Religious free speech and anti-discrimination laws in Australia

This thesis addresses the delicate relationship between Religious Free Speech and Australian Anti-discrimination laws. There are an increasing number of conflicts arising between religious and secular speech. Different opinions related to sensitive matters often result in social and legal disputes. Some of these disputes become complaints under Anti-discrimination laws and arguably lead to less freedom of conscience and speech. This thesis focuses on ‘the relationship between Religious Free Speech and Anti-discrimination laws’. This is done though critical analysis of relevant literature, cases and legislation, contextualising them in response to the questions proposed in the research paper

Product information management for complex modular security systems

Um sistema PIM gere toda a informação que possibilita a comercialização dos produtos através de diferentes canais. A sua importância durante o ciclo de vida de um produto aumentou devido à sofisticação técnica dos produtos, a gerir internamente e a publicar externamente. Sistemas, tais como o ERP e o CCMS, deverão integrar-se com um sistema PIM, o qual deve funcionar como a “espinha dorsal” da informação de produto. O presente projeto tem como objetivo principal a criação de uma solução para gerir a informação de produto para sistemas modulares complexos. A proposta de solução inclui a criação de uma ontologia para parte dos inúmeros sistemas disponíveis no catálogo de produtos de uma das maiores organizações multinacionais do setor de engenharia e tecnologia a nível mundial. O processo de criação da solução proposta baseou-se na metodologia de investigação pesquisa-ação e foi dividido em cinco fases. Na fase de diagnóstico descreveu-se e analisou-se a atual situação dos sistemas ERP e CCMS que gerem o catálogo online dos sistemas de produtos comercializados. Levantaram-se ainda as taxonomias de produto atuais e elaborou-se a proposta. Na fase de planeamento da ação descreveram-se a equipa de trabalho, a abordagem inspirada na metodologia Agile usada para desenvolver a solução, as reuniões de planeamento, os parceiros de trabalho, as ferramentas a usar e a sua justificação. Na fase de tomada de ação foi descrito o processo de criação da solução ontológica e o resultado final, incluindo a construção das novas taxonomias e a sua validação pelos especialistas. Propuseram-se exemplos e representações gráficas usando a ferramenta Protégé. Na fase de avaliação, a solução ontológica foi testada, tendo-se validado que os requisitos necessários foram satisfeitos pela estrutura. Na fase de especificação de aprendizagem propuseram-se os próximos passos para a implementação e gestão futura do modelo ontológico. Com esta solução, a organização poderá gerir mais eficientemente a informação de produto e a estrutura de dados. Ela possui versatilidade para gerir produtos individuais ou sistemas modulares complexos e melhorar a sua comunicação com o cliente. Além disso, a ontologia tem ainda um enorme potencial se combinada com técnicas de IA. Algumas limitações do projeto e propostas de trabalhos futuros foram ainda apresentadas

Evolving meaning: using genetic programming to learn similarity perspectives for mining biomedical data

