The role of functional polymorphisms in immune response genes as biomarkers of BCG Immunotherapy outcome in bladder cancer: Establishment of a predictive profile in a Southern Europe population

OBJECTIVE: To evaluate the predictive value of genetic polymorphisms in the context of BCG immunotherapy outcome and create a predictive profile that may allow discriminating the risk of recurrence. MATERIAL AND METHODS: In a dataset of 204 patients treated with BCG, we evaluate 42 genetic polymorphisms in 38 genes involved in the BCG mechanism of action, using Sequenom MassARRAY technology. Stepwise multivariate Cox Regression was used for data mining. RESULTS: In agreement with previous studies we observed that gender, age, tumor multiplicity and treatment scheme were associated with BCG failure. Using stepwise multivariate Cox Regression analysis we propose the first predictive profile of BCG immunotherapy outcome and a risk score based on polymorphisms in immune system molecules (SNPs in TNFA-1031T/C (rs1799964), IL2RA rs2104286 T/C, IL17A-197G/A (rs2275913), IL17RA-809A/G (rs4819554), IL18R1 rs3771171 T/C, ICAM1 K469E (rs5498), FASL-844T/C (rs763110) and TRAILR1-397T/G (rs79037040) in association with clinicopathological variables. This risk score allows the categorization of patients into risk groups: patients within the Low Risk group have a 90% chance of successful treatment, whereas patients in the High Risk group present 75% chance of recurrence after BCG treatment. CONCLUSION: We have established the first predictive score of BCG immunotherapy outcome combining clinicopathological characteristics and a panel of genetic polymorphisms. Further studies using an independent cohort are warranted. Moreover, the inclusion of other biomarkers may help to improve the proposed model.

Audiologists’ preferences for patient-centredness: a cross-sectional questionnaire study of cross-cultural differences and similarities among professionals in Portugal, India and Iran

Objective Patient-centredness has become an important aspect of health service delivery; however, there are a limited number of studies that focus on this concept in the domain of hearing healthcare. The objective of this study was to examine and compare audiologists’ preferences for patient-centredness in Portugal, India and Iran. Design The study used a cross-sectional survey design with audiologists recruited from three different countries. Participants A total of 191 fully-completed responses were included in the analysis (55 from Portugal, 78 from India and 58 from Iran). Main outcome measure The Patient–Practitioner Orientation Scale (PPOS). Results PPOS mean scores suggest that audiologists have a preference for patient-centredness (ie, mean of 3.6 in a 5-point scale). However, marked differences were observed between specific PPOS items suggesting these preferences vary across clinical situations. A significant level of difference (p<0.001) was found between audiologists’ preferences for patient-centredness in three countries. Audiologists in Portugal had a greater preference for patient-centredness when compared to audiologists in India and Iran, although no significant differences were found in terms of age and duration of experience among these sample populations. Conclusions There are differences and similarities in audiologists’ preferences for patient-centredness among countries. These findings may have implications for the training of professionals and also for clinical practice in terms of optimising hearing healthcare across countries.

Time-domain optimization of amplifiers based on distributed genetic algorithms

Thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the subject of Electrical and Computer Engineering

A plugin for spatial and thematic comparison in the cadastral domain.

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Investigating habitat association of breeding birds using public domain satellite imagery and land cover data.

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies

Hepatitis C viral load does not predict disease outcome: going beyond numbers

The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index). Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and treatment variables (dosage, time of treatment, type of interferon) within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV) and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.

Sistema de apoio à racionalização da utilização de energia eléctrica

Esta dissertação descreve o sistema de apoio à racionalização da utilização de energia eléctrica desenvolvido no âmbito da unidade curricular de Tese/Dissertação. O domínio de aplicação enquadra-se no contexto da Directiva da União Europeia 2006/32/EC que declara ser necessário colocar à disposição dos consumidores a informação e os meios que promovam a redução do consumo e o aumento da eficiência energética individual. O objectivo é o desenvolvimento de uma solução que permita a representação gráfica do consumo/produção, a definição de tectos de consumo, a geração automática de alertas e alarmes, a comparação anónima com clientes com perfil idêntico por região e a previsão de consumo/produção no caso de clientes industriais. Trata-se de um sistema distribuído composto por front-end e back-end. O front-end é composto pelas aplicações de interface com o utilizador desenvolvidas para dispositivos móveis Android e navegadores Web. O back-end efectua o armazenamento e processamento de informação e encontra-se alojado numa plataforma de cloud computing – o Google App Engine – que disponibiliza uma interface padrão do tipo serviço Web. Esta opção assegura interoperabilidade, escalabilidade e robustez ao sistema. Descreve-se em detalhe a concepção, desenvolvimento e teste do protótipo realizado, incluindo: (i) as funcionalidades de gestão e análise de consumo e produção de energia implementadas; (ii) as estruturas de dados; (iii) a base de dados e o serviço Web; e (iv) os testes e a depuração efectuados. (iv) Por fim, apresenta-se o balanço deste projecto e efectuam-se sugestões de melhoria.

