Doctor Pharmaceuticae - Dpharm / The use of efavirenz (EFV) in the first trimester of pregnancy remains controversial. In South Africa, the use of EFV-containing antiretroviral therapy (ART) as part of a Fixed Dose Combination (FDC) during the first trimester of pregnancy started in April, 2013. Literature to date has reported conflicting outcomes following the use of EFV-containing ART during the first trimester of pregnancy. The objectives of the study were to determine the prevalence of adverse pregnancy outcomes among HIV-positive pregnant women treated with EFV-containing ART and compare these results with those of pregnant women treated with NVP-containing ART and HIV-negative pregnant women in resource-limited settings. In addition, the study also aimed to determine the effect of the time of initiation of ART on the prevalence of adverse pregnancy outcomes.

Le collage structural est une technique d’assemblage de plus en plus demandée aujourd’hui dans beaucoup de domaines comme l’automobile, l’aéronautique, l’aérospatial et dans d’autres domaines comme la construction, le sport et les loisirs. Cette technique très avantageuse, permet l’assemblage de matériaux semblables ou différents à l’aide d’un adhésif, la réduction importante du poids et la répartition uniforme des charges sur l’assemblage. Malgré ses avantages, le collage souffre encore de quelques inconvénients liés à l’existence de défauts dans les joints de colle. Parmi eux, il existe des défauts qui sont situés à l’interface colle/substrat comme un « kissing bond » ou un mauvais état de surface, qui restent indétectables ou difficilement détectables utilisant les techniques de contrôle non destructives. Donc, afin de prendre en compte l’existence des défauts d’adhésion dans les assemblages collés lors de la phase de conception, il est nécessaire de fournir un modèle analytique capable de prédire la propagation de fissure. Dans cette thèse, un modèle analytique qui prédit la propagation de fissure et qui évalue la résistance effective d’un assemblage collé contenant des défauts d’adhésion a été développé. Un défaut a généralement une géométrie complexe, et une étude générique est difficilement réalisable ce qui nous amène à considérer des géométries de défauts idéales. Le modèle a été vérifié par des expériences réalisées sur des éprouvettes DCB. Des simulations numériques utilisant la méthode de zone cohésive ont été réalisées également pour décrire plus complètement le processus de décohésion et simuler les essais expérimentaux. La dernière partie de ce travail a été dédiée à l’étude de la fissuration des éprouvettes en alliage de titane. Profitant de la collaboration avec Safran et Alphanov, les substrats ont subi un traitement de surface laser en laissant des zones non traitées. Le but de cette partie était de vérifier le modèle analytique proposé avec des configurations plus complexes. / Structural adhesive bonding has known an increasing use in many fields like aeronautics, aerospace and automotive and other fields like construction and sports. This very advantageous technique allows the assembly of similar or different materials using an adhesive, the significant reduction in weight and a uniform distribution of loads on the assembly. Despite its advantages, the bonding still suffers from some disadvantages related to the existence of defects in the bonded joints. Among them, there are defects that are located at the interface glue / substrate as "kissing bond" or poor surface due to bad surface treatment, which remain undetectable or hardly detectable using non-destructive control techniques. Therefore, in order to take into account the existence of adhesion defects in bonded assemblies during the design phase, it is necessary to provide an analytical model capable of predicting crack propagation and estimate the criticality of a defect. In this thesis, an analytical model that predicts crack propagation and evaluates the effective strength of a bonded assembly containing adhesion defects has been developed. A defect usually has a complex geometry, and a generic study is difficult to achieve, which leads us to consider ideal defect geometries. The model was verified by experiments performed on DCB specimens. Numerical simulations using the cohesive zone method were also performed to more fully describe the decohesion process and to simulate the experimental tests. The last part of this work was devoted to the study of titanium alloy assembly containing patterns. Taking advantage of the collaboration with Safran and Alphanov, the substrates underwent a laser surface treatment leaving untreated areas. The purpose of this part was to check the proposed analytical model with more complex configurations.

