Laser thermal ablation (LTA) is an in situ ablative technique that induces heat destruction of liver tumours. Despite increasing clinical use of LTA, reports of long-term outcomes and limitation of treatment in specific cohorts of patients with liver tumours are lacking. In addition, the mechanisms of action of therapy have not been fully elucidated. This study highlights the long-term clinical results and limitations of LTA in the treatment of a cohort of patients with unresectable colorectal liver metastases and examines the mechanisms of action of thermal ablative injury in a murine model.

Resumo: A variabilidade genética é um dos fatores mais importantes para o melhoramento de plantas, a partir do qual será conduzido todo o processo seletivo. Essa variabilidade pode ser ampliada através da utilização de cruzamentos múltiplos e melhor explorada sob diferentes métodos de condução das populações segregantes. O objetivo do presente trabalho foi detectar variabilidade através de estimativas de parâmetros genéticos em genótipos derivados do avanço de gerações por três diferentes métodos de condução: Single Seed Descent (SSD), Single Pod Descent (SPD) e Genealógico (Pedigree). O experimento foi conduzido em casa de vegetação climatizada e na área experimental do Departamento de Produção Vegetal da Faculdade de Ciências Agrárias e Veterinárias, Unesp-Jaboticabal. O delineamento utilizado foi o de blocos aumentados, onde foram avaliados 324 genótipos de soja na geração F7 previamente desenvolvidos no Programa de Melhoramento de Soja da FCAV/UNESP, oriundos de cruzamentos biparentais, quádruplos e óctuplos. Foram obtidas estimativas de variâncias, herdabilidades e ganhos genéticos para os três tipos de cruzamentos nos três métodos. Pela análise de divergência foram agrupados os genótipos mais similares para cada método. Os métodos SSD e SPD foram os mais promissores para aumentos de variabilidade nos três tipos de cruzamentos. O método genealógico promoveu as maiores estimativas de herdabilidade e os maiores ganhos genéticos. Os genótipos de cruzamentos quádruplos foram os que mais se agruparam / Abstract: Genetic variability is one of the most important factors for plant breeding, which lead the selective process. This variability can be enlarged by multiple crosses and explored under different breeding methods on segregate populations. Thus, the aim of this work was to detect variability using genetic parameters estimates in genotypes obtained by different methods: Single Seed Descent (SSD), Single Pod Descent (SPD) e Pedigree. The experiment was conducted in a greenhouse, under controlled conditions, and in the experimental field of Crop Production Department at Faculdade de Ciências Agrárias e Veterinárias, Unesp-Jaboticabal. Augmented blocks was used as the experimental design. 324 soybean genotypes in generation F7 from FCAV Soybean Breeding Program, derived from 2-way, 4-way and 8-way crosses, were evaluated. Variance, heritability and genetic gains estimates were obtained for the three types of crosses on three methods. By divergence analysis, most similar genotypes were grouped for each method. SSD and SPD methods were the most promising for variability increases. Pedigree method has promoted the higher estimates for heritability and genetic gains. Genotypes from four-way crosses were highly grouped / Orientadora: Maria Aparecida Pessôa da Cruz Centurion / Coorientador: Marcelo Marchi Costa / Banca: João Carlos de Oliveira / Banca: Ivana Marino Bárbaro / Mestre

