Intervenção da fisioterapia em indíviduos com osteoartrose do joelho: características da prática clínica, resultados obtidos e fatores de prognóstico para os resultados de sucesso

RESUMO:Introdução: O conhecimento acerca da prática da Fisioterapia, bem como a influência das características dos indivíduos com Osteoartrose do joelho (OA) no prognóstico dos resultados alcançados com a Fisioterapia, tem sido alvo de estudo em vários países. No entanto em Portugal, estudos desta natureza são escassos ou inexistentes. Objetivo: Este trabalho teve dois principais objetivos: Por um lado pretendeu caracterizar a prática da Fisioterapia e determinar os seus resultados em indivíduos com OA do joelho ao nível da intensidade da dor, incapacidade funcional e perceção global de melhoria; Por outro, identificar fatores preditivos para os resultados de sucesso após a intervenção da Fisioterapia. Metodologia: Trata-se de um estudo de coorte prospetivo com 77 participantes que foram avaliados antes e após a intervenção (8 semanas), com um follow-up de 3 meses. Procedeu-se à caracterização da prática da Fisioterapia quanto às modalidades utilizadas, número de sessões de tratamento e duração do episódio de cuidados. Os resultados obtidos foram medidos após intervenção (8 semanas) e num follow-up (3 meses), através da Escala Numérica da Dor (END), da versão Portuguesa do Questionário Knee Injury and Osteoarthritis Outcome Score (KOOS-PT), e da versão Portuguesa da Patient Global Impression of Change Scale (PGIC-PT). As características sociodemográficas e clínicas foram incluídas como potenciais fatores de prognóstico com base no critério de pontuação ≥5 na PGIC-PT e a análise dos dados foi realizada através do método de regressão logística multivariado no sentido de identificar as associações entre as variáveis na baseline e as variáveis de resultado (p<0.05). Resultados: Os resultados obtidos revelaram que existe uma grande diversidade de modalidades e procedimentos terapêuticos realizados pelos fisioterapeutas no tratamento da OA do joelho (em média 4 modalidades por utente), sendo os exercícios, a eletroterapia e a terapia manual, as intervenções mais frequentemente realizadas. Os resultados da intervenção revelaram uma redução significativa da intensidade da dor e da incapacidade funcional (medida pelas diferentes dimensões da KOOS-PT) às 8 semanas e aos 3 meses (p=0,001). A probabilidade de obter bons resultados na percepção de melhoria para realizar actividades da vida diária, está significativamente associada com a pontuação na dimensão KOOS AVD (OR=1,106, 95% IC 1,056-1,159) e com a intensidade da dor, (OR=0,543, 95% IC 0,300-0,983), na baseline. A probabilidade de obter bons resultados na percepção de melhoria relativa à dor, está significativamente associada com a pontuação na dimensão KOOS DOR (OR=1,116, 95% IC 1,030-1,209), e dimensão KOOS ADL (OR=1,123, 95% IC 1,014-1,243), na baseline. Conclusões: Os resultados do presente estudo revelam que a intervenção em Fisioterapia em casos de OA do joelho, apesar de utilizar uma grande diversidade de modalidades terapêuticas, proporciona uma redução significativa dos níveis de dor e incapacidade funcional em utentes com OA do joelho. Os resultados do presente estudo sugerem ainda que o sucesso da intervenção pode ser predito a partir de variáveis clinicas na baseline.------------ABSTRACT:Introduction: The knowledge about the practice of physical therapy, as well as the influence of the characteristics of subjects with knee osteoarthritis (OA) in the prognosis of the results achieved with physiotherapy, have been studied in several countries. However in Portugal, such studies are scarce or nonexistent. Objective: This study had two main aims: on one hand sought to characterize the practice of physical therapy and determine their outcomes in subjects with OA of the knee joint at the level of pain intensity, functional disability and global perception of improvement; Secondly, to identify predictive factors for successful outcomes after the intervention of physiotherapy. Methods: This was a prospective cohort study with 77 participants who were evaluated before and after the intervention (8 weeks), with a follow-up of 3 months. Proceeded to characterize the practice of physical therapy as modalities used, number of treatment sessions and duration of the period of care. The results were measured after intervention (8 weeks) and a follow-up (3 months) by a Numerical Rating Scale (NRS), the Portuguese version of the Knee Injury and Osteoarthritis Questionnaire Outcome Score (KOOS-PT) and the Patient Global Impression of Change Scale- Portuguese Version (PGIC-PT). The sociodemographic and clinical characteristics were included as potential prognostic factors based on scoring criteria≥5 na PGIC-PT and data analysis was performed using the method of multivariate logistic regression to identify associations between variables at baseline and outcome variables (p<0.05). Results: The results revealed that there is a great diversity of modalities and therapeutic procedures performed by physiotherapists in the treatment of knee OA (average 4 per user modes), with exercises, electrotherapy and manual therapy interventions most frequently performed. The results of intervention showed a significant reduction in the severity of pain and functional disability (measured by the different dimensions of the KOOS-PT) at 8 weeks and at 3 months (p = 0.001). The probability of getting good results in the perception of improvement to perform activities of daily living, is significantly associated with scores on the dimension KOOS ADL (OR=1,106, 95% CI 1,056-1,159) and the intensity of pain (OR = 0.543, 95% CI 0.300 to 0.983) at baseline. The probability of getting good results in the perception of improvement of the pain is significantly associated with scores on the KOOS PAIN (OR = 1.116, 95% CI 1.030 to 1.209) and KOOS ADL (OR = 1.123, 95% CI 1.014 to 1.243) at the baseline. Conclusions: The results of this study show that Physiotherapy treatment in cases of knee OA, provide a significant reduction of pain and disability among users with knee OA, despite the wide variety of therapeutic modalities. The results of this study also suggest that the success of the intervention can be predicted from clinical variables at baseline.

