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R D Snee

Publications and source records attributed to R D Snee.

17 recordsLinked to original sources
PubMed1984

A procedure for the statistical evaluation of Ames Salmonella assay results. Comparison of results among 4 laboratories.

Ames Salmonella test data collected in our laboratory and 3 National Cancer Institute contract laboratories were analyzed to study the distribution of experimental errors associated with the test. It is shown that the Poisson distribution is not appropriate, and that the power transformation model Y = (revertants/plate)lambda, with lambda = 0.2 as estimated by the methods of Box and Cox, produced a measurement scale on which the experimental errors could be adequately described by a normal (Gaussian) distribution with a constant variance. The modeling procedure enables one to properly use analysis of variance, regression analysis, and Student's t test to analyze Ames Salmonella test results, and well-known statistical quality control procedures to monitor laboratory performance. The method detects weak mutagenic activity and measures the amount and uncertainty of the increase in revertants/plate. The development of the power transformation model is discussed and examples of its use in the interpretation of Ames Salmonella assay results are included.

Laboratories↗
PubMed1982

Models for the relationship between blood lead and air lead.

A "lead exposure" model is proposed for the relationship between blood lead and air lead. Unlike the commonly-used log-log model, this model describes blood lead as a function of both air lead exposure and lead intake from sources other than the air (i.e., food, water, etc.). The blood lead-air lead relationship at low air lead levels is also studied. It is shown that the mathematical characteristics of the log-log model can result in an overestimate of the effect of air lead on blood lead at air lead levels less than 1 to 2 micrograms/m3. The lead exposure model is shown to give a good description of data collected in studies in which subjects' air lead levels were measured by personal monitor.

Air Pollutants↗
PubMed1982

A statistical method for analysis of mouse lymphoma L5178Y cell TK locus forward mutation assay. Comparison of results among three laboratories.

Analysis of data from our laboratory and that of two National Cancer Institute contractor laboratories indicate the random variation in the results of the mouse lymphoma L5178Y cell TK locus mutation assay can be adequately described by a lognormal distribution. This indicates that transformation of mutant frequencies to logarithms enables one to properly use well-known statistical techniques such as analysis of variance, regression analysis, and Student's t-test for the interpretation of data from this assay. The consistency of the lognormal distribution among laboratories is demonstrated. Three examples which illustrate the mechanics and interpretation of the proposed methodology are included. It is concluded that the method is effective in identifying weak mutagens as well as enabling the user to compute the uncertainty associated with an observed increase in mutagenic activity.

Analysis of Variance↗
PubMed1981

Evaluation of studies of the relationship between blood lead and air lead.

An evaluation of the major studies of the effects of airborne lead on blood lead levels of male and female adult and child populations is presented. Analysis of these studies shows that the blood lead-air lead slope for adults is approximately 1.0 for both men and women. This implies that an exposure to an additional 1 microgram Pb/m3 of air can result in an increase of approximately 1 microgram Pb/100 ml of blood. The precision of the slope for adults is rarely better than +/- 0.5 to +/- 0.7 and can be as large as +/- 1.0. A large portion of this uncertainty in the calculated slope is due to blood lead measurement error. The slope of the blood lead-air lead response for children ranges from 0.7 to 1.4 and is approximately the same as that for adults. The accuracy of this number is less clear for children than adults due to the small data base. Many of the studies of children have been on populations living in the vicinity of smelters. It is questioned whether these data are representative of the air lead exposure of children living in urban and suburban communities.

Air Pollutants↗
PubMed1981

Design of a statistical method for the analysis of mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase locus of cultured Chinese hamster ovary cells.

Mutagenesis data collected in the mammalian cell CHO/HGPRT assay were analyzed to study the distribution of the experimental errors associated with the test. The data neither followed the widely assumed Poisson distribution nor satisfied the usual statistical assumptions of normality and homogeneous variance of experimental errors. We transformed the data by using the power formula Y = (X + A) gamma where X is the observed mutation frequency, Y is the transformed frequency, and A and gamma are constants determined by the procedure of Box and Cox. Setting A = 1 and gamma = 0.15 we produced transformed values for which the assumptions of homogeneous variance and normal distribution were satisfied. This transformation enables one to properly use Student's t-test and dose-response analysis of variance to analyze CHO/HGPRT results. The experimental design for CHO/HGPRT mutagenesis assays is also discussed.

Animals↗
PubMed1979

Automated enzymatic assay for plasma ammonia.

An enzymatic method for determining plasma ammonia with the Du Pont Automatic Clinical Analyzer (aca) is described. The assay requires a sample volume of 500 muL for a kinetic ammonia measurement. The reaction is initiated with glutamate dehydrogenase and the rate of depletion of NADPH is monitored with two measurements, 17 s apart, at 340 nm. Reaction conditions have been optimized for maximum sensitivity through both one-factor-at-a-time and multiple variable response surface optimization techniques. Linearity to 1000 mumol of ammonia per liter of plasma has been achieved. No significant interferences were observed from anticoagulants or endogenous blood components, including pyruvate and oxalacetate. Use of the coenzyme NADPH (instead of NADH) in this aca procedure eliminates the lengthy pre-incubation otherwise required for endogenous dehydrogenase reactions.

Adenosine Diphosphate↗
PubMed1979

Response-surface co-optimization of reaction conditions in clinical chemical methods.

We describe the theory and applications of the response-surface approach to simultaneous optimization (co-optimization of multiple interdependent variables. The co-optimization experiments are designed according to a selected response-surface model. Computer-assisted analysis includes fitting the data to the model, testing the resulting fit for statistical validity, and plotting contour maps of the model for simple interpretation. Co-optimizations of the reaction parameters of three methods--creatine kinase, lipase, and aspartate aminotransfrease--are discussed to illustrate the application of the approach. In contrast to the commonly used optimization strategies in which each factor is varied in turn while the others are kept constant, the response-surface approach allows study of several responses (reaction rates, sensitivities) and effects (linear, curvature, interaction) at the same time. It also allows determination of accurate optima, which is necessary for the formulation of analytically reliable clinical methods.