A redistribuição e ativação elétrica dos dopantes tipo n (As e Sb) e tipo p (Ga e In) em Si com excesso de vacâncias foram analisadas. As vacâncias foram geradas por implantação iônica de altas doses de oxigênio ou nitrogênio em alta temperatura, de acordo com procedimentos já estudados. Em seguida foram implantados os dopantes com dose de 5x1014 cm-2 a 20 keV na região rica em vacâncias. Dopagens idênticas foram realizadas em amostras de Si sem vacâncias e em SIMOX. Em seguida foram feitos recozimentos a 1000ºC por 10 s ou 15 min. Os perfis atômicos dos dopantes foram medidos com Medium Energy Ion Scattering e os perfis dos dopantes ativados, com Hall diferencial. A redistribuição e as propriedades elétricas de cada um dos dopantes no Si sem vacâncias foram bastante similares às observadas no SIMOX, porém várias diferenças foram observadas em relação às amostras com excesso de vacâncias. As vacâncias reduziram a ativação elétrica do As e do Sb, mas proporcionaram maior estabilidade da ativação após recozimentos longos. A redistribuição destes dopantes foi infuenciada pelo íon usado na geração das vacâncias, ou seja, nitrogênio ou oxigênio. O oxigênio proporcionou maior dose retida de As e o nitrogênio, maior dose retida de Sb. Já para o Ga e o In, as vacâncias tiveram papel fundamental na sua redistribuição, diminuindo a difusão para fora das amostras e garantindo maior dose retida. A ativação elétrica do Ga e especialmente a do In foram baixas, onde observamos forte influência do íon pré-implantado, principalmente o oxigênio. / The redistribution and electrical activation of n type (As and Sb) and p type (Ga and In) dopants in Si with excess vacancy concentration were analyzed. The vacancies were formed by high dose ion implantation of oxygen or nitrogen at high temperature, following previously studied procedures. Dopants were implanted to a dose of 5x1014 cm-2 at 20 keV in the vacancy rich regions of the samples. Identical doping implantations were performed in bulk Si and SIMOX. Samples were then submitted to thermal annealing at 1000ºC for 10 s or 15 min. The dopants atomic profiles were obtained by Medium Energy Ion Scattering and the active dopant profiles, by differential Hall measurements. The redistribution and the electrical properties of each dopant in bulk Si were similar to those observed in SIMOX, but several differences were observed in the vacancy-rich samples. Vacancies reduced the electrical activation of As and Sb, although the activation was maintained stable after long annealing times. The redistribution of these dopants was, otherwise, dominated by the ion used in the vacancy generation, i.e., nitrogen or oxygen. The presence of oxygen resulted in larger As retained dose, while the presence of nitrogen, in larger Sb retained dose. Regarding the p type dopants, Ga and In, the vacancies played an important role in their redistribution, reducing their out-diffusion and allowing larger retained doses. Ga and especially In electrical activation was low, where strong influence of the pre-implanted ions was observed, especially oxygen.

The thesis deals with the analysis of quality management system in a selected organization and with tasks assigned by the organization's quality manager. The company is Aspera, spol. s r.o., specifically its metal manufacturing centre Aspera Technology in České Budějovice. The thesis is divided into a theoretical and a practical part. The theoretical part is based on study of scientific literature and focuses on quality definition, history of quality management, quality management system principles and concepts and quality management tools, especially process flowchart, Pareto diagram and FMEA. The practical part describes the company, its manufacturing centre and its quality management system. The next part deals with the three assigned tasks. First, designated company processes are described and visualized in the form of flowcharts. Second, weak points and risks of these processes are analysed using FMEA and corrective actions are recommended. Third, the most significant internal defects are identified using Pareto chart and cost analysis. At the end of the thesis some suggestions for improvement are provided. The suggestions were observed during an internship in the company and should enhance the quality management system and help the overall operation of the company processes.

La miniaturisation technologique augmente la sensibilité des circuits intégrés auxdéfauts et nous observons à chaque nouvelle génération technologique une dégradation rapidedu rendement de fabrication et de la fiabilité. Les mémoires occupent la plus grande partie dela surface des SoCs et contiennent la vaste majorité des transistors. De plus, pour augmenterleur densité elles sont conçues de façon très serrée. Elles concentrent ainsi la plus grandepartie des défauts de fabrication et représentent aussi les parties les plus sensibles face auxperturbations. Elles sont par conséquent les parties des SoCs les plus affectées par ladégradation du rendement de fabrication et de la fiabilité. L’objectif de cette thèse est deproposer des architectures combinant de façon optimale : algorithmes de test, architecturesBIST, et codes correcteurs d’erreurs afin de proposer des solutions efficaces pourl’amélioration du rendement de fabrication et de la fiabilité des mémoires embarquées. / Nanometric scaling increases the sensitivity of integrated circuits to defects andperturbations. Thus, each new generation of manufacturing process is accompanied by a rapiddegradation of manufacturing yield and reliability. Embedded memories occupy the largestpart of the area of SoCs and comprise the vast majority of transistors. In addition, forincreasing the integration density, they are designed very tightly to the design and electricalrules. Hence, embedded memories concentrate the majority of the manufacturing defectsaffecting a SoC, and are also more sensitive to perturbations. Thus, they are the parts of theSoC the most affected by the deterioration of manufacturing yield and reliability. This thesisdevelops repair architectures optimally combining test algorithms, BIST architectures, anderror correcting codes, in order to propose effective solutions for improving themanufacturing yield and reliability of embedded memories affected by high defect densities.

