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S Zacks

Publications and source records attributed to S Zacks.

6 recordsLinked to original sources
PubMed1999

Constructing meiotic maps with known error probability.

We propose methods to construct meiotic gene maps while controlling the probability of a decision-error. First, a single step gene ordering procedure is presented whose decision-error probability is bounded above by a prespecified threshold. The bound for the error probability is valid under quite general circumstances. The ordering procedure is optimal in the sense of having maximal predictive probability of correct ordering among all procedures subject to the same bound on the error probability. Second, to reduce the number of hypotheses to be tested, a stepwise ordering procedure is presented. A Monte Carlo simulation study demonstrated the integrity of the proposed error bound for the stepwise procedure under a wide variety of situations, including data coming from different laboratories and marker typing errors. The stepwise procedure was applied to version 2 of the public database maintained by the Cooperative Human Linkage Center and maps of the 23 chromosomes were generated such that the probability that the order of the markers in a given chromosome is incorrect is less than 1%.

Algorithms↗
PubMed1998

Cancer phase I clinical trials: efficient dose escalation with overdose control.

We describe an adaptive dose escalation scheme for use in cancer phase I clinical trials. The method is fully adaptive, makes use of all the information available at the time of each dose assignment, and directly addresses the ethical need to control the probability of overdosing. It is designed to approach the maximum tolerated dose as fast as possible subject to the constraint that the predicted proportion of patients who receive an overdose does not exceed a specified value. We conducted simulations to compare the proposed method with four up-and-down designs, two stochastic approximation methods, and with a variant of the continual reassessment method. The results showed the proposed method effective as a means to control the frequency of overdosing. Relative to the continual reassessment method, our scheme overdosed a smaller proportion of patients, exhibited fewer toxicities and estimated the maximum tolerated dose with comparable accuracy. When compared to the non-parametric schemes, our method treated fewer patients at either subtherapeutic or severely toxic dose levels, treated more patients at optimal dose levels and estimated the maximum tolerated dose with smaller average bias and mean squared error. Hence, the proposed method is promising alternative to currently used cancer phase I clinical trial designs.

Antineoplastic Agents↗
PubMed1995

Risk prediction with linked markers: pedigree analysis.

Rogatko [1995: Am J Med Genet 59:14-23] has proposed a method for risk prediction with linked markers. The actual implementation of this method required that the analytical forms of likelihood and risk functions be specified. It is impractical to obtain the explicit analytical form of these functions in large phase unknown pedigrees. When large phase unknown pedigrees are encountered, the compound risk can be approximated by a transformation of the discrete distribution obtained by computing the likelihood and risk functions over a grid of points. We propose a method to compute genetic risks when the functional form of the pedigree likelihood is unknown. The method was evaluated using a simple pedigree by comparing the results when functional forms were and were not known. This method was also applied to estimate genetic risks for a single pedigree with nonsyndromal X-linked mental retardation using 3 genetic markers linked to the putative disease gene. Linkage data from an extended pedigree were combined with genome mapping data, and recurrence risk distributions were calculated for members of the pedigree. The results suggest that the proposed method provides accurate risk estimate for genetic diseases. Computer programs are available to apply this method whenever genetic markers are suspected of being linked to a disease gene.

Female↗
PubMed1993

Ordering genes: controlling the decision-error probabilities.

Determination of the relative gene order on chromosomes is of critical importance in the construction of human gene maps. In this paper we develop a sequential algorithm for gene ordering. We start by comparing three sequential procedures to order three genes on the basis of Bayesian posterior probabilities, maximum-likelihood ratio, and minimal recombinant class. In the second part of the paper we extend sequential procedure based on the posterior probabilities to the general case of g genes. We present a theorem that states that the predicted average probability of committing a decision error, associated with a Bayesian sequential procedure that accepts the hypothesis of a gene-order configuration with posterior probability equal to or greater than pi *, is smaller than 1 - pi *. This theorem holds irrespective of the number of genes, the genetic model, and the source of genetic information. The theorem is an extension of a classical result of Wald, concerning the sum of the actual and the nominal error probabilities in the sequential probability ratio test of two hypotheses. A stepwise strategy for ordering a large number of genes, with control over the decision-error probabilities, is discussed. An asymptotic approximation is provided, which facilitates the calculations with existing computer software for gene mapping, of the posterior probabilities of an order and the error probabilities. We illustrate with some simulations that the stepwise ordering is an efficient procedure.

Algorithms↗
PubMed1991

Characterization of Cobblestone mitral valve interstitial cells.

Mitral valve interstitial cells (MVICs) are important in the structure and function of the valve. In a cell culture system that used explants to harvest MVICs, we found that after several passages, some of the cultures at confluence formed a monolayer of cobblestone-shaped cells (CB type). The rest of the cultures were, however, different, consisting of elongated cells (EL type) that formed overlapping orthogonal patterns. When compared with the MVICs-EL, cells from cultures of MVICs-CB were less adherent to a plastic substratum initially than were MVICs-EL and were more sensitive to trypsinization following culture for 3 to 7 days. Ultrastructurally, the cultures of MVICs-CB showed prominent Golgi's complexes and endoplasmic reticulum and fewer microfilaments when compared with those of MVICs-EL. Most strikingly, the CB cells contained much less alpha-smooth-muscle cell actin compared with that of EL cells. The MVICs-CB were not endothelial cells as they did not show the characteristic dense peripheral band that was present in endothelial cells in a confluent monolayer and showed only trace amounts of fluorescence when incubated with 1,1-dioctadecyl 1-3,3,3,3 tetramethyl-indocarbocyanine-percholate (Dil-)--acetylated low-density lipoprotein compared with large amounts of fluorescence with endothelial cells. Cells that were morphologically similar to MVICs-CB were present in the in vivo valve as well and also formed small islands of cells even in the primary cultures that grew out of the explant. The findings supported the hypothesis that MVICs-CB represent a distinct phenotype of the MVICs that is different from that of the MVICs-EL and is not that of either endothelial or medial smooth-muscle cells.

Actin Cytoskeleton↗