Cette thèse approfondit l'étude de nanoparticules d'or de 5 nm de diamètre recouvertes de diamideéthanethioldiethylènetriaminepentacétate de gadolinium (DTDTPA:Gd), un agent de contraste pour l'imagerie par résonance magnétique (IRM). En guise de ciblage passif, la taille des nanoparticules a été contrôlée afin d'utiliser le réseau de néovaisseaux poreux et perméable des tumeurs. De plus les tumeurs ont un drainage lymphatique déficient qui permet aux nanoparticules de demeurer plus longtemps dans le milieu interstitiel de la tumeur. Les expériences ont été effectuées sur des souris Balb/c femelles portant des tumeurs MC7-L1. La concentration de nanoparticules a pu être mesurée à l'IRM in vivo . La concentration maximale se retrouvait à la fin de l'infusion de 10 min. La concentration s'élevait à 0.3 mM dans la tumeur et de 0.12 mM dans le muscle environnant. Les nanoparticules étaient éliminées avec une demi-vie de 22 min pour les tumeurs et de 20 min pour le muscle environnant. Les nanoparticules ont été fonctionnalisées avec le peptide Tat afin de leur conférer des propriétés de ciblage actif La rétention de ces nanoparticules a ainsi été augmentée de 1600 %, passant d'une demi-vie d'élimination de 22 min à 350 min. La survie des souris a été mesurée à l'aide de courbes Kaplan-Meier et d'un modèle mathématique évalue l'efficacité de traitements. Le modèle nous permet, à l'aide de la vitesse de croissance des tumeurs et de l'efficacité des traitements, de calculer la courbe de survie des spécimens. Un effet antagoniste a été observé au lieu de l'effet synergétique attendu entre une infusion de Au@DTDTPA:Gd et l'irradiation aux rayons X. L'absence d'effet synergétique a été attribuée à l'épaisseur du recouvrement de DTDTPA:Gd qui fait écran aux électrons produits par l'or. De plus, le moyen d'ancrage du recouvrement utilise des thiols qui peuvent s'avérer être des capteurs de radicaux. De plus, contrairement a ce qui était escompté, un effet chimiothérapeutique de ces nanoparticules a été observé in vitro et in vivo . Par contre, le mécanisme précis de cet effet est encore à être expliquer, mais on sait déjà que les nanoparticules d'or affectent les fonctions des macrophages ainsi que l'angiogenèse.

The hydro power industry stands for new challenges due to a more fluctuating production fromwind and solar power. This requires more regulation of the production in the hydro powerstations, which increases maintenance demands. An oil leakage has not only consequencessuch as downtimes and maintenance costs, but also an environmental impact. Skellefte ̊aKraft is working towards reaching a condition based maintenance. Therefore, the purpose ofthis master thesis is to develop a model using a feedforward neural network to predict the oillevel in the control system of a Kaplan turbine and map which sensor signals that are required.The thesis will cover data from two hydro power stations, Grytfors and B ̊atfors, each ofwhich has two units, G1 and G2. Due to limitations of the database Skellefte ̊a Kraft areusing, the data has minute resolution and covers two months, December and January. Themodel is developed in MATLAB using their Deep Learning toolbox and the neural networkfeedforwardnet. Before training and testing the model, an optimization was done. Grytforshas a full range of sensor signals while B ̊atfors has half the amount and therefore, the datafor Grytfors was used in the optimization. A grid search was done to optimize the hyperpa-rameters using cross validation. To map which input parameters that are required a featureselection was done.From the result of the feature selection, power, accumulator levels 1 and 2 and pressurewere chosen as the input parameters for Grytfors. For B ̊atfors, all of the the existing sensorsignals were used instead. The model is then trained and tested for the two different powerstations. For Grytfors, the predicted oil level follows the pattern of the real oil level but thetest error is around 15-20 liter. Four different tests were done for B ̊atfors. The two firstfor unit 1, the third for unit 2 and the fourth on both units to investigate the potential of ageneral model for one power station. For B ̊atfors, the first two tests have test errors of around4-6 liters. The third and fourth tests have test errors of around 1.5 liter. In the first twotests, the December data contains a potential refill sequence and in the third test, for unit2, the data contains start and stop sequences. The results showed the importance of havingcomprehensive training data.

