The HIF1A Functional Genetic Polymorphism at Locus +1772 Associates with Progression to Metastatic Prostate Cancer and Refractoriness to Hormonal Castration

The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT.

The Oncological and Functional Risks of the Organ Preservation Experimental Treatment Approach

We increasingly face conservative surgery for rectal cancer and even the so called ‘wait and see’ approach, as far as 10–20% patients can reach a complete pathological response at the time of surgery. But what can we say to our patients about risks? Standard surgery with mesorectal excision gives a <2% local recurrence with a post operative death rate of 2–8% (may reach 30% at 6 months in those over 85), but low AR has some deterioration in bowel function and in low cancer a permanent stoma may be required. Also a long-term impact on urinary and sexual function is possible. Distant metastasis rate seem to be identical in the standard and conservative approach. It is difficult to evaluate conservative approach because a not clear standardization of surgery for low rectal cancer. Rullier et al tried to clarify, and they found identical results for recurrence (5–9%), disease free survival (70%) at 5y for coloanal anastomosis and intersphinteric resection. Other series have found local recurrence higher than with standard approach and functional results may be worse and, in some situations, salvage therapy is compromised or has more complications. In this context, functional outcomes are very important but most studies are incomplete in measuring bowel function in the context of conservative approach. In 2005 Temple et al made a survey of 122/184 patient after sphinter preserving surgery and found a 96.9% of incomplete evacuation, 94.4% clustering, 93.2% food affecting frequency, 91.8% gas incontinence and proposed a systematic evaluation with a specific questionnaire. In which concerns ‘Wait and see’ approach for complete clinical responders, it was first advocated by Habr Gama for tumors up to 7cm, with a low locoregional failure of 4.6%, 5y overall survival 96%, 72% for disease free survival; one fifth of patients failed in the first year; a Dutch trial had identical results but others had worse recurrence rates; in other series 25% of patients could not be salvaged even with APR; 30% have subsequent metastatic disease what seems equal for ‘wait and see’ and operated patients. In a recent review Glynne Jones considers that all the evaluated ‘wait and see’ studies are heterogeneous in staging, inclusion criteria, design and follow up after chemoradiation and that there is the suggestion that patients who progress while under observation fare worse than those resected. He proposes long-term observational studies with more uniform inclusion criteria. We are now facing a moment where we may be more aggressive in early cancer and neoadjuvant treatment to be more conservative in the subsequent treatment but we need a better stratification of patients, better evaluation of results and more clear prognostic markers.

Structural and functional studies of PpcA: a key protein in the electron transfer pathways of Geobacter sulfurreducens

Dissertação para obtenção do Grau de Doutor em Bioquímica, ramo de Biotecnologia

Flexural strengthening by means of a arc overlay in the tension zone

Dissertação para obtenção do Grau de Mestre em Engenharia Civil – Perfil de Estruturas

Contributo para a validação da versão portuguesa da Quebec Back Pain Disability Scale : fiabilidade e poder de resposta em utentes com dor lombar crónica

