Clinical and genetic factors predicting response to therapy in patients with Crohn’s disease

Aim - To identify clinical and/or genetic predictors of response to several therapies in Crohn’s disease (CD) patients. Methods - We included 242 patients with CD (133 females) aged (mean ± standard deviation) 39 ± 12 years and a disease duration of 12 ± 8 years. The single-nucleotide polymorphisms (SNPs) studied were ABCB1 C3435T and G2677T/A, IL23R G1142A, C2370A, and G9T, CASP9 C93T, Fas G670A and LgC844T, and ATG16L1 A898G. Genotyping was performed with real-time PCR with Taqman probes. Results - Older patients responded better to 5-aminosalicylic acid (5-ASA) and to azathioprine (OR 1.07, p = 0.003 and OR 1.03, p = 0.01, respectively) while younger ones responded better to biologicals (OR 0.95, p = 0.06). Previous surgery negatively influenced response to 5-ASA compounds (OR 0.25, p = 0.05), but favoured response to azathioprine (OR 2.1, p = 0.04). In respect to genetic predictors, we observed that heterozygotes for ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids (OR 2.51, p = 0.04), while homozygotes for Casp9 C93T SNP had a lower chance of responding both to corticosteroids and to azathioprine (OR 0.23, p = 0.03 and OR 0.08, p = 0.02,). TT carriers of ABCB1 C3435T SNP had a higher chance of responding to azathioprine (OR 2.38, p = 0.01), while carriers of ABCB1 G2677T/A SNP, as well as responding better to azathioprine (OR 1.89, p = 0.07), had a lower chance of responding to biologicals (OR 0.31, p = 0.07), which became significant after adjusting for gender (OR 0.75, p = 0.005). Conclusions - In the present study, we were able to identify a number of clinical and genetic predictors of response to several therapies which may become of potential utility in clinical practice. These are preliminary results that need to be replicated in future pharmacogenomic studies.

Fatores determinantes da maturidade e composição da dívida das empresas portuguesas cotadas

Mestrado em Contabilidade e análise financeira

Comparison of inverse planning systems based on biological or physical factors: Pinnacle®, Corvus® and Monaco®

Radiotherapy (RT) is one of the most important approaches in the treatment of cancer and its performance can be improved in three different ways: through the optimization of the dose distribution, by the use of different irradiation techniques or through the study of radiobiological initiatives. The first is purely physical because is related to the physical dose distributiuon. The others are purely radiobiological because they increase the differential effect between the tumour and the health tissues. The Treatment Planning Systems (TPS) are used in RT to create dose distributions with the purpose to maximize the tumoral control and minimize the complications in the healthy tissues. The inverse planning uses dose optimization techniques that satisfy the criteria specified by the user, regarding the target and the organs at risk (OAR’s). The dose optimization is possible through the analysis of dose-volume histograms (DVH) and with the use of computed tomography, magnetic resonance and other digital image techniques.

Leitura à primeira vista ao piano: relatório de estágio

A frequência de um Estágio de Ensino Especializado proporciona uma oportunidade de proximidade entre futuro docente e aluno. A observação de metodologias e o envolvimento com a música e contexto musical das escolas e alunos é algo fundamental para a formação correcta de docentes. Devido ao carácter prático do ensino de um instrumento, esta interacção demonstra-se fundamental para a experiência pedagógica. Neste estágio pretendeu-se aumentar o grau de qualidade de ensino e o número de ferramentas pedagógicas, comparando-as com ferramentas aprendidas e articuladas por experiência pré-adquirida como docente. A pedagogia de ensino de piano tem vindo a sofrer várias modificações e adaptações, como reflexo do meio e dos recursos disponíveis. A existência de conservatórios onde os alunos podem frequentar um grande número de disciplinas trouxe vantagens significativas para a sua cultura musical. Embora o estudo do instrumento continue a ser a prática principal, a diminuição nos horários de estudo obriga a uma selecção criteriosa dos conteúdos programáticos deste instrumento, de modo a não por em causa o desenvolvimento técnico dos alunos. Uma área raramente encontrada nestes conteúdos é a leitura à primeira vista. A investigação aqui apresentada pretendeu compreender como se realiza a leitura à primeira vista de uma partitura ao piano e como se pode desenvolver esta competência. Recorrendo a fontes bibliográficas consultadas e à análise de métodos de ensino representativos, foram alvo de investigação a forma como um leitor lê à primeira vista uma partitura, qual a importância do tacto e da visão, e até que ponto esta competência pode ser estudada e desenvolvida. Quais são os factores-chave da leitura à primeira vista? Até que ponto a prática ao instrumento pode influenciar esta capacidade? Embora a leitura à primeira vista tenha sido retirada como disciplina e forma de avaliação em vários estabelecimentos de ensino, a realização de alguns inquéritos pretendeu avaliar a importância dada a esta disciplina, entre professores e alunos.

Determining the number of clusters in categorical data

Cluster analysis for categorical data has been an active area of research. A well-known problem in this area is the determination of the number of clusters, which is unknown and must be inferred from the data. In order to estimate the number of clusters, one often resorts to information criteria, such as BIC (Bayesian information criterion), MML (minimum message length, proposed by Wallace and Boulton, 1968), and ICL (integrated classification likelihood). In this work, we adopt the approach developed by Figueiredo and Jain (2002) for clustering continuous data. They use an MML criterion to select the number of clusters and a variant of the EM algorithm to estimate the model parameters. This EM variant seamlessly integrates model estimation and selection in a single algorithm. For clustering categorical data, we assume a finite mixture of multinomial distributions and implement a new EM algorithm, following a previous version (Silvestre et al., 2008). Results obtained with synthetic datasets are encouraging. The main advantage of the proposed approach, when compared to the above referred criteria, is the speed of execution, which is especially relevant when dealing with large data sets.

Pulmonary tuberculosis and associated factors: a systematic review and meta-analysis

Objectives - To identify associated factors for PTB in studies published recently and to quantify significant combined measures for PTB risk factors previously identified.

Influencing factors on the buying behavior in the software market

The case of desktop Operating System and Office Suite choices considering Proprietary and Open Source Software alternatives.

Gestão de risco no Sector Automóvel - O caso do grupo Soluções Automóveis Globais

Mestrado em Controlo de Gestão e dos Negócios