professionnelle et comparée de Bordeaux)
The defense will take place at 9h00 - En visio totale En visio totale
in front of the jury composed of
- Lalina COULANGE - Full professor - Université de Bordeaux - Directeur de these
- Hersant MAGALI - Professeur - CREN (UR2661), Nantes Université - Rapporteur
- Chaachoua HAMID - Professeur - LIG (UMR 5217), Université Grenoble Alpes - Rapporteur
- Constantin CéLINE - Maître de conférences - MCF, LIRDEF, Univ Montpellier, Univ Montpellier Paul Valéry - Examinateur
- Train GRéGORY - Maître de conférences - MCF, Lab-E3D (EA 7441), Université de Bordeaux - Examinateur
This thesis provides an in-depth analysis of the learning of elementary algebra by Lebanese students at the point where they first engage with this learning. It examines how these students produce and interpret algebraic expressions intended to model relationships between geometric quantities, with a focus on the obstacles they encounter and the underlying thought processes. Situated within the field of mathematics education, it draws on the theoretical framework of frame changes and conversions between registers of representation to shed light on the transitions from arithmetic to algebra. The empirical study is based on two successive questionnaires administered to a representative sample of students, together with a detailed analysis of a collective correction session that was fully recorded and transcribed. The tasks proposed to the students are graded to reflect increasing complexity, progressing from simple additive relationships to multiplicative and mixed ones. Quantitative analysis highlights high success rates on additive tasks and markedly greater difficulties with multiplicative and mixed tasks, confirming the existence of a critical threshold in the entry into algebra. The qualitative study of erroneous productions reveals characteristic implicit modes of reasoning, such as confusion between “two times x” and “x²,” assimilation of additive repetition to exponentiation, or partial interpretation of graphical codings of quantities. The analysis of the correction session underscores the ambivalent role of teacher language, which, depending on its formulation, can either support the construction of meaning or reinforce misconceptions. By combining quantitative and qualitative perspectives, this research contributes to a deeper understanding of students' cognitive and linguistic processes and offers concrete avenues for designing teaching situations that foster the articulation between visual, symbolic and verbal registers, particularly in a school context marked by challenging learning conditions.
Identify and understand the different types of learning and their developmental potential in an action-based training program aimed at the professional integration of young people who are far from employment.
by Marilène SERIAU (Bordeaux Population Health Research Center)
The defense will take place at 14h00 - Salle 218 Département HSE, IUT de Bordeaux, 15 rue Naudet 33190 Gradignan
in front of the jury composed of
- Vanina MOLLO - Maîtresse de conférences - Université de Toulouse/INP - Rapporteur
- Vincent GROSSTEPHAN - Professeur des universités - Université Aix-Marseille - Rapporteur
- Gaëtan BOURMAUD - Maître de conférences - Université Paris 8 - Examinateur
- Anne BATIONO-TILLON - Professeure - Haute école pédagogique Vaud - Examinateur
- Alain GARRIGOU - Professeur - Université de Bordeaux - Directeur de these
This thesis focuses on the study of the links between different forms of learning and development identified in an action-training program aimed at the professional integration of young people far from employment. Through the formative intervention that we carried out, this thesis story shows how participatory work with the design team of the system was able to contribute to co-identifying the cultural-historical contradictions of the systems studied in order to characterize micro-innovations. Cultural-historical contradictions are embodied in the field through dilemmas and conflicts; they represent the essence of the functioning of an activity system (AS) and can give rise to micro-innovations if they are debated. On the other hand, this thesis work highlights the challenge for the company of revealing these contradictions as well as the work of preventing the risks of disruption in the learning of young people that may have resulted from them. The methodology used combines the traditional practices and methods of French-speaking ergonomics and those of the Cultural-Historical Activity Theory (CHAT). Our methodology articulates three scales of analysis presented in the form of three hypotheses which correspond to three distinct and interrelated ZDP. Through these hypotheses, the forms of development among learners are first questioned at the individual level; these analyses give rise to the identification of a hypothesis of contradiction: the SA would be shared between integration and training. The conditions of exercise of the training activity of the supervisors are then analyzed, which leads to confirming our hypothesis of contradiction. Finally, we question the contributions of our training intervention and present the participatory work carried out with the team based on the identified contradiction. The results show that through the STEP program, learners develop more than just skills: through the pedagogy implemented, they develop a certain form of autonomy and carry out work to appropriate the mediated tools in line with the ZDP expected by the program. The results also show that some Steppers open “another ZDP”, characterized by defensive learning that can lead to a form of agency and a form of disruption. The analyses of the conditions in which the supervisors' training activity is carried out highlight a certain number of interpersonal conflicts and intrapersonal dilemmas, which are symptoms of the contradiction identified between integration and training. Finally, the results highlight the contributions of our training intervention, reflecting the interest of the participatory dimension in a transformative aim. The hybrid approach between ergonomics and CHAT that we have chosen to adopt highlights the importance of identifying the gaps between the prescribed and the real in the work of uncovering the cultural-historical contradictions of the systems studied.