Obesity, a condition of excess body fat, is one of the most complex problems facing health systems. Lifestyle management programs that combine diet, physical activity, and intensive behavioral therapy have been shown by research to support a degree of weight loss that produces health benefits (i.e., at least a 3-5% initial body weight). However, it has been difficult for research-developed programs to be delivered in typical practice to have a meaningful impact. Integrated research-practice partnerships that involve the coming together of academic researchers, health system administrators, and program delivery staff may help overcome this gap, especially during this transformational time in the healthcare sector. This dissertation aimed to develop an understanding of how using the integrated research-practice approach would facilitate and sustain evidence-based lifestyle management strategies across a health system to treat obesity among patients and employees. An integrated research-practice partnership with Carilion Clinic, a health system in western Virginia, served as an example for the study. From 2013-2016, the Carilion Clinic integrated research-practice partnership conducted a series of trials testing different strategies for delivering weight loss and weight loss maintenance support. An evaluation guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework was conducted to describe implementation processes and outcomes for each strategy. Lessons learned from the evaluation support the value of the integrated-research practice partnership approach as a solution for overcoming gaps in obesity care. A shared priority perspective between research and practice was identified as the powerful process for supporting facilitation and sustainability of strategies. In addition, findings from the evaluation produced evidence to inform the future development of a system for Carilion Clinic to help patients and employees lose weight and keep it off through lifestyle management. / Ph. D.

Early childhood is a critical period for literacy development and US research has found that 35 per cent of children enter public schools with low levels of the skills needed to learn to read. Visiting US academic Professor Lynn Williams will present a lecture about how children acquire literacy skills on Thursday 8 November at Charles Sturt University (CSU) Bathurst Campus. Associate Professor Sharynne McLeod, from CSU’s School of Teacher Education, said that Professor Williams has a distinguished career in teaching and writing about speech and language development and disorders in children. “Her lecture, Contexts for facilitating emergent literacy skills, will summarize the findings from a range of studies in order to assist early childhood educators, speech-language pathologists, and families in their roles to prevent later reading difficulties for young children,” Dr McLeod said.

Les systèmes de santé "apprenants" (SSA) présentent une approche complémentaire et émergente aux problèmes de la recherche translationnelle en couplant de près les soins de santé, la recherche et le transfert de connaissances. Afin de permettre un flot d’informations cohérent et optimisé, le système doit se doter d’une plateforme intégrée de partage de données. Le travail présenté ici vise à proposer une approche de partage de données unifiée pour les SSA. Les grandes approches d’intégration de données sont analysées en fonction du SSA. La sémantique des informations cliniques disponibles dans les sources biomédicales est la résultante des connaissances des modèles structurelles des sources mais aussi des connaissances des modèles terminologiques utilisés pour coder l’information. Les mécanismes de la plateforme unifiée qui prennent en compte cette interdépendance sont décrits. La plateforme a été implémentée et testée dans le cadre du projet TRANSFoRm, un projet européen qui vise à développer un SSA. L’instanciation du modèle de médiation pour le projet TRANSFoRm, le Clinical Data Integration Model est analysée. Sont aussi présentés ici les résultats d’un des cas d’utilisation de TRANSFoRm pour supporter la recherche afin de donner un aperçu concret de l’impact de la plateforme sur le fonctionnement du SSA. Au final, la plateforme unifiée d’intégration proposée ici permet un niveau d’expressivité suffisant pour les besoins de TRANSFoRm. Le système est flexible et modulaire et le modèle de médiation CDIM couvre les besoins exprimés pour le support des activités d’un SSA comme TRANSFoRm. / Learning health systems (LHS) are gradually emerging and propose a complimentary approach to translational research challenges by implementing close coupling of health care delivery, research and knowledge translation. To support coherent knowledge sharing, the system needs to rely on an integrated and efficient data integration platform. The framework and its theoretical foundations presented here aim at addressing this challenge. Data integration approaches are analysed in light of the requirements derived from LHS activities and data mediation emerges as the one most adapted for a LHS. The semantics of clinical data found in biomedical sources can only be fully derived by taking into account, not only information from the structural models (field X of table Y), but also terminological information (e.g. International Classification of Disease 10th revision) used to encode facts. The unified framework proposed here takes this into account. The platform has been implemented and tested in context of the TRANSFoRm endeavour, a European project funded by the European commission. It aims at developing a LHS including clinical activities in primary care. The mediation model developed for the TRANSFoRm project, the Clinical Data Integration Model, is presented and discussed. Results from TRANSFoRm use-cases are presented. They illustrate how a unified data sharing platform can support and enhance prospective research activities in context of a LHS. In the end, the unified mediation framework presented here allows sufficient expressiveness for the TRANSFoRm needs. It is flexible, modular and the CDIM mediation model supports the requirements of a primary care LHS.

