A técnica da remoção seletiva de tecido cariado (RSTC) para lesões de cárie profundas em dentina de dentes decíduos e permanentes, já é consenso na literatura e é sustentada por pesquisas que demonstram excelentes resultados clínicos, radiográficos e microbiológicos. No entanto, a longevidade de restaurações adesivas realizadas após a RSTC, principalmente na dentição decídua, vem gerando algumas dúvidas e preocupações quanto ao seu desempenho, merecendo esclarecimentos. O objetivo deste estudo randomizado, controlado e multicêntrico foi comparar a taxa de sucesso de restaurações adesivas realizadas em dentes decíduos posteriores após a remoção total (RTTC) ou seletiva (RSTC) de tecido cariado ao longo de 30 meses. Métodos: Crianças de 4 a 8 anos de idade portadoras de pelo menos duas lesões cavitadas ativas em metade interna de dentina (metade interna da dentina na avaliação do RX interproximal e com pelo menos 1mm de dentina separando a lesão cariosa da polpa) e que se enquadrassem nos critérios de inclusão e exclusão participaram do estudo. Para cada criança os dentes (no mínimo dois, mas podendo ser mais) foram aleatoriamente divididos de acordo com os seguintes tratamentos: RTTC (grupo controle) ou RSTC (grupo teste). Nos casos em que ocorreu exposição pulpar, o dente foi devidamente tratado e excluído da amostra, os dados em relação ao tipo de remoção de tecido cariado que levou à exposição foram coletados. Quatro instituições participaram do estudo (Universidade Federal do Rio Grande do Sul; Universidade de São Paulo; Universidade Peruana Cayetano Heredia; Universidade Internacional do Equador), resultando em quatro odontopediatras que realizaram os procedimentos de remoção de tecido cariado e posterior restauração em resina composta, avaliadas clinicamente no baseline, 6, 12, 18, 24 e 30 meses. Todos os procedimentos foram realizados sob anestesia local e isolamento absoluto. Características sociodemográficas foram coletadas no baseline e características clínicas como índice ceod/CPOD, índice de placa visível (IPV) e índice de sangramento gengival (ISG) foram coletados em todos os períodos de acompanhamento. Em todos os momentos experimentais foram avaliados os aspectos clínicos das restaurações por um examinador cego e calibrado através do índice FDI adaptado. Para determinar as taxas de sucesso das restaurações de resina composta foram geradas curvas de sobrevida com o estimador Kaplan-Meyer para cada grupo avaliado, assim como as taxas de falha anual das restaurações. O modelo de regressão de Cox com falhas compartilhadas foi realizado para avaliar diferenças nas taxas de sobrevida das restaurações de acordo com o tratamento, instituição e características clínicas e demográficas da amostra. Resultados: Cento e seis crianças (51 meninos e 55 meninas) colaboraram com 278 dentes submetidos a restaurações adesivas, 137 após RTTC e 141 após RSTC. Oito exposições pulpares ocorreram no grupo da RTTC e quatro no grupo da RSTC. A taxa global de sucesso das restaurações foi 87,1% (85,4% para RTTC e 88,7% para RSTC) e o tempo médio de sobrevida foi de 30 meses. A taxa anual de falha foi de 7% após 24 meses de acompanhamento. Não houve diferença no risco de falha (TR) de acordo com o grupo de tratamento (TR 0,75; IC 95%: 0,38-1,46) e instituição (USP TR 0,44; IC 95%: 0,94-2,09; PERU TR 0,92; IC 95%: 0,26-3,19 EQUADOR TR 1,39; IC 95%: 0,45-4,28). Foram encontradas observações análogas em relação a todas as variáveis clínicas e demográficas. Conclusões: As restaurações adesivas realizadas em dentes decíduos com lesões cavitadas profundas em dentina apresentam sobrevida satisfatória após 33 meses de acompanhamento, independentemente da técnica realizada para remoção de tecido cariado. / The selective caries removal technique (SCR) for active deep carious lesions in deciduous and permanent teeth is already a consensus in the literature and is supported by studies that demonstrate excellent clinical, radiographic and microbiological results. However, the longevity of restorations performed after the SCR, mainly in primary dentition, has generated some doubts and concerns about its performance, deserving clarification. This multicenter study aimed to compare the success rate of adhesive restorations performed on