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Motor learning allows animals, including human beings, to acquire skills that are essential for efficient interactions with the environment. This ability to learn new motor skills is of great practical relevance for daily-life activities (such as when learning to drive), but also for motor rehabilitation after a lesion of the nervous system (such as a stroke). For a long time, motor learning has been mainly conceptualized as a process allowing to iteratively correct movements based on sensory information (e.g., visual, somatosensory). Importantly though, in the last years, there has been an increased appreciation that motor learning also results from other mechanisms including reinforcement learning, a process through which appropriate actions are selected through outcome-based feedback (e.g., success or failure). As such, recent evidence shows that reinforcement feedback and mo-tivation can be beneficial for motor learning both in healthy individuals and neurological populations. Despite the potential importance of these findings to improve current rehabil-itation protocols, the mechanisms underlying reinforcement-related improvements in mo-tor learning remain largely unexplored. This PhD aimed at providing deeper mechanistic understanding of reinforcement learning of motor skills through behavioral analyses, neuroimaging and non-invasive brain stimulation. In Study 1, I found that enhancing motivation (by providing monetary reward for good performance) during a motor training can lead to persistent improvements in performance that are not obtained with reinforce-ment feedback only, and are related to an increased regulation of motor variability based on previous outcomes. In Study 2, I investigated the effect of reward timing (i.e., the delay between the end of movement execution and reward receipt) on motor learning and found that delaying reward by only a few seconds could strongly influence motor learning dynamics and consolidation. Finally, in Study 3, I inves, (MED - Sciences médicales) -- UCL, 2023

Type 2 diabetes (T2D) is one of the most prevalent chronic condition in older people, a heterogeneous population in terms of health status. Consequently, risks and benefits of glycaemic control by glucose-lowering treatment may differ considerably between patients and must be wisely balanced to avoid harmful consequences, i.e. hypoglycaemic events. This can be achieved by individualising treatment goals according to patient’s characteristics. This thesis (i) reviewed recommendations from recent Clinical Practice Guidelines for individualised glycaemic management in older people with T2D, (ii) assessed the application of these recommendations in clinical practice, and (iii) described the metabolic heterogeneity in older people with T2D. The results provide strong encouragement to follow more assiduously recommendations for individualising the glycaemic management in older patients with T2D, and to continue research in this field to provide high-level evidence recommendations., (MED - Sciences médicales) -- UCL, 2022

Ovarian tissue cryopreservation followed by autotransplantation is an effective way of restoring fertility in cancer patients with premature ovarian failure due to gonadotoxic treatment. This technique is indicated for women who cannot delay anticancer therapy and prepubertal girls. The first part of my thesis was focused on investigating the risk of reseeding cancer cells along with the transplanted tissue in patients with central nervous system tumors. The second part aimed to characterize density and growth of follicles in ovarian tissue from Turner girls whom the ovarian tissue is quickly depleted at a young age., (MED - Sciences médicales) -- UCL, 2022

Chemotherapy and radiotherapy can induce permanent infertility of the treated patient. For prepubertal boys, no option is currently available for the restauration of fertility after anti-cancer treatments. This represents a major concern that moved several centers all over Europe and North America to develop fertility preservation programs that though experimental, are met with high rates of acceptance by the patients and their parents. As no mature gametes can be found in the testicle before puberty, the only available option is the preservation of spermatogonia, diploid germ cells that are precursors of spermatozoa. Retrieval of immature testicular tissue (ITT) through a small biopsy is a safe and efficient method to preserve germ cells before exposure to gonadotoxic treatments. Amongst the several alternatives currently under-study for fertility restoration, transplantation of frozen-thawed ITT fragments is the most promising option. This procedure has not been performed yet on human subjects, although the xeno-transplantation of such fragments to the nude mice provided a valuable model to study. However, every report on human ITT xeno-transplants described an arrest of spermatogenesis at the pachytene spermatocytes stage and an important germ cells loss. After multiple reports of failed attempts at improving the transplantation procedure through in vivo administration of antioxidants or hormonal supplementation and in vitro culture with supporting molecules before grafting, application of tissue engineering led to promising results in autografts of mice testicular tissue. Indeed, administration of nanoparticles delivering Vascular endothelial growth factor (VEGF) and encapsulation in an alginate matrix improved respectively short-term vascularization and spermatogonial survival. The purpose of our project was to obtain a further improvement of testicular tissue transplantation technique applying tissue engineering. In the first part of the experience, we compare, (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022

