Thesis submitted in fulfilment of the requirements for the award of the degree of Master of Technology Radiography (Diagnostic) in the Faculty of Health and Wellness Sciences at the Cape Peninsula University of Technology 2009 / Since their discovery in 1895, the use of x-rays is continuously evolving in medicine making the diagnosis of injuries and diseases more practicable. It is therefore not surprising that x-rays contribute 90% of the radiation dose to the population from manmade sources (DWP, 1992). Moreover, these radiation doses are associated with both fatal and non-fatal cancer risk that is detrimental to adults between 20 to 60 years (Wall, 1996). Radiation dose to individuals therefore needs to be actively monitored in order to minimise such risk. Barium contrast examinations were characterised as one of the radiological examinations that contributed enormously to the collective dose to the patients in the radiology department (DWP, 1992). Determining the diagnostic reference levels of such examinations would reduce the over-exposure of individuals to ionising radiation. Currently in South Africa (SA), there are no diagnostic dose reference levels for barium meal (BaM) and barium enema (BaE) examinations. This study therefore investigated the radiation doses delivered to patients referred for BaM and BaE, obtained potential regional reference doses for these examinations, compared the radiation doses obtained with those from similar dosimetry studies and investigated sources of dose variation among the study sites. A total of 25 BaM and 30 BaE patients in the age range 18 to 85 years, weighing 50 kg to 90 kg, at 3 hospitals in the Western Cape, SA were investigated. The radiation dose to the patients was measured using Dose Area Product (DAP) meters that were permanently fitted onto fixed fluoroscopy units at these 3 hospitals. The third quartile DAP values were 20.1 Gycm2 and 36.5 Gycm2 for BaM and BaE respectively. The median DAP values were 13.6 Gycm2 and 27.8 Gycm2 for BaM and BaE respectively. The median values were recommended as the potential Diagnostic Reference Levels for BaM and BaE as they are less affected by outlying values of under or over- weight (Yakoumakis, Tsalafoutas, Sandilos, Koulentianos et al, 1999). The weights of the patients, fluoroscopy time, the number of images obtained, the use of digital or conventional fluoroscopy equipment and the level of training of the radiologists were the factors considered for dose variation among the 3 hospitals.

Orientador: José Ricardo de Arruda Miranda / Banca: Luciana Aparecida Cora / Banca: José Morceli / Inclui 1 CD-Rom / Resumo: Avaliar formas farmacêuticas sólidas in vivo fornece um entendimento mais profundo quando um efeito sistêmico ou local é desejado. Geralmente, estes estudos são realizados por meio da cintilografia e técnicas biomagnéticas. A Ressonância Magnética (RM) vem sendo aplicada em tecnologia farmacêutica sendo que estes estudos são realizados com comprimidos marcados por partículas de óxido de ferro ou por gadolíneo em pó. Este estudo propõe a utilização da RM para monitorar o processo de desintegração in vitro e in vivo de comprimidos contendo açaí (Euterpe oleracea) como agente de contraste natural. O açaí é uma fruta presente em abundância na região norte do Brasil com a propriedade de atuar como agente de contraste oral em imagens obtidas por RM. Comprimidos obtidos com diferentes desintegrantes (croscarmelose sódica, crospovidona e mistura efervescente) foram marcados com açaí e revestidos com uma solução de polímero pH-independente. As formas farmacêuticas foram avaliadas in vitro e in vivo em um equipamento de RM de 0,5 T. Os resultados mostraram que o açaí é um forte agente de contraste e pode ser empregado em estudos farmacêuticos. Foi possível definir a imagem do comprimido e quantificar o processo de desintegração. Não foram encontradas diferenças (p>0,7) no tempo de desintegração avaliado in vitro nas medidas empregando-se comprimidos de crospovidona (14±1 min) e croscarmelose (15±1 min). No entanto, comparando-se com os comprimidos efervescentes (6±1 min), o tempo de desintegração foi significantemente diferente (p<0,01). Foi possível obter as imagens ponderadas em T1 dos comprimidos no estômago humano com qualidade razoável. O tempo de desintegração dos comprimidos in vivo foi 14±1 min. Este estudo mostrou que a RM é uma técnica capaz de monitorar o processo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The performance of pharmaceutical dosage forms must be fully investigated in vivo to provide more reliable information when a local or systemic effect is desirable. Generally, in vivo investigation on the behavior of dosage forms has been made by using gammascintigraphy and biomagnetic techniques. Magnetic resonance (MR) methods have become established tools in the drug discovery and development process. Most of MR studies have been made with tablets labeled with iron oxide particles or dry gadolinium chelates (Gd- DOTA) powder. The aim of this study was to evaluate the disintegration process of tablets labeled with açai (Euterpe oleraceae) in vitro and in human stomach. Açai is a typical fruit from Amazonia, and has been recognized for its