Indicadores de prognóstico em utentes com disfunção do ombro submetidos a uma intervenção terapêutica direcionada para a estabilidade dinâmica da escápulo-torácica

RESUMO: Introdução/ Objetivo: Segundo a revisão sistemática de Chester e colaboradores (2013b)apenas dois fatores de prognóstico demonstraram uma associação consistente com o resultado que foram a duração dos sintomas e a funcionalidade na avaliação inicial. O objetivo do estudo é identificar indicadores de bom e mau prognóstico em utentes com disfunção do complexo articular do ombro (DCAO), tendo por base, aspetos da avaliação inicial do utente e critérios de alta de abolição da dor, aumento da funcionalidade e da estabilidade dinâmica considerando uma intervenção terapêutica direcionada para o aumento da estabilidade dinâmica da escápulo-torácica. Metodologia: Efetuou-se um estudo de coorte clínico retrospetivo. Para tal, aplicou-se um protocolo de intervenção terapêutica e analisou-se os resultados. A amostra foi constituída por 82 indivíduos com DCAO [53 com síndrome do conflito subacromial (SCSA) e 29 com instabilidade da glenoumeral (IGU)], residentes nos distritos de Lisboa, Setúbal e Santarém com o intuito de iniciar tratamento de fisioterapia. A análise dos dados foi efetuada tendo em consideração dois procedimentos: análise univariada (através do método de Kaplan-Meier para cada CVP) e análise multifatorial (pela análise de regressão de Cox e regressão logística nos grupos de utentes com SCSA, IGU e DCAO). Resultados: O tempo mediano de continuação no tratamento em fisioterapia foi de 7 semanas para os utentes com SCSA e 6 semanas para utentes com IGU. Segundo o teste de Logrank, na análise univariada, existem sete e oito covariáveis preditoras (CVP) com associação estatisticamente significativa (p<0,05) para o subgrupo SCSA e IGU, respectivamente. De acordo com estes resultados, a primeira parte da DASH e a SPADI são as únicas CVP com associação comuns às duas disfunções. Pela análise multifatorial e, em congruência com o teste de Wald, nenhuma das CVP contribui estatisticamente para o modelo preditivo de continuidade do tratamento de fisioterapia em qualquer um dos três modelos estudados: subgrupo SCSA, subgrupo IGU e utentes com DCAO. Conclusão: Por uma análise univariada verificou-se que existem CVP associadas à alta dos tratamentos em fisioterapia e estas não são as mesmas em ambas as DCAO. Contudo, a magnitude do efeito de cada CVP nos modelos multifatoriais definidos para os grupos de utentes com SCSA, IGU e DCAO não demonstraram valor estatisticamente significativo pelo que não foi possível determinar modelos de prognóstico em utentes com DCAO.-------------ABSTRACT: Background/ Purpose: According with the systematic review from Chester and collaborators (2013b) just two prognostic factors demonstrated a consistent association with the outcome: the duration of symptoms and functionality in the initial assessment. The purpose of the study is to identify indicators of good and poor prognosis in patients with shoulder’s dysfunctions, based on aspects of the initial assessment and discharge criteria of absence of pain, increased functionality and dynamic stability considering a therapeutic intervention used to increase the dynamic stability of scapulo-thoracic. Methodology: It was conducted a retrospective study of clinical cohort. For this purpose it was applied a protocol with therapeutic intervention and the results were analyzed. The sample consisted of 82 individuals with shoulder’s dysfunction (53 with subacromial impingement (SIMP) and 29 with shoulder instability (SINS) residing in the districts of Lisbon, Setúbal and Santarém in order to start physiotherapy. Data analysis was performed taking into account two procedures: univariate analysis [using the Kaplan-Meier method for each co-variant predictor variable (CVP)] and multifactorial analysis [analysis by Cox regression and logistic regression on groups of patients with SIMP, SINS and shoulder’s dysfunction (SD)]. Results: The median time of follow-up treatment at physical therapy was 7 weeks for patients with SIMP and 6 weeks for patients with SINS. According to the Logrank test in the univariate analysis, there are seven and eight CVP with a statistically significant association (p<0.05) for the patients with SIMP and SINS, respectively. According to these results, the first part of the DASH and SPADI are the only CVP common to both disorders association. By multifatorial analyses, and in agreement with the Wald test, none of the CVP contributes statistically to the predictive model of continuity of physiotherapy treatment in any of the three studied models: patients with SIMP, patients with SINS and patients with SD. Conclusion: In an univariate analysis, it was verified that there are CVP associated with discharge from treatments of physical therapy and these are not the same in both SD. However, the magnitude of effect of each CVP in multifactorial models for defined patients groups with SIMP, SINS and SD showed no statistically significant. Therefore, it was not possible to determine prognostic models for patients with SD.