Tese de mestrado, Bioinformática e Biologia Computacional, Universidade de Lisboa, Faculdade de Ciências, 2019Nos últimos anos, as ontologias biomédicas tornaram-se fundamentais para descrever o conhecimento biológico na forma de grafos de conhecimento. Consequentemente, foram propostas várias abordagens de mineração de dados que tiram partido destes grafos de conhecimento. Estas abordagens baseiam-se em representações vetoriais que podem não capturar toda a informação semântica subjacente aos grafos. Uma abordagem alternativa consiste em utilizar a semelhança semântica como representação semântica. No entanto, como as ontologias podem modelar várias perspetivas, a semelhança semântica pode ser calculada tendo em consideração diferentes aspetos. Deste modo, diferentes tarefas de aprendizagem automática podem exigir diferentes perspetivas do grafo de conhecimento. Selecionar os aspetos semânticos mais relevantes, ou a melhor combinação destes para suportar uma determinada tarefa de aprendizagem não é trivial e, normalmente, exige conhecimento especializado. Nesta dissertação, apresentamos uma nova abordagem usando a Programação Genética sobre um conjunto de semelhanças semânticas, cada uma calculada com base num aspeto semântico dos dados, para obter a melhor combinação para uma dada tarefa de aprendizagem supervisionada. A metodologia inclui três etapas sequenciais: calcular a semelhança semântica para cada aspeto semântico; aprender a melhor combinação desses aspetos usando a Programação Genética; integrar a melhor combinação com o algoritmo de classificação. A abordagem foi avaliada em nove conjuntos de dados para prever a interação entre proteínas. Nesta aplicação, a Gene Ontology foi utilizada como grafo de conhecimento para suportar o cálculo da semelhança semântica. Como referência, utilizámos uma variação da abordagem proposta com estratégias manuais frequentemente utilizadas para combinar os aspetos semânticos. Os resultados demonstraram que as combinações obtidas com a Programação Genética superaram as combinações escolhidas manualmente que emulam o conhecimento especializado. A nossa abordagem foi também capaz de aprender modelos agnósticos em relação à espécie usando diferentes combinações de espécies para treino e teste, ultrapassando assim as limitações de prever interações entre proteínas para espécies com poucas interações conhecidas. Esta nova metodologia supera as limitações impostas pela necessidade de selecionar manualmente os aspetos semânticos que devem ser considerados para uma dada tarefa de aprendizagem. A aplicação da metodologia à previsão da interação entre proteínas foi bem-sucedida, perspetivando outras aplicações.In recent years, biomedical ontologies have become important for describing existing biological knowledge in the form of knowledge graphs. Data mining approaches that work with knowledge graphs have been proposed, but they are based on vector representations that do not capture the full underlying semantics. An alternative is to use machine learning approaches that explore semantic similarity. However, since ontologies can model multiple perspectives, semantic similarity computations for a given learning task need to be fine-tuned to account for this. Obtaining the best combination of semantic similarity aspects for each learning task is not trivial and typically depends on expert knowledge. In this dissertation, we developed a novel approach that applies Genetic Programming over a set of semantic similarity features, each based on a semantic aspect of the data, to obtain the best combination for a given supervised learning task. The methodology includes three sequential steps: compute the semantic similarity for each semantic aspect; learn the best combination of those aspects using Genetic Programming; integrate the best combination with a classification algorithm. The approach was evaluated on several benchmark datasets of protein-protein interaction prediction. The quality of the classifications is evaluated using the weighted average F-measure for each dataset. As a baseline, we employed a variation of the proposed methodology that instead of using evolved combinations, uses static combinations. For protein-protein interaction prediction, Gene Ontology was used as the knowledge graph to support semantic similarity, and it outperformed manually selected combinations of semantic aspects emulating expert knowledge. Our approach was also able to learn species-agnostic models with different combinations of species for training and testing, effectively addressing the limitations of predicting proteinprotein interactions for species with fewer known interactions. This dissertation proposes a novel methodology to overcome one of the limitations in knowledge graph-based semantic similarity applications: the need to expertly select which aspects should be taken into account for a given application. The methodology is particularly important for biomedical applications where data is often complex and multi-domain. Applying this methodology to protein-protein interaction prediction proved successful, paving the way to broader applications

Adherence to Glucose Monitoring with intermittently scanned Continuous Glucose Monitoring in patients with Type 1 Diabetes