functional properties for use as oral contrast agent for MR. Tablets obtained from different disintegrants (croscarmellose sodium, crospovidone and an effervescent blend) were labeled with açai and were coated by using pHindependent polymer solution. The dosage forms have been evaluated in vitro and in vivo in a 0.5 T magnetic resonance system. The results showed that açai may be employed as a useful contrast agent which for pharmaceutical purposes. It was able to define the image of the tablets and to quantify the disintegration process. The disintegration time evaluated in vitro for tablets obtained from crospovidone (14±1 min) and croscarmellose (15±1 min) it was not significantly different (p>0.7). However, in comparison with tablets obtained with effervescent blend (6±1 min), the disintegration time was significantly different (p<0.01). It was possible to obtain images of the tablets in human stomach in T1 weighting with reasonable quality. The disintegration time of tablets made from croscarmellose sodium obtained from in vivo measurements was 14±1 min. This study showed that MR technique... (Complete abstract click electronic access below) / Mestre

Com uma necessidade cada vez maior da utilização de materiais mais sustentáveis na construção civil, existe uma grande busca por novas substâncias que possam suprir as nossas necessidades de maneira mais “limpa”. O presente trabalho tem como foco propor uma metodologia de dosagem para a obtenção de solos artificialmente cimentados, com determinadas resistências e rigidezes, de maneira que eles sejam duráveis, com a adição de diferentes resíduos. O solo inicialmente estudado é a areia de Osório e os resíduos são a cal de carbureto e o pó de vidro. A cal de carbureto consiste basicamente de hidróxido de cálcio e o pó de vidro de sílica em estado amorfo, gerando assim uma combinação adequada para a ocorrência das reações pozolânicas. A metodologia de dosagem proposta relaciona as propriedades dos materiais com o fator η/Biv0,28, aos sete dias de cura, sendo η a porosidade do solo artificialmente cimentado e, Biv o teor volumétrico de agente cimentante no interior do mesmo (neste caso pó de vidro e cal de carbureto). O expoente externo 0,28 se assemelha ao encontrado em outras metodologias de dosagem para solos artificialmente cimentados com cimento Portland Com a finalidade de validar a metodologia proposta, para condições distintas das analisadas, foram executados ensaios com diferentes períodos de cura (180 dias), diferentes resíduos (cinza de casca de arroz) e um solo distinto (arenito Botucatu), chegando também a correlações do comportamento mecânico destes materiais com o fator η/Biv0,28. Os dados obtidos nesta pesquisa foram comparados com os resultados de outros pesquisadores que utilizaram cal com cinza volante de usinas de carvão juntamente com cal hidratada e de outros trabalhos que utilizaram cimento Portland, todos para criar solos artificialmente cimentados, e, mais uma vez, a metodologia proposta se mostrou eficaz. Foi possível ainda normalizar em função de um valor médio todos os resultados de rigidez, resistência e durabilidade obtendo assim equações únicas em função de η/Biv0,28 para todos os materiais analisados, chegando a uma correlação com mais de 1000 pontos no caso da resistência. / With a growing need for the use of more sustainable materials in construction, there is a great search for new substances that can meet our needs in a "cleaner" way. The present work aims to propose a dosing methodology for obtaining artificially cemented soils, with certain strengths and stiffness, so that they are durable, with the addition of different residues. The initially studied soil is the Osório sand and the residues are carbide lime and glass powder. The carbide lime basically consists of calcium hydroxide and the glass powder consists of silica in the amorphous state, thus generating a great combination for the occurrence of the pozolanic reactions. The proposed dosage methodology relates the properties of the materials with the factor η/Biv0.28, at the seven days of curing, in which η is the porosity of the artificially cemented soil and Biv is the volumetric content of the cementitious agent inside it (in this case powder glass and carbide lime) The external exponent 0.28 resembles that found in other dosing methodologies for artificially cemented soils with Portland cement. The methodology led to a unique correlation for all the dosages used. To validate the hypothesis which was raised, tests were carried out with different curing periods (180 days), different residues (rice husk ash) and a different soil (Botucatu sandstone), reaching optimum correlations. The data obtained in this research were compared with the results of other researchers who used lime with fly ash from coal plants together with hydrated lime and from other works that used Portland cement, all to create artificially cemented soils, and, once again, the proposed methodology proved to be excellent. It was also possible to normalize all the results of stiffness, strength and durability thus obtaining unique equations as a function of η/Biv0.28 for all materials analyzed, reaching a correlation with more than 1000 points.

