PubMed Health⌕ Search

Biomedical subjects

R Corley

Publications and source records attributed to R Corley.

18 recordsLinked to original sources
PubMed2005

Using physiologically-based pharmacokinetic modeling to address nonlinear kinetics and changes in rodent physiology and metabolism due to aging and adaptation in deriving reference values for propylene glycol methyl ether and propylene glycol methyl ether acetate.

Reference values, including an oral reference dose (RfD) and an inhalation reference concentration (RfC), were derived for propylene glycol methyl ether (PGME), and an oral RfD was derived for its acetate (PGMEA). These values were based on transient sedation observed in F344 rats and B6C3F1 mice during a two-year inhalation study. The dose-response relationship for sedation was characterized using internal dose measures as predicted by a physiologically-based pharmacokinetic (PBPK) model for PGME and its acetate. PBPK modeling was used to account for changes in rodent physiology and metabolism due to aging and adaptation, based on data collected during Weeks 1, 2, 26, 52, and 78 of a chronic inhalation study. The peak concentration of PGME in richly perfused tissues (i.e., brain) was selected as the most appropriate internal dose measure based on a consideration of the mode of action for sedation and similarities in tissue partitioning between brain and other richly perfused tissues. Internal doses (peak tissue concentrations of PGME) were designated as either no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs) based on the presence or the absence of sedation at each time point, species, and sex in the two-year study. Distributions of the NOAEL and LOAEL values expressed in terms of internal dose were characterized using an arithmetic mean and standard deviation, with the mean internal NOAEL serving as the basis for the reference values, which was then divided by appropriate uncertainty factors. Where data were permitting, chemical-specific adjustment factors were derived to replace default uncertainty factor values of 10. Nonlinear kinetics, which was predicted by the model in all species at PGME concentrations exceeding 100 ppm, complicate interspecies, and low-dose extrapolations. To address this complication, reference values were derived using two approaches that differ with respect to the order in which these extrapolations were performed: (1) default approach of interspecies extrapolation to determine the human equivalent concentration (PBPK modeling) followed by uncertainty factor application, and (2) uncertainty factor application followed by interspecies extrapolation (PBPK modeling). The resulting reference values for these two approaches are substantially different, with values from the latter approach being seven-fold higher than those from the former approach. Such a striking difference between the two approaches reveals an underlying issue that has received little attention in the literature regarding the application of uncertainty factors and interspecies extrapolations to compounds where saturable kinetics occur in the range of the NOAEL. Until such discussions have taken place, reference values based on the former approach are recommended for risk assessments involving human exposures to PGME and PGMEA.

Administration, Inhalation↗
PubMed2000

Early childhood heart rate does not predict externalizing behavior problems at age 7 years.

OBJECTIVE: In previous research, low resting heart rate in childhood and adolescence has been shown to predict aggressive and/or delinquent behavior at subsequent ages. It has been found that heart rate recorded as early as age 3 years could predict externalizing behavior at age 11 years. This study explored the possibility of a similar relationship between heart rate and externalizing behavior problems. METHOD: Heart rate recorded at ages 14, 20, 24, 36 months and 7 years was used to predict combined parental ratings on the Aggressive and Delinquent Behavior scales of the Child Behavior Checklist (CBCL/4-18) as well as the Externalizing composite scale measured at age 7 years. Subjects consisted of same-sex twin pairs, treated as singletons in the present study, participating in the MacArthur Longitudinal Twin Study. Subjects were grouped into high and low heart rate groups and also into high CBCL/4-18 scoring and low CBCL/4-18 scoring groups. RESULTS: Heart rate was not significantly related to scores on either of the 2 subscales or the Externalizing composite scale at any age. Heart rate group membership did not predict CBCL/4-18 scores. Conversely, CBCL/4-18 group membership did not predict heart rate at any age. CONCLUSION: In this sample, heart rate does not predict externalizing behavior at age 7.

