Thesis (Ph.D. (Tropical Medicine))--Mahidol University, 2006. / LICL has E-Thesis 0014 ; please contact computer services. LIRV has E-Thesis 0014 ; please contact circulation services.

[pt] Estudos sobre diagnóstico precoce de falhas em hidrogenadores vêm sendo realizados por várias empresas do setor elétrico brasileiro, visando o estabelecimento de uma nova estratégia de manutenção destas máquinas, de forma a reduzir custos de manutenção e operação, bem como aumentar a confiabilidade do sistema elétrico. Este trabalho tem por finalidade apresentar um Sistema Especialista para diagnóstico precoce de falhas eletromecânicas em hidrogenadores. O método de diagnóstico proposto baseia-se na análise de vibrações observadas no eixo da máquina. As informações de vibração são tratadas, essencialmente, através do seu aspectro de freqüência (Transformada de Fourier do sinal no tempo). Outras informações adicionais também são utilizadas pelo Sistema para o refinamento do diagnóstico final a ser obtido. O Sistema Especialista desenvolvido, denominado DIAGH, utiliza um Banco de Conhecimento que foi constituído a partir de informações heurísticas obtidas através de relatos de especialistas, que conseguiram estabelecer o relacionamento de certas freqüências encontradas em tais aspectros, com falhas ocorridas em hidrogenadores. O Sistema DIAGH foi testado, utilizando-se dados reais obtidos a partir de uma das unidades geradoras da usina de Porto Colômbia pertencentes à FURNAS Centrais Elétricas. / [en] Studies on early diagnosis of hydrogenerators failure have been developed in many Brazilian utilities, regarding the establishment of a new maintenance strategy for these machines. The objectives to be achieved are the reduction in operation and maintenance costs as well as the increase in the system reliability. This work aims at presenting an Expert System for the early diagnosis of eletromechanical failures in hydroelectrical generators. The proposed disagnostic method is based on the analysis of the vibrations observed on the mechine shaft. The measured shaft vibrations are represented in the frequency domain by using the Fast Fourier Tranform. Additional information is also used for the final diagnostic improvement. The Expert System built in this work, called DIAGH, uses a knowledge base which was formed from heuristic information of sécialists. This information is concerned with the relationship between the occurrence of certain frequencies and hydrogenerator faults. The DIAGH system was tested through rela data obtained from one of the generation units of Porto Colômbia Substation of FURNAS Centrais Elétricas.