Orientador: Júlio Defaveri / Resumo: A paracoccidioidomicose (Pbmicose) é micose sistêmica causada pelo fungo dimórfico Paracoccidioides brasiliensis, que acomete principalmente trabalhadores rurais do sexo masculino. A doença tem como principais manifestações clínicas a forma aguda/subaguda e a forma crônica. Métodos sorológicos têm considerável valor na Pbmicose e diferentes testes têm sido utilizados no diagnóstico e monitoramento da resposta do paciente ao tratamento. O objetivo deste estudo foi avaliar a IFI, a ID e o ELISA antes e após introdução do tratamento de pacientes com a forma aguda/subaguda e a forma crônica da Pbmicose. Para cada teste, os seguintes parâmetros foram avaliados: sensibilidade (SE), especificidade (EP), valor preditivo positivo (VPP), valor preditivo negativo (VPN) e eficiência (EF). No período pré-tratamento a IFI teve SE=92,3%, VPP= 87,5%, VPN= 92% e EF=88,6%. A ID teve SE=94,93%, VPP=97,4%, VPN=95% e EF=96,2%. Para o ELISA, SE=100%, VPP=95%, VPN=100% e EF=97,4%. No grupo de doadores de sangue, a EP da IFI, da ID e do ELISA foram, respectivamente, de 93,3%, 100% e 100%. Em soros de pacientes com outras micoses sistêmicas (histoplasmose, criptococose, actinomicose, aspergilose e adiaspiromicose), as EP para os testes foram de 60%, 90% e 80%, respectivamente. Durante o tratamento, maior correlação foi obtida entre a ID e o ELISA (r= 0,61591, p<0,05), obtendo-se baixas correlações com a IFI. O tempo necessário para negativar o ELISA (Md= 20,0 meses) foi maior do que a ID (Md= 13,5 meses). O ELISA se negativou em geral nove meses após a ID, o que sugere que este teste passe a ser um referencial para suspensão do tratamento de manutenção. Devido à sua elevada sensibilidade, especificidade, VPP, VPN e eficiência, o ELISA deve ser incluído na rotina sorológica de pacientes com Pbmicose. / Abstract: Pararaccidioidomycosis (Pbmycosis) is a systemic mycosis caused by the dimorphic fungus Paracoccidioiodes brasiliensis, which often affects rural workers, usually male adults. The overt disease is manifested by two clinical forms, acute/subacute and chronic forms. Serological methods are of considerable value in Pbmycosis, and various tests has been utilized in the diagnostic and monitoring the patient's response to treatment. The aim of this study was to evaluated the reliability of the double immunodiffusion test (ID), indirect immunofluorescence (IIF) and immunoenzymatic assay (ELISA) in the pre-treatment and during the period of treatment of patients with acute/subacute and chronic forms of Pbmycosis. For each test the following parameters were evaluated: Sensitivity (SE), Specificity (SP), Positive and Negative Predictive Values (PPV and NPV) and Efficiency (EF). In the pre-treatment period these values for IFI were SE=92.3%, PPV=87.5%, NPV=92% and EF=88.6%. For ID: SE=94.9%, PPV=97.4%, NPV=95% EF=96.2%. For ELISA: SE=100%, PPV=95%, NPV=100% and EF=97.4%. In the group of blood donors, for IFI, ID and ELISA the ES were, respectively, 93.3%, 100% and 100%. In patients with other deep mycosis (histoplasmosis, cryptococcosis, actinomycosis, aspergillosis and adiaspiromycosis) the ES for these tests were respectively 60%, 90% and 80%. During the period of treatment, the highest correlation was observed between ID and ELISA (r= 0,61591, p<0,05), and the lowest correlations with IFI. The time elapsed to negative the ELISA was larger (Md=20 months) than for ID (Md= 13,5 meses). In overall, the ELISA negativated nine months after ID. This result suggests that the ELISA may be a referential test to monitoring the time for interruption of the treatment in Pbmycosis. Moreover, owing to its high values of SE, SP, PPV, NPV and EF, ELISA should be included in the serological routine for patients with Pbmycosis. / Mestre