Arousal↗
PubMed2000

An exploration of the genetic and environmental etiology of heart rate in infancy and middle childhood.

Heart rate was recorded on 210 MZ and 174 DZ same sex twin pairs participating in the MacArthur Longitudinal Twin Study (MALTS) at age 14, 20, 24, 36 months and 7 years. Heart rate was monitored in the laboratory at all ages. At ages 14 to 36 months, heart rate was monitored prior to a set of cognitive tasks. At age 7 years heart rate was recorded during a mood-eliciting videotaped presentation. At this age only heart rate monitored during neutral portions of the presentation were used. Mean heart rate declines substantially across this age range, but is similar in boys and girls and for MZ and DZ twins at each age. Heart rate is moderately correlated across all time points suggesting that individual differences in heart rate are relatively stable over this age range. Multivariate genetic and environmental models were fitted to the raw data. In general, genetic factors contribute to the stability of individual differences over time. Shared and non-shared environment factors tended to be occasion specific, with non-shared environment contributing substantially to the individual variation at each age. Shared environment and non-shared environment also contributed a modicum to the stability across time. Thus, individual differences in resting heart rate is a relatively stable, heritable trait from infancy to early childhood.

Affect↗
PubMed1999

Altruistic moral judgment among older adults.

This study investigated altruistic moral judgment among the elderly, and examined its relationships to demographic and personality variables, self-reported helping, and subjective social integration (the perception that one is integrated into one's social milieu). The moral judgment interview included three stories, each of which contained a moral dilemma. Participants solved each dilemma and gave reasons for their solutions. The moral dilemmas and scoring system emphasized the positive, prosocial aspects of morality, rather than a prohibition-oriented approach. The categories used most often were, in descending order of frequency 1) pragmatic needs-of-others oriented reasons, 2) empathy-based reasons, 3) reasons based on internalized and/or abstract moral principles, and 4) hedonistic reasons. Of the higher levels of moral judgment, only reasoning based on abstract internalized principles had significant positive relationships with self-reported helping, the personality correlates of helping, and with subjective social integration into one's social milieu.

Aged↗
PubMed1998

Multivariate path analysis of specific cognitive abilities data at 12 years of age in the Colorado Adoption Project.

A parent-offspring multivariate conditional path model was fitted to specific cognitive abilities data from the Colorado Adoption Project (CAP) when the offspring were 12 years of age. The sample included 175 adoptees, 175 sets of adoptive parents, 175 biological mothers, 34 biological fathers, and 209 nonadopted children and their parents. Consistent with results obtained from multivariate genetic analyses of CAP data obtained at earlier ages, the effects of familial environmental transmission on individual differences in specific cognitive abilities were not significant. Assuming complete isomorphism (i.e., that the genetic and environmental etiologies of individual differences are the same) between the child and the adult measures, the heritability estimates for verbal, spatial, perceptual speed, and visual memory were .26, .35, .38, and .53, respectively. Although the heritability estimate for visual memory is somewhat higher than those for verbal, spatial, and perceptual speed abilities, these estimates are not significantly different. These estimates are higher than those obtained when the adoptees and controls were 4 years old (Rice et al., 1986, 1989); thus, heritabilities of specific cognitive abilities may increase as a function of cognitive development. Alternatively, genetic stability from childhood to adulthood may be greater from 12 years than from 4 years, which would be interpreted as greater heritability by the CAP parent-offspring design. The genetic correlations among the four measures were substantial, ranging from .27 between verbal and spatial abilities to .78 between spatial ability and perceptual speed. However, differences among these correlations are not significant, suggesting that their covariation may be due to general cognitive ability. Finally, estimates of bivariate-heritability indicate that on average about half of the phenotypic correlations among the four specific cognitive ability measures are due to genetic effects.

Adoption↗
PubMed1998

Adoption results for self-reported personality: evidence for nonadditive genetic effects?

