Guided imagery, a therapeutic technique in which a healer directs an individual to visualize a scene or sensations, has existed for millennia and is often used within healthcare settings today. A small, though growing number of studies among clinical samples demonstrate that guided imagery produces positive effects such as decreased pain and anxiety. Few studies have dismantled this intervention in order to isolate its active ingredients, and even fewer studies have determined for whom this intervention works. The current study sought to address these gaps in the literature by examining the effects of guided imagery on mood and anxiety among a college sample. The effects of a single session of non-directive guided imagery were examined through a repeated measures, pre-test post-test design with three experimental conditions. Multivariate analysis of data from 107 adults showed that following a distress induction, guided imagery significantly decreased anxiety and negative affect. However, guided imagery did not produce significantly greater changes in mood and anxiety than quiet rest or attention control conditions as hypothesized. Individual difference variables hypothesized as moderators (trait absorption, imagery vividness, imagery control) did not predict outcome; however, self-reported engagement in the experimental conditions predicted magnitude of change in outcome. The discussion outlines potential reasons for these unique findings as well as clinical implications and future directions for research.

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L’amélioration du développement du médicament est un véritable défi et ceci encore plus dans le domaine de l’oncologie dans lequel le besoin d’avoir de nouvelles alternatives thérapeutiques est primordial. De plus, on note que le taux d’approbation des nouveaux anticancéreux après leur entrée en phase 1 fait partie des plus bas taux de toutes les aires thérapeutiques. De ce fait, ce processus doit être amélioré et l’utilisation de nouvelles approches faisant le lien entre développement préclinique et clinique par anticipation des propriétés pharmacocinétiques et d’efficacité pourrait être une perspective intéressante.L’objectif de ce travail est l’élaboration de stratégies basées sur la modélisation mathématique de données précliniques in vivo et in vitro afin d’anticiper le comportement chez l’homme d’un nouvel inhibiteur de bcl-2 développé par les Laboratoires Servier pour soutenir le développement clinique. Ce projet a été mené suivant différentes étapes :Premièrement, un modèle semi-mécanistique décrivant le mode d’action de la molécule a été établi chez la souris.Une stratégie d’extrapolation inter-espèces des caractéristiques PK utilisant la modélisation PBPK a été effectuée afin d’anticiper les profils temps-concentration chez l’homme.Des stratégies d’extrapolation de la partie PD basées sur différentes hypothèses ont été proposées pour prédire une efficacité chez l’homme et des doses à tester lors de l’étude clinique.Les prédictions obtenues ont ainsi été comparées aux résultats cliniques issus de la première étude réalisée chez l’homme confirmant le caractère utile de telles approches et la supériorité des stratégies bâties à l’aide de concepts semi-mécanistiques par rapport aux approches plus empiriques.Ce projet souligne donc le grand intérêt d’élaborer des approches translationnelles inter-espèces durant le développement du médicament et pourrait favoriser leur utilisation afin d’accélérer le développement de nouvelles entités, diminuant ainsi les risques d’échecs ainsi que les coûts financiers / Improvement of drug development is a very challenging question and even more in the field of oncology wherein the need for new medicines is crucial. In addition, the rate of approval for anticancer drugs after entry in phase I clinical trial was reported as one of the lowest of all therapeutic areas. Thereby, this process has to be improved, and the use of new approaches fulfilling the gap between preclinical and clinical settings by anticipating human pharmacokinetics and efficacy could be an interesting solution.The work is focused on the building of strategies based on mathematical modeling of in vivo and in vitro preclinical data to anticipate the behavior of a new bcl-2 inhibitor developed by Servier laboratories in human to support clinical development. This project was elaborated following different steps:Firstly, a semi-mechanistic relationship was established in mice to describe the mechanism of action of the compound.PK extrapolation strategy using PBPK modeling was performed to anticipate human concentration-time profiles.PD extrapolation strategies based on different assumptions were proposed to predict human efficacy and doses to be tested in clinical trial.Predictions obtained were consequently compared to clinical results from a First in Human study confirming the usefulness of such approaches and the superiority of mechanism-based strategies compared to more empirical approaches.Therefore, this project highlights the large interest of elaborating interspecies translational approaches during drug development and could promote their use to accelerate new entities development, decreasing the risks of failure and financial costs.

This thesis uses language corpora to analyze Czech translations of a linguistically asymmetric phenomenon of German privatives ending in -frei and -los from three perspectives: translation typology (micro-stylistics and macro-stylistics), Popovič's stylistic adequacy (shifts of expression: intensification of expression, attenuation of expression, correspondence of expression) and potentially intrinsic feature of German privatives to perceive the fact of absence ("privation") as positive or negative. Privatives are adjectives that express the absence of substance or quality that is represented in their first (left) component; in the context of this work they are limited to adjectives ending in -frei, -los, -arm and -leer. In the Introduction the current state of research is outlined and its time and local limitations are explained. It is emphasized that corpus is here used not just for translation as such but also for theory of translation. The hypothesis starts from the assumption that German privatives as phenomena of grammar have no equivalent on this level in Czech; therefore a direct translation equivalent is often missing. For this reason it is also probable that the translator will have to decide for such Czech translation of one German privative that comprises more words or even a whole...