Nous considérons des modèles de régression où la variable expliquée est censurée à droite aléatoirement. Nous proposons de nouveaux estimateurs de la fonction de régression dans des modèles paramétriques, et nous proposons une procédure de test non paramétrique d'adéquation à ces modèles. Nous prolongeons ces méthodes à l'étude du modèle semi-paramétrique "single-index", généralisant ainsi des techniques de réduction de dimension utilisées en l'absence de censure. Nous nous penchons tout d'abord sur le cas d'un modèle où la variable de censure est indépendante de la variable expliquée ainsi que des variables explicatives. Nous travaillons dans un second temps dans un cadre moins restrictif où la variable expliquée et la censure sont indépendantes conditionnellement aux variables explicatives. Une difficulté spécifique à ce dernier type de modèle tient en l'impossibilité des techniques actuelles à estimer une espérance conditionnelle (de façon paramétrique ou non) en présence de plus d'une<br />variable explicative. Nous développons une nouvelle approche de réduction de la dimension afin de résoudre ce problème.

<p>En av de mest debatterade politiska frågorna de senaste åren har varit den påstått kraftiga ökningen av antalet sjukskrivningar. Parallellt med sjukskrivningarna har även antalet förtidspensionärer ökat. En grupp som inte uppmärksammas lika ofta av varken politikerna eller medierna är de människor som både är sjukskrivna och arbetslösa, och det är den gruppen som vår uppsats kommer att kretsa kring. Syftet med denna uppsats är att utvärdera försäkringskassans och arbetsförmedlingens samverkan kring den gemensamma kundgruppen sjukskrivna arbetslösa. Denna samverkan har bedrivits i Uppsala län sedan september 2003. Närmare bestämt avser vi att besvara frågan om det går att påvisa en behandlingseffekt av den arbetslivsinriktade rehabilitering som ges inom ramen för samverkan? Den metod som vi använder oss av i uppsatsen för att testa samverkansprojektet är Kaplan-Meiers product-limit estimator. Material till undersökning kommer från den uppföljningsfil, i vilken försäkringskassans samverkanshandläggare regelbundet för in uppgifter om alla samverkansärenden. Vi kan med våran undersökning inte finna något stöd för att behandlingen har någon effekt för dem som deltar i samverkansprojektet. Begränsningar i materialet gör dock att vi inte vill dra några mer långtgående slutsatser angående effekten. Istället förespråkar vi att det görs ytterligare undersökningar av samverkan kring arbetslösa sjukskrivna.</p>

In this paper we propose two simple algorithms to estimate parameters £] and baseline survival function in Cox proportional hazard model with application to Massachusetts Health Care Panel Study (MHCPS) (Chappell, 1991) data which is a left truncated and interval censored data. We find that, in the estimation of £] and baseline survival function, Kaplan and Meier algorithm is uniformly better than the Empirical algorithm. Also, Kaplan and Meier algorithm is uniformly more powerful than the Empirical algorithm in testing whether two groups of survival functions are the same. We also define a distance measure D and compare the performance of these two algorithms through £] and D.

En av de mest debatterade politiska frågorna de senaste åren har varit den påstått kraftiga ökningen av antalet sjukskrivningar. Parallellt med sjukskrivningarna har även antalet förtidspensionärer ökat. En grupp som inte uppmärksammas lika ofta av varken politikerna eller medierna är de människor som både är sjukskrivna och arbetslösa, och det är den gruppen som vår uppsats kommer att kretsa kring. Syftet med denna uppsats är att utvärdera försäkringskassans och arbetsförmedlingens samverkan kring den gemensamma kundgruppen sjukskrivna arbetslösa. Denna samverkan har bedrivits i Uppsala län sedan september 2003. Närmare bestämt avser vi att besvara frågan om det går att påvisa en behandlingseffekt av den arbetslivsinriktade rehabilitering som ges inom ramen för samverkan? Den metod som vi använder oss av i uppsatsen för att testa samverkansprojektet är Kaplan-Meiers product-limit estimator. Material till undersökning kommer från den uppföljningsfil, i vilken försäkringskassans samverkanshandläggare regelbundet för in uppgifter om alla samverkansärenden. Vi kan med våran undersökning inte finna något stöd för att behandlingen har någon effekt för dem som deltar i samverkansprojektet. Begränsningar i materialet gör dock att vi inte vill dra några mer långtgående slutsatser angående effekten. Istället förespråkar vi att det görs ytterligare undersökningar av samverkan kring arbetslösa sjukskrivna.

