Made available in DSpace on 2016-04-26T14:57:49Z (GMT). No. of bitstreams: 1 Leandro Alberto de Paiva Siqueira.pdf: 3521197 bytes, checksum: 69a587110b1ceae987343d261e25189e (MD5) Previous issue date: 2009-10-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Beginning in the 1990s, diverse habits, conducts, and daily-life behaviors, when practised in excess, in an uncontrolled or repetitive manner began to be biologized by psychiatry and progressively included in diagnostic manuals of mental disorders. Generically known by the term compulsions, these "new mental disorders" group together thoughts and desires that provoke discomfort, fear, and anxiety the activities whose engagement brings pleasure such as playing, eating, buying, doing physical exercise, working, sex, surfing the internet, using substances that alter perception, relationships, and religion. The emergency of compulsions as a new "epidemic" to be combatted against occurred at the same that psychiatry went through a reformulating process of its practices and knowledge thanks to new computo-informational technologies, the development of modern psychopharmaceuticals, and the incorporation of the contents regarding the mental and human behavior produced by the neurosciences. This research aims to trace a genealogy of compulsions in order to problematize dispositifs of power that operate subjects at the moment when disciplinary societies, analyzed by Michel Foucault, come to be overlapped by control societies, as pointed out by Gilles Deleuze. In this change, the asylum no longer is the principal economy of power in the formatation of subjectivities, in order to be substituted by technologies that operate in open air and result in normalizations of the normal. They are technologies that combine subjections and machinic servitudes, promoting processes of (in)dividuation, and take place on an environment by means of flows of mental health that convokes the policing of "disfunctions", the auto-vigilance of behaviors and conducts, and the formation of organized groupings of carriers of disorders. Understood as unfoldings of neoliberal governamentality, compulsions are configured as one more dispositif of an "era of moderation and moderates" and of the proliferation of the sensations of liberty / A partir dos anos 1990, diversos hábitos, condutas e comportamentos da vida cotidiana, quando praticados em excesso, de maneira descontrolada ou repetitiva passaram a ser biologizados pela psiquiatria e progressivamente incluídos em manuais de diagnósticos de transtornos mentais. Conhecidos genericamente pelo termo compulsões, estes novos transtornos mentais reúnem desde pensamentos e desejos que provocam desconforto, medo e ansiedade a atividades cujo engajamento traz prazer como jogar, comer, comprar, fazer exercícios físicos, trabalhar, sexo, navegar na Internet, usar substâncias que alterem a percepção, relacionamentos e religião. A emergência das compulsões como nova epidemia a ser combatida ocorreu simultaneamente à psiquiatria passar por um processo de reformulação de suas práticas e conhecimentos graças às novas tecnologias computoinformacionais, ao desenvolvimento de modernos psicofármacos e à incorporação de conteúdos sobre o mental e o comportamento humano produzidos pelas neurociências. Esta pesquisa visa traçar uma genealogia das compulsões a fim de problematizar dispositivos de poder que operam assujeitamentos no momento em que as sociedades disciplinares, analisadas por Michel Foucault, passam a ser sobrepostas pelas sociedades de controle, como apontou Gilles Deleuze. Neste deslocamento, o manicômio deixa de ser a principal economia de poder na formatação de subjetividades, para ser substituído por tecnologias que operam a céu aberto e procedem a normalizações do normal. São tecnologias que combinam sujeições e servidões maquínicas, promovendo processos de (in)dividuação, e incidem sobre o ambiente por meio de fluxos da saúde mental que convocam ao policiamento de disfunções , à autovigilância de comportamentos e condutas e à formação de agrupamentos organizados de portadores de transtornos. Entendidas como desdobramentos da governamentalidade neoliberal, as compulsões configuram-se como mais um dispositivo de uma era da moderação e dos moderados em meio à proliferação de sensações de liberdade

