Hepatitis B vaccine - proposal for a standardized assessment of immune response

The authors developed a comparative study of the various methods of assessment of immune response to Hepatitis B vaccine. Eighty-six health care professionals underwent a vaccination programme with three doses of plasma-derived vaccine against Hepatitis B (H-B-Vax, Merck, Sharp & Dohme) given intra-muscularly. Assessment of immune response was carried out three months after the end of the programme, by radioimmunoassay (RIA) and enzymeimmunoassay (EIA). The results showed that the semi-quantitative assessment of Anti-HBs antibodies by RIA or EIA was perfectly comparable to the reference method (quantitative determination of antibodies by RIA). In view of these findings, the authors suggest a standardization of assessment of immune response to the vaccine, thus permitting correct planning of booster doses and easier comparison between different studies

The role of the efflux mechanisms in multidrug resistance in Mycobacterium tuberculosis

Abstract The emergence of multi and extensively drug resistant tuberculosis (MDRTB and XDRTB) has increased the concern of public health authorities around the world. The World Health Organization has defined MDRTB as tuberculosis (TB) caused by organisms resistant to at least isoniazid and rifampicin, the main first-line drugs used in TB therapy, whereas XDRTB refers to TB resistant not only to isoniazid and rifampicin, but also to a fluoroquinolone and to at least one of the three injectable second-line drugs, kanamycin, amikacin and capreomycin. Resistance in Mycobacterium tuberculosis is mainly due to the occurrence of spontaneous mutations and followed by selection of mutants by subsequent treatment. However, some resistant clinical isolates do not present mutations in any genes associated with resistance to a given antibiotic, which suggests that other mechanism(s) are involved in the development of drug resistance, namely the presence of efflux pump systems that extrude the drug to the exterior of the cell, preventing access to its target. Increased efflux activity can occur in response to prolonged exposure to subinhibitory concentrations of anti-TB drugs, a situation that may result from inadequate TB therapy. The inhibition of efflux activity with a non-antibiotic inhibitor may restore activity of an antibiotic subject to efflux and thus provide a way to enhance the activity of current anti-TB drugs. The work described in this thesis foccus on the study of efflux mechanisms in the development of multidrug resistance in M. tuberculosis and how phenotypic resistance, mediated by efflux pumps, correlates with genetic resistance. In order to accomplish this goal, several experimental protocols were developed using biological models such as Escherichia coli, the fast growing mycobacteria Mycobacterium smegmatis, and Mycobacterium avium, before their application to M. tuberculosis. This approach allowed the study of the mechanisms that result in the physiological adaptation of E. coli to subinhibitory concentrations of tetracycline (Chapter II), the development of a fluorometric method that allows the detection and quantification of efflux of ethidium bromide (Chapter III), the characterization of the ethidium bromide transport in M. smegmatis (Chapter IV) and the contribution of efflux activity to macrolide resistance in Mycobacterium avium complex (Chapter V). Finally, the methods developed allowed the study of the role of efflux pumps in M. tuberculosis strains induced to isoniazid resistance (Chapter VI). By this manner, in Chapter II it was possible to observe that the physiological adaptation of E. coli to tetracycline results from an interplay between events at the genetic level and protein folding that decrease permeability of the cell envelope and increase efflux pump activity. Furthermore, Chapter III describes the development of a semi-automated fluorometric method that allowed the correlation of this efflux activity with the transport kinetics of ethidium bromide (a known efflux pump substrate) in E. coli and the identification of efflux inhibitors. Concerning M. smegmatis, we have compared the wild-type M. smegmatis mc2155 with knockout mutants for LfrA and MspA for their ability to transport ethidium bromide. The results presented in Chapter IV showed that MspA, the major porin in M. smegmatis, plays an important role in the entrance of ethidium bromide and antibiotics into the cell and that efflux via the LfrA pump is involved in low-level resistance to these compounds in M. smegmatis. Chapter V describes the study of the contribution of efflux pumps to macrolide resistance in clinical M. avium complex isolates. It was demonstrated that resistance to clarithromycin was significantly reduced in the presence of efflux inhibitors such as thioridazine, chlorpromazine and verapamil. These same inhibitors decreased efflux of ethidium bromide and increased the retention of [14C]-erythromycin in these isolates. Finaly, the methods developed with the experimental models mentioned above allowed the study of the role of efflux pumps on M. tuberculosis strains induced to isoniazid resistance. This is described in Chapter VI of this Thesis, where it is demonstrated that induced resistance to isoniazid does not involve mutations in any of the genes known to be associated with isoniazid resistance, but an efflux system that is sensitive to efflux inhibitors. These inhibitors decreased the efflux of ethidium bromide and also reduced the minimum inhibitory concentration of isoniazid in these strains. Moreover, expression analysis showed overexpression of genes that code for efflux pumps in the induced strains relatively to the non-induced parental strains. In conclusion, the work described in this thesis demonstrates that efflux pumps play an important role in the development of drug resistance, namely in mycobacteria. A strategy to overcome efflux-mediated resistance may consist on the use of compounds that inhibit efflux activity, restoring the activity of antimicrobials that are efflux pump substrates, a useful approach particularly in TB where the most effective treatment regimens are becoming uneffective due to the increase of MDRTB/XDRTB.