posterior deciduous teeth after total or selective caries removal over 30 months Methods: Children between 4 - 8 years old with at least two active cavitated lesions in deep dentin (inner half of the dentin in the evaluation of the interproximal RX and with at least 1mm of dentin separating the carious lesion of the pulp) and that met the inclusion and exclusion criteria participated in the study. For each child, teeth were randomized and submitted to one of the treatment groups: total caries removal (TCR - control group) or SCR (test group). Children could have more than 2 teeth included. In cases of pulp exposure, data were analyzed and the tooth was excluded from the sample. Four institutions participated in the study (Federal University of Rio Grande do Sul, Peruvian University Cayetano Heredia and International Universidad of Ecuador), resulting in four pediatric dentists who performed the caries removal procedures and subsequent restorations in composite resin. Clinical evaluation was performed at baseline, 6, 12, 18, 24 and 30 months. All procedures were performed under local anesthesia and rubber dam use. Sociodemographic characteristics were collected at the baseline and clinical characteristics as dmft and visible plaque and gingival bleeding index were collected in all follow-up periods. Radiographs were taken only at baseline and restorations were clinically assessed at baseline, 6, 12, 18, 24 and 33 months by a blinded, trained and calibrated operator in each institution. The characteristics of the restorations were recorded according to an adaptation of the FDI criteria. Survival estimates for restoration longevity were evaluated using the Kaplan-Meier method. We also estimated the annual failure rate of the restorations. Cox regression model with shared frailty was performed to assess differences in survival rates of the restoration according to the intervention treatment, institution and clinical and demographic characteristics of the sample. Results: one hundred and six children (51 boys and 55 girls) collaborated with 278 teeth submitted to adhesive restorations (137 after TCR and 141 after SCR). Pulp exposure occurred in eight teeth (2.8%) allocated to TCR, and in four (1.4%) allocated to SCR group. The overall success rate of restorations was 87.1% (85.4% for TCR and 88.7% for SCR) and mean survival time was 30.3 months. The annual failure rate was 7% after 24 months of follow-up. There were no differences in the risk of failure according to the treatment group (HR 0.75;95%CI:0.38-1.46) and institution (USP HR 0.44;95%CI:0.94-2.09; PERU HR 0.92;95%CI:0.26-3.19; ECUADOR HR 1.39;95%CI:0.45-4.28). Analogous observations were found regarding all the clinical and demographic variables. Conclusions: Composite restorations of active deep carious lesions performed in posterior primary teeth show satisfactory survival of 87.1% after 33 months of follow-up, regardless of the technique performed for carious tissue removal.

This dissertation proposes a suite of novel Bayesian semiparametric estimators for a proportional hazard function associated with the gaptimes, or inter-arrival times, of a counting process in survival analysis. The Cox model is applied and extended in order to identify the subsequent effect of an event on future events in a system with renewal. The estimators may also be applied, without changes, to model the effect of a point treatment on subsequent events, as well as the effect of an event on subsequent events in neighboring subjects. These Bayesian semiparametric estimators are used to analyze the survival and reliability of the New York City electric grid. In particular, the phenomenon of "infant mortality," whereby electrical supply units are prone to immediate recurrence of failure, is flexibly quantified as a period of increased risk. In this setting, the Cox model removes the significant confounding effect of seasonality. Without this correction, infant mortality would be misestimated due to the exogenously increased failure rate during summer months and times of high demand. The structural assumptions of the Bayesian estimators allow the use and interpretation of sparse event data without the rigid constraints of standard parametric models used in reliability studies.

