S-thiolated protein profile to assess the redox-modulation effects of antiretroviral drugs

Efavirenz (EFV) is an anti-HIV drug that has been associated to neurotoxicity. The 8-hydroxy-efavirenz metabolite has been described as the responsible for its long-term neurotoxic effects. Upon bioactivation this metabolite is able to generate electrophilic species, forming protein adducts and eliciting oxidative stress. S-thiolation of proteins (e.g. S-glutathionylation) has been suggested as a mechanism of protein regulation by the redox status. The present study is aimed to investigate if S-thiolated proteins plasma profile (RSSP) is associated with EFV-neurotoxicity. The RSSP was assessed in an animal model of EFV-induced neurotoxicity. The animal RSSP was compared to the one obtained in a cohort of HIV-infected patients on EFV. The dependence on 8-hydroxy-efavirenz generation and the influence of infection in RSSP profile were also assessed in the clinical study. This profile was also compared to the one obtained in patients on nevirapine (NVP), a non-neurotoxic antiretroviral of the same class of EFV. The same RSSP was found in animal model and patients on EFV. This profile is characterized by increased S-glutathionylation and decreased S-cysteinylation of proteins. This is mainly observed in patients that form higher 8-hydroxy-efavirenz, which is in accordance with higher risk of neurotoxicity. RSSP of patients on NVP was the opposite of the one observed for EFV. This might explain why EFV is mostly metabolized by liver, but is barely hepatotoxic. No influence of HIV-infection in RSSP was found. Summing up, we conclude that RSSP profile might be associated with EFV-induced neurotoxicity, suggesting that it is a suitable tool for therapeutic drug monitoring aimed at managing toxic events. Moreover, as EFV and NVP presented a different RSSP signature, this tool might be used for assessing antiretroviral redox-modulation effects and quantification of drug-induced oxidative stress. This knowledge might have important implications for toxicity risk assessment, antiretroviral prescription and drug development

Bonus systems in an open portfolio

In this paper, we study bonus systems in an open portfolio, i.e. we consider that a policyholder can transfer his policy to a different insurance company at any time. We make use of inhomogeneous Markov chains to model the system and show, under reasonable assumptions, that the stationary distribution is independent of the market shares, and is easily calculated.info:eu-repo/semantics/publishedVersio

Ratemaking of dependent risks

We start by describing how, in some cases, we can use variance-related premium principles in ratemaking, when the claim numbers and individual claim amounts are independent. We use quasi-likelihood generalized linear models, under the assumption that the variance function is a power function of the mean of the underlying random variable. We extend this approach to the cases where the claim numbers are correlated. Some alternatives to deal with dependent risks are presented, taking explicitly into account overdispersion. We present regression models covering the bivariate Poisson, the generalized bivariate negative binomial and the bivariate Poisson–Laguerre polynomial, which nest the bivariate negative binomial. We apply these models to a portfolio of the Portuguese insurance company Tranquilidade and compare the results obtained.info:eu-repo/semantics/publishedVersio

Optimal bonus scales under path-dependent bonus rules

Bonus malus systems have been studied by several authors under the framework of Markov chains. Optimal scales have been deduced by Norberg (1976), Borgan, Hoem & Norberg (1981) and Gilde & Sundt (1989). In these articles the authors assumed that the bonus system forms a first order Markov chain. In the present paper we deduce the optimal scales, using the same criteria as in the cited papers, for bonus systems that are not first order Markovian processes, but that can be regarded as Markovian by increasing the number of states of the system.info:eu-repo/semantics/publishedVersio

Applying the proportional hazard premium calculation principle

We discuss the application of the proportional hazard premium calculation principle in the parametric and non parametric framework. In the parametric approach, we propose a method to calculate the premium of a compound risk when the severity distribution is subexponential. In the non parametric approach, the use of the empirical distribution to calculate the premium using the proportional hazard principle leads to a systematic underestimation of the premium. After studying the bias of the premium calculated using this non-parametric approach we use the bootstrap technique with subsampling to reduce it.info:eu-repo/semantics/publishedVersio

Comparing risk adjusted premiums from the reinsurance point of view

In this paper we compare, from the point of view of reinsurance, the several risk adjusted premium calculation principles considered in Wang (1996b). We conclude that, with the exception of the proportional hazard (PH) premium calculation principle, all the others behave in a way similar to the expected value principle. We prove that the stop loss reinsurance premium when calculated using the PH premium principle gives a higher premium than any of the other transforms, provided that the priority is big enough. We observe a similar behaviour with respect to excess of loss reinsurance in all the examples given. We also study the behaviour of the adjustment coefficient, both from the insurer's and the reinsurer's point of view as functions of the priority, when the PH principle is used as opposed to the expected value principle.info:eu-repo/semantics/publishedVersio

