The "global" financial crisis (GFC) emerged during 2008 and it was mainly triggered by the sub-prime mortgage crisis (SMC) in the United States of America. The main aims of this thesis is to conduct an econometric analysis of the financial crisis and household savings in South Africa and also to provide a rationale that will facilitate a policy attention on Domestic Resource Mobilisation (DRM) through household savings. The study uses quarterly time series data for the period 199401 to 201102 obtained on-line from the South African Reserve Bank (SARB). The research is based on the Keynesian saving function, which is a complement of the consumption function. The model will be estimated by using a cointegrating vector autoregressive (CVAR) framework, which allows for endogeneity of the regressors. To check robustness on the cointegration results, the study employs the second empirical technique based on Generalized Impulse Response Function (GIRF) analysis and Variance Decomposition. The regression equation of household savings is expressed as a function of household disposable income, household debt to disposable income, real GOP, interest rate, inflation rate and foreign savings. The variables are tested for the presence of a unit root by the application of the Augmented Dickey-Fuller (AOF), Phillips-Perron (PP) Kwiatkowski, Phillips, Schmidt and Shin (KPSS) tests. The findings of the study are that all variables have unit roots. The cointegration model emphasises the presence of a long run equilibrium relationship between dependent and independent variables. The CVAR reveals the short run of the dynamic household savings model. Taking this into consideration, the study concludes that household debt has a huge influence on the level of household savings. The econometric analysis also revealed that household savings in South Africa actually improved during the period associated with the GFC. It could be postulated that South African households responded to their deteriorating financial situations by reducing their average spending and increasing their savings. Variance decomposition analysis revealed that 'own shocks' constitute the predominant source of variations in household saving therefore household savings can be explained by the disturbances in macroeconomic variables in the study. The study recommends the promotion of household savings and economic growth in order to reduce the dependence of South Africa on foreign savings. DRM is therefore enhanced by a higher level of household savings, which can facilitate higher levels of investment and economic growth. / Thesis (PhD (Economics) North-West University, Mafikeng Campus, 2012

O estudo de métodos estatísticos na avaliação de métodos diagnósticos tem aumentado consideravelmente nas últimas décadas. Desde o início, quando Yerushalmy (1947) publicou seu traba lho sobre confiabilidade do roentgeno grama na identificação da tuberculose, novas metodologias surgiram para que fosse possível a obtenção de valores de sensibilidade e especificidade de testes diagnósticos. A sensibilidade é definida como a probabilidade de o teste sob investigação fornecer um resultado positivo, dado que o indivíduo é realmen te portador da enfermidade. A especifi cidade, por sua vez, é definida como a probabilidade de o teste fornecer um resultado negativo, dado que o indivíduo está livre da enfermidade. Na prática, é comum ocorrerem situações em que uma proporção de indivíduos selecionados não pode ter o estado real da doença verificado, por se tratar de procedimentos invasivos, como no diagnóstico de câncer de pulmão, ou quaisquer outros casos em que são envolvidos riscos, portanto não praticá veis, nem éticos, ou ainda por serem de alto custo. Assim, em vez de se contornar o proble ma, muitos estudos de avaliação de performance de testes diagnósticos são elaborados apenas com informações de indivíduos verificados. Esse procedimento pode levar a resultados viesados. É o chamado viés de verificação, que consiste no cálculo de estimativas de sensibilidade e especi ficidade de testes diagnósticos quando apenas os indivíduos verificados pelo padrão ouro são inseridos na análise e os não verificados são descartados ou considerados livres de doença. Este trabalho apresenta uma revisão das metodologias já propostas para se calcularem a sensibilidade e a especificidade