ED Mathématiques et Informatique
STATEFUL PARTIAL-ORDER REDUCTION METHODS FOR CONCURRENT SYSTEMS WITH BLOCKING INSTRUCTIONS
by Sarah LARROZE-JARDINÉ (LaBRI - Laboratoire Bordelais de Recherche en Informatique)
The defense will take place at 14h00 - Amphi du LaBRI 351, cours de la Libération F-33405 Talence cedex
in front of the jury composed of
- Frédéric HERBRETEAU - Maître de conférences - LaBRI - Directeur de these
- Loïc HéLOUëT - Directeur de recherche - INRIA Rennes - Rapporteur
- Igor WALUKIEWICZ - Directeur de recherche - LaBRI - CoDirecteur de these
- Didier LIME - Professeur des universités - Ecole centrale de Nantes - Rapporteur
- Silvano DAL ZILLIO - Chargé de recherche - Laas - Examinateur
- Marthe BONAMY - Directrice de recherche - LaBRI - Examinateur
We consider the verification of concurrent systems, and in particular ensuring that an undesired behavior cannot occur during the execution of the system. A concurrent system consists of different processes operating independently and interacting with each other through communications or shared variables. Such systems can be represented by a network of processes, each process modeled by an automaton. Communications are modeled by shared actions of distinct processes. The execution of such a system can be represented by a graph. States of this graph contain a location for each process and a valuation for the variables of the system. Edges between states represent the execution of actions. An undesired behavior of such a system can be modeled as a set of bad states. An execution has undesired behavior if a bad state occurs during the execution. This way verification is reduced to a reachability problem in a network of automata. In our case of study, we consider the reachability of final states. The state explosion problem is the main challenge in solving the reachability problem for concurrent systems. For example, if we consider a system of n processes that can each execute a local action, there are n! runs of this system, each corresponding to a different interleaving of the n actions. If the processes do not interact with each other in this system, say they have no variables in common, each of these n! runs leads to the same final state and all these runs can be considered equivalent. To verify if a final state is reachable in this case, it is sufficient to explore only one interleaving of actions and the ordering of actions is irrelevant. This is the idea behind partial-order reduction method developed in the 90s. These methods exploit independency between actions in order to avoid exploring two equivalent runs. These methods have shown to be very efficient on some concurrent systems. Partial-order reduction methods were first introduced as static methods, that is in each state reached during the exploration, the algorithm chooses which actions to explore. This kind of methods only allow to consider static independency between actions, which limits the gains that the methods can offer. The idea of a dynamic algorithm is to detect independency between actions during the execution of the system. During the execution, the actions to be explored from a given state are chosen during the exploration of this state according to what has already been explored. This approach has been applied to stateless exploration, that is when only the current execution is stored during the exploration. The notion of optimality for such method has been introduced in. Stateless algorithms explore the tree of runs of the system. This can be exponentially bigger than the graph, or a transition system representing these runs. This is why we develop stateful dynamic partial-order reduction methods. Storing states allows keeping track of what has been previously explored and we can then implement an algorithm with covering. Indeed, sleep sets are used in order to avoid exploring too many equivalent executions but they can also lead to the exploration of a same state several times with different sleep sets. Then, since we store the states, we can see if a duplicated node of the graph can be covered by an other one, that is a node from which the same executions can be explored. Another novelty is that we allow processes to be blocked due to unavailable communications, we also allow branching. Branching corresponds to several outgoing edges in a client locations, without restriction on the servers communicating on those edges. Nevertheless, we do not allow cycles on client processes. There is no restriction on the server processes.
