Abstract This work engaged Finnish females affected with osteoarthritis (OA) of the hand to define the role of common sequence variations within the genes of the important structural protein of cartilage, aggrecan (AGC1), and the genes of inflammatory mediators, the interleukin 1 gene cluster and interleukin 6 (IL6), as possible risk factors for the disease. Also, a genome-wide linkage analysis was performed in a sample consisting of Finnish families with multiple individuals affected with hip and knee OA in order to reveal new chromosomal areas that are likely to contain disease associated variations. OA is a chronic disease that leads to the degeneration of articular cartilage in synovial joints. The etiology of the disease is for the most part unknown. Joints of the hand, hip and knee are most commonly affected, and obesity, trauma and excess mechanical stress are known risk factors for the disease. OA also has a significant genetic component. AGC1 carries a variable number of tandem repeats (VNTR) polymorphism, which may be significant for the biomechanical properties of cartilage. It was shown that the most common allele with 27 tandem repeats is protective against hand OA (HOA) (odds ratio 0.46, 95% confidence interval 0.27–0.78). Also, carrying two copies of any of the shorter or longer alleles increased the risk of the disease. Inflammation seems to play a role in the etiology of OA and certain polymorphisms within the interleukin 1 gene cluster and IL6 have been previously shown to increase the transcription of these molecules and to associate with OA. In this study it was shown that the G alleles in three common IL6 promoter single nucleotide polymorphism (SNP) sites are associated with the risk of more severe forms of HOA (p =  0.001 for GGG haplotype). A SNP in IL1B associated with the bilateral form of the disease (p =  0.006) and two IL1B-IL1RN extended haplotype alleles were associated with the same phenotype. Genome-wide and fine mapping linkage analyses recognized chromosomal locus 2q21 with a multipoint LOD score of 3.96. Despite the association analyses of several candidate genes within the locus, no disease-associating sequence variants were identified.

Record linkage is the task of identifying records within one or multiple databases that refer to the same entity. Currently, there exist many different approaches for record linkage. Some approaches incorporate the use of heuristic rules, mathematical models, Markov models, or machine learning. This thesis focuses on the application of record linkage to genealogical records within family trees. Today, large collections of genealogical records are stored in databases, which may contain multiple records that refer to a single individual. Resolving duplicate genealogical records can extend our knowledge on who has lived and more complete information can be constructed by combining all information referring to an individual. Simple string matching is not a feasible option for identifying duplicate records due to inconsistencies such as typographical errors, data entry errors, and missing data. Record linkage algorithms can be classified under two broad categories, a rule-based or heuristic approach, or a probabilistic-based approach. The Cocktail Approach, presented by Shirley Ong Ai Pei, combines a probabilistic-based approach with a rule-based approach for record linkage. This thesis discusses a re-implementation and adoption of the Cocktail Approach to genealogical records.

KTH Campus is open to the city but when we walk around we feel it is very isolated. Most people gather in the south square or in the triangle park in the middle. These two gathering points are separated from each other. Drottning Kristinas Väg acts as a quick path for cars. Along this road there are many empty outdoor spaces but most of them are not used by people. It is such a waste. Then how to make better use of the existing parks or squares and how to use parks or squares as linkage of public spaces are what I want to explore.

