Educar e habilitar profissionais em grande número é um desafio de gestão que se apresenta de forma prática aos gestores e administradores universitários, quaisquer que sejam as suas formações iniciais. Os desafios tornam-se ainda maiores, dado o quadro institucional e o ambiente competitivo em que as Instituições de Ensino Superior (IES) se inserem. A gestão por competências tem se mostrado valiosa no mundo empresarial; contudo, a sua introdução como instrumento de gestão nas Instituições de Ensino Superior (IES) ainda é incipiente. Nesse contexto, o papel dos gestores é de fundamental importância para mobilizar e articular as competências dos indivíduos e das equipes para o alcance das estratégias definidas para a instituição. Com o presente estudo, foi possível identificar, através de um estudo qualitativo com base em entrevistas, as principais competências que o gestor educacional utiliza nas atividades diárias. Como resultado da pesquisa, foi observado que: a) existe homogeneidade de entendimento conceitual, por parte dos entrevistados, quanto à noção de Competência; b) os elementos facilitadores para o desenvolvimento do processo de gestão por competências estão relacionados aos valores e à natureza de cada IES; e c) os entrevistados mencionaram diferentes maneiras através das quais são desenvolvidas as competências para qualificar os profissionais ligados à gestão educacional em cursos de Administração; entre elas destacamse: as capacitações e/ou processos de desenvolvimento que tem origem na aprendizagem formal; o autodesenvolvimento; e a aprendizagem na prática. / To educate and qualify professionals in great number is a management challenge present in the practical way of the managers and coordinators at the university level, independently of their initial formations. The challenges become more critical due to the institutional competitive context where the Superior Learning Institutions develop their activities. The management by competencies has been shown to be valuable in the industry world, but its introduction as a management tool in the Superior Learning Institutions is still incipient. In this context, the role played by managers is very important to mobilize and articulate the individual and group competencies to reach the strategies defined to the organization. In the present study it was possible to identify, by a multiple case study based on interviews, the main competencies used by managers in their daily routine practice. As results, we observed the following: a) there is an homogeneity of conceptual understanding by the interviewees regarding to the competency meaning; b) the facilitation tools for the development of the management by competencies are related to the values and nature of every Superior Learning Institution; and c) the interviewee pointed out different ways to develop competencies to qualify professionals working in the educational management in Administration courses, mainly skills and/or process of development originated in the formal learning; the self-development; and the practical learning.

Educar e habilitar profissionais em grande número é um desafio de gestão que se apresenta de forma prática aos gestores e administradores universitários, quaisquer que sejam as suas formações iniciais. Os desafios tornam-se ainda maiores, dado o quadro institucional e o ambiente competitivo em que as Instituições de Ensino Superior (IES) se inserem. A gestão por competências tem se mostrado valiosa no mundo empresarial; contudo, a sua introdução como instrumento de gestão nas Instituições de Ensino Superior (IES) ainda é incipiente. Nesse contexto, o papel dos gestores é de fundamental importância para mobilizar e articular as competências dos indivíduos e das equipes para o alcance das estratégias definidas para a instituição. Com o presente estudo, foi possível identificar, através de um estudo qualitativo com base em entrevistas, as principais competências que o gestor educacional utiliza nas atividades diárias. Como resultado da pesquisa, foi observado que: a) existe homogeneidade de entendimento conceitual, por parte dos entrevistados, quanto à noção de Competência; b) os elementos facilitadores para o desenvolvimento do processo de gestão por competências estão relacionados aos valores e à natureza de cada IES; e c) os entrevistados mencionaram diferentes maneiras através das quais são desenvolvidas as competências para qualificar os profissionais ligados à gestão educacional em cursos de Administração; entre elas destacamse: as capacitações e/ou processos de desenvolvimento que tem origem na aprendizagem formal; o autodesenvolvimento; e a aprendizagem na prática. / To educate and qualify professionals in great number is a management challenge present in the practical way of the managers and coordinators at the university level, independently of their initial formations. The challenges become more critical due to the institutional competitive context where the Superior Learning Institutions develop their activities. The management by competencies has been shown to be valuable in the industry world, but its introduction as a management tool in the Superior Learning Institutions is still incipient. In this context, the role played by managers is very important to mobilize and articulate the individual and group competencies to reach the strategies defined to the organization. In the present study it was possible to identify, by a multiple case study based on interviews, the main competencies used by managers in their daily routine practice. As results, we observed the following: a) there is an homogeneity of conceptual understanding by the interviewees regarding to the competency meaning; b) the facilitation tools for the development of the management by competencies are related to the values and nature of every Superior Learning Institution; and c) the interviewee pointed out different ways to develop competencies to qualify professionals working in the educational management in Administration courses, mainly skills and/or process of development originated in the formal learning; the self-development; and the practical learning.