In this dissertation we solve the nonidentifiability problem of Archimedean copula models based on dependent censored data (see [Wang, 2012]). We give a set of identifiability conditions for a special class of bivariate frailty models. Our simulation results show that our proposed model is identifiable under our proposed conditions. We use EM algorithm to estimate unknown parameters and the proposed estimation approach can be applied to fit dependent censored data when the dependence is of research interest. The marginal survival functions can be estimated using the copula-graphic estimator (see [Zheng and Klein, 1995] and [Rivest and Wells, 2001]) or the estimator proposed by [Wang, 2014]. We also propose two model selection procedures for Archimedean copula models, one for uncensored data and the other one for right censored bivariate data. Our simulation results are similar to that of [Wang and Wells, 2000] and suggest that both procedures work quite well. The idea of our proposed model selection procedure originates from the model selection procedure for Archimedean copula models proposed by [Wang and Wells, 2000] for right censored bivariate data using the L2 norm corresponding to the Kendall distribution function. A suitable bootstrap procedure is yet to be suggested for our method. We further propose a new parameter estimator and a simple goodness-of-fit test for Archimedean copula models when the bivariate data is under fixed left truncation. Our simulation results suggest that our procedure needs to be improved so that it can be more powerful, reliable and efficient. In our strategy, to obtain estimates for the unknown parameters, we heavily exploit the concept of truncated tau (a measure of association established by [Manatunga and Oakes, 1996] for left truncated data). The idea of our goodness of fit test originates from the goodness-of-fit test for Archimedean copula models proposed by [Wang, 2010] for right censored bivariate data.

Introdução: O prognóstico dos carcinomas epidermóides de laringe é limitado e a taxa de sobrevida em cinco anos é menor que 70%. A relação de características clínicas e epidemiológicas tem sido investigada na sobrevida de pacientes com tumores de laringe, mas pouco se conhece sobre o efeito dos polimorfismos genéticos no prognóstico da doença. Objetivo: Estudar o papel dos polimorfismos genéticos de genes relacionados aos processos de invasão e metástase (MMP1 e MMP3), de inflamação (Interleucina 2, Interleucina 6, LTA) e reparo de DNA(XRCC1) no prognóstico do carcinoma epidermóide de laringe. Material e métodos: Coorte com 170 pacientes com carcinoma epidermóide de laringe,confirmados por exame anátomo-patológico. Os casos tiveram origem em estudo caso-controle conduzido em cinco hospitais de São Paulo, um hospital em Porto Alegre e outro em Goiânia. As informações sobre o status vital dos pacientes foram levantadas dos prontuários médicos e dos bancos de óbitos municipais e estaduais. A extração do DNA das amostras de sangue dos pacientes foi realizada pelo Instituto de Medicina Tropical da USP e a genotipagem dos polimorfismos genéticos pela Fundação Hemocentro de Ribeirão Preto da Faculdade de Medicina da USP. Resultados: Os polimorfismos genéticos estudados (MMP1 1607, MMP1 -519,MMP3 -1171, IL2 -384, IL2 114, IL6 -174, LTA 252 e XRCC1) não apresentaram efeitos com significância estatística na sobrevida global ou específica pela doença quando analisados isoladamente. Para a sobrevida global, o consumo excessivo de álcool, em g/L/dia, reduziu a sobrevida dos pacientes (80-119 g/L/dia: hazard ratio(HR)=4,0 intervalos com 95% de confiança (IC95%)=1,10-14,53; _120 g/L/dia: HR=5,6 IC95%=1,71-18,24). No modelo de Cox múltiplo, quando ajustados pelo polimorfismo genético MMP3 -1171, a sobrevida piorou para esses pacientes (80-119 g/L/dia: HR=4,9 IC95%=1,07-22,91; _120 g/L/dia: HR=6,3 IC95%=1,49-26,84). Para a sobrevida específica pela doença, o estadiamento clínico IV reduziu a sobrevida dos pacientes (HR=3,5 IC95%=1,67-7,28). No modelo de Cox múltiplo,com ajuste pelos polimorfismos genéticos IL6 -174 e MMP1 1607, a sobrevidaespecífica pela doença piorou para esses pacientes (HR=4,7 IC95%=1,38-16,25).Conclusões: Na coorte examinada, somente três dos oito polimorfismos genéticos estudados relacionaram-se com a sobrevida global e específica pela doença, porém apenas alterando o efeito dos valores dos HR brutos dos fatores consumo de álcool e estadiamento clínico, respectivamente na sobrevida global e sobrevida específica pela doença. Isoladamente, nenhum polimorfismo genético estudado interferiu na sobrevida dos pacientes com câncer de laringe. / Introduction: The prognosis of laryngeal squamous cell carcinoma is limited and survival rate is lower than 70%. The relationships between