Il est généralement admis que la vision joue un rôle prépondérant dans la formation des représentations spatiales. Qu’advient-il alors lorsqu’un individu est atteint de cécité? Dans le premier volet de cette thèse, les habiletés spatiales des personnes aveugles ont été examinées à l’aide de différentes tâches et comparées à celles de personnes voyantes effectuant les mêmes tâches avec les yeux bandés. Dans une première étude, les capacités de rotation mentale ont été évaluées à l’aide d’une épreuve d’orientation topographique tactile. Les résultats obtenus montrent que les personnes aveugles parviennent généralement à développer des capacités de rotation mentale similaires à celles de personnes voyantes et ce, malgré l’absence d’information de nature visuelle. Dans une seconde étude, nous avons utilisé différentes tâches spatiales nécessitant l’utilisation de la locomotion. Les résultats obtenus montrent que les personnes aveugles font preuve d’habiletés supérieures à celles de voyants lorsqu’elles doivent apprendre de nouveaux trajets dans un labyrinthe. Elles parviennent également à mieux reconnaître une maquette représentant un environnement exploré précédemment. Ainsi, l’absence de vision ne semble pas entraver de manière significative la formation de concepts spatiaux. Le second volet de cette thèse s’inscrit dans la lignée des études sur la plasticité cérébrale chez les personnes aveugles. Dans le cas présent, nous nous sommes intéressés à l’hippocampe, une structure profonde du lobe temporal dont le rôle au plan spatial a été établi par de nombreuses études animales ainsi que par des études cliniques chez l’humain incluant l’imagerie cérébrale. L’hippocampe joue un rôle particulièrement important dans la navigation spatiale. De plus, des changements structuraux de l’hippocampe ont été documentés en relation avec l’expérience des individus. Par exemple, l’étude de Maguire et al. (2000) a mis en évidence de telles modifications structurelles de l’hippocampe chez des chauffeurs de taxi. À l’instar de ces derniers, les personnes aveugles doivent emmagasiner de nombreuses informations au sujet de leur environnement puisqu’elles ne peuvent bénéficier de la vision pour mettre à jour les informations sur celui-ci, sur leur position dans l’espace et sur la position des objets se trouvant hors de leur portée. Nous avons montré, pour la première fois, une augmentation du volume des hippocampes chez les personnes aveugles en comparaison avec les personnes voyantes. De plus, cette augmentation de volume était positivement corrélée à la performance à une tâche d’apprentissage de trajets. Les résultats présentés dans cette thèse permettent d’appuyer les études antérieures qui soutiennent que les personnes aveugles parviennent à compenser leur déficit et à développer des habiletés spatiales comparables, voire supérieures, à celles de personnes voyantes. Ils permettent également d’apporter un éclairage nouveau sur le concept de plasticité cérébrale présent chez cette population en montrant pour la première fois un lien entre le volume de l’hippocampe et les habiletés spatiales chez les personnes aveugles. / It is well known that the visual modality plays a key role in the development of spatial representations. Hence, one may wonder how complex spatial abilities develop and how the brain is able to adapt in the absence of this modality. In order to answer such questions we investigated the spatial abilities and cerebral plasticity of both early and late blind individuals in comparison to sighted blindfolded individuals. The first experiment was designed to assess mental rotation abilities. A tactile topographical orientation task was used. The results show that blind individuals are able to develop mental rotation abilities similar to those of sighted ones. In the second experiment, we used different spatial tasks requiring the use of locomotion and wayfinding. Results show that blind individuals are better than their sighted counterparts at learning new routes in a maze. They also perform better when having to recognize a small-scale model representing a real-size spatial layout they had previously explored. Thus, the absence of vision does not appear to significantly impede the formation of spatial concepts. The second part of this thesis is in line with studies on brain plasticity in blind individuals. We measured morphological changes in the hippocampus, a medial structure of the temporal lobe. Animal lesion-based and human brain imaging studies have shown that the hippocampus plays an important role in the processing of spatial information and in spatial navigation. Furthermore, structural changes in the hippocampus have been documented in relation to the ‘spatial’ experience of individuals. For instance, Maguire and colleagues (2000) have shown structural differences in the hippocampus of well-trained taxi drivers in comparison to individuals without extensive spatial training. Like taxi drivers, blind individuals require extensive storage of information regarding their environment. This is essentially because they cannot rely on visual cues to create a representation of the spatial organization of their environment, nor can they continuously visually update their position in space and the spatial coordinates of objects outside of their reach. Here we show for the first time an increase in the volume of the hippocampus in blind compared to sighted individuals. Moreover, this increase in hippocampal volume was positively correlated with performance on the route-learning task described above. Overall, the results not only support previous findings showing that blind individuals can develop spatial abilities similar or superior to those of sighted individuals, but also shed light on the concept of brain plasticity by showing for the fist time a correlation between hippocampal volume and spatial abilities in the blind.