Les données expérimentales sur les propriétés thermodynamiques des mélanges entrant dans la composition des nouvelles générations de carburants sont rares ou entachées d’erreur. L’objectif de cette thèse est de contribuer à l’alimentation de base de données thermophysique de corps purs et de mélanges entrant dans la composition des carburants formés de biodiesel/diesel dans une large gamme de pression et de température (1 Pa à 200 kPa). Grâce à l’appareil statique disponible au laboratoire (UMR 5615) et aux différentes méthodologies mises au point pour la détermination des équilibres de phase, l’acquisition de données fiables a été obtenue pour 8 corps purs et leurs mélanges binaires. Les valeurs relatives aux pressions de vapeur des corps purs sont en bon accord avec la littérature dans le domaine des pressions moyennes. En revanche pour les faibles pressions de vapeur (inférieures à 1 kPa) et pour les mélanges binaires étudiés, les pressions de vapeur obtenues sont originales. Les deux modèles thermodynamiques NRTL et UNIQUAC ont restitué les résultats expérimentaux de façon satisfaisante.L’étude des propriétés volumétriques par la mesure de la densité, nous a permis d’interpréter les différentes interactions qui peuvent exister dans un mélange binaire constitué d’un ester et d’un alcane / Experimental data of thermodynamic properties of mixtures used in the composition of new fuel generations are very rare in the literature.The aim of this thesis is to contribute to setting up a thermophysical database of constituents used in the composition of biodiesel / diesel mixtures over a wide range of pressure and temperature (1 Pa to 200 kPa).Thanks to the static apparatus available in the laboratory (UMR 5615-Lyon1) and to the various methodologies developed to determine phase equilibrium, the acquisition of reliable data has been obtained for 8 pure substances and their binary mixtures. The vapor pressures of the pure compounds are in good agreement with the literature data in the range above 1 kPa whereas no data has been found to compare with experimental values of the pure compounds or mixtures below 1 kPa.A good correlation of the experimental results was obtained using two thermodynamic models, NRTL and UNIQUAC.The study of the volumetric properties obtained by densimetry, led us to interpret the different interactions that could exist in a binary mixture consisting of ester and alkane and to estimate quantitatively the different contributions to the excess molar volume

[pt] A empresa petrolífera estudada define a meta para o estoque total de petróleo utilizando inúmeros fatores, porém não considera em sua metodologia os custos despendidos no transporte marítimo. Durações de estadia acima do padrão geram custos adicionais substanciais no processo de movimentação de petróleo e o conhecimento dos fatores que afetam a estadia pode auxiliar na identificação das ações que devem ser tomadas para redução dos custos. Desta forma, com o propósito de contribuir para a redução dos custos de transporte marítimo, o objetivo do trabalho é verificar a dependência entre a estadia de navios em um grande terminal da empresa e outras variáveis da cadeia de suprimentos. Os dados históricos de estadia de navios, estoque, produção, refino, venda e compra de petróleo, nos anos de 2016 e 2017, foram obtidos dos sistemas internos da companhia, e foram avaliados estatisticamente. A regressão que melhor explicou a quantidade de navios aguardando atracação no terminal estudado conteve como variáveis independentes o estoque total da empresa, o refino, o estoque de petróleo dos terminais e refinarias atendidas pelo terminal estudado e o valor da quantidade de navios aguardando atracação no período anterior. Utilizando a equação do modelo selecionado, é constatado que elevações no estoque total de petróleo provocam um aumento no custo de estadia 11 porcento maior que o aumento do custo financeiro do estoque. Assim, com base nos resultados obtidos, esse trabalho propõe que o impacto do nível de estoque na estadia dos navios deve ser considerado no cálculo do estoque meta, o que trará ganhos de dezenas de milhões de dólares ao ano para a empresa estudada. / [en] The petroleum company studied sets the target for the total oil stock using many factors, but does not consider in its methodology the costs incurred in shipping. Length of stay above the standard will generate significant additional costs in the oil transportation. Knowledge of the factors that affect the stay can help identify the actions that must be taken to reduce costs. Thus, in order to contribute to the reduction of shipping costs, the objective of this work is to verify the dependence between the stay of ships in a large terminal of the company and other variables of the supply chain. The historical data on the duration of the ship stay, inventory, production, refining, sale and purchase of oil in the years 2016 and 2017 were obtained from the company s internal systems and were statistically evaluated. The regression that best explained the number of ships waiting berthing at the terminal studied contained as independent variables the company s total oil stock, the refining, the oil stock of the terminals and refineries served by the terminal studied and the number of ships waiting berthing in the previous period. Using the equation of the selected model, increases in the total oil inventory cause a 11 percent higher excess of stay cost than the increase in the financial cost of the stock. Thus, based on the results obtained, this work proposes that the impact of the inventory level on the ship s stay have to be considered in the calculation of the target stock, which will bring tens of millions of dollars a year earnings for the company studied.

