Educational researchers are often interested in phenomena that unfold over time within a person and at the same time, relationships between their characteristics that are stable over time. Since variables in a longitudinal study reflect both within- and between-person effects, researchers need to disaggregate them to understand the phenomenon of interest correctly. Although the person-mean centering technique has been believed as the gold standard of the disaggregation method, recent studies found that the centering did not work when there was a trend in the predictor. Hence, they proposed some detrending techniques to remove the systematic change; however, they were only applicable to multilevel models. Therefore, this dissertation develops novel detrending methods based on structural equation modeling (SEM). It also establishes the links between centering and detrending by reviewing a broad range of literature. The proposed SEM-based detrending methods are compared to the existing centering and detrending methods through a series of Monte Carlo simulations. The results indicate that (a) model misspecification for the time-varying predictors or outcomes leads to large bias of and standard error, (b) statistical properties of estimates of the within- and between-person effects are mostly determined by the type of between-person predictors (i.e., observed or latent), and (c) for unbiased estimation of the effects, models with latent between-person predictors require nonzero growth factor variances, while those with observed predictors at the between level need either nonzero or zero variance, depending on the parameter. As concluding remarks, some practical recommendations are provided based on the findings of the present study. / Doctor of Philosophy / Educational researchers are often interested in longitudinal phenomena within a person and relations between the person's characteristics. Since repeatedly measured variables reflect their within- and between-person aspects, researchers need to disaggregate them statistically to understand the phenomenon of interest. Recent studies found that the traditional centering method, where the individual's average of a predictor was subtracted from the original predictor value, could not correctly disentangle the within- and between-person effects when the predictor showed a systematic change over time (i.e., trend). They proposed some techniques to remove the trend; however, the detrending methods were only applicable to multilevel models. Therefore, the present study develops novel detrending methods using structural equation modeling. The proposed models are compared to the existing methods through a series of Monte Carlo simulations, where we can manipulate a data-generating model and its parameter values. The results indicate that (a) model misspecification for the time-varying predictor or outcome leads to systematic deviation of the estimates from their true values, (b) statistical properties of estimates of the effects are mostly determined by the type of between-person predictors (i.e., observed or latent), and (c) the latent predictor models require nonzero growth factor variances for unbiased estimation, while the observed predictor models need either nonzero or zero variance, depending on the parameter. As concluding remarks, some recommendations for the practitioners are provided.

Genetic association studies usually include related individuals. Meanwhile, high-throughput sequencing technologies produce data of multiple genetic variants. Due to linkage disequilibrium (LD) and familial relatedness, the genotype data from such studies often carries complex correlations. Moreover, missing values in genotype usually lead to loss of power in genetic association tests. Also, repeated measurements of phenotype and dynamic covariates from longitudinal studies bring in more opportunities but also challenges in the discovery of disease-related genetic factors. This dissertation focuses on developing novel statistical methods to address some challenging questions remaining in genetic association studies due to the aforementioned reasons. So far, a lot of methods have been proposed to detect disease-related genetic regions (e.g., genes, pathways). However, with multiple-variant data from a sample with relatedness, it is critical to account for the complex genotypic correlations when assessing genetic contribution. Recognizing the limitations of existing methods, in the first work of this dissertation, the Adaptive-weight Burden Test (ABT) --- a score test between a quantitative trait and the genotype data with complex correlations --- is proposed. ABT achieves higher power by adopting data-driven weights, which make good use of the LD and relatedness. Because the null distribution has been successfully derived, the computational simplicity of ABT makes it a good fit for genome-wide association studies. Genotype missingness commonly arises due to limitations in genotyping technologies. Imputation of the missing values in genotype usually improves quality of the data used in the subsequent association test and thus increases power. Complex correlations, though troublesome, provide the opportunity to proper handling of genotypic missingness. In the second part of this dissertation, a genotype imputation method is developed, which can impute the missingness in multiple genetic variants via the LD and the relatedness. The popularity of longitudinal studies in genetics and genomics calls for methods deliberately designed for repeated measurements. Therefore, a multiple-variant genetic association test for a longitudinal trait on samples with relatedness is developed, which treats the longitudinal measurements as observations of functions and thus takes into account the time factor properly. / PHD

