No description available.

Personalised medicine describes the practice of tailoring medical care to the individual characteristics of each patient. Fundamental to this practice is the identification of markers associated with differential treatment response. Such markers can be identified through the assessment of treatment effect modification using statistical methods. Randomised controlled trials provide the optimal setting for evaluating differential response to treatment. Due to restrictions regarding sample size, study length and ethics, observational studies are more appropriate in many circumstances, particularly for the identification of markers associated with adverse side-effects and long term response to treatments. However, the analysis of observational data raises some additional challenges. The overall aim of this thesis was to develop statistical methodology for the analysis of observational data, specifically primary care databases, to identify and evaluate markers associated with differential treatment response. Three aspects of the assessment of treatment effect modification in an observational setting were addressed. The first aspect related to the assessment of treatment effect modification on the additive measurement scale which corresponds to a comparison of absolute treatment effects across patient subgroups. Various ways in which this can be assessed in an observational setting were reviewed and a novel measure, the ratio of absolute effects, which can be calculated from certain multiplicative regression models, was proposed. The second aspect regarded the confounding adjustment and it was investigated how the presence of interactions between the moderator and confounders on both treatment receipt and outcome can bias estimates of treatment effect modification if unaccounted for using Monte Carlo simulations. It was determined that the presence of bias differed across different confounding adjustment methods and, in the majority of settings, the bias was reduced when the interactions between the moderator and confounders were accounted for in the confounding adjustment model. Thirdly, it has been proposed that patient data in observational studies be organised into and analysed as series of nested nonrandomised trials. This thesis extended this study design to evaluate predictive markers of differential treatment response and explored the benefits of this methodology for this purpose. It was suggested how absolute treatment effect estimates can be estimated and compared across patient subgroups in this setting. A dataset comprising primary care medical records of adults with rheumatoid arthritis was used throughout this thesis. Interest lay in the identification of characteristics predictive of the onset of type II diabetes associated with steroid (glucocorticoid) therapy. The analysis in this thesis suggested older age may be associated with a higher risk of steroid-associated type II diabetes, but this warrants further investigation. Overall, this thesis demonstrates how observational studies can be analysed such that accurate and meaningful conclusions are made within personalised medicine research.

Made available in DSpace on 2014-06-11T19:24:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-08-28Bitstream added on 2014-06-13T19:31:34Z : No. of bitstreams: 1 luchesi_d_me_botfca.pdf: 1478619 bytes, checksum: fe1ce4874b37fec4f5c704c741316db9 (MD5) / A agroinformática, termo criado para referenciar a informática aplicada à agricultura, vem ganhando espaço e se organizando nesse novo processo de modernização da agricultura na tentativa de contribuir tanto no aumento da produtividade quanto da qualidade. A informática no ambiente agrícola se encontra presente em diversas propriedades rurais, tanto na área administrativa como na área de gestão proporcionando coordenação nas atividades, uma maior agilidade no fluxo de informações e redução de erros nas operações internas. Em função da crescente presença da informática na agricultura e da utilização de dispositivos de aquisição automática de dados no campo, a presente pesquisa apresenta o desenvolvimento de um programa computacional, Ener Sys, desenvolvido com o objetivo de transformar dados meteorológicos no setor de agroenergia. A partir de um dispositivo automático de aquisição de dados (Campbell Scientific modelo CR23X), desenvolveu-se um sistema computacional para melhor classificar e visualizar os dados de uma forma rápida e simples para o profissional envolvido com as alterações meteorológicas da área sob estudo. O sistema proposto utilizou as seguintes tecnologias computacionais: a linguagem de programação Personal Home Page Hypertext Preprocessor e o banco de dados Firebird. Os resultados obtidos ao término da pesquisa apontam que a abordagem deste trabalho facilitou o acesso a informações armazenadas em grandes massas de dados. O 2 programa computacional desenvolvido, reuniu em uma base unificada, os dados coletados através de um sistema eletrônico de aquisição de dados e facilitou o processamento dos dados proporcionando ganhos na visualização das informações como temperatura (oC), umidade (%), velocidade do vento (m.s-2), direção do vento (graus), chuva (mm) e irradiância (horizontal e vertical). / The agro-informatics, term used as reference to the informatics applied to the agriculture, it has been gaining space and getting organized on this new process of agriculture modernization to try to contribute both to the productivity increase and quality. The informatics at the agricultural environment can be found in many rural properties both in the administrative area and management area, providing coordination in the activities, a better agility with the information flow and error cutback in the internal operations. Due to the growing presence of the informatics in the agriculture and the use of automatic data acquisition devices in the field, this study presents a computer program, Ener Sys, developed with the purpose of transform meteorological data in the agro sector. From an automatic device of data acquisition (Campbell Scientific model CR23X) it was developed a computer system to better classify and visualize the data on a fast and simple way to the professional involved with the study of meteorological variations in this area. The suggested system used the following computer technologies: the Personal Home Page Hypertext Preprocessor programming language and the database Firebird. The results obtained at the end of the research show that the approach of this study made easier the access to the information stored in large amounts of data. The computer program developed, put together in one base, the data collected through an electronic system of data acquisition and made easy the data processing providing a gain on the visualization of information such as temperature (oC), humidity (%), wind speed (m.s-2), wind direction (degrees), rain (mm) and irradiance (horizontal and vertical).

