Compared to microarray-based genotyping, next-generation whole genome-sequencing (WGS) studies have the strength to provide greater information for the identification of rare variants, which likely account for a significant portion of missing heritability of common human diseases. In WGS, family-based studies are important because they are likely enriched for rare disease variants that segregate with the disease in relatives. We propose a multilevel model to detect disease variants using family-based WGS data with longitudinal measures. This model incorporates the correlation structure from family pedigrees and that from repeated measures. The iterative generalized least squares (IGLS) algorithm was applied to estimation of parameters and test of associations. The model was applied to the data of Genetic Analysis Workshop 18 and compared with existing linear mixed effect (LME) models. The multilevel model shows higher power at practical p-value levels and a better type I error control than LME model. Both multilevel and LME models, which utilize the longitudinal repeated information, have higher power than the method that only utilize data collected at one time point.

Introdução A mortalidade infantil (MI) no Município de São Paulo (MSP) apresenta queda, principalmente a partir da década de 80, entretanto é possível que existam diferenças regionais importantes entre Subprefeituras uma vez que estas apresentam características sócio-ambientais que podem influenciar neste indicador. Objetivo Descrever e analisar a evolução da MI no período de 2000 a 2007, segundo Subprefeituras do MSP. Métodos Estudo ecológico longitudinal, com 31 unidades de análise (Subprefeituras). Utilizou-se, para a análise estatística, o modelo de regressão linear multinível, considerando-se, como variável resposta, o CMI e oito anos de observação (2000 a 2007). O modelo incluiu variáveis relacionadas aos serviços de saúde. Resultados A queda da MI não ocorre de modo homogêneo entre as Subprefeituras evidenciadas pelas diferentes inclinações das retas e interceptos observados e estimados. Após a análise pelo modelo multinível observou-se redução da MI no período de 18,8% com declínio médio de 0,300/00nv ao ano Pelo modelo, 51% da variabilidade da MI se explica por características contextuais das Subprefeituras. No período de estudo, o CMI aumenta: 0,0560/00nv para cada 1% de aumento na proporção de mães com pré-natal inadequado, 0,2140/00nv para cada 1% de aumento na proporção da população exclusivamente usuária SUS, 0,0390/00nv para cada aumento na taxa de leitos obstétricos SUS. O CMI diminui: 0,1910/00nv para cada 1% de aumento na proporção de recuperação da vitalidade do nv. Conclusão A MI apresenta tendência de queda no período de 2000 a 2007 de modo não homogêneo segundo Subprefeitura. As variáveis que apresentaram associação com a MI são: o ano de observação, proporção de nascidos vivos de mães que realizaram até 6 consultas pré-natal (pré-natal inadequado); taxa de leitos obstétricos do Sistema Único de Saúde (SUS); proporção da população exclusivamente usuária do SUS e proporção de recuperação da vitalidade do nascido vivo. Na região periférica do MSP onde se encontram as maiores proporções da população exclusivamente usuária SUS, é também onde se apresentam os maiores CMI. / Introduction - Infant mortality (IM) in São Paulo (MSP) has declined, especially from the 80s. However, there may be important regional differences between Districts as their socio-environmental characteristics may influence this indicator. Objective - To describe and analyze IM trend in the period from 2000 to 2007, according to the Districts of MSP. Method - Ecological longitudinal study comprising 31 units of analysis (Districts). Linear multilevel regression model was used for statistical analysis. Infant Mortality Rate (IMR) and eight years of observation (2000-2007) were used as dependent variables. The model included variables related to health services. Results The decrease in IM does not occur homogeneously between Districts as evidenced by the different slopes and intercepts of the observed and estimated lines. A multilevel model showed an 18.8% reduction in IM in the period with an average decline of 0,300/00 living born (lb) per year. According to the model, 51% of the IM variability can be explained by contextual features of districts. During the study period, IMR increases: 0,0560/00lb for every 1% increase among mothers with inadequate prenatal care, 0,2140/00lb for every 1% increase among users of the Unified Health System (UHS), 0,0390/00lb for each increase in the UHS obstetric beds rate. IMR decreases 0,1910/00lb for every 1% increase in the vitality proportion of recovery of live births. Conclusion - IM shows a declining trend over the period from 2000 to 2007 in a non-homogeneous way according to District. The variables that were associated with IMR: year of observation, proportion of live births from mothers who had up to 6 prenatal visits (inadequate prenatal care), Unified Health System (UHS) obstetric beds rate, proportion of UHS users and vitality recovery of live birth proportion. The highest IMR is found in peripheral region of MSP where the largest proportion of UHS users is found.