A utilização do concreto auto-adensável (CAA) vem aumentando consideravelmente, no Brasil e no mundo. Com isso, há mais interesse em estudos práticos e teóricos a respeito do material, porém a maioria realizada está centrada em propriedades mecânicas da mistura no estado endurecido. Poucos estudos estão voltados para uma das áreas de maior lacuna: a dosagem. Os métodos de dosagem existentes para o CAA ou são experimentais, baseados na experiência do executor, ou são dependentes de tabelas determinadas a partir de materiais de difícil reprodução em outros locais. Com o intuito de ajudar a resolver este problema, foi proposto um método de dosagem experimental para CAA nesta tese. Este método visa a dosagem de CAA através de ensaios simples que determinem a composição dos agregados, de forma que o empacotamento granular apresente a menor quantidade de vazios possível, a fim de se minimizar o consumo de pasta na mistura. O método utiliza conceitos novos e já consagrados de outros métodos, como o IPT/EPUSP (Helene e Terzian, 1992), o proposto por Tutikian (2004), o de O´Reilly (1992) e o Modelo de Empacotamento Compressivo (CPM) (De Larrard, 1999). Para a comprovação da eficácia deste método, foram dosadas seis famílias de CAA, sendo três com areia fina e outras três com cinza volante, formando pares dosados por diferentes métodos. Entre as seis famílias, duas utilizaram o método de Tutikian (2004) e quatro o método proposto, porém primeiramente com uma faixa de agregado graúdo e após com duas granulometrias de brita, proporcionando famílias com o esqueleto granular mais compacto. Por fim, foi realizada uma família de concreto convencional (CCV). Os CAA dosados através deste novo método são de obtenção mais simples e menos trabalhosa, dependendo menos da experiência do executor, e os resultados mostraram que estes podem ser mais econômicos e com as propriedades no estado endurecido similares ou até vantajosas em relação às dos CCV e a dos outros CAA, principalmente o com duas granulometrias de agregado graúdo. / The utilization of self compacting concrete (SCC) has been increasing considerably throughout Brazil and the world. Hence, there has been more interest in theoretical and practical studies regarding the issue; however, the majority of such studies have been focused on the mechanical properties of the mixture in the hardened state. Very few studies have been focused on the subject of the dosage. The existing methods of dosage for SCC are either experimental, based on the experience of the executor, or are dependent on customized charts based on local materials which are very difficult to reproduce. With the intention to aid in the solution of this problem, an experimental dosage method was proposed in this thesis. This method aims at the dosage of SCC through simple tests that determine the composition of the aggregates, so that the packing density presents the least amount of voids, in order to minimize the consumption of binder in the mixture. The method uses new concepts and some concepts already determined from other methods, such as the IPT/EPUSP (Helene e Terzian, 1992), the one proposed by Tutikian (2004), the O´Reilly (1992) and the Compressive Packing Model (CPM) (De Larrard, 1999). In order to substantiate the efficienty of this method, six families of SCC were carried out, three of those with fine sand and the remaining three with fly ash, forming three pairs dosed by different methods. Amongst the six families, two used the Tutikian method (2004) and the other four families used the proposed method, which were divided into two subgroups; two with one class of gravel and the remaining subgroup utilizing two classes of gravel, supplying each family with a more compact granular skeleton. As a control group, a test family of conventional concrete (CCV) was produced. The SCC designed through this new method is simpler to obtain and requires less labor, depending less on the experience of the executor. The results present themselves as more economical and with the properties in the hardened state quite similar or even enhanced in relation to the ones of the CCV and the other SCC, specially with two classes of gravel.