Esta tese é composta por cinco estudos que tiveram como objetivo geral investigar a exposição à violência direta (ser a vítima) e indireta (ser testemunha) e suas relações com bem-estar subjetivo e sintomas de depressão, ansiedade e estresse em adolescentes de escolas públicas da cidade de Porto Alegre - RS. O primeiro capítulo apresenta uma revisão sistemática de literatura sobre exposição à violência na adolescência e suas relações com saúde mental. O segundo capítulo é um estudo de adaptação e validação da Escala de Depressão, Ansiedade e Estresse para Adolescentes (EDAE-A). O terceiro capítulo, estudo empírico, teve como objetivo investigar a prevalência de exposição de adolescentes à violência direta e indireta e sua associação com idade, sexo, reprovação escolar e configuração familiar. Já o quarto estudo, também empírico, investigou as relações entre exposição à violência direta e indireta, bem-estar subjetivo e sintomas de depressão, ansiedade e estresse. Por fim, o quinto capítulo apresenta o relato da experiência de devolução dos dados da pesquisa que teve como objetivo discutir violências(s) cotidianas. Participaram 426 adolescentes de escolas públicas, de 12 a 18 anos, que responderam a uma ficha de dados sociodemográficos e aos instrumentos Triagem de Exposição à Violência de Crianças na Comunidade, Escala de Depressão, Ansiedade e Estresse para Adolescentes (EDAE-A), Escala de Afetos Positivos (AP) e Afetos Negativos (AN) e a Escala Multidimensional de Satisfação de Vida para Adolescentes (EMSVA). Análises descritivas e inferenciais foram realizadas. Os resultados desta tese indicaram a alta prevalência de exposição direta e indireta dos adolescentes à violência e a associação com sintomas internalizantes. A adaptação e validação do instrumento EDAE-A possibilitaram a avaliação conjunta das variáveis depressão, ansiedade e estresse, demonstrando boas propriedades psicométricas. A construção do Índice de Bem-Estar Subjetivo, englobando a satisfação de vida e afetos positivos e negativos, deve ser mais bem explorada em pesquisas futuras. Finalmente, a intervenção focal realizada com os adolescentes demonstrou o quanto a violência é naturalizada no contexto escolar, indicando a necessidade de trabalhos preventivos e interventivos para essa população. Limitações e sugestões para novos estudos são descritas. / This thesis is comprised of five studies that had as main objective to investigate the exposure to direct violence (being victim) and indirect (being witness) and their relationship with subjective well-being and symptoms of depression, anxiety and stress in adolescents from public schools of the city of Porto Alegre - RS. The first chapter presents a systematic review of literature on exposure to violence in adolescence and its relationship with mental health. The second chapter is a study of adaptation and validation of the Depression, Anxiety and Stress Scale for Adolescents (DASS-A). The third chapter (a empirical study) aimed to investigate the prevalence of adolescent exposure to direct and indirect violence and its association with age, sex, school failure and family configuration. The fourth study (which is also empirical) investigated the relationship between exposure to direct and indirect violence, subjective well-being and symptoms of depression, anxiety and stress. Finally, the fifth chapter presents a report about the experience of informing the participants about the results of the research with the aim of discussing violence(s) in the daily life. The participants were 426 adolescents from public schools, 12-18 years old, who responded the sociodemographic form and the following instruments Screening of Exposure to Violence of Children in the Community; Depression, Anxiety and Stress Scale for Adolescents (DASS-A); Positive Affects (PA) and Negative Affects (NA) and the Multidimensional Life Satisfaction Scale for Adolescents (MLSSA). Descriptive and inferential analyses were performed. The results of this thesis indicated a high prevalence of direct and indirect exposure of adolescents to violence and the association with internalizing symptoms. The adaptation and validation of instrument DASS-A allowed the joint assessment of the variables depression, anxiety and stress, demonstrating good psychometric properties. The construction of the Subjective Well-being Index, encompassing life satisfaction besides positive and negative affects, should be further explored in future research. Finally, the focal intervention realized with the adolescents demonstrated how much the violence is naturalized in the school context, indicating the necessity of preventive and interventional actions for this population. Limitations and suggestions for further research are described.

