Aplicação do Seis Sigma na avaliação da inexatidão dos resultados laboratoriais do parâmetro cortisol sérico

No desenvolvimento deste caso de estudo, dentro do Programa Nacional de Avaliação Externa da Qualidade do Instituto Nacional de Saúde Doutor Ricardo Jorge utilizou-se o Seis Sigma como metodologia e como métrica, de maneira a estruturar de forma intuitiva a sua aplicação na resolução de problemas e definir o principal objetivo. Como metodologia, o Seis Sigma recorre a diversas técnicas e ferramentas da qualidade, que visam a melhoria contínua de procedimentos. Enquanto métrica, o Seis Sigma apresenta uma meta a atingir para a qualidade. O ideal seria atingir-se a meta dos Seis Sigma, que significa 3,4 defeitos por milhão de oportunidades (taxa de defeitos de um determinado procedimento). Para reduzir a variabilidade de resultados entre laboratórios, referentes ao parâmetro Cortisol Sérico, aplicou-se o ciclo DMAIC (Define – Measure – Analyze – Improve – Control), a que correspondem cinco etapas diferentes. Em cada uma destas etapas utilizam-se as técnicas e ferramentas da qualidade, como referido anteriormente acerca do Seis Sigma enquanto metodologia, com o objetivo de melhorar processos. Inicia-se a primeira etapa com a identificação do problema e finaliza-se a última com o controlo e monitorização dos efeitos provocados pelas ações de melhoria implementadas. O objetivo dos programas de Avaliação Externa da Qualidade do Programa Nacional de Avaliação Externa da Qualidade é avaliar a performance quanto à variabilidade/uniformidade de resultados entre os laboratórios participantes. É de extrema importância a harmonização de resultados clínicos entre laboratórios, pois são estes resultados que fornecem informações ao profissional de saúde, sobre o estado de saúde do paciente, auxiliando no diagnóstico, tratamento e controlo de doenças. Caso isto não aconteça, será um fator crítico que pode fazer a diferença na saúde pública. Foram identificadas as causas de erros sistemáticos, causas de inexatidão laboratorial, a nível de métodos, equipamentos, reagentes e calibradores utilizados em laboratório e implementadas ações de melhoria mais relevantes. No final obteve-se um nível de qualidade sigma superior ao inicial, tal como tinha sido previsto nos objetivos. O nível da qualidade deve ser controlado ao longo do tempo, com o objetivo de identificar novas anomalias e melhorar continuamente.

Phage display as a tool for generation of bio-therapeutic agents for breast cancer

Notch is a conserved signalling pathway, which plays a crucial role in a multiple cellular processes such as stem cell self-renewal, cell division, proliferation and apoptosis. In mammalian, four Notch receptors and five ligands are described, where interaction is achieved through their extracellular domains, leading to a transcription activation of different target genes. Increased expression of Notch ligands has been detected in several types of cancer, including breast cancer suggesting that these proteins represent possible therapeutic targets. The goal of this work was to generate quality protein targets and, by phage display technology, select function-blocking antibodies specific for Notch ligands. Phage display is a powerful technique that allows the generation of highly specific antibodies to be used for therapeutics, and it has also proved to be a reliable approach in identifying and validating new cancer-related targets. Also, we aimed at solving the tri-dimensional structure of the Notch ligands alone and in complex with selected antibodies. In this work, the initial phase focused on the optimization of the expression and purification of a human Delta-like 1 ligand mutant construct (hDLL1-DE3), by refolding from E. coli inclusion bodies. To confirm the biological activity of the produced recombinant protein cellular functional studies were performed, revealing that treatment with hDLL1-DE3 protein led to a modulation of Notch target genes. In a second stage of this study, Antibody fragments (Fabs) specific for hDLL1-DE3 were generated by phage display, using the produced protein as target, in which one good Fab candidate was selected to determine the best expression conditions. In parallel, multiple crystallization conditions were tested with hDLL1-DE3, but so far none led to positive results.