Introdução A mortalidade infantil (MI) no Município de São Paulo (MSP) apresenta queda, principalmente a partir da década de 80, entretanto é possível que existam diferenças regionais importantes entre Subprefeituras uma vez que estas apresentam características sócio-ambientais que podem influenciar neste indicador. Objetivo Descrever e analisar a evolução da MI no período de 2000 a 2007, segundo Subprefeituras do MSP. Métodos Estudo ecológico longitudinal, com 31 unidades de análise (Subprefeituras). Utilizou-se, para a análise estatística, o modelo de regressão linear multinível, considerando-se, como variável resposta, o CMI e oito anos de observação (2000 a 2007). O modelo incluiu variáveis relacionadas aos serviços de saúde. Resultados A queda da MI não ocorre de modo homogêneo entre as Subprefeituras evidenciadas pelas diferentes inclinações das retas e interceptos observados e estimados. Após a análise pelo modelo multinível observou-se redução da MI no período de 18,8% com declínio médio de 0,300/00nv ao ano Pelo modelo, 51% da variabilidade da MI se explica por características contextuais das Subprefeituras. No período de estudo, o CMI aumenta: 0,0560/00nv para cada 1% de aumento na proporção de mães com pré-natal inadequado, 0,2140/00nv para cada 1% de aumento na proporção da população exclusivamente usuária SUS, 0,0390/00nv para cada aumento na taxa de leitos obstétricos SUS. O CMI diminui: 0,1910/00nv para cada 1% de aumento na proporção de recuperação da vitalidade do nv. Conclusão A MI apresenta tendência de queda no período de 2000 a 2007 de modo não homogêneo segundo Subprefeitura. As variáveis que apresentaram associação com a MI são: o ano de observação, proporção de nascidos vivos de mães que realizaram até 6 consultas pré-natal (pré-natal inadequado); taxa de leitos obstétricos do Sistema Único de Saúde (SUS); proporção da população exclusivamente usuária do SUS e proporção de recuperação da vitalidade do nascido vivo. Na região periférica do MSP onde se encontram as maiores proporções da população exclusivamente usuária SUS, é também onde se apresentam os maiores CMI. / Introduction - Infant mortality (IM) in São Paulo (MSP) has declined, especially from the 80s. However, there may be important regional differences between Districts as their socio-environmental characteristics may influence this indicator. Objective - To describe and analyze IM trend in the period from 2000 to 2007, according to the Districts of MSP. Method - Ecological longitudinal study comprising 31 units of analysis (Districts). Linear multilevel regression model was used for statistical analysis. Infant Mortality Rate (IMR) and eight years of observation (2000-2007) were used as dependent variables. The model included variables related to health services. Results The decrease in IM does not occur homogeneously between Districts as evidenced by the different slopes and intercepts of the observed and estimated lines. A multilevel model showed an 18.8% reduction in IM in the period with an average decline of 0,300/00 living born (lb) per year. According to the model, 51% of the IM variability can be explained by contextual features of districts. During the study period, IMR increases: 0,0560/00lb for every 1% increase among mothers with inadequate prenatal care, 0,2140/00lb for every 1% increase among users of the Unified Health System (UHS), 0,0390/00lb for each increase in the UHS obstetric beds rate. IMR decreases 0,1910/00lb for every 1% increase in the vitality proportion of recovery of live births. Conclusion - IM shows a declining trend over the period from 2000 to 2007 in a non-homogeneous way according to District. The variables that were associated with IMR: year of observation, proportion of live births from mothers who had up to 6 prenatal visits (inadequate prenatal care), Unified Health System (UHS) obstetric beds rate, proportion of UHS users and vitality recovery of live birth proportion. The highest IMR is found in peripheral region of MSP where the largest proportion of UHS users is found.

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The issue of behavioural intentions has attracted the attention of hotel marketers and academics because favourable behavioural intentions help hotels to retain customers. The marketing literature has identified that service quality, perceived value, image, customer satisfaction and demographic variables are significant determinants of behavioural intentions. This suggests that behavioural intentions are a multi-dimensional concept. Despite the importance of behavioural intentions, there is limited research on this construct in the hotel industry. The aim of this research was to gain an empirical understanding of behavioural intentions in the Taiwan hotel sector. A multi-level model was used as a framework for the analysis. The dimensions of service quality as perceived by hotel customers were identified through the literature review and focus group discussions. Hypotheses were formulated and tested to examine the interrelationships between behavioural intentions, service quality, customer satisfaction, perceived value and image, and to determine if perceived value plays a moderating role between service quality and customer satisfaction. Finally, customer perceptions of these constructs were compared based on demographic factors such as age, gender and income. The findings of this study were based on the analysis of a sample of 580 customers who had stayed at a five-star hotel in Kaohsiung City of Taiwan. Support was found for the use of a multi-level model and the primary dimensions: Interaction Quality, Physical Environment Quality and Outcome Quality, as broad dimensions of service quality. The 12 sub-dimensions of service quality, as perceived by hotel customers, were identified. These were: Employees’ Conduct, Employees’ Expertise, Employees’ Problem-Solving, Customer-to-Customer Interaction, Décor & Ambience, Room Quality, Availability of Facility, Design, Location, Valence, Waiting Time and Sociability. The results indicated that each of the primary dimensions varied in terms of their importance to overall perceived service quality, as did the sub-dimensions of the primary dimensions. In addition, the statistical results supported a relationship between perceived value and service quality, image and service quality, customer satisfaction, perceived value, image and service quality, and behavioural intentions, image and customer satisfaction. The results also revealed that customer perceptions of the constructs were primarily affected by their purpose of travel and occupation. The results contribute to the services marketing theory by providing an empirically based insight into the service quality, perceived value, image, customer satisfaction and behavioural intentions constructs in the Taiwan hotel industry. This research also provides an analytical framework for understanding the effects of the three primary dimensions on service quality and the effect of service quality on constructs, such as, perceived value, image, customer satisfaction and behavioural intentions. This study will assist the management of the hotel industry to develop and implement a market-oriented service strategy in order to achieve a high quality of service, upgrade customers’ levels of satisfaction, and create favourable future behavioural intentions.