RESUMO: Um dos principais resultados das intervenções de Fisioterapia dirigidas a utentes com Dor Lombar Crónica (DLC) é reduzir a incapacidade funcional. A Quebec Back Pain Disability Scale (QBPDS) é um instrumento amplamente aceite a nível internacional na medição do nível de incapacidade funcional reportada pelos indivíduos com DLC. O objetivo deste estudo é dar um contributo para a adaptação cultural da versão portuguesa da QBPDS (QBPDS-VP) e investigar o poder de resposta e interpretabilidade da escala. Metodologia: Realizou-se um estudo metodológico, multicentro, baseado num coorte prospetivo de 132 utentes com DLC. Os utentes foram recrutados a partir da lista de espera de 16 serviços de Medicina Física e de Reabilitação/Fisioterapia de várias áreas geográficas de Portugal. A QBPDS- VP foi administrada 3 vezes, em 3 momentos de recolha de dados distintos: T0 - momento inicial (utentes em lista de espera); T1 - 1 semana de intervalo (início dos tratamentos de Fisioterapia); e T2 - 6 semanas de intervalo (pós-intervenção de Fisioterapia). Os dados recolhidos em T0 foram utilizados para a análise fatorial e para o estudo da consistência interna (n=132); os dados da amostra emparelhada de T0 e T1 (n=132) para a fiabilidade teste-reteste; e os dados da amostra emparelhada de T0 e T2 (n=120) para a análise do poder de resposta e interpretabilidade. A âncora externa utilizada foi a perceção global de mudança, neste caso a PGIC- VP, que foi respondida em T1 e T2. O nível de significância para o qual os valores se consideraram satisfatórios foi de p≤ 0,05. O tratamento dos dados foi realizado no software IBM SPSS Statistics (versão 20). Resultados: A QBPDS- VP é uma escala unidimensional, que revela uma excelente consistência interna (α de Cronbach= 0,95) e uma fiabilidade teste-reteste satisfatória (CCI= 0,696; IC 95%: 0,581–0,783). Esta escala demonstrou um poder de resposta moderado, quando aplicada em utentes com DLC ( = 0,426 e AAC= 0,741; IC 95%: 0,645 – 0,837). A Diferença Mínima Detetável (DMD) estimada foi de 19 pontos e as estimativas da Diferença Mínima Clinicamente Importante (DMCI) variaram entre 7 (pelo método curva ROC) e 8 pontos (pelo método “diferença média de pontuação”). A estimativa pela curva ROC deriva do ponto ótimo de corte de 6,5 pontos, com Área Abaixo da Curva (AAC)= 0,741, sensibilidade de 72%, e especificidade de 71%. Uma análise complementar da curva ROC baseada nas diferenças de pontuações da QBPDS, expressa em percentagem, revelou um ponto ótimo de corte de - 24% (AAC= 0,737, sensibilidade de 71%, e especificidade de 71%). Para pontuações iniciais da QBPDS- VP mais altas (≥34 pontos), foi encontrado um ponto ótimo de corte de 10,5 pontos (AAC= 0,738, sensibilidade de 73%, e especificidade de 67%). Conclusão: A QBPDS-VP demonstrou bons níveis de fiabilidade e poder de resposta, recomendando-se o seu uso na medição e avaliação da incapacidade funcional de utentes com DLC. A DMD estimada, de 19 pontos, determinou uma amplitude válida da QBPDS-VP de 19 a 81 pontos. Este estudo propõe estimativas de DMCI da QBPDS- VP numa aplicação específica da escala (em utentes com DLC que são referidos para a intervenção de Fisioterapia). A pontuação inicial da QBPDS- VP deve ser considerada na interpretação de mudanças de pontuação, após a intervenção de Fisioterapia.------------ ABSTRACT: One of the main results of physiotherapy interventions for patients with Chronic Low Back Pain (CLBP) is decrease the functional disability. The Quebec Back Pain Disability Scale (QBPDS) is an instrument widely accepted internationally, in measuring the level of disability reported by individuals with CLBP. The purpose of this study is to contribute to the cultural adaptation of the Portuguese version of QBPDS (QBPDS - PV) and investigate the Responsiveness and Interpretability of QBPDS-PV. Methodology: This was a methodological and multicenter study, based on a sample of 132 subjects with CLBP. The patients were recruited from the waiting lists of 16 medicine rehabilitation service, in many Portugal districts. The Quebec Back Pain Disability Scale was administered in three different moments: T0 – baseline (patients in the waiting list); T1- one week after T0 (the beginning of treatment); and T2 – six weeks after T1 (the posttreatment). The data collected at T0 were used for factor analysis and to study the internal consistency (n = 132); paired sample data of T0 and T1 (n=132) were used for test-retest reliability, and sample data paired for T0 and T2 (n=120) used for responsiveness and interpretability analysis. The external anchor was the global perception of change, measured by the Portuguese version of Patient’s Global Impression of Change (PGIC) Scale. The minimal level of significance established was p ≤ 0,05. Data analysis was performed using the IBM SPSS Statistics software (version 20). Results: The QBPDS-PV is a unidimensional scale, demonstrates an excellent internal consistency (Cronbach's α=0.95) and satisfactory test-retest reliability (ICC= 0.696, 95% CI: 0.581–0.783). The scale revealed moderate responsiveness when applied to patients with CLBP ( = 0.426 and AUC= 0.741, 95% CI: 0.645 - 0.837). The Smallest Detectable Change (SDC) was 19 points, whereas the Minimal Clinically Important Change (MCIC) ranged between 7 (ROC curve method) and 8 points (by the "mean difference score"). The estimate was derived from the ROC curve by an optimal cutoff point of 6.5 points, with Area Under the Curve (AUC)= 0.741, sensitivity 72%, and specificity of 71%. A complementary analysis of the ROC curve based on differences in QBPDS scores from baseline, expressed in percentage, revealed an optimal cutoff point of -24% (AUC= 0.737, sensitivity of 71%, and specificity of 71%). For the highest initial scores of QBPDS-PV (≥ 34 points) was found an optimal cutoff of 10.5 points (AUC= 0.738, sensitivity of 73%, and specificity 67%). Conclusion: The QBPDS-PV demonstrated good levels of reliability and responsiveness, being recommended its use in the measurement and evaluation of disability of patients with CLBP. The SDC of 19 points determined the QBPDS‟ scale width of 19 to 81. This study proposes MCIC values for QBPDS –PV for this specific setting (in CLBP patients who are referred for physiotherapy intervention). The QBPDS –PV baseline score have to be taken into account while interpreting the score change after physiotherapy intervention.