För att kunna möta framtidens striktare reningskrav för avloppsvatten och en ökad belastning på grund av befolkningstillväxt bygger Stockholm Vatten och Avfall (SVOA) om Henriksdals reningsverk inom projektet Stockholms Framtida Avloppsvattenrening (SFA). En av de större förändringarna i det framtida Henriksdals reningsverk är införandet av MBR-teknik, där slam och vatten avskiljs genom membranfiltrering. Separationen medför förändrade egenskaper hos slammet då en större andel av partiklarna kan avskiljas från utgående vatten jämfört med avskiljning från konventionella sedimentationsbassänger. På Hammarby Sjöstadsverk drivs en pilotanläggning där MBR-teknik undersöks inför implementering i framtida Henriksdals reningsverk. Denna studie har undersökt skillnader i mängd partiklar, organiskt innehåll, filtrerbarhet, sedimenteringsegenskaper och förtjockningskapacitet hos överskottslam från MBR-linjen på Hammarby Sjöstadsverk (ÖS-MBR) och Henriksdals reningsverk (ÖS-CAS). Detta för att ge underlag till optimering av framtida slambehandling på Henriksdals reningsverk. Därutöver har massbalans för förtjockningsförsöken beräknats. Resultatet av studien visar att egenskaperna hos ÖS-MBR och ÖS-CAS skiljer sig tydligt för torrsubstans (TS), totalt suspenderade partiklar (TSS) och filtrerbarhet (TTF). Ingen skillnad i slamvolymindex (SVI) kunde verifieras i studien. Efter förtjockning av slammen i en trumsil, med olika polymertillsats, uppvisade ÖS-MBR högre TSS i rejektvattnet än ÖS-CAS. Denna skillnad indikerar att partiklar i ÖS-MBR har mindre benägenhet att binda till polymeren som användes, än partiklar i ÖS-CAS. Det är därför av betydelse att pröva ut rätt typ av polymer vid förtjockning av ÖS-MBR, för att nå målet på en TSS under 1000 mg/L i rejektvattnet. Därtill uppvisade ÖS-MBR högre TS i det förtjockade slammet än ÖS-CAS. Detta skulle kunna indikera att ÖS-MBR är lättare att förtjocka än ÖSCAS, men det kunde dock inte bekräftas av massbalanserna. Slutligen kunde denna studie inte samstämmigt visa på en skillnad i potentialen att förtjocka de båda slammen då fördelningen av partiklar mellan förtjockat slam och rejektvatten varierade i varje försök. Däremot minskade TSS i rejektvattnet med högre dos av polymer medan samma samband inte gällde för TS i det förtjockade slammet där dosen polymer, efter en viss mängd, hade en begränsad påverkan på TS. En viktig aspekt som påverkade förtjockningskapaciteten i denna studie var igensättning av trumsilen. Centrifuger, som kommer att användas i framtida Henriksdals reningsverk, kommer inte uppvisa samma typ av störningar i driften. / To comply with future stricter regulations on treated wastewater and an increasing load on the system due to a growing population, the Stockholm Vatten och Avfall Company (SVOA) is upgrading the Henriksdal wastewater treatment plant within the project Stockholm’s Future Wastewater Treatment (SFA). One of the main changes in the future plant is the introduction of MBR-treatment, where sludge and water will be separated through the use of membranes. This separation will change the composition of the sludge by removing a larger fraction of particles from the effluent than what can be achieved in conventional sedimentation basins. Hammarby Sjöstadsverk operates a pilot plant with a MBR-process, where the technology is evaluated before the implementation in the future Henriksdal wastewater treatment plant. This study examines the difference in the sludge characteristics, i.e. sedimentation, filterability, and the potential for thickening of excess sludge from the MBR-process in Hammarby Sjöstadsverk (ÖS-MBR) and from the activated sludge process in the current Henriksdal wastewater treatment plant (ÖS-CAS). Furthermore, a mass balance and a sensitivity analysis has been used within this study. The study aimed at providing decision support for optimisation of the sludge treatment at the future Henriksdal wastewater treatment plant once the MBR process is implemented. The results of this study show that the characteristics of ÖS-MBR and ÖS-CAS differ considerably in total solids (TS), total suspended solids (TSS) and filterability (TTF). No difference in sludge volume index (SVI) could be verified between the two types of sludges. After thickening in a rotary drum screen with different doses of polymer, the TSS in the reject water was higher for the ÖS-MBR than the ÖS-CAS. This difference indicates that particles in ÖS-MBR are less attracted to the particular thickening polymer used, than the particles in ÖS-CAS. Therefore, it is important to select the correct type of polymer when thickening ÖS-MBR in order to reach the target TSS of 1000 mg/L in the reject water. In addition, the thickened ÖS-MBR showed higher TS than ÖS-CAS. This could indicate that ÖS-MBR would be easier to thicken; however, this is not confirmed by the mass balances. In the end, this study could not conclusively show any trend in the level of thickening between the two types of sludges because the distribution of particles varied in each trial. Nevertheless, while a higher dosage of polymer evidently reduced the TSS in the reject water, the same was not true for the TS in the thickened sludge, which seems to be less affected by the dose of polymer after a certain level. An important consideration in this study was the clogging of the drum screen. However, centrifuges, which will be used in the future Henriksdal wastewater treatment plant, do not have the same operational problems.

