Condições músculo-esqueléticas como as desordens da articulação temporomandibular (ATM) são as principais causas de dor não odontogênica na região orofacial e incluem um grupo de condições usualmente acompanhadas de dor na região das ATMs e dos músculos mastigatórios, limitação da abertura bucal e dores de cabeça. Pacientes com desordens da articulação temporomandibular (DTM) também podem apresentar desordens relacionadas ao estresse caracterizadas por alterações somáticas e psicológicas como fadiga, distúrbios do sono, ansiedade e depressão. A causa exata das DTMs ainda não é completamente entendida, mas acredita-se que envolva fatores fisiológicos, comportamentais e ambientais. É possível que alguns sintomas de DTM e dor orofacial sejam apenas manifestações somáticas de estresse emocional. De fato, situações de estresse promovem uma série de mudanças fisiológicas e comportamentais que podem afetar os sistemas hormonais e de neurotransmissores. Estudos demonstraram que o CRF e seus receptores medeiam respostas comportamentais, endócrinas e autonômicas para o estresse, além de estar envolvidos em outras funções, como na modulação nociceptiva. O objetivo deste trabalho foi avaliar a nocicepção e o comportamento emocional em ratos com inflamação persistente nas ATMs, induzida por administração de adjuvante completo de Freund (CFA) em diferentes situações de estresse (agudo - EA, crônico repetido - ECR e crônico variado - ECV), bem como a ação do antidepressivo tricíclico (inibidor da recaptação de catecolaminas), imipramina, nessas respostas. Ainda, investigou-se o possível envolvimento de receptores CRF do núcleo central da amígdala (CEA) na modulação nociceptiva de animais com inflamação persistente das ATMs. Os resultados mostraram que a inflamação persistente das ATMs promoveu alodinia mecânica orofacial e hiperalgesia secundária. O EA per se promoveu analgesia nos animais sem inflamação das ATMs, além de reverter a alodinia mecânica e a hiperalgesia secundária induzidos pelo CFA intra-articular. Ainda, o ECV e o ECR promoveram per se hiperalgesia nos animais sem inflamação, mas não alteraram o efeito da administração intra-articular de CFA. Em adição, a inflamação persistente das ATMs promoveu alterações comportamentais com efeitos ansiogênicos significativos que não foram alterados pela exposição dos animais ao EA ou ECR. Em contrapartida, o ECV demonstrou efeito ansiogênico nos animais sem inflamação, porém não houve alterações nos animais com inflamação persistente nas ATMs. Em adição, a administração de imipramina reverteu a hiperalgesia, exercendo, dessa forma, efeito analgésico, e o efeito ansiogênico causado pelo CFA intra-articular. Com relação ao envolvimento de receptores para CRF no CEA verificamos que sua ativação promoveu analgesia nos animais sem inflamação das ATMs e ainda reverteu a hiperalgesia decorrente da administração intra-articular do CFA. Assim, nossos resultados sugerem que a inflamação persistente nas ATMs induzida por CFA produz efeitos ansiogênicos e aumenta a sensibilidade nociceptiva, bem como situações de estresse agudo e crônico podem modular essas alterações. Ainda, os efeitos da inflamação persistente podem ser revertidas pelo tratamento sistêmico com imipramina, e pela administração de agonista de receptores CRF no CEA. / Musculoskeletal conditions such as disorders of the temporomandibular joint (TMJ) are the main cause of non-odontogenic pain in the orofacial region and include a group of conditions usually accompanied by pain in TMJ region and masticatory muscles, limitation of mouth opening and headache. Patients with temporomandibular joint disorders (TMD) may also show related stress disorders characterized by somatic and psychological changes such as fatigue, sleep disturbances, anxiety and depression. The exact cause of TMD is not yet completely clarified, but is believed to involve physiological, behavioral and environmental factors. It is possible that some symptoms of TMD and orofacial pain are only somatic manifestations of emotional stress. In fact, stressful situations promote a series of physiological and behavioral changes that may affect hormonal and neurotransmitter systems. Studies have shown that CRF and its receptors mediate behavioral, endocrine and autonomic responses to stress, in addition to being involved in other functions such as nociceptive modulation. The aim of this study was to evaluate emotional behavior and nociception in rats with persistent inflammation in TMJ induced by administration of complete Freund\'s adjuvant (CFA) in different stress situations (acute stress - AS, chronic restraint stress - CRS and unpredictable chronic stress - UCS) and the action of the tricyclic antidepressant (catecholamine