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.

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Le comportement en fatigue de l’acier à très haute résistance (THR) X23NiCoCrMoAl13-6-3 étudié est caractérisé par une dispersion dans les performances de tenue en fatigue. Deux modes d’amorçages de fissures sont observés sur sa courbe de Wöhler : le premier mode correspondant à des amorçages de fissures à partir d’inclusions non métalliques en surface des éprouvettes menant aux plus faibles durées de vie. Le second mode correspond à des amorçages de fissures en interne sur inclusions menant à de longues durées de vie et à des fissures en forme d’œil de poisson (« fish-eye »). Le lien entre les conditions d’essai (niveau de sollicitation, température et environnement), la nature et la localisation du site d’amorçage et la durée de vie résultante n’est jusqu’alors pas clairement identifié. L’objectif de ce travail de thèse est donc de mieux appréhender les mécanismes physiques à l’origine des différents types d’amorçage et de propagation en fatigue menant à la dispersion en durée de vie.La première partie de ce document présente la caractérisation microstructurale multi-échelle de l’acier THR avec l’identification des entités microstructurales et de leurs dimensions caractéristiques. Ensuite, l’analyse des faciès de rupture a permis de caractériser de manière approfondie les zones associées aux différents stades de propagation de la fissure de fatigue. Pour l’amorçage en surface, on trouve : 1) la particule rompue 2) la propagation sous air 3) la rupture ductile finale. Pour les amorçages en interne deux stades supplémentaires sont observés : 1.a) formation d’une zone à grains fins (« fine granular area, (FGA) ») autour de la particule si sa taille est inférieure à une taille critique et 1.b) propagation sous vide. La mécanique linéaire de la rupture est utilisée pour estimer le facteur d’intensité des contraintes de la fissure, Kmax, pour chacune de ces zones.Le facteur Kmax associé à la transition entre FGA et fish-eye se révèle être constant à une température donnée. Cette transition se caractérise par une taille de zone plastique en pointe de fissure de l’ordre de trois fois la largeur des lattes de martensite. Lorsque la température augmente, le Kmax en fin de FGA diminue mais la taille de la zone plastique reste constante. Le caractère cristallographique, pseudo stade I, de la propagation dans la FGA est mis en évidence. Il a été de plus confirmé qu’une FGA pouvait se former en cours de propagation de fissures à partir d’éprouvettes entaillées (SENT), sous vide sollicitées à Kmax faible. Le caractère cristallographique a été confirmé par analyse EBSD 3D du faciès de rupture. Un calcul de durée de vie en propagation pure sous air et sous vide a montré que les durées de vie peuvent varier d’un ordre de grandeur en fonction de l’environnement. / The fatigue behavior of a very high strength steel X23NiCoCrMoAl13-6-3 shows a large scatter in fatigue life. Two fatigue crack initiation scenarios are found. They are separated by a plateau in the Wöhler curve: the first one corresponds to crack initiation at the specimen surface from non-metallic inclusions leading to short fatigue lives. The second scenario corresponds to internal crack initiation from particles leading to so-called fish-eye cracks. The link between test conditions (load level, temperature and environment), the nature and location of the crack initiation site and the associated fatigue life has yet not been clearly established. The objective of the present PhD project is to better understand the physical mechanisms leading to the different fatigue crack initiation and propagation mechanisms.In the first part of the thesis the microstructure of the very high strength steel was studied at multiple scales and its main constituents and their respective sizes were identified.Further, the analysis of the fatigue tests by fractography has permitted to identify the different characteristic fatigue crack propagation stages. For surface fatigue crack initiation, the following stages were found: 1) a broken particle 2) fatigue crack propagation in air 3) the final ductile fracture. For internal fatigue crack initiation two more fatigue crack propagation stages are observed: 1.a) formation of a fine granular area (FGA) for small particles and 1.b) propagation in vacuum. Linear elastic fracture mechanics are used to evaluate the stress intensity factor, Kmax for each of these zones.Kmax revealed to be constant at the end of the FGA. The size of the plastic zone at the end of the FGA was calculated and corresponded to three times the width of the martensite laths. Tests at different temperatures (20°C, 200°C and 400°C) revealed a decreasing FGA size with increasing temperature at constant applied stress amplitude. As a consequence, the critical stress intensity factor varied as the FGA decreased with temperature. In contrast, the critical plastic zone size remained constant and equal to the sizes of microstructural features. This represents a strong similarity between crystallographic, stage I-like, crack propagation and FGA formation in a vacuum. This was further confirmed as an FGA was formed during crack propagation using SENT samples in vacuum and for low Kmax levels. The crystallographic character was verified by an SEM/FIB analysis of the fracture surface. A fatigue life prediction, assuming propagation only, showed that the fatigue life can vary by an order of magnitude as a function of the test environment corresponding to surface and internal crack initiation.