Orientador: Saulo Philipe Sebastião Guerra / Banca: Odivaldo José Seraphim / Banca: Carlos Roberto Pereira Padovani / Resumo: A agroinformática, termo criado para referenciar a informática aplicada à agricultura, vem ganhando espaço e se organizando nesse novo processo de modernização da agricultura na tentativa de contribuir tanto no aumento da produtividade quanto da qualidade. A informática no ambiente agrícola se encontra presente em diversas propriedades rurais, tanto na área administrativa como na área de gestão proporcionando coordenação nas atividades, uma maior agilidade no fluxo de informações e redução de erros nas operações internas. Em função da crescente presença da informática na agricultura e da utilização de dispositivos de aquisição automática de dados no campo, a presente pesquisa apresenta o desenvolvimento de um programa computacional, Ener Sys, desenvolvido com o objetivo de transformar dados meteorológicos no setor de agroenergia. A partir de um dispositivo automático de aquisição de dados (Campbell Scientific modelo CR23X), desenvolveu-se um sistema computacional para melhor classificar e visualizar os dados de uma forma rápida e simples para o profissional envolvido com as alterações meteorológicas da área sob estudo. O sistema proposto utilizou as seguintes tecnologias computacionais: a linguagem de programação Personal Home Page Hypertext Preprocessor e o banco de dados Firebird. Os resultados obtidos ao término da pesquisa apontam que a abordagem deste trabalho facilitou o acesso a informações armazenadas em grandes massas de dados. O 2 programa computacional desenvolvido, reuniu em uma base unificada, os dados coletados através de um sistema eletrônico de aquisição de dados e facilitou o processamento dos dados proporcionando ganhos na visualização das informações como temperatura (oC), umidade (%), velocidade do vento (m.s-2), direção do vento (graus), chuva (mm) e irradiância (horizontal e vertical). / Abstract: The agro-informatics, term used as reference to the informatics applied to the agriculture, it has been gaining space and getting organized on this new process of agriculture modernization to try to contribute both to the productivity increase and quality. The informatics at the agricultural environment can be found in many rural properties both in the administrative area and management area, providing coordination in the activities, a better agility with the information flow and error cutback in the internal operations. Due to the growing presence of the informatics in the agriculture and the use of automatic data acquisition devices in the field, this study presents a computer program, Ener Sys, developed with the purpose of transform meteorological data in the agro sector. From an automatic device of data acquisition (Campbell Scientific model CR23X) it was developed a computer system to better classify and visualize the data on a fast and simple way to the professional involved with the study of meteorological variations in this area. The suggested system used the following computer technologies: the Personal Home Page Hypertext Preprocessor programming language and the database Firebird. The results obtained at the end of the research show that the approach of this study made easier the access to the information stored in large amounts of data. The computer program developed, put together in one base, the data collected through an electronic system of data acquisition and made easy the data processing providing a gain on the visualization of information such as temperature (oC), humidity (%), wind speed (m.s-2), wind direction (degrees), rain (mm) and irradiance (horizontal and vertical). / Mestre