This thesis will study how scientific research environments should be designed, specifically addressing the issues beyond mere needs of research scientists. Assuming that the purpose of research is to create new knowledge and foster discoveries, as well as positively influence the community in its processes and results, this thesis will explore the potential of the influence of this building typology that has not been previously considered enough. The objectives of the thesis are on one hand, the changes in science disciplines and their reflections in the evolution among this building type, on the other hand, the impacts of research environment on scientific evolution. The question is, beyond support, can architecture promote and nurture science and enlighten scientists toward a new understanding of scientific activities? Based on this research, it is assumed that good science happens in spaces that are transparent and dynamically communicative. The methodologies, which will be used to address these objectives, include literature review, exploration of case studies, surveys and interviews with scientists about their use of the laboratory buildings, and the design of a prototype building for scientific research.

For several decades now, physician-scientists have been referred to as an “endangered species.” Many factors have contributed to the dearth of clinical investigators, and training programs in clinical research are just one tool in a multi-pronged strategy to increase the number of successful physician-scientists working in health research. A qualitative approach that analyzes students’ educational goals and experiences can help fill the gaps in our knowledge about how best to train aspiring physician-scientists. This study was an interpretive phenomenology that evaluated the Master of Science program in Clinical and Translational Research (MSCTR) at the University of Cincinnati. The purpose of the study was to allow students to articulate their expectations, needs, and experiences in the MSCTR. The study included a group level assessment (GLA) and document review. Findings suggest several reasons students enrolled in the MSCTR, as well as some areas for improvement in the program: more physician-centered classes, a more directed curriculum, and a more cohesive course plan overall. Conclusions from these recommendations are that student perspectives can inform decisions around curricula and instructional methods in powerful ways, particularly when combined with a qualitative methodological approach. This study revealed several insights into how faculty and administrators can more effectively train physicians in research methodology. Training should be as applied and relevant as possible to make it directly applicable to clinical practice. This goal could be enhanced if classes – particularly statistics classes – were more physician-oriented. The curriculum of a clinical research training program for clinicians should be clear and directed, but with some flexibility and space within the curriculum for classes within areas of specialization. Collaboration should be integrated throughout, and courses should follow a logical, interconnected sequence.

Nous proposons dans ce travail une analyse multidimensionnelle du vieillissement langagier normal et du vieillissement pathologique de type Alzheimer. Une analyse comparative du discours oral spontané a été réalisée à travers trois niveaux linguistiques : 1) le niveau phonético-phonologique ; 2) le niveau lexico-sémantique ; 3) le niveau syntaxique. Nos résultats révèlent que le discours produit par les patients atteints de la maladie d’Alzheimer se distingue de celui des personnes âgées saines par une parole disfluente, une réduction significative de la diversité du vocabulaire et de l’informativité du discours, et enfin, par une réduction remarquable de la complexité syntaxique. L’ensemble de nos résultats entend contribuer à améliorer notre connaissance de la sémiologie linguistique de la maladie d’Alzheimer. Nous montrons ainsi qu’une meilleure connaissance des troubles du langage associés à cette pathologie pourrait contribuer de façon pertinente à améliorer le diagnostic précoce et/ou différentiel de la maladie d’Alzheimer. Du point de vue applicatif, l’enjeu de cette recherche translationnelle vise l’élaboration d’un outil d’évaluation du langage adapté à la personne âgée démente. A travers ce travail de thèse, nous espérons avoir contribué au développement futur d’une prise en charge non médicamenteuse de type orthophonique visant le maintien, voire l’amélioration, de la capacité communicative des patients souffrant de la maladie d’Alzheimer. / This study deals with a multidimensional analysis of language attrition in normal aging and in Alzheimer’s disease. A comparative analysis of spontaneous speech was conducted through three linguistic levels : 1) the phonetic-phonological level ; 2) the lexical-semantic level ; 3) the syntactic level. Our results show that the discourse produced by Alzheimer patients differs significantly from that produced by healthy elderly by a more disfluent speech, a significant reduction of the vocabulary diversity and discourse informativeness, and finally, by a remarkable reduction in syntactic complexity. Our results contribute to understand better the linguistic profile of Alzheimer’s patients. We show that a better understanding of language disorders associated with this pathology may contribute in a meaningful way to improve early and / or differential diagnosis of Alzheimer’s disease. In term of application, the goal of this research is to develop a language assessment tool adapted to the demented elderly. Through this work we hope to have contributed to the further development of speech therapy (i.e. non-pharmacological treatment) useful for the maintenance or improvement of the communicative capacity of patients suffering from Alzheimer’ disease.