O presente trabalho foi estruturado a partir de um estudo qualitativo baseado na experiência de planejamento estratégico em uma universidade. Teve por objetivo identificar as variáveis que intervêm na implementação daquele processo com a utilização da metodologia de desdobramento de diretrizes. O estudo qualitativo realizado adotou procedimentos que incluíram pesquisa individual com representantes dos segmentos da universidade. Os entrevistados representam os responsáveis pelas finalidades de planejamento, de supervisão geral e setorial, de execução do ensino, bem como de apoio técnico e assessoria. Os principais procedimentos adotados no desenvolvimento da pesquisa foram descrição, análise e interpretação. O planejamento estratégico, usualmente descrito como processo integrante da gestão empresarial, é apresentado como um recurso que capacita a instituição de ensino superior a atuar com eficiência e eficácia e a reagir com rapidez às demandas do seu entorno social. O desdobramento das diretrizes é mostrado como uma ferramenta que pode ser aplicada no detalhamento do plano estratégico, assim que as linhas de ação anuais estejam definidas. Resultaram do estudo a confirmação de que professores e funcionários necessitam de incentivo para atuar nesse processo e que fatores como liderança e comprometimento com resultados, esforço para o compartilhamento do propósito comum, motivação dos envolvidos e acompanhamento dos processos são essenciais para a implementação, com sucesso, do plano estratégico. / This paper is structured on qualitative studies carried out considering the strategic planning process in a university. Its aim is to identify variables which intervene in the implementation of the process using the policy deployment methodology. The qualitative study was carried out using procedures that included individual survey with the persons who are responsible for planning, general and sectorial supervision, teaching, as well as technical support and consultantship, of the many sectors of the university. Description, analysis and interpretation were the main procedures used in developing the survey. Strategic planning, usually described as a process of integration in management, is presented as a resource that enables a college or a university to act efficiently and effectively and react promptly to the demands of the social environment. The policy deployment is presented as a tool which can be applied in detailing the strategic planning as soon as the annual procedures have been defined. As a result of the study carried out it was confirmed that faculty and staff need stimuli in order to take part in the process and that aspects like leadership, commitment to results, effort in sharing common purposes, motivation of all involved individuals and the following-up of the processes are essential to the successful implementation of a strategic plan.

O presente trabalho foi estruturado a partir de um estudo qualitativo baseado na experiência de planejamento estratégico em uma universidade. Teve por objetivo identificar as variáveis que intervêm na implementação daquele processo com a utilização da metodologia de desdobramento de diretrizes. O estudo qualitativo realizado adotou procedimentos que incluíram pesquisa individual com representantes dos segmentos da universidade. Os entrevistados representam os responsáveis pelas finalidades de planejamento, de supervisão geral e setorial, de execução do ensino, bem como de apoio técnico e assessoria. Os principais procedimentos adotados no desenvolvimento da pesquisa foram descrição, análise e interpretação. O planejamento estratégico, usualmente descrito como processo integrante da gestão empresarial, é apresentado como um recurso que capacita a instituição de ensino superior a atuar com eficiência e eficácia e a reagir com rapidez às demandas do seu entorno social. O desdobramento das diretrizes é mostrado como uma ferramenta que pode ser aplicada no detalhamento do plano estratégico, assim que as linhas de ação anuais estejam definidas. Resultaram do estudo a confirmação de que professores e funcionários necessitam de incentivo para atuar nesse processo e que fatores como liderança e comprometimento com resultados, esforço para o compartilhamento do propósito comum, motivação dos envolvidos e acompanhamento dos processos são essenciais para a implementação, com sucesso, do plano estratégico. / This paper is structured on qualitative studies carried out considering the strategic planning process in a university. Its aim is to identify variables which intervene in the implementation of the process using the policy deployment methodology. The qualitative study was carried out using procedures that included individual survey with the persons who are responsible for planning, general and sectorial supervision, teaching, as well as technical support and consultantship, of the many sectors of the university. Description, analysis and interpretation were the main procedures used in developing the survey. Strategic planning, usually described as a process of integration in management, is presented as a resource that enables a college or a university to act efficiently and effectively and react promptly to the demands of the social environment. The policy deployment is presented as a tool which can be applied in detailing the strategic planning as soon as the annual procedures have been defined. As a result of the study carried out it was confirmed that faculty and staff need stimuli in order to take part in the process and that aspects like leadership, commitment to results, effort in sharing common purposes, motivation of all involved individuals and the following-up of the processes are essential to the successful implementation of a strategic plan.

