Determinação da protoporfirina-zinco por hematofluorímetro portátil : investigação sobre validade dos dados

RESUMO - A determinação da protoporfirina-zinco (PPZ) por meio de um hematofluorímetro portátil vem sendo descrita como apreciável contributo no contexto da vigilância de saúde de trabalhadores expostos a chumbo. Num estudo abrangendo 178 indivíduos (cerca de 60% dos quais referenciados como profissionalmente expostos àquele metal) foi testado o método e a técnica propostos e estudada a validade dos resultados assim obtidos. Concluiu-se que a determinação da PPZ em sangue colhido por punção capilar, por meio de hematofluorímetro portátil, oferece resultados fiáveis, permitindo, deste modo, o recurso a esta técnica de fácil execução e baixo custo.

Exploring Parallels Between Molecular Changes Induced in PNS by Aging and Demyelinating Neuropathies

The peripheral nervous system (PNS) is involved in many age-dependent neurological deficits, including numbness, pain, restless legs, trouble with walking and balance that are commonly found in the elderly. These symptoms generally result from demyelination and/or loss of axonal integrity. However, the precise identity of age-regulated molecular changes in either neuronal or glial compartments of the nerve is unclear. Interestingly, these deficiencies are also present in inherited neuropathies, where the expressivity of the rapid and early onset phenotypes is undeniably more severe than in normal aging. Nevertheless, especially the molecular changes underlying loss of axonal integrity in neuropathy condition are also poorly understood. To unravel molecular mechanisms affected by PNS aging, we used wildtype mice at 17 time-points from day of birth until senescence (28 months-old). For the neuropathy study, we focused on 56 day-old Schwann cell-specific neuropathy-inducing mutants, MPZCre/1/ LpinfE2-3/fE2-3 and MPZCre/1/ScapfE1/fE1 mice, that have, at this age, already developed neuropathic symptoms. Transcriptomes of dissected Schwann cell-containing endoneurium or sensory neuron-containing dorsal root ganglia have been analyzed throughout time or genotypes, using Illumina Bead Chips. Following data validation, we identified groups of differentially expressed genes in the development, aging and in the neuropathic mutants, in both glial and neuronal compartments. We detected substantial differences in the dynamics of changes in gene expression during development and aging between these two compartments. Furthermore, considering the above-mentioned phenotypic similarities, we integrated aging and mutant data. Interestingly, we observed that there are some parallels at the molecular level between processes involved in aging, which leads to less severe and more progressive PNS alterations, and in the rapid onset peripheral neuropathies. Apart from helping the understanding of molecular alterations underlying age-related PNS phenotypes, this data should also contribute to the identification of pathways that could be used as targets for therapeutical approaches to prevent complications associated with both aging and inherited forms of neuropathies.

Rôles des polymorphismes génétiques dans la détermination de la dose individuelle de la warfarine chez les patients traités avec de l’amiodarone