The aim of this project was to explore spinal and supra-spinal pain-motor interactions. First, I characterized the temporal profile and limb-specificity of the effects of a transient nociceptive stimulus on motor excitability assessed by transcranial magnetic stimulation (TMS). Secondly, I showed that the reflex elicited by intra-epidermal electrical stimulation of the sole of the foot could represent a « purer » measure of the RIII reflex than the response elicited by « conventional » transcutaneous electrical stimulation. Third, I characterized the changes in motor excitability in a state of central sensitization. In this study, high-frequency electrical stimulation of the skin does not induce sustained changes in the TMS-mapped representation of upper limb muscles. Finally, I setup the recording of functional magnetic resonance imaging (fMRI)- blood-oxygen-level-dependent (BOLD) responses elicited by TMS to explore pain-related changes in brain connectivity., (MED - Sciences médicales) -- UCL, 2022

Ovarian tissue cryopreservation and further transplantation has proved its effectiveness in restoring fertility after cancer, with over 200 live births worldwide to date. However, it is limited by massive ischemic damage that occurs shortly after transplantation, causing a significant decline in the ovarian reserve. This project aimed to develop a novel strategy using adipose tissue-derived stem cells (ASCs) for ovarian tissue transplantation, after our preliminary results revealed their impact on hypoxia and revascularization. ASCs are able to protect the ovarian reserve from hypoxic damage, thereby reducing follicle loss. Moreover, their secretome, rich in growth factors, is able to both enhance graft revascularization and reperfusion, and mitigate the primordial follicle burn-out due to abnormal activation soon after transplantation. The present work proved the effecicacy of ASC use in ovarian tissue transplantation, which is now one step closer to clinical application., (MED - Sciences médicales) -- UCL, 2022

Seizures are common in the neonatal period, affecting 1 to 3 per 1000 births, and are responsible for significant neurodevelopmental impairment. Etiologies of seizures in neonates can be broadly classified into acute provoked seizures and neonatal-onset epilepsies. The most common cause of acute seizures in neonates is hypoxic-ischemic encephalopathy, where a reduced flow of oxygenated blood to the brain before or during delivery leads to brain dysfunction. Other causes of acute seizures are stroke, infection, or acute electrolyte and glucose imbalances. On the other end of the spectrum, neonatal-onset epilepsies are a large group of rare and ultra-rare diseases. Early recognition of the etiology-specific electro-clinical phenotypes is essential for targeted treatment. This thesis advanced the field of seizures in neonates by analyzing how EEG background can inform subsequent seizure risk and by performing detailed electroclinical phenotyping of neonates with early-onset genetic epilepsies such as channelopathies and BRAT1 pathogenic variants., (MED - Sciences médicales) -- UCL, 2022

Selective internal radiation therapy (SIRT) is part of the treatment strategy of liver tumors. SIRT can be performed using resin or glass microspheres, demonstrating different chemico-physical and radioactive properties. Post therapy imaging using 90Y PET/CT can evaluate the deposition of the tumor-absorbed dose and predict the patient outcome. 90Y PET/CT can also precisely evaluate the heterogeneous distribution of the absorbed dose within the tumor by calculating a equivalent uniform dose (EUD). Tumor EUD is strongly correlated with survival of patients and reunifies the absorbed doses between resin and glass microspheres as well as those from external radiation beam therapy. Moreover, pre-therapy imaging using 99mTc macroaggregated albumin (MAA) can optimize the activity planning, predicting with high accuracy the absorbed dose to the healthy liver. Furthermore, the tumor targeting can be optimized using a specific catheter during the arteriography, named antireflux catheter (ARC). Using ARC, the absorbed dose can be significantly increased in neuroendocrine and HCC tumors, hence, increasing the tumor control probability., (MED - Sciences médicales) -- UCL, 2022

Surgical resection of colorectal liver metastases (CRLM) is the first choice of treatment when possible, aims to maximize patient survival and represents the only hope for a cure. In the last few years, the introduction of new molecules for neoadjuvant chemotherapy has made it possible to reduce tumour size to allow for a surgical resection, which may not otherwise have been feasible. Nonetheless, metastatic colorectal cancer continues to have a poor prognosis. In this thesis we undertook an in-depth analysis of the pathological characterization of CRLM to understand which parameters influence prognosis in a retrospective and in a prospective cohort of patients resected for CRLM. Then we explored the possible role of morphological heterogeneity of the pathological features regarding outcome. Our investigations demonstrated the clinical relevance of a complete pathological evaluation of all CRLM to stratify patient prognosis after surgery and attempted to provide another piece in the puzzle to understand tumoural heterogeneity and its possible influence on disease outcome., (MED - Sciences médicales) -- UCL, 2022

Amblyopia results from an abnormal binocular interaction, in the context of strabismus or uncorrected refractive errors, or from visual deprivation. Screening is important during pre-school years in order to start treatment while cerebral plasticity is optimal. Screening practices vary a lot between developed countries, with consequences on public health policies. Screening is based on the measure of visual acuity in young children. The technique of sweep visual evoked potentials allows an objective measure of visual acuity, without requiring participants to name optotypes, which is useful in pre-verbal children. Along with decreased visual acuity, amblyopia is associated with an absence of improvement with age of the characteristics of saccades. With respect to motor skills, altered binocular vision affects catching skills and balance. A better understanding of these deficits will allow for better treatment of amblyopia, which is the first cause of monocular vision loss in children., (MED - Sciences médicales) -- UCL, 2022