Educar e habilitar profissionais em grande número é um desafio de gestão que se apresenta de forma prática aos gestores e administradores universitários, quaisquer que sejam as suas formações iniciais. Os desafios tornam-se ainda maiores, dado o quadro institucional e o ambiente competitivo em que as Instituições de Ensino Superior (IES) se inserem. A gestão por competências tem se mostrado valiosa no mundo empresarial; contudo, a sua introdução como instrumento de gestão nas Instituições de Ensino Superior (IES) ainda é incipiente. Nesse contexto, o papel dos gestores é de fundamental importância para mobilizar e articular as competências dos indivíduos e das equipes para o alcance das estratégias definidas para a instituição. Com o presente estudo, foi possível identificar, através de um estudo qualitativo com base em entrevistas, as principais competências que o gestor educacional utiliza nas atividades diárias. Como resultado da pesquisa, foi observado que: a) existe homogeneidade de entendimento conceitual, por parte dos entrevistados, quanto à noção de Competência; b) os elementos facilitadores para o desenvolvimento do processo de gestão por competências estão relacionados aos valores e à natureza de cada IES; e c) os entrevistados mencionaram diferentes maneiras através das quais são desenvolvidas as competências para qualificar os profissionais ligados à gestão educacional em cursos de Administração; entre elas destacamse: as capacitações e/ou processos de desenvolvimento que tem origem na aprendizagem formal; o autodesenvolvimento; e a aprendizagem na prática. / To educate and qualify professionals in great number is a management challenge present in the practical way of the managers and coordinators at the university level, independently of their initial formations. The challenges become more critical due to the institutional competitive context where the Superior Learning Institutions develop their activities. The management by competencies has been shown to be valuable in the industry world, but its introduction as a management tool in the Superior Learning Institutions is still incipient. In this context, the role played by managers is very important to mobilize and articulate the individual and group competencies to reach the strategies defined to the organization. In the present study it was possible to identify, by a multiple case study based on interviews, the main competencies used by managers in their daily routine practice. As results, we observed the following: a) there is an homogeneity of conceptual understanding by the interviewees regarding to the competency meaning; b) the facilitation tools for the development of the management by competencies are related to the values and nature of every Superior Learning Institution; and c) the interviewee pointed out different ways to develop competencies to qualify professionals working in the educational management in Administration courses, mainly skills and/or process of development originated in the formal learning; the self-development; and the practical learning.

O presente trabalho foi estruturado a partir de um estudo qualitativo baseado na experiência de planejamento estratégico em uma universidade. Teve por objetivo identificar as variáveis que intervêm na implementação daquele processo com a utilização da metodologia de desdobramento de diretrizes. O estudo qualitativo realizado adotou procedimentos que incluíram pesquisa individual com representantes dos segmentos da universidade. Os entrevistados representam os responsáveis pelas finalidades de planejamento, de supervisão geral e setorial, de execução do ensino, bem como de apoio técnico e assessoria. Os principais procedimentos adotados no desenvolvimento da pesquisa foram descrição, análise e interpretação. O planejamento estratégico, usualmente descrito como processo integrante da gestão empresarial, é apresentado como um recurso que capacita a instituição de ensino superior a atuar com eficiência e eficácia e a reagir com rapidez às demandas do seu entorno social. O desdobramento das diretrizes é mostrado como uma ferramenta que pode ser aplicada no detalhamento do plano estratégico, assim que as linhas de ação anuais estejam definidas. Resultaram do estudo a confirmação de que professores e funcionários necessitam de incentivo para atuar nesse processo e que fatores como liderança e comprometimento com resultados, esforço para o compartilhamento do propósito comum, motivação dos envolvidos e acompanhamento dos processos são essenciais para a implementação, com sucesso, do plano estratégico. / This paper is structured on qualitative studies carried out considering the strategic planning process in a university. Its aim is to identify variables which intervene in the implementation of the process using the policy deployment methodology. The qualitative study was carried out using procedures that included individual survey with the persons who are responsible for planning, general and sectorial supervision, teaching, as well as technical support and consultantship, of the many sectors of the university. Description, analysis and interpretation were the main procedures used in developing the survey. Strategic planning, usually described as a process of integration in management, is presented as a resource that enables a college or a university to act efficiently and effectively and react promptly to the demands of the social environment. The policy deployment is presented as a tool which can be applied in detailing the strategic planning as soon as the annual procedures have been defined. As a result of the study carried out it was confirmed that faculty and staff need stimuli in order to take part in the process and that aspects like leadership, commitment to results, effort in sharing common purposes, motivation of all involved individuals and the following-up of the processes are essential to the successful implementation of a strategic plan.