The good, the bad and the ugly: The fall and resolution of Banco Espírito Santo

This case study – and accompanying teaching note – briefly describes the history of the Espírito Santo family, a banking dynasty who led one of Portugal’s leading economic and financial groups, along with its “crown jewel”, Banco Espírito Santo. It chronicles how the corporate governance issues at BES allowed the family to exploit the bank, its shareholders and its customers, so as to support its unprofitable non-financial businesses. This left the bank in a poor financial situation, which deteriorated beyond control, leaving regulators – whose actions are also analysed here – with no alternative, amidst a severe liquidity crisis, but to apply a resolution measure, pinning large losses on junior bondholders and shareholders before recapitalising the bank.

Semantics bias in cross-national comparative analyses : Is it good or bad to have "fair" health?

The Health Behavior in School-aged Children is a cross-national study collecting data on social and health indicators on adolescents in 43 countries. The study provides comparable data on health behaviors and health outcomes through the use of a common protocol, which have been a back bone of the study sine its initiation in 1983. Recent years, researchers within the study have noticed a questionable comparability on the widely used item on self-rated health. One of the four response categories to the item "Would you say your health is….?" showed particular variation, as the response category "Fair" varied from 20 % in Latvia and Moldova to 3-4 % in Bulgaria and Macedonia. A qualitative mini-survey of the back-translations showed that the response category "Fair" had a negative slant in 25 countries, a positive slant in 10 countries and was considered neutral in 9 countries. This finding indicates that there are what may be called semantic issues affecting comparability in international studies, since the same original word (in an English original) is interpreted differently across countries and cultures. The paper test and discuss a few possible explanations to this, however, only leaving to future studies to hold a cautious approach to international comparisons if working with the self-rated health item with four response categories.

Essays in health economics: Volume-Outcome Effect, upcoding behaviour and the evaluation of a short-term intervention program

Evidence in the literature suggests a negative relationship between volume of medical procedures and mortality rates in the health care sector. In general, high-volume hospitals appear to achieve lower mortality rates, although considerable variation exists. However, most studies focus on US hospitals, which face different incentives than hospitals in a National Health Service (NHS). In order to add to the literature, this study aims to understand what happens in a NHS. Results reveal a statistically significant correlation between volume of procedures and better outcomes for the following medical procedures: cerebral infarction, respiratory infections, circulatory disorders with AMI, bowel procedures, cirrhosis, and hip and femur procedures. The effect is explained with the practice-makes-perfect hypothesis through static effects of scale with little evidence of learning-by-doing. The centralization of those medical procedures is recommended given that this policy would save a considerable number of lives (reduction of 12% in deaths for cerebral infarction).