Introdução: O carcinoma hepatocelular (CHC) é o câncer primário de fígado mais comum. A cirrose hepática é o principal fator de risco para esse tumor. O rastreamento para o CHC em pacientes com cirrose tem sido recomendado há anos. Acredita-se que a detecção e o tratamento precoce do CHC melhorem a sobrevida dos pacientes. O objetivo deste estudo foi analisar a sobrevida dos pacientes cirróticos com CHC pequeno e identificar fatores preditivos de sobrevida no Brasil. Casuística e Métodos: Entre janeiro de 1998 e dezembro de 2003, 74 pacientes cirróticos com CHC foram avaliados. Eles preenchiam os seguintes critérios: CHC com até três nódulos e no máximo 30 mm de diâmetro cada. Os fatores preditores de sobrevida foram identificados através do método de Kaplan-Meier e o modelo de Cox. Resultados: A média de idade foi de 58 anos (32-77); 71% dos pacientes eram do sexo masculino; 64% tinham hepatite C; 60% eram Child-Pugh A, o valor mediano da pontuação de MELD foi de 11; 79% tinham hipertensão portal. No momento do diagnóstico, 71% tinham uma única lesão; o tamanho do principal tumor era menor que 20 mm em 47%; o valor médio de AFP foi de 131 ng/ml. Três pacientes tinham trombose de veia porta, sugestiva de invasão vascular. Cinqüenta pacientes (67,5%) foram incluídos na lista de transplante hepático, que foi realizado só em quatro pacientes. A ressecção cirúrgica do tumor foi possível em quatro pacientes. Quarenta e oito (64,8%) pacientes receberam tratamento ablativo percutâneo (ablação por radiofreqüência ou injeção percutânea de etanol). Nove pacientes não receberam nenhum tratamento específico para o tumor. A taxa de sobrevida geral foi de 80%; 62%; 41% e 17% em 12, 24, 36 e sessenta meses, respectivamente. O tempo médio de seguimento após o diagnóstico do CHC foi de 23 meses (mediana de 22 meses, variando de um a 86 meses) para todo o grupo. Durante o seguimento, ocorreram 39 óbitos ocorreram relacionados com insuficiência hepática ou progressão do CHC. A análise univariada dos 74 pacientes mostrou que escore MELD maior que 11 (p = 0,016), classificação de Child-Pugh B e C (p = 0,007), AFP > 100 ng/ml (p = 0,006), mais de uma lesão (p = 0,041), diâmetro do tumor > 20 mm (p = 0,009) e presença de invasão vascular (p < 0,0001) foram preditores independentes de sobrevida. A análise de regressão de Cox identificou invasão vascular (RR = 14,60 - IC 95% = 3,3 - 64,56 - p < 0,001) e tamanho do tumor > 20mm (RR = 2,14 - IC 95% = 1,07 - 4,2 - p = 0,030) como preditores independentes de pior sobrevida. O tratamento do CHC esteve relacionado com melhor sobrevida. Conclusão: A identificação de CHC pequeno com até 20 mm de diâmetro está relacionada com melhores taxas de sobrevida. Por outro lado, a presença de invasão vascular, apesar do tamanho pequeno das lesões, é um fator associado a péssimo prognóstico. / Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Liver cirrhosis is the major risk factor for this tumor. Screening for HCC in patients with cirrhosis has been recommended, in the belief that detection and treatment of early HCC improves patient survival. The aims of this study were to analyze the overall survival of small HCC in cirrhotic patients and identify independent predictors of survival, in Brazil. Methods: Between January 1998 and December 2003, seventy-four cirrhotic patients with hepatocellular carcinoma were evaluated satisfying the following criteria: HCC of 30 mm or smaller and a maximum of three lesions. Predictors of survival were identified using the Kaplan-Meier and the Cox model. Results: Mean age was 58 years-old (32-77), 71% of patients was male, 64% had hepatitis C, 60% were Child-Pugh A, mean MELD score was 11 and 79% had portal hypertension. At the time of diagnosis, 71% had one tumor, the size of the main tumor was smaller than 20 mm in 47%, mean AFP level was 131 ng/ml. Three patients had portal vein thrombosis, suggesting vascular invasion. Fifty patients (67.5%) were included in the liver transplant list, but it was performed in only four patients. Tumor resection was possible in four patients. Forty-eight (64.8%) patients received percutaneous treatment (radiofrequency ablation or percutaneous ethanol injection). Nine patients did not receive any cancer treatment. The overall survival rates were 80%, 62%, 41% and 17% at 12, 24, 36 and 60 months, respectively. The mean length of follow-up after HCC diagnosis was 23 months (median 22 months, range 1-86 months) for the entire group. During follow-up a total of 39 deaths related to liver failure or HCC progression occurred. Univariate analysis of the 74 patients showed that MELD score greater than 11 (p = 0.016), Child-Pugh classification (p = 0.007), AFP > 100 ng/ml (p = 0.006), more than one lesion (p = 0.041), tumor diameter > 20 mm (p = 0.009) and presence of vascular invasion (p < 0.0001) were significant predictors of survival. Cox regression analysis identified vascular invasion (RR = 14.60 - IC 95% = 3.3 - 64.56 - p < 0.001) and tumor size > 20mm (RR = 2.14 - IC 95% = 1.07 - 4.2 - p = 0.030) as independent predictors of decreased survival. Treatment of HCC was related to increased overall survival. Conclusion: Identification of small tumors of up to 20 mm diameter is related to increase survival. Nevertheless, vascular invasion, in spite of the small diameter of the lesions, is a factor associated with dismal prognosis.

>Magister Scientiae - MSc / Lung cancer remains the leading cause of cancer deaths worldwide, with the majority of cases attributed to non-small cell lung carcinomas. At the time of diagnosis, a large percentage of patients present with advanced stage of disease, ultimately resulting in a poor prognosis. The identification circulatory markers, overexpressed by the tumour tissue, could facilitate the discovery of an early, specific, non-invasive diagnostic tool as well as improving prognosis and treatment protocols. The aim was to analyse gene expression data from both microarray and RNA sequencing platforms, using bioinformatics and statistical analysis tools. Enrichment analysis sought to identify genes, which were differentially expressed (p < 0.05, FC > 2) and had the potential to be secreted into the extracellular circulation, by using Gene Ontology terms of the Cellular Component. Results identified 1 657 statically significant genes between normal and early lung cancer tissue, with only 1 gene differentially expressed (DE) between the early and late stage disease. Following statistical analysis, 171 DE genes selected as potential early stage biomarkers. The overall sensitivity of RNAseq, in comparison to arrays enabled the identification of 57 potential serum markers. These genes of interest were all downregulated in the tumour tissue, and while they did not facilitate the discovery of an ideal diagnostic marker based on the set criteria in this study, their roles in disease initiation and progression require further analysis.