Caracterização da intervenção da Fisioterapia em indivíduos com dor crónica lombar, e seus resultados a nível da dor e capacidade funcional

RESUMO: Objectivo: Este trabalho teve como objectivo contribuir para o processo de adaptação cultural da Quebec Back Pain Disability Scale (QBPDS), através do estudo da sua Validade de Constructo e Poder de Resposta, e caracterizar a intervenção realizada pela fisioterapia (FT) e os resultados obtidos em utentes com dor crónica lombar (DCL). Introdução: A redução da incapacidade funcional associada à DCL é um dos principais objectivos e resultados da intervenção da FT nestes utentes. Com o intuito de proceder à sua avaliação, pode recorrer-se a um conjunto de diferentes instrumentos de medida, sendo a QBPDS uma das escalas mais utilizadas para medir a incapacidade. Embora esta tenha sido anteriormente adaptada para a população portuguesa, não foram determinadas as suas propriedades psicométricas. Por outro lado, apesar da literatura referir que os serviços de FT são bastante procurados por indivíduos com DCL, em Portugal, a informação existente sobre a prática da FT nesta condição clínica e sobre os resultados obtidos é ainda escassa. Metodologia: Recorreu-se a um estudo de coorte prospectivo com uma amostra de conveniência, constituída por 119 indivíduos com DCL, que iniciaram fisioterapia em 16 centros/ hospitais/ clínicas de Fisioterapia/ utentes no domicílio, e cumpriam os critérios de inclusão e exclusão estabelecidos. Os utentes foram avaliados no momento pré-intervenção e num segundo momento até 6 semanas depois. As propriedades psicométricas da Quebec Back Pain Disability Scale –Versão Portuguesa (QBPDS-VP) avaliadas foram a Validade de Constructo e o Poder de Resposta. Posteriormente procedeu-se à caracterizar a prática da FT quanto às modalidades utilizadas, número de sessões de tratamento e duração do episódio de cuidados. Adicionalmente descreveu-se os resultados obtidos após a intervenção da FT, ao nível da dor e incapacidade. Resultados: Os resultados revelaram um resultado positivo para a Validade de Constructo da QBPDS-VP e um elevado Poder de Resposta (área abaixo da curva ROC = 0,736; IC95%=0,639-0,833). Apresenta ainda uma diferença mínima clinicamente importante (DMCI) de 7 pontos (sensibilidade =72,4% e especificidade = 69,8%). Aquando da intervenção da FT em casos de DCL, existe uma grande diversidade de modalidades realizadas combinadas em diferentes pacotes de intervenção, e verificou-se um número médio de sessões realizadas de 14,22 visitas por utente, numa duração de episódio de cuidados maioritariamente superior a 6 semanas. Os resultados da intervenção revelaram uma redução significativa da incapacidade funcional e da intensidade da dor (z= -7,440 e z=-6,625; respectivamente, p=0,000). Conclusão: Os resultados do presente estudo revelam que a QBPDS-VP possui uma boa Validade de Constructo e Poder de Resposta. Revela ainda que a intervenção da FT em casos de DCL, apesar de apresentar grande diversidade nas modalidades utilizadas por vezes até divergentes das recomendações dadas pelas normas de orientação clínica, e uma duração do episódio de cuidados aparentemente superior aos dados fornecidos pela literatura; proporciona uma redução significativa dos níveis de dor e incapacidade em utentes com DCL.------------ ABSTRACT: Objective: The aim of this study is to contribute to the process of cultural adaptation of the Quebec Back Pain Disability Scale (QBPDS), through the study of its Construct Validity and Responsiveness, and characterize the intervention performed by physical therapy (PT) and the results in patients with chronic low back pain (CLBP). Introduction: The reduction in functional disability associated with CLBP is one of the main purpose and results of physical therapy intervention in these patients. With the intention of evaluating them, the professionals can resort to a set of different measuring instruments, and the QBPDS is one of the most commonly used scales for measuring disability. Although this has been previously adapted for the Portuguese population, it was not determined its psychometric properties. Moreover, despite the literature noted that services for PT are quite sought by individuals with CLBP, in Portugal, the existing information on the practice of PT in this clinical condition and the results obtained are still scarce. Methodology: It was used a prospective cohort study with a convenience sample consisting of 119 individuals with CLBP, who started therapy at 16 centers / hospitals / Physiotherapy clinics / household physiotherapy, and fulfiled the inclusion and exclusion criteria established . The patients were assessed at pre-intervention and a second time after 6 weeks. Psychometric properties of the Quebec Back Pain Disability Scale-Portuguese version (QBPDS-VP) were evaluated to construct validity and responsiveness. Subsequently, it was proceeded to the characterization the practice of FT regarding to the modalities used, the number of treatment sessions and duration of the episode of care. Additionally it was described the results obtained after the intervention of the PT, the level of pain and the disability. Results: The results revealed a positive result for the Construct Validity of the QBPDS- VP and a high responsiveness (area under the ROC curve = 0.736, 95% CI 0.639 to 0.833). Minimal clinically important difference (MCID) also presents a 7-point (sensitivity = 72.4% and specificity = 69.8%). In the PT intervention in cases of CLBP there is a great diversity of procedures performed combined in different packages intervention, and it was found an average number of sessions of 14.22 visits per user, with a duration of the episode of care mostly higher to 6 weeks. The results of the intervention showed a significant reduction of disability and pain intensity (z = -7.440 z = -6.625, respectively, p = 0.000).Conclusion: The results of this study show that QBPDS-VP has a good construct validity and responsiveness. It also reveals that the PT intervention in cases of CLBP, despite showing great diversity in the methods used, that sometimes are also divergent to the recommendations given by clinical guidelines, and with a duration of episode of care apparently superior to data provided by the literature, provides an significant reduction in the levels of pain and disability in patients with DCL.