ED Sciences Chimiques
Novel photoactivatable fluorescent nanoparticles for image-guided cancer therapy
by Justine COUVEZ (Institut des Sciences Moléculaires)
The defense will take place at 14h00 - Salle de conférence 3ème EST Bâtiment A12, Université de Bordeaux, 351 Cr de la Libération, 33405 Talence
in front of the jury composed of
- Mireille BLANCHARD DESCE - Directrice de recherche - Université de Bordeaux - Directeur de these
- Rachel MEALLET - Professeur des universités - Université Paris SACLAY - Rapporteur
- Corinne CHANEAC - Professeur des universités - Sciences Sorbonne-Université - Rapporteur
- Anne-Laure BULIN - Chargée de recherche - Université de Grenoble Alpes - Examinateur
- Vincent SOL - Professeur - Université de Limoges - Examinateur
- Bruno QUESSON - Professeur - Université de Bordeaux - Examinateur
- Bich-Thuy DOAN - Chargée de recherche - Chimie ParisTech – Université PSL - Examinateur
- Olivier SANDRE - Directeur de recherche - Université de Bordeaux - CoDirecteur de these
The development of photoactivatable organic nanoparticles for cancer therapy offers a promising alternative to conventional treatments such as chemotherapy, radiotherapy, immunotherapy, and surgical resection. This emerging field finds its relevance particularly in photodynamic therapy (PDT) and photothermal therapy (PTT), two light-based approaches relying on photophysical/photochemical phenomena to fight cancer. These two approaches are attracting growing interest due to their ability to minimize side effects thanks to the fine control offered by light. The present research project focuses on the design and characterization of fluorescent polymeric nanoparticles, highly dispersible in aqueous media and which can be used as versatile platforms for the conjugation of photosensitizers or photothermal agents intended for PDT or PTT applications. The standardization of the synthesis and purification procedures of these nanoparticles, named sFONPs (Soft Fluorescent Organic Nanoparticles), enabled their comprehensive physicochemical and photophysical characterization as well as the evaluation of various conjugation strategies. The incorporation of various dyes on the sFONPs surface demonstrated the versatility of these systems, which exhibit tunable optical properties and high efficiency in light-to-energy conversion. Behavioural studies in biological environments and MRI-coupled thermometry have demonstrated that sFONPs possess strong potential compared to inorganic or hybrid nanomaterials, positioning them as promising candidates for treating digestive, particularly colorectal, cancers.
From dairy cream to butter : contribution to the multi-scale study of texturing through the control of fat crystallisation
by Valentin DEMAILLE (Institut de Chimie & de Biologie des Membranes & des Nano-objets)
The defense will take place at 14h00 - Amphi 3 16 avenue Pey Berland, 33600 Pessac
in front of the jury composed of
- Fernando LEAL-CALDERON - Professeur des universités - Université de Bordeaux - Directeur de these
- Michel LINDER - Professeur des universités - Université de Lorraine - Rapporteur
- Sabine DANTHINE - Professeure des universités - Université de Liège - Rapporteur
- Sophie LECOMTE - Directrice de recherche - Institut CBMN UMR 5248 - Examinateur
- Frédéric GAUCHERON - Docteur - CNIEL - Examinateur
- Raphaëlle SAVOIRE - Professeure des universités - Université de Bordeaux - CoDirecteur de these
Puff pastry butter production, intended for the manufacture of viennoiseries, requires specific functional properties, in particular suitable plasticity, sufficient mechanical strength, and optimal behavior during lamination. These characteristics directly depend on the crystalline structure of milk fat, itself modulated by its fatty acid and triglyceride composition as well as by the processing conditions applied throughout the butter-making process. Within the strict regulatory framework of the Charentes-Poitou Protected Designation of Origin (PDO), which prohibits any modification of composition or remelting after production, crystallization must therefore be controlled through precise management of processing parameters (temperature, shear, ...) along the entire production line. The first focus of this work was to study the variations in lipid composition of PDO milk fat, providing a more reliable approach than the traditionally used seasonal model. Analysis of fatty acid and triglyceride profiles made it possible to precisely identify compositional changes influencing thermal and textural properties, and to explain differences in butter firmness according to production periods. A second focus involved exploring, at laboratory and industrial scales, the combined influence of cream physical maturation profiles and churning conditions (pH, temperature, and speed). Design of experiments enabled the identification of key parameters governing final butter texture and suggested industrial possibilities to stabilize quality despite the seasonal variability of raw materials. In parallel, particular attention was accorded to the optimization of a novel post-production process, cold texturing. Trials carried out from pilot to industrial scale confirmed its potential to improve butter firmness and plasticity while fully complying with PDO regulations. Finally, complementary experiments on a simplified model system of anhydrous milk fat (AMF) were conducted to assess different crystallization methods and provide more comprehensions to the close relationship between thermal and structural properties of milk fat. Overall, this work has contributed to a better understanding and control of the relationships between composition, processing, and textural properties of PDO puff pastry butters. It opens concrete industrial perspectives to ensure consistent production and to strengthen the competitiveness of Charentes-Poitou butters in the market.