Yes / Objectives: To determine the impact of adherence to spectacle wear on visual acuity (VA) and developing literacy following vision screening at age 4–5 years. Design: Longitudinal study nested within the Born in Bradford birth cohort. Setting and participants: Observation of 944 children: 432 had failed vision screening and were referred (treatment group) and 512 randomly selected (comparison group) who had passed (<0.20 logarithm of the minimum angle of resolution (logMAR) in both eyes). Spectacle wear was observed in school for 2 years following screening and classified as adherent (wearing spectacles at each assessment) or non-adherent. Main outcome measures: Annual measures of VA using a crowded logMAR test. Literacy was measured by Woodcock Reading Mastery Tests-Revised subtest: letter identification. Results: The VA of all children improved with increasing age, −0.009 log units per month (95% CI −0.011 to −0.007) (worse eye). The VA of the adherent group improved significantly more than the comparison group, by an additional −0.008 log units per month (95% CI −0.009 to −0.007) (worse eye) and −0.004 log units per month (95% CI −0.005 to −0.003) in the better eye. Literacy was associated with the VA, letter identification (ID) reduced by −0.9 (95% CI −1.15 to −0.64) for every one line (0.10 logMAR) fall in VA (better eye). This association remained after adjustment for socioeconomic and demographic factors (−0.33, 95% CI −0.54 to −0.12). The adherent group consistently demonstrated higher letter-ID scores compared with the non-adherent group, with the greatest effect size (0.11) in year 3. Conclusions: Early literacy is associated with the level of VA; children who adhere to spectacle wear improve their VA and also have the potential to improve literacy. Our results suggest failure to adhere to spectacle wear has implications for the child’s vision and education. / AB is funded by a National Institute for Health Research Post- Doctoral Fellowship Award (PDF-2013-06-050). The Born in Bradford study presents independent research commissioned by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407-10044).

Objectives. To investigate diabetes prevalence, incidence, mortality trends, the effects of hyperglycaemia and blood pressure, diabetes and hypertension treatment, and the effect of screening detection on total and cardiovascular disease (CVD), myocardial infarction (MI) and stroke incidence. Study population and methods. Between 1972 and 2001 all patients with diabetes, some detected clinically and some by case-finding procedures (screening), were entered in a diabetes register at Laxå Primary Health Care Center in Sweden. The register included information on medical treatment and laboratory data as well as information on mortality and morbidity from National Registers. The register was supplemented with five non-diabetic subjects, matched to each diabetes patients by age, sex, and year of detection. Results. During the study period 776 new diabetes cases was found, 36 type 1 diabetes mellitus and 740 type 2 diabetes mellitus. Age standardised incidence and prevalence rates for type 1 and type 2 diabetes did not increase over time. Diabetic patients had 17% higher mortality rate than non-diabetic persons, 22% in women and 13% in men. The corresponding over-mortality in CVD was 33%, 41% in women and 27% in men. CVD mortality decreased across time in non-diabetic subjects and in diabetic men but not in diabetic women. Results regarding coronary heart disease (CHD) were similar. CVD incidence increased with fasting blood glucose (FBG), body mass index (BMI), mean arterial blood pressure (MABP), and decreased with metformin treatment and sulfonylurea. Myocardial infarction incidence increased with FBG, BMI and MABP, and decreased with metformin treatment. Stroke incidence increased with MABP. There was no difference in prognoses between those detected by screening or clinically. Conclusions. Diabetes prevalence and incidence did not change over time. The over-mortality according to diabetes was moderate. CVD and MI during follow up were negatively affected by hypertension and hyperglycaemia, and positively by pharmacological diabetic treatment. For stroke no pharmacological protective effect was seen. Screening did not improve prognosis.

Health-related quality of life (HRQL) has become an important outcome in asthma, since traditional outcomes, such as respiratory symptoms and pulmonary function, might not entirely express the patient’s perception of the limitations caused by the disease. The aim of this thesis was to study HRQL in asthma and to analyse if HRQL was related to asthma onset and prognosis. Other aims were to identify determinants of low HRQL in clinically-verified asthmatics, and to study whether low HRQL was a predictor of mortality. In 1990, a self-administered questionnaire was completed by 12,560 individuals from three age groups (16, 30-39, and 60-69 years) in two counties of Sweden. In a second phase, all subjects who reported a history of obstructive respiratory symptoms (n = 1,851) and 600 randomly-selected controls were invited to a clinical investigation including spirometry, allergy testing, and assessment of HRQL with the Gothenburg Quality of Life instrument. In 2003, the eligible subjects in the cohort (n=11,282) were sent a new questionnaire. Mortality data in the cohort was followed up during 1990–2008 using data from the National Board of Health and Welfare Mortality Database. The 616 subjects with clinically-verified asthma 1990 had significantly lower HRQL than subjects without asthma. In the 2003 follow-up, the 305 subjects with persistent asthma had a lower HRQL than the 155 subjects who showed improvement in asthma during the follow-up. Subjects who had developed asthma by the follow-up had a significantly lower HRQL at baseline than those who did not develop asthma. Significant determinants of quality of life in asthma were female sex, smoking habits, higher airway responsiveness to irritants, respiratory symptom severity, positive skin prick test, and absenteeism from work or school. Low HRQL was related to increased mortality, but this association was not found when analyzing the asthmatic group alone. In conclusion, measurements of HRQL are of value for evaluating both the impact and progression of asthma. / <p>medicine doktorsexamen</p>

This thesis explores cultural differences on interactive design features used in websites of South Korea and the United Kingdom from the perspective of both: professional website designers and end-users. It also investigates how the use of interactive design features from different cultures change over time. Four interaction types on websites; User to Interface (U2I), User to Content (U2C), User to Provider (U2P), and User to User (U2U) interactivity, and three interaction types on blogs; Blogger to Interface (B2I), Blogger to Content (B2C) and Blogger to Blogger (B2B) interactivity have been identified. Four cultural dimensions were used for the theoretical base of this study based on which four hypotheses were proposed in relation to the interaction types identified above; (a) High versus Low Context cultures for U2I, (b) High versus Low Uncertainty Avoidance for U2C, (c) High versus Low Power Distance for U2P and (d) Individualism versus Collectivism for U2U interactivity, in order to discover the effects of national cultures on interactivity in websites. We derived our own interactivity dimensions and mapped them to the four interaction types for websites and three for blogs. Interactive design features were derived from interactivity dimensions and examined in our studies. The findings revealed that there have been some changes towards homogeneity in the use of interactive design features on charity websites between South Korea and United Kingdom although there is still evidence of some cultural differences. With regard to end-users’ perspective, the result show that the use of interactive design features of blogs may be influenced by culture but this is only within a certain context. The findings also provide a valuable indication that users interacting within the same blog service can be considered as being shared concerns rather than shared national location, thus create a particular type of community in which bloggers are affected by social influence so they adopt a shared set of value, preferences and style that would indicate almost a common social culture. As a result, the cultural differences derived from their country of origin do not have that much impact.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

BACKGROUND: Little is known of the effects of obesity, body size and body composition, and blood pressure (BP) in childhood on hypertension (HBP) and cardiac structure and function in adulthood due to the lack of long-term serial data on these parameters from childhood into adulthood. In the present study, we are poised to analyze these serial data from the Fels Longitudinal Study (FLS) to evaluate the extent to which body size during childhood determines HBP and cardiac structure and function in the same individuals in adulthood through mathematical modeling. METHODS: The data were from 412 males and 403 females in the FLS. Stature and BMI parameters were estimated using the Preeze-Baines model and the third degree polynomial model to describe the timing, velocity and duration of these measure from 2 to 25 years of age. The biological parameters were related to adult BP and echocardiographic (Echo-) measurements using Generalized Linear Models (GLM). RESULTS: The parameters of stature and BMI were compared between male and female to their overall goodness of fit and their capabilities to quantify the timing, rate of increase, and duration of the growth events. For stature parameters, the age at onset and peak velocity was earlier for girls; but the peak velocity was greater in boys; the velocity at onset was about the same for boys and girls; and stature at onset, peak velocity and adult was greater for boys. For BMI parameters, boys tended to have larger BMI values than girls, but the rates of change in BMI were almost the same; there was no sex difference in the timing of BMI rebound, but there was for the age of the peak velocity of BMI and maximum BMI, both of which were earlier in girls than in boys. CONCLUSIONS: Changes in childhood stature and BMI parameters were related to adult BP and Echo-measurements more so in females than males. Also the relationship of the adult BP measurements with corresponding childhood biological parameters was stronger than the relationship for adult Echo-measurements.

A presente tese é formada por dois estudos envolvendo análises longitudinais de dados sobre um serviço especializado no atendimento fonoaudiológico a crianças com DEA. O serviço de atendimento realizado atualmente pelo LIFDEA tem mais de 30 anos de existência e, com intuito de reforçar a importância da prática baseada em evidência, buscou-se analisar os dados relacionados às crianças e adolescentes que realizaram avaliação e atendimento nos últimos 21 anos. O primeiro estudo contém uma descrição da história do LIFDEA, além de um levantamento do número de pacientes atendidos, seus dados sociodemográficos, tempo médio de atendimento, idade de início do tratamento e sua evolução, com base nos dados encontrados nos prontuários do arquivo morto. Para o Estudo 1 foram selecionados todos os prontuários de pacientes que realizaram terapia fonoaudiológica no LIFDEA entre janeiro de 1997 e dezembro de 2017. Nesse primeiro estudo não foi possível verificar que a idade de início do atendimento fonoaudiológico diminuiu com o passar os anos, sendo a média de 6 anos de idade no início da avaliação; com manutenção média de 3 anos e meio de terapia. Na tabulação de dados foi observado que o índice de abandono do tratamento é muito alto. Dentre os 340 pacientes analisados, 24% realizaram um ano ou menos de terapia. Concluiu-se no Estudo 1 que o número de indivíduos que desistem ou abandonam o atendimento é considerável e a idade de início da terapia não está relacionada à maior manutenção do tratamento. No segundo Estudo foi realizado um recorte nos dados levantados no Estudo 1, juntamente com os dados referentes aos pacientes que frequentaram o serviço entre os anos de 2011 e 2017. Este segundo estudo teve um enfoque na análise aprofundada e retrospectiva das avaliações mais aplicadas ao longo destes anos, ou seja, do PFC e do DSC. No Estudo 2 foram selecionados os pacientes que realizaram atendimento neste mesmo serviço entre os anos de 2011 e 2017 e que para os quais foram obtidos dados completos referentes ao protocolo do PFC aplicados semestralmente. Nos resultados do Estudo 2 foi possível observar que as funções comunicativas mais frequentes foram o JC, PE e XP, com uma média de nove funções em cada PFC analisado. Foram identificados os dados do DSC de 138 pacientes e o escore médio nessa verificação foi de 22 pontos. Alguns coeficientes do PFC indicam que há associação com o DSC. Há correlação negativa entre a idade de início e o número de atos comunicativos e correlação positiva entre o número de respostas apresentados no PFC, o escore do DSC e os atos comunicativos com funções mais interativas. Conclui-se que é possível observar evolução clínica a partir da análise destes dois protocolos em períodos de três anos de intervenção e que a idade no início da terapia fonoaudiológica está relacionada à maior evolução clínica / The present dissertation is comprised by two studies regarding the longitudinal analysis of the data referring to a specialized speech-language service to children with Autism Spectrum Disorders. The Speech-Language Research Laboratory on ASD has been providing services to this population for over 30 years and, aiming to point-out to the importance of evidence-based practice the study aimed to analyze the data referring to children and adolescents that received services in this service in the last 21 years. The first study describes the history of this Laboratory and the number of patients enrolled, their socialdemographic data, mean period of intervention, age in the intervention onset and clinical evolution, based on the data obtained in the data-bank. Data to the Study 1 were selected from all the records of patients enrolled in this Laboratory in the period from January 1997 to December 2017. In this first study we didn´t verify a decrease in the age of the beginning of the treatment. The mean age of intervention onset was 6 years and the average duration of the therapy was 3.5 years. In the data analyses it was observed that the dropt-out index is very high: of the 340 patients considered, 24% received less than one year of therapy. Study 1 concluded that the number of individuals that give-up or abandon the service is high and that the age at the onset of the treatment is not related to the adherence to the intervention process. The second study considered the data of patients that received services between 2011 and 2017. This study focused on the analyses of the Functional Communicative Profile and of the Social Cognitive Performance on a retrospective in-depth analysis. In Study 2 data refer to the patients that received therapy ion this service in the period determined and for whom there were complete data referring to