Global ETD Search

41	Analyse statistique de l’impact des mutations génotypiques du VIH-1 sur la réponse virologique au traitement antirétroviral / Statistical analysis of the impact of HIV-1 genotypic mutations on virological response to antiretroviral therapy Wittkop, Linda 01 December 2010 (has links) Les mutations de résistance génotypiques constituent un problème majeur pour l’optimisation du traitement antirétroviral chez les patients infectés par le VIH-1 naïfs au traitement ou prétraités. Cependant, l’analyse de l’impact des mutations sur la réponse au traitement est compliquée par i) le nombre élevé de mutations, ii) la colinéarité possible entre ces mutations, iii) le faible nombre de patients inclus dans les études et iv) la définition du critère de jugement. Les objectifs de cette thèse sont 1) de donner une vue d’ensemble et de discuter, en collaboration avec le réseau européen NEAT (European AIDS treatment network), les critères de jugement utilisés dans les essais cliniques récents et ceux utilisés lors de l’analyse des mutations de résistance, 2) d’évaluer l’impact des mutations génotypiques sur la réponse au traitement chez les patients naïfs dans le cadre d’une grande collaboration Européenne (EuroCoord-CHAIN) et 3) de comparer des méthodes adaptées pour les données à haute-dimension dans le but de construire un score génotypique pour la prédiction de la réponse virologique chez les patients prétraités. Les critères de jugement composites sont les plus utilisés dans les essais cliniques récents mais un critère purement virologique devrait être utilisé pour l’analyse de l’impact des mutations génotypiques. Les mutations de résistance transmises impactent sur la réponse à la première ligne de traitement si le traitement antirétroviral n’est pas adapté au génotype du virus du patient. L’analyse en composantes principales et l’analyse partial least square avaient une bonne capacité à prédire la réponse virologique mais n'étaient guère meilleures que le score génotypique. Nous allons continuer à travailler sur la comparaison de ces méthodes utilisant des critères de jugement différents dans le cadre de notre collaboration avec le Forum for collaborative HIV research. / Genotypic resistance mutations are a major concern for antiretroviral treatment optimisation in HIV-1 infected treatment naïve and treatment experienced patients. However, the analysis of the impact of genotypic mutations on treatment outcome is hampered by methodological issues such as the i) high number of possible mutations, ii) the potential collinearity between mutations, iii) the low number of patients included in those studies and iv) the definition of a virological endpoint. The objective of this thesis are 1) to give an overview and to discuss endpoints used in recent clinical trials in collaboration with European AIDS treatment network (NEAT) and those used in the context of drug resistance analysis, 2) to investigate the impact of genotypic resistance mutations on treatment outcome in treatment naïve patients in a huge European collaboration EuroCoord-CHAIN and 3) to compare methods adapted for high-dimensional data in order to construct a genotypic score to predict treatment outcome in treatment experienced patients. We saw that most of the endpoints used in recent clinical trials are composite endpoints but pure virological outcomes should be used for the evaluation of drug resistance mutations. Transmitted drug resistance mutations impact on virological outcome of initial antiretroviral therapy if the treatment of the patient is not adapted to the viral genotype the patient is harbouring. Principal component analysis and partial least square showed a good performance but had only a slightly better predictive capacity for a virologal outcome compared to the genotypic score. We continue working on the comparison of these and other methods using different endpoints in the context of a collaboration with the Forum for collaborative HIV research. Vih-1 Mutations génotypiques Définition du critère de jugement Analyse statistique Hiv-1 Genotypic mutations Antiretroviral drug resistance Endpoint definition Statistical analysis
42	Experimental studies on displacements of CO₂ in sandstone core samples Al-Zaidi, Ebraheam Saheb Azeaz January 2018 (has links) CO2 sequestration is a promising strategy to reduce the emissions of CO2 concentration in the atmosphere, to enhance hydrocarbon production, and/or to extract geothermal heat. The target formations can be deep saline aquifers, abandoned or depleted hydrocarbon reservoirs, and/or coal bed seams or even deep oceanic waters. Thus, the potential formations for CO2 sequestration and EOR (enhanced oil recovery) projects can vary broadly in pressure and temperature conditions from deep and cold where CO2 can exist in a liquid state to shallow and warm where CO2 can exist in a gaseous state, and to deep and hot where CO2 can exist in a supercritical state. The injection, transport and displacement of CO2 in these formations involves the flow of CO2 in subsurface rocks which already contain water and/or oil, i.e. multiphase flow occurs. Deepening our understanding about multiphase flow characteristics will help us building models that can predict multiphase flow behaviour, designing sequestration and EOR programmes, and selecting appropriate formations for CO2 sequestration more accurately. However, multiphase flow in porous media is a complex process and mainly governed by the interfacial interactions between the injected CO2, formation water, and formation rock in host formation (e.g. interfacial tension, wettability, capillarity, and mass transfer across the interface), and by the capillary , viscous, buoyant, gravity, diffusive, and inertial forces; some of these forces can be neglected based on the rock-fluid properties and the configuration of the model investigated. The most influential forces are the capillary ones as they are responsible for the entrapment of about 70% of the total oil in place, which is left behind primary and secondary production processes. During CO2 injection in subsurface formations, at early stages, most of the injected CO2 (as a non-wetting phase) will displace the formation water/oil (as a wetting phase) in a drainage immiscible displacement. Later, the formation water/oil will push back the injected CO2 in an imbibition