Yes / This study aimed to explore the challenges and barriers faced by staff involved in the delivery of the National Health Service (NHS) Health Check, a systematic cardiovascular disease (CVD) risk assessment and management program in primary care. Data have been derived from three qualitative evaluations that were conducted in 25 General Practices and involved in depth interviews with 58 staff involved all levels of the delivery of the Health Checks. Analysis of the data was undertaken using the framework approach and findings are reported within the context of research and practice considerations. Findings indicated that there is no ‘one size fits all’ blueprint for maximising uptake although success factors were identified: evolution of the programme over time in response to local needs to suit the particular characteristics of the patient population; individual staff characteristics such as being proactive, enthusiastic and having specific responsibility; a supportive team. Training was clearly identified as an area that needed addressing and practitioners would benefit from CVD specific baseline training and refresher courses to keep them up to date with recent developments in the area. However there were other external factors that impinged on an individual’s ability to provide an effective service, some of these were outside the control of individuals and included cutbacks in referral services, insufficient space to run clinics or general awareness of the Health Checks amongst patients. The everyday experiences of practitioners who participated in this study suggest that overall, Health Check is perceived as a worthwhile exercise. But, organisational and structural barriers need to be addressed. We also recommend that clear referral pathways be in place so staff can refer patients to appropriate services (healthy eating sessions, smoking cessation, and exercise referrals). Local authorities need to support initiatives that enable data sharing and linkage so that GP Practices are informed when patients take up services such as smoking cessation or alcohol harm reduction programmes run by social services.

Yes / Lung cancer remains a major cause of preventable death and early diagnosis is critical to improving survival chances. The chest X-ray (CXR) remains the most common initial investigation, but clinical pathways need to support timely diagnosis through, where necessary, escalation of abnormal findings to ensure priority reporting and early CT scan. This single-centre study included a retrospective evaluation of a rapid lung cancer CXR pathway in its first year of operation (May 2018-April 2019). The pathway was initially designed for primary care referrals but could also be used for any CXR demonstrating abnormal findings. A parallel cross-sectional survey of radiographers explored their understanding, adherence and concerns regarding their role in the pathway operation. Primary care referrals on the rapid diagnostic pathway were low (n = 51/21,980; 0.2%), with 11 (21.6%) requiring a CT scan. A further 333 primary care CXR were escalated by the examining radiographer, with 100 (30.0%) undergoing a CT scan. Overall, 64 of the CT scans (57.7%) were abnormal or demonstrated suspicious findings warranting further investigation. There were 39 confirmed primary lung carcinomas, most with advanced disease. Survey responses showed that most radiographers were familiar with the pathway but some expressed concerns regarding their responsibilities and limited knowledge of CXR pathologies. This baseline evaluation of the rapid lung cancer pathway demonstrated poor referral rates from primary care and identified the need for improved engagement. Radiographer escalation of abnormal findings is an effective adjunct but underlines the need for appropriate awareness, training, and ongoing support. Engagement of the multiprofessional team is critical in new pathway implementation. Rapid diagnostic pathways can enable early diagnosis and the radiographer has a key role to play in their success.