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O relacionamento de dados record linkage, originou-se na área da saúde pública e atualmente é aplicado em várias outras áreas como: epidemiologia, pesquisa médica, criação de ensaios clínicos, na área de marketing, gestão de relacionamento com o cliente, detecção de fraude, aplicação da lei e na administração do governo. A técnica consiste no processo de comparação entre dois ou mais registros em diferentes bases de dados e as principais estratégias de record linkage são: manual, deterministic record linkage (DRL) e probabilistic record linkage (PRL). Este estudoteve como objetivo aplicar o record linkage em bases de dados heterogêneas, utilizadas pela rede de atenção à saúde do município de Ribeirão Preto e identificar entre elas a melhor estratégia a ser adotada para a integração de bases de dados na área da saúde. As bases de dados da secretaria Municipal de Saúde de Ribeirão Preto (SMS-RP) e do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP/USP) foram objeto deste estudo, tendo como critério de inclusão apenas os registros de pacientes em que o município de residência informado correspondia ao município de Ribeirão Preto e o atendimento tivesse ocorrido na Unidade Básica Distrital e de Saúde (UDBS) - Centro Saúde Escola Joel Domingos Machado\" (CSE-Sumarezinho) nos anos de janeiro de 2006 a agosto de 2008 e no HCFMRP/USP. Foi selecionada uma amostra aleatória simples resultando em um conjunto de 1.100 registros de pacientes na base de dados do CSE-Sumarezinho e de 370.375 registros na base de dados do HCFMRP/USP. Foram, então, selecionadas quatro variáveis de relacionamento (nome, nome da mãe, sexo e data de nascimento). As estratégias adotadas foram: DRL exato, DRL com discordância em uma variável de relacionamento, e baseada em funções de similaridades (Dice, Levenshtein, Jaro e Jaro-Winkler) e, por fim, PRL. A estratégia DRL exato resultou em 334 registros pareados e na abordagem com discordância de uma variável foram 335, 343, 383 e 495, sendo as variáveis discordantes sexo, data de nascimento, nome e nome da mãe respectivamente. Quanto ao uso das funções de similaridades, as que mais se destacaram foram Jaro-Winkler e Jaro. Quanto à acurácia dos métodos aplicados, o PRL (sensibilidade = 97,75% (CI 95% 96,298,8) e especificidade = 98,55% (CI 95% 97,0-99,4)) obteve melhor sensibilidade e especificidade, seguido do DRL com as funções de similaridade Jaro-Winkler sensibilidade = 91,3% (CI 95% 88,793,4) e especificidade = 99% (CI 95% 97,6-99,7)) e Jaro (sensibilidade = 73,1% (CI 95% 69,476,6) e especificidade = 99,6% (CI 95% 98,5-99,9)). Quanto à avaliação da área sob a curva ROC do PRL, observou-se que há diferença estatisticamente significativa (p = 0,0001) quando comparada com os métodos DRL com discordância da variável nome da mãe, Jaro-Winkler e Jaro. Os resultados obtidos permitem concluir que o método PRL é mais preciso dentre as técnicas avaliadas. Mas as técnicas com a função de similaridade de Jaro-Winkler e Jaro também são alternativas viáveis interessantes devido à facilidade de utilização apesar de apresentarem o valor de sensibilidade ligeiramente menor que o PRL. / The record linkage originated in the area of public health and is currently applied in several other areas such as epidemiology, medical research, establishment of clinical trials, in the area of marketing, manager customer relationships, fraud detection, law enforcement and government administration. The technique consists on the comparison between two or more records in different databases and their key strategies are: manual comparison, Deterministic Record Linkage (DRL), and Probabilistic Record Linkage (PRL).This study aimed to apply the record linkage in heterogeneous databases, used by the network of health care in Ribeirão Preto and identify the best strategy to be adopted for the integration of databases in health care. The databases that were evaluated in this study were of the Municipal Health Department of Ribeirão Preto (SMS-RP) and of the Clinical Hospital of the School of Medicine of Ribeirao Preto (HCFMRP/USP) having as inclusion criterion only the records of patients in the county of residence reported corresponded to the city of Ribeirão Preto and care had taken place in the Basic District Health Unit (UDBS) - School Health Center \"Joel Domingos Machado\" (CSE-Sumarezinho) included in the years from January 2006 to August 2008 and in the HCFMRP/USP. Held to select a simple random sample resulted in a set of 1,100 patient records in the database of the CSE-Sumarezinho and 370,375 records in the database of HCFMRP/USP. Then there was the selection of four linking variables (name, mother\'s name, gender and birth date). The strategies adopted were: the exact DRL, DRL with one variable where the linking is disagreement, applied with similarity functions (Dice, Levenshtein, Jaro, and Jaro-Winkler), and, finally, PRL. The strategy of the exact DRL resulted in 334 matched records and strategy in dealing with disagreement of one variable were 335, 343, 383 and 495, to the following variables discordant gender, birth date, name and mother\'s name, respectively. Regarding the use of similarity functions which most stood out were Jaro and Jaro-Winkler. Regarding the accuracy of the methods applied, the PRL obtained better sensitivity and specificity (sensitivity = 97,75% (CI 95% 96,298,8) and specificity = 98.55% (95% CI 97.0 to 99.4)), followed by the DRL with the similarity functions Jaro-Winkler (sensitivity = 91.3% (95% CI 88.7 to 93.4) and specificity = 99% (95% CI 97.6 to 99, 7)) and then by Jaro (sensitivity = 73.1% (95% CI 69.4 to 76.6) = 99.6% and specificity (95% CI 98.5 to 99.9)). The evaluation of the area under the ROC curve in the PRL, was observed that there is statistically significant difference (p = 0.0001) if it is compared with the DRL methods when there is disagreement in the variable mother\'s name, as well as for Jaro and for Jaro-Winkler. The results indicate that the PRL method is most accurate among the techniques evaluated. Although the techniques with the similarity function of Jaro-Winkler and Jaro were also interesting viable options due to the ease of use, although having the sensitivity value slightly smaller than the PRL.