In the iron production processes, sinters and pellets are mostly used as raw materials due to their consistency with respect to physical and chemical properties. However, natural iron ores, as mined, are rarely used directly as a feed material for iron processing. This is mainly due to the fact that they have small contents of iron and high concentration of impurities. Moreover, they swell and disintegrate during the descent in the furnace as well as due to low melting and softening temperatures. This work involves an investigation of the parameters that influence the use of natural iron ores as a direct feed material for iron production. Furthermore, it points out ways in which these can be mitigated so as to increase their direct use in iron production. Natural iron ore from Muko deposits in south-western Uganda was used in this study. Initially, characterisation of the physical and chemical properties was performed, to understand the natural composition of the ore. In addition, investigations were done to study the low temperature strength of the ore and its behaviour in the direct reduction zone. Also, simulations were performed with three models using the experimental data from the direct reduction experiments in order to determine the best model for predicting the direct reduction kinetics of natural iron ores. Chemical analyses showed that the Muko ore represents a high grade of hematite with an Fe content of 68% on average. The gangue content (SiO2+Al2O3) in 5 of the 6 investigated iron ore samples was &lt; 4%, which is within the tolerable limits for the dominant iron production processes. The S and P contents were 0001-0.006% and 0.02-0.05% respectively. These can be reduced in the furnace without presenting major processing difficulties. With respect to the mechanical properties, the Muko ore was found to have a Tumble Index value of 88-93 wt%, an Abrasion Index value of 0.5-3.8 wt% and a Shatter Index value of 0.6-2.0 wt%. Therefore, the ore holds its form during the handling and charging processes. Under low temperature investigations, new parameters were discovered that influence the low temperature strength of iron oxides. It was discovered that the positioning of the samples in the reduction furnace together with the original weight (W0) of the samples, have a big influence on the low temperature strength of iron oxide. Higher mechanical degradation (MD) values were obtained in the top furnace reaction zone samples (3-25% at 500oC and 10-21% at 600oC). These were the samples that had the first contact with the reducing gas, as it was flowing through the furnace from top to bottom. Then, the MD values decreased till 5-16% at a 500oC temperature and 6-20% at a 600oC temperature in the middle and bottom reaction zones samples. It was found that the obtained difference between the MD values in the top and other zones can be more than 2 times, particularly at 500oC temperature. Furthermore, the MD values for samples with W0 &lt; 5 g varied from 7-21% well as they decreased to 5-10% on average for samples with W0 ≥ 5 g. Moreover, the MD values for samples taken from the top reaction zone were larger than those from the middle and bottom zones. During direct reduction of the ores in a H2 and CO gas mixture with a ratio of 1.5 and a constant temperature, the reduction degree (RD) increased with a decreased flow rate until an optimum value was established. The RD also increased when the flow rate was kept constant and the temperature increased. An optimum range of 3-4g was found for natural iron ores, within which the highest RD values that are realised for all reduction conditions. In addition, the mechanical stability is greatly enhanced at RD values &gt; 0.7. In the case of microstructure, it was observed that the original microstructure of the samples had no significant impact on the final RD value (only 2-4%). However, it significantly influenced the reduction rate and time of the DR process. The thermo-gravimetric data obtained from the reduction experiments was used to calculate the solid conversion rate. Three models: the Grain Model (GM), the Volumetric Model (VM) and the Random Pore Model (RPM), were used to estimate the reduction kinetics of natural iron ores. The random pore model (RPM) provided the best agreement with the obtained experimental results (r2 = 0.993-0.998). Furthermore, it gave a better prediction of the natural iron oxide conversion and thereby the reduction kinetics. The RPM model was used for the estimation of the effect of original microstructure and porosity of iron ore lumps on the parameters of the reduction process. / <p>QC 20130531</p> / Sustainable Technology Development in the Lake Victoria Region

O interesse pela quantificação da biomassa florestal vem crescendo muito nos últimos anos, sendo este crescimento relacionado diretamente ao potencial que as florestas tem em acumular carbono atmosférico na sua biomassa. A biomassa florestal pode ser acessada diretamente, por meio de inventário, ou através de modelos empíricos de predição. A construção de modelos de predição de biomassa envolve a mensuração das variáveis e o ajuste e seleção de modelos estatísticos. A partir de uma amostra destrutiva de de 200 indivíduos de dez essências florestais distintas advindos da região de Linhares, ES., foram construídos modelos de predição empíricos de biomassa aérea visando futuro uso em projetos de reflorestamento. O processo de construção dos modelos consistiu de uma análise das técnicas de obtenção dos dados e de ajuste dos modelos, bem como de uma análise dos processos de seleção destes a partir do critério de Informação de Akaike (AIC). No processo de obtenção dos dados foram testadas a técnica volumétrica e a técnica gravimétrica, a partir da coleta de cinco discos de madeira por árvore, em posições distintas no lenho. Na técnica gravimétrica, estudou-se diferentes técnicas de composição do teor de umidade dos discos para determinação da biomassa, concluindo-se como a melhor a que utiliza a média aritmética dos discos da base, meio e topo. Na técnica volumétrica, estudou-se diferentes técnicas de composição da densidade do tronco com base nas densidades básicas dos discos, concluindo-se que em termos de densidade do tronco, a média aritmética das densidades básicas dos cinco discos se mostrou como melhor técnica. Entretanto, quando se multiplica a densidade do tronco pelo volume deste para obtenção da biomassa, a utilização da densidade básica do disco do meio se mostrou superior a todas as técnicas. A utilização de uma densidade básica média da espécie para determinação da biomassa, via técnica volumétrica, se apresentou como uma abordagem inferior a qualquer técnica que utiliza informação da densidade do tronco das árvores individualmente. Por fim, sete modelos de predição de biomassa aérea de árvores considerando seus diferentes compartimentos foram ajustados, a partir das funções de Spurr e Schumacher-Hall, com e sem a inclusão da altura como variável preditora. Destes modelos, quatro eram gaussianos e três eram lognormais. Estes mesmos sete modelos foram ajustados incluindo a medida de penetração como variável preditora, totalizando quatorze modelos testados. O modelo de Schumacher-Hall se mostrou, de maneira geral, superior ao modelo de Spurr. A altura só se mostrou efetiva na explicação da biomassa das árvores quando em conjunto com a medida de penetração. Os modelos selecionados foram do grupo que incluíram a medida de