62,097 research outputs found
Selective COX-2 inhibitors and risk of myocardial infarction
No full textSelective inhibitors of cyclooxygenase- 2 ( COX- 2, ` coxibs') are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non- steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myocardial infarction and atherothrombotic events. This has led to the withdrawal of rofecoxib from global markets, and warnings have been issued by drug authorities about similar events during the use of celecoxib or valdecoxib/ parecoxib, bringing about questions of an inherent atherothrombotic risk of all coxibs and consequences that should be drawn by health care professionals. These questions need to be addressed in light of the known effects of selective inhibition of COX- 2 on the cardiovascular system. Although COX- 2, in contrast to the cyclooxygenase-1 ( COX- 1) isoform, is regarded as an inducible enzyme that only has a role in pathophysiological processes like pain and inflammation, experimental and clinical studies have shown that COX- 2 is constitutively expressed in tissues like the kidney or vascular endothelium, where it executes important physiological functions. COX- 2- dependent formation of prostanoids not only results in the mediation of pain or inflammatory signals but also in the maintenance of vascular integrity. Especially prostacyclin ( PGI(2)), which exerts vasodilatory and antiplatelet properties, is formed to a significant extent by COX- 2, and its levels are reduced to less than half of normal when COX- 2 is inhibited. This review outlines the rationale for the development of selective COX- 2 inhibitors and the pathophysiological consequences of selective inhibition of COX- 2 with special regard to vasoactive prostaglandins. It describes coxibs that are currently available, evaluates the current knowledge on the risk of atherothrombotic events associated with their intake and critically discusses the consequences that should be drawn from these insights. Copyright (C) 2005 S. Karger AG, Basel
Implementation of complex interactions in a Cox regression framework
No full textThe standard Cox proportional hazards model has been extended by functionally describable interaction terms. The first of which are related to neural networks by adopting the idea of transforming sums of weighted covariables by means of a logistic function. A class of reasonable weight combinations within the logistic transformation is described. Apart from the standard covariable product interaction, a product of logistically transformed covariables has also been included in the analysis of performance of the new terms. An algorithm combining likelihood ratio tests and AIC criterion has been defined for model choice. The critical values of the likelihood ratio test statistics had to be corrected in order to guarantee a maximum type I error of 5% for each interaction term. The new class of interaction terms allows interpretation of functional relationships between covariables with more flexibility and can easily be implemented in standard software packages
Elucidating the Binding Behavior of Highly Potent COX-2 Selective Inhibitors
No full textNon-steroidal anti-inflammatory drugs (NSAIDs) inhibit the cyclooxygenase enzymes (COXs), and are widely used for the treatment of inflammation, pain, and cancers. A selective inhibition of the COX-2 isoform is desirable, as this is overexpressed during inflammatory events. Therefore, many efforts have been directed toward the development of COX-2 selective inhibitors. Unfortunately, most of these inhibitors have been found to be highly cardiotoxic. Therefore, a deeper understanding of the molecular bases of COXs selective inhibition is of great demand. Recently, we have successfully used metadynamics to study the binding behavior of SC-558, a highly potent COX-2 selective inhibitor, in both COX-1 and COX-2. Following the line traced in our previous work, we have here extended the metadynamics studies on two highly potent COX-2 selective inhibitors, namely nimesulide and rofecoxib. Our results provide useful computational tools to design small organic molecules with fine-tuned COX-1/COX-2 potency and selectivity. Furthermore, these results can be of paramount importance in the design of less toxic novel anti-inflammatory drug candidates
A Note on Implementing Box-Cox Quantile Regression
No full textThe Box-Cox quantile regression model using the two stage method suggested by Chamberlain (1994) and Buchinsky (1995) provides a flexible and numerically attractive extension of linear quantile regression techniques. However, the objective function in stage two of the method may not exists. We suggest a simple modification of the estimator which is easy to implement. The modified estimator is still pn{consistent and we derive its asymptotic distribution. A simulation study confirms that the modified estimator works well in situations, where the original estimator is not well defined. --Box-Cox quantile regression,iterative estimator
An Arbitrage Approach to the Pricing of Catastrophe Options Involving the Cox Process
No full textWe investigate the valuation and hedging of catastrophe options, whose claim arrival process is modeled by the Cox process or a doubly stochastic Poisson process. Employing the non-arbitrage principle we obtain closed form formula for the pricing of the option. Various hedging parameters are also computed.catastrophe options, Cox process, pricing
Tie Turning Box-Cox including Quadratic Forms in Regression
No full textIn a regression model where a Box-Cox transformation is used on a positive independent variable X which appears only once in the equation, the effect of X on the dependent variable Y is either strictly increasing or decreasing over the whole range of X , since the transformation is a monotonic function of X , increasing or decreasing depending on the Box-Cox parameter ë. This paper considers the case where the variable X appears twice in the regression with two different Box-Cox parameters 1 ë and 2 ë , to allow a turning point in Y which can be a maximum or minimum. First and second-order conditions for the critical point are derived. This general specification includes as a special case the quadratic form in X where 1 ë and 2 ë are set equal to 1 and 2, respectively. If, instead of using the Box-Cox transformations, one uses simple powers of X , this form is equivalent to the Box-Cox form except that neither 1 ë nor 2 ë can be equal to zero, since in this case 1 ë X or 2 ë X reduces to a constant of value 1.Box-Cox Transformation, Quadratic Form, Asymmetric U-shaped Forms, Regression. Classification-JEL :
Informetrics on M. N. Srinivas
No full textM. N. Srinivas, the well known sociologist is widely recognised as architect of modern Indian sociology and social anthropology. His publications have been analysed by year, domain, authorship pattern, channels of communication used. Keywords, etc. The results indicate that the papers published by him are of a nature that qualify him to be a 'role model' for the younger generations to emulate.
By the end of 1995, Srinivas had to his credit 144 papers which, included 33 broad papers in sociology and anthropology; 18 papers in social change; 28 papers in village studies; 12 papers on religion; 17 papers on caste and 36 papers of general popular interest. The periods 1958-61 and 1974-77, when Srinivas was 38-41 and 58-61 years old. were his most productive periods with highest publication activity
C. W. M. Cox et A. Cameron. Monuments from Dorylaeum and Nacolea. (Monumenta Asiae Minoris Antiqua, vol. V)
No full textVollgraff W. C. W. M. Cox et A. Cameron. Monuments from Dorylaeum and Nacolea. (Monumenta Asiae Minoris Antiqua, vol. V). In: L'antiquité classique, Tome 8, fasc. 1, 1939. pp. 331-332
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