Twin studies consistently indicate moderate genetic influence on individual differences in personality as assessed using self-report questionnaires, with heritability estimates typically about 40%. In this first analysis of self-report personality data from the longitudinal Colorado Adoption Project, little evidence is found for additive genetic influence in parent-offspring and sibling adoption analyses based on a foundation sample of 245 adoptive families and 245 nonadoptive families with adopted and nonadopted children assessed yearly from 9 to 16 years. Although several factors might contribute to the discrepancy between twin and adoption results, we suggest that nonadditive genetic influence, which can be detected by twin studies but not by adoption studies, is a likely culprit. These findings have important implications for attempts to identify specific genes responsible for genetic influence on personality.

Adolescent↗
PubMed1998

Identification of a genetic region in mice that specifies sensitivity to propofol.

BACKGROUND: Long-sleep (LS) and short-sleep (SS) mice, initially selected for differential sensitivity to ethanol, also exhibit differential sensitivity to propofol. By interbreeding LS and SS mice to obtain progeny whose chromosomes are a patchwork of the LS and SS chromosomes, the authors determined whether differential propofol sensitivity cosegregates with any particular chromosomal region(s). Such cosegregation is the essence of genetic linkage mapping and a first step toward isolating a gene that can modulate propofol sensitivity in mammals. A gene underlying a quantitative trait such as anesthetic sensitivity is commonly called a quantitative trait locus (QTL). METHODS: The propofol dose was 20 mg/kg injected retroorbitally. Sensitivity was measured as the duration of the loss of righting reflex (LORR). The LORR and propofol brain levels at awakening were determined for 24 LSXSS recombinant-inbred (RI) strains, derived by intercrossing LS and SS for two generations followed by >20 generations of inbreeding. A genetic linkage between LORR and an albino mutation on chromosome 7 was investigated further using 164 second-generation progeny (F2s) from intercrossing inbred LS and inbred SS mice, similar to the LSXSS RIs except F2s are not inbred. The linkage between propofol sensitivity and the albino locus also was investigated using additional genetic markers on chromosome 7. Statistical significance was assessed by interval mapping using a regression method for RIs and Mapmaker/QTL (Whitehead Institute, Cambridge, MA) for F2s. RESULTS: Genetic mapping in the LSXSS RIs revealed a QTL tightly linked to the Tyr (albino) locus that accounts for nearly all of the genetic difference in propofol sensitivity between LS and SS mice. Analysis of propofol brain levels at awakening indicated that this QTL results from differential neurosensitivity. Mapping in F2s confirmed the genetic linkage to Tyr. Mice (ISS c/c x C57BL/6 c2j/C) that differed only by an albino mutation at Tyr were not differentially sensitive to propofol. CONCLUSIONS: A single QTL, called Lorp1, underlies most of the genetic difference in propofol neurosensitivity between LS and SS mice. Although this QTL is tightly linked to Tyr, propofol sensitivity is not modulated by albinism. For mapping this QTL, the LSXSS RIs proved to be an especially powerful resource, localizing the candidate-gene region to a 99% confidence interval of only 2.5 centimorgans.

Anesthetics, Intravenous↗
PubMed1997

A longitudinal twin study of intelligence in the second year.