penetração no lenho como variável preditora e , exceto o modelo de predição da biomassa de folhas, todos se mostraram adequados para aplicação na predição da biomassa aérea em áreas de reflorestamento. / Forest biomass measurement implies a destructive procedure, thus forest inventories and biomass surveys apply indirect procedure for the determination of biomass of the different components of the forest (wood, branches, leaves, roots, etc.). The usual approch consists in taking a destructive sample for the measurment of trees attributes and an empirical relationship is established between the biomass and other attributes that can be directly measured on standing trees, e.g., stem diameter and tree height. The biomass determination of felled trees can be achived by two techniques: the gravimetric technique, that weights the components in the field and take a sample for the determination of water content in the laboratory; and the volumetric technique, that determines the volume of the component in the field and take a sample for the determination of the wood specific gravity (wood basic density) in the laboratory. The gravimetric technique applies to all components of the trees, while the volumetric technique is usually restricted to the stem and large branches. In this study, these two techniques are studied in a sample fo 200 trees of 10 different species from the region of Linhares, ES. In each tree, 5 cross-sections of the stem were taken to investigate the best procedure for the determination of water content in gravimetric technique and for determination of the wood specific gravity in the volumetric technique. Also, Akaike Information Criterion (AIC) was used to compare different statistical models for the prediction o tree biomass. For the stem water content determination, the best procedure as the aritmetic mean of the water content from the cross-sections in the base, middle and top of the stem. In the determination of wood specific gravity, the best procedure was the aritmetic mean of all five cross-sections discs of the stem, however, for the determination of the biomass, i.e., the product of stem volume and wood specific gravity, the best procedure was the use of the middle stem cross-section disc wood specific gravity. The use of an average wood specific gravity by species showed worse results than any procedure that used information of wood specific gravity at individual tree level. Seven models, as variations of Spurr and Schumacher-Hall volume equation models, were tested for the different tree components: wood (stem and large branches), little branches, leaves and total biomass. In general, Schumacher-Hall models were better than Spurr based models, and models that included only diameter (DBH) information performed better than models with diameter and height measurements. When a measure of penetration in the wood, as a surrogate of wood density, was added to the models, the models with the three variables: diameter, height and penetration, became the best models.

Die Lebendspende von Leberlappen wird in der Zukunft gerade vor dem Hintergrund des stets weiter steigenden Bedarfs und des sich dazu diskrepant entwickelnden Mangels an Leichenorganen zur Transplantation eine zunehmend wichtige Rolle einnehmen, um Patienten im Endstadium einer Lebererkrankung kurativ zu versorgen. Umso mehr spielen Überlegungen zur Gewährleistung insbesondere der Sicherheit für einen gesunden Lebendspender eine Rolle, ohne Risiken für ihn eliminieren zu können. In diese Überlegungen gehen Weiterentwicklungen der Möglichkeiten für die spezielle Evaluation der Leber eines potenziellen Spenders anhand bildgebender Verfahren ein. Hier nehmen Methoden zur präoperativen Abschätzung der Gewichts- und Volumenverhältnisse einer potenziellen Spenderleber und ihrer Lappen einen besonderen Stellenwert ein, da bei entsprechend ungünstigen Voraussetzungen ein gesunder Mensch aus Gründen der Sicherheit für eine Lebendspende nicht in Frage kommt. Die vorliegende Arbeit zeigt anhand einer prospektiven Studie unterschiedliche Methoden der präoperativen CT-gestützten Volumetrie zur Evaluation von Lebern und ihrer beiden Lappen von potenziellen Lebendspendern auf. Dabei wurde ein neu entwickeltes Volumetrieverfahren klinisch erprobt und mit einem etablierten Verfahren verglichen. Als Referenzgrößen wurden erstmalig gleichermaßen intraoperativ gemessene Gewichte und Volumina der transplantieren rechten Leberlappen herangezogen. Hinsichtlich der auf CT-gestützter Volumetrie basierenden, präoperativen Abschätzung von intraoperativ zu erwartendem Gewicht und Volumen von rechten Leberlappen im Rahmen einer Lebendspende erwies sich das etablierte Verfahren bezüglich des Gewichts dem neu entwickelten Verfahren geringgradig überlegen, während das neu entwickelte Verfahren bezüglich des Volumens gegenüber dem etablierten Verfahren geringgradig besser abschnitt. Darüber hinaus resultierte aus den intraoperativ erhobenen Daten die Erkenntnis, dass die physikalische Dichte von gesundem Lebergewebe bei einer relativ hohen interindividuellen Streuung im Mittel um knapp 12% höher liegt als zumeist angenommen. In Zukunft werden Fortschritte technischer Verfahren sehr genaue virtuelle Trennungen von Lebern in ihre beiden Lappen ermöglichen. Gleichzeitig werden chirurgische Resektionstechniken verfeinert. Sowohl der virtuelle als auch der reale Ansatz haben den Anspruch, die avaskuläre und somit ideale Resektionsfläche zwischen beiden Leberlappen aufzusuchen, um gleichzeitig präoperativ exakte Gewichts- und Volumenabschätzungen zu ermöglichen und intraoperativ Risiken zu minimieren. Welchem dieser beiden Ansätze die stärkste Annäherung an diesen Anspruch oder dessen Vollendung zuerst gelingt, wird sich als Referenzmethode behaupten, an der sich der unterlegene Ansatz wird messen lassen müssen. / The increasing need of cadaveric liver grafts and the scarcity of living related liver transplants (LRLT) will play a critical role in the future treatment of patients suffering from end stage liver disease. Various considerations, including especially a safe outcome for the donor, are essential. However, risks can not be eliminated. These considerations can be influenced in the evaluation of a potential living donor. Accurate methods, including imaging modalities, for the preoperative estimation of the potential donor liver’s weight and volume are essential as an adverse condition would preclude a living donation for safety reasons. This thesis presents different methods of preoperative CT-based volumetric analyses for the evaluation the liver and both its lobes in potential living donors. A newly developed method of volumetric analysis was clinically tested and compared with an established method. Intraoperatively measured weights and volumes of transplanted right hepatic lobes were used as reference values. With regards to the weight, the established method proved to be mildly superior, while the newer method was slightly more accurate for volume. Additionally, it was discovered that the mean density of healthy liver tissue is approximately 12 percent higher than generally assumed but with a relatively high individual variation. Progress in technical methods will render possible very exact virtual divisions of the liver in both of its lobes. Both the virtual and surgical approach have a claim for finding the appropriate avascular and consequently ideal resection plane in order to minimize risks intraoperatively.

