Foram analisadas 197.032 doações no período de janeiro de 1998 a junho de 2008, realizadas no Banco de Sangue do Hospital de Clínicas de Porto Alegre. Os doadores de sangue foram triados por um teste de enzimaimunoensaio (EIE) de terceira geração para HTLV I/II. Também foram realizados testes para hepatites B e C, HIV 1/2, sífilis e doença de Chagas. Os dados das fichas cadastrais foram revisados após o diagnóstico do doador. Como teste confirmatório, foi utilizado o Western Blot (WB). Foram excluídos os doadores considerados negativos após a confirmação dos testes iniciais. Ao todo, 204 doadores foram reagentes para HTLV I ou II. A prevalência de HTLV I/II foi de 0,1%, sendo 0,08% do tipo I e 0,02% do tipo II. A média de idade foi de 38 anos; 73,5% dos doadores eram brancos e 53,9% do sexo feminino. Cerca de 65% deles completaram o ensino fundamental e apenas 1% o ensino superior; 59,3% eram procedentes de Porto Alegre. A frequência de casados e solteiros foi de 40,2% e 42,4%, respectivamente, sendo os demais separados, divorciados ou viúvos. Os soropositivos para HTLV apresentaram ainda 30,4% de coinfecção com os outros marcadores testados. AntiHCV e anti-HBc foram os marcadores com maior prevalência (19,1% e 18,6%, respectivamente), seguidos por VDRL (2,94%), anti-HIV 1/2 (2,45%) e doença de Chagas (1,96%). / A total of 197,032 donors from the Blood Bank of Hospital de Clínicas de Porto Alegre, in southern Brazil, were assessed from January 1998 to June 2008. Blood donors were screened for HTLV I/II using a third-generation enzyme immunoassay (EIA). Tests for hepatites B and C, HIV 1 and 2, syphilis and Chagas disease were also performed. The information on blood donor forms was reviewed after the diagnosis. The Western Blot (WB) was used as confirmatory test. Seronegative donors were excluded from the study after initial test results were confirmed. Two hundred and four donors were positive for HTLV I or II. The prevalence of HTLV I/II was 0.1% (0.08% for HTLV I and 0.02% for HTLV II). The mean age was 38 years, 73.5% were whites and there was a female predominance (53.9%). Approximately 65% of seropositive individuals had attended elementary school, only 1% had college education, and 59.3% came from Porto Alegre. The frequency of married and single individuals was similar (40.2 and 42.4%, respectively), whereas the remaining donors were separated, divorced or widowed. This population also showed 30.4% of coinfection, according to the other tested markers. Anti-HCV and anti-HBc were the most prevalent markers (19.1 and 18.6%, respectively), followed by VDRL (2.94%), anti-HIV 1/2 (2.45%), Chagas disease (1.96%).

Foram analisadas 197.032 doações no período de janeiro de 1998 a junho de 2008, realizadas no Banco de Sangue do Hospital de Clínicas de Porto Alegre. Os doadores de sangue foram triados por um teste de enzimaimunoensaio (EIE) de terceira geração para HTLV I/II. Também foram realizados testes para hepatites B e C, HIV 1/2, sífilis e doença de Chagas. Os dados das fichas cadastrais foram revisados após o diagnóstico do doador. Como teste confirmatório, foi utilizado o Western Blot (WB). Foram excluídos os doadores considerados negativos após a confirmação dos testes iniciais. Ao todo, 204 doadores foram reagentes para HTLV I ou II. A prevalência de HTLV I/II foi de 0,1%, sendo 0,08% do tipo I e 0,02% do tipo II. A média de idade foi de 38 anos; 73,5% dos doadores eram brancos e 53,9% do sexo feminino. Cerca de 65% deles completaram o ensino fundamental e apenas 1% o ensino superior; 59,3% eram procedentes de Porto Alegre. A frequência de casados e solteiros foi de 40,2% e 42,4%, respectivamente, sendo os demais separados, divorciados ou viúvos. Os soropositivos para HTLV apresentaram ainda 30,4% de coinfecção com os outros marcadores testados. AntiHCV e anti-HBc foram os marcadores com maior prevalência (19,1% e 18,6%, respectivamente), seguidos por VDRL (2,94%), anti-HIV 1/2 (2,45%) e doença de Chagas (1,96%). / A total of 197,032 donors from the Blood Bank of Hospital de Clínicas de Porto Alegre, in southern Brazil, were assessed from January 1998 to June 2008. Blood donors were screened for HTLV I/II using a third-generation enzyme immunoassay (EIA). Tests for hepatites B and C, HIV 1 and 2, syphilis and Chagas disease were also performed. The information on blood donor forms was reviewed after the diagnosis. The Western Blot (WB) was used as confirmatory test. Seronegative donors were excluded from the study after initial test results were confirmed. Two hundred and four donors were positive for HTLV I or II. The prevalence of HTLV I/II was 0.1% (0.08% for HTLV I and 0.02% for HTLV II). The mean age was 38 years, 73.5% were whites and there was a female predominance (53.9%). Approximately 65% of seropositive individuals had attended elementary school, only 1% had college education, and 59.3% came from Porto Alegre. The frequency of married and single individuals was similar (40.2 and 42.4%, respectively), whereas the remaining donors were separated, divorced or widowed. This population also showed 30.4% of coinfection, according to the other tested markers. Anti-HCV and anti-HBc were the most prevalent markers (19.1 and 18.6%, respectively), followed by VDRL (2.94%), anti-HIV 1/2 (2.45%), Chagas disease (1.96%).