Introduction : Bien que la pratique de l’usage de la warfarine se soit améliorée au cours de la dernière décennie, aucune recommandation claire basée sur le dosage de l’amiodarone n’a été jusqu’à maintenant standardisée, ce qui représente un grand obstacle pour les cliniciens. La warfarine a un index thérapeutique étroit nécessitant un suivi régulier et un ajustement individuel de la posologie, ceci afin de déterminer la dose thérapeutique, tout en prévenant les effets secondaires qui pourraient être fatals dans certains cas. La variabilité interindividuelle de la réponse à la warfarine dépend de plusieurs facteurs, dont l’âge, le sexe, le poids, l’alimentation et l’interaction médicamenteuse, mais ceux-ci n’expliquent que partiellement les différences de sensibilité à la warfarine. Les polymorphismes des gènes CYP2C9 et VKORC1 jouent un rôle important dans la réponse à la warfarine et expliquent jusqu’à 50% de la variabilité des doses. L’utilisation d’antiarythmiques telle l’amiodarone peut accentuer considérablement l’effet de la warfarine et nécessite généralement une diminution de 30 à 50% de la dose de la warfarine. Aucune étude à ce jour n’a tenté de déterminer l’utilité du génotypage des polymorphismes des gènes CYP2C9 et VKORC1 chez les patients sous traitement combiné de warfarine et amiodarone. Objectif : Notre étude a pour objectif tout d’abord de déterminer si des facteurs génétiques influencent la première dose de stabilisation de la warfarine chez les patients en FA après l’introduction de l’amiodarone. Nous allons également tenter de confirmer l’association préalablement rapportée entre les facteurs génétiques et la première dose de stabilisation de warfarine dans notre population à l’étude. Méthodes : Un devis de cohorte rétrospective de patients qui fréquentaient la clinique d'anticoagulothérapie de l’Institut de cardiologie de Montréal entre le 1er janvier 2007 et le 29 février 2008 pour l’ajustement de leur dose selon les mesures d'INR. Au total, 1615 patients ont été recrutés pour participer à cette étude de recherche. Les critères de sélection des patients étaient les patients avec fibrillation auriculaire ou flutter, ayant un ECG documenté avec l'un de ces deux diagnostics et âgé de moins de 67 ans, en raison d’une moindre comorbidité. Les patients souffrant d’insuffisance hépatique chronique ont été écartés de l’étude. Tous les patients devaient signer un consentement éclairé pour leur participation au projet et échantillon de sang a été pri pour les tests génétiques. La collecte des données a été effectuée à partir du dossier médical du patient de l’Institut de cardiologie de Montréal. Un formulaire de collecte de données a été conçu à cet effet et les données ont ensuite été saisies dans une base de données SQL programmée par un informaticien expert dans ce domaine. La validation des données a été effectuée en plusieurs étapes pour minimiser les erreurs. Les analyses statistiques utilisant des tests de régression ont été effectuées pour déterminer l’association des variants génétiques avec la première dose de warfarine. Résultats : Nous avons identifié une association entre les polymorphismes des gènes CYP2C9 et VKORC1 et la dose de la warfarine. Les polymorphismes génétiques expliquent jusqu’à 42% de la variabilité de dose de la warfarine. Nous avons également démontré que certains polymorphismes génétiques expliquent la réduction de la dose de warfarine lorsque l’amiodarone est ajoutée à la warfarine. Conclusion : Les travaux effectués dans le cadre de ce mémoire ont permis de démontrer l’implication des gènes CYP2C9 et VKORC1 dans la réponse au traitement avec la warfarine et l’amiodarone. Les résultats obtenus permettent d’établir un profil personnalisé pour réduire les risques de toxicité, en permettant un dosage plus précis de la warfarine pour assurer un meilleur suivi des patients. Dans le futur, d’autres polymorphismes génétiques dans ces gènes pourraient être évalués pour optimiser davantage la personnalisation du traitement.

Validación de la escala de calidad de vida MELASQoL, en un grupo de pacientes colombianas con melasma

El objetivo del estudio consistió en validar la escala de calidad de vida MELASQOL al idioma español en un grupo de mujeres colombianas con melasma. La muestra de estudio correspondió a 80 pacientes, las cuales asistieron a consulta de medicina estética de la IPS Quinta de Mutis de la Universidad del Rosario, por presentar melasma, se les pidió su participación y datos de ubicación telefónica para aplicarles la escala traducida al idioma español (MELASQOL-t) mediante la guía QoLMs (guidelines for cross-cultural adaptation of health-related), para validación de escalas propuesta por la OMS, en un segundo contacto vía telefónica. Una vez obtenida la respuesta telefónica a la escala de todas las pacientes, se procesaron los datos para validación mediante análisis estadístico; bajo los parámetros de congruencia interna, validez de criterio y reproducibilidad. Solo con una pequeña parte (n=10) de la muestra se efectuó un tercer contacto telefónico con fines estadísticos. El promedio de edad del grupo estudiado correspondió a 40±12 años, el estrato socioeconómico de mayor frecuencia fue el tres (3), con mayor distribución en el nivel educativo de estudios universitarios completos, se obtuvieron para los criterios de validación los siguientes datos: congruencia interna con a-cronbach=0.88, validez con rs=0.70-p<0.001 y reproducibilidad con coeficiente de correlación intraclase =0.959 (IC 95%: 0.986, p<0.001). La conclusión principal fue que la escala MELASQOL traducida al idioma español se validó bajo criterios adecuados, obteniendo buenos índices para medir calidad de vida en el grupo de mujeres colombianas con melasma estudiadas.