An unusual case of heart failure due to Plasmodium vivax infection with a favorable outcome

Although malaria is one of the oldest types of parasitic infection, we have recently witnessed substantial changes in the outcome of malarial infections. Severe Plasmodium vivax infections have recently become more frequent, and are occasionally associated with fatal outcomes. Cardiac arrhythmia and myocardial failure have also been reported, typically in association with Plasmodium falciparum infections. We report a case of myocarditis and heart failure, due to Plasmodium vivaxinfection, along with the favorable outcome.

Intraventricular hemorrhage in very low birth weight infants: associated risk factors and outcome in the neonatal period

Intraventricular hemorrhage (IVH) is a severe complication in very low birth weight (VLBW) newborns (NB). With the purpose of studying the incidence of IVH, the associated risk factors, and the outcomes for these neonates, we studied all the VLBW infants born in our neonatal unit. Birth weight, gestational age, presence of perinatal asphyxia, mechanical ventilation, length of hospitalization, apnea crisis, hydrocephalus, and periventricular leukomalacia were analyzed. The diagnosis of IVH was based on ultrasound scan studies (Papile's classification) performed until the tenth day of life and repeated weekly in the presence of abnormalities. Sixty-seven/101 neonates were studied. The mortality rate was 30.6% (31/101) and the incidence of IVH was 29.8% (20/67) : 70% grade I, 20% grade III and 10% grade IV. The incidence of IVH in NB <1,000 g was 53.8% (p = 0.035) and for gestational age <30 weeks was 47.3% (p = 0.04), both considered risk factors for IVH. The length of hospitalization (p = 0.00015) and mechanical ventilation (p = 0.038) were longer in IHV NB. The IVH NB had a relative risk of 2.3 of developing apnea (p = 0.02), 3.7 of hydrocephalus (p = 0.0007), and 7.7 of periventricular leukomalacia (p < 0.00001). The authors emphasize the importance of knowing the risk factors related to IVH so as to introduce prevention schemes to reduce IVH and to improve outcomes of affected newborns.

Use of corticosteroids and the outcome of infants with bronchopulmonary dysplasia

Ventilator-dependent premature infants are often treated with dexamethasone. Several trials showed that steroids while improve pulmonary compliance and facilitate extubation, some treated infants may have adverse effects, such as alterations of growth curves. We conducted this retrospective study to evaluate the effects of steroids on mechanical ventilation, oxygen therapy, hospital length stay and mortality, in ventilator-dependent infants with bronchopulmonary dysplasia (BPD) (defined as the need of oxygen supplementation at 28 days of life). Twenty-six newborns with BPD were evaluated during 9 -- 42 days postpartum (mean = 31 days) and were divided into two groups: Group I - 14 newborns that did not receive dexamethasone, and Group II - 12 newborns that received dexamethasone at 14 --21 days of life. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously for 3 days, after which the dose was tapered. RESULTS: There were no statistically significant differences in the mean length of mechanical ventilation (Group I - 37 days, Group II - 35 days); oxygen supplementation (Group I - 16 days, Group II - 29 days); hospital stay (Group I - 72 days, Group II - 113 days); mortality (Group I - 35.7%, Group II - 41.6%). At birth, Group II was lighter (BW: Group I - 1154 grams ± 302, Group II - 791 grams ± 165; p < 0.05) and smaller (height: Group I - 37.22 cm ± 3.3, Group II - 33.5 ± 2.4; p< 0.05) than Group I. At 40 weeks, there were no statistically significant differences between groups in relation to anthropometric measurements. CONCLUSIONS: The use of corticosteroids in bronchopulmonary dysplasic infants may influence the somatic growth during its use. However, after its suspension, a recovery seems to occur, suggesting that its influence could be transitory.