ED Entreprise Economie Société
Foreign doctoral students in Europe: permanence and research careers
by Andriy ROMANYUK (BSE - Bordeaux sciences économiques)
The defense will take place at 15h00 - Sala Seminari Monte Generoso Università degli Studi dell'Insubria, Via Monte Generoso, 71, 21100 Varese VA, Italie
in front of the jury composed of
- Michele PEZZONI - Associate Professor - Université Côte d'Azur - Rapporteur
- Mariapia MENDOLA - Full professor - Università degli Studi di Milano-Bicocca - Rapporteur
- Valerio STERZI - Full professor - Université de Bordeaux - Examinateur
- Alessia PISONI - Associate Professor - Università degli Studi dell'Insubria - Examinateur
This dissertation examines the mobility, retention, and career outcomes of foreign doctoral graduates in Europe, with a focus on France and the Netherlands. Using large-scale datasets that combine administrative records, theses, and scientific publications, it develops novel methodological tools and applies them to study how migration policies, academic careers, and student origins interact in shaping the trajectories of highly skilled migrants. The first chapter introduces a name-based classification methodology employing Long Short-Term Memory (LSTM) models to infer the regional origin of doctoral graduates in France between 1990 and 2020. The approach distinguishes French-sounding from foreign names and further classifies non-French individuals into twelve regions. Results document major shifts in France's international doctoral population, with a decline in Arabic-origin students and an increase in East Asian ones, while also highlighting challenges in distinguishing second-generation migrants from native-born French individuals. The second chapter investigates the impact of France's first dedicated visa scheme for foreign researchers, the carte de séjour “scientifique-chercheur” introduced in 1998, on the post-graduation stay rate of doctoral graduates. Using a new dataset of STEM graduates from 1992–2002 and applying a difference-in-differences approach, we find no evidence that the visa significantly affected retention patterns. While stay rates of non-EU graduates eventually converge with those of EU and French counterparts, this occurs only much later and appears unrelated to visa policy. The third chapter analyzes the publishing activity and mobility of STEM doctoral graduates from Dutch universities between 2000 and 2020. While natives and foreign-born graduates publish at similar rates and volumes, foreign-born graduates are substantially less likely to publish from the Netherlands after graduation, particularly if coming from outside the European Economic Area. Concerning out-migration, the chapter investigates the extent of positive self-selection and finds it limited to Dutch natives, whose most productive graduates are more likely to move abroad, especially to the United States. The analysis also shows that the introduction of selective immigration policies, starting 2004, had no discernible effect on retention rates. Together, these findings show that while migration policies play only a limited role in shaping doctoral graduates' retention in Europe, structural factors—such as funding schemes, origin composition, and academic career trajectories—remain central in understanding the mobility and contributions of international researchers.
ED Sciences de la Vie et de la Santé
Structural study of PatAB, a multidrug efflux pump from Streptococcus pneumoniae by cryo-EM.
by Paul NOURI (Institut de Chimie & de Biologie des Membranes & des Nano-objets)
The defense will take place at 14h00 - Amphitéatre IECB - 2 rue Robert Escarpit, 33607 PESSAC
in front of the jury composed of
- Olivier LAMBERT - Directeur de recherche - Université de Bordeaux - Directeur de these
- Guy SCHOEHN - Directeur de recherche - Université Grenoble Alpes - Examinateur
- Mélanie BONHIVERS - Directrice de recherche - Université de Bordeaux - Examinateur
- Manuela ZOONENS - Directrice de recherche - Université Paris Diderot - Rapporteur
- Isabelle BROUTIN - Directrice de recherche - Université Paris Cité - Rapporteur
In the face of the growing threat of antibiotic resistance, there is an urgent need to better understand its underlying mechanisms to develop strategies not only to combat but also to limit the emergence of multidrug-resistant strains. In this context, the present thesis aims on elucidating the molecular basis of active drug efflux in Streptococcus pneumoniae. Multridrug ABC (ATP-Binding Cassette) transporters play a key role in this resistance. Although their function has been extensively studied in recent years, the molecular mechanisms of action which couple drug recognition and transport with ATP/GTP hydrolysis remain poorly understood. The aim of this phD project was to conduct structural studies to gain deeper insight into the mechanism of action of the ABC multidrug transporter PatAB, which is involved in clinical resistance to fluoroquinolones (FQ). PatAB, composed of two subunits (PatA and PatB), forms an atypical heterodimer that operates asymmetrically, with two nucleotide-binding sites that are functionally non-equivalent. Moreover, unlike most ABC transporters that preferentially hydrolyse ATP, PatAB primarily uses GTP as its energy source, thereby defining a