Biomedical subjects

D B Clarkson

Publications and source records attributed to D B Clarkson.

4 recordsLinked to original sources

PubMed2005

Linear parameter haplotype models with stratification.

OBJECTIVES: The question of interest is estimating the relationship between haplotypes and an outcome measure, based upon unphased genotypes. The outcome of interest might be predicting the presence of disease in a logistic model, predicting a numeric drug response in a linear model, or predicting survival time in a parametric survival model with censoring. Explanatory variables may include phased haplotype design variables, environmental variables, or interactions between them. METHODS: We extend existing generalized linear haplotype models to parametric survival outcomes. To improve the stability of model variance estimates, a profile likelihood solution is proposed. An adjustment for population stratification is also considered. Here we investigate data sampled from known 'strata' (e.g., gender or ethnicity) that influence haplotype prior probabilities and thus the regression model weights. Differing linear model variance estimates, and the effect of stratification and departures from Hardy-Weinberg Equilibrium (HWE) on parameter estimates, are compared and contrasted via simulation. RESULTS: From simulations, we observed an improvement in statistical power when using a solution to profile likelihood equations. We also saw that stratification had little impact on estimates. Haplotypes that are not in HWE had a negative impact on power to test hypotheses. Finally, profile likelihood solutions for haplotypes deviating from HWE had improved power and confidence interval coverage of regression model coefficients.

Carcinoma, Squamous Cell↗

PubMed1997

Hazard regression with interval-censored data.

In a recent paper, Kooperberg, Stone, and Truong (1995a) introduced hazard regression (HARE), in which linear splines and their tensor products are used to estimate the conditional log-hazard function based on possibly censored, positive response data and one or more covariates. Model selection is carried out in an adaptive fashion using maximum likelihood estimation of the unknown coefficients, Rao and Wald statistics to carry out stepwise addition and deletion of basis functions, and the Bayesian Information Criterion (BIC) to select the final model. In the present paper, the HARE methodology is extended to accommodate interval-censored data, time-dependent covariates, and cubic splines. The presence of interval-censored data means that the log-likelihood function may no longer be concave, presenting additional numerical challenges. The extended methodology is applied to a data set containing both interval-censoring and time-dependent covariates. The new software will be available in a future release of S-Plus.

Acquired Immunodeficiency Syndrome↗

PubMed1982

Naloxone decreases consumption of liquid and solid sucrose in vagotomized rats.

Intraperitoneal injections of the opiate antagonist naloxone decreased food intake in both vagotomized and sham-vagotomized rats. Consumption of liquid and solid sucrose, which were used in order to equate baseline intake, was equally suppressed in both groups under food-deprivation and appetitively-motivated conditions at all doses of naloxone (1, 2, 4, and 8 mg/kg). It is concluded that, in contrast to previous findings, the vagus nerve does not mediate the suppressive effects of naloxone on feeding behavior.

Animals↗

PubMed1982

Inhibition of axoplasmic transport in the developing visual system of the rat-II, Quantitative analysis of alterations in transport of tritiated proline or fucose.

Developmental alterations in the amount of tritiated proline and fucose incorporated by retinal neurons and transported within axons of the optic nerve to the dorsal lateral geniculate nucleus and superior colliculus were measured at 1, 5, 10 and 15 days postnatal using quantitative autoradiography and liquid scintillation analysis. The amount of axon transport inhibition induced by introacular injections of colchicine (10-4 M-5 X 10-3M) and xylocaine (10-3 M-10-1 M) was also determined by this methodology. Grain counts of retinal autoradiograms obtained from animals of all ages employed in this study demonstrated that [3H] proline is rapidly incorporated by all retinal neurons but becomes increasingly concentrated within the inner nuclear, ganglion cell and optic fiber layers between 2h and 2 days after injection. [3H] fucose is preferentially taken up and concentrated within the plexiform and sensory element layers. Intraocular colchicine administered 24 h prior to isotope injection exhibited no significant effect on incorporation but depressed the amount of activity in the layer of optic fibers. Comparison of the effects of colchicine and xylocaine on axon transport of [3H] proline injected at 3 days of age revealed dose-dependent suppression of transport occurring up to six hr after isotope injection; however, with longer survival periods the effects of xylocaine were no longer significant whereas colchicine maintained suppression of axon transport to 20% of normal for periods of up to 10 days. Additionally, the rate and quantity of 3H] proline transported to the dorsal lateral geniculate nucleus and tectum of 1-15 day old animals was found to be inversely proportional to the age of the animal. Maximally-effective concentrations of colchicine, determined for each age level examined by the previous study to be highest compatible with the viability of the retino-fugal projection, 34 also reduced transport to from 20-40% of normal, being most effective in animals of 1-10 days of age. Autoradiographs of the optic disc demonstrated a colchicine-induced suppression of the amount of label in the exiting optic fibers and similar preparations of the tectum revealed an elimination of activity in the stratum griseum superficialis and stratum opticum which are normally heavily labeled following intraocular [3H] proline or fucose. Following [3H] fucose injection at 10 days of age, isotope appears in the contralateral visual cortex between 3 and 10 days later, indicating a substantial amount of transneuronal transfer of label which appeared to occur in concert with periods of maximal synaptogenesis. Injection of colchicine reduced the amount of label in the cortex to background levels. Concomitantly, autoradiographs of the dorsal lateral geniculate nucleus revealed cytoplasmic labeling of geniculate neurons in control animals but this was eliminated following colchicine injection...

Animals↗