Dans les réacteurs à fusion, le tungstène subira des contraintes sévères dont, l’irradiation neutronique induisant la création de défauts ponctuels, et l’implantation d’hélium. La compréhension du comportement synergique des défauts lacunaires et de l’hélium est cruciale pour modéliser le comportement des composants en tungstène des futurs réacteurs à fusion thermonucléaire.Cette étude utilise la spectroscopie d’annihilation des positons (PAS) pour déterminer la nature et l’évolution en température des défauts d’implantation et l’analyse par réaction nucléaire (NRA)couplée ponctuellement à la microscopie électronique pour suivre le comportement de l’hélium.Les défauts générés dépendent des paramètres d’implantation (nature des ions, énergie, fluence). Par implantation d’3He à 800 keV, des monolacunes ont été créées et sont mobiles entre 473 et 623 K.L’augmentation de la concentration initiale en monolacunes décale le seuil de migration vers les basses températures. Des implantations à fort dpa (Fe 10 MeV) génèrent des amas lacunaires. Les impuretés jouent un rôle prépondérant sur le comportement en température des défauts.Le comportement de l’hélium a été étudié sous trois conditions d’implantation différentes. Les implantations à basse énergie (0,32 keV) montrent la création de complexes hélium-lacune par mutation. Les implantations à 60 keV mettent en évidence la compétition entre la migration, à basse fluence et le piégeage de l’hélium, à haute fluence. Finalement, des implantations à haute énergie(500 keV) renseignent sur l’influence de la microstructure sur la distribution des bulles d’hélium. / In fusion reactors, tungsten suffers severe constraints such as an intense neutron irradiation which induces the creation of point defects, and implantation of helium. Understanding the interactions between point defects and helium is crucial to model the behavior of tungsten components for future nuclear fusion applications.This study rely on the use of Positron Annihilation Spectroscopy (PAS) to determine the nature and thermal evolution of implantation-induced defects, and Nuclear Reaction Analysis (NRA) occasionally coupled with electron microscopy to investigate the behavior of helium.The nature of implantation-induced defects depends on the implantation parameters (type of ion,energy, fluence). Implantations of 3He at 800 keV, lead to the creation of monovacancies which aremobile between 473 and 623 K. Increasing the initial concentration of monovacancies shifts themigration threshold toward low temperature. Implantations with high level of damage (Fe 10 MeV) generate vacancy clusters. The impurities play a dominant role on the thermal behavior of defects. The behavior of helium was studied under three different implantation conditions. Implantations at low energy - 0.32 keV - show the creation of helium-vacancy complex by mutation. Implantations at 60keV show the competition between migration - at low fluence - and trapping of helium - at high fluence. Finally, high energy implantations (500 keV) provide information about the influence of microstructure on the distribution of helium bubbles.