reuptake inhibitor), imipramine, in these responses. In addition, we investigated the possible involvement of CRF receptors in the central nucleus of the amygdala (CEA) in nociceptive modulation in animals with persistent inflammation of the TMJs. The results have shown that persistent TMJ inflammation produced mechanical orofacial allodynia and widespread secondary hyperalgesia. AS induced analgesia in animals without TMJ inflammation and reversed both mechanical allodynia and secondary hyperalgesia induced by intra-articular CFA injection. In addition, CRS and UCS induced hyperalgesia in animals without inflammation, but did not alter the effect of intra-articular administration of CFA. Also, the persistent inflammation of the TMJ promoted behavioral changes with significant ansiogenic effects that were not altered by exposure of the animals to AS or CRS. In contrast, UCS showed ansiogenic effect in animals without inflammation, but no changes in animals with persistent TMJ inflammation. In addition, administration of imipramine had an ansiogenic and analgesic effect, reversing the hyperalgesia caused by intra-articular CFA administration. Regarding the involvement of CRF receptors in the CEA this study demonstrated that this activation promoted analgesia in animals without inflammation of the TMJ and was able to reverse the hyperalgesia caused by intra-articular CFA administration. Thus, our results suggest that persistent temporomandibular inflammation induced by CFA produces anxiogenic effects and decreases nociceptive sensitivity and situations of acute and chronic stress can modulate these changes. In addition, these changes can be reversed by systemic treatment with imipramine and by administration of CRF receptor agonist in CEA.

L'humanité a longtemps été passionnée par la création de machines intellectuelles qui peuvent librement intéragir avec nous dans notre langue. Tous les systèmes modernes qui communiquent directement avec l'utilisateur partagent une caractéristique commune: ils ont un système de dialogue à la base. Aujourd'hui pratiquement tous les composants d'un système de dialogue ont adopté des méthodes statistiques et les utilisent largement comme leurs modèles de base. Jusqu'à récemment la génération de langage naturel (GLN) utilisait pour la plupart des patrons/modèles codés manuellement, qui représentaient des phrases types mappées à des réalisations sémantiques particulières. C'était le cas jusqu'à ce que les approches statistiques aient envahi la communauté de recherche en systèmes de dialogue. Dans cette thèse, nous suivons cette ligne de recherche et présentons une nouvelle approche à la génération de la langue naturelle. Au cours de notre travail, nous nous concentrons sur deux aspects importants du développement des systèmes de génération: construire un générateur performant et diversifier sa production. Deux idées principales que nous défendons ici sont les suivantes: d'abord, la tâche de GLN peut être vue comme la traduction entre une langue naturelle et une représentation formelle de sens, et en second lieu, l'extension du corpus qui impliquait traditionnellement des paraphrases définies manuellement et des règles spécialisées peut être effectuée automatiquement en utilisant des méthodes automatiques d'extraction des synonymes et des paraphrases bien connues et largement utilisées. En ce qui concerne notre première idée, nous étudions la possibilité d'utiliser le cadre de la traduction automatique basé sur des modèles ngrams; nous explorons également le potentiel de l'apprentissage discriminant (notamment les champs aléatoires markoviens) appliqué à la GLN; nous construisons un système de génération qui permet l'inclusion et la combinaison des différents modèles et qui utilise un cadre de décodage efficace (automate à état fini). En ce qui concerne le second objectif, qui est l'extension du corpus, nous proposons d'élargir la taille du vocabulaire et le nombre de l'ensemble des structures syntaxiques disponibles via l'intégration des synonymes et des paraphrases. À notre connaissance, il n'y a pas eu de tentatives d'augmenter la taille du vocabulaire d'un système de GLN en incorporant les synonymes. À ce jour, la plupart d'études sur l'extension du corpus visent les paraphrases et recourent au crowdsourcing pour les obtenir, ce qui nécessite une validation supplémentaire effectuée par les développeurs du système. Nous montrons que l'extension du corpus au moyen d'extraction automatique de paraphrases et la validation automatique sont tout aussi efficaces, étant en même temps moins coûteux en termes de temps de développement et de ressources. Au cours d'expériences intermédiaires nos modèles ont montré une meilleure performance que celle