Spatial analysis of the error in a model of soil nitrogen

Models of the dynamics of nitrogen in soil (soil-N) can be used to aid the fertilizer management of a crop. The predictions of soil-N models can be validated by comparison with observed data. Validation generally involves calculating non-spatial statistics of the observations and predictions, such as their means, their mean squared-difference, and their correlation. However, when the model predictions are spatially distributed across a landscape the model requires validation with spatial statistics. There are three reasons for this: (i) the model may be more or less successful at reproducing the variance of the observations at different spatial scales; (ii) the correlation of the predictions with the observations may be different at different spatial scales; (iii) the spatial pattern of model error may be informative. In this study we used a model, parameterized with spatially variable input information about the soil, to predict the mineral-N content of soil in an arable field, and compared the results with observed data. We validated the performance of the N model spatially with a linear mixed model of the observations and model predictions, estimated by residual maximum likelihood. This novel approach allowed us to describe the joint variation of the observations and predictions as: (i) independent random variation that occurred at a fine spatial scale; (ii) correlated random variation that occurred at a coarse spatial scale; (iii) systematic variation associated with a spatial trend. The linear mixed model revealed that, in general, the performance of the N model changed depending on the spatial scale of interest. At the scales associated with random variation, the N model underestimated the variance of the observations, and the predictions were correlated poorly with the observations. At the scale of the trend, the predictions and observations shared a common surface. The spatial pattern of the error of the N model suggested that the observations were affected by the local soil condition, but this was not accounted for by the N model. In summary, the N model would be well-suited to field-scale management of soil nitrogen, but suited poorly to management at finer spatial scales. This information was not apparent with a non-spatial validation. (c),2007 Elsevier B.V. All rights reserved.

Ferramenta computacional para dimensionamento e avaliação de desempenho de sistemas fotovoltaicos conectados à rede elétrica

Esta dissertação apresenta a utilização alguns modelos matemáticos disponíveis na literatura para representar as etapas de processamento da energia em um Sistema Fotovoltaico Conectado à Rede Elétrica (SFCR). Além disso, propõem-se dois modelos representativos do comportamento da potência elétrica em situações de limitação de potência do inversor e das perdas elétricas em função do carregamento. Todas as modelagens estão implementadas computacionalmente no ambiente GUIDE do MATLAB, o que permite a análise, auxilia no dimensionamento e viabiliza a simulação da operacionalidade e consequente contribuição energética de SFCRs com diferentes tamanhos relativos. No trabalho ainda é mostrada a interface da ferramenta computacional desenvolvida e a validação dos dados gerados pelo programa com dados medidos experimentalmente de SFCRs, a qual evidencia a eficácia dos modelos utilizados e a melhora na precisão. Ao final são mostradas estimativas energéticas para cinco cidades brasileiras, além de exemplos de análise dos dados gerados pela ferramenta computacional.

Desarrollo de un sistema de arañas inteligentes para la extracción de datos de empresas

