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Biomedical subjects

T P Speed

Publications and source records attributed to T P Speed.

46 records · Page 3Linked to original sources

Factors associated with human immunodeficiency virus seroconversion in homosexual men in three San Francisco cohort studies, 1984-1989.

A total of 83 HIV seroconversions occurred between 1984 and 1989 in three San Francisco cohorts of homosexual and bisexual men. A nested case-control analysis was performed to assess the risk of seroconversion associated with sexual practices. Strong associations were found with total number of intercourse partners and receptive anal intercourse. Weaker, but significant associations were found with receptive oral intercourse. Individuals reporting condom use with some partners were more likely to become infected than those reporting no condom use. Some of this difference was due to increased numbers of sexual partners among those reporting some condom use, but the association remained significant in multivariate analyses. This observation indicates there is some unmeasured risk associated with those using condoms, such as more HIV seropositive partners.

Cohort Studies↗

Robustness of the no-interference model for ordering genetic markers.

Under the assumption of no chromatid interference, we derive constraints on the probabilities of the different recombination patterns among m + 1 genetic loci. An application of these constraints is a proof that the ordering of the loci that maximizes the likelihood under the assumption of no interference is, in fact, a consistent estimator of the true order even when there is interference.

Chromatids↗

Estimating the fraction of invariable codons with a capture-recapture method.

A codon-based approach to estimating the number of variable sites in a protein is presented. When first and second positions of codons are assumed to be replacement positions, a capture-recapture model can be used to estimate the number of variable codons from every pair of homologous and aligned sequences. The capture-recapture estimate is compared to a maximum likelihood estimate of the number of variable codons and to previous approaches that estimate the number of variable sites (not codons) in a sequence. Computer simulations are presented that show under which circumstances the capture-recapture estimate can be used to correct biases in distance matrices. Analysis of published sequences of two genes, calmodulin and serum albumin, shows that distance corrections that employ a capture-recapture estimate of the number of variable sites may be considerably different from corrections that assume that the number of variable sites is equal to the total number of positions in the sequence.

Biological Evolution↗

Inner cell allocation in the mouse morula: the role of oriented division during fourth cleavage.

Two populations of blastomeres become positionally distinct during fourth cleavage in the mouse embryo; the inner cells become enclosed within the embryo and the outer cells form the enclosing layer. The segregation of these two cell populations is important for later development, because it represents the initial step in the divergence of placental and fetal lineages. The mechanism by which the inner cells become allocated has been thought to involve the oriented division of polarized 8-cell blastomeres, but this has never been examined in the intact embryo. By using the technique of time-lapse cinemicrography, we have been able for the first time to directly examine the division planes of 8-cell blastomeres during fourth cleavage, and find that there are three, rather than two, major division plane orientations; anticlinal (perpendicular to the outer surface of the blastomere), periclinal (parallel to the outer surface of the blastomere), and oblique (at an angle between the other two). The observed frequencies of each type of division plane orientation provide evidence that the inner cells of the morula must derive from oriented division of 8-cell blastomeres, in accordance with the polarization hypothesis. Analysis of fourth cleavage division plane orientation with respect to either lineage or division order reveals that it is not associated with lineage from either the 2- or the 4-cell stage, but has a slight statistical association with fourth cleavage division order. The lack of association between division plane orientation and lineage supports the prediction that packing patterns and intercellular interactions within the 8-cell embryo during compaction play a role in determining fourth cleavage division plane orientation and thus, the positional fate of the daughter 16-cell blastomeres.

Animals↗

Incorporating prior information into the analysis of contingency tables.

Contingency tables are often analyzed using log-linear models and in some situations prior information on the value of parameters in the log-linear model is available. In this article we describe a prior-posterior procedure that incorporates prior information directly into the analysis through a multivariate normal prior for the log-linear parameters. The mode and curvature of the posterior density are proposed as summary statistics.

Alcohol Drinking↗

Intestinal transport of monosaccharide after biliary diversion in the rat.

Sugar absorption is increased in rats with a bile fistula but approaches normal values with the addition of bile salt. It has therefore been suggested that bile salts have a physiological role in decreasing intestinal absorption of monosaccharides. In experiments using rats, jejunal and ileal uptake of arbutin, a glucose analogue was increased 5 days after creating a bile fistula but normal by the 10th day after operation. Bile fistula rats ate only about one third of the intake of normal rats in the first 5 days after operation. Control animals fed the same amount as the bile fistula group showed a similar increase in jejunal and ileal arbutin uptake. In both groups, on the 5th post-operative day, addition of taurocholate depressed arbutin uptake towards normal. In normal rats, taurocholate depressed arbutin uptake in the ileum but not the jejunum. These results suggest that increased monosaccharide uptake in bile fistula rats is related to semi-starvation and is not a specific effect of bile salts.

Animals↗

Incorporating crossover interference into pedigree analysis using the chi 2 model.

Crossover interference is now known to exist in humans but to date has been ignored in routine genetic mapping because of the computational burden involved. In a recent paper by Weeks et al. [Hum Hered 1993;43:86-97], interference was accounted for by the use of a variety of multilocus feasible map functions and a crossover model of Goldgar and Fain [Am J Hum Genet 1988;43:38-45]. In this paper, we present an alternative approach to incorporating crossover interference into multilocus likelihood computation, by modelling the underlying chiasma process directly using the chi 2 model, supplemented by an assumption of no chromatid interference. This procedure was applied to the same CEPH consortium chromosome 10 data set that was analyzed by Weeks et al. A fit to the data was achieved which was significantly better than that offered by the no-interference model, and comparable to the best of the alternatives considered by Weeks et al. We briefly discuss the relative merits of the different models for interference.

Chi-Square Distribution↗

The effects of genotyping errors and interference on estimation of genetic distance.

Analysis of linkage data has typically been carried out assuming genotyping errors are absent. Recent studies have shown, however, that the impact of ignoring genotyping errors can be great, especially in dense marker maps [Buetow, Am J Hum Genet 1991; 49:985-994; Lincoln and Lander, Genomics 1992; 14:604-610]. Because most organisms exhibit positive chiasma interference, we use the chi 2 model [Foss et al., Genetics 1993; 144:681-691] to examine the role interference plays in the estimation of genetic distance in the presence of genotyping errors. For simplicity, we confine our analyses to samples of 1,000 fully informative gametes. Our results support previous findings that ignoring errors inflates distance estimates. The larger the error rate, the greater the inflation. For a given error rate, the relative error in estimated genetic distance is greatest when interference is known to be weak or absent. An approximation to relative error which quantifies the relation to distance, error rate, and interference is provided. Robustness of estimation to error misspecification is also investigated. When the assumed error rate is too low, distance is overestimated while interference is underestimated. The situation is reversed when too large an error rate is assumed (interference is overestimated, and distance underestimated). Unfortunately, the joint estimation of distance and interference is not very robust to error misspecification.

Genetic Linkage↗