Saúde mental, qualidade de vida e acesso aos cuidados de saúde na comunidade brasileira de Lisboa

Introdução: A utilização de serviços de saúde tem implicações importantes para o estado de saúde das populações. As políticas de imigração adoptadas nos países de destino têm influência no estado de saúde das comunidades imigrantes. Políticas que limitam o acesso de imigrantes aos cuidados de saúde aumentarão a vulnerabilidade e os riscos na saúde. Apesar da imigração promover uma série de rupturas na vida do sujeito, migrar, por si só, não pode ser considerado como factor de risco no âmbito da saúde e da saúde mental. O peso dos determinantes socioeconómicos tem ganho relevância no estudo das migrações, estado de saúde geral e mental. Isto porque, em geral, os imigrantes estão em situação mais precária do que a população autóctone. O estatuto socioeconómico baixo, as condições precárias de habitação e de trabalho, a falta de suporte social e a irregularidade jurídica são indicadores de risco acrescido para a saúde mental. Neste sentido é um desafio de monta os governos estabelecerem medidas sustentadas e, simultaneamente, integradoras dos imigrantes. Em Portugal, considera-se que há escassez de estudos relacionados com a área das migrações e da saúde.Metodologia: Estudo exploratório, descritivo e transversal. A finalidade foi a de identificar o estado de saúde, saúde mental e qualidade de vida da comunidade brasileira residente em Lisboa e o seu acesso aos serviços de saúde. Este estudo teve como principais objectivos a caracterização sociodemográfica, a identificação de variáveis inerentes ao processo migratório, a identificação da auto-apreciação do estado de saúde, a caracterização do acesso aos cuidados de saúde, a identificação do grupo em provável sofrimento psicológico, a comparação entre os resultados dos imigrantes juridicamente regulares e irregulares e a comparação entre a população imigrante e a população portuguesa. Inicialmente, foi prevista a utilização da técnica de amostragem de propagação geométrica ou snowball, pois a amostra tornar-se-ia maior à medida que os próprios inquiridos identificam outros potenciais respondentes. Ao longo do estudo, a metodologia inicial mostrou-se insuficiente para estabelecer uma amostra mais representativa dos imigrantes juridicamente irregulares. Para este feito, foi utilizada a metodologia de amostragem por conveniência e o local escolhido para a recolha da amostra foi o Consulado do Brasil em Lisboa. O instrumento de recolha de dados empregue baseou-se no questionário utilizado no 4º Inquérito Nacional de Saúde. O MHI-5 (Mental Health Index 5) é um instrumento de saúde mental e é parte integrante do inquérito, sendo recomendado pela Organização Mundial de Saúde. Consta de cinco itens relativos à saúde mental e os resultados são classificados através de um indicador que mede a existência de provável sofrimento psicológico. Foram incluídos no estudo 213 brasileiros. De seguida, procedeu-se ao tratamento estatístico dos dados. Resultados: A população inquirida é jovem, a maior parte tem entre 18 e 44 anos. As mulheres representam mais de metade da amostra. A taxa de actividade é elevada e a taxa de desemprego é similar à nacional. A inserção laboral prioritária é nos segmentos pouco qualificados ou de semi-qualificação. Aproximadamente um terço dos inquiridos afirmou ser beneficiário do Sistema Nacional de Saúde. A autoapreciação do estado de saúde é classificada como bastante positiva, assim como a qualidade de vida. O provável sofrimento psicológico, definido no MHI-5 pelo ponto de corte no score 52, atinge 23,3% dos participantes. Os homens apresentam melhores resultados do que as mulheres. Além disso, para os valores mais baixos no MHI-5 foram encontradas relações com as longas jornadas de trabalho e o diagnóstico de doença crónica.Discussão: O presente estudo apresenta limitações em relação à dimensão da amostra e à provável existência de enviesamento pela ausência de aleatorização. Apesar da legislação portuguesa garantir o acesso aos serviços de saúde e garantir a equidade no caso dos imigrantes que fazem descontos para a Segurança Social, apenas um terço referiu ser beneficiário do Sistema Nacional de Saúde. Este dado pode ser justificado por factores como o cumprimento da lei por alguns serviços e, também, pela falta de conhecimento da legislação e da forma de funcionamento do Serviço Nacional de Saúde por parte dos imigrantes. O facto das mulheres representarem o maior grupo em provável sofrimento psicológico é consistente com a literatura. As hipóteses levantadas para explicar este resultado podem ser agrupadas em: artefactos metodológicos, causalidade biológica e determinação social. Em relação ao instrumento, é possível que o MHI-5 se comporte de forma diferente no que diz respeito ao género.