L'objectif général du travail de cette thèse est de proposer des méthodes robustes pour permettre d'obtenir des critères sur l'évolution de la pathologie tumorale à partir d'études dynamiques. Actuellement, l'appréciation de l'efficacité d'un traitement antiangiogénique (destruction des vaisseaux alimentant la tumeur) repose principalement sur l'imagerie fonctionnelle dont l'objectif est de quantifier la microcirculation tumorale à partir d'acquisitions dynamiques de perfusion. Cependant, différentes limites concernant le suivi de la réponse précoce des lésions par imagerie existent (mauvaise maîtrise des mouvements respiratoires, pas de consensus sur les paramètres permettant de quantifier la microcirculation tumorale, estimation paramétrique faite à partir de données extrêmement bruitées et pour un grand nombre de zones - une estimation par voxel de la séquence dynamique d'images). Dans un contexte clinique extrêmement contraignant, nous avons mis en place un cadre rigoureux comprenant l'ensemble des étapes nécessaires pour une caractérisation plus fiable de la microcirculation tumorale à partir de séquences d'images acquises sous perfusion de produit de contraste : les contributions principales de cette thèse couvrent ainsi l'optimisation des paramètres de reconstruction, le développement d'une méthode de recalage adaptée à nos données, la sélection argumentée d'un modèle de perfusion et enfin le développement d'une méthode robuste d'estimation des paramètres. Ces travaux permettent d'envisager l'utilisation des modèles de perfusion pour la caractérisation et la prédiction de la réponse d'un patient à différents traitements antitumoraux.

Par le passé, la collaboration entre le Centre d'Imagerie Médicale de Sherbrooke (CIMS) et le Groupe de Recherche en Appareillage Médicale de Sherbrooke (GRAMS) a permis de développer le scanner LabPET. Celui-ci fut le premier scanner de Tomographie d'Émission par Positrons (TEP) commercial utilisant des photodiodes à effet avalanche (PDA) comme détecteur. Depuis, cette collaboration a permis de faire évoluer le scanner afin d'améliorer cette modalité d'imagerie et d'y ajouter la tomodensitométrie (TDM). Les attentes pour la prochaine génération du scanner sont donc grandes. Cette nouvelle génération du scanner, le LabPET II, verra les deux modalités nativement intégrées et elles utiliseront la même chaine de détection. Ce scanner se verra doté de nouveaux détecteurs organisés en matrices de 64 cristaux de 1,1 par 1,1 mm². Cette nouvelle matrice, associée à ses deux matrices de 32 PDA, a prouvé sa capacité à fournir une résolution spatiale inférieure au millimètre. L'utilisation de ce nouveau module de détection pourra donc permettre au LabPET II d'être le premier scanner bimodal (TEP/TDM) commercial atteignant une résolution submillimétrique. Ce scanner permettra de s'approcher un peu plus de la résolution spatiale ultime en TEP tout en permettant une bonne localisation anatomique grâce à l'ajout d'une imagerie TDM rudimentaire. Pour atteindre ces objectifs, une intégration complète de l'électronique frontale a été nécessaire. Dans les versions précédentes, seuls les préamplificateurs de charge et les filtres de mise en forme étaient intégrés; dans cette nouvelle version, toute l'électronique analogique ainsi que la numérisation et les liens de communications devront être intégrés. Pour ce faire, la technique de temps de survol au-dessus d'un seuil (ou ToT pour «Time-over-Threshold») a été préférée à la solution utilisée par le LabPET I qui nécessitait un convertisseur analogique-numérique par canal. La contrepartie de cette solution est l'obligation de maintenir la tension de base à une valeur fixe et commune à tous les canaux. Le circuit de polarisation des PDA a aussi dû être intégré dans l'ASIC, car il occupait énormément de place sur la carte d'électronique frontale du LabPET 1. Dans ce mémoire seront décrits la conception, l'intégration et les tests de ces deux circuits du système. Ils ont démontré leur efficacité tout en n'occupant que très peu de place dans le circuit intégré spécialisé (ASIC) du «module de détection». Au vu des sources bibliographiques recensées, le module de détection du LabPET II devrait être l'un de ceux ayant la plus forte densité de canaux (environ 45 par centimètre carré) et le seul combinant électronique analogique faible bruit, numérique et haute tension (~450 V). La réalisation de cette nouvelle génération devrait permettre au partenariat CIMS/GRAMS de réaffirmer leur position de leader dans le domaine en améliorant les outils d'imagerie à la disposition des chercheurs en médecine préclinique.