Objetivo: Este estudo tem como objetivo prever o comportamento da adesão ao Intermittently scanned continuous glucose monitoring (isCGM) de pacientes com diabetes tipo 1. Métodos: A população em estudo foram pacientes com Diabetes Mellitus Tipo 1 seguidos na consulta de "Bombas infusoras de insulina" do Centro Hospitalar de São João e que utilizam o Sistema FreeStyle Libre(r) (FL), um dispositivo isCGM. Foram avaliados quanto à caracterização sociodemográfica e clínica, crenças e preocupações sobre Diabetes Mellitus, bem como as perceções quanto ao isCGM. Os dados da monitorização da glicose foram colhidos para caracterizar os padrões de monitorização e para avaliar a adesão ao isCGM - média de scans/dia com o FL. Resultados: Participaram neste estudo 72 pacientes com média de 30,36 anos (sd=11,35). Foram realizados uma média de 7 scans/dia. Os preditores de adesão encontrados foram: Idade (β=0,191, p=0,006), Tempo em alvo (β= 0,530, p=0,002), Necessidade isCGM (β=2,631, p=0,048), Índice de Massa Corporal (β=-0,549, p=0,017) e Sexo (β=-3,996; p=0,011). Conclusão: Este estudo enfatiza a relevância da adesão à monitorização da glicose no controlo da Diabetes Mellitus Tipo 1 e conclui que homens de idades mais jovens, com níveis de índice de massa corporal mais altos, menor tempo no alvo e que relatam menor necessidade de isCGM aderem menos ao isCGM. Assim, esses pacientes devem ser acompanhados de perto e objeto de estratégias personalizadas que promovam a adesão ao tratamento.Purpose: This study aims to predict the Intermittently scanned continuous glucose monitoring (isCGM) adherence behavior of patients with Type 1 Diabetes. Methods: Patients with Type 1 Diabetes mellitus using FreeStyle Libre(r) System (FL), a isCGM device, that attended the "Insulin Infusion Pump clinic" at Centro Hospitalar de São João were enrolled and evaluated for sociodemographic and clinical characterization, beliefs and concerns about Diabetes Mellitus, as well as isCGM's perceptions. Intermittently scanned continuous glucose monitoring data were collected to characterize monitoring patterns and to measure isCGM's adherence - FL average of scans/day. Results: Seventy-two patients with a mean of 30.36 years (sd=11.35) participate in this study. A median of 7 scans/day was performed. The adherence predictors found was Age (β=0.191, p=0.006), Time in target (β= 0.530, p=0.002), isCGM Necessity (β=2.631, p=0.048), Body Mass Index (β=-0.549, p=0.017) and Sex (β=-3.996; p=0.011). Conclusions: This study emphasizes the relevance of glucose monitoring adherence in disease control and shows that males of younger ages, presenting with higher body mass index levels, lower time in target, and reporting lower isCGM necessity are less adherent to isCGM. Therefore, these patients should be closely followed and object of personalized strategies to promote treatment adherence

Improving the anti-tumor immune responses against cancer cells

Cancer is one of the leading causes of death worldwide. Dendritic cells (DCs) can capture cancer antigens and present them to T lymphocytes, after a maturation process, inducing specific immune responses. Sialyl-Tn (STn) is a tumor-associated carbohydrate antigen that is expressed by several carcinomas. STn downregulates the immune responses towards STn-expressing tumor cells by inducing a tolerogenic phenotype on DCs. For this reason, a successful therapeutic approach against this antigen has to take in consideration the activation of the immune response. The main goal of this thesis was to assess if the use of anti-STn antibodies to block the STn antigen could improve anti-tumor immune responses by reestablishing the mature phenotype on DCs. To do this, STn-expressing cancer cell lines were cultured and DCs were obtained from differentiation of monocytes. Initially, the work comprised the development and characterization of anti-STn antibodies produced by the group through hybridoma technology, using mainly ELISA and flow cytometry. Three hybridoma clones producing IgM anti-STn antibodies were obtained and will be further characterized. A second part of the work included a functional in vitro characterization of humanized anti-STn antibodies. This comprised the establishment of co-cultures between cancer cells and DCs and assessment of the immune response of DCs against STn-expressing cancer cells, with and without STn blockade by those antibodies. The expression of MHC-II and co-stimulatory molecules was assessed by flow cytometry, and the expression of cytokines was assessed by ELISA and RT-PCR. However, the reestablishment of the mature phenotype was not observed. The work developed contributed to understanding that further improvements and assays are necessary; and also that the production of antibodies comprises many variants that can be modified throughout the development and characterization procedures, thus being a long process and needing many optimizations before success can be achieved

Using AFM to study erythrocytes’ biophysical properties on Stroke and Amyotrophic Lateral Sclerosis