quando existe o viés de verificação, bem como uma análise detalhada da influência da proporção de indivíduos não verificados, o efeito do tamanho amostral e a escolha de distri buições a priori, quando utilizada a metodologia bayesiana, no cálculo dessas estimativas. Também foi introduzida uma metodologia, sob enfoque bayesiano, para a estimação das medidas de desempenho de dois testes diagnósticos, na presen ça do viés de verificação. / The study of statistical methods on diagnostic tests evaluation has increa sed in the last decades. Since the beginning, when Yerushalmy (1947) published his work about trustwor thiness of the roentgenogram in the identification of the tuberculosis, new methodologies had appeared and so that it was possible to get values of sensi tivity and specificity of diagnostic tests. Sensitivity is defined as the probability of the test under inquiry supply a positive result, since that the individual is really carrying on the disease. The specificity, in the other hand, is defined as the probability of the test supply a negative result, since that the individual is free of the disease. In practice, it is usual to occur situations where a proportion of selected individuals cannot have verified the real state of the illness, to the fact that the verification test can be an invasive procedure, as in the diagnosis of lung cancer, or any other cases where risks are involved, therefore not practicable, nor ethical, or still procedures with high cost. Thus, instead of solve the problem, many studies of evaluation of performance of diagnostic tests are elaborated only using the information of verified individuals. This procedure can leads to biased results. This is known as verification bias, that consists of the calculation of estimates of sensitivity and specificity of diagnostic tests when only the individuals verified by the gold standard test are inserted in the analysis and the unverified ones, discarded or considered that they are free of the disease. This work presents a revision of the methodologies already proposed to calculate sensitivity and the specificity in the presence of the verifi cation bias, as well as a detailed analysis of the influence of the propor tion of individuals not verified, the effect of the sample size and the influ ence of choosing different prior densi ties, when using the bayesian methodo logy, in the calculation of these estima tes. It was also introduced a bayesian methodology to estimate performance measures of two diagnostic tests when the verification bias is present.

A pluralização dos atendimentos e sua garantia de realização em todos os níveis de atenção conforme os princípios estabelecidos pelo Sistema Único de Saúde (SUS) fizeram com que o atual cenário da saúde pública ganhasse grande complexidade envolvendo o financiamento e suporte para a manutenção desses serviços. Nesse contexto, alguns trabalhos na literatura relatam um excesso no uso desses recursos diagnósticos, que ocorre muitas vezes desnecessariamente, aumentando a chance de riscos à saúde do paciente e sobrecarregando demasiadamente o orçamento financeiro dos serviços de saúde, em particular o hospital. O que ocorre muitas vezes é a falta de critério nas solicitações e problemas de interpretação dos exames, desconhecimento sobre custos dos procedimentos realizados, entre outros fatores que se mostram mais elevados dependendo da complexidade do ambiente do serviço de saúde, do quadro clínico do paciente e da experiência do profissional médico. Dessa forma, é escopo desse projeto avaliar os resultados qualitativos, quantitativos e os custos dos principais parâmetros laboratoriais de exames solicitados nas áreas clínicas de Cardiologia e Endocrinologia da divisão de Clínica Médica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), e sua correlação com o que está descrito na literatura, objetivando identificar se o uso dos recursos diagnósticos estão sendo utilizados de forma racional e coerente. Para a realização desse estudo, foi realizada uma análise retrospectiva dos prontuários de pacientes pelo sistema HC-Athos em regime de primeira consulta e retorno, e também, de informações e metodologias relacionadas ao custeio de exames laboratoriais junto ao Centro de Custo do HCFMRP-USP, nas áreas clínicas de Endocrinologia, ambulatórios (ENA, END, ETP) e Cardiologia (CAA), no período de Julho de 2012 à Julho de 2013. Observando a análise dos elementos dos exames em ambos amulatórios, os resultados foram próximos: em Cardiologia a taxa média de elementos alterados foi de 20,79%, ao passo que em endocrinologia, o valor médio foi de 22,39%. Dessa forma, com base no que está descrito por alguns autores na literatura, esses achados podem sugerir a possibilidade de haver requisição sem necessidade dos exames laboratoriais. Em relação ao estudo de custos, observamos que existe uma diferença significativa para a relação: valor real gasto (HCFMRP-USP)/valor recebido(SUS). Na cardiologia onde o déficit foi mais elevado, 39,45%, contra os 12,80% observados em endocrinologia. Analisando cada exame separadamente nos dois ambulatórios, observa-se que há situações onde a relação do custo entre real gasto/valor recebido chega a ser bem discrepante, como a variação de 51 à 60% em exames como hemograma, uréia, creatinina, T3 e T4 total. Analisando esses achados, podemos concluir que há de certa forma um subfinanciamento do SUS em relação aos procedimentos laboratoriais realizados pelos hospitais. Com exceção de alguns exames, que isoladamente mostraram relação positiva, o saldo final considerando os exames mais comumente realizados foi negativo, ou seja, nos exames de maior demanda e faturamento, o resultado mostrou se preocupante. / The increasing demand of medical care and its realization warranty on all levels of care according to the principles established by the Unified Health System (SUS) made the current situation of public health gain great complexity involving funding and support to maintain these services. In this context, some studies in the literature report an excess in the use of these diagnostic tools, which is often unnecessarily, increasing the chance of risks to the health of the patient and overly burdening the financial budget of health services, particularly the hospital. What often happens is the lack of criteria in requests and problems of interpretation of the tests, ignorance about costs of the procedures performed, and other factors which show higher depending on the complexity of the health care environment, the patient\'s condition and the doctor\'s professional experience. Thus, is scope of this project, evaluate the qualitative and quantitative results, and the costs of major laboratory parameters tests requested in the clinical areas of Cardiology and Endocrinology of the University Hospital, Faculty of Medicine of RibeirãoPreto, University of São Paulo (HCFMRP-USP), and its correlation with what is described in the literature in order to identify whether the use of diagnostic resources are being used in a rational and coherent manner. To carry out this study, a retrospective analysis of medical records of patients at HC-Athos system in first consultation and return was carried out, and also, information and methodologies related to the cost of laboratory tests by the HCFMRP- USP Cost Center in the clinical areas of Endocrinology, outpatient clinics (ENA, END, ETP) and Cardiology (CAA) in the period July 2012 to July 2013. Noting the analysis of elements in both outpatient examinations, the results were similar: in Cardiology the average rate of change elements was 20.79%, while in endocrinology, the average value was 22.39%. Thus, based on what is described by some authors in the literature, these findings may suggest the possibility of request without laboratory tests. Regarding the study costs, we note that there is a significant difference to the relationship: real amount spent (HCFMRP- USP) / cash received (SUS). In cardiology where the deficit was higher, 39.45%, against 12.80% observed in endocrinology. Analyzing each exam separately in the two clinics, it is observed that there are situations where the ratio of the cost of real expenditure / amount received comes to be well outlier, as the range of 51 to 60% in exams such as blood count, urea, creatinine, T3 and T4 total. Analyzing these findings, we conclude that there is something of a SUS underfunded in relation to laboratory procedures performed by hospitals. Except for some tests, which alone showed a positive relationship, the final balance considering the most commonly performed tests was negative, that means, in higher demand and revenue tests, the results showed worrying.