The different strategies of tissue engineering for functional reconstruction of critical-size bone defects require a thorough knowledge of physiological mechanisms of bone repair. Bone healing is a complex process affected by various mediators. Several investigations have studied the gene expression 1 to 3 days after an acute or experimental fracture. Little is known about the humoral and cellular in vivo reaction in the early stages of bone healing. In contrast to other methods of molecule sampling and detection, which usually lead to the inhibition of the biological activity following complex sample preparation and quantification, microdialysis is a real-time monitoring technique which can be applied in living tissues providing a strong link between analytical methodology and biochemistry. In this study, the optimal conditions for microdialysis in a critical size rat long bone defect model for both in vivo and in vitro analyses were developed. Mediators and components of the extracellular matrix occurring in the first 24 to 48 hours of bone healing locally and systemically were monitored via microdialysis and blood sampling, respectively. Furthermore, novel proteins and their modulation were explored during this time frame. In vitro microdialysis was used to optimize the condition for protein recovery. Addition of bovine serum albumin (BSA) resulted in an enhanced recovery of interleukin (IL)-6. The maximal relative recovery (RR) was from 15.0% without BSA and 23.6% with BSA, while the maximal RR of transforming growth factor (TGF)-β1 was 11.2% with BSA and the concentration of TGF-β1 was below the detection limit of enzyme-linked immunosorbent assay (ELISA) without BSA. Using in vivo microdialysis, total protein concentrations varied between 0.20±0.12 mg/mL and 0.44±0.18 mg/mL. Among the mediators produced in the fracture hematoma within 24 h after the injury, IL-6 was secreted with the highest concentration of 309.1 pg/mL between 12 and 15 h after creation of the critical size bone defect. Meanwhile, the detectable concentrations of TGF-β1 in microdialysates ranged from 3.6 to 44.0 pg/mL and in blood plasma TGF-β1 was constantly producted ranging from 656.3 to 8398.2 pg/mL for 24 h after bone defct. Moreover, another constant producted growth factor in blood plasma was PDGF-BB and the concentration ranged from 222.1 to 589.4 pg/mL for 8 h after bone defect. Using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), 36 proteins were identified in the microdialysates over 8 h, and 884 proteins were identified on probes which were implanted into the bone defect over 24 h. Among the proteins identified in the hematoma, only a minority originated from the extracellular space. Protein analysis indicated five pathways associated with bone healing that were overrepresented after creating soft tissue and bone defects, of which FGF signaling was specific for bone defects. Furthermore, C-X-C motif ligands CXCL-1, CXCL-2, CXCL-3, CXCL-4, CXCL-5, CXCL-7, rodent bone protein (RoBo-1), insulin-like growth factor (IGF)-I, and chitinase-3-like protein 1 were detected in the fracture hematoma. These proteins are potentially associated to early bone healing. As seen by histological analysis, polymorphonuclear leukocytes (PMNs) and lymphocytes penetrated into the fracture hematoma immediately after surgery and peaked at 24 h. This study for the first time presents data from both the local and systemic acute response to bone and soft tissue injury in a small animal model. The results of mcrodialysis sampling may serve as a baseline for future investigations on different models and time frames. Several proteins and pathways have been identifeid as potentially important for early bone regeneration warranting in depth analysis in further studies. / Zur Entwicklung neuer Strategien der Geweberegenerierung in kritischen Knochendefekten, die sich durch Selbstheilungsprozesse nicht schließen, ist das Verständnis der beteiligten physiologischen Prozesse essentiell. Der Wiederaufbau von Gewebe, wie etwa während Knochenheilungsprozesse ist komplex reguliert und erfordert das koordinierte Zusammenspiel