Las investigaciones traslacionales tienen el objetivo de poner a disposición de investigaciones las evidencias obtenidas en investigaciones básicas para ensayos clínicos. Para facilitar la investigación traslacional es necesario relacionar dicha información mediante la integración de repositorios de información biológica y médica. Debido a la complejidad, cantidad, diversidad y rápida evolución de la información biológica, es imposible gestionar los repositorios biológicos de manera manual ya que supondría una gran inversión en tiempo y en esfuerzo. Por lo tanto, cada vez más es necesario dotar de nuevas herramientas de gestión que faciliten esta tarea y pueda ser realizada de manera autónoma. Esta tesis presenta un entorno para la gestión e integración semántica utilizado las tecnologías de la Web semántica, las cuales son utilizadas para representar, almacenar, explotar y guiar el proceso de integración de la información y conocimiento. Como resultado principal se integraron repositorios de genes y proteínas ortólogas con enfermedades genéticas. / Translational research aims to connect basic biomedical researches with clinical research in order to reach new conclusions based on biomedical evidences. To facilitate the translational research, biological and biomedical information must be related. So, we need to integrate biological and biomedical repositories. Life sciences is a knowledge based discipline, in the data and knowledge is represented through vast amounts of complex and changing information stored in disparate resources and in machine-unfriendly formats. Therefore, the availability of computational methods for organizing, accessing and retrieving information in a systematic way has become crucial for the progress of research in life sciences. In this thesis, we present a framework for the semantic management and integration using semantic web technologies. This framework assists life scientists in the exploration of orthologs/genetic diseases research paths by providing a precise, explicit meaning for information units and intertwining such information.

Introduction Occupational therapists are concerned with enabling people to perform the daily life tasks they need, want, or are expected to perform for fullest possible integration into community living and participation in society. Children with mild disabilities have problems performing personal and instrumental activities of daily living (ADL) tasks at home or school, and that can limit their full integration and participation in their homes and school lives. There is a need, therefore, to identify their specific problems with ADL task performance so as to be able to develop effective interventions. Not only, there is a need for evidence related to effectiveness of occupational therapy interventions for children with mild disabilities, but also a need for valid occupational-therapy-specific evaluation tools for use with children. Purpose The purpose of this thesis was to contribute evidence to support the valid use of the Assessment of Motor and Process Skills (AMPS) with children, including children living in Middle Europe. More specifically, I aimed to evaluate validity evidence from different sources related to the use of the AMPS in occupation-based and occupation-focused evaluation and intervention. Method This thesis consisted of four studies, implemented in two phases. Phase one focused on evaluation of a) validity evidence of the AMPS scales in relation to internal structure and stability of item difficulty calibration values for a Middle European sample compared to samples from other world regions (Study I); b) the stability of the mean AMPS measures between typically-developing children from Middle Europe and from other world regions (Study II); and c) the sensitivity of the AMPS measures to discriminate between typically-developing children and children with and at risk for mild disabilities (Study III). Participants for phase one were from both Middle Europe and from other world regions and they were selected from the AMPS database, Ft. Collins, Colorado, USA. Data were analyzed using many-facet Rasch analyses, ANOVAs, regression analyses, related post-hoc tests, and effect size calculations. Phase two of the research project focused on evaluating validity evidence for the use of the AMPS as a standardized, occupation-based, and occupation-focused evaluation tool in the context of a feasibility study with children with mild disabilities implemented in a Swiss setting (Study IV). Data were analyzed based on feasibility objectives and the principles of deductive content analysis. The evaluation of validity evidence of the AMPS in relation to consequences of testing and test fairness was a focus of all studies (Studies I to IV). Results In Study I, data for 1346 participants from Middle Europe and 144,143 participants from other world regions were analyzed. The participants were between the ages of 3 and 103 years, and they were well or had a variety of diagnoses. The results revealed that overall the item difficulty calibration values of the AMPS remained stable and that only one out of 36 ADL items of the AMPS demonstrated DIF, but this DIF did not lead to DTF (i.e., all measures fell within 95% confidence bands). In Study II, data for 11,189 typically-developing children from Middle Europe and other world regions who were between the ages of 2 and 15 were analyzed. The results of ANOVAs revealed significant effects for mean ADL motor and for ADL process ability measures by region and a significant age by region interaction effect for mean ADL process ability. Out of 168 estimated contrasts between Middle Europe and the other world regions for mean ADL motor and ADL process ability, only seven were statistically significant (4.17%), and only two were more than ±1 SE from the international means. In Study III, regression analyses of data for 10,998 children, 4 to 15 years, who were typically-developing or with mild disabilities, revealed significant age by group interaction effects. Post hoc t tests revealed significant group differences in ADL ability at all ages beyond the age of 4. ADL process ability effect sizes were moderate to large at all ages and ADL motor ability effect sizes were mostly moderate to large age 6 and above. In Study IV, the use of the AMPS within the context of a feasibility study based on data of 17 Swiss children with mild disabilities was evaluated. The analyses revealed several strengths and problems that were related to the time, equipment, and materials for administering the AMPS, the adherence to standardized administration procedures, the scope of the AMPS as a test of ADL performance, and the reliable rating by the blinded rater. Conclusion This thesis provided evidence to support the validity of the AMPS measures and scales when used to evaluate quality of ADL task performance of persons from Middle Europe. Additionally, this thesis provided evidence that the international age-normative means of the AMPS are likely applicable to children from Middle Europe. Moreover, the findings supported the sensitivity of the AMPS measures to discriminate between typically-developing children and children with and at risk for mild disabilities. When it comes to implementation of the AMPS in the context of a feasibility study, the findings indicated both strengths and problems in using the AMPS as an outcome measure that need to be considered when planning further studies.