Classical design thinking to organization design in the tourism sector

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Retaining MBAs, from employees' point of view

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

The influence of animation on functional food intake in children

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

EDP InovCity pilot study proposal: A set-top box interface

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Study and characterization of the ZnPc:C60/MoOx interface in organic solar cells by means of photoelectron spectroscopy

Dissertation to obtain the academic degree of Master in materials engineering submitted to the Faculty of science and engineering of Universidade Nova de Lisboa

Structural and functional characterization of the gene products responsible for phototrophic iron oxidation by purple bacteria

Dissertação para a obtenção de grau de doutor em Bioquímica pelo Instituto de Tecnologia Química e Biológica. Universidade Nova de Lisboa

Architettura Prefabbricata –L’obra Colombo a Lisbona Project Management’s Point of View

L'Edilizia Ingegneria Materiali Tecnologia

Isolation and functional characterization of mononuclear phagocytes from human lepromatous lesions

In the present study, inflammatory cells from human lepromatous lesions were isolated by enzymatic dissociation of tissue. They were maintained in culture up to five days and their morphologic, cythochemicaland functional characteristics were described.

Brain-computer interface (BCI): a methodological proposal to assess the impacts of medical applications in 2022

Based on the report for “Project IV” unit of the PhD programme on Technology Assessment (Doctoral Conference) at Universidade Nova de Lisboa (December 2011). This thesis research has the supervision of António Moniz (FCT-UNL and ITAS-KIT) and Armin Grunwald (Karlsruhe Institute of Technology-ITAS, Germany). Other members of the thesis committee are Mário Forjaz Secca (FCT-UNL) and Femke Nijboer (University of Twente, Netherlands).