Critérios de adequação em ecocardiografia e a repercussão clinica no outcome do paciente: a realidade do Lister Hospital - East and North Hertfordshire NHS Trust, Reino Unido

RESUMO - Introdução: Os critérios de adequação (Appropriate Use Criteria - AUC) em Ecocardiografia Transtorácica (ETT) foram publicados com o intuito de permitir o uso racional da ecocardiografia, de influenciar decisões clinicas, prestar cuidados de saúde de elevada qualidade e melhorar o outcome dos pacientes. A relação entre a adequação destes e o seu impacto clinico ainda não se encontra largamente estudada. Objectivo: Neste estudo pretendeu-se avaliar o grau de adesão aos AUC em ETT, em diferentes contextos de atendimento e de acordo com diferentes especialidades, bem como o impacto clínico do exame no outcome do paciente, num hospital público terciário no Reino Unido. Metodologia: 859 ETTs realizados consecutivamente no mês de Janeiro de 2014, foram revistos por forma a avaliar a sua adequação e foram classificados como adequados, incertos ou inadequados de acordo com as guidelines de 2011. De seguida os registos dos pacientes foram revistos com o intuito de avaliar o impacto clinico dos ETTs e foram classificados de acordo com uma das 3 seguintes categorias: (1) alteração ativa dos cuidados – por continuação ou descontinuação dos cuidados como resultado do ETT, (2) continuação dos cuidados – sem continuação ou descontinuação dos cuidados, mas comunicação ao paciente dos resultados do ETT, (3) sem alteração dos cuidados – os cuidados ao paciente já estavam a ser aplicados previamente ao resultado do ETT, causa de sintomas já estabelecida no momento da requisição para exame, exame prévio explicativo dos sintomas e sem indicação aguda para novo ETT, terapêutica não alterada ou inexistência de documentação relativa aos achados ecocardiográficos. Pacientes cujos registos não se encontravam disponíveis foram excluídos (259). Todas as classificações foram avaliadas por uma cardiologista independente, sem relação direta com o estudo. Resultados: A nossa amostra apresentou uma média de idades de 63 ± 17 anos, com uma equilíbrio de géneros. A maioria dos exames foi solicitada em contexto de ambulatório (81,4%), pela Cardiologia (50,3%) e pela Medicina Geral e Familiar (13,4%). Relativamente aos achados ecocardiográficos dos exames, 7,6% demonstraram disfunção sistólica do ventrículo esquerdo moderada a grave, 4,0% revelaram doença valvular grave e 5,1% hipertensão pulmonar significativa. Em relação à adequação dos pedidos para ETTs, 76,5% foram adequados, 7,1% inadequados e 12,6% incertos. Relativamente ao impacto clínico dos ETTs, 42,7% dos exames revelaram uma alteração ativa nos cuidados, 15,6% mostraram uma continuação dos cuidados e 11,5% demonstraram não haver alteração nos cuidados. A idade (P=0,05), o contexto de atendimento (P<0,01) e o pedido realizado pela especialidade medicina geral e familiar (MGF) (P=0,02) foram os preditores mais importantes de uma alteração ativa nos cuidados. Numa perspectiva de prestação de cuidados a uma população mais idosa, o contexto de atendimento, a presença de achados ecocardiográficos significativos e a não alteração dos cuidados apresentam uma relação significativa com a idade. Conclusões: Os dados demonstram que quase 8 em cada 10 ETTs foram considerados adequados e que 4 em cada 10 exames não apresentaram alteração ativa dos cuidados.

Good vibrations

The work reported in this thesis addresses the research question of when and how positive psychological states impact positive behavior and positive organizational development. We present two theoretical essays and three empirical studies to find possible answers to this question and we use a multitude of methodologies with different epistemological assumptions, including quantitative correlation analysis, social network analysis and qualitative grounded theory analysis. In the whole, our work shows that positive psychological states are fundamental to promote individual and organizational higher-levels of performance and well-being. It also points that the capability to induce positive psychological states in others (an “alter-positive” approach) is a powerful way to develop outstanding individuals and organizations. In a broader sense, it stresses the need to promote good vibrations as a fundamental route to create a better world.

