Thesis (doctoral)--Lund University, 1998. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Lund University, 1998. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Doctor Pharmaceuticae - Dpharm / The brain laterality of pharmacists may influence where the pharmacists are best suited to work. Brain laterality refers to the asymmetry of the hemispheres of the brain with regard to specific cognitive functions, such as objectivity and emotion. The left hemisphere functions objectively and rationally, whereas the right hemisphere is subjective and non-rational. Animal behaviour in the literature demonstrated an influence of brain laterality, thus selecting an ideal work environment may also be driven by brain laterality bias. Further support for the research included: amblyopia; hemiplegia; the WADA test. The research question investigated the matching of the brain laterality groups of pharmacists to their ideal work environments. The aims investigated: ear, eye, hand and foot dominance in determining brain laterality; influence of brain laterality and reductionistic variables on job choice; location of emotion generation and job choice. Five objectives investigated these aims: influence of brain laterality alone; influence of brain laterality and reductionistic variables; influence of a new brain laterality determining continuum; Propinquity Principle in achieving data; correctness of the Right Hemisphere Theory (RHT) or the Valence Theory (VT). The RHT suggests that the right hemisphere is dominant in processing all emotion. The VT argues that the left hemisphere is specialised in processing the positive emotions while the right hemisphere is specialised in processing the negative emotions. The resulting Null Hypothesis posits that there is no statistical difference between the different brain laterality groups enabling pharmacists to work competently in any placement. The Alternative Hypothesis was that there is a statistical difference between the brain laterality groups, thus brain laterality can be used to best place pharmacists into ideal placements.

Doctor Pharmaceuticae - Dpharm / The brain laterality of pharmacists may influence where the pharmacists are best suited to work. Brain laterality refers to the asymmetry of the hemispheres of the brain with regard to specific cognitive functions, such as objectivity and emotion. The left hemisphere functions objectively and rationally, whereas the right hemisphere is subjective and nonrational. Animal behaviour in the literature demonstrated an influence of brain laterality, thus selecting an ideal work environment may also be driven by brain laterality bias. Further support for the research included: amblyopia; hemiplegia; the WADA test. The research question investigated the matching of the brain laterality groups of pharmacists to their ideal work environments. The aims investigated: ear, eye, hand and foot dominance in determining brain laterality; influence of brain laterality and reductionistic variables on job choice; location of emotion generation and job choice. Five objectives investigated these aims: influence of brain laterality alone; influence of brain laterality and reductionistic variables; influence of a new brain laterality determining continuum; Propinquity Principle in achieving data; correctness of the Right Hemisphere Theory (RHT) or the Valence Theory (VT). The RHT suggests that the right hemisphere is dominant in processing all emotion. The VT argues that the left hemisphere is specialised in processing the positive emotions while the right hemisphere is specialised in processing the negative emotions. The resulting Null Hypothesis posits that there is no statistical difference between the different brain laterality groups enabling pharmacists to work competently in any placement. The Alternative Hypothesis was that there is a statistical difference between the brain laterality groups, thus brain laterality can be used to best place pharmacists into ideal placements. Global warming questions in the questionnaire determined positive and negative emotion as well as enthusiasm for global warming problems. In South Africa, probability cluster sampling was applied utilising postal and email methods. In the UK, non-probability purposive sampling was applied utilising four methods: snowballing, email, postal, and convenience sampling. Both countries produced similar results for the same sample size.