einer Vielzahl von Zellen und Mediatoren. Obwohl bereits in zahlreichen Studien die Veränderungen in der Genexpression in den ersten 3 Tagen nach einer akuten oder experimentell induzierten Fraktur untersucht wurden, ist noch immer wenig über die zellulären und humoralen Vorgänge in den frühen Phasen der Knochenheilung in vivo bekannt. Gebräuchliche Analysemethoden erfordern komplexe Verfahren zur Probenentnahme und Nachweisreaktionen währenddessen die biologische Aktivität der untersuchten Mediatoren häufig graduell verloren geht. Die Mikrodialyse hingegen kann in Echtzeit am lebenden Objekt und am Ort der Verletzung durchgeführt werden und bildet somit eine erfolgsversprechende Plattform um die Probengewinnung noch enger mit der anschließenden biochemischen Nachweistechnik zu verbinden. Im Rahmen dieser Arbeit wurden die optimalen Konditionen zur Mikrodialyse erstmals an einem kritischen Defektmodell eines Ratten-Röhrenknochens zur in vivo und in vitro Applikation ermittelt. Dazu wurde das Vorkommen verschiedener Komponenten der extrazellulären Matrix und ausgewählter Mediatoren während der ersten 24 bis 48 Stunden der Knochenheilung überwacht. Neben der durch Mikrodialyse gewonnenen Proben wurden auch Blutproben verarbeitet um sowohl die lokale, als auch systemische Konzentration der untersuchten Proteine zu erfassen. Durch eine Proteomanalyse konnten zudem bislang in diesem Prozess unbekannte Moleküle identifiziert und verfolgt werden. Zur Optimierung der Mikrodialyse wurden zunächst die Bedingungen hinsichtlich der Proteinrückgewinnung verbessert. Durch den Zusatz von Rinderserumalbumin (BSA) konnte die Rückgewinnung von Interleukin (IL)-6 erhöht werden. Die maximale relative Rückgewinnung (RR) konnte von 15.0% ohne BSA auf 23.6% mit BSA gesteigert werden. Noch dramatischer war dieser Effekt für den transforming growth factor (TGF)-β1 von dessen eingesetzter Menge in vitro 11.2% detektiert werden konnte, während in der BSA-freien Dialyselösung kein TGF-β1 nachgewiesen wurde. Die RR blieb stets unter der Detektionsgrenze des verwendeten enzyme-linked immunosorbent assay (ELISA). In vivo-Dialysate enthielten totale Proteinkonzentrationen zwischen 0,20±0,12 mg/mL und 0,44±0,18 mg/mL. Von den innerhalb von 24 h nach Verletzung im Frakturhämatom produzierten Mediatoren wurde IL-6 am stärksten exprimiert. Die höchsten Konzentrationen (309,1pg/mL) konnten hierfür nach 12 bis 15 Stunden nach Einführung des Defekts gemessen werden. Die Konzentrationslevel von TGF-β1 hingegegen betrug nur 3,6 bis 44,0 pg/mL.Mittels high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), konnten 36 Proteine in den über 8 Stunden gewonnenen Mikrodialysaten, und 884 Proteine von Explantaten, die 24 h im Knochendefekt integriert waren, identifiziert werden. Von den im Frakturhämatom identifizierten Proteinen war nur eine Minderheit extrazellulären Ursprungs. Durch die Proteomanalyse konnten fünf Signalwegskaskaden identifiziert werden. Von diesen trat „FGF (fibroblast growth factor) signaling“ ausschließlich in Knochendefekten, nicht jedoch in den zur Kontrolle mitgeführten reinen Weichgewebedefekten auf. Im Frakturhämatom konnten die, C-X-C motif-Liganden CXCL-1, CXCL-2,CXCL-3, CXCL-4, CXCL-5, CXCL-7, rodent bone protein (RoBo-1), insulin-like growth factor (IGF)-I, und das chitinase-3-like protein 1 nachgewiesen werden. Die identifizierten Proteine könnten von Bedeutung für die Steuerung früher Knochenheilungsprozesse sein. Histologische Untersuchungen zeigten, dass polymorphkernige Leukozyten (PMNs) und Lymphozyten sofort nach der Operation in das Frakturhämatom einwandern und ihre Anzahl nach etwa 24 h ihr Maximum erreicht. Diese Studie präsentiert erstmals Daten der lokal und systemisch ablaufenden zellulären und humoralen Vorgänge als Antwort auf einen Weichgewebs-bzw. Knochendefekt in einem Nagetier-Kleintiermodell. Die Mikrodialyse-Resultate stellen eine vielversprechende Grundlage für zukünftige Untersuchungen in anderen Modellen dar. Außerdem bilden die hier identifizierten Proteine und Signalwege eine Gruppe potenter Kandidaten für weiterführende Untersuchungen zur Knochenregeration.