obtenue par le modèle de référence basé sur les syntagmes et se sont révélés d'être plus robustes, pour le traitement des combinaisons inconnues de concepts, que le générateur à base des règles. L'évaluation humaine finale a prouvé que les modèles représent une alternative solide au générateur à base des règles / The humanity has long been passionate about creating intellectual machines that can freely communicate with us in our language. Most modern systems communicating directly with the user share one common feature: they have a dialog system (DS) at their base. As of today almost all DS components embraced statistical methods and widely use them as their core models. Until recently Natural Language Generation (NLG) component of a dialog system used primarily hand-coded generation templates, which represented model phrases in a natural language mapped to a particular semantic content. Today data-driven models are making their way into the NLG domain. In this thesis, we follow along this new line of research and present several novel data-driven approaches to natural language generation. In our work we focus on two important aspects of NLG systems development: building an efficient generator and diversifying its output. Two key ideas that we defend here are the following: first, the task of NLG can be regarded as the translation between a natural language and a formal meaning representation, and therefore, can be performed using statistical machine translation techniques, and second, corpus extension and diversification which traditionally involved manual paraphrasing and rule crafting can be performed automatically using well-known and widely used synonym and paraphrase extraction methods. Concerning our first idea, we investigate the possibility of using NGRAM translation framework and explore the potential of discriminative learning, notably Conditional Random Fields (CRF) models, as applied to NLG; we build a generation pipeline which allows for inclusion and combination of different generation models (NGRAM and CRF) and which uses an efficient decoding framework (finite-state transducers' best path search). Regarding the second objective, namely corpus extension, we propose to enlarge the system's vocabulary and the set of available syntactic structures via integrating automatically obtained synonyms and paraphrases into the training corpus. To our knowledge, there have been no attempts to increase the size of the system vocabulary by incorporating synonyms. To date most studies on corpus extension focused on paraphrasing and resorted to crowd-sourcing in order to obtain paraphrases, which then required additional manual validation often performed by system developers. We prove that automatic corpus extension by means of paraphrase extraction and validation is just as effective as crowd-sourcing, being at the same time less costly in terms of development time and resources. During intermediate experiments our generation models showed a significantly better performance than the phrase-based baseline model and appeared to be more robust in handling unknown combinations of concepts than the current in-house rule-based generator. The final human evaluation confirmed that our data-driven NLG models is a viable alternative to rule-based generators.

La neurobiologie à l'origine d'un comportement social des consommateurs d'opiacés et des personnes dépendantes reste largement méconnue, entravant le développement de nouveaux traitements efficaces contre les troubles de l'utilisation des opiacés. Cependant, des preuves précliniques récentes suggèrent que le système du facteur de libération de la corticotrophine (CRF) pourrait être impliqué. Dans cette optique, nous avons utilisé la méthode des tâches à trois chambres (3-CH) ainsi qu'une méthode génétique et pharmacologique pour évaluer l’impact de l’administration de la morphine et du sevrage sur le comportement social des souris vis-à-vis de l'utilisation du système CRF. Dans une première série d'expériences, nous avons constaté que les sujets mâles manifestaient un intérêt pseudo-social accru suscité par l'hostilité pendant le sevrage des opiacés, ce qui indiquait les effets à long terme de l'administration chronique de médicaments sur le fonctionnement social normal. Par ailleurs, les femelles ont manifesté moins d’intérêt social lors du sevrage aux opiacés, un phénotype qui reproduit plus facilement ce qui a été observé chez l’homme. Notamment, le déficit en récepteurs CRF1 a complètement sauvé ce dernier déficit social, ajoutant ainsi aux preuves croissantes liant le système CRF aux dysfonctionnements comportementaux induits par la substance. Dans une deuxième série d'expériences, nous avons étudié plus largement les