Os gliomas de vias ópticas (GVO) representam 5% dos tumores cerebrais pediátricos e geralmente aparecem histologicamente como astrocitomas de baixo grau. Por causa do curso imprevisto dos GVO, as opções de tratamento ainda são controversas, envolvendo vigilância, cirurgia, quimioterapia e radioterapia. Neste estudo, realizamos a análise volumétricas de gliomas de vias ópticas envolvendo as regiões óptico-quiasmáticas e hipotalâmica (GOQH) para comparar a evolução as neoplasias tratadas com e sem quimioterapia, comparando o volume e componentes das lesões. Foram analisados retrospectivamente 14 pacientes com (GOQH) que foram submetidos a Ressonância Magnética em nosso departamento de janeiro de 2000 a outubro de 2015. Um total de 45 RM de encéfalo foram incluídas, com uma média de 3,2 estudos/paciente. A avaliação das lesões foi realizada manualmente por um Neurorradiologista, usando o Software DISPLAY. Quatro destes pacientes eram portadores de NF-1. Oito foram tratados com quimioterapia, sendo carboplatina e vincristina (Carbo/VCR) os agentes de primeira linha. As medidas volumétricas foram realizadas com separação entre os componentes sólidos e císticos das neoplasia, usando as sequências FLAIR e T1 pós contraste, com o apoio de imagens ponderadas em T1 e T2. Um aumento de aproximadamente 30% do volume para as lesões sólidas e uma redução de 19,4% no volume das lesões sólido-císticas foram observados no período global após o tratamento com quimioterapia, porém ambos sem significância estatística. Entre os pacientes não tratados, observou-se uma redução de 16,6 % do volume global das lesões durante o período de acompanhamento. A avaliação da eficácia do tratamento para pacientes com GOQH é difícil, dada a raridade de casos e heterogeneidade radiológica. Os dados de algumas publicações argumentam que o valor da quimioterapia é controverso e não se correlaciona com a resposta radiológica. Em nosso estudo observamos uma pequena redução do volume de neoplasias entre os pacientes tratados e não tratados com quimioterapia, porém sem significância estatística. Ensaios clínicos prospectivos são necessários para melhor avaliar o efeito da quimioterapia sobre OPG. / Optic pathway gliomas (OPG) represent 5% of pediatric brain tumors and generally appear histologically as low-grade astrocytomas. Because of the unpredictable course of OPG, adequate treatment method has been controversial, involving surveillance, surgery, chemotherapy and radiotherapy. In this study, we use volumetric imaging to compare evolution between OPG treated with and without chemotherapy, analyzing the volume and components of the lesions. We retrospectively analyzed 14 patients with OPG who underwent MRI in our department from January 2000 to October 2015. A total of 45 brain MRI were included, with an average of 3,2 studies/patient. The assessment of lesions was manually performed by a neuroradiologist, using software DISPLAY. Four of these patients had NF-1. Eight were treated with chemotherapy, using carboplatin and vincristine (Carbo/VCR) as first-line agents. Volumetric measurements of tumors were segmented into solid and cystic components using FLAIR and T1 weighted images after Gadolinium sequences, with support of T1 and T2 weighted images. An increase of approximately 30% of volume for solid lesions and a decrease of 19,4% for solid-cystic lesions were noted following chemotherapy in overall period, both with no statistical significance. Among patients not treated with chemotherapy, we observed a reduction of 16% in overall volume of the lesions Evaluation of treatment efficacy for OPG patients is difficult, given the rarity of cases and radiological heterogeneity. Data from some publications argued that the value of chemotherapy is controversial and does not correlate with radiological response. From our study we observed a small volume reduction of neoplasms among patients treated and not treated with chemotherapy. Larger prospective clinical trials are needed to better evaluate the effect of chemotherapy on OPG.