displacement. Generally, the main concern for most of the CO2 sequestration projects is the storage capacity and the security of the target formations, which directly influenced by the dynamic of CO2 flow within these formations. Any change in the state of the injected CO2 as well as the subsurface conditions (e.g. pressure, temperature, injection rate and its duration), properties of the injected and present fluids (e.g. brine composition and concentration, and viscosity and density), and properties of the rock formation (e.g. mineral composition, pore size distribution, porosity, permeability, and wettability) will have a direct impact on the interfacial interactions, capillary forces and viscous forces, which, in turn, will have a direct influence on the injection, displacement, migration, storage capacity and integrity of CO2. Nevertheless, despite their high importance, investigations have widely overlooked the impact of CO2 the phase as well as the operational conditions on multiphase characteristics during CO2 geo-sequestration and CO2 enhanced oil recovery processes. In this PhD project, unsteady-state drainage and imbibition investigations have been performed under a gaseous, liquid, or supercritical CO2 condition to evaluate the significance of the effects that a number of important parameters (namely CO2 phase, fluid pressure, temperature, salinity, and CO2 injection rate) can have on the multiphase flow characteristics (such as differential pressure profile, production profile, displacement efficiency, and endpoint CO2 effective (relative) permeability). The study sheds more light on the impact of capillary and viscous forces on multiphase flow characteristics and shows the conditions when capillary or viscous forces dominate the flow. Up to date, there has been no such experimental data presented in the literature on the potential effects of these parameters on the multiphase flow characteristics when CO2 is injected into a gaseous, liquid, or supercritical state. The first main part of this research deals with gaseous, liquid, and supercritical CO2- water/brine drainage displacements. These displacements have been conducted by injecting CO2 into a water or brine-saturated sandstone core sample under either a gaseous, liquid or supercritical state. The results reveal a moderate to considerable impact of the fluid pressure, temperature, salinity and injection rate on the differential pressure profile, production profile, displacement efficiency, and endpoint CO2 effective (relative) permeability). The results show that the extent and the trend of the impact depend significantly on the state of the injected CO2. For gaseous CO2-water drainage displacements, the results showed that the extent of the impact of the experimental temperature and CO2 injection rate on multiphase flow characteristics, i.e. the differential pressure profile, production profile (i.e. cumulative produced volumes), endpoint relative permeability of CO2 (KrCO2) and residual water saturation (Swr) is a function of the associated fluid pressure. This indicates that for formations where CO2 can exist in a gaseous state, fluid pressure has more influence on multiphase flow characteristics in comparison to other parameters investigated. Overall, the increase in fluid pressure (40-70 bar), temperature (29-45 °C), and CO2 injection rate (0.1-2 ml/min) caused an increase in the differential pressure. The increase in differential pressure with increasing fluid pressure and injection rate indicate that viscous forces dominate the multi-phase flow. Nevertheless, increasing the differential pressure with temperature indicates that capillary forces dominate the multi-phase flow as viscous forces are expected to decrease with this increasing temperature. Capillary forces have a direct impact on the entry pressure and capillary number. Therefore, reducing the impact of capillary forces with increasing pressure and injection rate can ease the upward migration of CO2 (thereby, affecting the storage capacity and integrity of the sequestered CO2) and enhance displacement efficiency. On the other hand, increasing the impact of the capillary force with increasing temperature can result in a more secure storage of CO2 and a reduction in the displacement efficiency. Nevertheless, the change in pressure and temperature can also have a direct impact on storage capacity and security of CO2 due to their impact on density and hence on buoyancy forces. Thus, in order to decide the extent of change in storage capacity and security of CO2 with the change in the above-investigated parameters, a qualitative study is required to determine the size of the change in both capillary forces and buoyancy forces. The data showed a significant influence of the capillary forces on the pressure and production profiles. The capillary forces produced high oscillations in the pressure and production profiles while the increase in viscous forces impeded the appearance of these oscillations. The appearance and frequency of these oscillations depend on the fluid pressure, temperature, and CO2 injection rate but to different extents. The appearance of the oscillations can increase CO2 residual saturation due to the re-imbibition process accompanied with these oscillations, thereby increasing storage capacity and integrity of the injected CO2. The differential pressure required to open the blocked flow channels during these oscillations can be useful in calculating the largest effective pore diameters and hence the sealing efficiency of the rock. Swr was in ranges of 0.38-0.42 while KrCO2 was found to be less than 0.25 under our experimental conditions. Increasing fluid pressure, temperature, and CO2 injection rate resulted in an increase in the KrCO2, displacement efficiency (i.e. a reduction in the Swr), and cumulative produced volumes. For liquid CO2-water drainage displacements, the increase in fluid pressure (60-70 bar), CO2 injection rate (0.4-1ml/min) and salinity (1% NaCl, 5% NaCl, and 1% CaCl2) generated an increase in the differential pressure; the highest increase occurred with increasing the injection rate and the lowest with increasing the salinity. On the other hand, on the whole, increasing temperature (20-29 °C) led to a reduction in the differential pressure apart from the gradual increase occurred at the end of flooding.