effets initiaux de la morphine sur les activités « naturellement » gratifiantes. Nous avons constaté qu'une seule et même administration aiguë d'une dose relativement faible du médicament suffisait à la fois à générer une récompense cérébrale et à induire de profonds déficits en intérêt social et en motivation liée à l'alimentation, fournissant ainsi des preuves expérimentales initiales du « détournement » du cerveau. Il est intéressant de noter que l'administration systémique d'antalarmine, antagoniste du récepteur de la CRF, a complètement inversé ce dernier déficit social, ce qui indique que le système CRF joue un rôle essentiel dans la médiation de la diminution de l'intérêt suscité par les substances pour des activités rémunératrices «naturellement» et renforce la notion de potentiel thérapeutique du ciblage de la CRF. / The neurobiology underlying poor social behavior of opiate users and dependent individuals remains largely unknown, hampering the development of noveleffective therapies for opiate use disorders. However, recent pre-clinical evidence suggests that the corticotropin-releasing factor (CRF) system might be involved.In this light, we employed the three-chamber (3-CH) task and genetic/pharmacological approaches to assess the impact of morphine administrationand withdrawal upon social behavior in mice with regard to the CRF system. In a first set of experiments, we found that male subjects displayed increasedhostility-driven pseudo-social interest during opiate withdrawal, indicative of longlasting effects of chronic drug administration upon normal social functioning. On theother hand, female subjects displayed lower social interest during opiate withdrawal, a phenotype that more straightforwardly replicates what observed in humans.Notably, CRF1 receptor-deficiency completely rescued the latter social deficit, adding to the growing evidence linking the CRF system to substance-induced behavioraldysfunctions. In a second set of experiments, we investigated the initial effects of morphine more widely on naturally” rewarding activities. We found that a single, acuteadministration of a relatively low dose of the drug was sufficient to produce brain reward and at the same time to induce profound deficits in social interest and fooddriven motivation, providing initial experimental evidence of “hijacking” of brain reward systems by substances of abuse. Interestingly, systemic administration of the CRF receptor antagonist antalarmin completely reversed the latter social deficit, indicating a critical role of the CRF system in mediating substance-induced decreased interest for “naturally” rewarding activities and strengthening the notion of a therapeutic potential for CRF-targeting pharmacological agents.

Brustschmerz ist ein häufiges Symptom. Er bedarf einer schnellen Differenzierung zum Ausschluss lebensbedrohlicher Erkrankungen wie zum Beispiel eines Myokardinfarktes oder einer Aortendissektion. Hierzu wurden Chest Pain Units (CPU) und Brustschmerzambulanzen (BSA) gegründet. Im Jahr 2008 führte die Deutsche Gesellschaft für Kardiologie Mindeststandards für deren Ausstattung und Struktur ein. 2009 wurde die zwei Jahre zuvor gegründete BSA am Herzzentrum Leipzig (HZL) zertifiziert. In dieser Arbeit wurde eine retrospektive Analyse von 2.220 Patientendaten aus dem Jahr 2009 durchgeführt. Bei steigenden Patientenzahlen wurde die BSA am häufigsten montags sowie in den Mittagsstunden aufgesucht. Dabei zeigte die Symptomdauer eine Spannweite von wenigen Minuten bis zu mehreren Jahren. Der größte Anteil mit 19,1 % der Patienten kam mit einer Symptomdauer zwischen einer Woche und einem Monat, 11,6 % der Patienten innerhalb von sechs Stunden. Symptome und Begleiterkrankungen boten eine große Variabilität. 24,7 % der Patienten stellten sich ohne Schmerzen vor. 66,4 % der Patienten verblieben ambulant und durchschnittlich verbrachten die Patienten 4,8 Stunden in der BSA. 59,9 % der Patienten ohne primär ersichtliche, kardiale Symptomkonstellation zeigten eine kardiale Erkrankung. Selbsteinweiser und ärztlich eingewiesene Patienten sowie stationäre und ambulante Verläufe zeigten Unterschiede in Symptomen, Begleiterkrankungen, Untersuchungen, Interventionen und Entlassungsdiagnosen. 26,9 % der Patienten erhielten eine Herzkatheteruntersuchung. Davon erfolgte bei 31,4 % eine Intervention, in 62,4 % der Fälle eine medikamentöse Therapie. Eine KHK war bei 19,1 % der Patienten die Entlassungsdiagnose. In der Hälfte der Fälle wurde damit erstmals diese Diagnose gestellt. Aus Symptomen, Symptomdauer und kardiovaskulären Risikofaktoren wurde der Symptome-30-2-CRF-Score abgeleitet, welcher bei ≤ 9 Punkten eine KHK ablehnt und bei Werten ≥ 14 Punkten den Verdacht auf eine KHK bekräftigt.