Abuse and maltreatment in the elderly

Introduction: The aging population is increasing worldwide, but the abuse and mistreatment in the elderly (often silenced forms) has also been increasing, with strong implications for their quality of life. Objective: To identify forms of abuse and ill-treatment in the elderly, as well as the determinants of these abuses. Methodology: This is a quantitative study, of the non-experimental, descriptive, cross-sectional type attended by 135 Portuguese elderly. It uses the Family APGAR Scale and the Question to Elicit Elder Abuse (QEEA), which was applied between January and June 2013, in the elderly residing in the central of Portugal. Results: The data shows that 23.5% of the elderly have suffered some kind of abuse, these being especially of the emotional kind and neglect. We also found that the most abused elders were unmarried and widows, those who had lower academic qualifications, those who reported feeling lonely and less healthy and even those who perceive to integrate families with some degree of dysfunction. Conclusion: We found that the abuse and mistreatment are present in the everyday life of many seniors and are a difficult subject to approach. The evidence, invite us to reflect on the development of intervention strategies, particularly at the levels of emotional abuse, neglect, promotion of health and family functioning in order to contribute to the reduction or extinction of abuse and ill-treatment in the elderly.Resumo Introdução: O envelhecimento da população tem vindo a aumentar a nível mundial, contudo também têm aumentado os abusos e maus-tratos nos idosos, (muitas vezes em formas silenciadas), com fortes implicações na sua qualidade de vida. Objetivo: Identificar formas de abusos e maus-tratos em idosos, assim como os fatores determinantes desses abusos. Metodologia: Trata-se de um estudo quantitativo, do tipo não experimental, descritivo e transversal, no qual participaram 135 idosos portugueses. Foi utilizada uma escala de APGAR-Familiar e o Question to Elicit Elder Abuse (QEEA) que foi aplicada entre Janeiro e Junho de 2013, em idosos que residem na região centro do país e na comunidade. Resultados: Os dados mostram que 23,5% dos idosos já sofreu algum tipo de maus tratos, sendo estes sobretudo do tipo emocional e negligencia. Verificámos ainda que os idosos mais abusados eram os solteiros e viúvos, os que possuíam menores habilitações académicas, aqueles que referiam sentir solidão e menor saúde e ainda os que percepcionam integrar famílias com alguma disfunção. Conclusão: Verificámos que os abusos e maus tratos estão presentes no quotidiano de muitos idosos e constituem tema de difícil abordagem. As evidências encontradas, convidam-nos à reflexão sobre o desenvolvimento de estratégias de intervenção, sobretudo aos níveis dos abusos emocionais, negligência, promoção da saúde e funcionalidade familiar no sentido de contribuir para a diminuição ou extinção dos abusos e maus-tratos em idosos

Os sistemas de trocas locais na promoção da economia solidária e do desenvolvimento local: o exemplo da Granja do Ulmeiro

Classificação JEL: D71; D74A necessidade de implementação de sistemas alternativos de desenvolvimento com enfoque no local levou à criação de novas estruturas sociais que fossem capazes de enfrentar os novos desafios da economia global. A economia solidária e os seus princípios assentes na cooperação e na solidariedade impõem-se como uma importante ferramenta na sustentação dessas estruturas. Um exemplo disso, são os sistemas de trocas locais que vêm, assim, colmatar algumas das necessidades que as comunidades locais sente m através do fortalecimento de laços sociais entre os seus membros. Deste modo, partindo dos conceitos de desenvolvimento local e economia solidária, procede-se à análise dos sistemas de trocas locais e solidárias, do ponto de vista teórico e empírico, discutindo-se a sua viabilidade enquanto promotores de desenvolvimento local e impulsionadores da solidariedade numa região. O estudo empírico recaiu sobre o trabalho da associação AJP (Acção para a Justiça e Paz) que abriu caminho para a implementação de mercados solidários na Granja do Ulmeiro, localizada no concelho de Soure, distrito de Coimbra. Tendo em conta o contexto da região, analisa-se a evolução desses eventos e o seu impacto na comunidade, relacionando -os com os princípios do desenvolvimento local e da economia solidária, de acordo com a perspectiva dos participantes, dos agentes locais e de quem colaborou de perto com a associação .The need of implementation of local -focused alternative development systems led to the creation of new social structures that could be able to face the new challenges of the global economy. Solidarity economics and its principles settled in cooperation and solidarity impose themselves as an important tool in the support of those structures. One example of this reality, are the local exchange systems that emerged to fulfill some of the needs that local communities feel through the strengthening of social bonds between its members. Thus, an analysis of the local and mutual exchange systems is made, built on the concepts of local development and solidarity economics, from the theoretical and empirical point of view, arguing its viability as promoters of local development and impellers of solidarity in a certain region. The empirical study fell upon the work of the association AJP (Acção para a Justiça e Paz) that opened the way for the implementation of solidarity markets in Granja do Ulmeiro , located in the region of Soure, Coimbra. Given the context of the region, it is analysed the evolution of those events and its impact in the community , relating them with the principles of local development and solidarity economics, according to the participants, local agents and the association workers perspective