1,721,080 research outputs found
Do CYP3A and ABCB1 genotypes influence the plasma concentration and clinical outcome of donepezil treatment?
No full textClinical impact of CYP2D6 polymorphisms in patients with Alzheimer's disease in therapy with donepezil
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin mainenance dose and metabolic clearance
No full textA pharmacometric model describing the relationship between warfarin dose and INR response with respect to variations in CYP2C9, VKORC1, and age
No full textThe objective of the study was to update a previous NONMEM model to describe the relationship between warfarin dose and international normalized ratio (INR) response, to decrease the dependence of the model on pharmacokinetic (PK) data, and to improve the characterization of rare genotype combinations. The effects of age and CYP2C9 genotype on S-warfarin clearance were estimated from high-quality PK data. Thereafter, a temporal dose-response (K-PD) model was developed from information on dose, INR, age, and CYP2C9 and VKORC1 genotype, with drug clearance as a covariate. Two transit compartment chains accounted for the delay between exposure and response. CYP2C9 genotype was identified as the single most important predictor of required dose, causing a difference of up to 4.2-fold in the maintenance dose. VKORC1 accounted for a difference of up to 2.1-fold in dose, and age reduced the dose requirement by similar to 6% per decade. This reformulated K-PD model decreases dependence on PK data and enables robust assessment of INR response and dose predictions, even in individuals with rare genotype combinations
A PK-PD model for predicting the impact of age, CYP2C9, and VKORC1 genotype on individualization of warfarin therapy
No full textThe aim of this study was to characterize the relationship between warfarin concentrations and international normalized
ratio (INR) response and to identify predictors important for dose individualization. S- and R-warfarin concentrations,
INR, and CYP2C9 and VKORC1 genotypes from 150 patients were used to develop a population pharmacokinetic/
pharmacodynamic model in NONMEM. The anticoagulant response was best described by an inhibitory EMAX model,
with S-warfarin concentration as the only exposure predictor for response. Delay between exposure and response was
accounted for by a transit compartment model with two parallel transit compartment chains. CYP2C9 genotype and age
were identified as predictors for S-warfarin clearance, and VKORC1 genotype as a predictor for warfarin sensitivity.
Predicted INR curves indicate important steady-state differences between patients with different sets of covariates;
differences that cannot be foreseen from early INR assessments alone. It is important to account for CYP2C9 and VKORC1
genotypes and age to improve a priori and a posteriori individualization of warfarin therapy
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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