novel subfamily of ABC transporters. To characterize these specific features at the structural level, the strategy consisted of determining the structure of PatAB using cryo-electron microscopy combined with single-particle image analysis. As PatAB is a membrane protein, its structural analysis using this approach requires it to be extracted from its lipid environment in order to stabilise it in a mimetic environment. To assess the impact of this change of environment on PatAB structure, several surfactants (detergents and polymers) were used. The structures obtained in the presence of detergents revealed PatAB in an “inward-facing” conformation, ready to accommodate its substrate. However, these analyses also highlighted a pronounced flexibility of the PatA subunit, resulting in the absence of its nucleotide-binding domain (NBD). The use of amphipathic polymers allowed the determination of PatAB structures in two distinct conformations, one with the NBD of PatA and the other without the NBD, suggesting that the flexibility of PatA may be modulated by the stabilization conditions. In parallel, the potential effect of pH on PatAB conformational changes was investigated. At pH6, only one conformation was observed, whereas at pH 5, two conformations were detected underscoring the role of pH in modulating PatAB conformations. Furthermore, analysis of PatAB in the presence of GTP and orthovanadate, which stabilizes the interaction of GTP with the NBDs of both subunits, revealed two conformations. The first shows PatAB in an “inward-facing” conformation and lacking the PatA NBD, a conformation very similar to that described with detergents. The second displayed PatAB with both NBDs in interaction, without evidence of conformational rearrangement in the transmembrane domain. Altogether, these results demonstrate a remarkable flexibility of the NBD domain of PatA, and that this flexibility could be modulated by some physicochemical factors, highlighting a novel mode of operation and regulation of PatAB.
The pupillary evoked response: a study of the cingulo-coeruleus pathways in rodents and humans
by Vianney SALVI (Institut de neurosciences cognitives et intégratives d'Aquitaine)
The defense will take place at 14h00 - Amphithéâtre BBS Batiment Bordeaux Biologie Santé, 2 Rue Dr Hoffmann Martinot, 33000, Bordeaux
in front of the jury composed of
- Thomas MICHELET - Maître de conférences - Université de Bordeaux - Directeur de these
- Julie DUQUE - Professeure des universités - Institute of Neuroscience Université catholique Louvain - Examinateur
- Marc LANDRY - Professeur des universités - Institut des Maladies Neurodégénératives - Examinateur
- Luis GARCIA-LARREA - Directeur de recherche - Centre de Recherche en Neurosciences de Lyon - Examinateur
- Marianne BENOIT-MARAND - Professeure des universités - Laboratoire de Neurosciences Expérimentales et Cliniques - Rapporteur
- Céline AMIEZ - Directrice de recherche - Stem-cell & Brain Research Institute - Rapporteur
The organization of the cingulate cortex (CC) has been the subject of intensive studies, highlighting its central role in motor control, cognition, and arousal regulation. One key anatomical pathway through which the CC influences behavior is its efferent connection to the locus coeruleus (LC), a brainstem nucleus responsible for cortical noradrenaline (NA) release. Despite this anatomical link, the functional organization of CC subregions in modulating LC-NA activity remains largely unexplored. This thesis investigates the CC-LC circuits in both rodent and human models by using pupil-evoked responses (PERs) as a non-invasive index of LC-NA system engagement. In rodents, intracortical stimulation across eight CC areas revealed that anterior- (ACC) and midcingulate (MCC) subregions evoked rare autonomic effects but robust pupil dilation, with amplitude increasing along the caudorostral and dorsoventral axes. PERs were abolished following DSP-4-mediated depletion of the LC-NA system, confirming the critical role of this system in the PERs. These findings suggest a clear functional parcellation of the rodent CC in its capacity to drive LC activity. To explore the relevance of this organization in humans, we applied single-pulse transcranial magnetic stimulation (TMS) to homologous CC subregions in healthy participants, specifically the pregenual anterior cingulate cortex (pACC) and anterior mid-cingulate cortex (aMCC). TMS evoked intensity-dependent PERs, with aMCC stimulation producing fast, phasic responses and pACC stimulation yielding more sustained effects. These PERs were dissociable from global autonomic effects. Intracortical stimulation in humans (epileptic patients) corroborated these findings, showing significant PERs without general autonomic activation. These results demonstrate that specific subregions of the CC can differentially drive LC-NA activity consistently across species. Furthermore, high-intensity stimulation of the CC improved behavioral performance, consistent with phasic LC-mediated enhancement of cognitive performance. The use of PER as a biomarker thus provides a novel, non-invasive tool to probe the CC–LC circuits and opens new avenues for investigating its role in arousal regulation, motor control, and cognition under normal as well as pathological conditions.