Frailty as a predictor of short-term adverse outcomes

The objectives of this study were to compare how different frailty measures (Frailty Phenotype/FP, Groningen Frailty Indicator/GFI and Tilburg Frailty Indicator/TFI) predict short-term adverse outcomes. Secondarily, adopting a multidimensional approach to frailty (integral conceptual model–TFI), this study aims to compare how physical, psychological and social frailty predict the outcomes. A longitudinal study was carried out with 95 community-dwelling elderly. Participants were assessed at baseline for frailty, determinants of frailty, and adverse outcomes (healthcare utilization, quality of life, disability in basic and instrumental activities of daily living/ADL and IADL). Ten months later the outcomes were assessed again. Frailty was associated with specific healthcare utilization indicators: the FP with a greater utilization of informal care; GFI with an increased contact with healthcare professionals; and TFI with a higher amount of contacts with a general practitioner. After controlling for the effect of life-course determinants, comorbidity and adverse outcome at baseline, GFI predicted IADL disability and TFI predicted quality of life. The effect of the FP on the outcomes was not significant, when compared with the other measures. However, when comparing TFI’s domains, the physical domain was the most significant predictor of the outcomes, even explaining part of the variance of ADL disability. Frailty at baseline was associated with adverse outcomes at follow-up. However, the relationship of each frailty measure (FP, GFI and TFI) with the outcomes was different. In spite of the role of psychological frailty, TFI’s physical domain was the determinant factor for predicting disability and most of the quality of life.

An Extension of Estimation of Domain of Attraction for Fractional Order Linear System Subject to Saturation Control

This paper employs the Lyapunov direct method for the stability analysis of fractional order linear systems subject to input saturation. A new stability condition based on saturation function is adopted for estimating the domain of attraction via ellipsoid approach. To further improve this estimation, the auxiliary feedback is also supported by the concept of stability region. The advantages of the proposed method are twofold: (1) it is straightforward to handle the problem both in analysis and design because of using Lyapunov method, (2) the estimation leads to less conservative results. A numerical example illustrates the feasibility of the proposed method.

The influence of the human genome on chronic viral hepatitis outcome

The mechanisms that determine viral clearance or viral persistence in chronic viral hepatitis have yet to be identified. Recent advances in molecular genetics have permitted the detection of variations in immune response, often associated with polymorphism in the human genome. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virulence of microbial agents. Several recent advances concerning the influence of human genes in chronic viral hepatitis B and C are discussed in this article: a) the associations between human leukocyte antigen polymorphism and viral hepatic disease susceptibility or resistance; b) protective alleles influencing hepatitis B virus (HBV) and hepatitis C virus (HCV) evolution; c) prejudicial alleles influencing HBV and HCV; d) candidate genes associated with HBV and HCV evolution; d) other genetic factors that may contribute to chronic hepatitis C evolution (genes influencing hepatic stellate cells, TGF-beta1 and TNF-alpha production, hepatic iron deposits and angiotensin II production, among others). Recent discoveries regarding genetic associations with chronic viral hepatitis may provide clues to understanding the development of end-stage complications such as cirrhosis or hepatocellular carcinoma. In the near future, analysis of the human genome will allow the elucidation of both the natural course of viral hepatitis and its response to therapy.

Paracoccidioidomycosis in children: clinical presentation, follow-up and outcome

From February, 1981 to May, 2001, 63 children under 15 y old (ages 2 - 15 y, median = 8 y, mean ± 1 SD = 8 ± 3 y) presenting 70 episodes of Paracoccidioidomycosis were admitted. The main clinical manifestations and laboratory features observed upon admission were: lymph node enlargement (87.1%), fever (75.7%), weakness (48.6%), pallor (41.4%), hepatomegaly (40%), splenomegaly (35.7%), anemia (90%), hypergammaglobulinemia (88.5%), eosinophilia (75.5%) and hypoalbuminemia (72.5%). Moderate to severe malnutrition was detected in 35.7% of the episodes (Gomez's criterion). Radiographic and technetium studies showed bone lesions in 20 of the episodes, most of them being multiple lytic lesions, involving both long (70%) and plain bones (30%). First line treatment consisted of an association of sulfametoxazole-trimethoprin, which was used, exclusively, in 50 episodes. Follow-up of hemoglobin levels, number of eosinophils in the peripheral blood, albumin and gammaglobulin serum levels revealed significant sequential improvement one and six months after hospital admission, being quite useful to evaluate treatment effectiveness. Six patients died (9.3%) and four developed sequelae (6.3%) . In conclusion, the juvenile and disseminated forms can be observed in about 70% of the episodes of PCM occurring in children younger than 15 y old, most of them presenting with a febrile lymphoproliferative syndrome associated to anemia, eosinophilia and hypergammaglobulinemia.