La cosmétique valorise des extraits de plantes en les intégrant dans des produits de soin. Ces extraits constituent les ingrédients actifs de la formule cosmétique. Les plantes sont diverses, riches et contiennent de nombreux composés d’intérêt biologique. La phytochimie s’intéresse à décrire le contenu métabolique d’extraits de plantes. Mais la caractérisation moléculaire de ces matrices complexes reste un défi majeur aujourd’hui. En effet, les étapes de traitements de données sont longues et laborieuses. Un outil de profilage métabolique, GAINS, a ainsi été développé afin de traiter de façon automatisée les données issues d’analyses en chromatographie liquide couplée à la spectrométrie de masse haute résolution. Il constitue un support au phytochimiste car le traitement automatisé des données permet de gagner du temps par rapport à un traitement manuel. Cet outil associé à une vaste base de données de produits naturels permet d’attribuer des candidats potentiels aux pics détectés. GAINS fait aussi appel à un module de fragmentation in silico afin d’étayer les propositions de candidats. Cela permet de comparer le spectre de fragmentation modélisé des candidats avec le spectre de fragmentation expérimental.L’ensemble des études phytochimiques réalisées pour identifier ou isoler des composés va de pair avec l’étude du potentiel d’effet biologique des extraits sur la peau, organe ciblé par les cosmétiques. Cela sert à découvrir les actions bénéfiques que peut avoir l’extrait. En connaissant le contenu phytochimique, on peut expliquer et rationaliser les tests d’activités biologiques. Le développement d’un actif anti-âge à partir de la salicaire, une plante de la région Centre-Val de Loire, en est l’exemple. / The cosmetic field valorizes plant extracts by integrating them in care products. These extracts constitute the active ingredients of the cosmetic formulation. Plants are diverse, rich and contain numerous compounds of biological interest. Phytochemistry is a way to describe the metabolic content of plant extracts. But molecular characterization of these complex matrices remains a major challenge nowadays. Indeed,steps of data treatment are time-consuming and laborious. In this way, a tool of metabolic profiling, GAINS, has been developed in order to treat in an automatized way data from analyses performed in liquid chromatography coupled with high-resolution mass spectrometry. It constitutes a real support for phytochemists because automatized data treatment allows gaining time compared to manual treatment. This tool, associated with a large database of natural compounds make possible to assign potential candidates to detected peaks. GAINS appeals a module of in silico fragmentation for holding candidates assignments up.This permits to compare modeled spectrum of fragmentation of candidates with experimental spectrum off ragmentation.The whole set of phytochemical studies realized to identify or isolate compounds goes hand in hand with the study of potential biological effects of extracts to the skin, targeted organ by skin-care products. This allows the discovery of beneficial actions that the extract could have. By knowing the phytochemical content, it is possible to explain and rationalize assays about biological activities. The development of an anti-aging ingredient from purple loosestrife, a plant occurring in the region Centre-Val de Loire, is an example of it.

Pour augmenter les performances de nos composants électroniques, les fabricants ont recourt à de nouveaux matériaux tels que les terres rares. Malgré leur nom, les terres rares sont présentes en quantité sur le globe terrestre mais de façon diluée dans les minerais extraits. L’extraction de ces éléments est peu effectuée en Europe mais majoritairement en Asie où les procédés chimiques de séparations employés sont parfois peu respectueux de l’environnement. De plus les industriels européens sont contraints économiquement par le marché asiatique pour l’achat de ces matières premières. En revanche l’Europe dispose d’une grande quantité de déchets électroniques contenant les éléments d’intérêts. Les procédés de recyclage sont donc primordiaux pour réduire notre dépendance économique et répondre aux besoins d’une économie circulaire. Des procédés de recyclage comme par exemple, l’extraction liquide-liquide existent déjà, mais la diversité des déchets présents nécessite d’adapter le procédé en fonction du lot de déchets afin d’améliorer le rendement. Mais l’optimisation d’un procédé nécessite des expérimentations qui peuvent prendre plusieurs années. L’objectif de la thèse est de trouver des moyens innovants pour réduire le temps nécessaire à l’étude d’un système d’extraction liquide-liquide de quelques années à quelques semaines. Pour cela le domaine a besoin