Chemical and sensory study of red wines obtained from marc pressing
by Margot LAROSE (Oenologie)
The defense will take place at 9h00 - Amphitéatre 210 Chem. de Leysotte, 33140 Villenave-d'Ornon
in front of the jury composed of
- Stéphanie MARCHAND-MARION - Professeure des universités - Institut des Sciences de la Vigne et du Vin - Directeur de these
- Aurélie ROLAND - Maîtresse de conférences - Institut Agro Montpellier - Rapporteur
- Cédric SAUCIER - Professeur des universités - Institut Agro Montpellier - Rapporteur
- Barry SMITH - Professeur - Institute of Philosophy at the School of Advanced Study - University of London - Examinateur
The pressing of grape pomace is a widespread practice in winemaking. In the Bordeaux vineyard, press wines account for approximately 15% of the total volume of wine produced. However, scientific knowledge about these so-called press wines remains limited. Their production methods and uses rely mainly on the empirical expertise of professionals within the wine industry. This doctoral research aims to establish a knowledge base defining the identity of press wines, combining sensory perception with chemical composition. In the first stage, a study was conducted to describe how the concept of press wines is perceived by different actors in the wine sector, by the technical team of Château Montrose, and by the reference oenologist specialized in press wines. This approach confirmed the existence of a genuine concept of press wines, demonstrating that they are not merely a by-product of vinification but rather a multifunctional oenological tool in their own right, which should be better understood and managed to ensure the quality of Bordeaux wines intended for aging. This part of the work also aimed to identify the criteria associated with the quality and blending potential of press wines. These criteria proved to be multifactorial, complex, and projective in nature, requiring a fine technical and sensory approach as well as a high level of expertise. The second part of the study focused, on the one hand, on comparing the chemical composition of press wines with that of their corresponding free-run wines, and on the other, on investigating the chemical differences among three categories of press wines defined by their blending potential. A total of 358 single-varietal red wines, produced from two Bordeaux grape varieties (Merlot and Cabernet-Sauvignon) and across four vintages (2021, 2022, 2023, and 2024), were analyzed. A wide range of volatile and non-volatile compounds was quantified. The results show that, contrary to the limited data available in the literature, press wines are not simply “more concentrated in all constituents except alcohol.” In fact, they are characterized by higher pH and volatile acidity, as well as greater concentrations of phenolic compounds. These observations indicate that press wines are generally richer in phenolic compounds but poorer in aromatic volatile compounds and ethanol. While these results reveal consistent trends between wine types, other parameters are strongly influenced by vintage and grape variety. These findings are consistent with the sensory perception of press wines, which are typically used to enhance “structure”, particularly the “tannic dimension”of wine blends. No clear correlations were observed between chemical composition and sensory categorization. The targeted analytical approaches employed do not, on their own, provide a consistent or reproducible explanation of press wine quality across different vintages and grape varieties. In conclusion, this thesis provides a solid database on the chemical composition and sensory characteristics of red wines obtained from pomace pressing. It also opens new avenues for research, particularly regarding the criteria used to categorize press wines and their aging potential within blends.
