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.

The impact of family control on firm's return

Family firm is a field of growing interest. The aim of this article is to understand whether CEOs identity impacts family firm’s stock returns. From a sample of Portuguese and Spanish family firms findings show that who manages the firms result in significantly different risk exposure. Moreover, we find that the abnormal return found by Fahlenbrach (2009) to founder-controlled firms disappear when we use valueweighted portfolios and include two new factors: market aggregate illiquidity and debt intensity to the four-factor Carhart model. Finally, our results explain why the majority of family firm is controlled by its founder.

Factors influencing amblyopia rehabilitation in occlusive therapy

Amblyopia develops in an early period and is a decrease of visual acuity (unilateral or bilateral) caused by a deprivation of vision or abnormal binocular interaction. Prognosis of Amblyopia is better when occlusive treatment is implemented in an early stage. Visual acuity of amblyopic eye does not improve without effective occlusive therapy. The aim of this study is to identify potential risk factors of noncompliance with treatment when it is implemented by parents in amblyopic children.

Risk factors for non compliance using occlusive therapy: a case study

Purpose: compliance with treatment is a common problem when treating amblyopic patients. Visual acuity of amblyopic eye does not improve without effective occlusive therapy. The aim of this study is to identify potential risk factors of non-compliance with treatment when it is implemented by family in amblyopic children. Setting: a quantitative transversal study was performed in a public hospital and in a private clinic in Lisbon.

Lifestyle factors influence in the frequency in buccal micronucleus

Genomic damage is probably the most important fundamental cause of development and degenerative disease. It is also well established that genomic damage is produced by environmental exposure to genotoxins, medical procedures (e.g. radiation and chemicals), micronutrient deficiency (e.g. folate), lifestyle factors (e.g. alcohol, smoking, drugs and stress), and genetic factors such as inherited defects in DNA metabolism and/or repair. Tobacco smoke has been associated to a higher risk of development of cancer, especially in the oral cavity, larynx and lungs, as these are places of direct contact with many carcinogenic tobacco’s compounds. Alcohol is definitely a recognized agent that influence cells in a genotoxic form, been citied as a strong agent with potential in the development of carcinogenic lesions. Epidemiological evidence points to a strong synergistic effect between cigarette smoking and alcohol consumption in the induction of cancers in the oral cavity. Approximately 90% of human cancers originate from epithelial cells. Therefore, it could be argued that oral epithelial cells represent a preferred target site for early genotoxic events induced by carcinogenic agents entering the body via inhalation and ingestion. The MN assay in buccal cells was also used to study cancerous and precancerous lesions and to monitor the effects of a number of chemopreventive agents.

Sistema de apoio à decisão para a classificação de risco em projectos de tecnologias de informação

O trabalho que a seguir se apresenta tem como objectivo descrever a criação de um modelo que sirva de suporte a um sistema de apoio à decisão sobre o risco inerente à execução de projectos na área das Tecnologias de Informação (TI) recorrendo a técnicas de mineração de dados. Durante o ciclo de vida de um projecto, existem inúmeros factores que contribuem para o seu sucesso ou insucesso. A responsabilidade de monitorizar, antever e mitigar esses factores recai sobre o Gestor de Projecto. A gestão de projectos é uma tarefa difícil e dispendiosa, consome muitos recursos, depende de numerosas variáveis e, muitas vezes, até da própria experiência do Gestor de Projecto. Ao ser confrontado com as previsões de duração e de esforço para a execução de uma determinada tarefa, o Gestor de Projecto, exceptuando a sua percepção e intuição pessoal, não tem um modo objectivo de medir a plausibilidade dos valores que lhe são apresentados pelo eventual executor da tarefa. As referidas previsões são fundamentais para a organização, pois sobre elas são tomadas as decisões de planeamento global estratégico corporativo, de execução, de adiamento, de cancelamento, de adjudicação, de renegociação de âmbito, de adjudicação externa, entre outros. Esta propensão para o desvio, quando detectada numa fase inicial, pode ajudar a gerir melhor o risco associado à Gestão de Projectos. O sucesso de cada projecto terminado foi qualificado tendo em conta a ponderação de três factores: o desvio ao orçamentado, o desvio ao planeado e o desvio ao especificado. Analisando os projectos decorridos, e correlacionando alguns dos seus atributos com o seu grau de sucesso o modelo classifica, qualitativamente, um novo projecto quanto ao seu risco. Neste contexto o risco representa o grau de afastamento do projecto ao sucesso. Recorrendo a algoritmos de mineração de dados, tais como, árvores de classificação e redes neuronais, descreve-se o desenvolvimento de um modelo que suporta um sistema de apoio à decisão baseado na classificação de novos projectos. Os modelos são o resultado de um extensivo conjunto de testes de validação onde se procuram e refinam os indicadores que melhor caracterizam os atributos de um projecto e que mais influenciam o risco. Como suporte tecnológico para o desenvolvimento e teste foi utilizada a ferramenta Weka 3. Uma boa utilização do modelo proposto possibilitará a criação de planos de contingência mais detalhados e uma gestão mais próxima para projectos que apresentem uma maior propensão para o risco. Assim, o resultado final pretende constituir mais uma ferramenta à disposição do Gestor de Projecto.