Na otimização de produtos e processos industriais todas as medidas de qualidade devem ser consideradas simultaneamente. No setor alimentício para a avaliação de produtos são considerados, além de medidas usuais de qualidade, dados de painéis sensoriais. Esta dissertação apresenta o estudo de um método desenvolvido especificamente em um contexto de otimização de produtos com variáveis sensoriais: o método de Comparação Indireta aos Pares (CIP). Para coleta de dados, o CIP baseia-se na comparação pareada de amostras e para análise de dados utiliza elementos do AHP (Processo Analítico Hierárquico, na sigla em inglês). Neste método, são propostas extensões com vistas a torná-lo mais confiável e aumentar sua aplicabilidade. Para atingir esse propósito são feitas adaptações em diferentes procedimentos de coleta de dados sensoriais, assim como a validação de valores de referência utilizados na análise de dados e a construção de tabelas com valores de referência para casos onde o método CIP é aplicado. As melhorias propostas no método de CIP são ilustradas através de uma aplicação prática em uma empresa alimentícia, onde, deseja-se otimizar o processo de desenvolvimento de uma barra de chocolate. O método CIP é utilizado para determinar o percentual de ingredientes utilizados na formulação da barra de chocolate. / In the optimization of products and industrial processes several quality measures must be considered simultaneously. When analyzing food products, in addition to the usual measures of quality, the performance of products as measured by a sensory panel should be also taken into account. In this thesis we analyze a method developed specifically for the optimization of products with sensory variables: the Indirect Pairwise Comparison (IPC) method. Regarding the sensory data collection the IPC is based in the pairwise comparison of samples; as for data analysis, the method uses elements of the AHP (Analytical Hierarchical Process). Extensions are proposed in the IPC in order to improve its reliability and applicability. For that matter we propose adaptations in different procedures for sensory data collection. We also validate some reference values used in the IPC’s data analysis framework and develop tables with reference values for special cases where the IPC method is applied. The proposed improvements are illustrated through a practical application in a food industry. In the case study it is desired to optimize the development of a chocolate bar. The IPC is used to determine the percentage of ingredients used in the product recipe.

This thesis examines the indirect impact of natural hazards on infrastructure networks. It addresses several key themes and issues for hazard assessment, network modelling and risk assessment using the case study of landslides impacting the national road network in Scotland, United Kingdom. The research follows four distinct stages. First, a landslide susceptibility model is developed using a database of landslide occurrences, spatial data sets and logistic regression. The model outputs indicate the terrain characteristics that are associated with increased landslide potential, including critical slope angles and south westerly aspects associated with increased rates of solar irradiance and precipitation. The results identify the hillslopes and road segments that are most prone to disruption by landslides and these indicate that 40 % (1,700 / 4,300 km) of Scotland s motorways and arterial roads (i.e. strategic road network) are susceptible to landslides and this is above previous assessments. Second, a novel user-equilibrium traffic model is developed using UK Census origin-destination tables. The traffic model calculates the additional travel time and cost (i.e. indirect impacts) caused by network disruptions due to landslide events. The model is applied to calculate the impact of historic scenarios and for sets of plausible landslide events generated using the landslide susceptibility model. Impact assessments for historic scenarios are 29 to 83 % greater than previous, including £1.2 million of indirect impacts over 15 days of disruption at the A83 Rest and Be Thankful landslide October 2007. The model results indicate that the average impact of landslides is £64 k per day of disruption, and up to £130 k per day on the most critical road segments in Scotland. In addition to identifying critical road segments with both high impact and high susceptibility to landslides, the study indicates that the impact of landslides is concentrated away from urban centres to the central and north-west regions of Scotland that are heavily reliant on road and haulage-based industries such as seasonal tourism, agriculture and craft distilling. The third research element is the development of landslide initiation thresholds using weather radar data. The thresholds classify the rainfall conditions that are most commonly associated with landslide occurrence in Scotland, improving knowledge of the physical initiation processes and their likelihood. The thresholds are developed using a novel optimal-point threshold selection technique, high resolution radar and new rain variables that provide spatio-temporally normalised thresholds. The thresholds highlight the role of the 12-day antecedent hydrological condition of soils as a precursory factor in controlling the rain conditions that trigger landslides. The new results also support the observation that landslides occur more frequently in the UK during the early autumn and winter seasons when sequences or clustering of multiple cyclonic-storm systems is common in periods lasting 5 to 15 days. Fourth, the three previous elements are combined to evaluate the landslide hazard of the strategic road segments and a prototype risk assessment model is produced - a catastrophe model. The catastrophe model calculates the annual average loss and aggregated exceedance probability of losses due to the indirect impact of landslides in Scotland. Beyond application to cost-benefit analyses for landslide mitigation efforts, the catastrophe model framework is applicable to the study of other natural hazards (e.g. flooding), combinations of hazards, and other infrastructure networks.

