Indiana University

About: Indiana University is a education organization based out in Bloomington, Indiana, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 64480 authors who have published 150058 publications receiving 6392902 citations. The organization is also known as: Indiana University system & indiana.edu.

Clinical significance of the cytochrome P450 2C19 genetic polymorphism.

Abstract: Cytochrome P450 2C19 (CYP2C19) is the main (or partial) cause for large differences in the pharmacokinetics of a number of clinically important drugs. On the basis of their ability to metabolise (S)-mephenytoin or other CYP2C19 substrates, individuals can be classified as extensive metabolisers (EMs) or poor metabolisers (PMs). Eight variant alleles (CYP2C19*2 to CYP2C19*8) that pre-diet PMs have been identified. The distribution of EM and PM genotypes and phenotypes shows wide interethnic differences. Nongenetic factors such as enzyme inhibition and induction, old age and liver cirrhosis can also modulate CYP2C19 activity. In EMs, ∼80% of doses of the proton pump inhibitors (PPIs) omeprazole, lansoprazole and pantoprazole seem to be cleared by CYP2C19, whereas CYP3A is more important in PMs. Five-fold higher exposure to these drugs is observed in PMs than in EMs of CYP2C19, and further increases occur during inhibition of CYP3A-catalysed alternative metabolic pathways in PMs. As a result, PMs of CYP2C19 experience more effective acid suppression and better healing of duodenal and gastric ulcers during treatment with omeprazole and lansoprazole compared with EMs. The pharmacoeconomic value of CYP2C19 genotyping remains unclear. Our calculations suggest that genotyping for CYP2C19 could save approximately $US5000 for every 100 Asians tested, but none for Caucasian patients. Nevertheless, genotyping for the common alleles of CYP2C19 before initiating PPIs for the treatment of reflux disease and H. pylori infection is a cost effective tool to determine appropriate duration of treatment and dosage regimens. Altered CYP2C19 activity does not seem to increase the risk for adverse drug reactions/interactions of PPIs. Phenytoin plasma concentrations and toxicity have been shown to increase in patients taking inhibitors of CYP2C19 or who have variant alleles and, because of its narrow therapeutic range, genotyping of CYP2C19 in addition to CYP2C9 may be needed to optimise the dosage of phenytoin. Increased risk of toxicity of tricyclic antidepressants is likely in patients whose CYP2C19 and/or CYP2D6 activities are diminished. CYP2C19 is a major enzyme in proguanil activation to cycloguanil, but there are no clinical data that suggest that PMs of CYP2C19 are at a greater risk for failure of malaria prophylaxis or treatment. Diazepam clearance is clearly diminished in PMs or when inhibitors of CYP2C19 are coprescribed, but the clinical consequences are generally minimal. Finally, many studies have attempted to identify relationships between CYP2C19 genotype and phenotype and susceptibility to xenobiotic-induced disease, but none of these are compelling.

Sex Determination: Why So Many Ways of Doing It?

Abstract: Sexual reproduction is an ancient feature of life on earth, and the familiar X and Y chromo- somes in humans and other model species have led to the impression that sex determination mecha- nisms are old and conserved. In fact, males and females are deter- mined by diverse mechanisms that evolve rapidly in many taxa. Yet this diversity in primary sex-deter- mining signals is coupled with conserved molecular pathways that trigger male or female develop- ment. Conflicting selection on dif- ferent parts of the genome and on the two sexes may drive many of these transitions, but few systems with rapid turnover of sex determi- nation mechanisms have been rig- orously studied. Here we survey our current understanding of how and why sex determination evolves in animals and plants and identify important gaps in our knowledge that present exciting research op- portunities to characterize the evo- lutionary forces and molecular pathways underlying the evolution of sex determination.

Transformational and transactional leadership and salesperson performance

Abstract: This study examines the impact of transformational and transactional leader behaviors on the sales performance and organizational citizenship behaviors of salespeople, as well as the mediating role played by trust and role ambiguity in that process. Measures of six forms of transformational leader behavior, two forms of transactional leader behavior, trust, and role ambiguity were obtained from 477 sales agents working for a large national insurance company. Objective sales performance data were obtained for the agents, and their supervisors provided evaluations of their citizenship behaviors. The findings validate not only the basic notion that transformational leadership influences salespeople to perform “above and beyond the call of duty” but also that transformational leader behaviors actually have stronger direct and indirect relationships with sales performance and organizational citizenship behavior than transactional leader behaviors. Moreover, this is true even when common method biases are controlled. The implications of these findings for future research are discussed.

Cross-Functional Product Development Teams, Creativity, and the Innovativeness of New Consumer Products

Abstract: Multiple studies have found that the primary determinant of new product failure is an absence of innovativeness—the extent to which a new product provides meaningfully unique benefits. Given the persistence of this finding and the growing use of cross-functional teams in new product development projects, the authors examine how innovativeness is affected by various characteristics of cross-functional teams and contextual influences on the team. On the basis of a study of 141 cross-functional product development teams, the authors find that innovativeness is positively related to the strength of superordinate identity in the team, encouragement to take risk, customers’ influence, and active monitoring of the project by senior management. Beyond a moderate level, social cohesion among team members has a negative effect on innovativeness. The effect of superordinate identity on innovativeness is strengthened by encouragement to take risk and weakened by social cohesion. Functional diversity has no e...

The Measurement of Entrepreneurial Orientation

Abstract: This article explores how the concept of entrepreneurial orientation (EO) has been portrayed and assessed in prior research. The challenges and decision criteria associated with formative versus reflective measurement approaches are reviewed. It is argued that, as a latent construct, EO exists apart from its measures and that researchers are free to choose whichever measurement approach best serves their research purposes, recognizing that unidimensional versus multidimensional EO measurement models are consistent with fundamentally different conceptualizations of the EO construct. Recommendations are offered regarding potentially appropriate formative and reflective measures of EO.