Na engenharia em geral existem técnicas consagradas de construção e materiais com comportamentos exaustivamente estudados para um melhor aproveitamento de suas características a favor do engenheiro. Pode-se dizer que uma construção está cada vez mais integrada com o meio ambiente, tanto na economia de materiais quanto no reaproveitamento dos mesmos. O uso mais racional dos materiais também é uma importante alternativa para minimizar custos em uma obra, tais como transporte, escolha do material mais adequado a ser utilizado, tanto por suas características quanto por sua disponibilidade de uso. Já foram realizadas e ainda hoje têm sido realizadas inúmeras pesquisas sobre solos artificialmente cimentados na Universidade Federal do Rio Grande do Sul, visando seu emprego como camada de suporte para fundações superficiais, no encapsulamento de solos contaminados e como barreiras de contenção de contaminação. Analisando as características mecânicas de areia fina artificialmente cimentada, o objetivo desta pesquisa é verificar a validade do uso do fator vazios/cimento na estimativa da resistência à compressão simples, rigidez inicial, resistência à compressão triaxial em condições drenadas com medidas de G0, comportamento tensão-dilatância e comportamento tensão-deformação da areia de Osório. Para tanto foi verificado que o fator vazios/cimento mostrou-se ser um parâmetro muito eficaz e confiável no que diz respeito à previsão de comportamento do material para dosagem de solo-cimento, em projetos geotécnicos que utilizem a areia de Osório. / In traditional engineering, there are special construction techniques and exhausted studies in materials behavior, for a better employment of it due to the characteristics by the engineer. Today, constructions are increasingly integrated in the environment, both in the economy as in the reuse of materials from them. The more rational use of materials is also important alternative to minimize costs in a work such as transportation, choice of the most appropriate material to be used, either by their characteristics, or their availability for use. Many researches have been made until today on artificially cemented soils in the Federal University of Rio Grande do Sul, targeting their employment as layer of support for foundations surface in the encapsulation of contaminated soil and barriers of contamination containment. Analyzing the mechanical characteristics of fine artificially cemented sand, the objective of this research is to verify the validity of the use of the void/cement ratio in the estimation of the unconfined compressive strength, initial stiffness, triaxial compressive strength in drained conditions with measures of shear modulus (G0), stress-dilatancy behavior and stress-strain behavior of the Osório sand. Thus was verified that the void/cement ratio has proven to be a very effective and reliable parameter regarding prediction of material behavior for soil-cement, dosage in geotechnical projects that use the sand of Osório.

Orientador: Sergio Santos Muhlen / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica e de Computação / Made available in DSpace on 2018-08-14T23:21:55Z (GMT). No. of bitstreams: 1 Ferraz_MarianaSacriniAyres_M.pdf: 4432455 bytes, checksum: 653b956278da2f0d25423b525a3311d0 (MD5) Previous issue date: 2009 / Resumo: Exames de cateterismo que utilizam fluoroscopia, como a angioplastia coronariana, são responsáveis por altas doses de radiação (maiores que na radiologia convencional), tanto para os pacientes como para a equipe médica. O uso intensivo dos raios X faz com que aumentem os riscos radiológicos, em decorrência da alta exposição cumulativa durante a vida dos cardiologistas intervencionistas e suas equipes. Os principais riscos decorrentes de altas doses de raios X são: câncer, cataratas, malformações e danos ao feto de mulheres grávidas. A geração de raios X com tecnologia pulsada, que se tornou disponível aos hospitais, representa uma potencial redução da dose de radiação recebida pela equipe profissional. O montante de redução da dose ainda é objeto de controvérsias na literatura, mas alguns autores descrevem reduções de até 70%. Este trabalho teve por objetivo o estudo da dose ocupacional no Laboratório de Cateterismo Cardíaco da UNICAMP. Foram comparadas as doses recebidas pela equipe para a fluoroscopia contínua e pulsada, e a diminuição proporcionada pela troca do equipamento de fluoroscopia contínua pelo pulsado no Laboratório foi quantificada. As diminuições encontradas para os médicos, principal e auxiliar, foram de 5,2% e 13,7% respectivamente. Para os enfermeiros e auxiliares de enfermagem foram de 7,5% e 8,2%. Além disso, foram calculadas as doses