Magnetic Resonance Imaging, Computed Tomography, and other image modalities are routinely used to visualize a particular structure in the patient's body. The classification of the image region corresponding to this structure is called segmentation. For applications in Neuroscience, it is important for the segmentation of a brain scan to represent the boundary of the brain as a folded surface with no holes. However the segmentation of the brain generally exhibits many erroneous holes. Consequently we have developed an algorithm for automatically correcting holes in segmented medical scans while preserving the accuracy of the segmentation. Upon concepts of Discrete Topology, we remove the holes based on the smallest modification to the image. First we detect each hole with a front propagation and a Reeb graph. Then we search for a number of loops around the hole on the isosurface of the image. Finally we correct the hole in the image using the loop that minimizes the modification to the image. At each step we limit the size of the data in memory. With these contributions our algorithm removes every hole in the image with high accuracy and low complexity even for images too large to fit into the main memory. To help doctors and scientists to obtain segmentations without holes, we have made our software publicly available at http://www.OpenTopology.org. / Les images par Résonance Magnétique, la Tomographie par Rayons X et les autres modalités d'imagerie médicale sont utilisées quotidiennement pour visualiser une structure particulière dans le corps du patient. La classification de la région de l'image qui correspond à cette structure s'appelle la segmentation. Pour des applications en Neuroscience, il est important que la segmentation d'une image du cerveau représente la surface extérieure du cerveau comme une surface pliée sans trous. Cependant la segmentation du cerveau présente généralement de nombreux trous. Par conséquent, nous avons développé un algorithme pour corriger automatiquement les trous dans les images médicales segmentées tout en préservant la précision de la segmentation. Sur des concepts de Topologie Discrète, nous enlevons les trous en fonction de la plus petite modification apportée à l'image. D'abord nous détectons chaque trou avec un certain nombre de boucles autour du trou sur l'isosurface de l'image. Finalement nous corrigeons le trou dans l'image en utilisant la boucle qui minimise la modification de l'image. A chaque étape, nous limitons la taille des données en mémoire. Grâce à ces contributions notre algorithme enlève tous les trous dans l'image avec une grande précision et une faible complexité même pour des images trop grandes pour tenir dans la mémoire de l'ordinateur. Pour aider les médecins et les chercheurs à obtenir des segmentations sans trous, nous avons rendu notre logiciel disponible publiquement à http://www.OpenTopology.org.

Treatment planning for radiation therapy inherently involves tradeoffs, such as between tumor control and normal tissue sparing, between time-efficiency and dose quality, and between nominal plan quality and robustness. The purpose of this thesis is to develop methods that can facilitate decision making related to such tradeoffs. The main focus of the thesis is on multicriteria optimization methods where a representative set of treatment plans are first calculated and the most appropriate plan contained in this representation then selected by the treatment planner through continuous interpolation between the precalculated alternatives. These alternatives constitute a subset of the set of Pareto optimal plans, meaning plans such that no criterion can be improved without a sacrifice in another. Approximation of Pareto optimal sets is first studied with respect to fluence map optimization for intensity-modulated radiation therapy. The approximation error of a discrete representation is minimized by calculation of points one at the time at the location where the distance between an inner and outer approximation of the Pareto set currently attains its maximum. A technique for calculating this distance that is orders of magnitude more efficient than the best previous method is presented. A generalization to distributed computational environments is also proposed. Approximation of Pareto optimal sets is also considered with respect to direct machine parameter optimization. Optimization of this form is used to calculate representations where any interpolated treatment plan is directly deliverable. The fact that finite representations of Pareto optimal sets have approximation errors with respect to Pareto optimality is addressed by a technique that removes these errors by a projection onto the exact Pareto set. Projections are also studied subject to constraints that prevent the dose-volume histogram from deteriorating. Multicriteria optimization is extended to treatment planning for volumetric-modulated arc therapy and intensity-modulated proton therapy. Proton therapy plans that are robust against geometric errors are calculated by optimization of the worst case outcome. The theory for multicriteria optimization is extended to accommodate this formulation. Worst case optimization is shown to be preferable to a previous more conservative method that also protects against uncertainties which cannot be realized in practice. / En viktig aspekt av planering av strålterapibehandlingar är avvägningar mellan behandlingsmål vilka står i konflikt med varandra. Exempel på sådana avvägningar är mellan tumörkontroll och dos till omkringliggande frisk vävnad, mellan behandlingstid och doskvalitet, och mellan nominell plankvalitet och robusthet med avseende på geometriska fel. Denna avhandling syftar till att utveckla metoder som kan underlätta beslutsfattande kring motstridiga behandlingsmål. Primärt studeras en metod för flermålsoptimering där behandlingsplanen väljs genom kontinuerlig interpolation över ett representativt urval av förberäknade alternativ. De förberäknade behandlingsplanerna utgör en delmängd av de Paretooptimala planerna, det vill säga de planer sådana att en förbättring enligt ett kriterium inte kan ske annat än genom en försämring enligt ett annat. Beräkning av en approximativ representation av mängden av Paretooptimala planer studeras först med avseende på fluensoptimering för intensitetsmodulerad strålterapi. Felet för den approximativa representationen minimeras genom att innesluta mängden av Paretooptimala planer mellan inre och yttre approximationer. Dessa approximationer förfinas iterativt genom att varje ny plan genereras där avståndet mellan approximationerna för tillfället är som störst. En teknik för att beräkna det maximala avståndet mellan approximationerna föreslås vilken är flera storleksordningar snabbare än den bästa tidigare kända metoden. En generalisering till distribuerade beräkningsmiljöer föreslås även. Approximation av mängden av Paretooptimala planer studeras även för direkt maskinparameteroptimering, som används för att beräkna representationer där varje interpolerad behandlingsplan är direkt levererbar. Det faktum att en ändlig representation av mängden av Paretooptimala lösningar har ett approximationsfel till Paretooptimalitet hanteras via en metod där en interpolerad behandlingsplan projiceras på Paretomängden. Projektioner studeras även under bivillkor som förhindrar att den interpolerade planens dos-volym histogram kan försämras. Flermålsoptimering utökas till planering av rotationsterapi och intensitetsmodulerad protonterapi. Protonplaner som är robusta mot geometriska fel beräknas genom optimering med avseende på det värsta möjliga utfallet av de föreliggande osäkerheterna. Flermålsoptimering utökas även teoretiskt till att innefatta denna formulering. Nyttan av värsta fallet-optimering jämfört med tidigare mer konservativa metoder som även skyddar mot osäkerheter som inte kan realiseras i praktiken demonstreras experimentellt. / <p>QC 20130527</p>