La réponse tissulaire des patients soumis à une radiothérapie, malgré des protocoles de traitement identiques, est variable avec des extrêmes importants. Une des questions posées à la radiobiologie est d'expliquer ces variations (approche a posteriori) et si possible de les prévoir (approche a priori). La réponse d'un organisme et de tissus complexes à la radiothérapie est la résultante de nombreux déterminants. Certains appartiennent à la dynamique et à l'homéostasie tissulaire (inflammation, cytokines, etc.) d'autre à la sensibilité et à la réponse cellulaire (sensibilité intrinsèque, réparation de l'ADN, régulation de la mort cellulaire, etc.). Concernant les déterminants cellulaires, l'Equipe d'Accueil a proposé de classer les humains en 3 groupes de radiosensibilités différentes, le premier considéré comme normal est de loin le plus important (près de 75% des individus), le groupe II de radiosensibilité intermédiaire représente la majeure partie des individus pour lesquels une réponse anormale est constatée après radiothérapie. Le groupe III rassemble des pathologies particulièrement rares associées à une hyper-radiosensibilité marquée, voire très marquée. Les patients du groupe II présentent donc une réponse thérapeutique inattendue et / ou des effets secondaires précoces ou tardifs sévères à des doses d'irradiation dont on attend une tolérance normale. Les patients du groupe II peuvent aussi être caractérisés par une forte prédisposition au cancer et aux tumeurs radio induites. Il existe une variabilité intrinsèque liée à des facteurs endogènes tels que la qualité de réparation de l'ADN, ou la production spontanée de micronoyaux ; et des facteurs exogènes. A cet égard, certaines médications sont susceptibles de modifier la réponse cellulaire à la radiothérapie, telles que les statines, les anticoagulants ou les antiagrégants plaquettaires. Approche a posteriori : par une étude clinique unicentrique de 65 patients atteints de cancers de la prostate et traités par le même radiothérapeute dans les mêmes conditions, la fréquence et la gravité des effets secondaires rectaux par rapport à la prise ou non de statines ont été étudiées : un effet radioprotecteur des statines vis-à-vis de la rectite radique a été mis en évidence in vivo sur des arguments statistiques pertinents. Approche a priori : par l'étude de la réponse cellulaire et moléculaire aux radiations de fibroblastes humains (notamment issus de tissus intestinaux sains). Ont été étudiés : la réparation et la signalisation des cassures double-brin de l'ADN par l'analyse des foci nucléaires H2AX et pATM ; le transit radioinduit de la protéine ATM du cytoplasme vers le noyau a été observé pour la première fois sur des fibroblastes humains rectaux. Les statines semblent accélérer ce transit, produisant un effet modérateur de la sévérité des rectites. L’étude des différents produits antioxydants et stimulateurs de la réparation de l’ADN a permis de montrer que les statines ont effet non équivoqué sur la réparation cellulaire après irradiation. Ces résultats ouvrent des perspectives pour des études plus approfondies de l'usage de médications facilement accessibles capables de moduler la gravité des effets secondaires de la radiothérapie. / The tissue response of patients undergoing radiotherapy, despite identical treatment protocols, could have important variations. One of the questions asked to the radiobiology is to explain these variations (a posteriori approach) and if possible to predict it (a priori approach). The response of an organism and complex tissues to radiotherapy is the result of many determinants. Some belong to the tissue dynamics and homeostasis (inflammation, cytokines, etc.) and others to the sensitivity and cellular response (intrinsic sensitivity, DNA repair, regulation of cell death, etc.). About cellular determinants, our research team proposed to classify humans into three groups of different radiosensitivity levels, the first considered as normal is by far the largest (almost 75% of individuals), group II of intermediate radiosensitivity represents the majority of individuals having an abnormal response to radiotherapy. Group III gathers extremely rare conditions associated with marked or very marked hyper-radiosensitivity which are usually life threatening. Therefore patients in group II show either unexpected therapeutic response or severe radiation early or late side effects after doses for which normal tolerance is expected. Patients in group II can also be characterized by a strong predisposition to cancer and radiation-induced tumors. There is an inherent variability related to endogenous factors, such as the quality of DNA repair, or the spontaneous production of micronuclei; and exogenous factors. In this regard, certain medications may alter the cellular response to radiation therapy, such as statins, antiplatelet agents or anticoagulants. A posteriori approach: a single-center clinical study of 68 patients with prostate cancer treated by the same radiation oncologist in the same conditions, the frequency and severity of rectal side effects are compared to the use or not of statins : a radioprotective effect of statins toward radiation proctitis cannot be excluded. A priori approach: by studying the cellular and molecular radiation response in human fibroblasts (especially from healthy bowel tissue). Were studied: signaling and repair of DNA double-strand breaks by analysis of nuclear foci of MRE11; H2AX and pATM; radiation induced ATM protein transit from the cytoplasm to the nucleus was observed for the first time in rectal tissue fibroblasts. Statins appear to speed up this transit, making possible a radioprotective effect. These results open perspectives for further studies for the use of medications readily available that can modulate the severity of side effects of radiotherapy.