Return premiums of sustainable companies listed on the Spanish stock market

The purpose of this paper is to analyze whether companies with a greater commitment to corporate social responsibility (SRI companies) perform differently on the stock market compared to companies that disregard SRI. Over recent years, this relationship has been taken up at both a theoretical and practical level, and has led to extensive scientific research of an empirical nature involving the examination of the relationships existing between the financial and social, environmental and corporate governance performance of a company and the relationship between SRI and investment decisions in the financial market. More specifically, this work provides empirical evidence for the Spanish market as to whether or not belonging to a group of companies the market classes as sustainable results in return premiums that set them apart from companies classed as conventional, and finds no differences in the stock market performance of companies considered to be SRI or conventional.

The risk-return trade-off in Europe: A temporal and cross-sectional analysis

This paper analyzes the risk-return trade-off in European equities considering both temporal and cross-sectional dimensions. In our analysis, we introduce not only the market portfolio but also 15 industry portfolios comprising the entire market. Several bivariate GARCH models are estimated to obtain the covariance matrix between excess market returns and the industrial portfolios and the existence of a risk-return trade-off is analyzed through a cross-sectional approach using the information in all portfolios. It is obtained evidence for a positive and significant risk-return trade-off in the European market. This conclusion is robust for different GARCH specifications and is even more evident after controlling for the main financial crisis during the sample period.

Good deals in markets with frictions

This paper studies a portfolio choice problem such that the pricing rule may incorporate transaction costs and the risk measure is coherent and expectation bounded. We will prove the necessity of dealing with pricing rules such that there exists an essentially bounded stochastic discount factor, which must be also bounded from below by a strictly positive value. Otherwise good deals will be available to traders, i.e., depending on the selected risk measure, investors can build portfolios whose (risk, return) will be as close as desired to (−infinity, infinity) or (0, infinity). This pathologic property still holds for vector risk measures (i.e., if we minimize a vector valued function whose components are risk measures). It is worthwhile to point out that essentially bounded stochastic discount factors are not usual in financial literature. In particular, the most famous frictionless, complete and arbitrage free pricing models imply the existence of good deals for every coherent and expectation bounded (scalar or vector) measure of risk, and the incorporation of transaction costs will not guarantee the solution of this caveat.

A comparative study of alternative approaches for common factors identification

Preliminary version

Criação de valor, gestão de risco e as medidas de performance ajustadas ao risco: aplicação do RAROC - Risk Adjustment Return on Capital - ao grupo crédito agrícola

Mestrado em Contabilidade e Gestão das Instituições Financeiras

Factors related with adiponectinemia in obese and normal-weight women and with its variation in weight loss programs