O relacionamento de dados record linkage, originou-se na área da saúde pública e atualmente é aplicado em várias outras áreas como: epidemiologia, pesquisa médica, criação de ensaios clínicos, na área de marketing, gestão de relacionamento com o cliente, detecção de fraude, aplicação da lei e na administração do governo. A técnica consiste no processo de comparação entre dois ou mais registros em diferentes bases de dados e as principais estratégias de record linkage são: manual, deterministic record linkage (DRL) e probabilistic record linkage (PRL). Este estudoteve como objetivo aplicar o record linkage em bases de dados heterogêneas, utilizadas pela rede de atenção à saúde do município de Ribeirão Preto e identificar entre elas a melhor estratégia a ser adotada para a integração de bases de dados na área da saúde. As bases de dados da secretaria Municipal de Saúde de Ribeirão Preto (SMS-RP) e do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP/USP) foram objeto deste estudo, tendo como critério de inclusão apenas os registros de pacientes em que o município de residência informado correspondia ao município de Ribeirão Preto e o atendimento tivesse ocorrido na Unidade Básica Distrital e de Saúde (UDBS) - Centro Saúde Escola Joel Domingos Machado\" (CSE-Sumarezinho) nos anos de janeiro de 2006 a agosto de 2008 e no HCFMRP/USP. Foi selecionada uma amostra aleatória simples resultando em um conjunto de 1.100 registros de pacientes na base de dados do CSE-Sumarezinho e de 370.375 registros na base de dados do HCFMRP/USP. Foram, então, selecionadas quatro variáveis de relacionamento (nome, nome da mãe, sexo e data de nascimento). As estratégias adotadas foram: DRL exato, DRL com discordância em uma variável de relacionamento, e baseada em funções de similaridades (Dice, Levenshtein, Jaro e Jaro-Winkler) e, por fim, PRL. A estratégia DRL exato resultou em 334 registros pareados e na abordagem com discordância de uma variável foram 335, 343, 383 e 495, sendo as variáveis discordantes sexo, data de nascimento, nome e nome da mãe respectivamente. Quanto ao uso das funções de similaridades, as que mais se destacaram foram Jaro-Winkler e Jaro. Quanto à acurácia dos métodos aplicados, o PRL (sensibilidade = 97,75% (CI 95% 96,298,8) e especificidade = 98,55% (CI 95% 97,0-99,4)) obteve melhor sensibilidade e especificidade, seguido do DRL com as funções de similaridade Jaro-Winkler sensibilidade = 91,3% (CI 95% 88,793,4) e especificidade = 99% (CI 95% 97,6-99,7)) e Jaro (sensibilidade = 73,1% (CI 95% 69,476,6) e especificidade = 99,6% (CI 95% 98,5-99,9)). Quanto à avaliação da área sob a curva ROC do PRL, observou-se que há diferença estatisticamente significativa (p = 0,0001) quando comparada com os métodos DRL com discordância da variável nome da mãe, Jaro-Winkler e Jaro. Os resultados obtidos permitem concluir que o método PRL é mais preciso dentre as técnicas avaliadas. Mas as técnicas com a função de similaridade de Jaro-Winkler e Jaro também são alternativas viáveis interessantes devido à facilidade de utilização apesar de apresentarem o valor de sensibilidade ligeiramente menor que o PRL. / The record linkage originated in the area of public health and is currently applied in several other areas such as epidemiology, medical research, establishment of clinical trials, in the area of marketing, manager customer relationships, fraud detection, law enforcement and government administration. The technique consists on the comparison between two or more records in different databases and their key strategies are: manual comparison, Deterministic Record Linkage (DRL), and Probabilistic Record Linkage (PRL).This study aimed to apply the record linkage in heterogeneous databases, used by the network of health care in Ribeirão Preto and identify the best strategy to be adopted for the integration of databases in health care. The databases that were evaluated in this study were of the Municipal Health Department of Ribeirão Preto (SMS-RP) and of the Clinical Hospital of the School of Medicine of Ribeirao Preto (HCFMRP/USP) having as inclusion criterion only the records of patients in the county of residence reported corresponded to the city of Ribeirão Preto and care had taken place in the Basic District Health Unit (UDBS) - School Health Center \"Joel