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of US cancer related deaths. This study assessed the oncologic benefit of a neoadjuvant chemotherapy (NAC) treatment strategy for patients with clinical Stage I/II PDAC. Methods: Patients with biopsy confirmed PDAC and clinical Stage I/II disease were treated with a protocol of NAC. The primary study endpoint was median overall survival (OS). Kaplan-Meier survival curves were compared using the log-rank test. Results: 56 patients met inclusion criteria. Of these, 21 patients (38%) had Stage I disease and 35 (62%) had Stage II disease. The median OS for the entire study population was 18.7 months. A total of 22 (39%) patients were managed with NAC+S; 34 (61%) received NAC alone. Median OS and 2-year survival rates were greater in those completing NAC+S compared to NAC alone (median OS 28.8 months vs. 17.3 months: p=0.05; 2-year OS: 55% vs 21%: p=0.01) . Interestingly, patients managed with NAC who were not candidates for surgical resection after restaging demonstrated a survival advantage (17.3 months) compared to what was previously reported in historical controls. Conclusion: NAC+S provided a significant 11.5 month improvement in median OS compared to treatment with NAC alone. Modern NAC may contribute a significant oncologic benefit in the overall treatment strategy for patients with Stage I/II PDAC, even if surgery is not ultimately pursued.

Pendant longtemps, les exégètes du Nouveau Testament ont examiné les textes évangéliques en considérant leurs racines judaïques comme principal contexte d'interprétation. Cette approche exégétique a permis de mieux comprendre les symboles, les valeurs ainsi que les préoccupations des premiers chrétiens en lien avec la tradition juive. Plus récemment, des exégètes ont utilisé la méthode d'analyse sociohistorique afin d'attirer notre attention sur l'Empire romain comme contexte primordial pour la compréhension des textes du Nouveau Testament. De ces auteurs, mentionnons Richard Horsley, professeur de religion à l'Université du Massachusetts aux États-Unis, qui a été un des premiers à présenter cette compréhension différente de l'influence de l'Empire sur le message évangélique. Horsley prétend que les écrits du Nouveau Testament sont des textes anti-impériaux à l'exemple des mouvements de révolte présents dans la Palestine du premier siècle. Pour arriver à cette conclusion, Horsley perçoit dans les textes fondateurs du Christianisme une multitude de références à César et aux valeurs impériales auxquels les auteurs s'opposent parfois de façon claire, parfois de façon subtile dans leurs textes. En contrepartie, des exégètes bibliques et des théologiens réfutent cette allégation de Horsley. Parmi eux, mentionnons Seyoon Kim, professeur du Nouveau Testament au Fuller Theological Seminary en Californie, Scot McKnight, professeur du Nouveau Testament au Northern Seminary en Illinois, et Joseph B. Modica, professeur associé en études bibliques à l'Eastern University en Pennsylvanie. Ils soulèvent différents problèmes dans la méthode interprétative de Horsley. Par exemple, pour Kim, les auteurs du Nouveau Testament ne cherchent nullement à renverser le pouvoir terrestre en place. En empruntant le vocabulaire de la propagande impériale, les auteurs du Nouveau Testament veulent faire comprendre le message que Jésus est le Seigneur des seigneurs, que le Royaume de Dieu n'est pas de ce monde, mais du domaine spirituel, et que la libération promise par Jésus n'est pas contre César, mais contre Satan et le pouvoir du péché. Afin de vérifier ces différentes positions herméneutiques, nous ferons l'analyse narratologique et lexicographique du récit lucanien de la Nativité. Nous ferons également un exercice comparatif de cet épisode néotestamentaire avec des textes de la propagande impériale afin de déterminer si oui ou non l'auteur évangélique utilise réellement un vocabulaire impérial, et, le cas échéant, d'observer quel usage il en fait.