clinical and epidemiological characteristics have been fully investigated on the survival of patients with laryngeal tumors, but the effect of genetics polymorphisms on squamous cell carcinoma of larynx is not well-known. Objective: To study the role of genetic polymorphisms of genes related to the processes of invasion and metastasis (MMP1 and MMP3), inflammation (Interleukin 2, Interleukin 6, and LTA) and repair of DNA (XRCC1) in the prognosis of laryngeal squamous cell carcinoma. Material and methods: Cohort with 170 laryngeal squamous cell carcinoma patients with histological confirmation. The cases have their origin in a case-control study carried out in hospitals of Sao Paulo, Porto Alegre and Goiania. The information about vital status of patients had been raised from medical records. The extraction of DNA was carried out by Institute of Tropical Medicine of USP and genotyping was carried out by the Center of Cellular Therapy of the Hemocentro of Ribeirao Preto of Medical School of USP. Results: The studied genetic polymorphisms (MMP1 1607, MMP1 -519, MMP3 -1171, IL2 -384, IL2 114, IL6 -174, LTA 252 and XRCC1), separately analyzed, did not have any statistical significant effect on the overall and cause-specific survival. High levels of alcohol consumption (g/L/day) reduced the overall survival (80-119 g/L/day: hazard ratio(HR)=4.0 intervals with 95% of confidence (95%CI)=1.10-14.53; _120 g/L/day:HR=5.6 95%CI=1.71-18.24). Multiple Cox model revealed, when adjusted for MMP3 -1171 genetic polymorphism, lower survival for those patients (80-119g/L/day: HR=4.9 95%CI=1.07-22.91; _120 g/L/day: HR=6.3 95%CI=1.49-26.84). The clinical staging (CS) IV was a factor for low cause-specific survival (CS IV:HR=3.5 95%CI 1.67-7.28). In the multiple Cox model, adjusted for genetic polymorphism IL6 -174 and MMP1 1607, the survival of those patients droppe(HR=4.7 95%CI=1.38-16.25). Conclusions: In this cohort, only three of eight genetic polymorphisms studied were showed to be related with overall and causespecific survival, however only modifying the effect of unadjusted HR of alcohol consumption and tumor clinical staging in the overall and cause-specific survival respectively. None of the studied genetic polymorphisms, when analyzed separately,affected the survival of laryngeal cancer patients.

Introdução: Tem sido um desafio determinar o verdadeiro impacto clínico do Acinetobacter spp., devido a predileção desse microrganismo em colonizar e infectar pacientes críticos, os quais apresentam prognóstico ruim independente de complicações infecciosas secundárias. Objetivo: Avaliar se a sobrevida de pacientes com bacteremia por Acinetobacter spp. é menor em relação a de pacientes com bacteremia causada por outras bactérias prevalentes em unidade de terapia intensiva. Método: Trata-se de um estudo de coorte retrospectivo de pacientes internados nas unidades de terapia intensiva do Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, que desenvolveram bacteremia no período de 1 de janeiro de 2010 a 31 de dezembro de 2011. Pacientes com bacteremia por Acinetobacter spp. foram comparados a pacientes com bacteremia causada por outros patógenos (Klebsiella pneumoniae, Staphylococcus aureus, Enterobacter spp., Enterococcus spp. e Pseudomonas aeruginosa). Foi realizada análise de sobrevida em 30 dias. O método de Kaplan-Meier e teste de log-rank foram usados para determinar a sobrevida global. Fatores prognósticos potenciais foram identificados por análise bivariada e regressão multivariada de Cox. Resultados: 141 pacientes foram avaliados. Não houve diferenças entre os pacientes com bacteremia por Acinetobacter spp. e outros patógenos com relação à idade, sexo, APACHE II, índice de comorbidade de Charlson e tipo de infecção. A análise bivariada mostrou que idade > 60 anos, diabetes mellitus, infecção por Acinetobacter spp., tratamento inadequado, score de Pitt > 3, presença de choque séptico, uso de ventilação mecânica, uso de acesso central e número de falência de órgãos > 2 foram significativamente associados a pior prognóstico. Foram realizados dois modelos de análise de regressão logística. O modelo A mostrou que tratamento inadequado e score de Pitt > 3 pontos foram estatisticamente associados com letalidade. No modelo B, infecção por Acinetobacter spp. (HR = 1,93 IC 95%: 1,25-2,97) e idade > 60 anos foram fatores prognósticos independentes. Conclusão: Pacientes com bacteremia por Acinetobacter spp. apresentaram menor sobrevida em relação a pacientes com bacteremia causada por outras bactérias prevalentes em unidade de terapia intensiva / Introduction: It has been challenging to determine the true clinical impact of Acinetobacter spp., given the predilection of this pathogen to colonize and infect critically ill patients, who often have