Much has been written about the desperate need to seek alternative solutions to the urban traffic congestion problems we face today. To manage these problems, three main streams of intervention have evolved from supply, demand and land-use management paradigms. Whilst their underlying measures all have the ability to reduce traffic congestion one way or another, little has been done to integrate the measures of each stream using a qualitative decision framework or process enabling the selection of site specific measures appropriate to local traffic and transport conditions. To this end the study reports the results of an empirical investigation by which a Multi-Criteria Analysis based Dynamic Adaptive Decision Framework (D.A.D.F.) were developed. This screens selected measures identifying those that have the potential to alleviate site specific road based traffic congestion. The product of the screening process is a set of sustainable measures transposed into an integrated strategy tailored to address local traffic congestion issues. Once the D.A.D.F. was developed, its usefulness and workability was tested by applying it to a case study. The case study results demonstrated that the D.A.D.F. is capable of producing integrated strategies with the ability to manage traffic congestion, encourage sustainable development and alleviate some site specific development challenges within the context of the study areas. Going beyond developing the decision framework, the study recommends positioning the D.A.D.F. within the South African planning system as part of a Traffic Congestion Management Plan (T.C.M.P.), setting out its likely components within the local context. It is concluded that the main innovation of the study is the development of the D.A.D.F., the T.C.M.P., the recommendations to situate both in the planning system and the comprehensive, but still transparent, approach undertaken to create integrated strategies for specific local conditions consisting of elements that work together to produce cumulative short to long term effects that attain a balanced set of environmental, social and economic goals - all imperative for sustainable development. / Thesis (Ph.D. (Town and Regional Planning))--North-West University, Potchefstroom Campus, 2008.

Much has been written about the desperate need to seek alternative solutions to the urban traffic congestion problems we face today. To manage these problems, three main streams of intervention have evolved from supply, demand and land-use management paradigms. Whilst their underlying measures all have the ability to reduce traffic congestion one way or another, little has been done to integrate the measures of each stream using a qualitative decision framework or process enabling the selection of site specific measures appropriate to local traffic and transport conditions. To this end the study reports the results of an empirical investigation by which a Multi-Criteria Analysis based Dynamic Adaptive Decision Framework (D.A.D.F.) were developed. This screens selected measures identifying those that have the potential to alleviate site specific road based traffic congestion. The product of the screening process is a set of sustainable measures transposed into an integrated strategy tailored to address local traffic congestion issues. Once the D.A.D.F. was developed, its usefulness and workability was tested by applying it to a case study. The case study results demonstrated that the D.A.D.F. is capable of producing integrated strategies with the ability to manage traffic congestion, encourage sustainable development and alleviate some site specific development challenges within the context of the study areas. Going beyond developing the decision framework, the study recommends positioning the D.A.D.F. within the South African planning system as part of a Traffic Congestion Management Plan (T.C.M.P.), setting out its likely components within the local context. It is concluded that the main innovation of the study is the development of the D.A.D.F., the T.C.M.P., the recommendations to situate both in the planning system and the comprehensive, but still transparent, approach undertaken to create integrated strategies for specific local conditions consisting of elements that work together to produce cumulative short to long term effects that attain a balanced set of environmental, social and economic goals - all imperative for sustainable development. / Thesis (Ph.D. (Town and Regional Planning))--North-West University, Potchefstroom Campus, 2008.