Yes

Ce manuscrit est consacré au développement de méthodes de dérivation intra-capillaire ultrasensible et de méthodes de séparation électrocinétique hautement résolutives en vue d’une intégration dans un outil microfluidique de diagnostic de la maladie d’Alzheimer. La partie bibliographique situe d'abord le contexte épidémiologique et neurophysiopathologique de la maladie d’Alzheimer ainsi que les outils de diagnostic actuellement utilisés. Ensuite, l'état de l'art sur l'utilisation de méthodes de séparation électrocinétique, ainsi que les outils analytiques disponibles pour améliorer l’analyse d’échantillon biologique sont présentés. La partie expérimentale a porté tout d'abord sur le développement de méthodes de dérivation intra-capillaire permettant une détection ultrasensible de biomarqueurs de la maladie d’Alzheimer, en particulier l’ubiquitine, dans le liquide céphalo-rachidien. Le travail expérimental s’est ensuite prolongé par le développement d’une méthode de séparations hautement résolutives en puce en verre de différentes formes de peptides beta-amyloïdes, biomarqueurs pertinents en vue d’un diagnostic de la maladie d’Alzheimer. Pour terminer, l’apport de deux nouveaux substrats polymériques, le COC et le thiolène, pour la microfabrication de puce d’électrophorèse capillaire a été démontré. / This work is dedicated to the development of highly sensitive intra-capillary derivatization methods and highly resolutive electrokinetic separation methods, with the aim to integrate them in a microfluidic diagnostic tool of Alzheimer’s disease. The bibliographic chapter explains the epidemiologic and neurophysiopathologic background of Alzheimer’s disease and describes the diagnostic tools currently used. Then, a state of the art related to the use of electrokinetic separation methods, as well as the analytical techniques available to improve the analyses of biological samples, is presented. The first experimental part focused on the development of intra-capillary derivatization methods allowing highly sensitive detection of Alzheimer’s disease biomarkers, especially ubiquitine, in the cerebrospinal liquid. The second part was dedicated to the development of a capillary electrophoresis method, in a glass chip, capable of separating with a high resolution different forms of beta-amyloid peptides, which are relevant biomarkers of Alzheimer’s disease. Finally, the usefulness of new polymeric materials, such as COC and thiolene, for the manufacturing of microchip device was demonstrated. A careful study of their physico-chemical properties led to the development of relevant strategies for surface treatment, so as to minimize the adsorption of proteins. For the first time, a thiolene chip covered with a new copolymer allowed an electrokinetic separation of proteins.

Os rins desempenham um papel fundamental no sistema urinário e sua principal função é a filtração do sangue. Uma das causas que podem comprometer o funcionamento dos rins é a Insuficiência Renal Aguda (IRA) que é definida como a diminuição da taxa de filtração glomerular (TFG) de forma rápida e inesperada, causando a perda da função renal. Essa doença apresenta um número significativo de internações e também óbitos. O marcador padrão usado nos exames laboratoriais é a creatinina sérica, no entanto, a concentração da creatinina sérica pode variar dependendo de vários fatores, como idade, sexo, nutrição, entre outros. Além disso, sua concentração não varia consideravelmente nas primeiras indicações da lesão renal. Dessa forma, o diagnóstico é tardio e a função renal já pode estar comprometida. A proteína cistatina C (CST3) vem sendo indicada como um novo marcador para a doença, mostrando superioridade especialmente para detectar pequenas variações da TFG. A concentração da cistatina C não varia significativamente com a idade, sexo e massa muscular. Assim, foi desenvolvido um imunossensor para detectar a cistatina C, usando a configuração de transistor de efeito de campo de porta estendida e separada (SEGFET). Os eletrodos foram caracterizados por várias técnicas como MEV, microscopia de força atômica, técnicas eletroquímicas e também foi analisada a sensibilidade do ouro. As etapas de construção do imunossensor, e a interação do anticorpo com concentrações crescentes da proteína foram verificadas através de técnicas eletroquímicas, na faixa de concentração de 3 a 100 ng.mL-1. Nas medidas no SEGFET observou-se uma mudança significativa da corrente após a adição da cistatina C e para as substâncias interferentes não. O imunossensor apresentou alta sensibilidade detectando concentrações bem baixas da proteína alvo. A curva analítica &#916;IDS% x [CST3] obteve-se L.D. = 0,75 ng.mL-1, L.Q. = 2,27 ng.mL-1 e r = 0,98122. A curva analítica &#916;VGS% x [CST3] obteve-se L.D. = 0,28 ng.mL-1, L.Q. = 0,87 ng.mL-1 e r = 0,99846. Embora tenha algumas limitações o imunossensor é inovador e apresenta muitas vantagens podendo ser aplicado futuramente para o diagnóstico da doença. / The kidneys play a key role in the urinary system and its main function is the filtration of blood. One of the causes that can compromise the functioning of the kidneys is the Acute Kidney Injury (AKI), which is defined as the quickly and unexpected decrease in Glomerular Filtration Rate (GFR), causing the loss of kidney function. This disease presents a significant number of hospitalizations and also deaths. The standard marker used in laboratory tests is serum creatinine, however, serum creatinine concentration may vary depending on a number of factors, such as age, sex, nutrition, and so on. In addition, its concentration does not vary considerably in the first indications of renal injury. Thus, the diagnosis is delayed and renal function may already be compromised. The cystatin C protein (CST3) has been indicated as a new marker for the disease, showing superiority especially for detecting small variations in GFR. The concentration of cystatin C does not vary significantly with age, sex and muscle mass. Thus, an immunosensor was developed to detect cystatin C using the extended and a separate gate field effect transistor (SEGFET) configuration. The electrodes were characterized by several techniques such as SEM, atomic force microscopy, electrochemical techniques and also the sensitivity of gold was analyzed. The construction of the immunosensor, and the interaction of the antibody with increasing concentrations of the protein were verified by electrochemical techniques, in the concentration range of 3 to 100 ng.mL-1. In the measurements in the SEGFET a significant change of the current was observed after the addition of cystatin C and for the interfering substances there was no difference. The immunosensor showed high sensitivity detecting very low concentrations of the target protein. The analytical curve &#916;IDS% x [CST3] was obtained L.D. = 0,75 ng.mL-1, L.Q. = 2,27 ng.mL-1 and r = 0,98122. The analytical curve &#916;VGS% x [CST3] was obtained L.D. = 0,28 ng.mL-1, L.Q. = 0,87 ng.mL-1 and r = 0,99846. Although it has some limitations the immunosensor is innovative and presents many advantages and can be applied in the future to diagnose the disease.