The scope of this thesis was to develop novel human biomarkers to optimise Vagus Nerve Stimulation (VNS) for epilepsy, which is currently ineffective in up to one third of the implanted patients. The research addressed two axes: the peripheral activation of vagal fibres and the central effects of VNS on the brain. The explorations were aimed at understanding the acute effects in epileptic patients, with particular regard to their intensity-dependency. Hence, both dosing biomarkers – aiming to optimize the choice of stimulation parameters – and response biomarkers – which could correlate with a successful clinical success – were sought. Experiments involving peripheral electrophysiology research were conducted, with the aim to develop and validate the novel technique of VNS-induced Laryngeal Motor Evoked Potentials (LMEPs), a potential marker of effective nerve activation. At central level, electroencephalography was applied to search for VNS response biomarkers, by means of connectivity and network analyses. Furthermore, a proof-of-concept research led to the characterisation of acute VNS-induced pupillary responses., Cette thèse a pour but de développer de nouveaux biomarqueurs pour l’amélioration de la thérapie par stimulation du nerf vague (VNS) dans l’épilepsie, qui est à présent inefficace jusqu’à un tiers des patients implantés. La recherche porte sur deux axes : au niveau périphérique, sur l’exploration de l’activation des fibres nerveuses vagales ; au niveau central, sur les effets de la VNS sur le cerveau. Cette thèse a abordé les effets aigus de la VNS, en insistant particulièrement sur l’influence de l’intensité de stimulation. Ainsi, tant des biomarqueurs visant à optimiser le choix des paramètres de stimulation, que des biomarqueurs de réponse ont été explorés. Les expériences d’électrophysiologie périphérique ont mené au développement des potentiels évoqués moteurs du larynx (LMEPs), qui sont proposés comme marqueur d’activation nerveuse induite par la VNS. Sur le plan central, l’électroencéphalographie a été étudiée afin d’extraire des biomarqueurs de réponse à la VNS, moyennant des analyses de connectivité fonctionnelle et de réseau. En outre, des réponses pupillaires induites par la VNS ont été prouvées et proposées comme biomarqueurs centraux., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022

Temperature sensing is involved in many different functions, ranging from fundamental homeostatic regulation to complex inferential processes on outside world properties. Due to the technical difficulty of generating well controlled cooling stimuli, significantly less research has been conducted on cold than on heat perception. The availability of new stimulators, enabling the generation of fast and strong cold stimuli, opens new experimental possibilities. This PhD dissertation aimed to develop new techniques to probe human innocuous cold perception, use these new techniques to probe the neurophysiological mechanisms underlying human cold perception, and assess whether these new techniques could be of interest in a clinical setting. These efforts were directed more specifically in two directions: improving the psychophysical assessment of cold detection and developing stimuli and analysis techniques allowing the exploration of cold evoked activity with electroencephalography., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022

Traumatic events are prevalent worldwide and particularly in regions affected by armed conflicts such as the Eastern Democratic Republic of Congo. However, their link with mental and physical health outcomes still needs to be explored. Furthermore, there is a need to identify intrapersonal and interpersonal factors that may influence such relationship. This PhD explored the role of emotion regulation and social support in the occurrence of psychopathological and somatic symptoms in traumatic contexts. Our study populations encompassed three different samples, respectively patients consulting in internal medicine, patients with violence-induced injuries and health workers at frontline in the first wave of the Covid-19 pandemic. Our results showed an association of trauma-related disorders and hypertension with both emotion regulation and social support in the contexts of traumatic events. Our observations point to the necessity to develop interventions in the prevention and treatment of hypertension and trauma related disorders in the aftermath of traumatogenic events, (MED - Sciences médicales) -- UCL, 2022

This thesis, which includes clinical and laboratory research, was meant to advance liver surgery thanks to pharmacology. Since immunosuppression, as well as rejection, is detrimental, we investigated in adult liver transplantation whether induction with depleting antibodies helps minimise immunosuppression after one year. Early histological rejection was attenuated. As organ shortage and increasing indications widen the gap between supply and demand, there is little alternative to live-donor liver transplantation. Managing a small-for-size liver in the donor or in recipient remains a challenge, where hypoxia-signalling pathways play a role. Can hypoxia gene signature be induced by means of a pharmacological stabilisation of its downstream transducers? We studied the histological and functional changes caused by roxadustat, a selective stabiliser of these transcription factors, in a model of liver resection. The drug reduced steatosis and ballooning, markers of hepatocellular injury., (MED - Sciences médicales) -- UCL, 2022