This thesis examines demographic manifestations of son preference in three parts. Part I develops a simulation model that formalises the decision to practice prenatal sex selection through a "ready, willing and able" framework. The model is calibrated to South Korean and Indian sex ratio at birth (SRB) trajectories. Simulations reveal how SRB distortions in both countries have emerged despite declining son preference due to the rapid diusion of ultrasound combined with growing propensities to abort as a result of weakening norms for large families. Part II examines the potential role of big data to indirectly estimate the SRB at the subnational level in India. States with distorted SRBs tend to display a relatively high Google search activity for ultrasound. SRB "now-casts" generated using search volumes perform better than lagged variable models in high birth registration states. Part III examines the relationship between prenatal sex selection and postnatal excess female child mortality in two studies. The first applies lifetable techniques to decompose population changes in child sex ratios into a fertility component attributable to prenatal sex selection and a mortality component attributable to sex-differentials in postnatal survival. This study finds that although reductions in numbers of excess female deaths have accompanied increases in "missing" female births in all countries experiencing SRB distortions, excess female mortality has persisted in some but not in others. The second study uses birth histories of the Demographic and Health Surveys for six countries that have witnessed SRB distortions - India, Nepal, Pakistan, Azerbaijan, Armenia and Albania - to examine if differential mortality change by sex can be explained by the uptake of prenatal sex selection. This study finds that changes in prenatal sex selection only explain mortality change in India. Across all countries, although patterns of mortality disadvantage are concentrated amongst less educated mothers, prenatal sex selection is strongest among the better educated. Differential sorting into the two behaviours offers an explanation for why the effect for prenatal sex selection is generally weak.

Hypertension is the chronic elevation in blood pressure that is regulated in part through the retention and regulation of sodium retention and excretion in the kidneys. Hence the kidney has been considered the organ that regulates blood pressure. There are a cohort of patients that suffer with high blood pressure due to lack of 11β-hydroxysteroid dehydrogenase-type 2 (11β-HSD2) expression (which inactivates glucocorticoids (GCs), allowing selective activation of mineralocorticoid receptors (MR) by aldosterone) that results in hypertensive and increased salt appetite phenotypes - a condition known as syndrome of apparent mineralocorticoid excess (SAME). This disorder can be recapitulated in the mouse through the global deletion of 11β-HSD2, which results in over activation of the MR driving an elevation in blood pressure. However, the distinction between blood pressure elevation because of kidney dysfunction with loss of 11β-HSD2 or increased salt appetite due to loss of brain 11β-HSD2 expression is not clear from the global 11β-HSD2 knockout model. Salt appetite is regulated by regions of the brain out-with the blood-brain barrier, known as circumventricular organs. In the mouse, salt appetite is controlled by aldosterone-sensitive cells in the nucleus of the solitary tract (NTS) in the brain stem, where 11β-HSD2 is expressed to provide mineralocorticoid selectivity. However, in the fetal brain, 11β-HSD2 is widely expressed, protecting against adverse GC action that alters brain development and increases susceptibility to psychiatric disorders as adults. 11β-HSD2 deletion solely in the brain from embryonic day 12 resulting in GC fetal programming (HSD2BKO) causes effects on both behaviour and salt appetite. To determine the role of developmental versus adult expression of brain 11β- HSD2, mice with deletion of brain 11β-HSD2 from mid gestation (HSD2BKO) and mice with adult deletion of 11β-HSD2 in the NTS using lentivirus (HSD2.v- BKD) were compared. The phenotypes (salt appetite, blood pressure (BP), baroreceptor response (BRR) and cognition), can be categorised as either due to GC fetal programming (as indicated by HSD2BKO groups), or increased activation of MR in adult 11β-HSD2 expressing neurons (recapitulated in the HSD2.v-Cre groups). Salt appetite increased in both HSD2BKO and HSD2.v-BKD cohorts (mean percentage increase 65% n=8 and 46% n=6, compared to their respective controls), leading to an increased BP in both groups (+12% and +8%, respectively) as well as an impaired BRR, indicating all phenotypes are mediated by adult NTS neurons. However, spatial recognition memory (Object-in-Place task) is abolished in HSD2BKO mice, whereas, HSD2.v-BKD mice still retain short-term memory. Our data suggest that neural 11β-HSD2 protects against inappropriate activation of MR by corticosterone to regulate salt appetite and salt-induced rises in blood pressure. However, spatial recognition memory is not influenced by deletion of 11β-HSD2 in the adult