A sífilis é uma doença infecciosa, cujo agente etiológico é o Treponema pallidum. Pode ser transmitida sexualmente ou verticalmente, via placenta. Seus estágios variam entre sífilis primária, sífilis secundária, sífilis latente e sífilis congênita. Dentre os diagnósticos mais eficazes, encontram-se os testes sorológicos, porém os falsos positivos e falsos negativos no estágio primário levam à procura de uma forma mais eficaz de se determinar, precocemente, a doença. Além disso, por várias razões, nem sempre o profissional clínico suspeita das lesões presentes na mucosa oral, cogitando de outras hipóteses diagnósticas. O objetivo deste trabalho foi avaliar imuno-histoquimicamente e histoquimicamente lesões bucais biopsiadas cujo aspecto histológico levou à suspeita de sífilis, buscando identificar os microorganismos, bem como correlacionar o quadro sorológico quando positivo. Para o estudo foram incluídas 34 lesões suspeitas de sífilis, que foram submetidas à reação imuno-histoquímica com o anticorpo anti-treponema e técnica histoquímica de coloração pela prata. Dos 34 casos avaliados 13 foram positivos para o anticorpo anti-treponema, todos posteriormente diagnosticados como sífilis secundária, com positividade sorológica, exceto por um caso em que a sorologia não foi realizada. Quando se comparou os métodos de diagnóstico, a técnica de coloração por prata obteve sensibilidade de 46,15% e a de imuno-histoquímica foi de 92,3%. Os aspectos histológicos variaram em um grande número de achados, dentre eles: intensa exocitose, infiltrado inflamatório predominantemente plasmocitário (justaepitelial e perivascular), áreas de ulceração, epitélio paraqueratinizado, edema, espongiose e hiperplasia epitelial. A marcação imuno-histoquímica dos treponemas foi, principalmente, epitelial (61,5%) e esse método se mostrou um meio de diagnóstico rápido, simples e eficiente no diagnóstico de lesões orais de Sífilis. / Syphilis is an infectious disease, whose etiologic agent is Treponema pallidum. It can be transmitted sexually or vertically via the placenta. Its stages include primary syphilis, secondary syphilis, latent syphilis and congenital syphilis. Among the diagnoses most effective are the serological tests, but false positives and false negatives in the primary stage lead to demand for a more effective way to determine the disease earlier. In addition, for various reasons, not always the professional clinical suspicion of lesions present in the oral mucosa, thinking in other possible diagnoses. The objective of this study was to identify microorganisms and set the best way forward to a diagnostic framework confirmed positive serology. The results for syphilis lesions in the oral mucosa corresponded to 13 cases, all of secondary iinjuries,with positive serology for syphilis and in only one of them serology had not been held. In a comparison of diagnostic methods, the technique of silver staining achieved sensitivity of 46.15% and immunohistochemistry was 92.3%. The histological features varied in a large number of findings, including: intense exocytosis, inflammatory infiltrate, predominantly plasmacytic (banda-like and infiltrate perivascular), areas of ulceration, parakeratinized epithelium, edema, spongiosis and epithelial hyperplasia. The immunohistochemical staining of treponemes was mainly epithelial (61.5%) and this method was a rapid, simple and efficient means in the diagnosis of oral lesions of syphilis.