43	Interim monitoring efficacy, safety and futility in phase III clinical trials Li, Qing, January 2008 (has links) (PDF) Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Sept. 23, 2008). Includes bibliographical references.
44	The application of multivariate statistical analysis and optimization to batch processes Yan, Lipeng January 2015 (has links) Multivariate statistical process control (MSPC) techniques play an important role in industrial batch process monitoring and control. This research illustrates the capabilities and limitations of existing MSPC technologies, with a particular focus on partial least squares (PLS).In modern industry, batch processes often operate over relatively large spaces, with many chemical and physical systems displaying nonlinear performance. However, the linear PLS model cannot predict nonlinear systems, and hence non-linear extensions to PLS may be required. The nonlinear PLS model can be divided into Type I and Type II nonlinear PLS models. In the Type I Nonlinear PLS method, the observed variables are appended with nonlinear transformations. In contrast to the Type I nonlinear PLS method, the Type II nonlinear PLS method assumes a nonlinear relationship within the latent variable structure of the model. Type I and Type II nonlinear multi-way PLS (MPLS) models were applied to predict the endpoint value of the product in a benchmark simulation of a penicillin batch fermentation process. By analysing and comparing linear MPLS, and Type I and Type II nonlinear MPLS models, the advantages and limitations of these methods were identified and summarized. Due to the limitations of Type I and II nonlinear PLS models, in this study, Neural Network PLS (NNPLS) was proposed and applied to predict the final product quality in the batch process. The application of the NNPLS method is presented with comparison to the linear PLS method, and to the Type I and Type II nonlinear PLS methods. Multi-way NNPLS was found to produce the most accurate results, having the added advantage that no a-priori information regarding the order of the dynamics was required. The NNPLS model was also able to identify nonlinear system dynamics in the batch process. Finally, NNPLS was applied to build the controller and the NNPLS method was combined with the endpoint control algorithm. The proposed controller was able to be used to keep the endpoint value of penicillin and biomass concentration at a set-point. 621.3
45	USB host s mikrokontroléry PIC / USB Host with PIC Microcontrollers Kučera, Pavel January 2010 (has links) The aim of master thesis is implementation of USB host in a microcontroller PIC. The thesis contains description of ways of peripherals to computer connections with detailed description of USB bus. There are also discussed several approaches in implementations USB host for embedded systems. A concept of layered USB host system is designed on the basis of analysis of the state of the art. Finally, the designed system is implemented in microcontroller. Resulting firmware of development kit is tested on real USB device.