brain, confirmation that this phenotype is underpinned by developmental programming by GCs, which is observed in the 11β-HSD2 brain KO. Salt appetite has been shown to be centrally regulated through the adult deletion of 11β-HSD2. From this, our data suggest that an increased salt appetite is due to adult loss of function of 11β-HSD2 rather than GC programming during development. Highlighting the NTS as a region for drug delivery to try and control salt appetite in salt sensitive individuals who struggle with administering a recommended change in diet. To develop this further, minimally invasive modes of delivery of viruses and drugs into the brain were investigated. In so doing, a non-invasive and reversible method to temporarily disrupt the blood brain barrier (BBB) was optimised. The technique required acoustic insonation of ultrasonic contrast agents (CAs) (gas microbubbles) adjacent to the BBB. These microbubbles (SonoVueTM, Bracco) were delivered via tail vein injection into the vasculature. To target the BBB, an ultrasonic transducer was suspended and focused through coupling gel onto the area of interest in the brain with skull the intact. The optimisation of this technique required determination of the focal position of the 3.5MHz transducer that was utilised, in addition to optimisation of the pulse length, pulse repetition frequency and power output of the ultrasound beam to enable the BBB to be disrupted. In addition, measurement of the attenuation of the ultrasound beam through ex vivo mouse skulls were measured. These results showed a 50% reduction in pressure amplitude from the baseline of 335.2mV (Baseline mean = 100% +/-SEM 0 n=3 (No skull), five regions across the skull averaged 47.79% +/-SEM 1.913 n=25 (using 5 different animals). In in vivo mice, after co-injection of the microbubbles with Evans Blue and insonation of the brain, disruption of the BBB was confirmed by the presence of Evans Blue dye in the brain, with no measurable damage occurring in the brain. This was confirmed by cell and nuclear morphology with no red blood cell extravasation into the surrounding tissue. The parameters used to open the BBB used a peak negative pressure of 2.1MPa (single pulse), transducer frequency 3.5MHz, 35,000 cycles over a 10ms burst at a pulse repetition frequency of 10Hz. The technique when applied in vivo in recovery animals is speculated to work by the focused ultrasound causing the microbubbles to oscillate within the vasculature adjacent to the BBB, resulting in high-shear stresses being generated on the tight junctions within the BBB. The resultant gaps in the BBB allow free circulating compounds (e.g. large dye molecules (Evans Blue - 960.8g/mol molecular weight) and adeno-associated-viruses (25nm with a packing capacity of 4.5kb) within the blood to pass into the brain, but there is no penetration of red blood cells (7μm). Longitudinal mouse experiments demonstrated that within 12-hours these gaps close with no long-term damage observed. Currently, utilising this technique, successful passage of an adeno-associated virus expressing GFP (as a marker) has been shown to pass into the brain (n=6 for each cohort including control) - indicating that the virus requires the ultrasound and microbubbles to facilitate its movement into the brain. Further technique optimisation is being explored looking at the role of CAs used in the opening and disruption of the BBB, comparing composition and size of the CAs. Microbubbles (2-3μm) and nanobubbles (200nm) were compared as well as lipid and non-ionic surfactant surface compositions, using volume of drug delivery and degree of disruption as outputs. Using this technique, the hydrophilic drug mimic calcein was delivered into the brain (n=5 non-ionic surfactant nanobubble, n=5 lipid nanobubble). Results have indicated that the delivery of calcein is most efficient when using non-ionic surfactant nanobubbles as opposed to lipid nanobubbles - with a greater volume of the drug being delivered into the cerebral tissue. Furthermore, the concentration and surface composition of the nanobubble have an effect as to the size and potential damage to the brain when opening the BBB. In conclusion, it has been shown that it is possible to non-invasively open the BBB and deliver viruses and dye into the brain. In addition, this thesis has investigated the use of nanobubbles as both facilitators to opening the BBB and delivery vectors for potentially therapeutic drugs. Finally, a non-invasive opening of the BBB has been achieved using focused ultrasound. Ultimately this non-invasive opening of the BBB can be used to achieve delivery of larger molecules (such as antibodies and viruses) into the brain to target treatments. Focused ultrasound brain targeting can be applied to the potential treatment of salt appetite regulation in the NTS. For the individuals who suffer from salt sensitive hypertension, the NTS can be targeted to reduce the drive to ingest high salt diets. Furthermore, the continuation of research into the central control of BP, salt appetite and baroreceptor reflex control can become better understood, using less invasive delivery techniques to the brain.

