Orientador: Ana Gabriela Sálvio / Banca: Luciana Patrícia Abbade / Banca: Luiz Augusto Marcondes Fonseca / Resumo: Introdução: O melanoma cutâneo é o mais agressivo dos cânceres de pele. Sua incidência vem aumentando em todo o mundo e vários fatores têm sido atribuídos a este aumento. Estudos sobre o melanoma cutâneo com base em dados de registros populacionais são escassos no Brasil. Objetivos: Descrever os coeficientes de incidência (1996-2011) por melanoma cutâneo na cidade de Jaú, segundo: sexo, ano de diagnóstico, faixa etária, localização anatômica, estadio e tipo histológico. Descrever os coeficientes de mortalidade (1996-2011) por melanoma cutâneo na cidade de Jaú, segundo: sexo, ano do óbito e faixa etária. Analisar a tendência dos coeficientes de incidência (1996-2011), segundo: ano de diagnóstico, sexo e estadio. Analisar a tendência dos coeficientes de mortalidade (1996-2011) por melanoma cutâneo na cidade de Jaú, segundo: ano do óbito e sexo. Métodos: Foram analisados 162 casos novos de melanoma cutâneo diagnosticados no período de 1996 a 2011 fornecidos pelo Registro de Câncer de Base Populacional de Jahu e 39 óbitos por melanoma cutâneo ocorridos entre 1996 e 2011 fornecidos pelo Sistema de Informações sobre Mortalidade do Ministério da Saúde (SIM-MS). Foram calculados os coeficientes bruto e padronizado de incidência e de mortalidade, foi analisada a tendência destes coeficientes através do modelo de regressão. Resultados: O coeficiente médio de incidência (1996-2011) para o sexo feminino foi de 5,1 por 100.000 e para o sexo masculino foi de 4,8 por 100.000. Ambos não apresentaram tendência de crescimento ou queda no período (estabilidade). O coeficiente médio de mortalidade (1996-2011) para o sexo feminino foi de 1,4 por 100.000 e para o sexo masculino foi de 2,2 por 100.000, ambos também não apresentaram tendência de crescimento ou queda. Os coeficientes de incidência para os casos diagnosticados na fase inicial da doença, estadio 0, apresentaram tendencia de crescimento (r2=0,73; ... / Abstract: Introduction: The cutaneous melanoma is the most aggressive of the skin cancers. Its incidence is increasing all over the world and many factors are being assigned to this increase. Studies on cutaneous melanoma based on population-based registries are scarce in Brazil. Objectives: Describe the incidence rates (1996-2011) by cutaneous melanoma in the city of Jaú, according: sex, year of the diagnosis, age, anatomic location, stage and histological type. Describe the mortality coefficients (1996-2011) by cutaneous melanoma in the city of Jaú, according: sex, year of death and age. Analyze the tendency of the incidence coefficients (1996-2011), according: year of diagnosis, sex and stage. Analyze the tendency of the mortality coefficients (1996-2011) by cutaneous melanoma in the city of Jaú, according: year of death and sex. Methods: 162 new cases of cutaneous melanoma diagnosed in the period from 1996 to 2011 were analyzed and they were provided by the Population-Based Cancer Registry of Jaú and 39 deaths by cutaneous melanoma occurred between 1996 and 2011 provided by the Mortality Information System of the Ministry of Health (SIM-MS). The crude and the standardized coefficients of incidence and mortality were calculated, the tendency of those coefficients were analyzed through the regression model. Results: The average incidence coefficient (1996-2011) for the feminine sex was 5.1 from 100,000 and for the masculine sex was 4.8 from 100,000. Both didn't present tendency of increasing or decreasing in the period (stability). The average mortality coefficient (1996-2011) for the feminine sex was 1.4 from 100,000 and for the masculine sex was 2.2 from 100,000, both also didn't present tendency of increasing or decreasing. The incidence coefficients for the cases diagnosed in the initial phase of the disease, stage 0, presented growing tendency (r2=0.73; p=0.03) and the cases of stage I and II, presented decreasing tendency (r2=0.98; ... / Mestre