Ovarian tissue cryopreservation and transplantation is an effective fertility preservation option. Even though use of cortical pieces is the technique routinely applied in clinical practice with >200 live births reported worldwide, it is severely hampered by massive follicle loss occurring after avascular transplantation, a phenomenon known as follicle burnout, considerably limiting graft lifespan. On the other hand, whole ovary cryopreservation has been proposed to patients in the past, but while researchers are still struggling with the risk of losing the entire organ after vascular anastomosis, women are returning to oncofertility units to have their fertility restored, urging to develop safe and effective ways to address their issue. In this context, the present work aimed to (i) assess the impact of freezing, in vitro culture and grafting on molecular pathways involved in follicle burnout and (ii) develop an original technique to manage patients having a stored frozen whole ovary., La congélation et transplantation de tissu ovarien est une option efficace pour préserver la fertilité. Bien que l'utilisation de strips corticaux soit la technique de choix avec >200 naissances rapportées dans le monde, elle est sévèrement entravée par la perte massive de follicules survenant après greffe, aussi connue sous le nom de burnout folliculaire, limitant considérablement la durée de vie des greffons. D'autre part, la congélation d’ovaires entiers fut proposée aux patientes par le passé. Tandis que les chercheurs se débattent encore avec le risque de perdre l'organe après anastomose vasculaire, les femmes reviennent vers les unités d'oncofertilité pour restaurer leur fertilité, incitant le développement de moyens sûrs et efficaces pour répondre à leurs attentes. Le présent travail visait à (i) évaluer l'impact de la congélation, de la culture et de la greffe sur les voies moléculaires impliquées dans le burnout folliculaire et (ii) développer une technique originale pour prendre en charge les patientes ayant un ovaire entier congelé., (MED - Sciences médicales) -- UCL, 2022

The olfactory disorders, formerly neglected, were recognized worldwide with the COVID-19 outbreak. Management of olfactory disorders requires appropriate tools of investigation. The Sniffin`Sticks test is widely used in Europe as a standard test to assess olfaction. However, up to now, there is no version adapted to Sub-Saharan African populations. This PhD thesis aimed at assessing the applicability of the Sniffin`Sticks test in the population of South-Kivu. Overall, we conducted three studies. In the first study, we selected odours that were poorly recognised in the identification test with the standard version of the Sniffin'stick test and proposed to replace them with culturally appropriate odours in an adapted version. In the second study, we found that the adapted version led to a higher rate of correctly identified odours and we defined normative values for the South Kivu population. In the third study, using the adapted version, we found that hyposmia predominated when the cause was an upper respiratory tract infection, while anosmia predominated when the cause was non-infectious. Our results point to the necessity of adapting the Sniffin`Sticks test by using both adapted odors and normative values specific to this population., Les troubles olfactifs, autrefois négligés, ont été reconnus dans le monde entier avec l'épidémie de COVID-19. La prise en charge des troubles olfactifs nécessite des outils d'investigation adaptés. Le Sniffin`Sticks test est largement utilisé en Europe comme test standard pour évaluer l'olfaction. Cependant, à ce jour, il n'existe pas de version adaptée aux populations d'Afrique subsaharienne. Cette thèse de doctorat visait à évaluer l'applicabilité du Sniffin`Sticks test dans la population du Sud-Kivu. Dans l'ensemble, nous avons mené trois études. Dans la première étude, nous avons sélectionné des odeurs mal reconnues lors du test d'identification avec la version standard du Sniffin’stick test et avons proposé de les remplacer par des odeurs culturellement appropriées dans une version adaptée. Dans la deuxième étude, nous avons constaté que la version adaptée conduisait à un taux plus élevé d'odeurs correctement identifiées et nous avons défini des valeurs normatives pour la population du Sud-Kivu. Dans la troisième étude, en utilisant la version adaptée, nous avons constaté que l'hyposmie prédominait lorsque la cause était une infection des voies respiratoires supérieures, alors que l'anosmie l'était lorsque la cause était non infectieuse. Nos résultats soulignent la nécessité d'adapter le Sniffin`Sticks test en utilisant à la fois des odeurs adaptées et des valeurs normatives propres à cette population., (MED - Sciences médicales) -- UCL, 2022

