Les neutrophiles infiltrent la muqueuse colique inflammatoire en maladie de Crohn (CD). Cependant, on ignore l’existence d’une corrélation entre la sévérité endoscopique et la fréquence et/ou l’activation des neutrophiles et autres granulocytes. Une cohorte de 73 patients atteints de CD fut recrutée prospectivement. Les participants furent stratifiés selon la Classification de Montréal ou subdivisés selon le phénotype endoscopique (phénotype typique vs apparence endoscopique « UC-Like »). L’index d’Harvey Bradshaw (HBI) et le Simple Endoscopic score (SES-CD) furent calculés au moment de la coloscopie. La fréquence et l’expression de CD66b et de CD64 sur les granulocytes furent évaluées en cytométrie de flux sur des échantillons sanguins et des biopsies coliques. Le SES-CD corrélait avec l’expression du CD66b sur les neutrophiles coliques et du CD64 sur les neutrophiles circulants en présence de maladie active avec comportement inflammatoire (B1). Les fréquences des neutrophiles et des basophiles mais non des eosinophiles étaient augmentées au sein de la muqueuse inflammatoire, mais la fréquence des neutrophiles coliques n’était corrélée avec le SES-CD uniquement en présence d’un phénotype endoscopique « UC-like ». Deux scores d’activation granulocytaire étaient discriminant entre les individus avec maladie légère et sévère dans l’ensemble de la cohorte avec maladie active. L’activation des granulocytes dans le sang et la muqueuse colique corrèle avec le SES-CD dans des sous-groupes de patients avec une maladie B1, alors que les scores d’activation granulocytaire pourraient être pertinent cliniquement pour évaluer la sévérité de la maladie et possiblement avoir une valeur prognostique parmi les individus avec maladie active. / Neutrophils infiltrate the inflamed colon in Crohn’s disease (CD). However, correlation between endoscopic severity, and frequency and/or activation of neutrophils and other granulocytes like basophils and eosinophils remains to be investigated. A cohort of 73 CD patients was prospectively enrolled according to endoscopic severity and treatment history. Patients with active disease were stratified according to Montreal classification or subdivided into typical CD and UC-like endoscopic features. Harvey Bradshaw Index (HBI) and Simple Endoscopic score (SES-CD) were performed at the time of ileocolonoscopy. Frequency and expression of CD66b and CD64 on granulocytes were assessed in paired blood and colonic biopsies using flow cytometry. SES-CD correlated with neutrophil CD66b expression in mucosa but not blood and conversely, with neutrophil CD64 expression in blood but not mucosa in CD patients with inflammatory (B1) active disease. Frequencies of neutrophils and basophils but not eosinophils, increased in inflamed colon, but only in a subgroup of CD patients presenting “UC-like” endoscopic features were the frequencies of colonic neutrophils correlated with SES-CD. Furthermore, a neutrophil activation score (CD66b X CD64 on neutrophils) and a blood granulocyte score (CD66b on eosinophils X CD64 on neutrophils) discriminated between mild and severe disease in the entire cohort of patients with active disease. Activation of granulocytes in blood and/or mucosa correlated with SES-CD in subgroups of patients with B1 inflammatory disease while granulocyte activation scoring systems may be clinically relevant to evaluate disease severity and predict prognosis in the entire cohort of active disease patients.

In 1994, Tennessee, the third largest tobacco-producing state in the U.S., preempted tobacco regulation. However, in 2005, higher educational institutions were exempted from this preemption and the 2007 Non-Smoker Protection Act required educational facilities to create smoke-free environment. To this date, while all higher educational institutions have some sort of smoke-free policy, East Tennessee State University is the only public institution with a tobacco-free policy. We investigated attitudes and behaviors of the university personnel, the most stable segment of the population, toward the policy and compliance with it using an internet-based survey. All employees (2,318) were invited to participate in a survey; 58% responded. Bivariate analyses found 79% of the respondents favored the policy. Multiple variable logistic regression analyses found support for the policy was higher among females [OR = 3.14; 95% CI (1.68, 5.86)], administrators/professionals [OR = 3.47; 95% CI (1.78, 6.74)], faculty [OR = 2.69; 95% CI (1.31, 5.53)] and those affiliated with the College of Medicine [OR = 4.14; 95% CI (1.45, 7.85)]. While only 67 employees (5.6% of sample) reported they have not complied with the policy, around 80.8% reported observing someone engaged in non-compliance. The high level of support for the policy suggests it should be promoted throughout the higher education system and nationwide. At the same time, in preemptive states, higher educational institutions should be targeted as venues for strong tobacco-free policies. The gap in compliance, however, implies in tobacco-friendly environments, a tobacco-free campus policy with no reporting and enforcement mechanisms could lead to high levels of non-compliance.