En el caso del almacenamiento de los residuos radioactivos los flujos osmóticos pueden ser relevantes y requieren un análisis en detalle. El residuo nuclear bituminizado (BW) será almacenado mediante contenedores en cavidades excavadas en la Boom Clay, que es una arcilla marina que presenta propiedades favorables para limitar y retrasar la migración de los contaminantes radioactivos. La interacción entre los dos materiales es un proceso acoplado químico-hidro-mecánico y depende de la respuesta hidromecánica de la Boom Clay y del BW. En condiciones de almacenamiento, el contacto del BW, que contienen cantidades importantes de NaNO3, con el agua subterránea induce la hidratación por gradientes osmóticos y el consiguiente hinchamiento, además de la difusión de la sal disuelta hacia la Boom Clay. Se pueden distinguir dos tipos de afecciones: la perturbación geomecánica causada por el hinchamiento del BW y el aumento de presión en el BW y cambio de las distribución de tensiones en la roca, y la perturbación físico química por la migración de grandes cantidades de sales. El objetivo de esta tesis es: (i) Mejorar la comprensión de los procesos que controlan la absorción de agua y el consecuente hinchamiento del BW que contengan sales (NaNO3), y (ii) Investigar los posibles efectos de la concentración de fluidos de los poros sobre el hinchamiento, la compresibilidad y comportamiento de corte de la Boom Clay. En primer lugar, se ha desarrollado una formulación para el análisis de la deformación inducida por la disolución de sales en medio poroso con contacto con agua. Las ecuaciones planteadas incluyen los flujos acoplados de agua y soluto. Se presenta también un trabajo teórico que ayuda a la comprensión del comportamiento mecánico del BW. Se considera este material como una mezcla de bitumen y cristales de NaNO3. Se ha desarrollado un modelo elasto-viscoplástico que describe el comportamiento de fluencia del BW considerando el comportamiento de fluencia de sus constituyentes. El modelo constitutivo elasto-viscoplástico ha sido implementado en el programa CODE_BRIGHT. Los resultados se han comparado con observaciones experimentales. Se ha estudiado el comportamiento a largo plazo del BW en contacto con agua al simular ensayos de hinchamiento por absorción de agua bajo condiciones confinadas. El análisis numérico ha demostrado ser capaz de proporcionar una representación satisfactoria de los principales patrones observados en su comportamiento. En lo que respecta al segundo objetivo de la tesis, se ha propuesto una formulación para el análisis de las deformaciones inducidas por procesos osmóticos en un medio poroso de doble estructura. Esta formulación distingue dentro del material un nivel micro-estructural y otro macro-estructural con cambios químicos que tienen un efecto significativo en la micro-estructura. Se han obtenido las ecuaciones básicas que describen los flujos acoplados de agua y solutos y el transporte de sus componentes a través de los macroporos así como las ecuaciones de balance de masa para agua y soluto en los macroporos y microporos. La formulación propuesta ha sido aplicada particularmente para analizar cualitativamente el efecto de la succión osmótica sobre el hinchamiento de los suelos arcillosos. Se han analizado los efectos a corto y largo plazo. Se ha investigado también la influencia del aumento de la concentración del fluido en los poros sobre las propiedades geotécnicas y el comportamiento de la Boom Clay no saturada. Se ha llevado a cabo un programa sistemático de investigación experimental, con control de succión osmótica y matricial, con el fin de investigar el efecto del incremento de la concentración del fluido de poros sobre la resistencia de corte y el cambio volumétrico bajo condiciones edométricas. Se ha observado, que bajo condiciones parcialmente saturadas, un cambio en la salinidad provoca una disminución en la compresibilidad y en la resistencia de corte del material. / For deep storage of high-level nuclear waste osmotic flows can be significant and so require a careful analysis. In Belgium, The bituminized nuclear waste (BW) named Eurobitum contained in metallic drums will be placed inside a tunnel or a shaft excavated in the Boom Clay, which is 100 m thick marine clay presenting favourable properties to limit and delay the migration of the leached radionuclides over extended periods of time. In Geological disposal conditions, contact of the bituminized radioactive waste which contains high amounts of highly soluble salt (NaNO3) with groundwater will result in water uptake and swelling of the waste and in subsequent diffusion of the dissolved salt through the host clay formation. Basically, two types of disturbance can be distinguished: A geo-mechanical perturbation, caused by the swelling of the waste and the increase of the pressure in and around the waste and a physico-chemical perturbation by the release of large amounts of NaNO3 and other soluble salts. In this context the aim of this thesis is: (i) to improve the understanding of the processes controlling the water uptake and the subsequent swelling of bituminized waste containing soluble salts (NaNO3), and (ii) to investigate of the possible effects of the increase of pore fluid concentration on swelling, compressibility and shear behaviour of Boom Clay. A formulation has been proposed for the analysis of deformation induced by dissolution of salts in porous media in contact with water. The equations include the effect of coupled transport phenomena and the formulation has been included as an extension in the coupled THM program CODE_BRIGHT. A theoretical and experimental work aiming at understanding the mechanical behaviour of the Bituminized Waste has been presented.This material is considered for this purpose as a mixture of bitumen and crystals of NaNO3. An elasto-viscoplastic model has been developed that describes the creep behaviour of BW considering the constituents' creep behaviour. The elasto-viscoplastic constitutive model has been implemented into CODE_BRIGHT. The modelling results have been compared with the experimental data. The impact of osmotic forces on the swelling of the material has been investigated by simulating water uptake swelling tests under confined conditions and comparing the predictions with experimental results. The numerical analysis has proven to be able to furnish a satisfactory representation of the main observed patterns of the behaviour. In regard to the second objective of this thesis, a formulation has been proposed for the analysis of deformations induced by osmotic processes in double structure porous media. The formulation is based on the distinction within the material of a microstructural and a macrostructural levels with chemical changes having a significant effect on the microstructure. A macroscopic description of the system is provided. Then the basic equations describing coupled flows of water and solutes and the transport of its components through macropores and mass balance equations for water and solute in macro and micro pores have been obtained. The proposed formulation has been particularly applied to analyze qualitatively the effect of osmotic suction on swelling of clayey soils. Transient and long term effects have been analyzed. The influence of pore fluid concentration on the geotechnical properties and behavior of Boom Clay under partially saturated conditions has been investigated. A systematic experimental research program involving osmotic suction and matric suction controlled experiments has been carried to investigate the effect of the increase of pore fluid concentration on shear strength and on the volume change behaviour under odometer stress state conditions. It has been observed that under partially saturated conditions a change in salinity causes a decrease in compressibility and shear strength.