Thesis (MSc)--University of Stellenbosch, 2007. / ENGLISH ABSTRACT: While research and population surveys in HIV/AIDS are well established in developed countries, Sub-Saharan Africa is still experiencing scarce HIV/AIDS information. Hence it depends on results obtained from models. Due to this dependence, it is important to understand the strengths and limitations of these models very well. In this study, a simple mathematical model is formulated and then extended to incorporate various features such as stages of HIV development, time delay in AIDS death occurrence, and risk groups. The analysis is neither purely mathematical nor does it concentrate on data but it is rather an exploratory approach, in which both mathematical methods and numerical simulations are used. It was found that the presence of stages leads to higher prevalence levels in a short term with an implication that the primary stage is the driver of the disease. Furthermore, it was found that time delay changed the mortality curves considerably, but it had less effect on the proportion of infectives. It was also shown that the characteristic behaviour of curves valid for most epidemics, namely that there is an initial increase, then a peak, and then a decrease occurs as a function of time, is possible in HIV only if low risk groups are present. It is concluded that reasonable or quality predictions from mathematical models are expected to require the inclusion of stages, risk groups, time delay, and other related properties with reasonable parameter values. / AFRIKAANSE OPSOMMING: Terwyl navorsing en bevolkingsopnames oor MIV/VIGS in ontwikkelde lande goed gevestig is, is daar in Afrika suid van die Sahara slegs beperkte inligting oor MIV/VIGS beskikbaar. Derhalwe moet daar van modelle gebruik gemaak word. Dit is weens hierdie feit noodsaaklik om die moontlikhede en beperkings van modelle goed te verstaan. In hierdie werk word ´n eenvoudige model voorgelˆe en dit word dan uitgebrei deur insluiting van aspekte soos stadiums van MIV outwikkeling, tydvertraging by VIGS-sterftes en risikogroepe in bevolkings. Die analise is beklemtoon nie die wiskundage vorme nie en ook nie die data nie. Dit is eerder ´n verkennende studie waarin beide wiskundige metodes en numeriese simula˙sie behandel word. Daar is bevind dat insluiting van stadiums op korttermyn tot ho¨er voorkoms vlakke aanleiding gee. Die gevolgtrekking is dat die primˆere stadium die siekte dryf. Verder is gevind dat die insluiting van tydvestraging wel die kurwe van sterfbegevalle sterk be¨ınvloed, maar dit het min invloed op die verhouding van aangestekte persone. Daar word getoon dat die kenmerkende gedrag van die meeste epidemi¨e, naamlik `n aanvanklike styging, `n piek en dan `n afname, in die geval van VIGS slegs voorkom as die bevolking dele bevat met lae risiko. Die algehele gevolgtrekking word gemaak dat vir goeie vooruitskattings met sinvolle parameters, op grond van wiskundige modelle, die insluiting van stadiums, risikogroepe en vertragings benodig word.