Towards the Certification of Multicore Platforms in the Avionics Domain

Poster presented in Work in Progress Session, The 28th GI/ITG International Conference on Architecture of Computing Systems (ARCS 2015). 24 to 27, Mar, 2015. Porto, Portugal.

Towards the Certification of Multicore Platforms in the Avionics Domain

Presented at Work in Progress Session, The 28th GI/ITG International Conference on Architecture of Computing Systems (ARCS 2015). 24 to 27, Mar, 2015. Porto, Portugal.

Interactional strategies between terminologist and domain specialist. Putting order into our universe: the concept of Blended Learning

A presente comunicação visa discutir as mais-valias de um desenho metodológico sustentado numa abordagem conceptual da Terminologia aplicado ao exercício de harmonização da definição do cenário educativo mais promissor do Ensino Superior actual: o blended learning. Sendo a Terminologia uma disciplina que se ocupa da representação, da descrição e da definição do conhecimento especializado através da língua a essência deste domínio do saber responde a uma necessidade fundamental da sociedade actual: putting order into our universe, nas palavras de Nuopponen (2011). No contexto descrito, os conceitos, enquanto elementos da estrutura do conhecimento (Sager, 1990) constituem um objecto de investigação de complexidade não despicienda, pois apesar do postulado de que a língua constitui uma ferramenta fundamental para descrever e organizar o conhecimento, o princípio isomórfico não pode ser tomado como adquirido. A abordagem conceptual em Terminologia propõe uma visão precisa do papel da língua no trabalho terminológico, sendo premissa basilar que não existe uma correspondência unívoca entre os elementos atomísticos do conhecimento e os elementos da expressão linguística. É pela razões enunciadas que as opções metodológicas circunscritas à análise do texto de especialidade serão consideradas imprecisas. Nesta reflexão perspectiva-se que o conceito-chave de uma abordagem conceptual do trabalho terminológico implica a combinação de um processo de elicitação do conhecimento tácito através de uma negociação discursiva orientada para o conceito e a análise de corpora textuais. Defende-se consequentemente que as estratégias de interacção entre terminólogo e especialista de domínio merecem atenção detalhada pelo facto de se reflectirem com expressividade na qualidade dos resultados obtidos. Na sequência do exposto, o modelo metodológico que propomos sustenta-se em três etapas que privilegiam um refinamento dessa interacção permitindo ao terminólogo afirmar-se como sujeito conceptualizador, decisor e interventor: (1) etapa exploratória do domínio-objecto de estudo; (2) etapa de análise onamasiológica de evidência textual e discursiva; (3) etapa de modelização e de validação de resultados. Defender-se-á a produtividade de uma sequência cíclica entre a análise textual e discursiva para fins onomasiológicos, a interacção colaborativa e a introspecção.

Primary Antiphospholipid Syndrome: Pregnancy Outcome in a Portuguese Population

Introduction:Women with antiphospholipid syndrome(APS) may suffer from recurrent miscarriage, fetal death, fetal growth restriction (FGR), pre-eclampsia, placental abruption, premature delivery and thrombosis. Treatment with aspirin and low molecular weight heparin (LMWH) combined with close maternal-fetal surveillance can change these outcomes. Objective: To assess maternal and perinatal outcome in a cohort of Portuguese women with primary APS. Patients and Methods: A retrospective analysis of 51 women with primary APS followed in our institution (January 1994 to December 2007). Forty one(80.4%) had past pregnancy morbidity and 35.3%(n=18) suffered previous thrombotic events. In their past they had a total of 116 pregnancies of which only 13.79 % resulted in live births. Forty four patients had positive anticardiolipin antibodies and 33 lupus anticoagulant. All women received treatment with low dose aspirin and LMWH. Results: There were a total of 67 gestations (66 single and one multiple). The live birth rate was 85.1%(57/67) with 10 pregnancy failures: seven in the first and second trimesters, one late fetal death and two medical terminations of pregnancy (one APS related). Mean (± SD) birth weight was 2837 ± 812 g and mean gestational age 37 ± 3.3 weeks. There were nine cases of FGR and 13 hypertensive complications(4 HELLP syndromes). 54.4% of the patients delivered by caesarean section. Conclusions: In our cohort, early treatment with aspirin and LMWH combined with close maternal-fetal surveillance was associated with a very high chance of a live newborn.