a poor prognosis irrespective of secondary infective complications. Objective: The aim of this study was to assess whether the survival of patients with Acinetobacter spp. bacteremia is lower than that of patients with bacteremia caused by other bacteria prevalent in intensive care unit. Setting: A retrospective review of medical records was conducted for all patients admitted to the ICUs who developed bacteremia from January 2010 through December 2011. Patients with Acinetobacter spp. were compared with those with other pathogens (Klebsiella pneumoniae, Staphylococcus aureus, Enterobacter spp., Enterococcus spp., Pseudomonas aeruginosa). We did a 30-day survival analysis. The Kaplan-Meier method and log-rank test were used to determine the overall survival. Potential prognostic factors were identified by bivariate and multivariate Cox regression analysis. Results: 141 patients were evaluated. No differences between patients with Acinetobacter spp. and other pathogens were observed with regard to age, sex, APACHE II score, Charlson Comorbidity Score and type of infection. Bivariate analysis showed that age > 60 years, diabetes mellitus, Acinetobacter spp. infection, inappropriate treatment, Pitt Bacteremia score >3, presence of septic shock, mechanical ventilation, use of central line and number of organ failures > 2 were significantly associated with a poor prognosis. We did two models of logistic regression analysis. Model A showed that inappropriate treatment and Pitt score > 3 points were statistically associated with mortality. In model B, Acinetobacter spp. infection (HR= 1.93, 95%CI: 1.25-2.97) and age > 60 years were independent prognostic factors. Conclusion: Patients with Acinetobacter spp. bacteremia had lower survival compared with patients with bacteremia caused by other bacteria prevalent in intensive care unit

O melanoma ungueal compreende cerca de 0,7 a 3,5% de todos os tipos de melanoma. Devido à dificuldade no diagnóstico precoce, seu prognóstico é reservado quando comparado às demais formas de melanoma. A amputação falangeana se propõe a extirpar o tumor respeitando os princípios da cirurgia oncológica, apesar de acarretar déficit funcional e estigmas sociais, além de não prolongar a sobrevida, particularmente nos casos iniciais. Abordagens mais conservadoras, como a cirurgia funcional, são utilizadas em casos in situ ou microinvasivos, que consistem na remoção de todo o complexo ungueal e preservação da falange distal, com bom resultado cosmético e funcional. Este estudo retrospectivo propõe comparar a sobrevida de pacientes tratados em cada uma das técnicas mencionadas, a partir de dados coletados de prontuários. Não houve alteração da sobrevida dos pacientes com melanoma ungueal tratados com amputação ou cirurgia funcional / Nail melanoma represents about 0.7-3.5% of all types of melanoma. Because its early diagnosis is difficult, the prognosis is conservative when compared with other forms of melanoma. The phalangeal amputation is intended to excise the tumor according to the cancer surgery principles, despite resulting in functional deficit and social stigmata and failing to extend survival, especially in early cases. More conservative approaches, such as functional surgery, have been used in \'in situ\' or microinvasive cases, which consist of removing the entire nail complex and preserving the distal phalange, provide good aesthetic and functional results. This retrospective study proposes to compare the survival of patients treated with each of these techniques by reviewing the data collected from their medical records. No changes were observed in the survival of nail melanoma patients treated with amputation or functional surgery

This work develops a marginal screening test to detect the presence of significant predictors for a right-censored time-to-event outcome under a high-dimensional accelerated failure time (AFT) model. Establishing a rigorous screening test in this setting is challenging, not only because of the right censoring, but also due to the post-selection inference. The oracle property in such situations fails to ensure adequate control of the family-wise error rate, and this raises questions about the applicability of standard inferential methods. McKeague and Qian (2015) constructed an adaptive resampling test to circumvent this problem under ordinary linear regression. To accommodate right censoring, we develop a test statistic based on a maximally selected Koul--Susarla--Van Ryzin estimator from a marginal AFT model. A regularized bootstrap method is used to calibrate the test. Our test is more powerful and less conservative than the Bonferroni correction and other competing methods. This proposed method is evaluated in simulation studies and applied to two real data sets.