ED Sciences Physiques et de l'Ingénieur
Study and characterization of superficial gravitational instabilities in a Pyrenean context
by Julian BRUNEAU (I2M - Institut de Mécanique et d'Ingénierie de Bordeaux)
The defense will take place at 9h00 - Amphitéatre bâtiment B6 Batiment B6 Av. des Facultés, 33600 Pessac Université de Bordeaux
in front of the jury composed of
- Jean-François LATASTE - Professeur des universités - Université de Bordeaux - Directeur de these
- Thomas LEBOURG - Professeur des universités - Université côte d'Azur - Rapporteur
- Stéphanie GAUTIER-RAUX - Maîtresse de conférences - Université de Montpellier - Rapporteur
- Muriel GASC - Directrice de recherche - CEREMA - Examinateur
- Yannick THIERY - Docteur - BRGM Aquitaine - Examinateur
- Alain DENIS - Professeur des universités - Université de Bordeaux - CoDirecteur de these
In view of the events recorded in recent years in the Pyrenean valleys, it appears that the risk of landslides cannot be neglected. The research conducted in this thesis focuses on landslides in a sector of the Ossau Valley through a multidisciplinary approach. By concentrating on moraine movements, the study of the Massif des 5 Monts (Laruns) combines geological, geomorphological, topographical, geophysical, and statistical investigations. The objective is to better understand the triggering factors and to propose appropriate methods for assessing landslide hazards. The first chapter presents the main issues related to landslides, including social, economic, and environmental aspects. It emphasizes that landslide hazards, which are difficult to quantify precisely, remain largely underestimated today. The second chapter introduces the tools and methods used, such as GPS measurements, the construction of a terrain model derived from photogrammetric or lidar data, and geophysical investigations based on electrical resistivity tomography. The third chapter describes the characteristics of the study site, placing it within its regional and historical context. The geology and geomorphology of the Pyrenean valleys are presented, with particular attention to moraine formations. Climatic factors, which play a major role in slope movements, are also discussed. The results of the field investigations are presented and discussed in the fourth chapter. The Digital Terrain Models developed for detailed site characterization, combined with GNSS monitoring carried out over three years, reveal several elements suggesting the presence of deep-seated landslides. Numerous methodological aspects are also addressed, allowing the refinement of monitoring strategies at both local and regional scales. Geophysical investigations complement these approaches by providing a better understanding of the geological nature of the formations, their interfaces, and the volumes involved. Finally, the fifth chapter proposes a statistical approach covering a broader Pyrenean area that includes five valleys. This study is based on available databases related to climatic information and quantifies the relationships between monthly and seasonal climate variations, such as temperature and precipitation, and the occurrence of landslides. Overall, the research and results contribute to a better understanding of landslide hazards, including triggering mechanisms, volumes involved, and sensitivity parameters. In the context of climate change, marked by an increase in extreme events, this knowledge is essential for improving prevention strategies, territorial management, and for strengthening the resilience of exposed areas and populations.
ED Sociétés, Politique, Santé Publique
From ostracism to radicalization: An exploration of basic psychological processes
by Adèle COTTIN (Laboratoire de Psychologie)
The defense will take place at 9h30 - Amphithéâtre Pitres Bâtiment P Campus Victoire 3ter Place de la Victoire 33000 Bordeaux
in front of the jury composed of
- François RIC - Professeur des universités - Université de Bordeaux - Directeur de these
- Marie-Pierre FAYANT - Professeure des universités - Université Paris Cité - Rapporteur
- Rainer GREIFENEDER - Professor - Basel University - Rapporteur
- Théodore ALEXOPOULOS - Professeur des universités - Université de Bordeaux - Examinateur
- Jessica MANGE - Maîtresse de conférences - Université de Caen Normandie - Examinateur
This dissertation investigates whether ostracism—being excluded or ignored by others—increases individuals' susceptibility to radicalization, based on the assumption that ostracized individuals are primarily motivated to restore a sense of social integration. If so, they should be more likely to affiliate with anyone who offers them inclusion. In some contexts, radical groups may become particularly appealing not because of their ideology, but rather because they are among those providing a clear offer of belonging. To examine this idea, we first tested whether receiving a sign of inclusion from another person would lead ostracized participants to follow that person's opinion more, as a mean of trying to regain social integration (Studies 1a–1c). Because results were inconclusive, we next questioned the seemingly obvious link between ostracism and the motivation to affiliate. Across correlational, experimental, and meta-analytical approaches (Studies 2–4), we found that this link was far less established than assumed. We then turned to more implicit processes of reconnection, testing whether signs of inclusion from a third party would capture ostracized participants' attention more strongly than that of included individuals (Studies 5a–5b). Again, the results were inconsistent. Finally, given the mixed findings throughout the dissertation regarding need threat, we examined whether effects of ostracism on psychological needs depend on methodological factors. Results showed that observed effects varied according to item wording and temporal framing (Study 6). Taken together, this body of work provides no clear evidence that ostracism increases susceptibility to radicalization. More broadly, our findings also challenge the underlying assumption that ostracism straightforwardly increases social reconnection: The decrease in belonging following ostracism was not systematic, and it did not consistently extend to affiliative motivation or conformity. These results highlight the need to reconsider whether and how exclusion is linked to openness to radical groups, as well as the methodological tools used to capture the underlying psychological processes.