INTRODUCAO: A comunicação interatrial tipo \"ostium secundum\" é um defeito cardíaco congênito caracterizado pela deficiência parcial ou total da lâmina da fossa oval, também chamada de septo primo. Corresponde a 10 a 12% do total de cardiopatias congênitas, sendo a mais frequente na idade adulta. Atualmente a oclusão percutânea é o método terapêutico de escolha em defeitos com características anatômicas favoráveis para o implante de próteses na maioria dos grandes centros mundiais. A ecocardiografia transesofágica bidimensional com mapeamento de fluxo em cores é considerada a ferramenta padrão-ouro para a avaliação anatômica e monitoração durante do procedimento, sendo crucial para a ótima seleção do dispositivo. Neste sentido, um balão medidor é introduzido e insuflado através do defeito de forma a ocluí-lo temporariamente. A medida da cintura que se visualiza no balão (diâmetro estirado) é utilizada como referência para a escolha do tamanho da prótese. Recentemente a ecocardiografia tridimensional transesofágica em tempo real tem sido utilizada neste tipo de intervenção percutânea. Neste estudo avaliamos o papel da mesma na ótima seleção do dispositivo levando-se em consideração as dimensões e a geometria do defeito e a espessura das bordas do septo interatrial. METODO: Estudo observacional, prospectivo, não randomizado, de único braço, de uma coorte de 33 pacientes adultos portadores de comunicação interatrial submetidos a fechamento percutâneo utilizando dispositivo de nitinol autocentrável (Cera ®, Lifetech Scientific, Shenzhen, China). Foram analisadas as medidas do maior e menor diâmetro do defeito, sua área e as medidas do diâmetro estirado com balão medidor obtidas por meio das duas modalidades ecocardiográficas. Os defeitos foram considerados como elípticos ou circulares segundo a sua geometria; as bordas ao redor da comunicação foram consideradas espessas (>2 mm) ou finas. O dispositivo selecionado foi igual ou ate 2 mm maior que o diâmetro estirado na ecocardiografia transesofágica bidimensional (padrão-ouro). Na tentativa de identificar uma variável que pudesse substituir o diâmetro estirado do balão para a ótima escolha do dispositivo uma série de correlações lineares foram realizadas. RESULTADOS: A idade e peso médio foram de 42,1 ± 14,9 anos e 66,0 ± 9,4kg, respectivamente; sendo 22 de sexo feminino. Não houve diferenças estatísticas entre os diâmetros maior e menor ou no diâmetro estirado dos defeitos determinados por ambas as modalidades ecocardiográficas. A correlação entre as medidas obtidas com ambos os métodos foi ótima (r > 0,90). O maior diâmetro do defeito, obtido à ecoardiografia transesofágica tridimensional, foi a variável com melhor correlação com o tamanho do dispositivo selecionado no grupo como um todo (r= 0,89) e, especialmente, nos subgrupos com geometria elíptica (r= 0,96) e com bordas espessas ao redor do defeito (r= 0,96). CONCLUSÃO: Neste estudo em adultos com comunicações interatriais tipo ostium secundum submetidos à oclusão percutânea com a prótese Cera ®, a ótima seleção do dispositivo pôde ser realizada utilizando-se apenas a maior medida do defeito obtida na ecocardiografia transesofágica tridimensional em tempo real, especialmente nos pacientes com defeitos elípticos e com bordas espessas. / INTRODUCTION: The ostium secundum atrial septal defect is a congenital heart disease characterized by partial or total deficiency of the fossa ovalis, also known as the septum primum. It corresponds to 10-12% of all congenital heart defects, being the most frequently found in adulthood. Currently, percutaneous closure is the therapeutic method of choice for defects with suitable anatomic features for device implantation in most centers in the world. Bi-dimensional transesophageal echocardiography with color flow mapping is considered the gold-standard tool for anatomic assessment and procedural monitoring, being crucial for optimal device selection. In this regard, a sizing balloon is introduced and inflated across the defect with temporary occlusion. The waist measurement seen on the balloon (stretched diameter) is used as a reference for selection of device size. Recently, real time three-dimensional transesophageal echocardiography has been utilized in this type of percutaneous intervention. In this study we assessed the role of this modality in optimal device selection taking into consideration the dimensions and the geometry of the defect and the thickness of the interatrial septum rims. METHODS: Observational, prospective, non-randomized, single-arm study of a cohort of 33 adults with atrial septal defects submitted to percutaneous closure using a self-centered nitinol device (Cera (TM), Lifetech Scientific, Shenzhen, China). The largest and the smallest diameter of the defect, its area and the measurements of the stretched diameter of the sizing balloon were assessed by both echocardiographic modalities. The defects were considered as elliptical or circular according to their geometry; the rims surrounding the defect were considered thick (> 2 mm) or thin. The selected device was equal to or 2 mm larger than the stretched diameter on bi-dimensional transesophageal echocardiography (gold-standard). In an attempt to identify a variable that could replace the stretched balloon diameter, a series of linear correlations were performed. RESULTS: The mean age and weight were 42.1 ± 14.9 years and 66.0 ± 9.4 kgs, respectively; being 22 of the female gender. There were no statistical differences between the largest and smallest diameters of the defects and the stretched diameters determined by both echocardiographic modalities. The correlation between the measurements obtained by both methods was excellent (r > 0.90). The largest defect diameter obtained by three-dimensional transesophageal echocardiography was the variable that showed the best correlation with the selected device size in the entire group (r= 0.89), especially in the subgroups with elliptical geometry (r= 0.96) and with thick rims surrounding the defect (r=0.96). CONCLUSIONS: In this study in adults with ostium secundum atrial septal defects submitted to percutaneous occlusion with the Cera (TM) device, optimal device selection could be performed using solely the largest diameter of the defect obtained by real time three-dimensional transesophageal echocardiography, especially in patients with elliptical defects and thick rims.