O desenvolvimento de métodos para o tratamento de omissões nos dados é recente na estatística e tem sido alvo de muitas pesquisas. A presença de omissões em covariáveis é um problema comum na análise estatística e, em particular nos modelos de análise de sobrevivência, ocorrendo com freqüência em pesquisas clínicas, epidemiológicas e ambientais. Este trabalho apresenta propostas bayesianas para a análise de dados de sobrevivência com omissões nas covariáveis considerando modelos paramétricos da família Weibull e o modelo semi-paramétrico de Cox. Os métodos estudados foram avaliados tanto sob o enfoque paramétrico quanto o semiparamétrico considerando um conjunto de dados de portadores de insuficiência cardíaca. Além disso, é desenvolvido um estudo para avaliar o impacto de diferentes proporções de omissão. / The development of methods dealing with missing data is recent in Statistics and is the target of many researchers. The presence of missing values in the covariates is very common in statistical analysis and, in particular, in clinical, epidemiological and enviromental studies for survival data. This work considers a bayesian approach to analise data with missing covariates for parametric models in the Weibull family and for the Cox semiparametric model. The studied methods are evaluated for the parametric and semiparametric approaches considering a dataset of patients with heart insufficiency. Also, the impact of different omission proportions is assessed.

Introdução: A leucemia é o tipo mais comum de câncer em crianças de 0 a 14 anos. Estudos apontam que, em diversos países do mundo, as taxas de incidência estão aumentando, ou se mantêm estáveis, e que, por outro lado, as taxas de mortalidade estão caindo. Em países desenvolvidos, a leucemia é considerada uma doença curável, possuindo taxas de sobrevida superiores a 80%. Objetivos: Descrever a epidemiologia da leucemia na infância no município de São Paulo, no período de 1997 a 2013, analisando as tendências de incidência e mortalidade, e as taxas de sobrevida, segundo sexo, faixa etária, tipo de leucemia e região administrativa. Métodos: As taxas brutas e ajustadas de incidência e mortalidade foram calculadas segundo sexo e idade. Foram estimados modelos de regressão polinomial e calculados os percentuais anuais de mudança (Annual Percentual Change, APC) das taxas de incidência e mortalidade. Foi calculado o estimador não paramétrico produto limite de Kaplan-Meier e utilizado o teste de logrank para comparação das curvas de sobrevida. Foi construído o modelo de riscos proporcionais de Cox para estimar as hazard ratios de cada variável de estudo. Resultados: Foram contabilizados 2028 casos novos e 660 óbitos por leucemias, em crianças de 0 a 14 anos, no município de São Paulo, no período estudado. A taxa de incidência foi de 49,8 casos por 1 milhão de crianças e a taxa de mortalidade foi de 15,7 óbitos por 1 milhão de crianças, sendo mais frequente o subtipo leucemia linfoide aguda, entre o sexo masculino, na faixa etária de 0 a 4 anos. No período de 1997 a 2013, a taxa de incidência por leucemia em crianças no município de São Paulo foi decrescente (APC= -2,7%). Já a taxa de mortalidade, no geral, se manteve estável, mas foi decrescente para algumas características específicas, tais como, para sexo masculino (APC= -1,9%) e para o subtipo das leucemias mieloides agudas (APC= -1,8%). As taxas de sobrevida foram de 86%, 73% e 68%, respectivamente, após 12, 36 e 60 meses, bem abaixo do que se observa nos países desenvolvidos. Conclusão: Os percentuais e taxas de mortalidade e incidência da leucemia em crianças no município de São Paulo se assemelham aos valores encontrados na América Latina. O comportamento da tendência das taxas de incidência se difere ao encontrado na maioria dos países e o comportamento da tendência das taxas de mortalidade acompanha o padrão mundial. A leucemia em crianças é considerada uma doença curável, porém as taxas de sobrevida encontradas estão bem abaixo do esperado. Esta análise com dados do registro de câncer de base populacional mostra o panorama da leucemia em crianças no município de São Paulo. Estes resultados poderão ser utilizados desde a gestão dos serviços de saúde, a dar suporte a pesquisas futuras, sobre etiologia da doença. / Introduction: Leukemia is the most common type of cancer in children 0-14 years old. Studies show that, in several countries around the world, incidence rates are increasing, or remain stable, and that, on the other hand, mortality