Data from 408 pairs of identical and same-sex fraternal twins assessed at home and in the laboratory at 14, 20, and 24 months are used to describe cognitive development in the second year and to identify genetic and environmental influences on phenotypic similarity. The primary dependent variables are the Bayley Mental Development Index and separate constructs (based on items from the Bayley and the Sequenced Inventory of Communication Development) to measure nonverbal ability, expressive language, and receptive language. These variables are supplemented with laboratory tests of word comprehension, visual attentiveness, and memory for locations. Various patterns of development emerge for separate constructs, for females versus males on each construct, and for individuals across constructs. These data suggest developmental transitions for many infants during the second year, but the timing of these transitions varies by measure. The dependent variables tend to be intercorrelated and are reasonably stable for individuals, with greater stability late in the second year, suggesting either increasing stability or more effective measurement. Expressive and receptive language scores are correlated and have comparable patterns of change within individuals, but there are also differences (e.g., receptive language accounts for the most variance in MDI at each age and across ages). There are genetic effects on MDI at each age and effects of shared environment at 20 and 24 months. Analyses of separate constructs reveal distinct patterns. Effects on nonverbal abilities are entirely genetic. Effects on language are primarily environmental, but genetic influence emerges for expressive language at 20 and 24 months and for receptive language at 14 months. Visual attentiveness tended to reveal effects comparable to the nonverbal construct, and word comprehension was related to the receptive composite. Scores on the memory for locations task were relatively uninformative. A Cholesky decomposition is used to identify influences that account for the same variance at each age (i.e., promote continuity) and that account for new variance at each assessment (i.e., promote change) and to explore overlap and distinctiveness among measures at each age.

Age Factors↗
PubMed1996

Do animal models have a place in the genetic analysis of quantitative human behavioural traits?

It seems that the genetic basis of common psychiatric diseases such as schizophrenia and manic-depressive psychosis is amenable to the genetic mapping strategies that have been successful in other complex disorders such as diabetes. The next challenge is the genetic dissection of quantitative behavioural traits such as mood, personality and intelligence. Quantitative traits pose new problems for gene cloning experiments. We argue that one way forward is by using animal models. One of the features of quantitative traits is that the DNA sequence variants which are responsible for them are unlikely to be immediately recognizable. In contrast to many qualitative traits where a discrete phenotypic difference is often the consequence of an inactivating mutation, the allelic variation responsible for quantitative traits probably has a more subtle basis. This distinction means that strategies to clone the genetic basis of quantitative behavioural traits will have to rely on functional assays of alleles thought to be important in determining the phenotype. We suggest that an efficient strategy for detecting sequences that give rise to quantitative behavioural traits can be devised in the mouse. The importance and utility of the mouse for quantitative trait analysis make it worthwhile to investigate mouse models of human behaviour; these advantages outweigh the difficulties that arise in attempts to validate the animal models. As an example we review the evidence that validates rodent emotionality as an animal model for susceptibility to human anxiety. We show that there is good evidence that rodent emotionality is a central nervous system state with a genetic basis, and that there are neuropharmacological and neuroanatomical parallels with human anxiety. Furthermore, our own work has shown that the genetic basis of the trait is relatively simple, and that the task of characterizing it at a molecular level is feasible. We expect that future experiments will show us how genetic variation gives rise to quantitative behavioural traits.

Animals↗
PubMed1995

A simple genetic basis for a complex psychological trait in laboratory mice.

Psychological traits are commonly inferred from covariation in sets of behavioral measures that otherwise appear to have little in common. Emotionality in mice is such a trait, defined here by covariation in activity and defecation in a novel environment and emergence into the open arms of an elevated plus maze. Behavioral and quantitative trait analyses were conducted on four measures obtained from 879 mice from an F2 intercross. Three loci, on murine chromosomes 1, 12, and 15, were mapped that influence emotionality. This trait, inferred from studies of strain, sex, and individual differences in rodents, may be related to human susceptibility to anxiety or neuroticism.

Animals↗
PubMed1995

Assessing adolescents' prosocial behavior: the Family Helping Inventory.

This study examined the structure and psychometric properties of a self-report measure of adolescents' helping behavior within the family--the Family Helping Inventory (FHI)--and of its two scales, the Sibling Helping Scale (SHS) and the Parent Helping Scale (PHS). The FHI was administered to 202 adolescents along with several existing measures of prosocial tendencies and with a measure of Machiavellianism. Factor analyses yielded four internally consistent subscales for the SHS and five for the PHS, all of which were conceptually related to inventories reflecting family support among adults. Both convergent and discriminant validity were demonstrated as well.