Il est généralement admis que la vision joue un rôle prépondérant dans la formation des représentations spatiales. Qu’advient-il alors lorsqu’un individu est atteint de cécité? Dans le premier volet de cette thèse, les habiletés spatiales des personnes aveugles ont été examinées à l’aide de différentes tâches et comparées à celles de personnes voyantes effectuant les mêmes tâches avec les yeux bandés. Dans une première étude, les capacités de rotation mentale ont été évaluées à l’aide d’une épreuve d’orientation topographique tactile. Les résultats obtenus montrent que les personnes aveugles parviennent généralement à développer des capacités de rotation mentale similaires à celles de personnes voyantes et ce, malgré l’absence d’information de nature visuelle. Dans une seconde étude, nous avons utilisé différentes tâches spatiales nécessitant l’utilisation de la locomotion. Les résultats obtenus montrent que les personnes aveugles font preuve d’habiletés supérieures à celles de voyants lorsqu’elles doivent apprendre de nouveaux trajets dans un labyrinthe. Elles parviennent également à mieux reconnaître une maquette représentant un environnement exploré précédemment. Ainsi, l’absence de vision ne semble pas entraver de manière significative la formation de concepts spatiaux. Le second volet de cette thèse s’inscrit dans la lignée des études sur la plasticité cérébrale chez les personnes aveugles. Dans le cas présent, nous nous sommes intéressés à l’hippocampe, une structure profonde du lobe temporal dont le rôle au plan spatial a été établi par de nombreuses études animales ainsi que par des études cliniques chez l’humain incluant l’imagerie cérébrale. L’hippocampe joue un rôle particulièrement important dans la navigation spatiale. De plus, des changements structuraux de l’hippocampe ont été documentés en relation avec l’expérience des individus. Par exemple, l’étude de Maguire et al. (2000) a mis en évidence de telles modifications structurelles de l’hippocampe chez des chauffeurs de taxi. À l’instar de ces derniers, les personnes aveugles doivent emmagasiner de nombreuses informations au sujet de leur environnement puisqu’elles ne peuvent bénéficier de la vision pour mettre à jour les informations sur celui-ci, sur leur position dans l’espace et sur la position des objets se trouvant hors de leur portée. Nous avons montré, pour la première fois, une augmentation du volume des hippocampes chez les personnes aveugles en comparaison avec les personnes voyantes. De plus, cette augmentation de volume était positivement corrélée à la performance à une tâche d’apprentissage de trajets. Les résultats présentés dans cette thèse permettent d’appuyer les études antérieures qui soutiennent que les personnes aveugles parviennent à compenser leur déficit et à développer des habiletés spatiales comparables, voire supérieures, à celles de personnes voyantes. Ils permettent également d’apporter un éclairage nouveau sur le concept de plasticité cérébrale présent chez cette population en montrant pour la première fois un lien entre le volume de l’hippocampe et les habiletés spatiales chez les personnes aveugles. / It is well known that the visual modality plays a key role in the development of spatial representations. Hence, one may wonder how complex spatial abilities develop and how the brain is able to adapt in the absence of this modality. In order to answer such questions we investigated the spatial abilities and cerebral plasticity of both early and late blind individuals in comparison to sighted blindfolded individuals. The first experiment was designed to assess mental rotation abilities. A tactile topographical orientation task was used. The results show that blind individuals are able to develop mental rotation abilities similar to those of sighted ones. In the second experiment, we used different spatial tasks requiring the use of locomotion and wayfinding. Results show that blind individuals are better than their sighted counterparts at learning new routes in a maze. They also perform better when having to recognize a small-scale model representing a real-size spatial layout they had previously explored. Thus, the absence of vision does not appear to significantly impede the formation of spatial concepts. The second part of this thesis is in line with studies on brain plasticity in blind individuals. We measured morphological changes in the hippocampus, a medial structure of the temporal lobe. Animal lesion-based and human brain imaging studies have shown that the hippocampus plays an important role in the processing of spatial information and in spatial navigation. Furthermore, structural changes in the hippocampus have been documented in relation to the ‘spatial’ experience of individuals. For instance, Maguire and colleagues (2000) have shown structural differences in the hippocampus of well-trained taxi drivers in comparison to individuals without extensive spatial training. Like taxi drivers, blind individuals require extensive storage of information regarding their environment. This is essentially because they cannot rely on visual cues to create a representation of the spatial organization of their environment, nor can they continuously visually update their position in space and the spatial coordinates of objects outside of their reach. Here we show for the first time an increase in the volume of the hippocampus in blind compared to sighted individuals. Moreover, this increase in hippocampal volume was positively correlated with performance on the route-learning task described above. Overall, the results not only support previous findings showing that blind individuals can develop spatial abilities similar or superior to those of sighted individuals, but also shed light on the concept of brain plasticity by showing for the fist time a correlation between hippocampal volume and spatial abilities in the blind.