O estudo de métodos estatísticos na avaliação de métodos diagnósticos tem aumentado consideravelmente nas últimas décadas. Desde o início, quando Yerushalmy (1947) publicou seu traba lho sobre confiabilidade do roentgeno grama na identificação da tuberculose, novas metodologias surgiram para que fosse possível a obtenção de valores de sensibilidade e especificidade de testes diagnósticos. A sensibilidade é definida como a probabilidade de o teste sob investigação fornecer um resultado positivo, dado que o indivíduo é realmen te portador da enfermidade. A especifi cidade, por sua vez, é definida como a probabilidade de o teste fornecer um resultado negativo, dado que o indivíduo está livre da enfermidade. Na prática, é comum ocorrerem situações em que uma proporção de indivíduos selecionados não pode ter o estado real da doença verificado, por se tratar de procedimentos invasivos, como no diagnóstico de câncer de pulmão, ou quaisquer outros casos em que são envolvidos riscos, portanto não praticá veis, nem éticos, ou ainda por serem de alto custo. Assim, em vez de se contornar o proble ma, muitos estudos de avaliação de performance de testes diagnósticos são elaborados apenas com informações de indivíduos verificados. Esse procedimento pode levar a resultados viesados. É o chamado viés de verificação, que consiste no cálculo de estimativas de sensibilidade e especi ficidade de testes diagnósticos quando apenas os indivíduos verificados pelo padrão ouro são inseridos na análise e os não verificados são descartados ou considerados livres de doença. Este trabalho apresenta uma revisão das metodologias já propostas para se calcularem a sensibilidade e a especificidade quando existe o viés de verificação, bem como uma análise detalhada da influência da proporção de indivíduos não verificados, o efeito do tamanho amostral e a escolha de distri buições a priori, quando utilizada a metodologia bayesiana, no cálculo dessas estimativas. Também foi introduzida uma metodologia, sob enfoque bayesiano, para a estimação das medidas de desempenho de dois testes diagnósticos, na presen ça do viés de verificação. / The study of statistical methods on diagnostic tests evaluation has increa sed in the last decades. Since the beginning, when Yerushalmy (1947) published his work about trustwor thiness of the roentgenogram in the identification of the tuberculosis, new methodologies had appeared and so that it was possible to get values of sensi tivity and specificity of diagnostic tests. Sensitivity is defined as the probability of the test under inquiry supply a positive result, since that the individual is really carrying on the disease. The specificity, in the other hand, is defined as the probability of the test supply a negative result, since that the individual is free of the disease. In practice, it is usual to occur situations where a proportion of selected individuals cannot have verified the real state of the illness, to the fact that the verification test can be an invasive procedure, as in the diagnosis of lung cancer, or any other cases where risks are involved, therefore not practicable, nor ethical, or still procedures with high cost. Thus, instead of solve the problem, many studies of evaluation of performance of diagnostic tests are elaborated only using the information of verified individuals. This procedure can leads to biased results. This is known as verification bias, that consists of the calculation of estimates of sensitivity and specificity of diagnostic tests when only the individuals verified by the gold standard test are inserted in the analysis and the unverified ones, discarded or considered that they are free of the disease. This work presents a revision of the methodologies already proposed to calculate sensitivity and the specificity in the presence of the verifi cation bias, as well as a detailed analysis of the influence of the propor tion of individuals not verified, the effect of the sample size and the influ ence of choosing different prior densi ties, when using the bayesian methodo logy, in the calculation of these estima tes. It was also introduced a bayesian methodology to estimate performance measures of two diagnostic tests when the verification bias is present.

Scrapie is a transmissible spongiform encephalopathy (TSE) of sheep and goats, for which there is currently no ante-mortem diagnostic test. A rapid, ante-mortem diagnostic test for scrapie would also potentially be important for other TSEs such as bovine spongiform encephalopathy (BSE) and variant Creutzfeldt Jakob's disease (vCJD). The hypothesis of this study was that there is differential gene expression in the blood and peripheral tissues of scrapie infected animals, and that a panel of differentially expressed genes could be identified and used as surrogate markers of infection. An expression screening approach, using real-time PCR and an EST microarray, was used to identify genes that were differentially expressed between SSBP/1 infected and mock-infected control sheep. The animals used in this study were New Zealand Cheviot sheep of three genotypes, the highly susceptible VRQ/VRQ (incubation time 193 ± 12 days), the intermediately susceptible VRQ/ARR (incubation time 325 ± 36 days) and the disease resistant ARR/ARR (no clinical signs of disease), experimentally infected with scrapie strain SSBP/1 and sacrificed at various time points post infection. No differentially expressed candidates were identified in blood. Other microarray experiments in our group had demonstrated evidence of differential expression in spleen fractions enriched for follicular dendritic cells (FDCs). These data were analysed and candidates were selected for quantitative real-time PCR validation, with a view to assessing the expression of validated candidates in blood as a more targeted approach to identifying markers of infection. The gene Early Growth Response 1 (EGR1) emerged as an interesting candidate as its expression was found to be significantly up-regulated in FDC-enriched spleen samples of VRQ/VRQ and ARR/ARR animals over a number of time points post infection. EGR1 expression was steady among all mock-infected controls. There was, however, no evidence of differential expression of EGR1 in blood. This is the first report of differential expression of EGR1 in preclinical spleen samples in sheep. EGR1 is an attractive candidate for a surrogate marker of preclinical infection, as its levels rise very early after infection and remain elevated for a sustained amount of time in the VRQ/VRQ sheep. Elevated expression is also detectable in VRQ/ARR and in ARR/ARR sheep. Further studies with larger sample numbers would be necessary to more accurately estimate the extent of differential expression and to assess its true worth as a diagnostic marker. Expression studies in samples from other TSEs and non-TSE neuropathological disease would also be necessary to establish whether differential expression of EGR1 is specific to TSE disease.