Les grammaires de dépendance permettent de construire une organisation hiérarchique syntaxique des mots d’une phrase. La construction manuelle des arbres de dépendances étant une tâche exigeant temps et expertise, de nombreux travaux cherchent à l’automatiser. Visant à établir un processus léger et facilement adaptable nous nous sommes intéressés à l’apprentissage non supervisé de dépendances, évitant ainsi d’avoir recours à une expertise coûteuse. L’état de l’art en apprentissage non supervisé de dépendances (DMV) se compose de méthodes très complexes et extrêmement sensibles au paramétrage initial. Nous présentons dans cette thèse un nouveau modèle pour résoudre ce problème d’analyse de dépendances, mais de façon plus simple, plus rapide et plus adaptable. Nous apprenons une famille de grammaires (PCFG) réduites à moins de 6 non terminaux et de 15 règles de combinaisons des non terminaux à partir des étiquettes grammaticales. Les PCFG de cette famille que nous nommons DGdg (pour DROITE GAUCHE droite gauche) se paramètrent très légèrement, ainsi elles s’adaptent sans effort aux 12 langues testées. L’apprentissage et l’analyse sont effectués au moins deux fois plus rapidement que DMV sur les mêmes données. Et la qualité des analyses DGdg est pour certaines langues proches des analyses par DMV. Nous proposons une première application de notre méthode d’analyse de dépendances à l’extraction d’informations. Nous apprenons par des CRF un étiquetage en fonctions « sujet », « objet » et « prédicat », en nous fondant sur des caractéristiques extraites des arbres construits. / Dependency grammars allow the construction of a hierarchical organization of the words of sentences. The one-by-one building of dependency trees can be very long and it requries expert knowledge. In this regard, we are interested in unsupervised dependency learning. Currently, DMV give the state-of-art results in unsupervised dependency parsing. However, DMV has been known to be highly sensitive to initial parameters. The training of DMV model is also heavy and long. We present in this thesis a new model to solve this problem in a simpler, faster and more adaptable way. We learn a family of PCFG using less than 6 nonterminal symbols and less than 15 combination rules from the part-of-speech tags. The tuning of these PCFG is ligth, and so easily adaptable to the 12 languages we tested. Our proposed method for unsupervised dependency parsing can show the near state-of-the-art results, being twice faster. Moreover, we describe our interests in dependency trees to other applications such as relation extraction. Therefore, we show how such information from dependency structures can be integrated into condition random fields and how to improve a relation extraction task.