Com a redução progressiva dos custos de sequenciamento completo do genoma humano, os estudos populacionais tornam-se viáveis. A interpretação dos dados e integração com informações clínicas, entretanto, apresentam-se como desafios crescentes. O conhecimento sobre a variabilidade genética e sua interação com fenótipos complexos podem ser ampliados com estudos de grande porte em populações miscigenadas, em particular de sociedades com heterogeneidades sociais, culturais e históricas, ainda pouco representadas globalmente na área da genômica. Este trabalho apresenta um conjunto de estudos colaborativos que se basearam em uma amostra de natureza representativa de idosos da cidade de São Paulo (amostra SABE, aproximadamente 1400 indivíduos) e em de octogenários cognitivamente saudáveis (amostra 80+, aproximadamente 130 indivíduos). Além de questionários e testes, DNA dos participantes foi obtido e exomas sequenciados para cerca de 600 indivíduos. Esta base permitiu a construção de grupos controles para diversos estudos de associação de variantes causais ou de suscetibilidade a doenças raras como distrofia muscular de cinturas, tumores do sistema endócrino e síndrome de Noonan, entre outras, além de integrar, como referência populacional local, o sistema de análise de variantes do serviço de diagnóstico molecular do Centro de Pesquisas sobre o Genoma Humano e Células-tronco da Universidade de São Paulo. Por ser uma amostra de idosos, além de permitir a construção de uma base eficiente para controles comparativos de doenças raras ou de início precoce, tornou-se possível a execução de projetos sobre envelhecimento cerebral através do recrutamento cerca de 580 indivíduos para ressonância magnética. Estudos com marcadores de demências, como polimorfismos do gene APOE (associado à doença de Alzheimer) indicaram que a população brasileira apresenta riscos diferenciais em relação a populações de outros países, provavelmente devido à estrutura populacional única do ponto de vista de ancestralidade genética e composição socio-econômica. Por fim, os estudos com ressonância magnética e genômica permitiram a investigação do fenótipo de lateralidade cerebral, que engloba dominâncias manual e de linguagem, que está presente de forma variável em seres humanos e está envolvida com distúrbios neuropsiquiátricos como dislexia e esquizofrenia. Foi possível detectar associação entre variantes do gene FOXP2, implicado no neurodesenvolvimento da linguagem, e endofenótipos assimétricos de tratos de substância branca envolvidos na produção da fala. O presente trabalho abre caminho para diversos novos projetos dada a escala de dados sociodemográficas, clínicos, funcionais e genômicos / Due to the progressive reduction of genome sequencing costs, population studies become feasible. Interpretation of subsequent data and integration with clinical information, however, impose a growing challenge. The knowledge about genetic variability and its interaction with complex phenotypes could be expanded with large scale admixed population studies, particularly in those samples that live in socially, culturally and historically heterogeneous communities, so far globally underrepresented in the genomics field. This thesis presents a collection of collaborative studies that were based on a population-representative sample of elderly from the city of São Paulo (SABE sample, approximately 1400 subjects) and a cognitively healthy octogenarians sample (80+ group, approximately 130 subjects). Comprehensive questionnaires and functional tests were obtained, along with DNA from all subjects and exome sequences from about 600 of them. This database allowed the assembly of control groups to several association studies with causal and susceptibility variants to rare disorders such as limb-girdle muscular dystrophy, endocrine system tumors and Noonan syndrome, among others, and, in addition, composed as a local population reference the analyses\' protocols in the molecular diagnosis service of the Human Genome and Stem-cell Research Center at the University of São Paulo. As this is an elderly sample, it was possible not only to build an efficient control group to compare with patients affected by rare or early onset disorders, but to promote projects on brain aging through recruitment of about 580 subjects to magnetic resonance imaging (MRI). Studies with markers of dementia, such as APOE gene polymorphisms (involved in Alzheimer\'s disease), suggested that the Brazilian population might present different risks compared to other countries, probably due to its unique population structure from the genetic ancestry standpoint and socioeconomic composition. As a final project, MRI and genomics studies were performed to investigate the phenotype of brain laterality, which comprises handedness and language dominance and it is variable among humans, with involvement with neuropsychiatric disorders such as dyslexia and schizophrenia. It was possible to detect an association between variants of FOXP2 gene, which is involved in neurodevelopmental processes of language, and asymmetry endophenotypes of white matter tracts that form the speech production circuitry. This effort opens several pathways to develop new projects due to the scale of sociodemographic, clinical, functional and genomic data