Present demagnetization methods for large power system transformers are time consuming and can be dangerous to persons performing demagnetization. The work of this thesis was to develop improved demagnetization methods and to construct an automated instrument that would implement the methods developed. One previously developed method was analyzed for effectiveness. Then, two new methods for demagnetization were developed and also analyzed for effectiveness. An automated test instrument prototype was redesigned to be able to accommodate these methods and to improve the safety of the user. The previously developed method attempts demagnetization based on current flow behavior characteristics. The first new method is a magnetic flux estimation based on saturation time. The second new method is also based on measuring saturation time, modified to account for the variable voltage loss due to wire resistance. The second of the two new methods developed proved to be the most effective for demagnetization and was able to demagnetize a transformer within an error margin of 2%. The instrument designed to perform the demagnetization with this new routine is now in early production stages for an expanded field trial with transformer maintenance teams.

The utilitarian theory contemplates rewarding the risks of inventors by providing them with a defined period of exclusivity to recoup their investment. For inventions requiring further investment, patents enable the creation of financial relationships between inventors and investors by providing patent exclusivity during the commercialization process. Innovation, contrasted from invention and conceptualized as commercialization, however, does not necessarily form the best means for delivering to the public inventions intended to improve health. Although patent policy conflates the economic growth and health improvement objectives of innovation, these goals do not always align. While the exercise of BRCA patents instantiates exclusive practicing of patents that failed to adequately deliver health technology, the patent system does not need significant change. Rather, to maintain the expectations of patent holders while balancing the needs of the public, current practices should continue with the encouragement of the creation of voluntary patent pools.

The utilitarian theory contemplates rewarding the risks of inventors by providing them with a defined period of exclusivity to recoup their investment. For inventions requiring further investment, patents enable the creation of financial relationships between inventors and investors by providing patent exclusivity during the commercialization process. Innovation, contrasted from invention and conceptualized as commercialization, however, does not necessarily form the best means for delivering to the public inventions intended to improve health. Although patent policy conflates the economic growth and health improvement objectives of innovation, these goals do not always align. While the exercise of BRCA patents instantiates exclusive practicing of patents that failed to adequately deliver health technology, the patent system does not need significant change. Rather, to maintain the expectations of patent holders while balancing the needs of the public, current practices should continue with the encouragement of the creation of voluntary patent pools.