Stroke is the most common cause of death worldwide. It is associated with high fibrinogen levels in plasma. Fibrinogen promotes clot formation, which in some situations can promote venous thromboembolism. Amyotrophic Lateral Sclerosis (ALS) is a devastating and fatal neurodegenerative disease, leading to severe respiratory insufficiency and hypoxia. The main goals of this study were: (i) to study the influence of fibrinogen on erythrocytes adhesion in stroke patients; and, (ii) to evaluate morphological and elasticity changes on erythrocytes from ALS patients. Human blood samples from stroke and ALS patients were analysed and compared with healthy donors (control). Samples were analysed by Atomic Force Microscopy (AFM) and through haemorheological parameters. AFM was used to measure fibrinogen-erythrocyte and erythrocyte-erythrocyte interactions, as well as erythrocyte stiffness and morphology. Erythrocyte membrane fluidity and zeta-potential were also assessed on ALS. Erythrocytes from stroke patients are less deformable and have more propensity to aggregate. Fibrinogen-erythrocytes interactions on stroke are stronger than for the control group. They also have an increased concentration of ´ fibrinogen variant. These changes could be associated with high risk of cardiovascular events and a worst prognostic of the disease. Erythrocytes from ALS patients are more capable to deform and present morphological changes. Changes in erythrocytes physical-chemical and electrical properties and on their membrane organization were also observed. These findings could help to consider the fibrinogen-erythrocyte binding as a new cardiovascular risk factor for stroke disease. Understanding the role of fibrinogen on erythrocyte aggregation may be relevant for potential future drug interventions to reduce aggregation and enhance microcirculatory flow conditions. Fibrinogen in ALS disease could promote venous thrombotic events. In the future, finding a molecular biomarker of early respiratory dysfunction in ALS disease that could comprise prognostic value will be essential

The epidemiology of infective endocarditis in Portugal : Prevalence, incidence, risk factors, management and prognosis of infective endocarditis in a general population