Die Psychologie der Lebensspanne und die Soziologie des Lebensverlaufs betonen die Bedeutung von Kontexten für den Erwerb individueller Fähigkeiten und die Entwicklung im Leben. In Übereinstimmung mit diesen konzeptionellen Annahmen zeigen Studien, dass verschiedene Kontexte die Entwicklung individueller Bereiche beeinflussen. Jedoch ist wenig darüber bekannt, wie kontextuelle Faktoren in der zweiten Lebenshälfte Wohlbefinden formen und wie Wohlbefinden in diesen Lebensphasen von sich schnell verändernden Kontexten beeinflusst wird. In dieser Dissertation werden unter Anwendung des Ökosystemischen Ansatzes von Bronfenbrenner drei Kontexte unterschiedlicher Proximität untersucht, in die die Entwicklung des individuellen Wohlbefindens eingebettet ist. Als erster Kontext wird die vielfältige Ökologie des Lebens und Sterbens in den ehemaligen Regionen Ost- und Westdeutschland herangezogen, um herauszufinden wie dieses Makrosystem Wohlbefinden in den letzten Lebensjahren gestaltet. Als zweiter Kontext wird die Bedeutung des Exosystems von Gesundheitseinrichtungen in Landkreisen (z.B. Anzahl stationärer Pflegereinrichtungen) auf Wohlbefindensverläufe am Lebensende beleuchtet. Als dritten Kontext untersuchen wir, wie das Mikrosystem sozialer Ökologien und Situationen momentanes, affektives Wohlbefinden gestaltet, sowie Altersunterschiede in diesen Assoziationen. Gemeinsam zeigen die drei Studien dieser Dissertation, dass Ökologien auf regionaler, dienstleistender und sozialer Kontextebene Entwicklung von Wohlbefinden in der zweiten Lebenshälfte beeinflussen. Diese Arbeit zeigt, dass Kontexte sowohl kognitives als auch affektives Wohlbefinden und innerhalb des letzteren sowohl Valenz und Aktivierung beeinflussen, und untersucht länger- und kurzfristige Kontext-Wohlbefindens-Assoziationen in späteren Lebensphasen. Die Ergebnisse liefern erste Vorschläge für Interventionen und veränderbare regionale Faktoren für die Erhaltung oder Verbesserung von Wohlbefinden. / Lifespan psychology and life course sociology have long acknowledged the role of context for individual functioning and development throughout life. Consistent with these conceptual notions, empirical studies show that various contextual factors influence development of individual-level outcomes. However, we know little about how contextual factors shape individual-level well-being and how well-being is influenced by fast changing contexts in the second half of life. Applying Bronfenbrenner’s model of human ecology as the overarching theoretical frame, this dissertation examines three sets of contexts that differ in the degree of proximity in which individual well-being and its development is embedded in. As a first context, the multifaceted ecology of living and dying in former regions of East and West Germany is used to investigate how the macrosystem shapes individual well-being in the last years of life. For a second context, the role of the exosystem of county-level health care features (e.g., number of inpatient care facilities) on late-life trajectories in well-being is examined. As a third context, we examine how the microsystem of social ecologies and situations influences momentary affective well-being and how these associations differ across age. Jointly, the three studies in this dissertation show that regional, service, and social ecologies profoundly shape development in well-being during the second half of life. To conclude, this dissertation shows that these contexts influence both cognitive and affective components of well-being, among the affective domain two facets (valence and arousal), and investigates long-term and short-term contextwell- being associations in later life phases. Results provide initial suggestions for interventions and malleable regional factors to maintain or improve well-being.