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A Computational Fluid Dynamics (CFD) tool is developed in this thesis to solve complex fluid-structure interaction (FSI) problems. The fluid domain is based on Smoothed Particle Hydro-dynamics (SPH) and the structural domain employs large-deformation Finite Element Method (FEM). Validation tests of SPH and FEM are first performed individually. A loosely-coupled SPH-FEM model is then proposed for solving FSI problems. Validation results of two benchmark FSI problems are illustrated (Antoci et al., 2007; Souto-Iglesias et al., 2008). The first test case is flow in a sloshing tank interacting with an elastic body and the second one is dam-break flow through an elastic gate. The results obtained with the SPH-FEM model show good agreement with published results and suggest that the SPH-FEM model is a viable and effective numerical tool for FSI problems. This research is then applied to simulate a two-dimensional free-stream flow interacting with a deformable, pressurized surface, such as an ACV/SES bow seal. The dynamics of deformable surfaces such as the skirt/seal systems of the ACV/SES utilize the large-deformation FEM model. The fluid part including the air inside the chamber and water are simulated by SPH. A validation case is performed to investigate the application of SPH-FEM model in ACV/SES via comparison with experimental data (Zalek and Doctors, 2010). The thesis provides the theory of the SPH and FEM models incorporated and the derivation of the loosely-coupled SPH-FEM model. The validation results have suggested that this SPH-FEM model can be readily applied to skirt/seal dynamics of ACV/SES interacting with free-surface flow. / Ph. D.

Objectives: To explore environmental and individual factors that are associated with child development and to investigate whether the strength of these associations differs according to the age of the children. Design: Cross-sectional study. Setting: This study was part of the LIFE Child study, a large cohort study conducted in Leipzig, Germany. Participants: 778 children aged between 0.5 and 6 years (48.6% girls, mean age=2.67 years). Outcome measures: The outcomes were cognitive development, language development, body and hand motor skills, social- emotional development, and tracing skills, measured with a standardised development test. We analysed the associations between development and gestational age, socioeconomic status (SES), sex, behavioural difficulties, siblings, sleep duration, breastfeeding duration and overweight/obesity. We also tested for interactions between these variables and child age or sex. Results: Higher gestational age (b ranging between 0.12 and 0.26) and higher SES (b ranging between 0.08 and 0.21) were associated with better outcomes in almost all developmental domains (all p<0.019). Children with older siblings had improved body and hand motor skills compared with children without older siblings (both b=0.55, all p<0.029). Boys had poorer scores than girls in body and hand motor skills and tracing (b=−0.45, −0.68 and −1.5, all p<0.019). Children with behavioural difficulties had significantly poorer outcomes in most developmental domains. Some of the associations with SES and sex were stronger in older than in younger children. Associations between gestational age and motor development were weaker in older children. We did not find significant associations between child development and sleep duration, breastfeeding duration or overweight/obesity. Conclusion: Some factors had a protective, others an adverse effect on development of children under 6 years of age. The effect of SES and sex increased, while the effect of gestational age decreased with age.:Inhaltsverzeichnis I. Abkürzungsverzeichnis 1 Einführung 1.1 Entwicklung 1.2 Entwicklungsdiagnostik 1.2.1 Der Entwicklungstest für Kinder zwischen 6 Monaten und 6 Jahren - Revision 1.3 Forschungsstand 1.3.1 Gestationsalter 1.3.2 Sozioökonomischer Status 1.3.3 Geschlecht 1.3.4 Verhalten 1.3.5 Ältere Geschwister 1.3.6 Schlafdauer 1.3.7 Stilldauer 1.3.8 Übergewicht/Adipositas 1.4 Ableitung der Rationale für die Studie 2 Publikation 3 Zusammenfassung der Arbeit 4 Literaturverzeichnis II. Darstellung des eigenen Beitrags III. Erklärung über die eigenständige Abfassung der Arbeit IV. Lebenslauf V. Danksagung

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