Brustschmerz ist ein häufiges Symptom. Er bedarf einer schnellen Differenzierung zum Ausschluss lebensbedrohlicher Erkrankungen wie zum Beispiel eines Myokardinfarktes oder einer Aortendissektion. Hierzu wurden Chest Pain Units (CPU) und Brustschmerzambulanzen (BSA) gegründet. Im Jahr 2008 führte die Deutsche Gesellschaft für Kardiologie Mindeststandards für deren Ausstattung und Struktur ein. 2009 wurde die zwei Jahre zuvor gegründete BSA am Herzzentrum Leipzig (HZL) zertifiziert. In dieser Arbeit wurde eine retrospektive Analyse von 2.220 Patientendaten aus dem Jahr 2009 durchgeführt. Bei steigenden Patientenzahlen wurde die BSA am häufigsten montags sowie in den Mittagsstunden aufgesucht. Dabei zeigte die Symptomdauer eine Spannweite von wenigen Minuten bis zu mehreren Jahren. Der größte Anteil mit 19,1 % der Patienten kam mit einer Symptomdauer zwischen einer Woche und einem Monat, 11,6 % der Patienten innerhalb von sechs Stunden. Symptome und Begleiterkrankungen boten eine große Variabilität. 24,7 % der Patienten stellten sich ohne Schmerzen vor. 66,4 % der Patienten verblieben ambulant und durchschnittlich verbrachten die Patienten 4,8 Stunden in der BSA. 59,9 % der Patienten ohne primär ersichtliche, kardiale Symptomkonstellation zeigten eine kardiale Erkrankung. Selbsteinweiser und ärztlich eingewiesene Patienten sowie stationäre und ambulante Verläufe zeigten Unterschiede in Symptomen, Begleiterkrankungen, Untersuchungen, Interventionen und Entlassungsdiagnosen. 26,9 % der Patienten erhielten eine Herzkatheteruntersuchung. Davon erfolgte bei 31,4 % eine Intervention, in 62,4 % der Fälle eine medikamentöse Therapie. Eine KHK war bei 19,1 % der Patienten die Entlassungsdiagnose. In der Hälfte der Fälle wurde damit erstmals diese Diagnose gestellt. Aus Symptomen, Symptomdauer und kardiovaskulären Risikofaktoren wurde der Symptome-30-2-CRF-Score abgeleitet, welcher bei ≤ 9 Punkten eine KHK ablehnt und bei Werten ≥ 14 Punkten den Verdacht auf eine KHK bekräftigt.

For individuals with type 2 diabetes, diabetic foot ulcers represent a significant health issue and the wound care cost is quite high. Currently, clinicians and nurses mainly base their wound assessment on visual examination of wound size and the status of the wound tissue. This method is potentially inaccurate for wound assessment and requires extra clinical workload. In view of the prevalence of smartphones with high resolution digital camera, assessing wound healing by analyzing of real-time images using the significant computational power of today’s mobile devices is an attractive approach for managing foot ulcers. Alternatively, the smartphone may be used just for image capture and wireless transfer to a PC or laptop for image processing. To achieve accurate foot ulcer image assessment, we have developed and tested a novel automatic wound image analysis system which accomplishes the following conditions: 1) design of an easy-to-use image capture system which makes the image capture process comfortable for the patient and provides well-controlled image capture conditions; 2) synthesis of efficient and accurate algorithms for real-time wound boundary determination to measure the wound area size; 3) development of a quantitative method to assess the wound healing status based on a foot ulcer image sequence for a given patient and 4) design of a wound image assessment and management system that can be used both in the patient’s home and clinical environment in a tele-medicine fashion. In our work, the wound image is captured by the camera on the smartphone while the patient’s foot is held in place by an image capture box, which is specially design to aid patients in photographing ulcers occurring on the sole of their feet. The experimental results prove that our image capture system guarantees consistent illumination and a fixed distance between the foot and camera. These properties greatly reduce the complexity of the subsequent wound recognition and assessment. The most significant contribution of our work is the development of five different wound boundary determination approaches based on different computer vision algorithms. The first approach employs the level set algorithm to determine the wound boundary directly based on a manually set initial curve. The second and third approaches are the mean-shift segmentation based methods augmented by foot outline detection and analysis. These two approaches have been shown to be efficient to implement (especially on smartphones), prior-knowledge independent and able to provide reasonably accurate wound segmentation results given a set of well-tuned parameters. However, this method suffers from the lack of self-adaptivity due to the fact that it is not based on machine learning. Consequently, a two-stage Support Vector Machine (SVM) binary classifier based wound recognition approach is