This article assesses the statistical consequences of computing detection-theoretic sensitivity measures (d') from response rates averaged across subjects. Collapsed d', based on such averaged proportions, underestimates true average d' to only a small degree in most cases, and its variability is less than that of averaged d'. We consider two other approaches to computing group sensitivity: transforming the individual response rates before averaging and using nonparametric measures. Careful application of detection theory in situations in which individual sensitivities cannot be computed is often better than these alternatives.
For most perceptual continua, observers' ability to discriminate exceeds their ability to identify. Certain dimensions, however, particularly in speech perception, are said to be "categorically" perceived, in the sense that they can be discriminated only as well as they can be labeled. This article offers a signal detection theory analysis of categorical perception; in previous models, lowthreshold assumptions have been made. Discrimination paradigms popularly used to test the categorical perception hypothesis, such as the ABX and samedifferent designs, are analyzed, and unbiased sensitivity measures (d r ) abstracted. A Thurstonian model is used to predict discrimination from identification under the hypothesis that perception is categorical. For cases in which perception is found not to be categorical, we show how the hypothesis of dual processing of phonemic and nonphonemic information can be distinguished from alternative models.
Methoxsalen inhibits nicotine first-pass metabolism of orally administered nicotine, and the combination directly reduces smoking in a laboratory setting. CYP2A6 inhibitors may have an important role in smoking cessation and tobacco exposure reduction.
The contribution of cytochrome P450 2D6 (CYP2D6) to the formation of hydrocodone's active metabolite, hydromorphone, was examined in vitro and in vivo. Human liver microsomes prepared from an individual homozygous for the D6-B mutation of the CYP2D6 gene catalyzed this reaction at a negligible rate. Urinary metabolic ratios of hydrocodone/hydromorphone were highly correlated with O-demethylation ratios for dextromethorphan, an established marker drug of CYP2D6 activity (rs = 0.85; n = 18). The kinetics of hydrocodone after a single oral dose and its partial metabolic clearance to hydromorphone were investigated in five extensive metabolizers of dextromethorphan, six poor metabolizers, and four extensive metabolizers after pretreatment with quinidine, a selective inhibitor of CYP2D6 activity. The mean values for partial metabolic clearance by O-demethylation in the three groups were 28.1 +/- 10.3, 3.4 +/- 2.4, and 5.0 +/- 3.6 ml/hr/kg, respectively. No statistically significant phenotypic differences in physiologic measures were observed. However, over the first hour after dosing, the extensive metabolizers reported more "good opiate effects" and fewer "bad opiate effects" than poor metabolizers and extensive metabolizers in whom CYP2D6 was inhibited by quinidine. These data establish the importance of CYP2D6 in the formation of hydromorphone from hydrocodone and suggest that the activity of this enzyme may limit the abuse liability of hydrocodone.
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