efetivas por procedimento para cada profissional, e foi feita uma análise dos dados dos dosímetros termoluminescentes usados em todo o período de funcionamento do Laboratório. Em conclusão, a diminuição proporcionada pela tecnologia pulsada não foi significativa, e neste trabalho são propostas novas estratégias para reduzir a dose ocupacional no Laboratório de Cateterismo. / Abstract: Procedures of catheterism using fluoroscopy, as coronary angioplasty, are responsible for high doses of radiation (higher than conventional radiology), not only for patients but for the medical staff as well. The intensive use of X-rays increases radiological risks, as a consequence of cumulative exposition, for cardiologists and their teams. The main risks resulted from high doses of X-rays are: cancer, cataracts, malformations, and damage to the fetuses of pregnant women. The production of X-rays with pulsed technology, which is now available in many hospitals, implies a potential reduction of the radiation dose received by the medical staff. The amount of dose reduction is still controversy in literature, but some authors report reductions up to 70%. This work aimed at study occupational dose in the Cardiac Catheterism Laboratory of UNICAMP. The doses received by the medical staff on the continuous and pulsed fluoroscopy modes were compared, and the dose reduction consequent to the change of technologies in the Laboratory (from continuous to pulsed fluoroscopy) was measured. The reductions found for main and auxiliary physicians were 5.2% and 13.7%, respectively. For nurses, auxiliary nurses and technicians, the reductions were 7.5% to 8.2%. Moreover, the effective dose of each procedure for each professional was calculated and data analysis of the thermoluminescent dosimeters used in the whole Laboratory working periods was made. In conclusion, the dose reduction caused by pulsed technology was not significant, and new strategies to reduce occupational doses in the Catheterism Laboratory are proposed. / Mestrado / Engenharia Biomedica / Mestre em Engenharia Elétrica

Níveis sangüíneos de ciclosporina A (CSA) que minimizam a rejeição celular aguda (RCA) no transplante renal com o menor efeito tóxico vêm sendo o alvo de recentes pesquisas. A escolha de terapia imunossupressora com várias drogas permite o uso de doses mais baixas e com menores efeitos colaterais. Níveis de CSA necessários para evitar RCA podem variar com diferentes esquemas terapêuticos. Este estudo prospectivo realizado em um único centro avaliou a eficácia e segurança de dois diferentes níveis sangüíneos de CSA através da área sob a curva de doze horas (AUC 0-12). Cinqüenta e oito receptores de transplante renal foram randomizados para dois grupos, 25 para o grupo AUC0-12 alta (9000-11000 ng.h/mL) e 33 para o grupo AUC0-12 baixa (5000-7000 ng.h/mL). Após a introdução da CSA, a AUC foi avaliada nos dias 4, 7, 14, 21, 28, 42, 56, 70, 84 e 90. Os grupos foram comparáveis em idade, sexo, cor, tipo de doador, uso de indução e outras drogas imunossupressoras. Não houve diferença estatística na incidência de RCA. Foi realizada análise dos pacientes que apresentaram RCA em comparação com os pacientes livres de RCA. A análise de regressão logística mostrou que é necessária uma AUC 0-12 >- 9500 ng.h/mL com especificidade de 84% e sensibilidade de 76%, AUC 0-4 4000 ng.h/mL com especificidade de 91% e sensibilidade de 84% e C2 (concentração sangüínea na segunda hora pós- 6 dose) com especificidade de 92% e sensibilidade de 84% >- 1450 ng/ml, para predizer ausência de RCA. Quando utilizada terapia de indução, níveis mais baixos de AUC0-12, AUC0-4 e C2 (8160 3636 ng.h/ml, 3146 +- 262 ng.h/ml, 1043 +- 151 ng/mL, respectivamente) foram necessários para evitar RCA, em relação aos pacientes que não rejeitaram e não receberam indução (11072 +- 3809 ng.h/ml, 5403 +- 1782 ng.h/ml e 1816 +- 151ng/mL, respectivamente). Esses dados confirmam a necessidade de altos níves de CSA, na ausencia de indução para prevenção de RCA nos três primeiros meses pós-transplante renal e, o emprego de indução permite que níveis sangüíneos mais baixos de CSA sejam empregados com o intuito de prevenir RCA nos primeiros 90 dias após transplante renal / Multiple-drug therapy allows the use of lower doses with fewer side effects. Cyclosporin A (CSA) levels necessary to avoid rejection may vary with different drug combinations. To address this issue, fifty-eight kidney transplant recipients were randomized into two groups: 25 patients to the twelve-hour area under the curve (AUC0-12) high arm (9000-11000 ng.h/mL) and 33 to the AUC0-12 low arm (5000-7000 ng.h/mL). After CSA introduction, AUC0-12 was measured at days 4, 7, 14, 21, 28, 