46	Trial design and analysis of endpoints in HIV vaccine trials / Schéma d’étude et analyses des données des essais vaccinaux du VIH Richert, Laura 28 October 2013 (has links) Des données complexes sont fréquentes dans les essais cliniques récents et nécessitent des méthodes statistiques adaptées. La recherche vaccinale du VIH est un exemple d’un domaine avec des données complexes et une absence de critères de jugement validés dans les essais précoces. Cette thèse d’Université concerne des recherches méthodologiques sur la conception et les aspects statistiques des essais cliniques vaccinaux du VIH, en particulier sur les critères de jugement d’immunogénicité et les schémas d’essai de phase I-II. A l’aide des données cytokiniques multiplex, nous illustrons les aspects méthodologiques spécifiques à une technique de mesure. Nous proposons ensuite des définitions de critères de jugement et des méthodes statistiques adéquates pour l'analyse des données d'immunogénicité multidimensionnelles. En particulier, nous montrons l’intérêt des scores multivariés non-paramétriques, permettant de résumer l’information à travers différents marqueurs d’immunogénicité et de faire des comparaisons inter- et intra-groupe. Dans l’objectif de contribuer à la conception méthodologique des nouveaux essais vaccinaux, nous présentons la construction d’un schéma d’essai optimisé pour le développement clinique précoce. En imbriquant les phases I et II d’évaluation clinique, ce schéma permet d’accélerer le développement de plusieurs stratégies vaccinales en parallèle. L’intégration d’une règle d’arrêt est proposée dans des perspectives fréquentistes et Bayesiennes. Les méthodes mises en avant dans cette thèse sont transposables à d’autres domaines d’application avec des données complexes, telle que les données d’imagerie ou les essais d’autres immunothérapies. / Complex data are frequently recored in recent clinical trials and require the use of appropriate statistical methods. HIV vaccine research is an example of a domaine with complex data and a lack of validated endpoints for early-stage clinical trials. This thesis concerns methodological research with regards to the design and analysis aspects of HIV vaccine trials, in particular the definition of immunogenicity endpoints and phase I-II trial designs. Using cytokine multiplex data, we illustrate the methodological aspects specific to a given assay technique. We then propose endpoint definitions and statistical methods appropriate for the analysis of multidimensional immunogenicity data. We show in particular the value of non-parametric multivariate scores, which allow for summarizing information across different immunogenicity markers and for making statistical comparisons between and within groups. In the aim of contributing to the design of new vaccine trials, we present the construction of an optimized early-stage HIV vaccine design. Combining phase I and II assessments, the proposed design allows for accelerating the clinical development of several vaccine strategies in parallel. The integration of a stopping rule is proposed from both a frequentist and a Bayesian perspective. The methods advocated in this thesis are transposable to other research domains with complex data, such as imaging data or trials of other immune therapies. Vaccin contre le VIH Marqueurs d’immunogénicité Données multidimensionnelles Variables résumées multivariées Critères de jugement Schémas d’essais cliniques optimisés HIV vaccine Immunogenicity markers Multidimensional data Multivariate summary measures Endpoint definitions Optimized clinical trial design
47	Les critères de jugement centrés sur le patient dans les essais cliniques en oncologie thoracique / Patient-centered clinical endpoints in lung cancer trials Fiteni, Frédéric 14 October 2016 (has links) La Survie globale (SG) est le critère de jugement de référence dans les essais cliniques en oncologie mais les critères de jugement dit intennédiaires centrés sur la tumeur qui sont évalués plus précocement sont de plus en plus utilisés comme critères substitutifs de la survie globale La qualité de vie (QdV) constitue un critère de jugement pour évaluer un bénéfice clinique direct pour le patient. Nos résultats ont montré que 32% des critères de jugement dans les essais de phase III de CBNPC avancés étaient pas du tout définis et seulement 43% était clairement défini et qu'aucun critère intermédiaire n'a démontré sa substitutivité sur la SG. Nous avons montré que la mesure, l'analyse et le report des données de QdV étaient hétérogènes entre les essais de phase III de CBNPC avancés d'où la nécessité de recommandations. Nous avons comparé longitudinalement la QdV chez 451 patients âgés de 70-89 ans atteints de CBNPC avancés randomisés entre une bichimiothérapie et une monochimiothérapie selon la technique du temps jusqu'à détérioration définitive (TJD) d'un score de QdV. Cette étude a montré : sur le plan clinique, le bénéfice du doublet de chimiothérapie pour les patients est renforcé par les données de QdV; sur le plan méthodologique: le TJD est une technique d'analyse faisable dans les essais de phase III de CBNPC et fournit des résultats faciles d'interprétation. Nous avons proposé l'utilisation de co-critères de jugement principaux associant QdV et critère centré sur la tumeur. Enfin, nous avons démontré la valeur pronostique de la dimension santé globale de QdV à baseline du questionnaire sur la SG chez les patients âgés atteints de CBNPC avancés. / Overall survival (OS) is the gold standard endpoint in oncology clinical trials. Nevertheless, intermediate tumor-centered endpoints which are assessed earlier are more and more used as surrogate of OS. Health-related quality of life is an endpoint which assesses a direct benefit for the patient. We demonstrated that 32% of endpoints in advanced non-small-cell lung phase III clinical trials were not defined at all, 