Infective endocarditis (IE) is an infrequent clinical condition with a challenging diagnosis and management. An infection of the endocardium, prosthetic or intracardiac devices predominantly caused by bacteria occurs, with a multisystemic involvement and heterogeneous clinical presentation. A long hospitalization course is usually mandatory. Despite several advances in the fields of medical imaging, microbiology techniques, antibiotic and cardiac surgery, complications are common, with fatal outcome still being a frequent finding. Its incidence rate in developed countries from Europe and North America is estimated between 3 and 12 per 100000 people. A progressive shift in the epidemiology of affected patients has been observed. Older patients, with a higher burden of comorbidities and long-term survivors of repaired structural or congenital heart disease have been progressively replacing the former stereotype of younger patients with rheumatic valve disease described in medical conferences more than one century ago. Likewise, more aggressive infectious agents such as Staphylococcus or Enterococcus have been replacing the dominance of Streptococcus in the last decades. Early aggressive surgical management of such patients has become the new standard. Still, prognosis continues poor with an in-hospital mortality rate ranging between 15 and 25%. In industrialized countries, a generalized growing trend noted in the incidence rate of IE and a shift in its epidemiology have been a consequence of the evolution in Medicine itself. Ageing of the population, with an increasing exposure to more invasive medical interventions, that in the case of structural heart disease have led to an increase in the prevalence of intracardiac devices and prosthesis carriers, have been in the cornerstone of these findings. In Portugal, ageing of the population has been well noted, consequently leading to a higher prevalence of comorbidities and structural heart disease. Nevertheless, there is limited understanding on the epidemiology and outcome of patients hospitalized with IE. Its impact, mainly assessed by the publication of single centre retrospective cross-sectional cohorts, lacks a populational perspective. International populational based analyses although useful, reveal significant variability. Prudence is required on the application of their conclusions in the Portuguese clinical setting. The main objectives in this thesis were: i) to provide a population-based analysis on the epidemiological and prognosis of IE in Portugal; ii) to identify temporal trends and predictors of incidence and mortality due to IE in Portugal; iii) to identify indicators of cardiac surgery for IE in Portugal and outcome (mortality); iv) to characterize the use of IE prophylaxis among physicians caring for high-risk patients in Portugal. With the purpose of understanding the published evidence on the epidemiology of IE in Portuguese hospital centres, we undertook a thorough systematic review of all relevant scientific publications concerning cohort studies of hospitalized patients with IE in Portuguese hospitals in the last three decades. The search resulted in the analysis of eighteen retrospective cohort studies, three of them exclusively surgical. One thousand eight hundred seventy two patients were described. Older patients, predominantly men with a higher involvement of native left heart valves were identified. Staphylococcus and Streptococcus were the most frequent infectious agents involved. Nearly 30% of total cohort underwent surgical intervention. Short-term mortality rate averaged 21.9% in the overall cohort, ranging between 13.1 to 16% in the post-operative subgroup. Afterwards, we conducted a nationwide retrospective temporal trend study on the incidence of IE in Portugal, between 2010 and 2018. Additionally, we analysed clinical characteristics, involved infectious agents, heart valve surgical intervention and outcomes of patients hospitalized with IE in that period. We used an administrative medical database derived from the Central Administration of Health System of the Portuguese Ministry of Health. The database included information derived from medical discharge reports of hospitalization episodes, including demographic and clinical diagnoses (coded using International Classification of Disease versions 9 and 10). Seven thousand five hundred seventy four patients were hospitalized with IE in Portuguese public hospitals between 2010 and 2018. Anonymised clinical data was used. Statistical analysis included univariate analysis and multivariate logistic regression models to evaluate factors associated with surgical intervention and all cause in hospital mortality. Odds Ratio (OR) and 95% confidence intervals (CIs) were reported for categorical variables. The analysis was conducted at a 5% level of significance. Between 2010 and 2018, 7574 episodes of hospitalization with IE were analysed. The annual incidence of IE in Portugal that period was 8.3 per 100000 people, higher in men (9.9 versus 6.8 in women per 100000 people) and peaking in patients older than 79 years old (40.6 per 100000 people). 12.4% of patients underwent cardiac valve surgery during the index hospitalization and one fifth of the total cohort died. Men were predominant (56.9% versus 43.1%). Women were older (76 versus 69 years old) and were less likely to undergo cardiac surgery (OR 0.48 – 95%CI 0.40-0.57, p< 0.001), but with a higher odd of dying in the postoperative period (OR 1.84, 95%CI 1.19-2.84, p=0.006). The sub-analysis of patients submitted to cardiac surgery (n= 937 patients) revealed that patients younger than 60 years old, with previous valve or congenital heart disease, infection with Streptococcus spp or the presence of heart failure, systemic embolization or acute renal failure were associated with a higher rate of intervention. In addition, the initial admission of a patient with a diagnosis of IE in a tertiary hospital with cardiac surgery unit was also related with cardiac surgery during the hospitalization. Nearly 74% of patients underwent single valve surgical intervention, with aortic valve being the most frequently involved. In-hospital all-cause postoperative mortality rate was 15.6%. Also, factors linked with in-hospital mortality were older age, female gender, liver, kidney and coronary disease, cardiac valve prosthesis, Staphylococcus spp, acute renal failure and sepsis during hospitalization. Furthermore, we conducted a retrospective temporal trend analysis of all patients whose basic cause of death was IE, in Portugal, between 2002 and 2018. Data was gathered from national death certificates. Three thousand six hundred thirty four people died from IE throughout the 17-year study period with an annual specific mortality rate of 2.1 per 100 000 people. 89% were at least 60 years old, and most were women (55%). Mortality rate was higher in colder months. Finally, we performed a cross sectional study based on a self-completed online questionnaire distributed to physicians, members of the Portuguese Society of Cardiology, evaluating the current practice regarding IE prophylaxis. 253 valid questionnaires were replied. 83% follow the European scientific orientations. 61% find IE prophylaxis challenging. Discrepancy between scientific orientations and some high-risk cardiac conditions or procedures was noted among responders. These findings provide novel insight into the epidemiology and prognosis of IE in Portugal. Additionally, they raise concern regarding temporal incidence, surgical management, and mortality trends compared to other developed countries settings. Our results support the implementation of a national multicentric clinical registry for further evaluation