L’utilisation des goujons collés dans les structures bois répond au souci de conservation du bâti et de discrétion de l’intervention. A ce jour, plusieurs procédés de caractérisation et de dimensionnement sont disponibles, sans pour autant donner un socle commun à l’évaluation de la résistance des assemblages collés. L’utilisation des goujons collés suscite des interrogations concernant leur tenue au feu. Bien que le matériau bois entourant les tiges de renforcement soit isolant, il est nécessaire de fournir de plus amples estimations concernant la tenue mécanique des polymères pour différentes températures que l’on pourrait trouver au sein d’une liaison au cours d’un incendie. La présente étude permet de coupler méthodes expérimentales et simulations numériques, afin d’appréhender les mécanismes gouvernant la rupture de ces assemblages. La caractérisation expérimentale permet d’estimer les propriétés mécaniques locales des assemblages suivant divers paramètres (les longueurs de scellement, l’orientation du fil du bois, l’essence de bois, ou encore la température d’exposition), ainsi que les propriétés intrinsèques aux matériaux constitutifs. Cette base de données expérimentale est indispensable pour l’ajustement du modèle aux éléments finis en élasticité linéaire. L’approche numérique met en évidence une présence importante de contraintes normales en tête de collage, avant l’apparition de contraintes de cisaillement. Les outils de la Mécanique Linéaire Élastique de la Rupture équivalente permettent d’établir des courbes de résistance liées à chaque mode de ruine (mode I et mode II). Enfin, afin de décrire précisément le processus complet de rupture de ces assemblages, un critère de rupture en mode mixte (mode I et mode II) est utilisé. Une formulation analytique permettant d’estimer la charge au pic est proposée et permettra la réalisation d’abaques de dimensionnement des assemblages par goujons collés, utilisables en bureau d’études. / Glued-in-rods lead to overcome the use of traditional bolted connections, preserve a large part of original timber and offer aesthetic benefits (since the repair is hidden in the cross sections of the members). Despite previous research programs in many countries, some design rules, predicting the axial strength of such connections, are available, but a common criterion is still lacking. However, the durability of this process according to fluctuating temperature is not well known. During fire exposure, connections are not directly in contact with flames, since they are isolated by surrounding wood. The current study combines experiments with finite element computations, in order to lead a better to a better knowledge about their mechanical and fracture behaviors. An important experimental campaign is carried out on such connections and provides the influence of various parameters, such as the anchorage length, the rod-to-grain angle, the specie of wood or the temperature exposure, on their mechanical behaviors. Moreover, the inherent mechanical properties of the rod and the adhesives used are also studied. The finite element modeling reproduces the experimental configuration, and reveals significant tensile stresses in comparison with shear stresses. Within the framework of equivalent linear elastic fracture mechanics, R-curves in mode I and mode II can be estimated for each specimen. Finally, a fracture criterion in mixed mode is used to describe the complete fracture process of glued-in rods. An analytical formulation is then proposed and allows the evaluation of peak load of each specimen. This approach leads to realize design tables, usable by design offices.

