Utilização de modelos farmacocinéticos de base fisiológica no desenvolvimento de novos fármacos

Nas últimas décadas tem-se verificado um aumento bastante acentuado da utilização de modelos in vitro e in silico para a obtenção de dados que permitem aumentar a eficácia de programas de desenvolvimento de novos fármacos. Actualmente são utilizados dois tipos de modelos para descrever a farmacocinética de compostos químicos em função do tempo: modelos empíricos farmacocinéticos e modelos farmacocinéticos baseados na fisiologia (PBPK). Modelos PBPK assumem que o corpo humano interage com os compostos químicos como um sistema integrado, pelo que um evento que ocorre numa zona do corpo poderá influenciar um evento a ocorrer noutra zona, aparentemente distinta. Estes modelos assumem que o organismo humano é constituído por “compartimentos” que representam fisiologicamente os órgãos, tecidos e outros espaços fisiológicos. Para a correcta utilização destes modelos é necessário determinar a estrutura do modelo e as suas características, escrever equações que o caracterizem, bem como definir e estimar os parâmetros deste. Estes modelos têm vindo a ser usados no campo toxicológico e farmacêutico cada vez com maior frequência. No futuro poder-se-ão transformar numa ferramenta universal.

Queda de pressão estática por meio de uma coluna de noz macadâmia

As unidades de beneficiamento de macadâmia adotam silos secadores distintos, para cada etapa de secagem, a fim de garantir a manutenção da qualidade do produto pela redução da umidade a níveis desejáveis. Diante da necessidade de quantificar a resistência apresentada pelas nozes, submetidas a diferentes fluxos de ar durante a secagem, bem como avaliar a possibilidade de utilização de modelos empíricos, que estimem o gradiente de pressão a partir da vazão de ar, conduziram-se vários testes em laboratório para obtenção de dados experimentais e ajuste de modelos. Frutos de macadâmia (M. integrifolia), com umidade de 0,11 b.s., após limpeza e classificação, foram colocados no interior de um protótipo constituído por uma coluna de chapa galvanizada (com tomadas para medição da pressão estática), plenum e ventilador, sendo submetidos a diferentes fluxos de ar. Os testes consistiram de três medidas por profundidade, para cada um dos três lotes de nozes, perfazendo um total de nove medidas de pressão estática por profundidade na coluna. Os resultados obtidos permitiram concluir que os fluxos de ar testados apresentaram efeito significativo sobre a queda de pressão estática na coluna de macadâmia, a qual aumentou linearmente com a profundidade. Os dados experimentais ajustaram-se muito bem aos modelos de Shedd e Hunter, sugerindo sua boa aplicabilidade para a macadâmia.

Thermal properties of passion fruit juice as affected by temperature and water content

The specific heat, thermal conductivity and density of passion fruit juice were experimentally determined from 0.506 to 0.902 (wet basis) water content and temperatures from 0.4 to 68.8C. The experimental results were compared with existing and widely used models for the thermal properties. In addition, based on empiric equations from literature, new simple models were parameterized with a subset of the total experimental data. The specific heat and thermal conductivity showed linear dependency on water content and temperature, while the density was nonlinearly related to water content. The generalized predictive models were considerably good for this product but the empiric, product-specific models developed in the present work yield better predictions. Even though the existing models showed a moderate accuracy, the new simple ones would be preferred, because they constitute an easier and direct way of evaluating the thermal properties of passion fruit juice, requiring no information about the chemical composition of the product, and a reduced time of the estimation procedure, as the new empiric models are described in terms of only two physical parameters, the water content and the temperature. © Copyright 2005, Blackwell Publishing All Rights Reserved.

Characterization of the methanol recovery process at Prio Biocombustíveis S. A.

In a industrial environment, to know the process one is working with is crucial to ensure its good functioning. In the present work, developed at Prio Biocombustíveis S.A. facilities, using process data, collected during the present work, and historical process data, the methanol recovery process was characterized, having started with the characterization of key process streams. Based on the information retrieved from the stream characterization, Aspen Plus® process simulation software was used to replicate the process and perform a sensitivity analysis with the objective of accessing the relative importance of certain key process variables (reflux/feed ratio, reflux temperature, reboiler outlet temperature, methanol, glycerol and water feed compositions). The work proceeded with the application of a set of statistical tools, starting with the Principal Components Analysis (PCA) from which the interactions between process variables and their contribution to the process variability was studied. Next, the Design of Experiments (DoE) was used to acquire experimental data and, with it, create a model for the water amount in the distillate. However, the necessary conditions to perform this method were not met and so it was abandoned. The Multiple Linear Regression method (MLR) was then used with the available data, creating several empiric models for the water at distillate, the one with the highest fit having a R2 equal to 92.93% and AARD equal to 19.44%. Despite the AARD still being relatively high, the model is still adequate to make fast estimates of the distillate’s quality. As for fouling, its presence has been noticed many times during this work. Not being possible to directly measure the fouling, the reboiler inlet steam pressure was used as an indicator of the fouling growth and its growth variation with the amount of Used Cooking Oil incorporated in the whole process. Comparing the steam cost associated to the reboiler’s operation when fouling is low (1.5 bar of steam pressure) and when fouling is high (reboiler’s steam pressure of 3 bar), an increase of about 58% occurs when the fouling increases.

Constructing and evaluating alternative prediction models for identifying clinically relevant cases in an STD clinic

Thesis (Master's)--University of Washington, 2016-06

Application of Mixture Models to Survival Data

Survival models are being widely applied to the engineering field to model time-to-event data once censored data is here a common issue. Using parametric models or not, for the case of heterogeneous data, they may not always represent a good fit. The present study relays on critical pumps survival data where traditional parametric regression might be improved in order to obtain better approaches. Considering censored data and using an empiric method to split the data into two subgroups to give the possibility to fit separated models to our censored data, we’ve mixture two distinct distributions according a mixture-models approach. We have concluded that it is a good method to fit data that does not fit to a usual parametric distribution and achieve reliable parameters. A constant cumulative hazard rate policy was used as well to check optimum inspection times using the obtained model from the mixture-model, which could be a plus when comparing with the actual maintenance policies to check whether changes should be introduced or not.