Analysis of outcome and cancer stem cells status in patients with resectable pancreatic adenocarcinoma

RESUMO: Actualmente, a única possibilidade de cura para doentes com adenocarcinoma do pâncreas (PDAC) é a ressecção cirúrgica, no início deste estudo, perguntamo-nos se os predictores clínico-patológicos clássicos de prognostico poderiam ser validados em uma grande cohort de doentes com cancro do pâncreas ressecável e se outros predictores clínicos poderiam ter um papel na decisão de que doentes beneficiariam de ressecção cirúrgica. No capítulo 2, observamos que até 30% dos doentes morrem no primeiro ano após a ressecção cirúrgica, pelo que o nosso objectivo foi determinar factores pré-operatórios que se correlacionam com mortalidade precoce após ressecação cirúrgica com recurso a um instrumento estatisticamente validado, o Charlson-Age Comorbidity Index (CACI), determinamos que um CACI score superior a 4 foi preditivo de internamentos prolongados (p <0,001), complicações pós-operatórias (p = 0,042), e mortalidade em 1 ano pós- ressecção cirúrgica (p <0,001). Um CACI superior a 6 triplicou a mortalidade no primeiro ano pós-cirurgia e estes doentes têm menos de 50% de probabilidade de estarem vivos um ano após a cirurgia. No capítulo 3, o nosso objectivo foi identificar uma proteína de superfície que se correlacionasse estatisticamente com o prognostico de doentes com adenocarcinoma do pâncreas e permitisse a distinção de subgrupos de doentes de acordo com as suas diferenças moleculares, perguntamo-nos ainda se essa proteína poderia ser um marcador de células-estaminais. No nosso trabalho anterior observamos que as células tumorais na circulação sanguínea apresentavam genes com características bifenotípica epitelial e mesenquimal, enriquecimento para genes de células estaminais (ALDH1A1 / ALDH1A2 e KLF4), e uma super-expressão de genes da matriz extracelular (colagénios, SPARC, e DCN) normalmente identificados no estroma de PDAC. Após a avaliação dos tumores primários com RNA-ISH, muitos dos genes identificados, foram encontrados co-localizando em uma sub-população de células na região basal dos ductos pancreáticos malignos. Além disso, observamos que estas células expressam o marcador SV2A neuroendócrino, e o marcador de células estaminais ALDH1A1/2. Em comparação com tumores negativos para SV2, os doentes com tumores SV2 positivos apresentaram níveis mais baixos de CA 19-9 (69% vs. 52%, p = 0,012), tumores maiores (> 4 cm, 23% vs. 10%, p = 0,0430), menor invasão de gânglios linfáticos (69% vs. 86%, p = 0,005) e tumores mais diferenciados (69% vs. 57%, p = 0,047). A presença de SV2A foi associada com uma sobrevida livre de doença mais longa (HR: 0,49 p = 0,009) bem como melhor sobrevida global (HR: 0,54 p = 0,018). Em conjunto, esta informação aponta para dois subtipos diferentes de adenocarcinoma do pâncreas, e estes subtipos co-relacionam estatisticamente com o prognostico de doentes, sendo este subgrupo definido pela presença do clone celular SV2A / ALDH1A1/2 positivo com características neuroendócrinas. No Capítulo 4, a expressão de SV2A no cancro do pâncreas foi validado em linhas celulares primárias. Demonstramos a heterogeneidade do adenocarcinoma do pâncreas de acordo com características clonais neuroendócrinas. Ao comparar as linhas celulares expressando SV2 com linhas celulares negativas, verificamos que as linhas celulares SV2+ eram mais diferenciadas, diferindo de linhas celulares SV2 negativas no que respeita a mutação KRAS, proliferação e a resposta à quimioterapia. No capítulo 5, perguntamo-nos se o clone celular SV2 positivo poderia explicar a resistência a quimioterapia observada em doentes. Observamos um aumento absoluto de clones celulares expressando SV2A, em múltiplas linhas de evidência - doentes, linhas de células primárias e xenotransplantes. Embora, tenhamos sido capazes de demonstrar que o adenocarcinoma do pâncreas é uma doença heterogénea, consideramos que a caracterização genética destes clones celulares expressando SV2A é de elevada importância. Pretendemos colmatar esta limitação com as seguintes estratégias: Após o tratamento com quimioterapia neoadjuvante na nossa coorte, realizamos microdissecação a laser das amostras primarias em parafina, de forma a analisar mutações genéticas observadas no adenocarcinoma pancreático; em segundo lugar, pretendemos determinar consequências de knockdown da expressão de SV2A em nossas linhas celulares seguindo-se o tratamento com gemicitabina para determinação do papel funcional de SV2A; finalmente, uma vez que os nossos esforços anteriores com um promotor - repórter e SmartFlare ™ falharam, o próximo passo será realizar RNA-ISH PrimeFlow™ seguido de FACS e RNA-seq para caracterização deste clone celular. Em conjunto, conseguimos provar com várias linhas de evidência, que o adenocarcinoma pancreático é uma doença heterogénea, definido por um clone de células que expressam SV2A, com características neuroendócrinas. A presença deste clone no tecido de doentes correlaciona-se estatisticamente com o prognostico da doença, incluindo sobrevida livre de doença e sobrevida global. Juntamente com padrões de proliferação e co-expressão de ALDH1A1/2, este clone parece apresentar um comportamento de células estaminais e está associado a resistência a quimioterapia, uma vez que a sua expressão aumenta após agressão química, quer em doentes, quer em linhas de células primárias.