Les aubes de turbines haute pression des turboréacteurs sont soumises à des chargements thermomécaniques sévères en service. Elles sont actuellement fabriquées par solidification dirigée sous forme de monocristaux orientés suivant la direction <001> le long de la direction principale de l'aube. La solidification peut entrainer dans certains cas l'apparition de défauts, notamment la formation de deux grains : l'aube est alors constituée de deux grains d'orientations différentes. L'objectif de cette thèse est d'étudier l'influence de la présence d'un joint de grains sur la durée de vie de l'aube en superalliage AM1. Dans un premier temps, nous avons réalisé une étude expérimentale sur aubes réelles afin de déterminer l'influence du joint de grains sur la rupture par fatigue en flexion à différentes températures. Pour cela, des entailles ont été usinées dans les aubes pour solliciter de façon préférentielle le joint de grains au sein de l'aube dans des essais de type flexion. Cette étude a permis de mettre en évidence le rôle du joint de grains sur la durée de vie de l'aube selon la température d'essai, l'orientation cristallographique relative des grains, la position du joint de grains et le type de sollicitation. Parallèlement, une étude exprimentale sur éprouvettes bi-cristallines de type fatigue oligocyclique a été conduite en traction compression, avec une contrainte principale de traction suivant la normale au plan moyen du joint. Ces essais ont permis de quantifier la réduction de durée de vie induite par la présence du joint de grains par rapport à une éprouvette monocristalline. Un critère de rupture a été ainsi introduit dans la loi d'endommagement développée par l'Onera pour le superalliage monocristallin d'AM1. Ce critère de durée de vie a été appliqué dans les simulations numériques des aubes remaillées et permet de faire une première estimation de la nocivité du joint de grains dans les aubes. / The high pressure turbine blade of aeroengine are submitted to severe thermomechanical loading in service. The turbine blade are curently manufactured by directionnal solidification with oriented single crystal on the direction <001>, along the principal direction of the blade.The solidification process can induce different defects in the structure.This study is focused on a particular defect: the formation of two crystals in a blade. Defective turbine blades are composed of two grains with different orientation.The aim of this present thesis is to study the influence of the grain boundary on AM1 superalloy blade fatigue life. First, experimental investigations have been performed to understand at different temperatures, the influence of grain boundaries on fatigue fracture due to bending loadings. Notches have been introduced on turbine blades in order to accentuate solicitations on grain boundary. These experiments have evidenced the major role of grain boundary and grains orientations on turbine blade fatigue life.Then another experimental investigation has been carried out under low cycle fatigue on bicrystal specimens with tension/compression loading; the tensile principal stress is along the normal direction of the grain boundary mean plane. These tests allowed quantification of the fatigue life decrease due to the presence of grain boundary compared to the fatigue life of single crystal specimens.A failure criterion have been introduced in the damage constitutive behavior of single crystal AM1 developped by the Onera. This lifetime prediction model have been implemented in FE simulations. It allows the evaluation of the sensivity of grain boundary on turbine blade.

In the first part of these studies, we have performed standard microsurgical procedures provide a solution for long standing bone and soft tissue defects, even in cases of longstanding osteomyelitis of long bones. When long bony segments are missing, the microvascular bone transfer provides a reliable method. In smaller soft tissue and bone defects, the application of a descending genicular osteomyocutaneous flap provides an option with low donor site morbidity. In the second part, we have focussed on reducing the donor site morbidity and expanded on the application of tissue engineering methods. MSCs derived from bone marrow can be injected percutaneous or be combined with an autologous bony scaffold for treatment of delayed union and nonunion. The outcome of our studies, however, limited in number of patients, clearly showed the possibilities and advantages of this new approach. A multimodality approach is essential, but it can provide promising solutions. Well-established microvascular and modern biotechnology methods will improve patient satisfaction and functional recovery in severe limb trauma, often the result of high-energy motorcycle accidents. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished