Objectives. Ascertain if there has been a secular trend in 3-months prevalence of casually reported back pain. Evaluate if such back pain predicts concurrent health as well as future sick leave, disability pension, hospitalization and survival. Study differences in diagnostic assessment and labelling between physicians. Evaluate if a comprehensive manual therapy programme reduces sickness absence. Materials and methods. Combined population samples from 1973 to 2003 with a total of 12,891 observations with self-reported back pain and covariates. 7,074 of these individuals were followed for an average of 8.5 years and outcomes were self-reported health as well as official register data on sick leave, disability pension, hospitalisation and mortality. The Gotland Low Back Pain Study, a randomised controlled trial with participation of two general practitioners and two orthopaedic surgeons treating 160 patients with acute/subacute low back pain, with 10 weeks diagnostic evaluation and treatment and a two-year follow up. Results. Back pain prevalence increased 16% per ten years (OR 1.16, 95%CI 1.11-1.22). Back pain was negatively associated with self-rated health (p<0.0001), increased the risk of disability pension (p<0.002), and hospital admissions (p<0.0005), but not number of days in hospital, sick leave or mortality. General practitioners used terms from manual medicine and reported more pseudoradicular pain, while orthopaedic surgeons used non-specific pain labels, reported more true radicular pain and used more x-ray examinations. Among those on sick leave at baseline, manual therapy patients showed faster return to work (HR 1.62, 95%CI 1.006–2.60) and a lower point-prevalence of sick leave than reference patients at end of treatment period (ratio 0.35, 95% CI 0.13–0.97) but not after two years. Conclusions. There was a strong secular trend towards increase in self-reported back pain from 1973 to 2003. Such pain had a negative effect on some of the health outcomes and does not appear to be harmless. Physicians from different specialities labelled the condition differently. The manual therapy programme proved to be more effective than the established treatment regarding return to work.

Este é um estudo ecológico misto onde o perfil de distribuição de chuvas e das variações térmicas foi relacionado à variação sazonal das taxas de incidência de leishmaniose visceral em vinte municípios brasileiros de transmissão intensa da doença, no período de 2001 a 2008. O objetivo foi identificar similaridades e diferenças entre os municípios estudados quanto à tendência temporal e sazonalidade da doença e à possível relação entre variações climáticas e a distribuição sazonal da doença. Os dados de incidência de leishmaniose visceral foram obtidos do Sistema de Informação de Agravos de Notificação (Sinan), os dados demográficos foram obtidos do Departamento de Informática do Sistema Único de Saúde (DATASUS), os dados pluviométricos e de temperatura foram obtidos do Sistema de Monitoramento Agrometeorológico do Ministério da Agricultura (AGRITEMPO). Os resultados são apresentados graficamente e mostram que a distribuição sazonal da incidência e períodos prováveis de transmissão são diferentes em vários municípios e acompanham as diferenças climáticas, sugerindo que as intervenções que visem diminuir a incidência devem ser pontuais, obedecendo às características de cada município. / This is a mixed ecological study where the distribution profile of rainfall and temperature variations were related to seasonal variation in the rate of incidence of visceral leishmaniasis in twenty highly endemic municipalities in the period from 2001 to 2008. The purpose was to identify similarities and differences between the municipalities studied concerning disease trends and seasonal patterns and regarding the potential relationships between climatic variations and the seasonal distribution of the disease. Incidence data on visceral leishmaniasis were obtained from the Sistema de Informação de Agravos de Notificaçao (Sinan), demographic data were obtained from the Departamento de Informática do Sistema Único de Saúde (DATASUS), the temperature and rainfall data were obtained from agrometeorological monitoring system of the Ministry of Agriculture (AGRITEMPO). The results are presented graphically and show that the seasonal distribution of the incidence and probable transmission periods are different in several municipalities and accompanying climatic differences, suggesting that interventions aimed at reducing the incidence must be punctual, according to the characteristics of each municipality.

Este é um estudo ecológico misto onde o perfil de distribuição de chuvas e das variações térmicas foi relacionado à variação sazonal das taxas de incidência de leishmaniose visceral em vinte municípios brasileiros de transmissão intensa da doença, no período de 2001 a 2008. O objetivo foi identificar similaridades e diferenças entre os municípios estudados quanto à tendência temporal e sazonalidade da doença e à possível relação entre variações climáticas e a distribuição sazonal da doença. Os dados de incidência de leishmaniose visceral foram obtidos do Sistema de Informação de Agravos de Notificação (Sinan), os dados demográficos foram obtidos do Departamento de Informática do Sistema Único de Saúde (DATASUS), os dados pluviométricos e de temperatura foram obtidos do Sistema de Monitoramento Agrometeorológico do Ministério da Agricultura (AGRITEMPO). Os resultados são apresentados graficamente e mostram que a distribuição sazonal da incidência e períodos prováveis de transmissão são diferentes em vários municípios e acompanham as diferenças climáticas, sugerindo que as intervenções que visem diminuir a incidência devem ser pontuais, obedecendo às características de cada município. / This is a mixed ecological study where the distribution profile of rainfall and temperature variations were related to seasonal variation in the rate of incidence of visceral leishmaniasis in twenty highly endemic municipalities in the period from 2001 to 2008. The purpose was to identify similarities and differences between the municipalities studied concerning disease trends and seasonal patterns and regarding the potential relationships between climatic variations and the seasonal distribution of the disease. Incidence data on visceral leishmaniasis were obtained from the Sistema de Informação de Agravos de Notificaçao (Sinan), demographic data were obtained from the Departamento de Informática do Sistema Único de Saúde (DATASUS), the temperature and rainfall data were obtained from agrometeorological monitoring system of the Ministry of Agriculture (AGRITEMPO). The results are presented graphically and show that the seasonal distribution of the incidence and probable transmission periods are different in several municipalities and accompanying climatic differences, suggesting that interventions aimed at reducing the incidence must be punctual, according to the characteristics of each municipality.

I evaluated twenty-eight years (1980-2007) of spatial-temporal water quality data from Deer Creek Reservoir in Utah. The data came from three sampling points representing the lotic, transitional and lentic zones. The data included measurements of climatological, hydrological and water quality conditions at four depths; Surface, Above Thermocline, Below Thermocline and Bottom. The time frame spanned dates before and after the completion of the Jordanelle Reservoir (1987-1992), approximately fourteen miles upstream of Deer Creek. I compared temporal groupings and found that a traditional month distribution following standard seasons was not effective in characterizing the measured conditions; I developed a more representative seasonal grouping by performing a Tukey-Kramer multiple comparisons adjustment and a Bonferronian correction of the Student's t comparison. Based on these analyses, I determined the best groupings were Cold (December - April), Semi-Cold (May and November), Semi-Warm (June and October), Warm (July and September) and Transition (August). I performed principal component analysis (PCA) and factor analysis (FA) to determine principal parameters associated with the variability of the water quality of the reservoir. These parameters confirmed our seasonal groups showing the Cold, Transition and Warm seasons as distinct groups. The PCA and FA showed that the variables that drive most of the variability in the reservoir are specific conductivity and variables related with temperature. The PCA and FA showed that the reservoir is highly variable. The first 3 principal components and rotated factors explained a cumulative 59% and 47%, respectively of the variability in Deer Creek. Both parametric and nonparametric approaches provided similar correlations but the evaluations that included censored data (nutrients) were considerably different with the nonparametric approach being preferred.

Introdução: A cada ano, são diagnosticados mais de um milhão de novos casos de câncer de mama em mulheres no mundo. Os países mais desenvolvidos apresentam as maiores incidências, enquanto a mortalidade é maior nos países em desenvolvimento. No Brasil, as incidências mais elevadas se localizam nas regiões Sul e Sudeste. Nos últimos cinco anos, a incidência de câncer de mama aumentou cerca de 30 por cento nos países do ocidente, porém, a partir do ano 2000, observa-se ligeiro decréscimo na mortalidade. A investigação simultânea sobre a incidência e a mortalidade pode fornecer informações sobre a etiologia da doença, e a análise dos efeitos da idade, período e da coorte facilita a compreensão dos mecanismos responsáveis pela variação nas tendências. Objetivos: Analisar as tendências da incidência e da mortalidade por câncer de mama feminino no município de São Paulo, segundo os efeitos da idade, período e coorte. Métodos: Foram analisadas a incidência no período de 1997 a 2005, e a mortalidade no período de 1982 a 2005. Os dados foram obtidos no Registro de Câncer de Base Populacional de São Paulo, no Sistema de Mortalidade do Ministério da Saúde (SIM-MS) e no Instituto Brasileiro Geografia e Estatística (IBGE). Os efeitos da idade, do período e da coorte na tendência dos coeficientes de incidência e mortalidade foram analisados pelo modelo de regressão de Poisson. Resultados: As tendências da incidência e da mortalidade aumentam com a idade, porém esse efeito é maior na mortalidade, sobretudo entre as mulheres com idade a partir dos 50 anos. O efeito do período apresentou tendência crescente para a incidência no período entre 2003 e 2005, que coincide com o início dos mutirões de mamografia no município de São Paulo. Para a mortalidade, a tendência foi decrescente no mesmo período. O efeito da coorte apresentou tendência decrescente a partir das coortes mais antigas, estável na maioria das gerações intermediárias, e decrescente nas coortes mais recentes tanto para incidência quanto para mortalidade. Conclusão: O padrão observado no município de São Paulo é semelhante ao observado em países mais desenvolvidos como Estados Unidos, Austrália e Reino Unido / Introduction: Every year, over one million new cases of breast cancer are diagnosed worldwide. Incidence rates are higher in industrialised countries; conversely, mortality rates are higher in developing countries. In Brazil, the highest incidence rates are found in southeastern and southern states. In the last five years, breast cancer incidence rates have increased approximately 30 per cent in most western countries, however, since 2000, a slight decrease has in mortality been observed. Simultaneous investigations on incidence and mortality provide important clues for disease aetiology, and the age-period-cohort model is an useful approach to understand time trends mechanisms. Objectives: To examine time trends in the female breast cancer incidence and breast cancer mortality by age, period and cohort effects. Methods: Incidence was analyzed between 1997 and 2005, and mortality was analyzed between 1982 and 2005. Data were obtained from São Paulo Cancer Registry, Mortality System of Health Ministry, and Brazilian Institute of Geography and Statistic. The effects of age, period and cohort were estimated using a Poisson regression model. Results: Time trends for breast cancer incidence and mortality increase across all age groups, but this effect is more pronounced in mortality rates, especially for women older than 50 years. Period effect in incidence increased between 2003 and 2005, and this coincide with the beginning of the mamography screening programs in São Paulo. The mortality decreased on the same period. The cohort effect in incidence and mortality suggested a decrease in older birth cohort, a levering between 1930 and 1969, and a slight decrease for women born after 1970s. Conclusion: The time trends patterns observed in São Paulo are similar to the ones observed in some developed countries, such United States, Australia and United Kingdom

Introdução: A cada ano, são diagnosticados mais de um milhão de novos casos de câncer de mama em mulheres no mundo. Os países mais desenvolvidos apresentam as maiores incidências, enquanto a mortalidade é maior nos países em desenvolvimento. No Brasil, as incidências mais elevadas se localizam nas regiões Sul e Sudeste. Nos últimos cinco anos, a incidência de câncer de mama aumentou cerca de 30 por cento nos países do ocidente, porém, a partir do ano 2000, observa-se ligeiro decréscimo na mortalidade. A investigação simultânea sobre a incidência e a mortalidade pode fornecer informações sobre a etiologia da doença, e a análise dos efeitos da idade, período e da coorte facilita a compreensão dos mecanismos responsáveis pela variação nas tendências. Objetivos: Analisar as tendências da incidência e da mortalidade por câncer de mama feminino no município de São Paulo, segundo os efeitos da idade, período e coorte. Métodos: Foram analisadas a incidência no período de 1997 a 2005, e a mortalidade no período de 1982 a 2005. Os dados foram obtidos no Registro de Câncer de Base Populacional de São Paulo, no Sistema de Mortalidade do Ministério da Saúde (SIM-MS) e no Instituto Brasileiro Geografia e Estatística (IBGE). Os efeitos da idade, do período e da coorte na tendência dos coeficientes de incidência e mortalidade foram analisados pelo modelo de regressão de Poisson. Resultados: As tendências da incidência e da mortalidade aumentam com a idade, porém esse efeito é maior na mortalidade, sobretudo entre as mulheres com idade a partir dos 50 anos. O efeito do período apresentou tendência crescente para a incidência no período entre 2003 e 2005, que coincide com o início dos mutirões de mamografia no município de São Paulo. Para a mortalidade, a tendência foi decrescente no mesmo período. O efeito da coorte apresentou tendência decrescente a partir das coortes mais antigas, estável na maioria das gerações intermediárias, e decrescente nas coortes mais recentes tanto para incidência quanto para mortalidade. Conclusão: O padrão observado no município de São Paulo é semelhante ao observado em países mais desenvolvidos como Estados Unidos, Austrália e Reino Unido / Introduction: Every year, over one million new cases of breast cancer are diagnosed worldwide. Incidence rates are higher in industrialised countries; conversely, mortality rates are higher in developing countries. In Brazil, the highest incidence rates are found in southeastern and southern states. In the last five years, breast cancer incidence rates have increased approximately 30 per cent in most western countries, however, since 2000, a slight decrease has in mortality been observed. Simultaneous investigations on incidence and mortality provide important clues for disease aetiology, and the age-period-cohort model is an useful approach to understand time trends mechanisms. Objectives: To examine time trends in the female breast cancer incidence and breast cancer mortality by age, period and cohort effects. Methods: Incidence was analyzed between 1997 and 2005, and mortality was analyzed between 1982 and 2005. Data were obtained from São Paulo Cancer Registry, Mortality System of Health Ministry, and Brazilian Institute of Geography and Statistic. The effects of age, period and cohort were estimated using a Poisson regression model. Results: Time trends for breast cancer incidence and mortality increase across all age groups, but this effect is more pronounced in mortality rates, especially for women older than 50 years. Period effect in incidence increased between 2003 and 2005, and this coincide with the beginning of the mamography screening programs in São Paulo. The mortality decreased on the same period. The cohort effect in incidence and mortality suggested a decrease in older birth cohort, a levering between 1930 and 1969, and a slight decrease for women born after 1970s. Conclusion: The time trends patterns observed in São Paulo are similar to the ones observed in some developed countries, such United States, Australia and United Kingdom

Population-based studies have been used to provide hypothesis about cancer etiology as well as in the identification of risk factors, and data have been obtained through population-based cancer registry databases. The aim of the study has been to describe time trends in cancer incidence and mortality in the population of Aracaju, Sergipe from 1996 to 2007. The methods used have consisted of an ecological study of time trends using data from the Population-based Cancer Registry of Aracaju and from The Mortality Database for the State of Sergipe. Incidence and mortality rates have then been calculated, based on official population counts and estimates. Time trends have been calculated by the Joinpoint Regression Program, National Cancer Institute, USA. The results showed rising incidence and mortality rates during the period of study. Cancer sites showing the highest age-standardized rates were; prostate, lungs, oral cavity, stomach, and colorectum in males; and breast, cervix, thyroid, colorectum, and uterine body in females. The sites exhibiting the highest age-standardized mortality rates were: prostate, lungs, stomach, oral cavity, and liver in males; and breast, lungs, cervix, uterine body, and colorectum in females. Incidence trends showed a rising pattern in males, but for females, only for crude rates until the year 2001. Mortality trends showed a ring pattern only in males. The features observed in the population studied have shown similarities with the ones observed in highincome areas, but conversely have shown, considering some cancer sites, such as cervix and oral cavity, the same pattern observed in low-income areas. / Os estudos populacionais têm sido frequentemente utilizados para a inferência de hipótese sobre a etiologia do câncer e na identificação dos fatores de risco, sendo os dados obtidos através do Registro de Câncer de Base Populacional. O estudo teve o objetivo de descrever as tendências de incidência e de mortalidade por câncer no município de Aracaju, Sergipe, no período 1996 a 2007. Como metodologia, foi realizado um estudo ecológico de séries temporais, utilizando os dados do Registro de Câncer de Base Populacional de Aracaju e do Sistema de Informação de Mortalidade para o estado de Sergipe, sendo então calculadas as taxas de incidência e de mortalidade por câncer, baseadas nas populações fornecidas ao DATASUS pelo Instituto Brasileiro de Geografia e Estatística. As análises das tendências foram calculadas pelo Joinpoint Regression Program do National Cancer Institute, USA. Os resultados obtidos revelaram taxas de incidência e de mortalidade crescentes durante o período. As topografias mais incidentes, usando a padronização pela população mundial, foram: próstata, brônquios e pulmões, lábio, cavidade oral e faringe, estômago e cólon e reto no gênero masculino; e mama, colo uterino, tireoide, cólon e reto e corpo uterino no feminino. As topografias de maior mortalidade foram: próstata, brônquios e pulmões, estômago, lábio, cavidade oral e faringe e fígado e vias biliares intra-hepáticas no gênero masculino; e mama, brônquios e pulmões, colo do útero, corpo do útero e cólon e reto no feminino. As tendências de incidência do câncer foram crescentes no gênero masculino; mas, no feminino, só para as taxas brutas e até o ano 2001. A mortalidade só apresentou tendências crescentes no gênero masculino. O padrão observado no estudo foi semelhante ao das regiões mais desenvolvidas, exceto por algumas topografias de câncer como colo uterino e cavidade oral, que continuaram apresentando padrão das áreas menos desenvolvidas.

Smoking prevalence among adolescents in the Middle East remains high while rates of smoking have been declining among adolescents elsewhere. The aims of this research were to (1) describe patterns of cigarette and waterpipe (WP) smoking, (2) identify determinants of WP smoking initiation, and (3) identify determinants of cigarette smoking initiation in a cohort of Jordanian school children. Among this cohort of school children in Irbid, Jordan, (age ≈ 12.6 at baseline) the first aim (N=1,781) described time trends in smoking behavior, age at initiation, and changes in frequency of smoking from 2008-2011 (grades 7 – 10). The second aim (N=1,243) identified determinants of WP initiation among WP-naïve students; and the third aim (N=1,454) identified determinants of cigarette smoking initiation among cigarette naïve participants. Determinants of initiation were assessed with generalized mixed models. All analyses were stratified by gender. Baseline prevalence of current smoking (cigarettes or WP) for boys and girls was 22.9% and 8.7% respectively. Prevalence of ever- and current- any smoking, cigarette smoking, WP smoking, and dual cigarette/WP smoking was higher in boys than girls each year (p These studies reveal intensive smoking patterns at early ages among Jordanian youth in Irbid, characterized by a predominance of WP smoking. WP may be a vehicle for tobacco dependence and subsequent cigarette uptake. The sizeable incidence of WP and cigarette initiation among students of both sexes points to a need for culturally relevant smoking prevention interventions. Gender-specific factors, refusal skills, and smoking cessation of both WP and cigarettes for youth and their parents/teachers would be important components of such initiatives.

The incidence of cutaneous malignant melanoma (CMM) is steadily increasing. Most of the patients have thin CMM with a good prognosis and a 5-year survival of about 90%. The prognosis is highly related to tumour thickness and clinical stage at diagnosis. Effective systemic treatment for patients with metastatic disease has only recently been available. This thesis aims to increase knowledge of trends in tumour thickness, prognostic factors, socioeconomic differences and medical costs in patients with CMM. The population-based Swedish melanoma register is the main source of data in all papers in the thesis. Papers I-III include patients from all of Sweden while paper IV is delimited to the County of Östergötland. Cox regression and logistic regression are the main multivariable methods used. Paper IV is focused on stage-specific costs of CMM by comparing direct healthcare costs to a general population. For men, there has been a shift over time towards thinner tumours at diagnosis accompanied by an improved survival. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men. Tumour ulceration, tumour thickness and Clark’s level of invasion all showed significant independent long-term prognostic information in T1 CMMs. By combining these factors, three distinct prognostic subgroups were identified. Lower level of education was associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. The direct healthcare costs for CMM patients were significantly higher than for the general population, independent of clinical stage. CMM patients diagnosed in clinical stage III-IV were associated with particularly high costs. Even though the survival among Swedish patients with CMM is among the highest in the world and still seems to improve, the results of this thesis emphasise the need of improved early detection strategies. This may be of particular concern in men, older women, and groups with a low level of education. The results also imply that the costs for the management of CMM patients may be reduced if early detection efforts are successful and lead to a more favourable stage distribution. The finding of a better risk stratification of thin CMMs may help to improve the management of this large patient group.

<p>cDNA microarrays is one of the first high-throughput gene expression technologies that has emerged within molecular biology for the purpose of functional genomics. cDNA microarrays compare the gene expression levels between cell samples, for thousands of genes simultaneously. </p><p>The microarray technology offers new challenges when it comes to data analysis, since the thousands of genes are examined in parallel, but with very few replicates, yielding noisy estimation of gene effects and variances. Although careful image analyses and normalisation of the data is applied, traditional methods for inference like the Student <i>t</i> or Fisher’s <i>F</i>-statistic fail to work.</p><p>In this thesis, four papers on the topics of empirical Bayes and full Bayesian methods for two-channel microarray data (as e.g. cDNA) are presented. These contribute to proving that empirical Bayes methods are useful to overcome the specific data problems. The sample distributions of all the genes involved in a microarray experiment are summarized into prior distributions and improves the inference of each single gene.</p><p>The first part of the thesis includes biological and statistical background of cDNA microarrays, with an overview of the different steps of two-channel microarray analysis, including experimental design, image analysis, normalisation, cluster analysis, discrimination and hypothesis testing. The second part of the thesis consists of the four papers. Paper I presents the empirical Bayes statistic <i>B</i>, which corresponds to a <i>t</i>-statistic. Paper II is based on a version of <i>B</i> that is extended for linear model effects. Paper III assesses the performance of empirical Bayes models by comparisons with full Bayes methods. Paper IV provides extensions of <i>B</i> to what corresponds to <i>F</i>-statistics.</p>