Ground level ozone is one of the most ubiquitous air pollutants in urban areas, and is generated by photochemical reactions of oxides of nitrogen (NOx) and volatile organic compounds (VOCs). The effectiveness of emission reduction strategies for ozone precursors is typically evaluated using gridded, photochemical air quality models. One of the underlying assumptions in these models is that industrial emissions are nearly constant, since many industrial facilities operate continuously at a constant rate of output. However, recent studies performed in the Houston-Galveston-Brazoria area indicate that some industrial emission sources exhibit high temporal emission variability that can lead to very rapid ozone formation, especially when emissions are composed of highly reactive volatile organic compounds. This work evaluates the impact of variable emissions from industrial sources on ground-level ozone formation in Houston area, utilizing a unique hourly emission inventory, known as the 2006 Special Inventory, created as a part of the second Texas Air Quality Study. Comparison of the hourly emissions inventory data with ambient measurements indicated that the impact of the variability of industrial source emissions on ozone can be significant. Photochemical modeling predictions showed that the variability in industrial emissions can lead to differences in local ozone concentrations of as much as 27 ppb at individual ozone monitor locations. The hourly emissions inventory revealed that industrial source emissions are highly variable in nature with diverse temporal patterns and stochastic behavior. Petrochemical and chemical manufacturing flares, which represent the majority of emissions in the 2006 Special Inventory, were grouped into categories based on industrial process, chemical composition of the flared gas, and the temporal patterns of their emissions. Stochastic models were developed for each categorization of flare emissions with the goal of simulating the characterized temporal emission variability. The stochastic models provide representative temporal profiles for flares in the petrochemical manufacturing and chemical manufacturing sectors, and as such serve as more comprehensive input for photochemical air quality modeling. / text

Der ischämische Schlaganfall, der durch eine akut auftretende Durchblutungsstörung des Gehirns zu einem plötzlichen Verschluss eines zerebrovaskulären Gefäßes und somit zu einer massiven und oft lebensgefährlichen Minderung der zerebralen Blutversorgung führt, zählt zu den dritthäufigsten Todesursachen beim Menschen in den Industrieländern der Erde. Da die verfügbaren Therapieverfahren bisher erheblichen Limitationen unterliegen und nicht für alle Patienten gleichermaßen geeignet sind, ist eine kontinuierliche Forschung an neuen Therapieverfahren sowie die Weiterentwicklung der bisher verfügbaren Behandlungsmethoden unabdingbar. Der Erfolg dieser Arbeiten ist von der Übertragbarkeit von Ergebnissen aus präklinischen Testverfahren in die Klinik abhängig. In der Vergangenheit konnten sich beispielsweise zahlreiche Medikamente, insbesondere die sogenannten Neuroprotektiva, trotz hervorragender präklinischer Ergebnisse nicht in der Klinik behaupten. Zahlreiche Untersuchungen, die die methodische Qualität tierexperimenteller Kleintierstudien evaluierten, deckten dabei signifikante Mängel und potentielle Gründe für den Misserfolg der Translation auf. Mit der zunehmenden Bedeutung von Großtierversuchen in im Forschungsfeld steigt die Notwendigkeit, auch diese Studien hinsichtlich ihrer methodischen Qualität zu überprüfen. Dies bildet den Schwerpunkt dieser Dissertation. Die vorliegende Dissertation überprüft anhand eines an speziellen schlaganfallspezifischen Leitlinien und Vorgaben angelehnten Qualitätsscores die methodische Qualität sowie Validität von Großtierversuchen in der translationalen Schlaganfallforschung. Anhand einer systematischen Literaturrecherche nach den Vorgaben der PRISMA-Leitlinien wurden von 1990-2019 publizierte präklinische Großtierstudien (n=208) identifiziert und analysiert. Der Qualitätsscore umfasste essentielle methodische Qualitätsmerkmale. Korrelationen der Studienqualität mit externen Faktoren wie der Tierart, dem Untersuchungsgegenstand, der Region, dem Einflussfaktor der publizierenden Zeitschrift sowie dem Erscheinen schlaganfallspezifischer Leitlinien (STAIR) wurden ebenfalls evaluiert. Gruppenvergleiche von jeweils 2 Gruppen wurden mit dem Wilcoxon-Rangsummentest für nicht-parametrische Daten überprüft, für Gruppenvergleiche von mehr als 2 Gruppen wurde der Kruskal-Wallis Test verwendet. Im Falle einer statistischen Signifikanz wurde diese mittels Dunn-Bonferroni post-hoc-Korrektur verifiziert. Die Korrelation zwischen der Studienqualität und dem Einflussfaktor wurde mit dem Rangkorrelationskoeffizient nach Spearman untersucht. Der Vergleich der tierarztspezifischen Gruppengrößen wurde mittels ANOVA untersucht, gefolgt von einer Dunn-Bonferroni post-hoc-Korrektur. Die Untersuchungen kamen zu dem Schluss, dass die methodische Qualität der bisherigen Großtierversuche als noch nicht optimal einzustufen ist. Studien wiesen insbesondere in methodischen Kriterien wie der Randomisierung, verdeckten Versuchsgruppenzuteilung, verblindeten Auswertung, primärer Endpunkte, der Effektstärkenberechnung, vorab erfolgten Stichprobenkalkulationen, Festlegung der Ein- und Ausschlusskriterien vor Versuchsbeginn, der Verifizierung der Infarktinduktion, der Dokumentation individueller Datenpunkte sowie einer Dokumentation möglicher Fehlerquellen sowie methodischer Limitierungen Mängel auf. Aufbauend auf den Analyseergebnissen wurden Empfehlungen für die translationale Schlaganfallforschung mit Großtieren erarbeitet. Diese sollen insbesondere zur Verbesserung der Studienplanung sowie des Studiendesigns, zu einer Erhöhung der Studientransparenz sowie zu einer kontinuierlichen, positiven Entwicklung der Studienqualität und zu einer erfolgreichen Translation von der Präklinik in die Klinik beitragen.:Inhaltsverzeichnis Widmung Inhaltsverzeichnis 1 Einleitung……………………………………………………………………………….. 