the Functional Communicative Profile obtained every semester. In the results of Study 2 it was possible to observe that the most frequent communicative functions were joint play, performative and exploratory, with an average of nine different functions in each protocol analyzed. Data about the Social Cognitive Performance of 138 patients were available and resulted on the average score of 22 points. Some results of the Functional Communicative Profile suggest that there is some association with the Social Cognitive Performance. There is a negative correlation between the age of the onset of the intervention and number of communicative acts expressed and positive correlation between the number of responses presented in the Functional Communication Profile, the Social Cognitive Performance score and the communicative acts with more interactive functions. It can be concluded that it is possible to observe clinical evolution over a three-year period based on the analyses of the two protocols used and that the age at the beginning of the intervention is associated to a larger clinical evolution

Neste estudo observacional longitudinal prospectivo, foram avaliados os parâmetros clínicos de 2257 sítios de 16 pacientes não fumantes em manutenção periodontal, através de sondagem computadorizada. Estes pacientes, tratados de periodontite crônica de moderada a severa, receberam manutenção periodontal trimestralmente durante dois anos. Na consulta inicial e aos 3, 6, 9, 12, 18 e 24 meses foram registrados, em seis sítios por dente, os parâmetros clínicos profundidade clínica de sondagem (PCS), retração gengival, nível clínico de inserção (NCI), sangramento e supuração à sondagem e presença de placa, além da mobilidade dentária. A mensuração e registro automatizado destas medidas foram realizados com precisão de 0,2 mm, sob pressão constante de 20 g. Todos os exames foram realizados pelo mesmo examinador, treinado e calibrado. Os sítios monitorados apresentaram, no período avaliado, redução de bolsa e ganho clínico de inserção significativos (p<0,00001). Considerando diferenças maiores do que 1 mm entre o NCI aos 24 meses e no exame inicial, 4,52% dos sítios apresentaram perda de inserção. O modelo multinível de regressão logística mostrou que, quanto menores o NCI e a PCS inicial do sítio, maiores seriam suas chances de perder inserção. Sítios com maiores frequências de presença de placa ou de sangramento à sondagem, bem como sítios proximais e em dentes com mobilidade, também tiveram maiores chances de perda de inserção. Sítios de alguns grupos dentários também apresentaram maiores chances deste desfecho. O reduzido número de sítios com perda de inserção e a melhora nos parâmetros clínicos detectados neste estudo demonstraram a importância de um programa de manutenção periodontal bem realizado e supervisionado, com intervalos regulares de três meses, na manutenção da saúde periodontal obtida com o tratamento. / In this prospective longitudinal observational study, the periodontal clinical parameters of 2257 sites of 16 non-smoking patients under maintenance were evaluated by computerized periodontal probing. These patients, who had been treated of moderate to severe chronic periodontitis, received periodontal maintenance every third month over two years. At baseline and at 3, 6, 9, 12, 18 and 24 months, the clinical parameters Probing Depth (PD), gingival recession, Clinical Attachment Level (CAL), bleeding and suppuration on probing and plaque presence, besides tooth mobility, were record at six sites per tooth. The measurement and automated recording of these measures was performed with resolution of 0.2 mm, under constant force of 20g. All examinations and measures were performed by the same trained and calibrated examiner. The monitored sites showed, in the evaluated period, significant (p<0.00001) pocket reduction and clinical attachment gain. When differences between the CAL at 24 months and at baseline greater than 1 mm were considered, 4.52% of the sites showed attachment loss. The multilevel logistic model showed that, the smaller the site NCI and PCS baseline values, the bigger its odds of loss attachment. Sites with higher frequencies of plaque presence or bleeding on probing, as well as proximal sites and sites in mobility teeth, showed bigger odds of attachment loss too. Sites in some tooth groups showed bigger odds of this outcome too. The reduced number of sites with attachment loss and the detected attachment gain in this trial demonstrated the importance of a well performed and supervised periodontal maintenance program, with regular intervals of three months, in the maintenance of the periodontal health obtained after treatment.