Exposição profissional ao chumbo : utilização do doseamento do ácido delta-aminolevulínico urinário na vigilância médica dos trabalhadores

RESUMO - O ácido δ-aminolevulínico presente na urina (ALA-U) é generalizadamente aceite como um indicador adequado para a vigilância de saúde de trabalhadores expostos a chumbo. A necessidade ou não de recurso a colheitas de urina de 24 horas para um correcto doseamento desse metabolito tem, entretanto, suscitado algumas dúvidas. Num estudo abrangendo 45 indivíduos (28 dos quais profissionalmente expostos a chumbo inorgânico) efectuou-se o doseamento do ALA em urinas colhidas durante 24 horas e em urina de colheita única. Confirmou-se a existência de uma boa correlação entre o ALA urinário e a plumbemia e que o tipo de colheita de urina efectuada não influencia significativamente essa associação. Contudo, pela apreciação das variações interindividuais registadas, parece aconselhável que seja privilegiado o doseamento em urinas de 24 horas.

Development and modulation of magnetic responsive supported ionic liquid membranes

The work presented in this thesis aims at developing a new separation process based on the application of supported magnetic ionic liquid membranes, SMILMs, using magnetic ionic liquids, MILs. MILs have attracted growing interest due to their ability to change their physicochemical characteristics when exposed to variable magnetic field conditions. The magnetic responsive behavior of MILs is thus expected to contribute for the development of more efficient separation processes, such as supported liquid membranes, where MILs may be used as a selective carrier. Driven by the MILs behavior, these membranes are expected to switch reversibly their permeability and selectivity by in situ and non-invasive adjustment of the conditions (e.g. intensity, direction vector and uniformity) of an external applied magnetic field. The development of these magnetic responsive membrane processes were anticipated by studies, performed along the first stage of this PhD work, aiming at getting a deep knowledge on the influence of magnetic field on MILs properties. The influence of the magnetic field on the molecular dynamics and structural rearrangement of MILs ionic network was assessed through a 1H-NMR technique. Through the 1H-NMR relaxometry analysis it was possible to estimate the self-diffusion profiles of two different model MILs, [Aliquat][FeCl4] and [P66614][FeCl4]. A comparative analysis was established between the behavior of magnetic and non-magnetic ionic liquids, MILs and ILs, to facilitate the perception of the magnetic field impact on MILs properties. In contrast to ILs, MILs show a specific relaxation mechanism, characterized by the magnetic dependence of their self-diffusion coefficients. MILs self-diffusion coefficients increased in the presence of magnetic field whereas ILs self-diffusion was not affected. In order to understand the reasons underlying the magnetic dependence of MILs self-diffusion, studies were performed to investigate the influence of the magnetic field on MILs’ viscosity. It was observed that the MIL´s viscosity decreases with the increase of the magnetic field, explaining the increase of MILs self-diffusion according to the modified Stokes- Einstein equation. Different gas and liquid transport studies were therefore performed aiming to determine the influence of the magnetic behavior of MILs on solute transport through SMILMs. Gas permeation studies were performed using pure CO2 andN2 gas streams and air, using a series of phosphonium cation based MILs, containing different paramagnetic anions. Transport studies were conducted in the presence and absence of magnetic field at a maximum intensity of 1.5T. The results revealed that gas permeability increased in the presence of the magnetic field, however, without affecting the membrane selectivity. The increase of gas permeability through SMILMs was related to the decrease of the MILs viscosity under magnetic field conditions.(...)

Impact of Black-Scholes assumptions on Delta Hedging

In this work we are going to evaluate the different assumptions used in the Black- Scholes-Merton pricing model, namely log-normality of returns, continuous interest rates, inexistence of dividends and transaction costs, and the consequences of using them to hedge different options in real markets, where they often fail to verify. We are going to conduct a series of tests in simulated underlying price series, where alternatively each assumption will be violated and every option delta hedging profit and loss analysed. Ultimately we will monitor how the aggressiveness of an option payoff causes its hedging to be more vulnerable to profit and loss variations, caused by the referred assumptions.