-------------------------------------------Introduction: The utilization of health services has important implications for the health state of the populations. The immigration policies adopted in the destiny countries are going to influence the health state of immigrant communities. Policies that limit the access of immigrants to health care are going to increase the vulnerability and the risk factor in health. Although immigration promotes several disruptive actions in ones life, migrating, on its own, cannot be considered as a risk factor for health and mental health. The preponderance of the socioeconomic factors has gained relevance in the study of migrations and also in the study of general health state and mental health. This happens because, in general, immigrants are in a more unfavorable situation compared with the destiny country population. The low socioeconomic status, the poor working and housing conditions, the lack of social support and the juridical irregularity are indicators of the incremented risk to mental health. Therefore, it is a major challenge for governments to find sustainable, and simultaneously, integrative measures for the immigrants. The studies related with the migrations and health in Portugal were considered to be few.Methods: It is an exploratory, descriptive and transversal study. The purpose is to identify the health state, mental health, quality of life and the access to health care of the Brazilian community resident in Lisbon. In addition, this study has as main goals the sociodemographic characterization, the variables identification inherent to the migrating process, the identification of the self-appreciation of health state, the characterization of the access to health care, the identification of the group in probable psychological suffer, the comparison between the results of regular and irregular immigrants and the comparison between the immigrant population and the Portuguese population. Initially it was predicted the utilization of the geometric propagation or “snowball”, as sampling technique, because the sample becomes larger as one answerer identify other potential answering persons. Along with the study, the methodology has shown insufficient to establish a more representative sample of the irregular immigrants. For this latter case, it was used a convenient sample methodology and the place chosen for the sample gathering was the “Consulate of Brazil in Lisbon”. The instrument was based in the questionnaire used in the “4th National Health Inquiry”. The MHI-5 (Mental Health Index 5) is a mental health instrument which is part of the enquiry and it is recommended by the World Health Organization. There are five items related to mental health and the results are classified through an indicator which measures the existence of a probable psychological suffer. It were included 213 Brazilian in the study. After, the statistical treatment of the data took place.Results: The answering population is young and the majority is between the 18 and 44 years of age. The women represent more than one half of the sample. The activity rate is high and the unemployment rate is similar to the national one. The priority labor insertion is in the few qualified or of semi-qualification segments. Approximately, one third of the answering people has stated to be beneficiary of the National Health System. The self-appreciation of the health state as well as the quality of life are classified as fairly positive ones. The probable psychological suffer, as defined in the MHI-5 through the cut point in the score below or equal to 52, reaches 23,3% of the sample population. Men show the better results than women. Further, for the lower values of MHI-5 it was found a relation with the long work periods and chronic disease diagnostic. Discussion: The present study evidences limitations in relation to the sample dimension and in relation to the existence of biases due to the lack of randomness. Although the Portuguese legislation guarantees the access to health services and the equality in the cases of the immigrants that do their Social Security discounts, only one third has mentioned to be beneficiary of the National Health System. This can be justified by several facts such as the non-fulfillment of law by some national services or the lack of knowledge of the legislation or the functioning process of the National Health System. Women representing the bigger group in probable psychological suffer has been coherent with the literature review. The hypothesis set to explain this result might be grouped in: methodological artifacts, biologic cause and social determination. In relation to the instrument used, it may be that MHI-5 behaves in a different way in respect to gender.