42, 56, 70, 84, and 90. The two groups were comparable regarding age, gender, race, donor type, induction therapy and other immunosuppressive drugs. There was no significant difference in the rate of acute cellular rejection episodes between the two groups. A retrospective analysis was carried out comparing rejectors to non-rejectors, related to induction therapy status. Logistic regression analysis revealed that an AUC0-12 >- 9000 ng.h/mL or AUC0-4 >-4000ng.h/mL or two-hour post-dose cyclosporin level (C2) of >- 1450 ng/mL predicted a rejection-free course. Lower levels of C2 and AUC 0-4 (1043 +-151 ng/mL and 3146 +- 262ng/mL, respectively) were required in non-rejecting patients when induction therapy was used

Submitted by Gabriela Lopes (gmachadolopesufpel@gmail.com) on 2016-09-27T14:16:41Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Raque Bartz Kneib.pdf: 709774 bytes, checksum: ed9b7474064e09348586e51c9221a9fa (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2016-09-28T17:06:46Z (GMT) No. of bitstreams: 2 Dissertação Raque Bartz Kneib.pdf: 709774 bytes, checksum: ed9b7474064e09348586e51c9221a9fa (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-28T17:06:46Z (GMT). No. of bitstreams: 2 Dissertação Raque Bartz Kneib.pdf: 709774 bytes, checksum: ed9b7474064e09348586e51c9221a9fa (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2014-07-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / A batata é o terceiro principal alimento produzido no mundo, e é um dos cultivos mais promissores para suprimir a fome em países em desenvolvimento. Cerca de 40 viroses infectam a cultura da batata, entre estas, o Potato virus Y (PVY) é, atualmente, o que causa maior impacto negativo na cultura. O PVY é transmitido de diversas formas, todas com controle e manejo deficitários, tornando a resistência genética a medida de controle mais eficaz. Esta resistência é controlada pelos genes Ry encontrados em espécies silvestres de batata. Marcadores do tipo SCAR (Sequence Characterized Amplified Region), os quais amplificam a região que contém o gene Ry, foram desenvolvidos e estão disponíveis para uso pelos programas de melhoramento de batata. Este trabalho foi realizado com o objetivo de aumentar a eficiência dos programas de melhoramento de batata em relação à resistência ao PVY fazendo uso da seleção assistida por marcadores moleculares. A dissertação foi dividida em dois capítulos. No primeiro, visando estimar a dosagem alélica do gene Ry e selecionar clones com múltiplas cópias do gene Ry para serem usados como genitores no programa de melhoramento de batata, foram genotipadas sete famílias clonais, envolvendo cinco genitores com resistência ao PVY, utilizando os marcadores SCAR RYSC3 e M45. Para o gene Ryadg, com base no marcador RYSC 3, dos cinco genitores resistentes ao PVY avaliados, quatro, C1883-22-97, C2372-02-02, C2388-01-02, e MB9846-1, são simplex, e o genitor C2389-01-02 é duplex. Para o gene Rysto, com base no marcador M45, dois genitores, C2388-01-02 e MB9846-1, são simplex, e o genitor C2389-01-02 é duplex. Para os genitores C1883-22-97 e C2372-02-02, as frequências observadas de presença do gene Rysto, nas progênies avaliadas, não se adequaram estatisticamente a nenhuma das constituições genotípicas propostas. No segundo capítulo, com objetivo de identificar germoplasma de batata com resistência extrema ao vírus Y associada aos componentes da aparência e do rendimento de tubérculos, além verificar as associações entre esses caracteres, foram avaliados clones portadores do gene Ry, oriundos de oito combinações genéticas distintas. As combinações genéticas C2389-01-02 x Asterix, e, BRS Ana x C1883-22-97, mostraram maior potencial para serem exploradas visando agregar a resistência ao vírus Y aos caracteres desejáveis de rendimento e de aparência de tubérculo. O grau de correlação entre caracteres indica fortíssima e direta associação entre aparência geral e aspereza de tubérculo; forte e direta associação da intensidade da cor de película com aspereza e aparência geral de tubérculo, entre número e massa média de tubérculo, entre massa média e cor da película, e entre massa total e número total de tubérculos; e forte e inversa associação de formato com cor da polpa, cor da película e massa média de tubérculos. Os resultados encontrados no nosso estudo mostraram que os marcadores moleculares RYSC3 e M45 são uma importante ferramenta para ser usada pelos programas de melhoramento de batata visando acelerar o processo de desenvolvimento de cultivares com resistência ao PVY. / Potato is the third main food crop in the world, and is one of the most promising crop to suppress hunger in developing countries. From the 40 