L’étude du temps de survenue d’un événement représente un champ très important des statistiques. Lorsque l’événement étudié est le décès, on cherche à décrire la survie des individus ainsi que leur taux de mortalité, c’est-à-dire la « force de mortalité » qui s’applique à un instant donné. Les patients atteints d’une maladie chronique présentent en général un excès de mortalité par rapport à une population ne présentant pas la maladie en question. En épidémiologie, l’étude du taux de mortalité en excès des patients, et notamment de l’impact des facteurs pronostiques sur celui-ci, représente donc un enjeu majeur de santé publique. D’un point de vue statistique, la modélisation du taux de mortalité (en excès) implique de prendre en compte les effets potentiellement non-linéaires et dépendants du temps des facteurs pronostiques ainsi que les interactions. Les splines de régression, polynômes par morceaux paramétriques et flexibles, sont des outils particulièrement bien adaptés pour modéliser des effets d’une telle complexité. Toutefois, la flexibilité des splines de régression comporte un risque de sur-ajustement. Pour éviter ce risque, les splines de régression pénalisées ont été proposées dans le cadre des modèles additifs généralisés. Leur principe est le suivant : à chaque spline peuvent être associés un ou plusieurs termes de pénalité contrôlés par des paramètres de lissage. Les paramètres de lissage représentent les degrés de pénalisation souhaités. En pratique, ils sont inconnus et doivent être estimés tout comme les paramètres de régression. Dans le cadre de cette thèse, nous avons développé une méthode permettant de modéliser le taux de mortalité (en excès) à l’aide de splines de régression multidimensionnelles pénalisées. Des splines cubiques restreintes ont été utilisées comme splines unidimensionnelles ou bien comme bases marginales afin de former des splines multidimensionnelles par produits tensoriels. Le processus d’optimisation s’appuie sur deux algorithmes de Newton-Raphson emboîtés. L’estimation des paramètres de lissage est effectuée en optimisant un critère de validation croisée ou bien la vraisemblance marginale des paramètres de lissage par un algorithme de Newton-Raphson dit externe. A paramètres de lissage fixés, les paramètres de régression sont estimés par maximisation de la vraisemblance pénalisée par un algorithme de Newton-Raphson dit interne.Les bonnes propriétés de cette approche en termes de performances statistiques et de stabilité numérique ont ensuite été démontrées par simulation. La méthode a ensuite été implémentée au sein du package R survPen. Enfin, la méthode a été appliquée sur des données réelles afin de répondre aux deux questions épidémiologiques suivantes : l’impact de la défavorisation sociale sur la mortalité en excès des patients atteints d’un cancer du col de l’utérus et l’impact de l’âge courant sur la mortalité en excès des patients atteints de sclérose en plaques / Time-to-event analysis is a very important field in statistics. When the event under study is death, the analysis focuses on the probability of survival of the subjects as well as on their mortality hazard, that is, on the "force of mortality" that applies at any given moment. Patients with a chronic disease usually have an excess mortality compared to a population that does not have the disease. Studying the excess mortality hazard associated with a disease and investigating the impact of prognostic factors on this hazard are important public health issues in epidemiology. From a statistical point of view, modelling the (excess) mortality hazard involves taking into account potentially non-linear and time-dependent effects of prognostic factors as well as their interactions. Regression splines (i.e., parametric and flexible piecewise polynomials) are ideal for dealing with such a complexity. They make it possible to build easily nonlinear effects and, regarding interactions between continuous variables, make it easy to form a multidimensional spline from two or more marginal one-dimensional splines. However, the flexibility of regression splines presents a risk of overfitting. To avoid this risk, penalized regression splines have been proposed as part of generalized additive models. Their principle is to associate each spline with one or more penalty terms controlled by smoothing parameters. The smoothing parameters represent the desired degrees of penalization. In practice, these parameters are unknown and have to be estimated just like the regression parameters. This thesis describes the development of a method to model the (excess) hazard using multidimensional penalized regression splines. Restricted cubic splines were used as one-dimensional splines or marginal bases to form multidimensional splines by tensor products. The optimization process relies on two nested Newton-Raphson algorithms. Smoothing parameter estimation is performed by optimizing a cross-validation criterion or the marginal likelihood of the smoothing parameters with an outer Newton-Raphson algorithm. At fixed smoothing parameters, the regression parameters are estimated by maximizing the penalized likelihood by an inner Newton-Raphson algorithm.The good properties of this approach in terms of statistical performance and numerical stability were then demonstrated through simulation. The described method was then implemented within the R package survPen. Finally, the method was applied to real data to investigate two epidemiological issues: the impact of social deprivation on the excess mortality in cervical cancer patients and the impact of the current age on the excess mortality in multiple sclerosis patients