El presente proyecto de fin de grado es uno de los resultados generados en un proyecto de financiación privada por parte de Telefónica consistente en el desarrollo y posterior implantación de un sistema para minería de datos de empresas presentes en Internet. Este TFG surge a partir de un proyecto que el grupo de investigación AICU-LABS (Mercator) de la UPM ha desarrollado para Telefónica, y tiene como elemento principal el desarrollo de Agentes web (también llamados robots software, “softbots” o “crawlers”) capaces de obtener datos de empresas a partir de sus CIF a través de internet. El listado de empresas nos los proporciona Telefónica, y está compuesto por empresas que no son clientes de Telefónica en la actualidad. Nuestra misión es proporcionarles los datos necesarios (principalmente teléfono, correo electrónico y dirección de la empresa) para la creación de una base de datos de potenciales clientes. Para llevar a cabo esta tarea, se ha realizado una aplicación que, a partir de los CIF que nos proporcionan, busque información en internet y extraiga aquella que nos interese. Además se han desarrollado sistemas de validación de datos para ayudarnos a descartar datos no válidos y clasificar los datos según su calidad para así maximizar la calidad de los datos producidos por el robot. La búsqueda de datos se hará tanto en bases de datos online como, en caso de localizarlas, las propias páginas web de las empresas. ABSTRACT This Final Degree Project is one of the results obtained from a project funded by Telefónica. This project consists on the development and subsequent implantation of a system which performs data mining on companies operating on the Internet. This document arises from a project the research group AICU-LABS (Mercator) from the Universidad Politécnica de Madrid has developed for Telefónica. The main goal of this project is the creation of web agents (also known as “crawlers” or “web spiders”) able to obtain data from businesses through the Internet, knowing only their VAT identification number. The list of companies is given by Telefónica, and it is composed by companies that are not Telefónica’s customers today. Our mission is to provide the data required (mainly phone, email and address of the company) to create a database of potential customers. To perform this task, we’ve developed an application that, starting with the given VAT numbers, searches the web for information and extracts the data sought. In addition, we have developed data validation systems, that are capable of discarding low quality data and also sorting the data according to their quality, to maximize the quality of the results produced by the robot. We’ll use both the companies’ websites and external databases as our sources of information.

A conceptual framework for enterprise management

This paper reports on the theoretical foundations and the practical reasons for the increasing popularity of the enterprise management perspective. Theoretical foundations are given that discuss vertically integrated, virtual and extended enterprises in terms of endogenous and exogenous factors, and the tensions that these create. An exploratory study in the German automotive industry using inductive grounded theory was conducted, involving data collection via 28 semi-structured interviews with 16 companies and data validation via a questionnaire survey receiving 110 responses from 52 companies. The research delivers a conceptual framework to show how enterprise structures emerge, depending on the prevailing type of core competencies that they use. Furthermore, it proposes contingency-planning recommendations to facilitate managing the change from one structure to another as the demands placed upon the enterprise change.

Numerical simulation for dynamic positioning in pack ice

This thesis investigates the numerical modelling of Dynamic Position (DP) in pack ice. A two-dimensional numerical model for ship-ice interaction was developed using the Discrete Element Method (DEM). A viscous-elastic ice rheology was adopted to model the dynamic behaviour of the ice floes. Both the ship-ice and the ice-ice contacts were considered in the interaction force. The environment forces and the hydrodynamic forces were calculated by empirical formulas. After the current position and external forces were calculated, a Proportional-Integral-Derivative (PID) control and thrust allocation algorithms were applied on the vessel to control its motion and heading. The numerical model was coded in Fortran 90 and validated by comparing computation results to published data. Validation work was first carried out for the ship-ice interaction calculation, and former researchers’ simulation and model test results were used for the comparison. With confidence in the interaction model, case studies were conducted to predict the DP capability of a sample Arctic DP vessel.

Two different 3D biogeochemical models for the NW mediterranean sea: validation with Meris data and intercomparison

Report for the scientific sojourn carried out at the University of New South Wales from February to June the 2007. Two different biogeochemical models are coupled to a three dimensional configuration of the Princeton Ocean Model (POM) for the Northwestern Mediterranean Sea (Ahumada and Cruzado, 2007). The first biogeochemical model (BLANES) is the three-dimensional version of the model described by Bahamon and Cruzado (2003) and computes the nitrogen fluxes through six compartments using semi-empirical descriptions of biological processes. The second biogeochemical model (BIOMEC) is the biomechanical NPZD model described in Baird et al. (2004), which uses a combination of physiological and physical descriptions to quantify the rates of planktonic interactions. Physical descriptions include, for example, the diffusion of nutrients to phytoplankton cells and the encounter rate of predators and prey. The link between physical and biogeochemical processes in both models is expressed by the advection-diffusion of the non-conservative tracers. The similarities in the mathematical formulation of the biogeochemical processes in the two models are exploited to determine the parameter set for the biomechanical model that best fits the parameter set used in the first model. Three years of integration have been carried out for each model to reach the so called perpetual year run for biogeochemical conditions. Outputs from both models are averaged monthly and then compared to remote sensing images obtained from sensor MERIS for chlorophyll.