SUMMARY The goal of the present thesis is to ascertain patients functional classes changes of various time after surgery, investigation of the other factors, which may stipulate recovery state (alive or die) and to estimate investigation of other factors, which may stipulate survival time. The investigation was carried out in two stages. During the first stage, the data was accumulated for processing (investigation of the pairwise independence of variables); the second stage implied solution of the statistical tasks (solution of the tasks, which correspond to the goals of the thesis). The methods of data analysis, the model of binary logistic regression, the descriptive methods for survival data and regression model for survival data were applied. 120 patients, who survived the mitral valve incompetence, were investigated and it was ascertained that functional class depends on difficulty of disease. The Sign‘s and Wilcoxon‘s tests assisted us in drawing the conclusion that statistical significance of surgery produce an impact upon the functional class to the 6‘th month and from 2‘th year to the 6‘th year. The model of the binary logistic regression assisted us in drawing the conclusion that functional class, acute disease and operation time produce an impact upon recovery state (alive or die).

A truncated sample consists of realizations of a pair of random variables (L, T) subject to the constraint that L ≤T. The major study interest with a truncated sample is to find the marginal distributions of L and T. Many studies have been done with the assumption that L and T are independent. We introduce a new way to specify a Cox model for a truncated sample, assuming that the truncation time is a predictor of T, and this causes the dependence between L and T. We develop an algorithm to obtain the adjusted risk sets and use the Kaplan-Meier estimator to estimate the Marginal distribution of L. We further extend our method to more practical situation, in which the Cox model includes other covariates associated with T. Simulation studies have been conducted to investigate the performances of the Cox model and the new estimators.

This thesis centers on nonparametric inferences of the cumulative hazard function of a right truncated variable. We present three variance estimators for the Nelson-Aalen estimator of the cumulative hazard function and conduct a simulation study to investigate their performances. A close match between the sampling standard deviation and the estimated standard error is observed when an estimated survival probability is not close to 1. However, the problem of poor tail performance exists due to the limitation of the proposed variance estimators. We further analyze an AIDS blood transfusion sample for which the disease latent time is right truncated. We compute three variance estimators, yielding three sets of confidence intervals. This work provides insights of two-sample tests for right truncated data in the future research.

BACKGROUND: Patient navigators have been shown to reduce cancer disparities among racial/ethnic minorities by improving timely diagnosis and treatment of cancer. We sought to determine if race/ethnicity and language concordance of patients and their navigator improved time to diagnostic resolution of breast and cervical cancer screening abnormalities. METHODS: Demographic data on patients and navigators from the Boston Patient Navigation Research Program were used to assess concordance by race, ethnicity, and language. Kaplan-Meier survival curves and Cox proportional hazards regression models examined the association of race/ethnicity and language concordance on time to definitive diagnosis of cancer screening abnormalities. All analyses were performed separately for breast and cervical groups. RESULTS: There were 1257 patients and 23 navigators in this study. In the breast group (n=655), 44% of patient-navigator pairs were concordant by race/ethnicity and 75% were language concordant. In the cervical group (n=602), 70% of patient-navigator pairs were race/ethnicity concordant and 87% were language concordant. There was no association with race/ethnicity concordance and time to diagnostic resolution for the breast group, aHR 1.19 (95% CI: 0.97, 1.46) or cervical group, aHR 1.23 (95% CI: 0.99, 1.53). However, in the stratified analysis, race/ethnicity concordance was associated with timelier resolution for minority women with breast and cervical cancer screening abnormalities but not for Whites. For cervical cancer screening abnormalities resolving in less than 90 days, language concordance was also associated with timelier resolution, aHR of 1.46 (95% CI: 1.18, 1.80) but there was no association in the breast group. In the subgroup analysis of Spanish concordance there was also an association of timelier resolution for those with cervical cancer screening abnormalities resolving in less than 90 days. CONCLUSION: Patient-navigator race/ethnicity concordance is associated with timelier diagnostic resolution of breast and cervical cancer screening abnormalities among minority women. Language concordance is also associated with timelier resolution in participants with cervical cancer screening abnormalities despite the availability and use of interpreters. Given poorer cancer outcomes among minority women, the use of patient navigators that are diverse by race/ethnicity and multilingual may help address barriers to care and improve health outcomes among low-income minorities.