Domingos Machado\" (CSE-Sumarezinho) included in the years from January 2006 to August 2008 and in the HCFMRP/USP. Held to select a simple random sample resulted in a set of 1,100 patient records in the database of the CSE-Sumarezinho and 370,375 records in the database of HCFMRP/USP. Then there was the selection of four linking variables (name, mother\'s name, gender and birth date). The strategies adopted were: the exact DRL, DRL with one variable where the linking is disagreement, applied with similarity functions (Dice, Levenshtein, Jaro, and Jaro-Winkler), and, finally, PRL. The strategy of the exact DRL resulted in 334 matched records and strategy in dealing with disagreement of one variable were 335, 343, 383 and 495, to the following variables discordant gender, birth date, name and mother\'s name, respectively. Regarding the use of similarity functions which most stood out were Jaro and Jaro-Winkler. Regarding the accuracy of the methods applied, the PRL obtained better sensitivity and specificity (sensitivity = 97,75% (CI 95% 96,298,8) and specificity = 98.55% (95% CI 97.0 to 99.4)), followed by the DRL with the similarity functions Jaro-Winkler (sensitivity = 91.3% (95% CI 88.7 to 93.4) and specificity = 99% (95% CI 97.6 to 99, 7)) and then by Jaro (sensitivity = 73.1% (95% CI 69.4 to 76.6) = 99.6% and specificity (95% CI 98.5 to 99.9)). The evaluation of the area under the ROC curve in the PRL, was observed that there is statistically significant difference (p = 0.0001) if it is compared with the DRL methods when there is disagreement in the variable mother\'s name, as well as for Jaro and for Jaro-Winkler. The results indicate that the PRL method is most accurate among the techniques evaluated. Although the techniques with the similarity function of Jaro-Winkler and Jaro were also interesting viable options due to the ease of use, although having the sensitivity value slightly smaller than the PRL.

Bipolar disorder and recurrent major depression are complex psychiatric illnesses with a substantial, yet unknown genetic component. Genetic studies have identified linkage of bipolar disorder and recurrent major depression with markers on chromosome 4p15-p16 in a large Scottish family and three smaller families. To focus the search for genetic factors for susceptibility to illness two approaches were adopted: a chromosome 4p15-p16 candidate gene study and a whole-genome linkage scan. In the first instance, phosphatidylinositol 4-kinase type-II beta (PI4K2B) was selected as a candidate gene. Analysis of haplotypes in the four linked families identified two regions, both of which were shared by three families. PI4K2B lies within one of these regions. PI4K2B is also a worthy functional candidate as it is a member of the phosphatidylinositol pathway, which is targeted by lithium for therapeutic effect in bipolar disorder. Expression studies at the allele-specific mRNA and protein level were performed in lymphoblastoid cell lines from the large Scottish family. There was no evidence for expression differences between affected and non-affected family members. However, a case-control association study showed preliminary evidence for association of schizophrenia but not bipolar disorder, with tagging single nucleotide polymorphisms from the PI4K2B genomic region. Second, the linkage evidence for bipolar disorder and recurrent major depression in the large Scottish family was re-examined. This was important because additional family members had been recruited and advances in technology made it feasible to cover all chromosome regions more densely than had been possible ten years ago. Stringent genotyping and pedigree error checks were performed to ensure an optimised dataset for analysis. Furthermore, the large family was divided in an informative manner for ease of analysis using both parametric and non-parametric methods, supplemented by haplotype analysis. Genome-wide significant evidence for linkage was observed on chromosome 4p15- p16 and genome-wide suggestive evidence was observed on chromosomes 8p21 and 1p36. The analysis clearly supports the evidence for a susceptibility locus of bipolar disorder and recurrent major depression on chromosome 4p15-p16, while identifying other genetic loci that may confer risk to psychiatric illness.