Adapted Control Methods for Cerebral Palsy Users of an Intelligent Wheelchair

The development of an intelligent wheelchair (IW) platform that may be easily adapted to any commercial electric powered wheelchair and aid any person with special mobility needs is the main objective of this project. To be able to achieve this main objective, three distinct control methods were implemented in the IW: manual, shared and automatic. Several algorithms were developed for each of these control methods. This paper presents three of the most significant of those algorithms with emphasis on the shared control method. Experiments were performed by users suffering from cerebral palsy, using a realistic simulator, in order to validate the approach. The experiments revealed the importance of using shared (aided) controls for users with severe disabilities. The patients still felt having complete control over the wheelchair movement when using a shared control at a 50% level and thus this control type was very well accepted. Thus it may be used in intelligent wheelchairs since it is able to correct the direction in case of involuntary movements of the user but still gives him a sense of complete control over the IW movement.

Forças em estruturas de acostagem descontínuas em zonas desabrigadas: avaliação de ferramentas de cálculo existentes

Dissertação para obtenção do grau de Mestre em Engenharia Civil na Área de especialização em Hidráulica

Utilização de técnicas de análise fotogramétricas em quebra-mares de taludes

Dissertação de Natureza Científica elaborada no Laboratório Nacional de Engenharia Civil (LNEC) para obtenção do grau de mestre em Engenharia Civil na Área de Especialização de Hidráulica no âmbito do protocolo de cooperação entre o ISEL e o LNEC

Analysis of Forest Fires by means of Pseudo Phase Plane and Multidimensional Scaling Methods

Forest fires dynamics is often characterized by the absence of a characteristic length-scale, long range correlations in space and time, and long memory, which are features also associated with fractional order systems. In this paper a public domain forest fires catalogue, containing information of events for Portugal, covering the period from 1980 up to 2012, is tackled. The events are modelled as time series of Dirac impulses with amplitude proportional to the burnt area. The time series are viewed as the system output and are interpreted as a manifestation of the system dynamics. In the first phase we use the pseudo phase plane (PPP) technique to describe forest fires dynamics. In the second phase we use multidimensional scaling (MDS) visualization tools. The PPP allows the representation of forest fires dynamics in two-dimensional space, by taking time series representative of the phenomena. The MDS approach generates maps where objects that are perceived to be similar to each other are placed on the map forming clusters. The results are analysed in order to extract relationships among the data and to better understand forest fires behaviour.

Feature Discretization with Relevance and Mutual Information Criteria

Feature discretization (FD) techniques often yield adequate and compact representations of the data, suitable for machine learning and pattern recognition problems. These representations usually decrease the training time, yielding higher classification accuracy while allowing for humans to better understand and visualize the data, as compared to the use of the original features. This paper proposes two new FD techniques. The first one is based on the well-known Linde-Buzo-Gray quantization algorithm, coupled with a relevance criterion, being able perform unsupervised, supervised, or semi-supervised discretization. The second technique works in supervised mode, being based on the maximization of the mutual information between each discrete feature and the class label. Our experimental results on standard benchmark datasets show that these techniques scale up to high-dimensional data, attaining in many cases better accuracy than existing unsupervised and supervised FD approaches, while using fewer discretization intervals.