developed and implemented. This approach consists of three major steps 1) unsupervised super-pixel segmentation, 2) feature descriptor extraction for each super-pixel and 3) supervised classifier based wound boundary determination. The experimental results show that this approach provides promising performance (sensitivity: 73.3%, specificity: 95.6%) when dealing with foot ulcer images captured with our image capture box. In the third approach, we further relax the image capture constraints and generalize the application of our wound recognition system by applying the conditional random field (CRF) based model to solve the wound boundary determination. The key modules in this approach are the TextonBoost based potential learning at different scales and efficient CRF model inference to find the optimal labeling. Finally, the standard K-means clustering algorithm is applied to the determined wound area for color based wound tissue classification. To train the models used in the last two approaches, as well as to evaluate all three methods, we have collected about 100 wound images at the wound clinic in UMass Medical School by tracking 15 patients for a 2-year period, following an IRB approved protocol. The wound recognition results were compared with the ground truth generated by combining clinical labeling from three experienced clinicians. Specificity and sensitivity based measures indicate that the CRF based approach is the most reliable method despite its implementation complexity and computational demands. In addition, sample images of Moulage wound simulations are also used to increase the evaluation flexibility. The advantages and disadvantages of three approaches are described. Another important contribution of this work has been development of a healing score based mechanism for quantitative wound healing status assessment. The wound size and color composition measurements were converted to a score number ranging from 0-10, which indicates the healing trend based on comparisons of subsequent images to an initial foot ulcer image. By comparing the result of the healing score algorithm to the healing scores determined by experienced clinicians, we assess the clinical validity of our healing score algorithm. The level of agreement of our healing score with the three assessing clinicians was quantified by using the Kripendorff’s Alpha Coefficient (KAC). Finally, a collaborative wound image management system between the PC and smartphone was designed and successfully applied in the wound clinic for patients’ wound tracking purpose. This system is proven to be applicable in clinical environment and capable of providing interactive foot ulcer care in a telemedicine fashion.

Les systèmes de télécommunications actuels nécessitent des filtres passe bande fonctionnant à des fréquences comprises entre 1 GHz et 10 GHz pour les systèmes les plus répandus, notamment la téléphonie mobile. Les filtres actuels sont reportés, donc non intégrés sur silicium. Ils présentent certains inconvénients : coût, place occupée, incompatibilité avec les technologies silicium...Une solution consiste à utiliser des résonateurs à ondes de volume, plus communément appelés BAW (Bulk Acoustic Waves). Ils présentent l'avantage d'être intégrables sur silicium. De nouvelles architectures nommées CRF (Coupled Resonator Filter) font appel à des résonateurs à ondes de volume (BAW) mais aussi à des structures utilisant des couplages acoustiques entre différentes couches. L'objectif du travail proposé est de modéliser les structures actuelles et en cours d'études pour obtenir des modèles de type circuits électriques. Ces modèles seront validés par des mesures effectuées au laboratoire sur des résonateurs BAW et sur des filtres qui sont réalisés par nos partenaires. La première partie des études portait sur le comportement RF sous faible et forte puissances, suivi du développement d'un modèle large bande simulé sous ADS décrivant le comportement des filtres BAW sous faible et forte puissances. Une optimisation du temps de mesure en fréquence est effectuée pour réduire le temps du test RF. La seconde partie de la thèse est orientée vers le développement d'une nouvelle méthode de test pseudo-temporelle des filtres hyperfréquences qui consiste à mesurer directement leur impact sur un signal numérique grâce au paramètre "EVM" (Error Vector Magnitude). Ce paramètre est relié au BER et nos travaux montrent qu'il permet également de retrouver en partie les paramètres S et détecter les filtres défaillants à partir d'une seule mesure. Cette nouvelle technique permettant le test de filtres à partir d'un seul point de mesure permet de réduire le temps et le coût de caractérisation à des fins industrielles. Ce travail s'est déroulé dans un cadre de collaborations avec le LETI et STMicroelectronics au sein du projet FAST labellisé par le pôle MINALOGIC.