1 2 Literaturübersicht………………………………………………………………………. 2 2.1 Der Schlaganfall des Menschen………………………………………………… 2 2.1.1 Die akute Schlaganfalltherapie…………………………………………….. 2 2.1.2 Die Rolle von Großtiermodellen in der präklinischen Schlaganfallforschung……………………………………………………………………… 4 2.2 Translation und Studienvalidität in der präklinischen Schlaganfallforschung 6 2.2.1 Leitlinien zur Sicherung des wissenschaftlichen Qualitätsstandards in der präklinischen Schlaganfallforschung………………………………………………..... 9 2.2.2 Die Bedeutung von systematischen Reviews und Meta-Analysen in der Sicherung wissenschaftlicher Qualitätsstandards……………………………………... 12 2.3.1 Ergebnisse aus systematischen Reviews und Meta-Analysen in der tierexperimentellen Schlaganfallforschung……………………………………………... 13 3 Material und Methoden……………………………...………………………………. 17 3.1 Auswahl der Studien……………………………………………………………. 17 3.1.1 Suchstrategie………………………………………………………………. 17 3.1.2 Ein- und Ausschlusskriterien..………….………………………………… 17 3.1.3 Ablauf der Studienselektion ………………………………………..…….. 18 3.2 Datenextraktion.………………………………………………………………… 19 3.2.1 Basisinformationen, Einschlussfaktor und tierartspezifische Gruppengrößen ……………………………………………………………………………. 19 3.3 Studienanalyse.…………………………………………………………………. 20 3.3.1 Analyse der Qualitätskriterien ……………………………………………. 20 3.3.2 Analyse der Studienqualität unter der Berücksichtigung nicht-experimenteller Einflussgrößen ………………………………………………………….. 20 3.4 Statistische Auswertung.……………………………………………………….. 22 4 Ergebnisse ……………………………………………………………………………. 24 4.1 Studienoutput, Basisinformationen.…………………………………………… 24 4.1.1 Gruppengrößen ……………………………………………………………. 26 4.2 Studienqualität.………………………………………………………………….. 28 4.2.1 Tierbezogene Angaben (Kategorie 1) …………………………………... 28 4.2.2 Studienplanung (Kategorie 2) ……………………………………………. 29 4.2.3 Studiendurchführung (Kategorie 3) ……………………………………… 29 4.2.4 Dokumentation der Studienresultate und -auswertung (Kategorie 4).. 30 4.3 Analysen der Studienqualität unter der Berücksichtigung nicht-experimenteller Einflussgrößen ………………………………………………………….. 31 4.3.1 Unterschiede der Studienqualität (regional, tierartspezifisch, interventionsabhängig) ……………………………………………………………………. 31 4.3.1 Entwicklung der Studienqualität nach Einführung der STAIR-Leitlinien 33 4.3.2 Beeinflussung der Studienqualität durch den Einflussfaktor..…………. 34 5 Diskussion …………………………………………………………………………….. 36 5.1 Einschätzung der Studienqualität und -validität von Großtierversuchen in der Schlaganfallforschung …………………………………………………………………….. 36 5.2 Empfehlungen für eine langfristige Verbesserung der Studienqualität und -validität ..……………………………………………………………………………………. 43 5.2.1 Empfehlungen für eine Verbesserung der Studienplanung und des Studiendesigns.……………………………………………………………………………. 44 5.2.2 Empfehlungen zur Erhöhung der Studientransparenz..……………….. 47 5.3 Ausblick ………………………………………………………………………….. 49 6 Zusammenfassung.………………………………………………………………….. 51 7 Summary ……………………………………………………………………………… 53 8 Literaturverzeichnis ………………………………………………………………….. 55 9 Anhang …………….………………………………………………………………….. 62 / Ischemic stroke, which is based on a sudden occlusion of a cerebral artery is characterized by a massive and often life-threatening reduction of cerebral blood supply. Being frequent, ischemic stroke accounts for one in three deaths in the industrialized nations. The complex pathophysiology an acute stroke and the lack of broadly applicable treatment options requires continuous research for novel and refinement of available treatment methods. The success of this work decisively depends on result transferability from preclinical test procedures to clinically available treatments. In the past, numerous drugs, predominantly neuroprotectants, did not show clinical efficacy despite excellent results in preclinical studies. Post-hoc analyses revealed methodological quality issues in most small animal studies that are believed to be responsible for the translational failure. Since large animal experiments become increasingly important in translational stroke research, the need to review these studies regarding their methodological quality became apparent. This dissertation addresses this point. The methodological quality and validity of large animal experiments in translational stroke research was evaluated by using a quality score. This score was based on stroke-specific guidelines and recommendations for high-quality research. Based on a systematic literature search according to the PRISMA guidelines, preclinical large animal studies published from 1990-2019 (n=208) were identified and analyzed. The quality score comprised essential methodological features. Correlations of study quality with external factors such as species, type of intervention, region, journal`s impact factor as well as the implementation of stroke specific guidelines in the past (STAIR) were also evaluated. Group comparisons of 2 groups each were checked with the Wilcoxon rank sum test for non-parametric data while Kruskal-Wallis