Aspartate Aminotransferases↗
PubMed1979

A useful method for the analysis of growth studies.

A group of parsimonious models for the analysis of animal growth curves is presented. The effects of correlations between the successive weights are reduced by analyzing the weight gained between the different weighing times. A model is developed for the resulting two-way table of group average gain curves (group by periods), using the two-way table modeling techniques proposed by Mandel. The coefficients in the fitted model are examined to determine what functions of the weight gain measurements will summarize the characteristics of the curves. In the second part of the analysis these statistics are computed for each animal and analyzed to determine the effects of the design variables on the growth of the animals. Experience has shown that in many instances total weight gain summarizes all the information in the curve. The conditions under which total gain provides an adequate summary are discussed. The model has been used in the analysis of rat, dog, hamster, guinea pig and swine growth curves. An example is included to illustrate the utility of the proposed approach.

Analysis of Variance↗
PubMed1976

Experiments on the effect of carbon monoxide on aminolevulinic acid dehydrase (ALAD).

The inverse relationship between blood lead concentration and aminolevulinic acid dehydrase (ALAD) is well known. Recently, it has been suggested that a similar relationship exists between carboxyhemoglobin (COHb) and ALAD activity. This study was undertaken to examine more closely the possible effect of carbon monoxide on ALAD. Blood from 19 human volunteers was analyzed for both carboxyhemoglobin and ALAD activity. Smokers had significantly lower concentrations of ALAD than nonsmokers and a rise in carboxyhemoglobin concentration was assocaited with a fall in ALAD activity. The in vitro bubbling of carbon monoxide into human blood did not significantly effect ALAD activity. Four groups of rats (10 per group) wre exposed to carbon monoxide or dietary lead acetate according to the following design: (I) Control--no Pb or CO; (II) 500 ppm Pb acetate in diet; (III) 250 ppm CO four hours/day X 5 days/week X 4 weeks; (IV) Both Pb and CO. Analysis of the rat data showed a significant depression of ALAD by lead. The activity of ALAD in the rats exposed to CO was significantly increased suggesting the possibility of an adaptive phenomenon.

Aminolevulinic Acid↗
PubMed1975

Recovery of blood lead concentration and of red cell 8-aminolevulinic acid dehydrase activity in dogs following return to normal diets after 75 weeks of lead feeding.

Blood lead concentration and red cell delta-aminolevulinic acid dehydrase (ALAD) activity were determined at intervals for eight months after symptom-free dogs, which had received 100 ppm or 500-1000 ppm of lead, by weight, in their diets for 75 1/2 weeks, were returned to a lead-free diet. Statistical treatment of the data disclosed a linear relationship between the logarithm of blood lead concentration or of ALAD activity and the logarithm of time (experimental week) during the recovery period. The calculated regressions predict that recovery of ALAD will occur before recovery of the blood lead concentration. Predicted recovery times depend on the levels selected as those which must be attained for recovery to be complete, as well as on the dosage of lead. The logarithm of the slope of the ALAD recovery regression of the individual dog has a linear relation to the percentage reduction in ALAD due to the lead, the regression accounting for 92% of the variance in the recovery rates. The slope of the blood lead recovery regression has a linear relation to the increase in blood lead for the dogs which received the low lead diet, but not for those which received the high lead diet.

Animals↗
PubMed1975

An epidemiologic approach to community air lead exposure using personal air samplers.

Accurate information on the relationship between blood lead and air lead is essential to any consideration of the possible effect of air lead on the body burden. Past studies of occupationally exposed workers have established that such a relationship exists at high levels of air lead exposure. No such information has been available for subjects exposed to the low air lead levels representative of present-day community exposure. Past studies in this area have suffered from inadequate information on actual lead exposure at the air lead levels of concern. Researchers have has to rely on air lead data obtained from stationary samp;ing stations. Because wide variations can exist betwween locations within a city such information could not be assumed to represent the exposure of any individual subject. At lbest they can be considered only approximations of actual exposures. The Naational Research Council recognized the deficiencies of past studies in their report "Airborne lead in perspective" and recommended that "more precise studies are needed of the relation between atmospheric lead in the urban environment and the concentration of lead in the blood, perphaps by the use of personal monitors". This paper describes the study which was undertaken to evaluate the effect of air lead exposure as measured with personal air sampling devices on indices of lead absorption such as blood lead, urine lead, DALA and ALAD activity...

Absorption↗
PubMedDate not supplied

Quantitative risk assessment: state-of-the-art for carcinogenesis.

A critical evaluation of the use of statistical models in carcinogenic risk assessment is made with emphasis on the strengths and weaknesses of current practice. The objective is to bring together information from the fields of toxicology and statistics to develop a sound scientific basis for making risk decisions. It is emphasized that risk assessment is a complex, multifaceted process that is not easily quantified and, at present, must be based on qualitative as well as quantitative information. It is evident that dose-response modeling of tumor incidence data from animal studies is of limited value in estimating human risk associated with low-dose chemical exposures. The models take into account only one part of the complex process and have no accepted basis in biology. The key decision points, qualitative factors, and quantitative considerations are identified and discussed and a risk assessment framework that incorporates these inputs is presented. A model that incorporates the tumorigenic dose-response information as well as the qualitative and quantitative biological factors that affect the estimate of risk is proposed. It is concluded that much work needs to be done before a completely quantitative approach to risk assessment is to be useful; in particular pharmacokinetic modeling should be pursued more aggressively.

Animals↗