La survie nette est un indicateur incontournable pour juger du control du cancer. Par définition, elle correspond à la survie que l’on observerait dans un monde hypothétique où le cancer étudié serait la seule cause possible de décès. L’objectif principal de cette thèse était de montrer l’intérêt de cet indicateur dans le cadre de la recherche clinique en prenant en compte quelques défis méthodologiques qui peuvent être rencontrés dans ce contexte. Nous avons présenté d’abord le concept de survie nette et ses méthodes d’estimation. Par la suite nous nous sommes intéressés à quelques problématiques rencontrées dans les essais cliniques à long terme lorsque l’on s’intéresse à l’estimation de la survie nette. Nous avons étudié également l’impact de l’utilisation de l’approche classique d’estimation de la survie nette dans les essais cliniques, i.e. la méthode cause-spécifique dans différentes configurations d’erreurs de classifications de la cause de décès. La deuxième problématique de cette thèse a porté sur la prise en compte du biais de sélection en termes de mortalité autres causes des patients. Nous avons proposé un modèle de mortalité en excès prenant en compte ce type de biais de sélection. Une troisième problématique qui est complémentaire à la deuxième est de prendre en compte inter-centres en même temps que le biais de sélection. Ce travail propose ainsi de nouveaux outils pouvant aider les spécialistes de la recherche clinique à évaluer de nouvelles stratégies thérapeutiques dans les essais cliniques en cancérologie, mais aussi dans d’autres domaines cliniques d’applications. / Net survival is a key indicator for measuring cancer control. By definition, it corresponds to the survival that would be observed in a hypothetical world where the cancer studied is the only possible cause of death. The main objective of this thesis was to show the interest of this indicator in the context of clinical research taking into account some methodological challenges that can be encountered. In this work, we have first presented the concept of net survival and its estimation methods. Subsequently, we were interested in some of the problems encountered in long-term clinical trials when the interest is in estimating net survival. We studied the impact of using the classic approach when estimating net survival in clinical trials, i.e. the cause-specific method in different configurations of misclassifications of the cause of death. The second objective of this thesis was to take into account the selection bias in terms of other causes mortality in the modeling of excess mortality, because of the noncomparability between patients from general population and those of clinical trials. We proposed an excess hazard model that corrects this type of selection bias. A third problem which is complementary to the second is to take into account the heterogeneity of patients in the different recruitment centers at the same time as the selection bias. This work proposes new tools which can help clinical research specialists to evaluate new therapeutic strategies in cancer clinical trials, but also in other areas of clinical application.

Inland salt lakes in Western Australia have been used by the mining industry for the disposal of excess water generated during the mining process. However, the impact of these operations on the salt lakes is poorly understood. This is mainly due to the lack of information on the biota and chemistry for the lakes. The main aim of this project was to develop a classification system for inland salt lakes of Western Australia based on abiotic and biotic factors such as sediment and water quality, invertebrates and algae to determine lakes with unique or significant features. Water and sediments collected from the salt lakes were generally characterised by an alkaline pH, high salinity and the majority of lakes being dominated by sodium and chloride. Concentrations of some metals were also high, particularly in surface water. A high degree of variation in water and sediment quality was demonstrated both within and between the study lakes. In addition, these parameters were shown to be influenced by geography, geology, stage of the hydrocycle within which the lake was sampled and the occurrence of dewatering discharge. Biota in the salt lakes must be able to cope in a harsh environment, adjusting to temporary water regime, high temperature, and high salinity. As such, the species richness of these systems is generally low. Diatoms (a group of algae) and invertebrates were investigated among the biota. A total of 56 diatom species were recorded from 24 lakes. The most common species were Amphora coffeaeformis, Hantzschia aff. baltica and Navicula aff. incertata. These species were shown to have broad tolerances to environmental variations. Sediment chemistry explained variations in diatom community structure, with zinc, moisture content and cobalt having the greatest and negative influence. / In terms of invertebrates, a total of 101 invertebrate taxa were recorded from 13 lakes in this study. Crustacea dominated and the greatest number of taxa was from the genus Parartemia. There were some differences in invertebrate community structure between lakes, most likely reflecting the high degree of speciation, and poor dispersal mechanisms of certain key species. Community structure was influenced by water quality, with phosphorus, bicarbonate and magnesium contributing to the variations in community structure. Among the 43 lakes chosen for this study a total of 17 lakes had received, or are currently receiving dewatering discharge. Sites receiving dewatering discharge generally reported higher concentrations of salts, nutrients and some metals in both water and sediments compared to natural lakes. Species richness of biota such as diatoms and invertebrates was lower at the lakes receiving dewatering discharge. However, the impact was generally localized within the pooled area of dewatering discharge. Also, despite these impacts, there appears to be signs of amelioration by flushing events. Currently there are no guidelines for water and sediment chemistry for inland salt lakes in Western Australia. Australian and New Zealand Environment and Conservation Council (ANZECC) guidelines are the most relevant available. Concentrations of cadmium, cobalt, chromium, copper, lead, nickel and zinc in surface water of the natural inland salt lakes were shown to exceed ANZECC guideline values. / Comparison with the relevant ANZECC sediment guidelines showed that they were applicable to the salt lakes, with the exception of nickel and chromium which were naturally high in the salt lake sediments. Classification of data using multivariate analysis was done for both dry and wet phases of the hydroperiod. Six groups were delineated for the sediment and diatom data, and four groups were defined for the water quality and invertebrate data. It was common for sites from particular lakes to fall in more than one group as a result of the variability in these systems. There are a number of practical applications of this system for the mining industry and it may be used as a predictive tool for determining the impact of dewatering discharge and highlighting unique salt lakes within the Goldfields of Western Australia.