d’une instrumentation dédiée pouvant analyser de façon automatique et rapide les procédés. Les travaux de cette thèse ont donc porté sur le développement d’un dispositif microfluidique d’extraction liquide-liquide associé à deux techniques principales d’analyses en ligne. La première technique d’analyse est basée sur une méthode de fluorescence des rayons X (XRF) pour déterminer la performance d’extraction. La seconde méthode est basée sur de la spectrométrie infrarouge à transformée de Fourrier (FTIR) afin d’étudier l’activité des solvants (aqueux et organiques), informant sur les mécanismes d’extraction. / To increase the performance of our electronic components, manufacturers are using new materials such as rare earth elements (REE). Despite their name, the REE are present in quantity on Earth but in a diluted way in the ores extracted. The extraction of these elements is little carried out in Europe but mainly in Asia where the chemical processes of separations employed are sometimes not very respectful of the environment. Moreover European manufacturers are economically constrained by the Asian market for the purchase of these raw materials. On the other hand, Europe has a large quantity of electronic waste containing the elements of interest. Recycling processes are therefore essential to reduce our economic dependence and meet the needs of a circular economy. Recycling processes such as, for example, liquid-liquid extraction already exist, but the diversity of the present waste requires to adapt the process according to the batch of waste in order to improve the yield. But the optimization of a process requires experiments that can take several years. The aim of the thesis is to find innovative ways to reduce the time needed to study a liquid-liquid extraction system from a few years to a few weeks. For this the domain needs a dedicated instrumentation that can analyse processes automatically and quickly. The work of this thesis is focused on the development of a microfluidic liquid-liquid extraction device associated with two main online analysis techniques. The first analytical technique is based on an X-ray fluorescence (XRF) method to determine the extraction performance. The second method is based on Fourier transform infrared spectrometry (FTIR) in order to study the activity of solvents (aqueous and organic), informing about extraction mechanisms.

No description available.

Les colonnes à bulles sont utilisées en minéralurgie et en traitement des eaux pour capturer différents types de particules. Leur capacité d’échange bénéficie aujourd’hui d’un regain d’intérêt pour assurer la production de micro-algues destinées à un usage médicinal, alimentaire, ou énergétique : les concentrations d’oxygène et de dioxyde de carbone peuvent être contrôlées grâce à la considérable aire interfaciale gaz-liquide dans la colonne à bulles. Une étude expérimentale en boucle fermée a été menée pour simuler le passage du gaz dans une succession de colonnes en série. Le modèle théorique associé confirme le rôle critique du diamètre des bulles lors du transfert de masse. Un générateur de micro-bulles (MBG) innovant a été conçu et testé. Le prototype est capable de produire des micro-bulles d’un diamètre moyen Dbubble = 0.252 mm. L’invention a été officiellement déclarée. Le dernier chapitre a pour objet l’amélioration des méthodes de traitement de Fluorescence Induite par Plan Laser (PLIF), qui permettent d’obtenir les coefficients de transfert de masse kl. La première correction présentée prend en compte les variations de l’extinction de la fluorescence due au pH pendant la calibration et a été évaluée sur une mesure de concentration de CO2 dans le sillage d’une bulle en ascension libre dans une colonne d’eau. La seconde correction proposée doit être appliquée quand la distance de la région de mesure où les variations de pH sont observées augmente. La nécessité de cette correction a été illustrée par un cas test dans le sillage d’un nuage de bulles en ascension libre dans une colonne d’eau / Bubble column are involved in many industrial fields ranging from chemical industry to mineral processing. It recently became an industrial stake for the production of micro-algae intended for medicinal