43% were not clearly defined and none ofthem has demonstrated its surrogacy on OS. We demonstrated the weakness and the heterogeneity of the measurement, analysis, and reporting of HRQoL in phase III advanced NSCLC trials. Precise and uniform recommendations are needed. We longitudinally compared HRQoL using tüne until definitive deterioration (TUDD) method in 451 patients aged 70-89 years with advanced NSCLC randomly assigned to receive a doublet of chemotherapy or a monochemotherapy. We demonstrated the benefit of the doublet chemotherapy in terms ofHRQoL. On a methodological point ofview TUDD method is feasible and provide clinically meaningful results. We proposed another approach which would be to combine intermediate endpoint• with HRQoL as co-primary endpoints. Finally, we demonstrated the additional prognostic value of HRQoL data at baseline to identify vulnerable subpopulations in elderly NSCLC patients. Critères de jugement Qualité de vie relative à la santé Cancer du poumon Méthodologie Essais cliniques Endpoints Patient-centered clinical endpoint Health-related quality of life Lung cancer Methodology Clinical trials 616.9
48	Poloha Orliczova prostoru a optimalita / Positioning of Orlicz space and optimality Musil, Vít January 2014 (has links) Given a rearrangement-invariant Banach function space Y (Ω), we consider the problem of the existence of an optimal (largest) domain Or- licz space LA (Ω) satisfying the Sobolev embedding Wm LA (Ω) !Y (Ω). We present a complete solution of this problem within the class of Marcinkiewicz endpoint spaces which covers several important examples.
49	GIS-based Episode Reconstruction Using GPS Data for Activity Analysis and Route Choice Modeling / GIS-based Episode Reconstruction Using GPS Data Dalumpines, Ron 26 September 2014 (has links) Most transportation problems arise from individual travel decisions. In response, transportation researchers had been studying individual travel behavior – a growing trend that requires activity data at individual level. Global positioning systems (GPS) and geographical information systems (GIS) have been used to capture and process individual activity data, from determining activity locations to mapping routes to these locations. Potential applications of GPS data seem limitless but our tools and methods to make these data usable lags behind. In response to this need, this dissertation presents a GIS-based toolkit to automatically extract activity episodes from GPS data and derive information related to these episodes from additional data (e.g., road network, land use). The major emphasis of this dissertation is the development of a toolkit for extracting information associated with movements of individuals from GPS data. To be effective, the toolkit has been developed around three design principles: transferability, modularity, and scalability. Two substantive chapters focus on selected components of the toolkit (map-matching, mode detection); another for the entire toolkit. Final substantive chapter demonstrates the toolkit’s potential by comparing route choice models of work and shop trips using inputs generated by the toolkit. There are several tools and methods that capitalize on GPS data, developed within different problem domains. This dissertation contributes to that repository of tools and methods by presenting a suite of tools that can extract all possible information that can be derived from GPS data. Unlike existing tools cited in the transportation literature, the toolkit has been designed to be complete (covers preprocessing up to extracting route attributes), and can work with GPS data alone or in combination with additional data. Moreover, this dissertation contributes to our understanding of route choice decisions for work and shop trips by looking into the combined effects of route attributes and individual characteristics. / Dissertation / Doctor of Philosophy (PhD) GPS time use diary episode extraction multinomial logit travel behavior mode detection episode reconstruction GIS map-matching route choice path size logit potential path area scale estimation Python ArcGIS activity analysis trip reconstruction smartphone global positioning system geographic information system toolkit work trip shop trip potential activity location land use activity episode travel episode stop episode transferability scalability modularity scripting big data travel survey respondent burden preprocessing multipath error tracking purpose detection segmentation data filter data smoothing fuzzy logic neural network decision tree rule-based algorithm trajectory point road network network dataset gateway shortest path horizontal dilution of precision HDOP commonality factor mode transfer point Halifax Nova Scotia Space-Time Activity Research variance inflation factor shapefile comma-separated values traveling salesman problem data mining branch-and-bound algorithm pedestrian network alternative route observed route route efficiency route attributes distance time heading bearing duration acceleration latitude longitude coordinate overlay analysis intersect shopping module data logger walk likelihood ratio test classification table path generation kappa statistic degrees data collection transportation research automate framework ArcToolbox spatio-temporal navigation positioning trace path spatial data topology horizontal accuracy SPSS Stata spatial resolution temporal resolution household survey trip reporting proximity analysis DMTI Desktop Mapping Technologies Inc. road intersection route overlap left turn right turn location analysis time geography spatial statistics buffer analysis cycling bus transit public transportation GEOIDE AGILE data need raw data urban canyon endpoint data cleaning elevation satellite outliers automatic processing nearest node classifier classification method short trip multi-point

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