was used for group comparisons of more than 2 groups. Statistical significance was verified using Dunn-Bonferroni post-hoc correction. The correlation between study quality and impact factor was examined using Spearman correlation coefficient. Comparison of individual group sizes was investigated using ANOVA, followed by a Dunn-Bonferroni post-hoc correction. The methodological quality of the previous large animal experiments was found mediocre with, among others, shortcomings identified in methodological criteria such as blinding and randomization, definition of primary endpoints, effect size estimation and a priori sample size calculation, determination and application of preset inclusion and exclusion criteria, verification of infarct induction, documentation of individual data points, as well as the documentation of possible sources of error and methodological limitations. In summary, resulting recommendations made below are based on these shortages and are intended to improve study planning and design, and to increase study transparency. Furthermore these recommendations are intended to impact positively and continuously study quality and validity as well as translational success.:Inhaltsverzeichnis Widmung Inhaltsverzeichnis 1 Einleitung……………………………………………………………………………….. 1 2 Literaturübersicht………………………………………………………………………. 2 2.1 Der Schlaganfall des Menschen………………………………………………… 2 2.1.1 Die akute Schlaganfalltherapie…………………………………………….. 2 2.1.2 Die Rolle von Großtiermodellen in der präklinischen Schlaganfallforschung……………………………………………………………………… 4 2.2 Translation und Studienvalidität in der präklinischen Schlaganfallforschung 6 2.2.1 Leitlinien zur Sicherung des wissenschaftlichen Qualitätsstandards in der präklinischen Schlaganfallforschung………………………………………………..... 9 2.2.2 Die Bedeutung von systematischen Reviews und Meta-Analysen in der Sicherung wissenschaftlicher Qualitätsstandards……………………………………... 12 2.3.1 Ergebnisse aus systematischen Reviews und Meta-Analysen in der tierexperimentellen Schlaganfallforschung……………………………………………... 13 3 Material und Methoden……………………………...………………………………. 17 3.1 Auswahl der Studien……………………………………………………………. 17 3.1.1 Suchstrategie………………………………………………………………. 17 3.1.2 Ein- und Ausschlusskriterien..………….………………………………… 17 3.1.3 Ablauf der Studienselektion ………………………………………..…….. 18 3.2 Datenextraktion.………………………………………………………………… 19 3.2.1 Basisinformationen, Einschlussfaktor und tierartspezifische Gruppengrößen ……………………………………………………………………………. 19 3.3 Studienanalyse.…………………………………………………………………. 20 3.3.1 Analyse der Qualitätskriterien ……………………………………………. 20 3.3.2 Analyse der Studienqualität unter der Berücksichtigung nicht-experimenteller Einflussgrößen ………………………………………………………….. 20 3.4 Statistische Auswertung.……………………………………………………….. 22 4 Ergebnisse ……………………………………………………………………………. 24 4.1 Studienoutput, Basisinformationen.…………………………………………… 24 4.1.1 Gruppengrößen ……………………………………………………………. 26 4.2 Studienqualität.………………………………………………………………….. 28 4.2.1 Tierbezogene Angaben (Kategorie 1) …………………………………... 28 4.2.2 Studienplanung (Kategorie 2) ……………………………………………. 29 4.2.3 Studiendurchführung (Kategorie 3) ……………………………………… 29 4.2.4 Dokumentation der Studienresultate und -auswertung (Kategorie 4).. 30 4.3 Analysen der Studienqualität unter der Berücksichtigung nicht-experimenteller Einflussgrößen ………………………………………………………….. 31 4.3.1 Unterschiede der Studienqualität (regional, tierartspezifisch, interventionsabhängig) ……………………………………………………………………. 31 4.3.1 Entwicklung der Studienqualität nach Einführung der STAIR-Leitlinien 33 4.3.2 Beeinflussung der Studienqualität durch den Einflussfaktor..…………. 34 5 Diskussion …………………………………………………………………………….. 36 5.1 Einschätzung der Studienqualität und -validität von Großtierversuchen in der Schlaganfallforschung …………………………………………………………………….. 36 5.2 Empfehlungen für eine langfristige Verbesserung der Studienqualität und -validität ..……………………………………………………………………………………. 43 5.2.1 Empfehlungen für eine Verbesserung der Studienplanung und des Studiendesigns.……………………………………………………………………………. 44 5.2.2 Empfehlungen zur Erhöhung der Studientransparenz..……………….. 47 5.3 Ausblick ………………………………………………………………………….. 49 6 Zusammenfassung.………………………………………………………………….. 51 7 Summary ……………………………………………………………………………… 53 8 Literaturverzeichnis ………………………………………………………………….. 55 9 Anhang …………….………………………………………………………………….. 62

Contexte : Jusqu'à présent, les résultats de la recherche de contextes environnementaux et les comportements antécédents de l’obésité pédiatrique n'ont pas été cohérents. But : L’objectif global de cette thèse est d'étudier l'association entre les caractéristiques des parcs, des écoles et des quartiers résidentiels avec des indicateurs liés à l'adiposité : 1) De regroupés les parcs par leurs caractéristiques saillantes et déterminer si certains " types " de parcs sont associés à l'activité physique (AP) et à l'adiposité ; 2) Décrire les écoles en fonction de leurs caractéristiques d’environnement bâties (EB) et sociales prédominantes pour l'AP et d’explorer leurs associations avec l'AP; 3) Déterminer si les caractéristiques théoriquement marchable de l'EB résidentiel sont associées aux comportements de mouvement de 24 heures (sommeil, sédentarité, AP légère (APL), AP modérée à vigoureuse (APMV)) dans les analyses transversales et prospectives. Méthodes : Les données proviennent de la cohorte QUALITY, une étude québécoise portant sur 630 enfants, âgés de 8 à 10 ans lors du recrutement, et ayant une histoire d’obésité parentale. Les environnements des parcs, des résidences et des écoles de 512 participants habitant la Région métropolitaine de Montréal ont été caractérisés. Les données comprenaient des données