Developing precision prevention strategies utilizing genomic risk prediction for dementia and cerebrovascular disease
by Timothy D'AOUST (Bordeaux Population Health Research Center)
The defense will take place at 14h30 - Centre Broca Amphi Centre Broca Neurocampus, 146 Rue Léo Saignat, 33000 Bordeaux
in front of the jury composed of
- Stéphanie DEBETTE - Professeur - Sorbonne Université SIS (Sciences, Ingénierie, Santé) - Directeur de these
- Hélène JACQMIN-GADDA - Professeur - Université de Bordeaux - Examinateur
- Cornelia VAN DUIJN - Full professor - University of Oxford - Rapporteur
- Vincent MOOSER - Full professor - McGill University - Rapporteur
- Josée DUPUIS - Full professor - McGill University - Examinateur
Stroke and dementia ranked 3rd and 8th, respectively, as leading causes of death in 2021, and the global burden of these conditions is projected to increase by two to threefold by 2050, mostly affecting low- and middle-income countries. Underlying both conditions is cerebral small vessel disease (cSVD), a common yet underrecognized pathology characterized by changes in the structure and function of small brain vessels detectable by brain magnetic resonance imaging (MRI). Genome-wide association studies (GWAS) have identified approximately 90 genetic loci associated with stroke, over 75 for dementia, and over 50 related to cSVD MRI markers. The effects of genetic variants from GWAS can be combined in polygenic risk scores (PRS) that quantify genetic predisposition to these conditions and associated traits. PRS are emerging as powerful genomic tools that have the potential to guide disease prevention and management by stratifying disease risk and predicting disease prognosis and response to therapy. In stroke and dementia, while PRS show predictive ability, key gaps remain: few studies have validated them longitudinally in diverse populations or clinical settings, and their added value beyond existing clinical risk models remains uncertain. There is also an opportunity to explore novel PRS approaches that more fully capture polygenic risk associated with vascular pathology or deconstruct genetic risk into biological pathways, particularly relevant for cSVD, for which mechanisms remain poorly understood. This thesis aimed to generate evidence for the application and refinement of PRS in cerebrovascular disease, with a focus on stroke, dementia, and cSVD. We leveraged individual-level clinical and genetic data from large population-based cohorts and biobanks, a memory clinic-based cohort, and the PRESTIGE-AF clinical trial. In the first part, we aimed to improve dementia risk prediction and stratification by developing an integrative PRS for dementia (iPRS-DEM), incorporating both neurodegenerative and vascular traits. iPRS-DEM predicted dementia across older community-persons, memory-clinic patients, and in a multi-ancestry biobank. We further demonstrated that alongside APOE ε4, iPRS-DEM may refine risk stratification and be particularly useful for the enrichment of clinical trials and primary prevention programs. In the second part, we evaluated existing PRS models in the PRESTIGE-AF trial of intracerebral hemorrhage (ICH) survivors with atrial fibrillation (AF) who are at high risk of both thromboembolic and bleeding events. We found that PRS, particularly AF-PRS, could provide clinically meaningful risk stratification for direct oral anticoagulation treatment in these patients. These findings underscored that PRS has the potential to guide optimal treatment strategies in contexts of clinical equipoise where uncertainty is greatest. Such scenarios may represent the most pragmatic starting point for PRS implementation in secondary stroke prevention. In the last part, we applied standard and pathway-based PRS to white matter hyperintensities, the most studied MRI marker of cSVD, in independent cohorts spanning the adult lifespan and clinical spectrum. We showed for the first time that a global WMH-PRS was associated with stroke and dementia, and through pathway-based PRS, we identified a set of biological pathways potentially implicated in cSVD across the lifespan. Our findings highlighted pathways involved in lipid metabolism, ciliogenesis, and signal transduction that may underlie hallmarks of cSVD pathology. This work demonstrated that PRS could be useful not only for improving disease risk prediction but also for delineating etiology in cSVD. Overall, this thesis generated valuable evidence for the use of PRS in cerebrovascular disease and their translation into clinical and public health practice.