Com a redução progressiva dos custos de sequenciamento completo do genoma humano, os estudos populacionais tornam-se viáveis. A interpretação dos dados e integração com informações clínicas, entretanto, apresentam-se como desafios crescentes. O conhecimento sobre a variabilidade genética e sua interação com fenótipos complexos podem ser ampliados com estudos de grande porte em populações miscigenadas, em particular de sociedades com heterogeneidades sociais, culturais e históricas, ainda pouco representadas globalmente na área da genômica. Este trabalho apresenta um conjunto de estudos colaborativos que se basearam em uma amostra de natureza representativa de idosos da cidade de São Paulo (amostra SABE, aproximadamente 1400 indivíduos) e em de octogenários cognitivamente saudáveis (amostra 80+, aproximadamente 130 indivíduos). Além de questionários e testes, DNA dos participantes foi obtido e exomas sequenciados para cerca de 600 indivíduos. Esta base permitiu a construção de grupos controles para diversos estudos de associação de variantes causais ou de suscetibilidade a doenças raras como distrofia muscular de cinturas, tumores do sistema endócrino e síndrome de Noonan, entre outras, além de integrar, como referência populacional local, o sistema de análise de variantes do serviço de diagnóstico molecular do Centro de Pesquisas sobre o Genoma Humano e Células-tronco da Universidade de São Paulo. Por ser uma amostra de idosos, além de permitir a construção de uma base eficiente para controles comparativos de doenças raras ou de início precoce, tornou-se possível a execução de projetos sobre envelhecimento cerebral através do recrutamento cerca de 580 indivíduos para ressonância magnética. Estudos com marcadores de demências, como polimorfismos do gene APOE (associado à doença de Alzheimer) indicaram que a população brasileira apresenta riscos diferenciais em relação a populações de outros países, provavelmente devido à estrutura populacional única do ponto de vista de ancestralidade genética e composição socio-econômica. Por fim, os estudos com ressonância magnética e genômica permitiram a investigação do fenótipo de lateralidade cerebral, que engloba dominâncias manual e de linguagem, que está presente de forma variável em seres humanos e está envolvida com distúrbios neuropsiquiátricos como dislexia e esquizofrenia. Foi possível detectar associação entre variantes do gene FOXP2, implicado no neurodesenvolvimento da linguagem, e endofenótipos assimétricos de tratos de substância branca envolvidos na produção da fala. O presente trabalho abre caminho para diversos novos projetos dada a escala de dados sociodemográficas, clínicos, funcionais e genômicos / Due to the progressive reduction of genome sequencing costs, population studies become feasible. Interpretation of subsequent data and integration with clinical information, however, impose a growing challenge. The knowledge about genetic variability and its interaction with complex phenotypes could be expanded with large scale admixed population studies, particularly in those samples that live in socially, culturally and historically heterogeneous communities, so far globally underrepresented in the genomics field. This thesis presents a collection of collaborative studies that were based on a population-representative sample of elderly from the city of São Paulo (SABE sample, approximately 1400 subjects) and a cognitively healthy octogenarians sample (80+ group, approximately 130 subjects). Comprehensive questionnaires and functional tests were obtained, along with DNA from all subjects and exome sequences from about 600 of them. This database allowed the assembly of control groups to several association studies with causal and susceptibility variants to rare disorders such as limb-girdle muscular dystrophy, endocrine system tumors and Noonan syndrome, among others, and, in addition, composed as a local population reference the analyses\' protocols in the molecular diagnosis service of the Human Genome and Stem-cell Research Center at the University of São Paulo. As this is an elderly sample, it was possible not only to build an efficient control group to compare with patients affected by rare or early onset disorders, but to promote projects on brain aging through recruitment of about 580 subjects to magnetic resonance imaging (MRI). Studies with markers of dementia, such as APOE gene polymorphisms (involved in Alzheimer\'s disease), suggested that the Brazilian population might present different risks compared to other countries, probably due to its unique population structure from the genetic ancestry standpoint and socioeconomic composition. As a final project, MRI and genomics studies were performed to investigate the phenotype of brain laterality, which comprises handedness and language dominance and it is variable among humans, with involvement with neuropsychiatric disorders such as dyslexia and schizophrenia. It was possible to detect an association between variants of FOXP2 gene, which is involved in neurodevelopmental processes of language, and asymmetry endophenotypes of white matter tracts that form the speech production circuitry. This effort opens several pathways to develop new projects due to the scale of sociodemographic, clinical, functional and genomic data