Cette thèse est consacrée aux méthodes statistiques d’extrapolation dans les essais de recherche de dose en pédiatrie. Dans un premier temps, nous réalisons une revue systématique de la littérature sur le sujet. Elle met en évidence la nécessité de proposer de nouvelles méthodes pour la conception des études d’escalade de dose chez l’enfant. Nous apportons des réponses à cette problématique en exploitant l’information disponible chez l’adulte. Dans une première série de travaux, nous étudions l’intérêt de la prédiction des paramètres pharmacocinétiques (PK) en pédiatrie à l’aide de méthodes d’extrapolation : l’allométrie et la maturation. Cette évaluation est réalisée à partir de données PK chez l’adulte et l’enfant pour la méfloquine. Faisant appel aux paramètres prédits, nous développons une approche pour choisir les temps de prélèvements (design) d’une étude PK. Nous recommandons un design obtenu par optimisation grâce à la méthode de D-optimalité en utilisant le logiciel PFIM. Ce design est ensuite validé à l’aide de simulations sur différents modèles. Une seconde série de travaux nous amène à proposer des recommandations pour la planification d’un essai de recherche de dose. Nous avançons d’abord des techniques pour choisir les doses à tester grâce à l’utilisation des données adultes et de l’extrapolation. Nous proposons ensuite une méthode proche de la méta-analyse pour prédire les probabilités de toxicités pour chaque dose. Enfin, nous employons la méthode de l’Effective sample size afin de construire une loi a priori lors de l’utilisation d’une estimation bayésienne. Nous validons ces recommandations sur une étude de cas en utilisant une méthode d’escalade de dose, la méthode de réévaluation séquentielle bivariée, pour laquelle nous évaluons à la fois la toxicité et l’efficacité. A partir de l’exemple de la molécule erlotinib, nous effectuons une série de simulations sur plusieurs scénarios afin d’illustrer les performances de la planification. / This thesis addresses extrapolation techniques for statistical models for dose-finding studies in pediatrics. After a litterature review on these clinical trials, we observed the need of methodological propositions for the planification of dose- finding studies in pediatrics. We deal with this issue using information from the adult population. In a first research, the objectives are to design a pharmacokinetic (PK) study by using information from adults and evaluate the robustness of the recommended design through a case study of mefloquine. Pediatric PK parameters are predicted from adult PK using extrapolation functions such as allometry and maturation. A D-optimal design for children is obtained with PFIM by assuming the extrapolated design. The robustness of the recommended design is evaluated in a simulation study with four different models and is compared to the empirical design used for the pediatric data. In a second research, we propose a global approach to conduct a pediatric dose-finding clinical trial using extrapolation from adult information. First, we extrapolate the dose-range from adults using allometry and maturation. Then, using an approach to meta-analysis, we choose the initial probabilities of toxicity for each dose. Finally, we use the effective sample size method to choose the prior distribution of parameters in a Bayesian setting. We perform a simulation study based on the molecule erlotinib to evaluate the performances of this global approach.

In the first chapter the paper is focused on sovereign rating, it describes the history and explains the basic characteristics in the context of its usual usage. In the second chapter the basics behind the Arrangement on Officially Supported Export Credits are explained. Because the main purpose of this paper is to compare sovereign rating and the country risk classification based on the Arrangement, the chapter focuses especially on the Knaepen Package that introduced country risk classification to the Arrangement. In the chapter there is also the introduction to the Malzkuhn-Drysdale Package. In the third and fourth chapter sovereign ratings and county risk classifications are compared on theoretical basis. There were used several different criteria, e.g. methodology of rating/classifying, time necessary for adjustment and criteria for evaluation. The fifth chapter is focused on Basel I-III, the connection between Basel capital adequacy and both credit risk evaluation systems is explained. In the following chapter, the question of guilt of rating agencies and their role in the outbreak of financial crisis is discussed. The last chapter is based on the case study that describes the difference between development of financial crisis in Italy and Greece and its impact on rating grades and country risk classification.

The primary focus of this thesis was to investigate the critical strain energy release rates (G) for mixed-mode (I/II) fracture of wood adhesive joints. The aims of the study were: (1) quantifying the fracture properties of two material systems, (2) analyzing the aspects that influence the fracture properties of bonded wood, (3) refining test procedures that particularly address layered orthotropic systems in which the layers are not parallel to the laminate faces, of which wood is often a particular case, and (4) developing testing methods that enhance the usefulness of performing mixed-mode tests with a dual-actuator load frame. The material systems evaluated experimentally involved yellow-poplar (Liriodendron tulipifera), a hardwood of the Magnoliaceae family, as adherends and two different adhesives: a moisture-cure polyurethane (PU) and a phenol/resorcinol/-formaldehyde (PRF) resin. The geometry tested in the study was the double cantilever beam that, in a dual-actuator load frame, can be used for testing different levels of mode-mixity. The mixed-mode loading condition is obtained by applying different displacement rates with the two independently controlled actuators of the testing machine. Characteristic aspects such as the large variability of the adhesive layer thickness and the intrinsic nature of many wood species, where latewood layers are alternated with earlywood layers, often combine to confound the measures of the critical values of strain energy release rate, Gc. Adhesive layer thickness variations were observed to be substantial also in specimens prepared with power-planed wood boards and affect the value of Gc of the specimens. The grain orientation of latewood and earlywood, materials that often have different densities and elastic moduli, limits the accuracy of traditional standard methods for the evaluation of Gc. The traditional methods, described in the standards ASTM D3433-99 and BS 7991:2001, were originally developed for uniform and isotropic materials but are widely used by researchers also for bonded wood, where they tend to confound stiffness variations with Gc variations. Experimental analysis and analytical computations were developed for quantifying the spread of Gc data that is expected to be caused by variability of the adhesive layer thickness and by the variability of the bending stiffness along wooden beams. / Ph. D.

