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At least 145 records · Page 8Linked to original sources

A statistical model to estimate variance in long term-low dose mutation assays: testing of the model in a human lymphoblastoid mutation assay.

Long term-low dose mutation assays offer a means to study the genetic effects of environmental mutagens at concentrations relevant to human exposure. These assays involve continuous induction of mutants, serial dilution of cultures and sampling to determine the mutant fraction as a function of time and mutagen concentration. An arithmetic model for the expected variance among identically treated cultures is presented. This model provides means to calculate a predicted variance of the mutant fractions and mutation rates in typical long term-low dose experiments. We have calculated the expected variances of the mutant fraction with this model and compared them to the observed variances among 4 independent experiments in which human lymphoblastoid cells were treated for 5, 10, 15 and 20 days with a non-toxic concentration of the mutagen 4-aminobiphenyl. Mutations at the HPRT locus were measured by determining the 6-thioguanine-resistant mutant fraction. The expected and observed variances of the mutant fractions are in close agreement. This model is adequate to predict the variance of the mutant fraction and should be useful in experimental design and objective evaluation of long term-low dose mutation assays.

Cells, Cultured

Intelligent dialogue based on statistical models of clinical decision-making.

The independence Bayesian model has been used widely in computer programs designed to support clinical decision-making. A reasoning strategy has been developed to enable these programs to conduct clinically pertinent dialogue and explain their reasoning. It has been implemented in a program for the diagnosis of acute abdominal pain based on the Bayesian model of de Dombal et al. Several features of the dialogue design have been adopted from artificial intelligence research, including shared initiative and critiquing. The program adopts a flexible goal-driven strategy, attempting to confirm the clinician's diagnosis or rule out the likeliest alternative. Symptoms and signs are selected in order of their expected weights of evidence in favour of the hypothesized disease.

Abdomen

Statistical models for the twinning rate.

Linear regression models are used to explain the variations in the twinning rates. Data sets from different countries are analysed and maternal age, parity and marital status are the main regressors. The model building technique is also used in order to study the secular decline in the twinning rate. Linear regression technique makes it possible to compare the effect of different factors but the method requires sufficiently disaggregated data.

Australia

Alternative statistical models for the examination of clinical positron emission tomography/fluorodeoxyglucose data.

This article describes a method for partitioning metabolic variability found in positron emission tomography/[18F]fluorodeoxyglucose studies. For the 15 subjects examined, 74.8% of the total metabolic variability could be ascribed to individual differences in global metabolic rate, whereas 15.8% of the total variability was consistent regional variation or pattern across subjects. Subsequently, the method of Q-component analysis is described for the identification of strong- and weak-pattern subjects. In addition, a standardization procedure that amplifies the observed pattern by removing systematic individual differences is described. Finally, the implications of these findings and methods for future and clinical studies are discussed.

Adolescent

Hematopoietic death of unprotected man from photon irradiations: statistical modeling from animal experiments.

Most estimates of the radiation dose lethal to 50 per cent of a human population are based on historical data taken from well-known experiences reflecting inadequately known physical and biological conditions, or from medical procedures where individual patients received advantages of modern clinical care. It has been debated as to whether the experience of unprotected man would more closely reflect that of hospital patients or of the radiobiological studies with large animals. The issue at question is whether the apparent two-fold or more increased susceptibility of large animals to death from bone marrow damage (compared with the majority of estimates for man) is due more to true interspecies differences or the lack of medical support. This study is an attempt to assess the radiosensitivity of unprotected man in terms of the composite animal experiments. Based upon an extensive data base containing 121 separate animals studies using 13 different species, an estimate of the mortality dose-response relationship due to a uniform, continuous field of photon radiation is predicted for 70 kg unprotected man. Man is assumed to have a level of radiation sensitivity similar to that of the species represented in the data base, after adjustment for body weight. The mathematical model used includes fixed terms to account for effects of body weight and dose rate, and random terms reflecting inter- and intra-species variation and experimental error. Point predictions and 95 per cent prediction intervals are given for the LD05, LD10, LD25, LD50, LD75, LD90, and LD95, for dose rates ranging from 0.01 to 0.5 Gy/min, and treatment times ranging from about 2 min to about 24 h. At 1 cGy/min our point prediction of the LD50 is 299 cGy with an associated 95 per cent prediction interval of (168 cGy, 535 cGy). The analogous values at 50 cGy/min are 183 cGy and (103 cGy, 326 cGy).

Animals

Statistical modeling of animal bioassay data with variable dosing regimens: example--vinyl chloride.

We consider animal bioassay experiments with variable dosing regimens in which groups of animals are dosed beginning at different ages and for varying durations. Two response models are discussed and then applied to data from an experiment on vinyl chloride exposure of F-344 rats, B6C3F1 and Swiss CD-1 mice, and Syrian Golden hamsters. The multistage model of Armitage and Doll, as extended by Whittemore, Day and Brown, and Crump and Howe, is used to estimate the dose effect on the ordered stages of tumor development. The data for all endpoints and species/strains examined consistently indicate a predominant effect on the first stage, suggesting that vinyl chloride is primarily a tumor initiator. This is consistent with evidence from two-stage experiments on this chemical. The second response model, new to this article, adjusts for survival nonparametrically. It is used to test for an age difference in susceptibility, to evaluate alternative exposure durations, and to compare the effectiveness of alternative dosing regimens for detecting carcinogenicity.

Animals