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by a predominant joint involvement. RA encompasses a wide spectrum of clinical disease severity spanning from limited, indolent oligoarticular involvement to severe, polyarticular destructive disease. Therapeutic armamentarium has greatly increased these last decades to involve drugs specifically targeting key inflammatory effectors. Again, response to therapy displays a wide heterogeneity across individuals, with some patients entering remission after 1st-line therapy while others suffer from “multi-resistant” RA. Importantly, accurate predictors of response to therapy are lacking. The target tissue of RA -the synovium- is the seat of alterations involving immune and resident cells. Just as clinical characteristics, features of synovial inflammation in RA are widely heterogenous from a cellular and molecular point-of-view. The development of minimally invasive biopsies techniques has enabled to study clinical correlates of synovial tissue heterogeneity in large cohorts of RA patients. While confounding factors (i.e. disease duration, ongoing treatment) may partially account for these variations, it remains unclear whether RA endotypes (commonly named “pathotypes”) can be defined based on synovial inflammatory pattern. The clinical benefit of defining such RA subgroups with different prognosis/response to therapy is evident and would represent a great step toward the grail of precision-medicine. Nevertheless, clinician scientists ought to temper their enthusiasm with a critical approach. In this thesis, I first explored the intra-patient heterogeneity (that is, across pairs of large and small joints) of synovial inflammatory features. I have shown that T cells infiltration and expression of TCR-signaling genes (and other RA-related pathways) are largely similar between pairs of joints from the same individuals. These observations have pathophysiological but also methodological impli, (MED - Sciences médicales) -- UCL, 2022

Depression and anxiety in youth are major public health concerns and represent a real challenge for care communities. This issue was further highlighted during the COVID-19 crisis with an increased prevalence and exacerbation of pre-existing symptoms. Yet, this is a crucial issue since psychological suffering in adolescence significantly disrupts daily life and is likely to persist or worsen in adulthood. It is therefore essential to put in place interventions for young people in psychological difficulties. However, there is a lack of evidence for an effective comprehensive strategy to alleviate depression and anxiety in youth. In adults, physical exercise has been introduced recently to the guidelines for depression treatment. Therefore, exercise as a complementary treatment in young people (10-24 years) should be also studied. In this context, the aim of this thesis is to investigate the antidepressant and anxiolytic effects of exercise in youth in school and psychiatric settings., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022

The management of dental emergencies is a central and essential issue in the daily practice of dentists. Through two clinical studies, we were able to identify new perspectives: 1/ The strategy of emergency management based on triage with the establishment of recommendations allowed to find an effective compromise between limiting the admission of patients and ensuring the control of their pain and the relief of their symptoms. 2/ More conservative management of irreversible pulpitis. Our data tend to support pulpotomy as an acceptable and more conservative permanent treatment option for irreversible pulpitis of mature molars. Our strategies could be considered as first-line treatments, thus providing additional steps in the therapeutic gradient., (DENT - Sciences dentaires) -- UCL, 2022

In medicine, a legacy effect is defined as the sustained beneficial effect of a given treatment on disease outcomes, even after cessation of the intervention. Initially described in optimized control of diabetes, it was also observed in clinical trials exploring intensification strategies for other cardiovascular risk factors, such as hypertension or hypercholesterolemia. Mechanisms of legacy were particularly deciphered in diabetes, leading to the concept of metabolic memory. Interestingly, epigenetic changes and reactive oxygen species (ROS) appear to be common features of “memory” of the vascular wall. In this thesis project, we developed an original model of “hypertension memory” in which we observed long term legacy effect on cardiovascular tissue of transient hypertension induced by Angiotensin II, and identified some regulators of this memory, including epigenetic modification. These data open the way for further understanding of legacy effect of cardiovascular risk factors on vascular tissue, and to further therapeutics possibilities to erase this memory., (MED - Sciences médicales) -- UCL, 2022

Heart failure with preserved ejection fraction is defined by the presence of symptoms of heart failure in the absence of a reduced left ventricular ejection fraction. The heart suffers from an impaired relaxation, leading to elevated filling pressures. This results in shortness of breath, congestion, and exercise intolerance with significant impact on the patient's quality of life and prognosis. The pathophysiological mechanisms are not yet fully elucidated but it now seems clear that the pro-inflammatory state and oxidative stress linked to the presence of metabolic comorbidities, such as obesity and diabetes, plays a key role in the development of the disease. The objective of this work is to better characterize these patients, particularly according to their metabolic profile, and to explore the pathophysiological mechanisms underlying different profiles., (MED - Sciences médicales) -- UCL, 2022

Ressources éducatives libres, Open educational resources, Cette ressource éducative libre (REL) a été produite dans le cadre de la démarche d’innovation pédagogique intitulée « Balado en soutien aux apprentissages socio-affectifs : limiter l’influence des biais sur la relation d’aide » qui a pour objectif de soutenir des apprentissages du domaine socioaffectif chez des personnes étudiantes engagées dans une formation en santé ou en relation d’aide. Cette REL comprend un balado (une introduction et 3 épisodes) ainsi que sa retranscription intégrale, un guide d’accompagnement pédagogique à l’attention des personnes enseignantes et un recueil de fiches de travail à l’attention des personnes étudiantes. Le balado et les documents de la REL peuvent être utilisés en combinaison ou séparément, selon le contexte d’apprentissage et les besoins pédagogiques.