Objective: To assess different factors influencing adiponectinemia in obese and normal-weight women; to identify factors associated with the variation (Δ) in adiponectinemia in obese women following a 6-month weight loss program, according to surgical/non-surgical interventions. Methods: We studied 100 normal-weight women and 112 obese premenopausal women; none of them was on any medical treatment. Women were characterized for anthropometrics, daily macronutrient intake, smoking status, contraceptives use, adiponectin as well as IL-6 and TNF-α serum concentrations. Results: Adiponectinemia was lower in obese women (p < 0.001), revealing an inverse association with waist-to-hip ratio (p < 0.001; r = –0.335). Normal-weight women presented lower adiponectinemia among smokers (p = 0.041); body fat, waist-to-hip ratio, TNF-α levels, carbohydrate intake, and smoking all influence adiponectinemia (r 2 = 0.436). After weight loss interventions, a significant modification in macronutrient intake occurs followed by anthropometrics decrease (chiefly after bariatric procedures) and adiponectinemia increase (similar after surgical and non-surgical interventions). After bariatric intervention, Δ adiponectinemia was inversely correlated to Δ waist circumference and Δ carbohydrate intake (r 2 = 0.706). Conclusion: Anthropometrics, diet, smoking, and TNF-α levels all influence adiponectinemia in normal-weight women, although explaining less than 50% of it. In obese women, anthropometrics modestly explain adiponectinemia. Opposite to non-surgical interventions, after bariatric surgery adiponectinemia increase is largely explained by diet composition and anthropometric changes.

Treatment outcomes in pulmonary tuberculosis and associated factors worldwide: a systematic review and meta-analysis

Introduction - The increasing of TB burden is usually related to inadequate case detection, diagnosis and cure. Global targets for TB control, adopted by the World Health Organization (WHO), are to detect 70% of the estimated incidence of sputum smear-positive TB and to cure 85% of newly detected cases of sputum smear-positive TB. Factors associated with unsuccessful treatment outcomes are closely related to TB risk factors. Objectives - To describe treatment success rates in pulmonary TB cases and to identify factors associated with unsuccessful treatment outcomes, according to ad-hoc studies.

Haptoglobin, acid phosphatase and demographic factors: obesity risk

The aim of this work is to study the risk of obesity posed by two genetic factors: haptoglobin phenotype and acid phosphatase phenotype, one enzymatic activity: acid phosphatase activity (ACP1), age and gender. Haptoglobin (Hp) is a protein of the immune system, and three phenotypes of Hp are found in humans: Hp1-1, Hp2-1, and Hp2-2. This protein is associated with a susceptibility to common pathological conditions, such as obesity. ACP1 is an intracellular enzyme The phenotypes of ACP1 (AA, AB, AC, BB, BC, CC) are also considered. We took a sample of 127 subjects with complete data from 714 registers. Since we intend to identify risk factors for obesity, an ordinal regression model is adjusted, using the Body Mass Index, BMI, to define weight categories. Haptoglobin phenotype, enzymatic activity of ACP1, acid phosphatase phenotype, age and gender are considered as regressor variables. We found three factors associated with an increased risk of obesity: phenotype Hp2-1 of haptoglobin (estimated odds ratio OR 11.54), phenotype AA of acid phosphatase (OR 33.788) and age (OR 1.39). The interaction between phenotype Hp2-1 and phenotype AC is associated with a decreased risk of obesity (OR 0.032); The interaction between phenotype AA and ACP1 activity is associated with a decreased risk of obesity (OR 0.954).

OsRMC, a negative regulator of salt stress response in rice, is regulated by two AP2/ERF transcription factors

High salinity causes remarkable losses in rice productivity worldwide mainly because it inhibits growth and reduces grain yield. To cope with environmental changes, plants evolved several adaptive mechanisms, which involve the regulation of many stress-responsive genes. Among these, we have chosen OsRMC to study its transcriptional regulation in rice seedlings subjected to high salinity. Its transcription was highly induced by salt treatment and showed a stress-dose-dependent pattern. OsRMC encodes a receptor-like kinase described as a negative regulator of salt stress responses in rice. To investigate how OsRMC is regulated in response to high salinity, a salt-induced rice cDNA expression library was constructed and subsequently screened using the yeast one-hybrid system and the OsRMC promoter as bait. Thereby, two transcription factors (TFs), OsEREBP1 and OsEREBP2, belonging to the AP2/ERF family were identified. Both TFs were shown to bind to the same GCC-like DNA motif in OsRMC promoter and to negatively regulate its gene expression. The identified TFs were characterized regarding their gene expression under different abiotic stress conditions. This study revealed that OsEREBP1 transcript level is not significantly affected by salt, ABA or severe cold (5 °C) and is only slightly regulated by drought and moderate cold. On the other hand, the OsEREBP2 transcript level increased after cold, ABA, drought and high salinity treatments, indicating that OsEREBP2 may play a central role mediating the response to different abiotic stresses. Gene expression analysis in rice varieties with contrasting salt tolerance further suggests that OsEREBP2 is involved in salt stress response in rice.