Evaluation of different methods for Plasmodia detection, in well defined population groups in an endemic area of Brazil

In Brazil, more than 500,000 new cases of malaria were notified in 1992. Plasmodium falciparum and P.vivax are the responsible species for 99.3% of the cases. For adequate treatment, precoce diagnosis is necessary. In this work, we present the results of the traditional Plasmodia detection method, thick blood film (TBF), and the results of alternative methods: Immunofluorescence assay (IFA) with polyclonal antibody and Quantitative Buffy Coat method (QBC)® in a well defined population groups. The analysis were done in relation to the presence or absence of malaria clinical symptoms. Also different classes of immunoglobulins anti-P.falciparum were quantified for the global analysis of the results, mainly in the discrepant results. We concluded that alternative methods are more sensitive than TBF and that the association of epidemiological, clinical and laboratory findings is necessary to define the presence of malaria.

Parallel sparse unmixing of hyperspectral data

In this paper, a new parallel method for sparse spectral unmixing of remotely sensed hyperspectral data on commodity graphics processing units (GPUs) is presented. A semi-supervised approach is adopted, which relies on the increasing availability of spectral libraries of materials measured on the ground instead of resorting to endmember extraction methods. This method is based on the spectral unmixing by splitting and augmented Lagrangian (SUNSAL) that estimates the material's abundance fractions. The parallel method is performed in a pixel-by-pixel fashion and its implementation properly exploits the GPU architecture at low level, thus taking full advantage of the computational power of GPUs. Experimental results obtained for simulated and real hyperspectral datasets reveal significant speedup factors, up to 1 64 times, with regards to optimized serial implementation.

A satisfação dos trabalhadores com as práticas de gestão de recursos humanos: o caso de uma Instituição do Ensino Superior Público em Portugal

Este estudo tem como objetivos: (1) conhecer as práticas desenvolvidas numa organização do Ensino Superior Público Português; (2) conhecer a tipologia das práticas de GRH de cariz tradicional e de cariz estratégico; (3) perceber em que medida as práticas de GRH estão relacionadas com a área de qualificação dos responsáveis do departamento de RH; (4) averiguar o grau de satisfação que os trabalhadores sentem com as Práticas de Gestão de Recursos Humanos desenvolvidas e a sua relação com a área de qualificação dos responsáveis do departamento de RH. Foi utilizada uma metodologia mista, que possibilita ampliar a obtenção de resultados em abordagens investigativas, proporcionando ganhos relevantes para a pesquisa. É realizado um primeiro estudo exploratório, que utiliza uma metodologia mista quantitativa e qualitativa, com recurso a uma entrevista semiestruturada e inquérito realizados aos responsáveis de RH, e que tem como objetivos identificar e caracterizar as Práticas de GRH vigentes na Organização e, consequentemente, averiguar se se aproximam das designadas na literatura, assim como averiguar o grau de intervenção do DRH no desenvolvimento das PGRH e caraterizar o perfil do responsável de RH na Organização, averiguando se a área de formação de RH influencia as Práticas de GRH desenvolvidas. No segundo estudo, recorremos a uma metodologia quantitativa com recurso ao inquérito por questionário, aplicado aos trabalhadores que exercem funções a tempo integral, para averiguar o grau de satisfação dos trabalhadores em relação às Práticas de Gestão de Recursos Humanos. Na compilação dos dois estudos foi nosso objetivo obter respostas às questões que orientaram a nossa investigação. Na parte final da dissertação são discutidos os principais resultados obtidos e apresentadas as conclusões do estudo aqui levado a cabo. Os resultados sugerem que: 1) as PGRH existentes são essencialmente de cariz tradicional, em especial a gestão administrativa; 2) as PGRH predominantes são: o Planeamento de Recursos Humanos, a Análise e Descrição de Funções, o Recrutamento e Seleção, a Formação e Desenvolvimento, a Gestão Administrativa, a Comunicação e a Partilha de Informação, Ética e Deontologia e o Estatuto Disciplinar; 3) existe pouco recurso ao outsourcing para as PGRH; 4) o grau de intervenção DRH baseia-se em atividades de cariz mais administrativo; 5) as práticas tradicionais de RH são aquelas que requerem mais tempo ao DRH; 6) não existe relação entre o tipo de PGRH e a área de qualificação do responsável do DRH; 7) as PGRH são realizadas seguindo essencialmente as normas legais e regras rígidas da GRH na AP; 8) algumas PGRH não são entendidas em contexto da AP, como importantes pelos gestores, embora já sejam desenvolvidos alguns procedimentos dessas práticas; 9) a PGRH da formação e desenvolvimento não é corretamente desenvolvida e não dá cumprimento ao estipulado na lei; 10) a gestão de carreiras e o sistema de compensação e recompensas são entendidas como inexistentes, porque não existem promoções e progressões desde 2005; 11) a avaliação do desempenho é um sistema burocrático e ritualista com fins de promoção e compensação, sem efeitos práticos no momento atual, e que causa insatisfação e o sentimento de injustiça; 12) existem problemas de comunicação quanto a partilha e uniformização de procedimentos entre UO; 13) a satisfação dos trabalhadores é maior com as PGRH de tipo tradicional, nomeadamente na gestão administrativa, recrutamento e seleção, análise e descrição de funções, acolhimento, integração e socialização 14) a satisfação é menor na gestão de carreiras, no sistema de compensação e recompensas e na avaliação do desempenho; 15) quanto a relação entre o grau de satisfação e as características sócio demográficas e profissionais dos inquiridos, os casos com significância mostram que os trabalhadores com 10 ou mais anos de antiguidade tendem a sentir mais satisfação com as práticas em GRH; 16) existe mais satisfação dos trabalhadores das UO onde o responsável de DRH possui formação na área de RH.