The treatment of chronic knee osteoarthritis pain remains a challenge. In recent years, genicular nerve blockade (GNB) and radiofrequency ablation (RFA) have emerged as promising alternatives, as they have several advantages over other conservative therapies. However, anatomical accuracy is critical in order to ensure a successful outcome. Despite the recent popularity of these techniques, there are many discrepancies on the innervation of the knee capsule and neural targets for GNB and RFA. This PhD thesis investigates the anatomical distribution of the nerves supplying the knee joint capsule, determines the neural targets and accurate anatomical landmarks for GNB and RFA, and validates new technique for fluoroscopic and ultrasound-guided GNB and RFA. Then, it compares the currently used technique with classical anatomical targets, to the above-developed new technique that uses revised targets, on cadavers first, then in patients suffering from chronic knee pain., (MED - Sciences médicales) -- UCL, 2021

Information theory has been often used to analyse the interactions of agents with their environment. For example, frameworks of bounded rationality focus on tradeoffs between utility maximisation and information processing cost. Alternatively, frameworks of planning frequently focus on casting exploration as potential information gain. Here, we will apply multi-variable information decomposition in order to isolate interactions between the agent, its past and future sensations, and its future self. We will then discuss intuition behind the resulting terms and connections to several popular frameworks. Afterwards, we will focus on active sensing - a decision making framework that formalizes exploration as reduction of uncertainty about the current state of the environment. Despite strong theoretical justifications, active sensing has had limited applicability due to difficulty in estimating information gain. Here we will address this issue by proposing a linear approximation to information gain and by implementing efficient gradient-based action selection within an artificial neural network setting. We will compare information gain estimation with state of the art, and validate our model on an active sensing task based on MNIST dataset., (MED - Sciences médicales) -- UCL, 2021

In the current setting of highlighting the clinical and prognostic importance of the right ventricle in innumerous diseases, the present thesis sought to contribute to the current state-of-the-art by addressing part of the gaps in evidence of validation and clinical application of deformation imaging modalities and pulmonary transit time by cardiac magnetic resonance in predicting outcome in heart failure and reduced ejection fraction (HFrEF). Accordingly, this work was aimed to first evaluate the variability day-to-day of these widely used deformation imaging techniques and of the pulmonary transit time by cardiac magnetic resonance. Secondly, to investigate the additional prognostic value of these techniques in HFrEF in direct comparison with cardiac magnetic resonance. This research work contributes to the advancement in the field of deformation imaging techniques and pulmonary transit time clinical implementation., (MED - Sciences médicales) -- UCL, 2021

With autonomic dysfunction playing a crucial role in the occurrence of atrial fibrillation, the rational was there to explore the technique of auricular transcutaneous vagus nerve stimulation as an adjunctive (cardio neuromodulatory) therapeutic approach for paroxysmal atrial fibrillation. The primary objective of the present thesis was to assess the driving physiological mechanisms of auricular transcutaneous vagus nerve stimulation on the autonomic nervous balance through heart rate variability and muscle sympathetic nerve activity, using a prototype hand-held device for electrical stimulation of the auricular branch of the vagus nerve. Then, the feasibility of the auricular transcutaneous vagus nerve stimulation biotechnology with application in paroxysmal atrial fibrillation was experimented., (MED - Sciences médicales) -- UCL, 2021

Open tibia fractures (OTF) can cause significant morbidity. These injuries justify early antibiotic therapy, adequate debridement, stable osteosynthesis, and early coverage of the fracture. The mostly poor infrastructural conditions concerning the provision of health services in developing countries (DCs) likely render adequate treatment of problematic fractures practically impossible. The hygienic conditions required for surgical treatment involving techniques of internal osteosynthesis may be insufficient; for cost reasons, the necessary devices including image intensifier and implants may be lacking in places where such treatment could indeed be offered. Thus, casting with plaster of Paris (POP) is still the commonly used restraint method due to its availability and low-cost. However, this method may cause many complications. In this context, the external fixator (EF) is still the implant of choice, which is also suitable for precarious areas. The EF has proven its usefulness in the treatment of open fractures. This alternative could be employed to circumvent the difficulties of implementing a classic osteosynthesis. There are many sophisticated external fixators on the market, but they are too expensive, which limits their usefulness in our country. This doctoral thesis investigated the locally-developed external fixator (LDEF) manufactured from available and easily accessible materials for treating shaft fractures of long bones, including the tibia. The first part of this thesis investigated the treatment of open fractures in DCs in sub-Saharan Africa. A prospective clinical study on the management of OTF in a reference health facility in Ivory Coast was carried out, as was a systematic review of literature concerning the treatment of OTF. This was meant to establish an inventory concerning the treatment of open tibia fractures. The second part of this thesis investigated the design and biomechanical aspects of different LDEFs. Design of the LDEF was made from, (MED - Sciences médicales) -- UCL, 2021