Magister Scientiae - MSc / Indinavir is a potent and well tolerated protease inhibitor drug used as a component of the highly active antiretroviral therapy (HAART) of HIV/AIDS, which results in pharmacokinetics that may be favourable or adverse. These drugs work by maintaining a plasma concentration that is sufficient to inhibit viral replication and thereby suppressing a patient’s viral load. A number of antiretroviral drugs, including indinavir, undergo metabolism that is catalysed by cytochrome P450-3A4 enzyme found in the human liver microsomes. The rate of drug metabolism influences a patient’s response to treatment as well as drug interactions that may lead to life-threatening toxic conditions, such as haemolytic anaemia, kidney failure and liver problems. Therapeutic drug monitoring (TDM) during HIV/AIDS treatment has been suggested to have a potential to reduce drug toxicity and optimise individual therapy. A fast and reliable detection technique, such as biosensing, is therefore necessary for the determination of a patient’s metabolic profile for indinavir and for appropriate dosing of the drugs. In this study biosensors developed for the determination of ARV drugs comprised of cysteamine self-assembled on a gold electrode, on which was attached 3-mercaptopropionic acid-capped palladium telluride (3-MPA-PdTe) or thioglycolic acid-capped palladium telluride (TGA-PdTe) quantum dots that are cross-linked to cytochrome P450-3A4 (CYP3A4) in the presence of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide. The quantum dots were synthesized in the presence of capping agents (3-MPA or TGA) to improve their stability, solubility and biocompatibility. The capping of PdTe quantum dots with TGA or 3-MPA was confirmed by FTIR, where the SH group absorption band disappeared from the spectra of 3-MPA-PdTe and TGA-PdTe. The particle size of the quantum dots (< 5 nm) was estimated from high resolution transmission electron microscopy (HRTEM) measurements. Optical properties of the materials were confirmed by UV-Vis spectrophotometry which produced absorption iii bands at ~320 nm that corresponded to energy band gap values of 3 eV (3.87 eV) for TGAPdTe (3-MPA-PdTe) quantum dots. The electrocatalytic properties of the quantum dots biosensor systems were studied by cyclic voltammetry (CV) for which the characteristic reduction peak at 0.75 V was used to detect the response of the biosensor to indinavir. Results for indinavir biosensor constructed with 3-MPA-SnSe quantum dots are also reported in this thesis. The three biosensors systems were very sensitive towards indinavir; and gave low limits of detection (LOD) values of 3.22, 4.3 and 6.2 ng/mL for 3-MPA-SnSe, 3-MPA-PdTe and TGA-PdTe quantum dots biosensors, respectively. The LOD values are within the ‘maximum plasma concentration’ (Cmax) value of indinavir (5 - 15 ng/mL) normally observed 8 h after drug intake.

Le mise en commun de la tomographie par émission de positons (TEP) et de la tomodensitométrie (TDM) sur des scanner bimodaux TEP/TDM a été un axe de recherche essentiel en imagerie ces vingt dernières années et a mené à un développement rapide de cette technique en clinique et en pré-clinique. Cependant, même si les deux modalités peuvent être juxtaposées sur le même statif, l’idée originelle de David W. Townsend prévoyait d’acquérir de manière simultanée les données TEP et TDM provenant du même champ de vue. Cela devrait permettre de connaître la position exacte du sujet lors de l’acquisition, et donc potentiellement de corriger de ses mouvements. C’est dans cet optique que nous avons développé le prototype ClearPET/XPAD : le premier scanner TEP/TDM simultané combinant les modules phoswich à scintillateurs du prototype ClearPET et un détecteur à pixels hybride développé au CPPM faisant face à une source de rayons X sur le même rotateur. Je présente les premières images TEP/CT simultanées de source ponctuelles, du fantôme Derenzo et d’une souris vivante acquises sur le prototype ClearPET/XPAD et discute les limites et les particularités de l’imagerie hybride TEP/TDM simultanée. / The combination of Positron Emission Tomography (PET) and X-ray Computerized Tomographie (CT) for PET/CT imaging has been an essential line of research in the previous decades and led to a rapid expansion of this technique in clinics and preclinics. However, even if the two modalities can be juxtaposed on the same gantry, the original concept invented by David W. Townsend foresaw to do both PET and CT imaging at the same time, while imaging a common Field-Of-View (FOV). This will allow to know the exact position of the animal during the scan and possibly to correct for the animal movements. Therefore we developed the ClearPET/XPAD prototype: the first simultaneous PET/CT scanner for mice combining on the same gantry ClearPET modules and the hybrid pixels camera XPAD3 facing an X-ray source. I present the first simultaneous PET/CT scans of point sources, of the Derenzo phantom and of a living mouse acquired with the ClearePET/XPAD prototype and discuss the limitations and prospects of simultaneous hybrid PET/CT imaging.