Clinician Scientists werden im Kontext einer Translationalen Forschung als Schlüsselfiguren thematisiert, insbesondere seit ihnen das Potenzial zugesprochen worden ist, biomedizinische Grundlagenforschung und medizinische Praxis auf praktische Weise miteinander verbinden zu können. Damit adressiert das Berufsbild des Clinician Scientists auf individueller Ebene das sogenannte ‚valley of death‘, welches metaphorisch zentrale Übersetzungslücken im biomedizinischen Erkenntnis- und Entwicklungsprozess markiert. Ungeachtet ihrer besonderen Position befinden sich Clinician Scientists noch immer in einer beruflichen Nische, der es offensichtlich nicht gelingt, die Translationsanforderungen auf der praktischen Ebene tatsächlich erfolgreich zu vermitteln. Vor diesem Hintergrund fragt die vorliegende Arbeit nach dem Professionszustand des Clinician Scientists und bedient sich dabei eines neo-pragmatischen Zugangs, der es ermöglicht Kritik und Empörung, welche die im Feld befindlichen Akteure gegenüber ihrer translationsorientierten Umwelt formulieren, für eine Soziologie der Kritik zu nutzen. Der analytische Bezugsrahmen ermöglicht sodann eine Beleuchtung des Professionszustands über individuelle Krisenzustände, die eine öffentliche Kritik an den eigenen professionellen Zuständen freisetzt. Die Arbeit leistet damit eine Beschreibung kritischer Potenziale, die im Kontext von Professionsentwicklungen gedeutet werden und offenbart im Ergebnis ein ambivalentes Verhältnis zwischen den Konzeptionen Translation und Profession: Ungeachtet ihres theoretisch augenscheinlich professionsfördernden Charakters avanciert die Translationale Forschung zum individuell-situativen Krisenherd und be- bzw. verhindert somit zugleich eine professionelle Entwicklung des Clinician Scientists. / Clinician scientists are described as a key solution towards the problem of translational research in the field of (bio)medicine, especially since they are perceived to have the potential to combine biomedical research and clinical practice. Translational research overall addresses the ‘translation gap’ between biomedical research findings on the one hand and clinical practice and applications on the other, which constitutes a major challenge towards the current biomedical research system. Despite their importance for translational problems clinician scientists still constitute a ‘rare breed’, struggling in fulfilling expectations of translational research on the individual level. In the light of this problematization, the cumulative thesis aims to explore the professional nature of the clinician scientist with the help of a neo-pragmatic approach by making use of critique and indignation individuals utter against their translational ecology. The analytical framework therefore allows to analyze professional development via individual situations of crisis. The thesis thus contributes to a description of critical potentials from individuals involved and reveals an ambivalent relationship between the concepts of translation and profession: despite its obviously supporting character translational research turns into a moment of crisis actually hindering and, respectively preventing clinician scientists from becoming a profession.