This work aims to provide new insights in three frequent viral infections after kidney transplantation (KT). We show that the de novo use of an mTOR inhibitor based immunosuppressive regimen is associated with a decreased incidence of cytomegalovirus disease after KT compared to the standard of care. We demonstrate that Norovirus is the leading cause of infectious diarrhea after KT and that pre-existing conditions determine the primary functional long-term consequences after post-KT diarrhea. We show that an aggressive minimization of immunosuppression to treat sustained BK virus (BKV) viremia does not improve long-term graft outcome compared to a more gradual reduction, but is associated with an increased risk of developing de novo donor specific antibodies. Finally, we show that urinary tract infection, BKV viremia and BKV nephropathy increase the urinary levels of CXCL9 and CXCL10. These confounding factors must be addressed before urinary CXCL9 and CXCL10 can be used as noninvasive diagnostic markers of acute rejection., (MED - Sciences médicales) -- UCL, 2021

While tissue engineering strategies for most organs stems primarily from a limited number of organ donors and side effects of immunosuppressive treatments, the demand for a transplantable artificial ovary (TAO) emerges as a procedure for fertility restoration in cancer survivors, who cannot benefit from available fertility restoration solutions. Indeed chemo- and radiotherapy can potentially be toxic for the ovaries, ultimately leading to sterility. This project represents the first attempt of ‘reverse engineering’ the human ovary. Reverse engineer biology means applying the engineering concept of taking apart a process or mechanism in order to understand it and re-engineer it (perhaps in a new way)—and applying it to the biological world. In this project, human ovarian cell’s microenvironment (matrisome) was deconstructed to better understand its proteomic, architectural and mechanical cues and their role in ovarian activity from prepuberty til menopause in order to reintegrate them into a biomimetic construct. Integrating these data will enable the TAO to be in the future a life changer for many female patients through making motherhood a possibility for them after cancer survival., (MED - Sciences médicales) -- UCL, 2021

Allergic contact dermatitis (ACD) is an immunological reaction that develops in sensitized subjects following exposure to exogenous substances with allergenic properties. We were interested in two allergens responsible for recent ACD epidemics, methylisothiazolinone (MI), a preservative present in cosmetic and industrial products, and isobornyl acrylate (IBOA), a monomer used in plastics and glues. On the one hand, we analyzed the gradual extinction of sensitization to MI following imposed restrictions of its use. On the other hand, we studied the emergence of cases of ACD from IBOA present in blood glucose sensors and insulin pumps. We collaborated to the identification of the responsible allergens, analyzed the concomitant sensitizations with sesquiterpene lactones and discussed the distinction between irritation and allergy. We commented on the need for a revision of the legislation on medical devices., (MED - Sciences médicales) -- UCL, 2021

Prosthetic joint infection (PJI) is a devastating complication of joint replacement surgeries, affecting 0.5 to 2% of patients following a hip or a knee arthroplasty. Its treatment is complicated by the rapid formation of bacterial biofilms on the implants’ surfaces. Biofilms are bacterial communities enveloped in a complex self-produced matrix that isolates bacteria from their environment, leading to an increased tolerance to antimicrobials. Therefore, new therapeutic options targeting biofilms are in development to improve the outcome of PJI. The objectives of this work were to investigate biofilm disruption using a standard irrigation technique (pulsed-lavage) or an enzyme combination targeting the matrix of the biofilms, and its impact on the susceptibility of bacteria to antibiotics. Pulsed-lavage and the enzymatic combination were studied in two successive in-vitro studies, using a model of biofilms grown on titanium alloy substrates. Our experiments showed that the successive application of biofilm disrupting treatments and antibiotics, used at clinically relevant concentrations, was synergistic. Considering these encouraging results, an in-vivo model of PJI was developed to study the use of the enzymatic combination as an adjuvant to a treatment with debridement, systemic antibiotics, and implant retention. Regrettably, the addition of the enzymatic combination did not appear to improve the outcome of the treatment. However, these experiments open new perspectives to optimize the use of enzymes in this setting, and the tools developed for this work could prove useful to investigate the application of other strategies for the treatment of PJI., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2021