>Magister Scientiae - MSc / The aim of this study was to compare the trough plasma levels of Aspen-Vancomycin® (AV); and Sandoz-Vancocin CP® (SV) in premature infants with suspected Methicillin Resistant Staphylococcus aureus (MRSA) infection. The study was designed as a prospective, double blind, randomised trial involving male and female premature infants admitted in the Neonatal Intensive care Unit (NICU) at Netcare Blaauwberg and N1-city Hospitals for treatment of suspected MRSA-infection between April 2012 and June 2013. The inclusion criteria were: 29-35 weeks postmenstrual age (PMA), informed and written consent from parents of each premature infant enrolled in the study. Blood samples (0.3-0.4ml) were collected for renal function test and vancomycin trough levels determination. Blood samples for vancomycin trough level assay were collected thirty minutes prior to the administration of the third dose of vancomycin. Statistical analysis was performed and estimation was made giving an indication of how many infants will be needed to make the study statistically significant. Wilcoxon Two-Sample test was performed to determine the p-values and Spearman correlation coefficients were used to determine the correlation between trough levels and variables. P-values < 0.05 were considered significant. A total of 19 premature infants met with study criteria, 10 (5 females and 5 males) received AV and 9 (6 females and 3 males) receive d SV. There was no statistical significant difference between the demographic (GA, BW, PMA, PNA, weight at trial entry, height at trial entry) and biological (albumin, serum creatinine concentration and glomerular filtration rate) parameters of the premature infants in the AV and SV group. There were no statistical significant difference between trough level 1 of AV and SV, although trough level 1 had a lower trend in the SV group (p=0.118). No AV trough level 1 was below the minimum effective concentration (<5μg/ml). It was found that 30% of AV trough level 1 was within the therapeutic range (5-10μg/ml) and 70% of AV trough level 1, were above minimum toxic concentration (>10mg/l). It was found that 22.2% of SV trough level 1 was below minimum effective concentration, 44.4% of SV trough level 1 was within therapeutic range and 33.3% of trough level 1 was above minimum toxic concentration. No correlation was found between trough level 1 and the demographic and biological parameters of the premature infants in the AV group. SV had a positive correlation with GA, BBW, PMA and a negative correlation with PNA