----------------------------- ABSTRACT: Currently, the only chance of cure for patients with pancreatic adenocarcinoma is surgical resection, at the beginning of my thesis studies, we asked if the classical clinicopathologic predictors of outcome could be validated in a large cohort of patients with early stage pancreatic cancer and if other clinical predictors could have a role on deciding which patients would benefit from surgery. In chapter 2, we found that up to 30% of patients die within the first year after curative intent surgery for pancreatic adenocarcinoma. We aimed at determining pre-operative factors that would correlate with early mortality following resection for pancreatic cancer using a statistically validated tool, the Charlson-Age Comorbidity Index (CACI). We found that a CACI score greater than 4 was predictive of increased length of stay (p<0.001), post-operative complications (p=0.042), and mortality within 1-year of pancreatic resection (p<0.001). A CACI score of 6 or greater increased 3-fold the odds of death within the first year. Patients with a high CACI score have less than 50% likelihood of being alive 1 year after surgery. In chapter 3 we aimed at identifying a surface protein that correlates with patient’s outcome and distinguishes sub-groups of patients according to their molecular differences and if this protein could be a cancer stem cell marker. The most abundant class of circulating tumor cells identified in our previous work was found to have biphenotypic features of epithelial to mesenchymal transition, enrichment for stem-cell associated genes (ALDH1A1/ALDH1A2 and KLF4), and an overexpression of extracellular matrix genes (Collagens, SPARC, and DCN) normally found in the stromal microenvironment of PDAC primary tumors. Upon evaluation of matched primary tumors with RNA-ISH, many of the genes identified were found to co-localize in a sub-population of cells at the basal region of malignant pancreatic ducts. In addition, these cells expressed the neuroendocrine marker SV2A, and the stem cell marker ALDH1A1/2. Compared to SV2 negative tumors, patients with SV2 positive tumors were more likely to present with lower CA 19-9 (69% vs. 52%, p = 0.012), bigger tumors (size > 4 cm, 23% vs. 10%, p= 0.0430), less nodal involvement (69% vs. 86%, p = 0.005) and lower histologic grade (69% vs. 57%, p = 0.047). The presence of SV2A expressing cells was associated with an improved disease free survival (HR: 0.49 p=0.009) and overall survival (HR: 0.54 p=0.018) and correlated linearly with ALDH1A2. Together, this information points to two different sub-types of pancreatic adenocarcinoma, and these sub-types correlated with patients’ outcome and were defined by the presence of a SV2A/ ALDH1A1/2 expressing clone with neuroendocrine features. In Chapter 4, SV2A expression in cancer was validated in primary cell lines. We were able to demonstrate pancreatic adenocarcinoma heterogeneity according to neuroendocrine clonal features. When comparing SV2 expressing cell lines with SV2 negative cell lines, we found that SV2+ cell lines were more differentiated and differ from SV2 negative cell lines regarding KRAS mutation, proliferation and response to chemotherapy. In Chapter 5 we aimed at determining if this SV2 positive clone could explain chemoresistance observed in patients. We found an absolute increase in SV2A expressing cells, with multiple lines of evidence, in patients, primary cell lines and xenografts. Although, we have been able to show evidence that pancreatic adenocarcinoma is a heterogeneous disease, our findings warrant further investigation. To further characterize SV2A expressing clones after treatment with neoadjuvant chemotherapy in our cohort, we have performed laser capture microdissection of the paraffin embedded tissue in this study and will analyze the tissue for known genetic mutations in pancreatic adenocarcinoma; secondly, we want to know what will happen after knocking down SV2A expression in our cell lines followed by treatment with gemcitabine to determine if SV2A is functionally important; finally, since our previous efforts with a promoter – reporter and SmartFlare™ have failed, we will utilize a novel PrimeFlow™ RNA-ISH assay followed by FACS and RNA sequencing to further characterize this cellular clone. Overall our data proves, with multiple lines of evidence, that pancreatic adenocarcinoma is a heterogeneous disease, defined by a clone of SV2A expressing cells, with neuroendocrine features. The presence of this clone in patients’ tissue correlates with patient’s disease free survival and overall survival. Together with patterns of proliferation and ALDH1A1/2 co-expression, this clone seems to present a stem-cell-like behavior and is associated with chemoresistance, since it increases after chemotherapy, both in patients and primary cell lines.

