Nicotine metabolism influences smoking behavior and differences in metabolism probably contribute to ethnic variability in lung cancer risk. We report here on the proportion of nicotine metabolism by cytochrome P450 2A6-catalyzed C-oxidation, UDP-glucuronosyl transferase 2B10 (UGT2B10)-catalyzed N-glucuronidation and flavin monooxygenase 3-catalyzed N-oxidation in five ethnic/racial groups and the role of UGT2B10 genotype on the metabolic patterns observed. Nicotine and its metabolites were quantified in urine from African American (AA, n = 364), Native Hawaiian (NH, n = 311), White (n = 437), Latino (LA, n = 453) and Japanese American (JA, n = 674) smokers. Total nicotine equivalents, the sum of nicotine and six metabolites, and nicotine metabolism phenotypes were calculated. The relationship of UGT2B10 genotype to nicotine metabolic pathways was determined for each group; geometric means were computed and adjusted for age, sex, creatinine, and body mass index. Nicotine metabolism patterns were unique across the groups, C-oxidation was lowest in JA and NH (P < 0.0001), and N-glucuronidation lowest in AA (P < 0.0001). There was no difference in C-oxidation among Whites and AA and LA. Nicotine and cotinine glucuronide ratios were 2- and 3-fold lower in AA compared with Whites. Two UGT variants, a missense mutation (Asp67Tyr, rs61750900) and a splice variant (rs116294140) accounted for 33% of the variation in glucuronidation. In AA, the splice variant accounted for the majority of the reduced nicotine glucuronidation. UGT2B10 variant allele carriers had increased levels of C-oxidation (P = 0.0099). Our data indicate that the relative importance of nicotine metabolic pathways varies by ethnicity, and all pathways should be considered when characterizing the role of nicotine metabolism on smoking behavior and cancer risk.

The genealogical relationships among naturally established seedlings and flowering individuals were analyzed for a large population of the dioecious plant species Chamaelirium luteum. Genetic likelihoods based on 11 electrophoretic markers of all possible parent pairs within flowering seasons from 1974 to 1981 preceding observed establishment of seedlings from 1976 to 1982 were evaluated; and most-likely parents for 283 seedlings were thus identified, enabling a partial reconstruction of the genealogy of this population. This information, combined with the map location of each plant, was used to analyze realized gene-flow patterns.Intermate distances showed more nearby matings than would the kind of pollen dispersal profile that could be expected under random mating. Overall, seedlings tended to undergo establishment at locations between their maternal and paternal parents, indicating localized genetic adaptation along environmental gradients. Finally, a negative correlation was observed between inflorescence size (reproductive effort) and number of progeny observed (reproductive success).Techniques of genealogy reconstruction have previously been limited to human populations. As seen in the present study, such techniques also show great promise for revealing the evolutionary behavior of natural populations.

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Examination of the concurrent and criterion validities of the General Ability Measure for Adults (GAMA) and the Wechsler Adult Intelligence Scale-Third Edition (WAIS-IH) in patients with traumatic brain injury (TBI). Study Design: Correlational methods and multivariate analyses of variance. Setting: Regional rehabilitation center. Participants: Prospective series of consecutive rehabilitation referrals, including 60 adults with TBI and no confounding premorbid histories. Main Outcome Measures: GAMA and WAIS-IH IQ and factor index scores were obtained within 1 year after injury and were compared with each other and with measures of injury severity. Results: GAMA and WAIS-III summary IQ scores demonstrated substantial covariance (supporting concurrent validity), but neither was sufficiently sensitive to injury severity. The WAIS-III Processing Speed (PS) index was the only measure that clearly demonstrated criterion validity. Conclusions: GAMA and WAIS-III summary IQ scores measure similar abilities but may not be sensitive to degree of injury severity in individuals with TBI. In contrast, the WAIS-III PS index appears to have promise in the evaluation of sequelae of TBI.

The validity of correcting for demographic variables when considering neuropsychological test scores was evaluated in a sample of 136 patients with traumatic brain injury (TBI) who had been screened carefully for premorbid or comorbid confounding factors. When considered in concert with neurological variables, age and education accounted for a significant proportion of the variance in raw scores on the Category Test and the Trail Making Test in the complete sample. Gender did not affect level of test performance. Correcting neuropsychological test scores for demographic variables did not significantly alter their success in identifying patients with severe TBI, but did lead to greater accuracy when classifying individuals with mild-moderate TBI. This investigation concluded that norms that consider the demographic background of the individual are likely to reflect more accurately the neuropsychological status of patients with TBI than interpretations that are based exclusively on raw data.