Na otimização de produtos e processos industriais todas as medidas de qualidade devem ser consideradas simultaneamente. No setor alimentício para a avaliação de produtos são considerados, além de medidas usuais de qualidade, dados de painéis sensoriais. Esta dissertação apresenta o estudo de um método desenvolvido especificamente em um contexto de otimização de produtos com variáveis sensoriais: o método de Comparação Indireta aos Pares (CIP). Para coleta de dados, o CIP baseia-se na comparação pareada de amostras e para análise de dados utiliza elementos do AHP (Processo Analítico Hierárquico, na sigla em inglês). Neste método, são propostas extensões com vistas a torná-lo mais confiável e aumentar sua aplicabilidade. Para atingir esse propósito são feitas adaptações em diferentes procedimentos de coleta de dados sensoriais, assim como a validação de valores de referência utilizados na análise de dados e a construção de tabelas com valores de referência para casos onde o método CIP é aplicado. As melhorias propostas no método de CIP são ilustradas através de uma aplicação prática em uma empresa alimentícia, onde, deseja-se otimizar o processo de desenvolvimento de uma barra de chocolate. O método CIP é utilizado para determinar o percentual de ingredientes utilizados na formulação da barra de chocolate. / In the optimization of products and industrial processes several quality measures must be considered simultaneously. When analyzing food products, in addition to the usual measures of quality, the performance of products as measured by a sensory panel should be also taken into account. In this thesis we analyze a method developed specifically for the optimization of products with sensory variables: the Indirect Pairwise Comparison (IPC) method. Regarding the sensory data collection the IPC is based in the pairwise comparison of samples; as for data analysis, the method uses elements of the AHP (Analytical Hierarchical Process). Extensions are proposed in the IPC in order to improve its reliability and applicability. For that matter we propose adaptations in different procedures for sensory data collection. We also validate some reference values used in the IPC’s data analysis framework and develop tables with reference values for special cases where the IPC method is applied. The proposed improvements are illustrated through a practical application in a food industry. In the case study it is desired to optimize the development of a chocolate bar. The IPC is used to determine the percentage of ingredients used in the product recipe.

The aim of this thesis is to create a calculation system of indirect costs in the commercial company. This calculation could be used in the accounting system of the company and thanks to that would be indirect cost divided automatically into individual items of goods. The calculation system is based on particular coefficients which are assigned in individual types of costs. New created system is tested on the specific sample of goods from the company. It is good to see weaknesses and deficiencies in suggested calculation. Conclusions from this analyse are specific values of profitability ratio Return on sales in every goods. The management of the company has to decide whether to revalue their goods or not. The decision is connected also with margin groups, in group A (which includes main goods) they could afford to move with selling prices. This prediction is based on outcome from competition analysis.

This diploma thesis deals with the economic and legal aspects of excise taxes in the EU. Excise taxes are among indirect taxes and can be divided into three basic groups: alcoholic beverages, tobacco products, and energy products and electricity. For individual commo-dities, EU Member States are harmonizing their legislation and minimum rates in order to prevent cross-border distortions of competition between EU countries. Part of the diploma thesis will be the analysis of the current situation in the field of excise taxes in the EU, the comparison of the individual commodities subject to these taxes.

The objective of the thesis is to investigate the development of excise taxes indicators in twenty-seven member states of the European Union (without Croatia due to the absence of data). The selected period for the analysis is the year 2004 - 2016. The main aim of the thesis is to define the groups of member states EU according to their importance and similarity with respect to the excise duties. With this aim is related the another important idea of the work. That is whether the indicators of excise duties are brought closer to the harmonization processes and if are the member states converging. The cluster analysis was used to achieve the main goal of the work. The data which is used in this analysis is obtained from Eurostat and European Commission databases. The results of cluster analyzes allow the member states to be divided into four of the most stable groups. The group of Nordic countries in Europe, group of border states, states of NMS-12 able to approach the EU-15 and other states of NMS-12. The cluster analyzes also shows that the original and new member states, that joined the EU in 2004 and later, are still different in the field of excise duties. Differences that exist despite the strict harmonization of individual tax systems, in particular the harmonization of excise rates, may be caused, in particular, to the historical roots of individual countries, but also by the economic and political situation.