Momentos de inovação e mudança na terapia cognitivo comportamental para a bulimia nervosa

Dissertação de mestrado em Psicologia Aplicada

Honours students: good marks and what else?

Currently in Portugal academic excellence in higher education is given recognition through merit prizes. Because honours students can be seen as having the potential to achieve imporant levels of professional expertise, especially if they have some personal skills, it is important to know not only the marks of the students but also the personal characteristics that contribute to academic success and which may also be important for career success. Some theoretical models of giftedness and excellence agree with this idea and this work considers the latest contribution of Renzulli (2005) where it is pointed out that excellent achievements result from the combination of motivational, intellectual and creative factors as well as from co-cognitive factors which are most associated with personality functioning in a particular context. The main purpose of this paper is to analyze how honours students differ from their classmates in various psychological dimensions: Cognition-creativity, Motivation and Learning Strategies, Persistence, Social Interaction, Drive for Excellence and Cultural Interest. These dimensions were measured by the Inventory of Psychological Characteristics Associated with Academic Performance (ICPADA), which was constructed taking into consideration the previous study of Scaeger et al. (2012). The sample included 914 Portuguese higher educatoin students from a first cycle degree in the Bologna process. Participants were selected from three different fields of study: Social and Human Sciences; Science and Technology; Arts and Humanities. The data collected through the administration of the ICPADA was presented, and the results revealed a higher self-perception by honours students in all areas analyzed, with the exception of the dimension of social interaction. In addition an interaction effect was revealed for persistence, social interaction, and cultural interest. The field of study and whether the participants were honours students or not were also taken into account. Some implications for future studies are presented here along with possible interventions for honours students.

Measuring university-to-work success: development of a new scale

Purpose – The purpose of this paper is to develop a subjective multidimensional measure of early career success during university-to-work transition. Design/methodology/approach – The construct of university-to-work success (UWS) was defined in terms of intrinsic and extrinsic career outcomes, and a three-stage study was conducted to create a new scale. Findings – A preliminary set of items was developed and tested by judges. Results showed the items had good content validity. Factor analyses indicated a four-factor structure and a second-order model with subscales to assess: career insertion and satisfaction, confidence in career future, income and financial independence, and adaptation to work. Third, the authors sought to confirm the hypothesized model examining the comparative fit of the scale and two alternative models. Results showed that fits for both the first- and second-order models were acceptable. Research limitations/implications – The proposed model has sound psychometric qualities, although the validated version of the scale was not able to incorporate all constructs envisaged by the initial theoretical model. Results indicated some direction for further refinement. Practical implications – The scale could be used as a tool for self-assessment or as an outcome measure to assess the efficacy of university-to-work programs in applied settings. Originality/value – This study provides a useful single measure to assess early career success during the university-to-work transition, and might facilitate testing of causal models which could help identify factors relevant for successful transition.

OPM3® Portugal project: information systems and technologies organizations: outcome analysis

Increasing the maturity in Project Management (PM) has become a goal for many organizations, leading them to adopt maturity models to assess the current state of its PM practices and compare them with the best practices in the industry where the organization is inserted. One of the main PM maturity models is the Organizational Project Management Maturity Model (OPM3®), developed by the Project Management Institute. This paper presents the Information Systems and Technologies organizations outcome analysis, of the assesses made by the OPM3® Portugal Project, identifying the PM processes that are “best” implemented in this particular industry and those in which it is urgent to improve. Additionally, a comparison between the different organizations’ size analyzed is presented.