viruses which infect potato growing fields, Potato virus Y (PVY) is currently considered the most important one. PVY is transmitted by several ways, all of them with limited control, begin genetic resistance the main way to control this important disease controlled by Ry genes. Molecular markers, which amplify the region containing Ry gene have been developed and are available to be used by potato breeding. This work was developed with the aim of increasing the efficiency of potato breeding programs for resistance to PVY making use of molecular assisted selection. The dissertation is divided into two chapters. In the first chapter, in order to estimate allelic dosage of Ry genes in clones used as genitors in the breeding program, progenies from seven families were genotyped with the markers RYSC3 and M45. For Ryadg gene, based on the marker RYSC, from the five PVY resistant parents analysed, four are simplex, C1883-22-97, C2372-02-02, C2388-01-02 and MB9846-1, and one is duplex, C2389- 01-02. For Rysto gene, based on the marker M45, both parents, C2388-01-02 and MB9846-1, are simplex, and the parent C2389-01-02 is duplex. For the C1883-22-97 and C2372-02-02, it was not possible to estimate the allelic dosage of the Rysto gene. In the second chapter, in order to identify germplasm with extreme resistance to PVY associated to desirable agronomic traits, clones carrying the Ry gene, belonging from eight different genetic combinations, were evaluated for characteres related to tuber appearance and yield. The genetic combinations C2389-01-02 x Asterix and BRS Ana x C1883-22-97 showed good potential to be exploited in order to add resistance to virus Y to traits related to yield and tuber appearance. The correlation between traits indicates very strong and direct association between tuber general appearance and roughness of tuber; strong and direct association of the intensity of the periderm color and tuber general appearance; between number of tubers per plant and average tuber weight; between average tuber weight and intensity of the periderm color and between the total mass of tubers per plant and total number of tubers per plant. Also, strong and inverse associations between tuber shape and flesh color and between periderm color and average tuber weight were detected. The results of our study showed that the molecular markers RYSC3 and M45 are important tools to be used by potato breeding programs to accelerate the development of cultivars with resistance to PVY.

Radiography is a common radiologic investigation despite abundant evidence of its limited diagnostic value. On the other hand, computed tomography (CT) has a high diagnostic value and is widely considered to be among the most important advances in medicine. However, CT exposes patients to a higher radiation dose and it might therefore not be acceptable simply to replace radiography with CT, despite the powerful diagnostic value of this technique. At the expense of reduced CT image quality, which could be adjusted to the diagnostic needs, low-dose CT of abdomen and lumbar spine can be performed at similar dose to radiography. The aim of the current thesis project was to evaluate low-dose CT of the abdomen and lumbar spine and to compare it with radiography. The hypothesis was that CT would give better image quality and diagnostic information compared to radiography at similar dose levels. Firstly, the diagnostic accuracy of low-dose CT of the abdomen was evaluated. Results showed that low-dose CT of abdomen has a high sensitivity and specificity compared to radiography, i.e., it has higher diagnostic accuracy. Similar results were obtained from our systematic review. Secondly, in a phantom study, an ovine phantom was scanned at various CT settings. The image quality was evaluated to obtain a protocol for the optimal settings for low-dose CT of lumbar spine at 1 mSv. This new protocol was then used in a clinical study to assess the image quality of low-dose CT of the lumbar spine and compare it to radiography. Results showed that low-dose CT has significantly better image quality than radiography. Finally, the impact of Iterative reconstruction (IR) on image quality of lumbar spine CT was tested. Iterative reconstruction is a recent CT technique aimed to reduce radiation dose and/or improve image quality. The results showed that the use of medium strength IR levels in the reconstruction of CT image improves image quality compared to filtered back projection. In conclusion, low-dose CT of the abdomen and lumbar spine, at about 1 mSv, has better image quality and gives diagnostic information compared to radiography at similar dose levels and it could therefore replace radiography.