Orientador: Ana Carla Pereira Latini / Banca: Alessandra Pontillo / Banca: James Venturini / Resumo: A hanseníase é uma doença infecciosa crônica, que acomete pele e sistema nervoso periférico e tem como agente etiológico o Mycobacterium leprae, um patógeno exclusivamente intracelular, que tem predileção por macrófagos e pelas células de Schwann. É um traço complexo e fatores genéticos do hospedeiro têm sido repetidamente implicados com o risco para a doença. A região cromossômica 6p21 vem sendo sistematicamente envolvida com a hanseníase, não só pelos genes do HLA de classe II, como também pelos estudos envolvendo marcadores em genes como o TNF e a LTA. O gene TLR1 também é um importante candidato e polimorfismos deste já têm sido associados com hanseníase per se e com reação hansênica. O objetivo desta pesquisa foi conduzir estudo de associação de base populacional do tipo caso-controle em hanseníase testando marcadores do tipo tag SNPs em genes candidatos da região cromossômica candidata 6p21 e do gene TLR1. Oitenta e nove marcadores do tipo tag SNPs, localizados em trinta e seis genes foram genotipados. O presente trabalho envolveu 1718 indivíduos, 981 casos e 737 controles, provenientes de dois estados brasileiros: Mato Grosso e São Paulo. As genotipagens da população de Rondonópolis, MT foram realizadas em plataforma de médio rendimento (VeraCode GoldenGate Genotyping Assay - Illumina) e as genotipagens da população de São Paulo foram feitas usando discriminação alélica baseada na tecnologia TaqMan (Applied Biosystems). Para as análises estatísticas foi empregado modelo de regressão logística, com correção para as co-variáveis etnia e sexo, usando o software R, para Windows. Treze genes localizados na região 6p21 tiveram marcadores associados com hanseníase per se. O alelo S do polimorfismo N248S do gene TLR1 também foi associado com susceptibilidade para hanseníase per se. Estes dados ressaltam o papel destes genes na susceptibilidade genética para a ... / Abstract: Leprosy is an chronic infectious disease that attacks skin and peripheral nervous system. The causative agent is Mycobacterium leprae, an obligate intracellular pathogen that infects macrophage and Schwann cells. It is a complex trait and host genetic factors have been extensively implicated in leprosy susceptibility. The chromosomal region 6p21 has been involved with leprosy susceptibility due to HLA class II, and TNF and LTA genes, as well. The TLR1 gene is also an important candidate gene and polymorphisms at this locus have been associated to leprosy per se and leprosy reactions. This research is a population-based association study in leprosy which tested tag SNPs located at candidate genes in chromosomal region 6p21 and in TLR1 gene. Eighty-nine markers distributed in thirty-six genes were genotyped. The present work enrolled 1,718 individuals, 981 cases and 737 controls from Mato Grosso and São Paulo States, Brazil. The genotypes for Rondonópolis population were obtained using by medium-scale genotyping platform (VeraCode GoldenGate Genotyping Assay - Illumina), while to São Paulo samples the genotyping were done by allelic discrimination based on TaqMan technology (Applied Biosystems). Statistical analysis were performed by logistic regression models adjusted for the covariates sex and ethnicity, using R software. Thirteen genes located at 6p21 region presented markers associated to leprosy per se. The S allele for N248S polymorphism at TLR1gene was also associated to leprosy susceptibility. These data show the role of these genes in genetic host resistance and susceptibility to leprosy and suggest the necessity of replication and functional studies in order to better explain their involvement with the disease / Mestre

Bibliography: leaves 263-270.

Made available in DSpace on 2014-06-11T19:30:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-31Bitstream added on 2014-06-13T19:19:07Z : No. of bitstreams: 1 000754767.pdf: 1885697 bytes, checksum: 2ed2ea03ad68b5ea2b12562ea9d0f63c (MD5) / A hanseníase é uma doença infecciosa crônica, que acomete pele e sistema nervoso periférico e tem como agente etiológico o Mycobacterium leprae, um patógeno exclusivamente intracelular, que tem predileção por macrófagos e pelas células de Schwann. É um traço complexo e fatores genéticos do hospedeiro têm sido repetidamente implicados com o risco para a doença. A região cromossômica 6p21 vem sendo sistematicamente envolvida com a hanseníase, não só pelos genes do HLA de classe II, como também pelos estudos envolvendo marcadores em genes como o TNF e a LTA. O gene TLR1 também é um importante candidato e polimorfismos deste já têm sido associados com hanseníase per se e com reação hansênica. O objetivo desta pesquisa foi conduzir estudo de associação de base populacional do tipo caso-controle em hanseníase testando marcadores do tipo tag SNPs em genes candidatos da região cromossômica candidata 6p21 e do gene TLR1. Oitenta e nove marcadores do tipo tag SNPs, localizados em trinta e seis genes foram genotipados. O presente trabalho envolveu 1718 indivíduos, 981 casos e 737 controles, provenientes de dois estados brasileiros: Mato Grosso e São Paulo. As genotipagens da população de Rondonópolis, MT foram realizadas em plataforma de médio rendimento (VeraCode GoldenGate Genotyping Assay – Illumina) e as genotipagens da população de São Paulo foram feitas usando discriminação alélica baseada na tecnologia TaqMan (Applied Biosystems). Para as análises estatísticas foi empregado modelo de regressão logística, com correção