Introduction Optimal nutrition is vital in the management of infants born preterm. Dietary fat in infancy is fundamental for the provision of energy for growth and development. Essential fatty acids, specifically Long Chain Polyunsaturated Fatty Acids (LC-PUFAs) such as docosahexaenoic acid (DHA), have been under investigation by several international research groups in the past decade. Essential fatty acids are critical in neurodevelopment as DHA is found in high proportions in structural lipids of cell membranes, particularly in the central nervous system (CNS). The accumulation of essential fatty acids and particularly DHA in the brain and retina occurs most rapidly during the perinatal period, therefore preterm infants are of particular concern (Singer, 2001). Current scientific consensus is that the optimum growth rate for preterm infants is equal to the in utero growth rate throughout the last trimester, however, failure to achieve the optimum intrauterine growth rate is common in preterm infants (Olhager and Forsum, 2003). Preterm infants require large amounts of energy and nutrients with which many infants are not provided or are not able to absorb, due to immature gastrointestinal and metabolic systems and other medical complications (Olhager and Forsum, 2003). There are a number of unresolved issues regarding optimal growth rate and total energy requirements (ER) for preterm infants. Hypotheses/Objectives This study is a “side study” to a double blind randomised controlled trial (RCT) of DHA supplementation in preterm infants. The hypothesis of this “side study” is that increased DHA during the neonatal period would increase total energy expenditure (TEE) and improve neurodevelopmental outcome. Specifically, at term postconceptual age (PCA) it was hypothesised that preterm infants receiving higher intake of DHA would have higher TEE’s due to the acceleration in brain maturation. Also, it was hypothesised that preterm infants receiving high levels of DHA would have TEE’s equivalent to term born infants due to their same brain maturation status. Other hypothesised effects of DHA supplementation include an accelerated maturation of the visual cortical pathways, and accelerated white matter (WM) tract development aiding in brain maturation. The first objective of this study was to measure TEE and ER in very preterm infants when they reached an age of 31-33 weeks post conceptional age (PCA). The effects of DHA supplementation on TEE, at simulated in utero levels, in very preterm infants (born < 33 weeks PCA), when assessed at term equivalent (40 weeks PCA) were studied. Another objective was to compare WM brain tissue volume at term PCA between two preterm groups and then with the term born infants. Visual latency was also compared between the two preterm infant groups and then with the term born infants. Methods TEE was measured using the doubly labelled water (DLW) method which is based on the differential elimination of 2H (deuterium) and 18O from the body subsequent to a loading dose of these isotopes. TEE was measured at the preterm age between 31-33 weeks PCA and again at term PCA. TEE measurements are made at term PCA in a term born control group. Brain assessment was by Magnetic Resonance Imaging and (MRI) and Visual Evoked Potential (VEP). Magnetic resonance imaging quantitatively measured brain volumes and WM. Visual evoked potential would provide information on visual latency and amplitude. Results The cohort consisted of 38 infants. The TEE of the very preterm infant group was measured at 31-33 weeks PCA. The mean (±standard deviation) (SD) TEE was calculated at 80(±27) kcal/kg/d, and using data in the literature for foetal energy accretion of 28kcal/kg/d, the mean ER was calculated to be 108(±27) kcal/kg/d. At term PCA TEE was calculated for the preterm DHA supplemented group to be 56(±19) kcal/kg/d and for the non-DHA supplemented group 70(±39) kcal/kg/d. These measurements were not statistically different. Flash VEP conducted on preterm given different amounts of DHA tested at term PCA found no statistically different measurements. When combining these results and comparing them to measurements of term born infants at term PCA, the right eye measurements showed that preterm infants had statistically greater latencies than term infants. When combining the left and right eye measurements the latencies no statistical significance was found. Amplitude was also not statistically significant between the groups. MRI measures at term PCA were not statistically different DHA supplemented and the non-DHA supplemented preterm infant group. When the preterm infant cohort was combined and compared to the term born infant group, the results showed that preterm infants imaged at term PCA had reduced WM development in a number of frontal lobe projections, and anterior and posterior commissarial pathways of the corpus callosum and corona radiata. Discussion The TEE and ER measurements in this study represent the largest preterm infant cohort to date. The ER values reported here are of value in allowing the calculation of appropriate feeding and nutritional strategies for preterm infants. Although no differences in TEE between the DHA and non DHA supplemented groups were found this may have been due to the small sample size. With regard to the latency outcomes, it can be speculated that if measurements were conducted at a later PCA the correlations may have been stronger and significant. Several other factors may have also affected the results, including alertness of the infant at the time of testing, thickness of the cranium, and other health factors could not be controlled for. This study contains the youngest cohort to be compared via Flash VEP. The MRI data did not find significant differences in brain volume and WM between the DHA supplemented and the non-DHA supplemented groups. The infant CNS is rapidly developing and there are multiple environmental factors which may have affected outcomes. The data did however find differences in WM development between the preterm and term infants. The reduced WM development found in the preterm infants compared to term born infants may provide some explanation for the correlation between preterm birth and poorer cognitive and functional outcomes. Larger studies which extend beyond the first months of life are recommended in order to investigate the long-term relationships between DHA supplementation, TEE and brain maturation.