Dagens samhälle har fått en explosiv utveckling som förverkligar mycket som för bara några år sedan var inte mer än fantasier.  Dagens utvecklingsförsprång ställer oss, byggnadskonstruktörer, inför rejäla utmaningar. Den globala folktillväxten ökar väsentligt vilket leder till tätbefolkade städer. Detta utvecklar ett stort utrymmesbehov hos många av oss. Allt detta resulterar i att efterfrågan på stora och öppna planlösningar ökar markant. En av dagens tendenser är att beställare och arkitekter har en benägenhet att tänja på gränserna på maximala spännvidder mellan bärande betongväggar, för bjälklagstjockleken 250 mm. Detta är ett tillfredsställande mått för att klara ljudklass B. Dessutom är det opraktiskt att variera bjälklagstjocklekar inom ett projekt, därför vill man ha uniformitet med samma tjocklek över projektet. För att vi ska kunna förverkliga vårt uppdrag har vi varit tvungna att genomgå en lång beräknings- och undersökningsprocess. I våra beräkningar har vi lagt fokus på två upplagsfall. Det första upplagsfallet ”fri-inspänd” och det andra fallet ”inspänd-yttre gavelvägg”. Första fallet har varit det värsta fallet i och med att vi bara har ett stöd som måste bära hela betongbjälklaget, vilket har varit en stor utmaning. Andra fallet var dock betydligt enklare på grund av de två stöden som utgjorde en stor del av ”arbetet” och lyfter upp bjälklaget, hela tyngden vilade inte på armeringen som i föregående fall. Inte bara spännvidden skall klaras utan även angiven sprickvidd på 0,3 mm. Examensarbetet består av förklarande fakta som är strikt relaterad till efterföljande beräkningar. Alla beräkningar har utförts för hand, utan programstöd. / Today's society has received a degenerate development embodying much that just a few years ago was no more than fantasies. This development sets us, structural engineers, facing real challenges. The global population growth increases significantly leading to densely populated cities. This develops a large space need for many of us. All this results in the increasing demand for large and open floor plans significantly. One of the current trends is that the clients and architects have a tendency to push the limits on maximum spans between bearing concrete walls, slabs for thickness 250 mm. This is a satisfactory measure of the concrete content to manage audio class B. Moreover, it is impractical to vary the slab thickness within a project, so he wants to have uniformity with the same thickness over the project. For us to be able to realize these long spans between bearing walls, we have been forced to undergo a long calculation and examination process. To begin with, we have studied the company's requirements and preferences, based on that, we started joists analysis. In our calculations, we have laid emphasis on two cases. The first circulation fall "free - clamped" and the second, "clamped- outer end wall." The first case has been the worst case, in that we only have one support that must bear the entire concrete slab, which has been a major challenge. Second case was considerably easier due to the two supports which made a large part of "work" and lifts the slab, the full weight rested not on the reinforcement as in the previous case. Not just the span must be met, but also given crack width of 0.3 mm. The thesis consists of explanatory facts that are strictly related to the subsequent calculations. All calculations have been performed by hand, without program support.