The epidemiologic transition ongoing in Sub-Saharan Africa(SSA) may contribute to growing burden of chronic kidney disease (CKD). In addition, the importance of genetic factors such as APOL1 renal risk variants, GSTM1 null-variant and SCT in the pathogenesis of CKD in African-Americans has been increasingly recognized, but the available evidence on those topics is scarce in Sub-Saharan Africa. We were able to randomly select and recruit more than 1300 subjects, from both an urban and a rural site, in South Kivu. Our research demonstrates a high prevalence of CKD (12%), which is largely driven by classical risk factors (age, gender, diabetes, hypertension and HIV). In addition, this thesis identifies APOL1 renal high-risk alleles and SCT as risk factors for low kidney function and/or albuminuria. The present work provides useful information for strengthening preventive strategies of CKD, in general population. Furthermore, better definition of genetic risk factors for CKD could transform the clinical management and open an avenue for precision medicine in SSA., La transition épidémiologique pourrait fort bien favoriser la maladie rénale chronique (MRC) en Afrique sub-Saharienne (ASS). En outre, les mutations dans le gène de l’APOL1, de GSTM1 et de l’hémoglobine S (HbAS) sont de plus en plus reconnues comme des facteurs de risque de MRC chez les Afro-Américains. Très peu d’études se sont attachées à ce sujet en en Afrique subsaharienne. Nous avons pu mener une vaste étude de population, qui a inclus plus de 1300 sujets, répartis sur un site urbain et un site rural du Sud Kivu. Notre recherche démontre une prévalence élevée de la MRC (12 %) au Sud-Kivu, largement liée à des facteurs de risque classiques notamment l’âge avancé, le sexe féminin, le diabète sucré, l’hypertension artérielle et l’infection à VIH. De plus, cette thèse a montré que les mutations dans le gène de APOL1 et de l’HbAS étaient associées à une baisse du débit de filtration et/ou une majoration d'albuminurie dans la population d’étude. Le présent travail fournit des informations utiles pour renforcer les stratégies de prévention de la MRC dans la population générale. De plus, une meilleure définition des facteurs de risque génétiques de la MRC pourrait transformer la pratique clinique et ouvrir une voie à la médecine de précision en ASS., (MED - Sciences médicales) -- UCL, 2021

Cervical insufficiency is one of the main causes leading to fetal losses and preterm birth. The standard treatment of cervical insufficiency is the transvaginal cerclage or, in some cases, the transabdominal cerclage (TAC). The success rate of TAC is very high. The hypothesis of the research project aimed at a better understanding of the positive value of TAC with a special focus on the fetal membranes. The project showed thickness changes in membranes with other special features in the genes expression, proteins localization and senescence. These changes could explain the success rate of TAC. A better understanding of these changes could be useful for further research in attempting a better knowledge of the mechanisms of the preterm birth and preterm premature rupture of membranes. Further research is needed to find new potential therapeutic approaches. The main objective is to reduce the prematurity., (MED - Sciences médicales) -- UCL, 2021

This work focuses on endodontically-treated molars because clinical studies have shown that this tooth group had the lowest probability of survival. To restore these teeth, direct resin-based composites have many advantages but may lead to clinical difficulties for dental practitioners, and are also associated with some major disadvantages. Classical crowns are traditionally recommended to restore indirectly highly damaged endodontically-treated molars. Cuspal coverage has indeed been described as a very important prerequisite to restore those highly damaged molars. However, recent data have challenged some of the broadly accepted guidelines, notably that peripherical preparation and a ferrule effect may not be needed. Developments in bonding strategies have also led to the development of aesthetic and less mutilating partial bonded indirect restorations instead of cemented full-crowns. The global purpose of this PhD thesis is to refine the criteria for the choice of bonding technique, restorative materials and substrate treatment restoring single endodontically-treated molar with indirect bonded restoration. The goal is to contribute to improve the understanding, practicality and efficiency of indirect bonded restoration made in resin-based composite to endodontically-treated molars., (DENT - Sciences dentaires) -- UCL, 2021

There is still much to be learned about the spontaneous epiphyseal collapse of the osteonecrotic femoral head. We used high resolution scanners to investigate the collapse of osteonecrotic femoral heads both in vitro and in vivo. We developed a method to obtain matched histology and µCT images of femoral heads, that were used to demonstrate that bone microfractures develop predominately within the necrotic territory and form cleavage planes in the superficial layer of the necrotic lesion. Our results demonstrate a positive correlation between the degree of epiphyseal collapse and the magnitude of bone resorption and cortical fractures, but not with trabecular fractures. In a large series of patients, CT detected fractures and bone resorption in 20 to 40% of non-collapsed osteonecrotic femoral heads. However, there was no difference in clinical and MRI data between femoral heads with and those without fracture or bone resorption., L’effondrement progressif, irréversible et apparemment spontané de la tête fémorale ostéonécrotique reste un phénomène mystérieux que nous avons approché en utilisant des scanners à haute résolution spatiale. Grâce à une méthode originale permettant d’apparier les images histologiques et µCT de têtes fémorales, nous avons démontré que les microfractures osseuses se développent quasi exclusivement en territoire nécrotique et forment des plans de clivage prédominant en surface des lésions. Le degré de déformation épiphysaire corrèle avec l’importance de la résorption osseuse et des fractures corticales mais pas avec l’importance des fractures trabéculaires. Dans 20 à 40 % de têtes fémorales nécrotiques non collabées d’une large série de patients, le CT démontre la présence de fractures et de résorption osseuse sans qu’il ne soit possible de dégager des différences d’aspect clinique ou IRM entre les têtes fémorales avec ou sans anomalies., (MED - Sciences médicales) -- UCL, 2021