rates are decreasing. In developed countries, leukemia is considered a curable disease, with survival rates above 80%. Objectives: To describe the epidemiology of childhood leukemia in the city of São Paulo from 1997 to 2013, analyzing trends in incidence and mortality, and survival rates, according to sex, age group, type of leukemia and administrative region. Methods: Crude and adjusted rates of incidence and mortality were calculated according to sex and age. Polynomial regression models were estimated and the Annual Percentual Change (APC) of the incidence and mortality rates were calculated. It was estimated the non-parametric Kaplan-Meier limit product estimator and the logrank test was used to compare the survival curves. The Cox proportional hazards model was constructed to estimate the hazard ratios of each study variable. Results: A total of 2028 new cases and 660 deaths by leukemias were recorded in children aged 0 to 14 years, in the city of São Paulo, during the period studied. The incidence rate was 49.8 cases per 1 million children and the mortality rate was 15.7 deaths per 1 million children, which most frequent being the acute lymphoid leukemia subtype among males in the age group of 0 to 4 years old, living in the Southeast region of the city of São Paulo. In the period from 1997 to 2013, the incidence rate by leukemia in children in the city of São Paulo decreased (APC = -2.7%). The overall mortality rate remained stable, and decreased to some specific characteristics, such as for males (APC = -1.9%) and for the acute myeloid leukemia subtype (APC = -1.8% ). Survival rates were 86%, 73% and 68%, respectively, after 12, 36 and 60 months, below of those observed in developed countries. Conclusion: The percentages and mortality and incidence rates by leukemia in children in the city of São Paulo are similar to those found in Latin America. The trends of incidence rates differs from that found in most countries and the trends of mortality rates follows the world standard. Leukemia in children is considered a curable disease, but the survival rates found are below of the developed countries. This analysis with data from the population-based cancer registry shows the picture of leukemia in children in the city of São Paulo. These results can be used since the management of the health services, to support future research on the etiology of the disease.

The primary objective of this thesis is to analyse the public private partnership (PPP) framework for infrastructure development in developing countries across the six regions of the world. The thesis utilises the World Bank's private participation in infrastructure (PPI) dataset for the period 1980–2014, and examines three thematic areas. The first comprises of an exploratory analysis of the PPI dataset. The second research area focuses on the relationship between countries' attractiveness for PPPs and the characteristics of the countries, including: macroeconomic and market; fiscal constraints; regulatory and governance; and experience in PPPs, by utilising the Zero-Inflated Negative Binomial and Cragg's Double Hurdle models in an attempt to model private investors' decision to engage in PPPs as separate participation and consumption decisions. The third research area employs the methodology of survival analysis to investigate the risk of failure of PPP projects based on the allocation of residual facility ownership between the partners. The thesis's primary contributions include the utilisation of a wider and more informative range of econometric methodologies which have not been previously applied to the PPI dataset, and for the first time also, provides a framework to select an appropriate structure for PPPs that will enhance project survival. A key finding of the thesis is that private investors prioritise macroeconomic and market variables, such as price stability over regulatory and governance variables, such as corruption, in their determination as to which country to engage in PPPs. Contrary to previous research, corruption was found to be of no consequence to private investors who wish to engage in PPPs even for developing countries. Another key finding is that PPP projects which confer residual ownership on the public sector have lower risk of failure than those for which such ownership is conferred on the private sector. Evidence also suggests that the size of the project and the participation of multilateral institutions in PPPs also affect the risk of project failure.