para as co-variáveis etnia e sexo, usando o software R, para Windows. Treze genes localizados na região 6p21 tiveram marcadores associados com hanseníase per se. O alelo S do polimorfismo N248S do gene TLR1 também foi associado com susceptibilidade para hanseníase per se. Estes dados ressaltam o papel destes genes na susceptibilidade genética para a... / Leprosy is an chronic infectious disease that attacks skin and peripheral nervous system. The causative agent is Mycobacterium leprae, an obligate intracellular pathogen that infects macrophage and Schwann cells. It is a complex trait and host genetic factors have been extensively implicated in leprosy susceptibility. The chromosomal region 6p21 has been involved with leprosy susceptibility due to HLA class II, and TNF and LTA genes, as well. The TLR1 gene is also an important candidate gene and polymorphisms at this locus have been associated to leprosy per se and leprosy reactions. This research is a population-based association study in leprosy which tested tag SNPs located at candidate genes in chromosomal region 6p21 and in TLR1 gene. Eighty-nine markers distributed in thirty-six genes were genotyped. The present work enrolled 1,718 individuals, 981 cases and 737 controls from Mato Grosso and São Paulo States, Brazil. The genotypes for Rondonópolis population were obtained using by medium-scale genotyping platform (VeraCode GoldenGate Genotyping Assay – Illumina), while to São Paulo samples the genotyping were done by allelic discrimination based on TaqMan technology (Applied Biosystems). Statistical analysis were performed by logistic regression models adjusted for the covariates sex and ethnicity, using R software. Thirteen genes located at 6p21 region presented markers associated to leprosy per se. The S allele for N248S polymorphism at TLR1gene was also associated to leprosy susceptibility. These data show the role of these genes in genetic host resistance and susceptibility to leprosy and suggest the necessity of replication and functional studies in order to better explain their involvement with the disease

Thesis (PhD (Biomedical Sciences. Molecular Biology and Human Genetics))--Stellenbosch University, 2008. / This series of studies includes both methodological analyses, aimed at furthering our understanding of, and improving the tools used in molecular epidemiology, and investigative projects which have used these tools to add to our knowledge of the M. tuberculosis epidemic. Using serial isolates from tuberculosis patients, we have investigated the evolutionary rate of the IS6110 RFLP pattern. In accordance with other studies, we determined a ½-life for this epidemiological marker of 10.69 years, confirming its appropriateness for this purpose. We also identified an initial, much higher apparent rate which we proposed was the result of pre-diagnostic evolution. In support of this, our investigations in the context of household transmission of M. tuberculosis revealed that IS6110-based evolution is closely associated with transmission of the organism, resulting in a strain population rate of change of 2.9% per annum. To accommodate evolution within estimates of transmission, we proposed that calculations incorporate the concept of Nearest Genetic Distance (cases most similar in RFLP pattern and most closely associated in time). We used this to create transmission chains which allowed for limited evolution of the IS6110 marker. As a result, in our study community, the estimated level of disease attributable to ongoing transmission was increased to between 73 and 88% depending on the Genetic Distance allowed. We identified the duration of a study as a further source of under-estimation of transmission. This results from the artefactual abridgement of transmission chains caused by the loss of cases at the temporal boundaries of a study. Using both real and simulated data, we showed that viewing a 12-year study through shorter window periods dramatically lowered estimates of transmission. This effect was negatively correlated with the size of a cluster. Various combinations of MIRU-VNTR loci have been proposed as an alternative epidemiological marker. Our investigations showed that, while this method yielded estimates of transmission similar to those of IS6110, there was discordance between the two markers in the epidemiological linking of cases as a result of their independent evolution. Attempting to compensate for this by allowing for evolution during transmission improved the performance of IS6110, but generally had a deleterious effect of that of MIRU-VNTR. However, this marker remains a valuable tool for higher phylogenetic analysis and we used it to demonstrate a correlation between sublineages of the Beijing clade and the regions in which they are found. We proposed that, either the host population had selected for a particular sublineage, or that specific sublineages had adapted to be more successful in particular human populations. We further explored the dynamics of the epidemic over a 12-year period in terms of the five predominant M. tuberculosis clades. We found that, while four of these clades remained relatively stable, the incidence of cases from the Beijing clade increased exponentially. This growth was attributed to drug-sensitive cases although drug-resistant Beijing cases also appeared to be more successful than their non-Beijing counterparts. Possible factors contributing to this clade’s success were a greater proportion of positive sputum smears and a lower rate of successful treatment.