<p><strong>Syfte:</strong> År 2005 infördes en ny lag, att företagen som gjorde avsättningar till periodiseringsfonder var tvungna att beskatta en schablonintäkt som erhölls från de gjorda avsättningarna. Problemet som uppsatsen berör är huruvida användandet av överavskrivningar hade förändrats efter att lagen tillkom för periodiseringsfonder jämfört med tidigare. Dessutom fokuserades det också på vilka konsekvenser obeskattade reserver har fått före och efter att lagen trädde i kraft. Syftet med examensarbetet är att kartlägga hur företagens vanor kring avskrivningar över plan förändrades efter införandet av schablonintäkten på periodiseringsfonder, och om överavskrivningar kan anses som ett substitut till periodiseringsfonder istället för ett komplement.</p><p> </p><p><strong>Metod: </strong>En undersökning gjordes på företagen som är listade på börslistan ”large cap”. De åren som undersökningen omfattade var åren 2003, 2004, 2005 och 2006. Företagen som användes var redan förutbestämda, varför urvalet blev ett subjektivt urval. Anledningen till det var för att undersökningen ämnade skapa en stor insikt i Sveriges ledande börsföretags resultatplanering. De data som insamlades hämtades från företagens årsredovisningar, och data sammanställdes i tabeller och diagram.</p><p> </p><p><strong>Resultat & slutsats: </strong>Resultatet för undersökningen visade på att företagen hade ett lågt användande av resultatjusteringar redan under år 2003, och det fortsatte att avta allt eftersom åren gick, emellertid fanns en tendens att företagen ökade sitt användande under år 2006.</p><p>Periodiseringsfonder var mer vanliga att använda för alla år förutom år 2005. Med detta som underlag blev slutsatsen att överavskrivningar inte är ett substitut till periodiseringsfonder. Vidare tycks företagen inse att det är billigare för dem att inte använda sig av obeskattade reserver, och betala skatten direkt, eftersom färre gjorde avsättningar.</p><p> </p><p><strong>Förslag till fortsattforskning:</strong> I uppsatsen koncentrerades urvalet till att enbart omfatta Sveriges 60 största börsnoterade företag, och forskningen bör utvidgas till att omfatta ett mer representativt urval i Sveriges företagsklimat. Anledningen till det är för att kunna erhålla en statistisk säkerställning kring användandet av obeskattade reserver.</p><p> </p><p><strong>Uppsatsens bidrag: </strong>Uppsatsen har skapat en större förståelse kring obeskattade reserver och i vilken omfattning de används bland företagens som tenderar att bestämma praxis. Vidare har också djupare kunskap erhållits kring vilken av de två bokslutsdispositionerna som är mest användbar, samt skatters påverkan på företagens valmöjligheter.</p> / <p><strong>Aim:</strong>  By the year 2005 a new law was introduced, the companies was now being charged with an interest income on the tax allocation reserve. The problem this thesis is based on is how the usage of excess depreciation had changed pre and post the new law was established because this tool do not have a fee for its usage. Additionally this thesis also focused on what consequences this law have had on the general usage of untaxed reserves. The purpose with the thesis is to get an understanding if the usage of excess depreciation changed after the tax allocation reserves was being taxed and if excess depreciation can be a substitute to tax allocation reserve instead of being a complement to it.</p><p> </p><p><strong>Method:</strong> A survey was performed, with the companies listed on the Stockholm stock exchange's large cap as the only objects in the survey. The sample of the survey was pre-decided; hence the sample of the survey was subjective, but also because the survey intended to create an insight in the income planning of the leading enterprises of the stock exchange in Stockholm. The years included in the survey were 2003, 2004, 2005 and 2006 and the data, foundation to the survey, was gathered from the companies' annual reports. </p><p> </p><p><strong>Result & Conclusions: </strong>The result of the survey showed that the companies had a low usage of appropriations, already back in 2003, which continued to decrease as the years went by however in the year 2006 a tendency was that the companies had increased their usage of untaxed reserves. Tax allocation reserves were more frequently used in all the years except in the year 2005. With regard to this information following conclusions could be made: excess depreciation could not be seen as a substitute to the tax allocation reserve. Moreover, a decrease in the usage of untaxed reserves could also be seen, as the companies realised that it would be cheaper for them not using them.<strong></strong></p><p> </p><p><strong>Suggestions for future research: </strong>The survey was narrowed to just include the sixty largest companies traded on the Stockholm exchange; hence the research should be extended to include a more representative sample of all the companies in Sweden. The reason is to find out if the usage in appropriations has changed to the degrees of being statistically significant.</p><p><strong> </strong></p><p><strong>Contribution of the thesis: </strong>The thesis has produced a greater understanding about appropriations and to what degree the companies who set praxis are using them. Furthermore, a comprehension about which of the two appropriations that is the most useful has been received, and also how much taxes influence the choices made by companies.</p>