New ultrasonic-based methods in proteomics

Dissertação apresentada para obtenção do Grau de Doutor em Bioquímica pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia.A presente dissertação foi preparada no âmbito do convénio bilateral existente entre a Universidade Nova de Lisboa e a Universidade de Vigo.

The influence of pre-departure training on expatriate adjustment: an empirical investigation with portuguese international assignees

This chapter examines the cross-cultural influence of training on the adjustment of international assignees. We focus on the pre-departure training (PDT) before an international assignment. It is an important topic because in the globalized world of today more and more expatriations are needed. The absence of PDT may generate the failure of the expatriation experience. Companies may neglect PDT due to cost reduction practices and ignorance of the need for it. Data were collected through semi-structured interviews to 42 Portuguese international assignees and 18 organizational representatives from nine Portuguese companies. The results suggest that companies should develop PDT programs, particularly when the cultural distance to the host country is bigger and when there is no previous experience of expatriation to that country in the company. The study is original because it details in depth the methods of PDT, its problems, and consequences. Some limitations linked to the research design and detailed in the conclusion should be overcome in future studies.

Using Baseline Methods to Identify Non-technical Losses in the Context of Smart Grids

Demand response has gained increasing importance in the context of competitive electricity markets and smart grid environments. In addition to the importance that has been given to the development of business models for integrating demand response, several methods have been developed to evaluate the consumers’ performance after the participation in a demand response event. The present paper uses those performance evaluation methods, namely customer baseline load calculation methods, to determine the expected consumption in each period of the consumer historic data. In the cases in which there is a certain difference between the actual consumption and the estimated consumption, the consumer is identified as a potential cause of non-technical losses. A case study demonstrates the application of the proposed method to real consumption data.

Consumers Performance Evaluation of the Participation in Demand Response Programs Using Baseline Methods

Demand response has gain increasing importance in the context of competitive electricity markets environment. The use of demand resources is also advantageous in the context of smart grid operation. In addition to the need of new business models for integrating demand response, adequate methods are necessary for an accurate determination of the consumers’ performance evaluation after the participation in a demand response event. The present paper makes a comparison between some of the existing baseline methods related to the consumers’ performance evaluation, comparing the results obtained with these methods and also with a method proposed by the authors of the paper. A case study demonstrates the application of the referred methods to real consumption data belonging to a consumer connected to a distribution network.