The receiver operating characteristic (ROC) curve methodology is the statistical methodology for assessment of the accuracy of diagnostics tests or bio-markers. Currently most widely used statistical methods for the inferences of ROC curves are complete-data based parametric, semi-parametric or nonparametric methods. However, these methods cannot be used in diagnostic applications with missing data. In practical situations, missing diagnostic data occur more commonly due to various reasons such as medical tests being too expensive, too time consuming or too invasive. This dissertation aims to develop new nonparametric statistical methods for evaluating the accuracy of diagnostic tests or biomarkers in the presence of missing data. Specifically, novel nonparametric statistical methods will be developed with different types of missing data for (i) the inference of the area under the ROC curve (AUC, which is a summary index for the diagnostic accuracy of the test) and (ii) the joint inference of the sensitivity and the specificity of a continuous-scale diagnostic test. In this dissertation, we will provide a general framework that combines the empirical likelihood and general estimation equations with nuisance parameters for the joint inferences of sensitivity and specificity with missing diagnostic data. The proposed methods will have sound theoretical properties. The theoretical development is challenging because the proposed profile log-empirical likelihood ratio statistics are not the standard sum of independent random variables. The new methods have the power of likelihood based approaches and jackknife method in ROC studies. Therefore, they are expected to be more robust, more accurate and less computationally intensive than existing methods in the evaluation of competing diagnostic tests.

Orientador: José Carlos de Figueiredo Pantoja / Resumo: O objetivo deste estudo foi avaliar novas estratégias de identificação e tratamento de mastite subclínica causada por Streptococcus agalactiae. Dois estudos foram conduzidos para alcançar os objetivos propostos: 1) um ensaio clínico randomizado, para avaliar a eficácia do tratamento de S. agalactiae com cloxacilina intramamária (CLOXIMM), cefquinoma intramamária (CEFIMM) e cefquinoma intramuscular (CEFIM); e avaliar a não-inferioridade da CLOXIMM em relação a CEFIMM. E, 2) um estudo de acurácia diagnóstica, para estimar a acurácia do Somaticell, California Mastitis Test (CMT) e do exame microbiológico do leite composto (leite dos quatro quartos) na detecção de quartos e animais infectados com S. agalactiae. Os resultados indicaram que quartos tratados com CEFIM apresentaram menor taxa de cura bacteriológica (55%) do que aqueles tratados com CLOXIMM (86%) ou CEFIMM (98%). A diferença na proporção de cura bacteriológica entre CEFIMM e CLOXIMM foi de 0,121 (intervalo de confiança de 95%: 0,056 - 0,184). A CLOXIMM foi considerada não inferior a CEFIMM quando margens de não inferioridade de 0,20 e 0,25 foram utilizadas. Contudo, a determinação da não inferioridade foi inconclusiva para margens de 0,10 e 0,15. A cultura do leite composto apresentou acurácia diagnóstica satisfatória (95,7%) quando comparada a cultura individual por quarto. Para identificação dos quartos infectados com S. agalactiae, o ponto de corte considerado mais adequado foi de 205.000 células/mL para o teste So... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of the present study was to assess new strategies to identify and treat Streptococcus agalactiae subclinical mastitis. Two studies were conducted to achieve the proposed objectives: 1) a randomized clinical trial, to assess the efficacy of intramammary cloxacillin (CLOXIMM), intramammary cefquinome (CEFIMM), and intramuscular cefquinome (CEFIM), to treat S. agalactiae intramammary infections (IMI); and assess whether CLOXIMM was non-inferior to CEFIMM to treat S. agalactiae IMI. And, 2) a diagnostic accuracy study, to estimate the accuracy of the Somaticell, California Mastitis Test (CMT), and the composite milk microbiological examination of milk to detect S. agalactiae IMI. Results indicated that the bacteriological cure rate was lower for quarters treated with CEFIM (55%), as compared with CLOXIMM (86%) or CEFIMM (98%). The bacteriological cure difference between CEFIMM and CLOXIMM was 0.121 (95% confidence interval: 0.056 - 0.184). The CLOXIMM was considered non-inferior to CEFIMM when the non-inferiority margins of 0.20 and 0.25 were considered. Nevertheless, determination of non-inferiority was inconclusive for margins of 0.10 and 0.15. Microbiological examination of composite milk was of high accuracy (95.7%), as compared with microbiological examination of quarter milk samples. The thresholds of 205,000 cells/mL for the Somaticell and of score 1 for the CMT can be considered the most appropriate for diagnosing S. agalactiae IMI. The higher sensitivity an... (Complete abstract click electronic access below) / Mestre