An interdisciplinary approach to respiratory health in African children exposed to urban indoor and outdoor air pollution
by Auriane PAJOT (Bordeaux Population Health Research Center)
The defense will take place at 14h00 - Salle 446 TP-4 146 rue Léo Saignat 33076 Bordeaux Cedex
in front of the jury composed of
- Olivier MARCY - Directeur de recherche - Université de Bordeaux - Directeur de these
- Véronique YOBOUE - Professeure - Université Félix Houphouët Boigny - CoDirecteur de these
- Isabelle BALDI - Professeure - DR, Inserm U1219, Université de Bordeaux - Examinateur
- Jean-François LéON - Directeur de recherche - LAERO, Université Paul Sabatier - Rapporteur
- Aristide BARTHéLéMY AKPO - Professeur - Université d'Abomey-Calavi - Examinateur
- Arnauld FIOGBE - Docteur - Centre National Hospitalier et Universitaire de pneumophtisiologie de Cotonou (CNHUPP) - Examinateur
- Chantal RAHERISON-SEMJEN - Professeure - Université des Antilles - Rapporteur
Exposure to fine particulate air pollution (PM2.5) is a major public health concern, responsible for approximately 7 million deaths each year. Owing to physiological and behavioral factors, children are particularly vulnerable: air pollution can lead to chronic respiratory diseases, exacerbate asthma, and trigger acute respiratory infections. While global air pollution levels are stabilizing or declining, they remain extremely high in sub-Saharan Africa, notably due to the widespread use of biomass for household cooking and food smoking. The lack of strict public policies and monitoring systems limits awareness and delays the implementation of interventions. Our objective was to document the challenges, determinants, and impacts on children's respiratory health of familial, occupational, and environmental exposure to air pollution. This work was conducted through an interdisciplinary approach among children living in urban areas of Abidjan, Côte d'Ivoire. The SEPol-CI study, conducted among 124 children (aged 5–10 years) from 65 households in an informal settlement in Abidjan, reported median 48-hour PM2.5 concentrations of 60.8 µg/m³ [45.6–96.2] indoors and 58.2 µg/m³ [45.1–82.0] outdoors, far exceeding WHO guidelines. Two-thirds of households used a gas–charcoal combination for cooking. Among the 124 children, 16.9% reported wheezing, 52.4% nocturnal dry cough, and 72.4% had lung function impairments (LFI) on spirometry. Although visible pollution sources were often recognized, their health effects remained largely unknown. The APIMAMA Kids study included 210 children (aged 0–16 years) from households of women using charcoal for cooking (Group [G]1), involved in fish smoking (G2), or using gas for cooking (G3). In a subsample of 29 children (aged ≥7 years), the study demonstrated the feasibility of ambulatory joint monitoring of respiratory function using portable spirometry and PM2.5 exposure over 7 days. Median hourly ambulatory PM2.5 concentrations were far above recommendations (164.2 µg/m³ [107.0–272.2]), and spirometry showed a significant decline in expiratory capacity within two hours following exposure to a pollution peak, highlighting the immediate impact of exposure on respiratory function. Girls involved in fish-smoking activities were exposed to major particulate peaks. Among the 210 children, the prevalence of respiratory symptoms (43.8%) and LFI (33.5%) was high. Study group was independently associated with the risk of respiratory symptoms and LFI, with higher risk observed in children from G1 compared with G2 and G3. Female sex, older age, and lower BMI-for-age Z-score were independently associated with LFI, suggesting underlying mechanisms and a dose–response relationship in the onset of functional impairment. This work highlights the high prevalence of respiratory symptoms and LFI among children living in precarious urban neighborhoods in Côte d'Ivoire, exposed to high to alarming levels of PM2.5, particularly due to domestic biomass combustion and fish-smoking activities. Despite the high prevalence of respiratory disorders, both adults and children lacked awareness of these risks. These findings underscore the urgent need to strengthen community awareness, integrate air quality monitoring into public health policies, and promote the adoption of cleaner household energy sources to durably protect children's respiratory health in Côte d'Ivoire and, more broadly, in sub-Saharan Africa.