administratives, de recensement et des observations directes y compris des questionnaires complétés par un membre du personnel de l’école. L'AP des jeunes a été auto rapporté et mesuré par accéléromètres au temps 0 et au suivi 2 ans plus tard. La sédentarité a été mesuré aux deux temps à l'aide d'accéléromètres et le sommeil a été calculé basé sur le temps pendant lequel l'accéléromètre n'était pas porté. L’adiposité a été mesuré avec un DXA au temps 0. L'indice de masse corporelle a été calculé aux deux temps. Les données ont été analysées avec l’analyse en composantes principales, l'analyse en grappes, la régression linéaire et logistique, les équations d'estimation généralisées et l'analyse des données compositionnelles. Résultats : Certaines caractéristiques particulières des parcs, des écoles et des aspects « marchables » des quartiers ont été associées aux résultats liés à l'adiposité chez les participants. Les types de parcs qui offraient des possibilités de jeux non structurés et une variété d'AP étaient associés à l'AP autodéclarée, et les parcs esthétiquement agréables étaient également associés à l’adiposité réduite. Les écoles qui offraient des possibilités de jeux non structurés et qui encourageaient l'AP étaient associées à l'AP. Les caractéristiques « marchables » des quartiers étaient associées à une augmentation de l'APMV et à une diminution du sommeil, de la sédentarité et de l'APL sur une période de 24 heures chez les filles. Conclusion : Cette thèse contribue à la littérature en examinant trois influences contextuelles importantes sur les résultats liés à l'adiposité chez les enfants. Ces environnements ont été caractérisés de façon objective, en opérationnalisant leurs principales caractéristiques et en utilisant des approches statistiques novatrices. Les résultats appuient le concept que la prévention de l'obésité et les efforts visants à accroître l'AP devraient inclure la prise en compte des EB et sociaux et devraient cibler les multiples facteurs qui favorisent des comportements sains chez les enfants. / Background: Paediatric obesity is a global public health concern. In order to identify potential population-based intervention and prevention strategies, environmental contexts are being investigated in relation to childhood obesity and antecedent behaviours, including physical activity (PA). However, to date, findings in the area have been inconsistent. Purpose: The overarching goal of this thesis is to investigate the association between features of parks, school and neighbourhood environments in relation to adiposity-related outcomes. Specifically: 1) To group and characterize parks by their salient features and to determine if certain park “types” are associated with PA and adiposity outcomes; 2) To characterise schools by their predominant built and social environmental features for PA and to explore associations between school features and PA in cross-sectional and prospective analyses; 3) To determine if theoretically walkable features of the neighbourhood built environment are associated with 24-hour movement behaviours (sleep, sedentary behaviour, light physical activity (LPA), moderate-to-vigorous physical activity (MVPA)) in cross-sectional and prospective analyses. Methods: Data were drawn from the QUALITY Cohort, a Quebec-based study of 630 children age 8-10 years at baseline with a parental history of obesity. Baseline park, residential and school environments of 512 participants living in the Montreal Metropolitan Area were characterised. Data included geographically linked census and administrative data and in-person observations. Questionnaires were completed by school principals or physical education teachers. PA was measured at baseline and follow up using self-reported questionnaires and by accelerometer. Sedentary time was measured at baseline and follow up using accelerometers while sleep time was calculated as the time the accelerometer was not worn. Body fat was measured using a DXA at baseline. Overweight and obesity was identified using body mass index computed from measured weight and height at baseline and follow up. Analyses included principal component analysis, cluster analysis, linear and logistic regression, generalized estimating equations and compositional data analysis. Results: Findings point to specific features of parks, schools and theoretically walkable neighbourhood features that are associated with adiposity-related outcomes in the youth participants. Notably, certain types of parks that provide opportunities for unstructured play and a variety of physical activities are associated with self-reported PA while aesthetically pleasing parks are also associated with body fat. Schools that provide opportunities for unstructured play and that promote PA are associated with accelerometer measured PA, and the associations are different between boys and girls. Lastly, theoretically walkable neighbourhood features are associated with an increase in MVPA and a slight decrease in sleep, sedentary time and LPA over a 24-hour period among girls only. Conclusion: This thesis contributes to the literature by considering three important contextual influences on children’s adiposity-related outcomes: parks, school and the residential environment. This is done by objectively characterizing these environments, by operationalising key characteristics of them, and by using innovative statistical approaches. Findings support the notion that obesity prevention and efforts to increase PA should include the consideration and modification of built and social environments and should target the multiple population-level factors that support healthy behaviours among children.