L’imagerie multi-modale Tomographie par émission de positons (TEP)/ Tomodensitométrie(TDM) est la modalité d’imagerie la plus utilisée pour le diagnostic et le suivi des patients en oncologie. Les images obtenues par cette méthode offrent une cartographie à la fois de la densité des tissus (modalité TDM) mais également une information sur l’activité métabolique des lésions tumorales (modalité TEP). L’analyse plus approfondie de ces images acquises en routine clinique a permis d’extraire des informations supplémentaires quant à la survie du patient ou à la réponse au(x) traitement(s). Toutes ces nouvelles données permettent de décrire le phénotype d’une lésion de façon non invasive et sont regroupées sous le terme de Radiomics. Cependant, le nombre de paramètres caractérisant la forme ou la texture des lésions n’a cessé d’augmenter ces dernières années et ces données peuvent être sensibles à la méthode d’extraction ou encore à la modalité d’imagerie employée. Pour ces travaux de thèse, la variabilité de ces caractéristiques a donc été évaluée sur les images TDM et TEP à l’aide d’une cohorte test-retest : pour chaque patient, deux examens effectués dans les mêmes conditions, espacés d’un intervalle de l’ordre de quelques jours sont disponibles. Les métriques reconnues comme fiables à la suite de cette analyse sont exploitées pour l’étude de la survie des patients dans le cadre du cancer du poumon. La construction d’un modèle pronostique à l’aide de ces métriques a permis, dans un premier temps, d’étudier la complémentarité des informations fournies par les deux modalités. Ce nomogramme a cependant été généré par simple addition des facteurs de risque. Dans un second temps, les mêmes données ont été exploitées afin de construire un modèle pronostique à l’aide d’une méthode d’apprentissage reconnue comme robuste : les machines à vecteurs de support ou SVM (support vector machine). Les modèles ainsi générés ont ensuite été testés sur une cohorte prospective en cours de recrutement afin d’obtenir des résultats préliminaires sur la robustesse de ces nomogrammes. / Positron emission tomography (PET) / Computed tomography (CT) multi-modality imaging is the most commonly used imaging technique to diagnose and monitor patients in oncology. PET/CT images provide a global tissue density description (CT images) and a characterization of tumor metabolic activity (PET images). Further analysis of those images acquired in clinical routine supplied additional data as regards patient survival or treatment response. All those new data allow to describe the tumor phenotype and are generally grouped under the generic name of Radiomics. Nevertheless, the number of shape descriptors and texture features characterising tumors have significantly increased in recent years and those parameters can be sensitive to exctraction method or whether to imaging modality. During this thesis, parameters variability, computed on PET and CT images, was assessed thanks to a test-retest cohort : for each patient, two groups of PET/CT images, acquired under the same conditions but generated with an interval of few minutes, were available. Parameters classified as reliable after this analysis were exploited for survival analysis of patients in the context of non-small cell lug cancer (NSCLC).The construction of a prognostic model with those metrics permitted first to study the complementarity of PET and CT texture features. However, this nomogram has been generated by simply adding risk factors and not with a robust multi-parametric analysis method. In the second part, the same data were exploited to build a prognostic model using support vector machine (SVM) algorithm. The models thus generated were then tested on a prospective cohort currently being recruited to obtain preliminary results as regards the robustness of those nomograms.

This master’s thesis dissertate the possibilities of the linkage between Asterisk softswitch and the 4th generation private branch exchange. This should create a new generation’s network, so-called NGN, by the convergence of existing telecommunication networks with an IP computer network. This master’s thesis is divided into several chapters. In introduction is described the evolution of the private branch exchanges as well as the principles of the voice digitizing, codecs and signaling commonly used in both TDM and VoIP networks. The main aim of this project is the configuration of Asterisk software exchange for connection with PBX Alcatel 4400 as well as public phone network PSTN. Another goal of this master’s thesis was the configuration of Alcatel PBX and diagnostics of CCS and CAS signaling on E1 interface. In conclusion there are summarized advantages of NGN networks and their utilization in the future.

Text and data mining can be a useful tool in such diverse fields as scientific research, journalism, culture and not least training of artificial intelligence and its importance is likely to only grow in the future. Despite its huge potential there are many indicators that copyright law restricts use of text and data mining – keeping users from optimal application. This thesis discusses possible barriers crated by EU copyright law, in particular in the light of the new exceptions provided by the Directive on Copyright and Related Rights in the Digital Single Market and finds that despite improvements in terms of legal certainty there are still obstacles to the efficient application of text and data mining.