Carbamazepine (CBZ) is a first-line drug used for the treatment of partial and tonic-clonic seizures. It is also the drug of choice for use during pregnancy and recommended for the treatment of seizure disorders in children. CBZ possesses the ability to induce metabolism of drugs that are transformed in the liver and has the unique ability to induce its own metabolism by a phenomenon known as ‘auto- induction’, where its biological half-life is significantly reduced during chronic administration. Large doses of CBZ are often prescribed as daily divided doses and this often adversely affects patient compliance, with the result that therapy is ineffective. A sustained-release dosage form containing CBZ is currently marketed as Tegretol® CR and the development of a generic product would provide patients with an equivalent product with a similar dosing frequency, at a reduced cost. Therefore, the development of a polymer-based matrix tablet was undertaken to produce a sustained-release dosage form of CBZ, since these dosage forms are relatively simple and cheap to produce when compared to other, more sophisticated forms of sustained-release technology. Preformulation studies were conducted to assess moisture content of excipients and dosage forms and to identify possible incompatibilities between CBZ and potential formulation excipients. Furthermore, studies were conducted to assess the potential for polymorphic transitions to occur during manufacture. Stability testing was conducted to assess the behaviour of the dosage forms under storage conditions that the product may be exposed to. Dissolution testing was undertaken using USP Apparatus 3, which allowed for a more realistic assessment and prediction of in vivo drug release rates. Samples were analysed using a high performance liquid chromatographic method that was developed and validated for the determination of CBZ. Tablets were manufactured by wet granulation and direct compression techniques, and the resultant drug release profiles were evaluated statistically by means of the f1 and f2 difference and similarity factors. The f2 factor was incorporated as an assessment criterion in the design of an artificial neural network that was used to predict drug release profiles and formulation composition. A direct compression tablet formulation was successfully adapted from a prototype wet granulation matrix formulation and a number of formulation variables were assessed to establish their effect(s) on the dissolution rate profile of CBZ that resulted from testing of the dosage forms. The particle size grade of CBZ was also investigated and it was ascertained that fine particle size grade CBZ showed improved drug release profiles when compared to the coarse grade CBZ which was desirable, since CBZ is a highly water insoluble compound. Furthermore, the impact of the viscosity grade and proportion of rate-controlling polymer, viz., hydroxypropyl methylcellulose was also investigated for its effect on drug release rates. The lower viscosity grade was found to be more appropriate for use with CBZ. The type of anti-frictional agent used in the formulations did not appear to affect drug release from the polymeric matrix tablets, however specific compounds may have an effect on the physical characteristics of the polymeric tablets. The resultant formulations did not display zero-order drug release kinetics and a first-order mathematical model was developed to provide an additional resource for athematical analysis of dissolution profiles. An artificial neural network was designed, developed and applied to predict dissolution rate profiles for formulation. Furthermore, the network was used to predict formulation compositions that would produce drug release profiles comparable to the reference product, Tegretol® CR. The formulation composition predicted by the network to match the dissolution profile of the innovator product was manufactured and tested in vitro. The formulation was further manipulated, empirically, so as to match the in vitro dissolution rate profile of Tegretol® CR, more completely. The test tablets that were produced were tested in two health male volunteers using Tegretol® CR 400mg as the reference product. The batch used for this “proof of concept” biostudy was produced in accordance with cGMP guidelines and the protocol in accordance with ICH guidelines. The test matrix tablets revealed in vivo bioavailability profiles for CBZ, however, bioequivalence between the test and reference product could not be established. It can be concluded that the polymeric matrix CBZ tablets have the potential to be used as a twice-daily dosage form for the treatment of relevant seizure disorders.