The neuropeptide, corticotropin-releasing factor (CRF), plays a critical role in the central regulation of various stress-related behaviours, including those unique to subjects with prior cocaine experience. The three series of experiments presented in this dissertation explored the role of two neurochemical systems, the teneurin C-terminal associated peptides (TCAP) and the endocannabinoids (eCBs), in several cocaine- and anxiety-related behaviours induced or mediated by CRF. The first series of experiments examined the effects of TCAP-1 on the reinstatement of cocaine seeking and expression of cocaine-induced behavioural sensitization. Repeated (5-day), but not acute, TCAP-1 treatment blocked the reinstatement of cocaine seeking induced by central injections of CRF. TCAP-1 was, however, without effect on footshock- or cocaine-induced reinstatement. Repeated TCAP-1 further interfered with the expression of behavioural sensitization to a CRF, but not a cocaine, challenge. These findings suggest that TCAP-1 normalizes CRF signaling dysregulated by cocaine exposure to interfere in the subsequent effects of CRF on cocaine-related behaviours. A parallel series of experiments investigated the role of eCB signaling at CB1 receptors in the reinstatement of cocaine seeking and cocaine-sensitized locomotion. Pretreatment with the CB1 receptor antagonist, AM251, selectively interfered with CRF-, but not footshock- or cocaine-induced reinstatement. AM251 further blocked the expression of behavioural sensitization induced by challenge injections of both CRF and cocaine. These findings reveal a mediating role for CB1 receptor transmission in the effects of CRF on cocaine-related behaviours. A final series of experiments examined the role of CB1 receptor transmission in the behavioural anxiety induced by central injections of CRF, and by withdrawal from chronic cocaine exposure. AM251, although itself anxiogenic, reversed anxiety induced by CRF and cocaine withdrawal. Furthermore, AM251 elevated plasma corticosterone levels, indicative of increased HPA axis activity, irrespective of CRF treatment or cocaine withdrawal. These findings suggest that CRF- and cocaine withdrawal-induced anxiety are mediated, at least in part, by CB1 receptor transmission, independent of HPA axis regulation. The collective findings are discussed within a framework of CRF-TCAP-eCB interactions, wherein TCAP-1 and AM251 are proposed to act in parallel to modulate amygdalar CRF transmission, and thus regulate the expression of cocaine- and anxiety-related behaviours.

The neuropeptide, corticotropin-releasing factor (CRF), plays a critical role in the central regulation of various stress-related behaviours, including those unique to subjects with prior cocaine experience. The three series of experiments presented in this dissertation explored the role of two neurochemical systems, the teneurin C-terminal associated peptides (TCAP) and the endocannabinoids (eCBs), in several cocaine- and anxiety-related behaviours induced or mediated by CRF. The first series of experiments examined the effects of TCAP-1 on the reinstatement of cocaine seeking and expression of cocaine-induced behavioural sensitization. Repeated (5-day), but not acute, TCAP-1 treatment blocked the reinstatement of cocaine seeking induced by central injections of CRF. TCAP-1 was, however, without effect on footshock- or cocaine-induced reinstatement. Repeated TCAP-1 further interfered with the expression of behavioural sensitization to a CRF, but not a cocaine, challenge. These findings suggest that TCAP-1 normalizes CRF signaling dysregulated by cocaine exposure to interfere in the subsequent effects of CRF on cocaine-related behaviours. A parallel series of experiments investigated the role of eCB signaling at CB1 receptors in the reinstatement of cocaine seeking and cocaine-sensitized locomotion. Pretreatment with the CB1 receptor antagonist, AM251, selectively interfered with CRF-, but not footshock- or cocaine-induced reinstatement. AM251 further blocked the expression of behavioural sensitization induced by challenge injections of both CRF and cocaine. These findings reveal a mediating role for CB1 receptor transmission in the effects of CRF on cocaine-related behaviours. A final series of experiments examined the role of CB1 receptor transmission in the behavioural anxiety induced by central injections of CRF, and by withdrawal from chronic cocaine exposure. AM251, although itself anxiogenic, reversed anxiety induced by CRF and cocaine withdrawal. Furthermore, AM251 elevated plasma corticosterone levels, indicative of increased HPA axis activity, irrespective of CRF treatment or cocaine withdrawal. These findings suggest that CRF- and cocaine withdrawal-induced anxiety are mediated, at least in part, by CB1 receptor transmission, independent of HPA axis regulation. The collective findings are discussed within a framework of CRF-TCAP-eCB interactions, wherein TCAP-1 and AM251 are proposed to act in parallel to modulate amygdalar CRF transmission, and thus regulate the expression of cocaine- and anxiety-related behaviours.