An experimental technique for conducting low speed impact of adhesively bonded automotive composite joints is presented. Based on the use of a modified drop tower, mode I, II, and mixed mode values for critical energy release rate were determined for a composite/epoxy system and used to create a fracture failure envelope. Because load measurements become erratic and unreliable at higher test rates, displacement-based relationships were used to quantify these energy release rates. Displacement data was collected with an imaging system that utilized edge detection to determine displacement profiles, end displacements, and opening displacements where applicable. Because of the resolution of the image-based approach used, determining crack length experimentally was extremely difficult. As a result, numerical methods were developed to objectively determine the crack length based on the available experimental data in mode I, II, and mixed mode I/II configurations. This numerical method uses a nonlinear fit to determine mode I crack lengths and a theoretical model based on cubic equations for mode II and mixed-mode I/II, where the coefficients of the equations are determined by using both boundary and transition conditions that are a result of the test setup. A double cantilever beam (DCB) geometry was chosen to collect mode I data, an end-loaded split (ELS) geometry was used for mode II, and a single leg bend (SLB) geometry was used for mixed-mode I/II. These geometries were used to determine the fracture characteristics of adhesively bonded automotive composites to create fracture failure envelopes as well as provide mode I, II, and mixed-mode I/II data to be used in finite element models. The chosen adhesive exhibited unstable, stick-slip crack growth, which resulted in very few data points being collected from each static DCB specimen as well as drastic drops in energy release rate between initiation and arrest points. Unstable growth also created issues in dynamic testing, as data points surrounding these "stick-slip" events were lost due to the insufficient sampling rate of the available imaging system. Issues also arose with differences between thick and thin composite adherend specimens. These differences could result from additional curing in thick adherend composite specimens due to the adherends retaining heat. DSC testing was conducted on uncured adhesive using a 2, 5, and 10 minute hold at the cure temperature, and significant additional curing was observed between the two and five minute cures. Due to the difference in relative stiffness between the 12 and 36 ply composite, the local loading rate at the crack tip was lower in the 12 ply adherends, possibly allowing for a larger plastic zone and thus a higher energy release rate. As a result, tests were conducted on 36 ply composite specimens at rates of 1 mm/min and 0.1 mm/min to determine if there were loading rate effects. This testing showed that higher initiation energy relase rates were found at the lower test rate, thus reinforcing the local loading rate theory. Due to issues with plastic deformation in aluminum adherends, mode II and mixed-mode I/II data were collected using only composite adherends. Only one data point was collected per specimen as the crack propagated directly into the composite after initiating from the precrack, thus multiple tests were conducted to collect sufficient data for constructing a failure envelope. Once mode I, II and mixed-mode I/II fracture data was collected, a fracture failure envelope was created. This failure envelope, combined with a predetermined factor of safety, could provide some of the necessary tools for design with this adhesive/composite system. / Master of Science

La premiere partie de ce memoire concerne la propagation de fissures en mode mixte I+II+III. Nous avons premierement complete le developpementdes F.I.C. en puissances de la longueur de l'extension etabli par Mouchrif, par la determination d'un operateur universel (independant du probleme) decrivant l'effet d'une longueur d'extension variable le long du front. Son calcul est effectue en utilisant une technique de developpements asymptotiques raccordes, puis le formalisme de Muskhelishvili couple a une technique de transformation conforme. Deuxiement, apres avoir presente les trajets de ssuration observes en presence de mode III, nous avons de ni des criteres permettant de predire la valeur de l'angle de branchement le long du frontdans le cas particulier du deversement ou tout le front tourne autour de la direction de propagation pour se rapprocher du mode I pur. Les valeurs obtenues concordent avec des resultats d'experiences en mode I+III et en modeI+II+III, qui nous sont partiellement dues.<br />La deuxieme partie est consacree au calcul des fonctions de poids tri-dimensionnelles d'une fissure d'interface semi-infinie. La methode de resolution est d'un type nouveau et ne necessite pas la resolution complete du probleme d'elasticite. La premiere etape consiste a determiner l'accroissement des F.I.C. dû a une perturbation coplanaire infinitesimale du front.<br />La deuxieme etape consiste a appliquer ce resultat aux chargements particuliers definissant les fonctions de poids et a une perturbation particuliereconservant la forme de la fissure. Nous obtenons ainsi des equations integro differentielles, qui deviennent apres transformation de Fourier le long du front, des equations differentielles ordinaires. La solution est obtenue sous forme analytique au premier ordre en $\epsilon$, constante ((bielastique)) des materiaux. En guise d'application, nous examinons le probleme de la stabilite de la forme rectiligne du front vis-a-vis de petites perturbations coplanaires.