Health scientists often rely on simulation models to reconstruct groundwater contaminant exposure data for retrospective epidemiologic studies. Due to the nature of historical reconstruction process, there are inevitably uncertainties associated with the input data and, therefore, with the final results of the simulation models, potentially adversely impacting related epidemiologic investigations. This study examines the uncertainties associated with the historically reconstructed contaminant fate and transport simulations for an epidemiologic study conducted at U.S. Marine Corps Base Camp Lejeune, North Carolina. To achieve an efficient uncertainty analysis, sensitivity analysis was first conducted to identify the critical uncertain variables, which were then adopted in the uncertainty analysis using an improved Monte Carlo simulation (MCS) method. Particularly, uncertainties associated with the historical contaminant arrival time were evaluated. To quantify the uncertainties in an efficient manner, a procedure identified as Pumping Schedule Optimization System (PSOpS) was developed to obtain the extreme (i.e., earliest and latest) contaminant arrival times caused by pumping schedule variations. Two improved nonlinear programming methods Rank-and-Assign (RAA) and Improved Gradient (IG) are used in PSOpS to provide computational efficiency. Furthermore, a quantitative procedure named Pareto Dominance based Critical Realization Identification (PDCRI) was developed to screen out critical realizations for contaminant transport in subsurface system, so that the extreme contaminant arrival times under multi-parameter uncertainties could be evaluated efficiently.

In the Amazonian region occurs a variation in the malaria incidence, which is related to the pluviometric variation annual. The mathematical model proposed here considers this seasonality and different treatment intensities accessible to the infected people. The numerical evidence the seasonal fluctuation and the relationship between the environment temperature and treatment efficiency, showing that the temperature increase strongly affects the extrinsic latent period,reducing the healthy care efficiency. Because malaria treatment already exists it should be import. For another hand, even the investment in treatment is an efficient form to block the epidemy, it is not always sufficient, because the protozoan has been more resistent to the medicine; then scientists are creating transgenic mosquitoes refractory to malaria to couple with wild one, generating descending transgenic. To avaliate this situation, we consider here a mathematical model that describes the relatioship between these populations. Then, we formulate and solve an optimal control problem indicating how the transgenic mosquitoes should be introduced in the environment. The numerical simulations show the effectiveness of the control. / Na Amazônia ocorre uma variação na incidência de malária que está intimamente relacionada à variação pluviométrica ao longo do ano. O modelo matemático aqui proposto considera esta sazonalidade e diferentes intensidades de tratamento acessíveis às pessoas infectadas. Experimentos numéricos descrevem a flutuação sazonal e evidenciam uma relação inversa entre a temperatura e eficiência do tratamento, mostrando que um aumento na temperatura afeta fortemente o período latente extrínseco, reduzindo a eficiência do investimento em saúde. Como o tratamento para os infectados existe, é importante concentrar esforços nesse sentido para obter sucesso no controle da malária. Por outro lado, embora o investimento em tratamento seja uma forma eficaz de impedir a epidemia, isso nem sempre é suficiente, pois é fato que o protozoário tem se mostrado cada vez mais resistente aos medicamentos; por esse motivo, cientistas estão criando mosquitos transgênicos refratários à malária que devem acasalar com os mosquitos selvagens, gerando descendência transgência. Para avaliar esta situação, consideramos neste trabalho um modelo matemático que descreve de maneira simplificada a relação entre estas duas populações. A partir desse modelo, formulamos e resolvemos um problema de controle ótimo indicando uma forma adequada de introduzir esses mosquitos transgênicos. Experimentos numéricos mostram a eficácia do controle adotado.