use, food or energy: the oxygen and carbon dioxide concentrations can be controlled via the efficient mass transfer induced by the significant gas-liquid interfaciale area into the bubble column. Firstly, experimental closed-loop study has been carried out to simulate the passage of gas in a succession of columns in series. The associated theoretical model confirms the critical importance of the bubble diameter for mass transfer.Therefore, an innovative Micro-Bubble Generator (MBG) has been designed and tested. The prototype is able to produce micro-bubbles of average diameter Dbubble = 0.252 mm. The invention has been officially declared. The last chapter aims at improving data treatment methods for Planar Laser-Induced Fluorescence (PLIF), which enables to obtain experimentally mass transfer coefficient kl through concentration measurements. The first presented correction takes into account variations of the fluorescence extinction due to pH during the calibration step, and has been evaluated on CO2 concentration measurement in the wake of a free rising bubble. The second proposed correction should be applied when the length in the measurement region over which pH variations are observed increases: variations of the extinction coefficient will affect the local incident light intensity and therefore the measurements. The need for this correction has been illustrated on a test case in the wake of a cloud of free rising bubbles

In der Behandlung der zervikalen Dystonie wird die Therapie mit Botulinumtoxin (BTX) erfolgreich angewendet. Neben dieser Therapie werden von Patienten oft alternative Therapien (CAM [Complementary and Alternative Medicine]) angesprochen und ausprobiert. Diese Studie geht der Frage nach, wie häufig CAM-Therapien genutzt werden, wie deren Wirkung bewertet wird und ob es Prädiktoren für die Therapiewahl gibt. Zur Datenerhebung wurden 265 Fragebögen von zwei Patientengruppen ausgewertet. Gruppe 1 (n=101) bestand aus Patienten der Botulinumtoxinsprechstunde des Universitätsklinikums Leipzig und der Paracelsus Klinik Zwickau. Gruppe 2 (n=165) wurde aus Mitgliedern des Selbsthilfeverbandes Bundesverband-Torticollis e.V. rekrutiert. Bei 86% der Patienten wurde die Therapie mit BTX angewendet. Von den Therapiemöglichkeiten der CAM wurden am häufigsten physikalische Therapien (Massagen n=171) genannt. Am besten bewertet wurden jedoch, neben der BTX-Therapie, spezielle physiotherapeutische sowie psychotherapeutische Verfahren. Die CAM-Therapien wurden häufig in Kombination mit der BTX-Therapie angewendet und von Patienten, deren Erkrankung einen langen chronischen Verlauf vorwies (>10 Jahre). Als Prädiktoren für die Wahl einer CAM-Therapie zeigten sich eine Zugehörigkeit zur Gruppe 2, aufgetretene Nebenwirkungen im Rahmen der BTX-Therapie, männliches Geschlecht und erhöhter Stress bei den Erkrankten. Außerdem fand sich ein signifikanter Unterschied zu einem höheren Bildungsabschnitt und Arbeit in gehobeneren Berufsgruppen bei Patienten, die vermehrt CAM Therapie anwenden. Zusammenfassend wurden CAM-Therapien, neben der Behandlung mit BTX, häufig von den Befragten angewendet. Hohe Zufriedenheitswerte erzielte eine Kombination mit physiotherapeutischen Verfahren oder Psychotherapie. Die Wahl von CAM-Therapien ist von der Erkrankungsdauer, Bildungslage und finanziellen Ressourcen abhängig.:1 EINLEITUNG 5 2 STAND DER FORSCHUNG 6 2.1 Definitionen 6 2.2 Epidemiologie 7 2.3 Pathologie 8 2.4 Klinisches Bild 11 2.5 Therapie 13 3 FRAGESTELLUNG UND HYPOTHESEN 24 4 STICHPROBE UND METHODE 25 4.1 Stichprobe 25 4.2 Erhebungsinstrument 26 4.3 Statistische Auswertung 28 5 ERGEBNISSE 30 5.1 Soziodemographische Daten 30 5.2 Krankheitsbezogene Merkmale 33 5.3 Therapie 35 5.4 Prädiktoren für die Therapiewahl 42 6 DISKUSSION 45 6.1 Das Patientenkollektiv 45 6.2 Diskussion der Botulinum-Toxin-Therapie 47 6.3 Diskussion der alternative Therapien 48 6.4 Diskussion der Prädiktoren für die Therapiewahl 54 6.5 Kritik 58 6.6 Schlussfolgerungen und Empfehlungen 59 7 ZUSAMMENFASSUNG 61 8 LITERATURVERZEICHNIS 64 9 ANLAGEN 72 9.1 Tabellen- und Abbildungsverzeichnis 9.2 Fragebogen 9.3 Erklärung der eigenständigen Abfassung der Arbeit 9.4 Curriculum Vitae 9.5 Veröffentlichungen und Vorträge 9.6 Danksagung