Contexte: L'obésité chez les jeunes représente aujourd’hui un problème de santé publique à l’échelle mondiale. Afin d’identifier des cibles potentielles pour des stratégies populationnelles de prévention, les liens entre les caractéristiques du voisinage, l’obésité chez les jeunes et les habitudes de vie font de plus en plus l’objet d’études. Cependant, la recherche à ce jour comporte plusieurs incohérences. But: L’objectif général de cette thèse est d’étudier la contribution de différentes caractéristiques du voisinage relativement à l’obésité chez les jeunes et les habitudes de vie qui y sont associées. Les objectifs spécifiques consistent à: 1) Examiner les associations entre la présence de différents commerces d’alimentation dans les voisinages résidentiels et scolaires des enfants et leurs habitudes alimentaires; 2) Examiner comment l’exposition à certaines caractéristiques du voisinage résidentiel détermine l’obésité au niveau familial (chez le jeune, la mère et le père), ainsi que l’obésité individuelle pour chaque membre de la famille; 3) Identifier des combinaisons de facteurs de risque individuels, familiaux et du voisinage résidentiel qui prédisent le mieux l’obésité chez les jeunes, et déterminer si ces profils de facteurs de risque prédisent aussi un changement dans l’obésité après un suivi de deux ans. Méthodes: Les données proviennent de l’étude QUALITY, une cohorte québécoise de 630 jeunes, âgés de 8-10 ans au temps 1, avec une histoire d’obésité parentale. Les voisinages de 512 participants habitant la Région métropolitaine de Montréal ont été caractérisés à l’aide de : 1) données spatiales provenant du recensement et de bases de données administratives, calculées pour des zones tampons à partir du réseau routier et centrées sur le lieu de la résidence et de l’école; et 2) des observations menées par des évaluateurs dans le voisinage résidentiel. Les mesures du voisinage étudiées se rapportent aux caractéristiques de l’environnement bâti, social et alimentaire. L’obésité a été estimée aux temps 1 et 2 à l’aide de l’indice de masse corporelle (IMC) calculé à partir du poids et de la taille mesurés. Les habitudes alimentaires ont été mesurées au temps 1 à l'aide de trois rappels alimentaires. Les analyses effectuées comprennent, entres autres, des équations d'estimation généralisées, des régressions multiniveaux et des analyses prédictives basées sur des arbres de décision. Résultats: Les résultats démontrent la présence d’associations avec l’obésité chez les jeunes et les habitudes alimentaires pour certaines caractéristiques du voisinage. En particulier, la présence de dépanneurs et de restaurants-minutes dans le voisinage résidentiel et scolaire est associée avec de moins bonnes habitudes alimentaires. La présence accrue de trafic routier, ainsi qu’un faible niveau de prestige et d’urbanisation dans le voisinage résidentiel sont associés à l’obésité familiale. Enfin, les résultats montrent qu’habiter un voisinage obésogène, caractérisé par une défavorisation socioéconomique, la présence de moins de parcs et de plus de dépanneurs, prédit l'obésité chez les jeunes lorsque combiné à la présence de facteurs de risque individuels et familiaux. Conclusion: Cette thèse contribue aux écrits sur les voisinages et l’obésité chez les jeunes en considérant à la fois l'influence potentielle du voisinage résidentiel et scolaire ainsi que l’influence de l’environnement familial, en utilisant des méthodes objectives pour caractériser le voisinage et en utilisant des méthodes statistiques novatrices. Les résultats appuient en outre la notion que les efforts de prévention de l'obésité doivent cibler les multiples facteurs de risque de l'obésité chez les jeunes dans les environnements bâtis, sociaux et familiaux de ces jeunes. / Background: Childhood obesity currently poses a major public health challenge worldwide. In an attempt to identify potential targets for population-based prevention strategies, neighbourhood environments are increasingly being investigated in relation to childhood obesity and its behavioural precursors. However, research to date is largely beset by inconsistencies in findings. Purpose: The overarching goal of this thesis is to investigate the contribution of different features of neighbourhood environments in relation to obesity and antecedent behaviours in children. Specific objectives are: 1) To examine associations between children’s residential and school neighbourhood food environments and their dietary intake and behaviours; 2) To examine shared exposure to features of residential neighbourhoods in relation to obesity among family triads (child, mother, and father) and among individual family members; 3) To identify specific combinations of individual, familial, and neighbourhood risk factors that best predict obesity in children, and determine whether these risk factor profiles also predict 2-year changes in obesity. Methods: Data were drawn from the QUALITY Cohort, a Quebec-based study of 630 children aged 8-10 years at baseline with a parental history of obesity. Baseline residential neighbourhood environments of 512 participants living in the Montreal Metropolitan Area were characterised using: 1) geographically linked census and administrative data computed for road network buffers centered on the residential and school locations; and 2) in-person neighbourhood observations conducted within the participants’ residential neighbourhoods. Neighbourhood measures included characteristics of the built, social, and food services environments. Obesity was determined using the body mass index (BMI) computed from measured weight and height at baseline and at follow up. Diet was measured using three 24-hour diet recalls at baseline. Different types of analyses were used including generalised estimating equations, multilevel regressions, and recursive partitioning. Results: Findings point to specific neighbourhood features that are associated with childhood obesity and diet. Most notably, increased availability of convenience stores and fast food restaurants within residential and school neighbourhoods is associated with poorer diets among children. High street-level traffic and low neighbourhood prestige and urban development in residential neighbourhoods are associated with obesity among family triads. Lastly, findings suggest that obesogenic neighbourhood environments characterised by socioeconomic disadvantage, fewer parks, and more convenience stores jointly predict childhood obesity within unique combinations of individual and familial risk factors. Conclusion: This thesis contributes to the literature on neighbourhood environments and childhood obesity by considering the influences of both residential and school neighbourhoods as well as familial environments, by objectively characterising neighbourhoods, and by using innovative statistical approaches. Findings furthermore support the notion that obesity prevention efforts should target multiple risk factors of childhood obesity within the built, social, and family environments of children.