Orientador: Jose Martins Filho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T10:19:13Z (GMT). No. of bitstreams: 1 Ratto_MariaTeresaQueirozFerreira_M.pdf: 3017256 bytes, checksum: e1d55f93f02774ebb108c29571886601 (MD5) Previous issue date: 2006 / Resumo: O presente estudo tem como objetivo verificar qual o atual estado da saúde bucal da criança e do jovem da faixa etária de 05 a 18 anos da educação básica de Escolas Públicas e Privadas do Centro da cidade de São Paulo em vista das normas de prevenção que vêm sendo aplicadas no Brasil desde aproximadamente 1970. Estabelecer uma associação entre consciência de hábitos de higiene oral, dieta alimentar e saúde bucal, em suma avaliar a associação de fatores concorrentes é também objeto deste trabalho. Foi desenvolvido um estudo transversal com uma amostra delimitada pela região central, centro sul e centro oeste da cidade de São Paulo. Foram examinados 506 indivíduos de 05 a 18 anos com uma equipe de examinadores previamente treinados. Aplicaram-se questionários sobre hábitos de higiene oral e um Recordatório Alimentar de 24 horas. Utilizou-se para análise dos dados teste Qui-quadrado. Quando os valores esperados são menores que 5, foi utilizado o teste exato de Fisher, sendo considerado significativa a associação quando o p-valor < ou = 0.05 / Mestrado / Saude da Criança e do Adolescente / Mestre em Saude da Criança e do Adolescente

Made available in DSpace on 2015-03-04T18:50:52Z (GMT). No. of bitstreams: 1 Tese_Ana_Wyse.pdf: 2000846 bytes, checksum: 92bfb0c607fa7c1745d9424164c49c63 (MD5) Previous issue date: 2007-04-09 / Conselho Nacional de Desenvolvimento Cientifico e Tecnologico / In the Amazonian region occurs a variation in the malaria incidence, which is related to the pluviometric variation annual. The mathematical model proposed here considers this seasonality and different treatment intensities accessible to the infected people. The numerical evidence the seasonal fluctuation and the relationship between the environment temperature and treatment efficiency, showing that the temperature increase strongly affects the extrinsic latent period,reducing the healthy care efficiency. Because malaria treatment already exists it should be import. For another hand, even the investment in treatment is an efficient form to block the epidemy, it is not always sufficient, because the protozoan has been more resistent to the medicine; then scientists are creating transgenic mosquitoes refractory to malaria to couple with wild one, generating descending transgenic. To avaliate this situation, we consider here a mathematical model that describes the relatioship between these populations. Then, we formulate and solve an optimal control problem indicating how the transgenic mosquitoes should be introduced in the environment. The numerical simulations show the effectiveness of the control. / Na Amazônia ocorre uma variação na incidência de malária que está intimamente relacionada à variação pluviométrica ao longo do ano. O modelo matemático aqui proposto considera esta sazonalidade e diferentes intensidades de tratamento acessíveis às pessoas infectadas. Experimentos numéricos descrevem a flutuação sazonal e evidenciam uma relação inversa entre a temperatura e eficiência do tratamento, mostrando que um aumento na temperatura afeta fortemente o período latente extrínseco, reduzindo a eficiência do investimento em saúde. Como o tratamento para os infectados existe, é importante concentrar esforços nesse sentido para obter sucesso no controle da malária. Por outro lado, embora o investimento em tratamento seja uma forma eficaz de impedir a epidemia, isso nem sempre é suficiente, pois é fato que o protozoário tem se mostrado cada vez mais resistente aos medicamentos; por esse motivo, cientistas estão criando mosquitos transgênicos refratários à malária que devem acasalar com os mosquitos selvagens, gerando descendência transgência. Para avaliar esta situação, consideramos neste trabalho um modelo matemático que descreve de maneira simplificada a relação entre estas duas populações. A partir desse modelo, formulamos e resolvemos um problema de controle ótimo indicando uma forma adequada de introduzir esses mosquitos transgênicos. Experimentos numéricos mostram a eficácia do controle adotado.