Validation of order rank scales based on compositional data analysis: a proposal

Usually, psychometricians apply classical factorial analysis to evaluate construct validity of order rankscales. Nevertheless, these scales have particular characteristics that must be taken into account: totalscores and rank are highly relevant

Simultaneous determination of antidementia drugs by HPLC-MS: validation data of the method and plasma level determinations in 300 patients

Aims: A rapid and simple HPLC-MS method was developed for the simultaneousdetermination of antidementia drugs, including donepezil, galantamine, rivastigmineand its major metabolite NAP 226 - 90, and memantine, for TherapeuticDrug Monitoring (TDM). In the elderly population treated with antidementiadrugs, the presence of several comorbidities, drug interactions resulting frompolypharmacy, and variations in drug metabolism and elimination, are possiblefactors leading to the observed high interindividual variability in plasma levels.Although evidence for the benefit of TDM for antidementia drugs still remains tobe demonstrated, an individually adapted dosage through TDM might contributeto minimize the risk of adverse reactions and to increase the probability of efficienttherapeutic response. Methods: A solid-phase extraction procedure with amixed-mode cation exchange sorbent was used to isolate the drugs from 0.5 mL ofplasma. The compounds were analyzed on a reverse-phase column with a gradientelution consisting of an ammonium acetate buffer at pH 9.3 and acetonitrile anddetected by mass spectrometry in the single ion monitoring mode. Isotope-labeledinternal standards were used for quantification where possible. The validatedmethod was used to measure the plasma levels of antidementia drugs in 300patients treated with these drugs. Results: The method was validated accordingto international standards of validation, including the assessment of the trueness(-8 - 11 %), the imprecision (repeatability: 1-5%, intermediate imprecision:2 - 9 %), selectivity and matrix effects variability (less than 6 %). Furthermore,short and long-term stability of the analytes in plasma was ascertained. Themethod proved to be robust in the calibrated ranges of 1 - 300 ng/mL for rivastigmineand memantine and 2 - 300 mg/mL for donepezil, galantamine and NAP226 - 90. We recently published a full description of the method (1). We found ahigh interindividual variability in plasma levels of these drugs in a study populationof 300 patients. The plasma level measurements, with some preliminaryclinical and pharmacogenetic results, will be presented. Conclusion: A simpleLC-MS method was developed for plasma level determination of antidementiadrugs which was successfully used in a clinical study with 300 patients.

Construction and validation of a scoring system for the selection of high-quality data in a Spanish population primary care database (SIDIAP)

Background Computerised databases of primary care clinical records are widely used for epidemiological research. In Catalonia, the InformationSystem for the Development of Research in Primary Care (SIDIAP) aims to promote the development of research based on high-quality validated data from primary care electronic medical records. Objective The purpose of this study is to create and validate a scoring system (Registry Quality Score, RQS) that will enable all primary care practices (PCPs) to be selected as providers of researchusable data based on the completeness of their registers. Methods Diseases that were likely to be representative of common diagnoses seen in primary care were selected for RQS calculations. The observed/ expected cases ratio was calculated for each disease. Once we had obtained an estimated value for this ratio for each of the selected conditions we added up the ratios calculated for each condition to obtain a final RQS. Rate comparisons between observed and published prevalences of diseases not included in the RQS calculations (atrial fibrillation, diabetes, obesity, schizophrenia, stroke, urinary incontinenceand Crohn’s disease) were used to set the RQS cutoff which will enable researchers to select PCPs with research-usable data. Results Apart from Crohn’s disease, all prevalences were the same as those published from the RQS fourth quintile (60th percentile) onwards. This RQS cut-off provided a total population of 1 936 443 (39.6% of the total SIDIAP population). Conclusions SIDIAP is highly representative of the population of Catalonia in terms of geographical, age and sex distributions. We report the usefulness of rate comparison as a valid method to establish research-usable data within primary care electronic medical records

Validation of order rank scales based on compositional data analysis: a proposal

Usually, psychometricians apply classical factorial analysis to evaluate construct validity of order rank scales. Nevertheless, these scales have particular characteristics that must be taken into account: total scores and rank are highly relevant