Adolescent↗
PubMed1993

Genetic change and continuity from fourteen to twenty months: the MacArthur Longitudinal Twin Study.

Genetic change as well as continuity was investigated within the domains of temperament, emotion, and cognition/language for 200 pairs of twins assessed at 14 and 20 months of age in the laboratory and home. The second year of life is marked by change rather than continuity: correlations from 14 to 20 months averaged about .30 for observational measures of temperament and emotion, about .40 for language measures, and about .50 for mental development. 2 types of genetic change were examined: changes in the magnitude of genetic influence (heritability) and genetic contributions to change from 14 to 20 months. In general, heritability estimates were similar at 14 and 20 months. Evidence for genetic influence on change from 14 to 20 months emerged for several measures, implying that heritability cannot be equated with stability. Analyses of continuity indicated that genetic factors are largely responsible for continuity from 14 to 20 months.

Child Development↗
PubMed1992

Identifying children in the Colorado Adoption Project at risk for conduct disorder.

Clustering techniques were used to identify a subsample of young adopted and nonadopted children in the Colorado Adoption Project at risk for conduct disorder. Although data from both boys and girls were analyzed, a cluster of girls large enough for subsequent statistical analysis could not be identified; therefore, results are reported for boys only. Identifying measures were selected based on the DSM-III-R diagnostic criteria. Cluster analyses confirmed the existence of a small group of boys who appeared to be significantly at risk. Subsequent parental and teacher ratings of these children verified the stability over time of the classification. The poor conduct group was significantly associated with difficult temperament in infancy, with poor conduct on the part of parents when they were youths, and with high achievement orientation in the home environment.

Adoption↗
PubMed1992

Temperament, emotion, and cognition at fourteen months: the MacArthur Longitudinal Twin Study.

200 pairs of twins were assessed at 14 months of age in the laboratory and home. Measures were obtained of temperament, emotion, and cognition/language. Comparisons between identical and fraternal twin correlations suggest that individual differences are due in part to heritable influences. For temperament, genetic influence was significant for behavioral observations of inhibition to the unfamiliar, tester ratings of activity, and parental ratings of temperament. For emotion, significant genetic influence was found for empathy and parental ratings of negative emotion. The estimate of heritability for parental report of expression of negative emotions was relatively high, whereas that for expression of positive emotions was low, a finding consistent with previous research. For cognition and language, genetic influence was significant for behavioral indices of spatial memory, categorization, and word comprehension. Shared rearing environment appears influential for parental reports of language and for positive emotions, but not for other measures of emotion or for temperament.

Cognition↗
PubMed1988

Multivariate diallel analysis of ethanol withdrawal symptoms in mice.

Mice from five highly inbred strains were crossed in a complete diallel design. Five hundred and fifty-five offspring were given a liquid diet containing ethanol as their sole food source for 9 days in an attempt to induce dependence. At 6 hr postwithdrawal on day 10, the mice were given a battery of physiological and behavioral measures designed to assess the symptoms of withdrawal. Littermate data were aggregated separately by sex and the aggregate litter mean data was employed in a multivariate extension of Hayman's diallel analysis. Hypothesis sums of squares and cross-products were tested against pooled-within-cell sums of squares and cross-products using Wilk's lambda as a criterion. For each sex, a highly significant additive effect was found, with some evidence for dominance effects as well, suggesting the raw materials are present for successful genetic selection. There was some evidence for dominance effects as well, but no evidence for maternal and other reciprocal effects was found for the set of seven measures. Composites derived from the additive and general dominance hypotheses correlation matrices and error correlation matrix were compared with a composite index currently being used in a multivariate selection study of ethanol dependence. Total ethanol consumption during the exposure period was positively correlated with low dependence between strains, and negatively correlated with measures of low dependence within cells.

Alcohol Drinking↗