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A John Bailer

Publications and source records attributed to A John Bailer.

17 recordsLinked to original sources
PubMed2006

Optimal experimental design for a nonlinear response in environmental toxicology.

A start-stop experiment in environmental toxicology provides a backdrop for this design discussion. The basic problem is to decide when to sample a nonlinear response in order to minimize the generalized variance of the estimated parameters. An easily coded heuristic optimization strategy can be applied to this problem to obtain optimal or nearly optimal designs. The efficiency of the heuristic approach allows a straightforward exploration of the sensitivity of the suggested design with respect to such problem-specific concerns as variance heterogeneity, time-grid resolution, design criteria, and interval specification of planning values for parameters. A second illustration of design optimization is briefly presented in the context of concentration spacing for a reproductive toxicity study.

Animals↗
PubMed2006

A simulation study comparing different experimental designs for estimating uptake and elimination rates.

The design of ecotoxicological studies requires decisions about the number and spacing of exposure groups tested, the number of replications, the spacing of sampling times, the duration of the study, and other considerations. For example, geometric spacing of sampling times or toxicant concentrations is often used as a default design. Optimal design methods in statistics can suggest alternative spacing of sampling times that yield more precise estimates of regression coefficients. In this study, we use a computer simulation to explore the impact of the spacing of sampling times and other factors on the estimation of uptake and elimination rate constants in an experiment addressing the bioaccumulation of a contaminant. Careful selection of sampling times can result in smaller standard errors for the parameter estimates, thereby allowing the construction of smaller, more precise confidence intervals. Thus, the effort invested in constructing an optimal experimental design may result in more precise inference or in a reduction of replications in an experimental design.

Animals↗
PubMed2006

Comparing median lethal concentration values using confidence interval overlap or ratio tests.

Experimenters in toxicology often compare the concentration-response relationship between two distinct populations using the median lethal concentration (LC50). This comparison is sometimes done by calculating the 95% confidence interval for the LC50 for each population, concluding that no significant difference exists if the two confidence intervals overlap. A more appropriate test compares the ratio of the LC50s to 1 or the log(LC50 ratio) to 0. In this ratio test, we conclude that no difference exists in LC50s if the confidence interval for the ratio of the LC50s contains 1 or the confidence interval for the log(LC50 ratio) contains 0. A Monte Carlo simulation study was conducted to compare the confidence interval overlap test to the ratio test. The confidence interval overlap test performs substantially below the nominal alpha = 0.05 level, closer to p = 0.005; therefore, it has considerably less power for detecting true differences compared to the ratio test. The ratio-based method exhibited better type I error rates and superior power properties in comparison to the confidence interval overlap test. Thus, a ratio-based statistical procedure is preferred to using simple overlap of two independently derived confidence intervals.

Animals↗
PubMed2005

Model uncertainty and risk estimation for experimental studies of quantal responses.

Experimental animal studies often serve as the basis for predicting risk of adverse responses in humans exposed to occupational hazards. A statistical model is applied to exposure-response data and this fitted model may be used to obtain estimates of the exposure associated with a specified level of adverse response. Unfortunately, a number of different statistical models are candidates for fitting the data and may result in wide ranging estimates of risk. Bayesian model averaging (BMA) offers a strategy for addressing uncertainty in the selection of statistical models when generating risk estimates. This strategy is illustrated with two examples: applying the multistage model to cancer responses and a second example where different quantal models are fit to kidney lesion data. BMA provides excess risk estimates or benchmark dose estimates that reflects model uncertainty.

Animals↗
PubMed2005

Comparison of step-stress data among multiple groups.

Ecotoxicological studies may use organism fitness (e.g., time until exhaustion in a swim test experiment) as an indicator of the impact of some toxic chemical. Failure time studies can use constant stress or may use a protocol in which the stress level is increased at specific times. In these step-stress tests, the units are tested at a given stress level for a predetermined amount of time. At the end of that time, if there are units surviving, the stress level is increased and held constant for another amount of time. This process is repeated until all of the test units fail or the predetermined test time has expired. The purpose of this study is to suggest a method for analyzing responses from step-stress studies. A likelihood-ratio test is developed for comparing the failure times in multiple groups based on a piecewise constant hazard assumption. This likelihood-ratio test can be extended to other piecewise distributions. A small simulation study compares this analysis procedure to other methods currently used to compare multiple groups with regard to type 1 error rate and power.

Computer Simulation↗
PubMed2004

Evaluation of toxic equivalency factors for induction of cytochromes P450 CYP1A1 and CYP1A2 enzyme activity by dioxin-like compounds.

The toxic equivalency factor (TEF) method has been used to characterize the toxicity of human mixtures of dioxin-like compounds and is being considered for use with other classes of potentially toxic agents. TEFs are estimated by examining the relative potencies of the various congeners for a series of biological and toxicological effects. In this paper, we consider changes in activity for two enzymes, cytochrome P450 1A1 (CYP1A1)-associated 7-ethoxyresorufin-O-deethylase (EROD) and CYP1A2-associated acetanilide-4-hydroxylase (A4H) activity, resulting from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) or a mixture of these agents. The ratio of median effective dose (ED50) is one way to estimate the relative potencies, especially for gene expression and protein endpoints. ED50's were estimated with a nonlinear regression model in which dose-related changes in mean responses are described by a Hill function. ED50's along with other model parameters were estimated by fitting this model to a given data set. Significant differences in estimated model parameters were tested by likelihood ratio methods. The estimated parameters indicated that congener-specific dose-response shapes were significantly different, that additivity failed for these congeners, and that the ratios of ED50's did not predict the response seen for the mixture. These results indicate that for some biological responses, the use of a single relative potency factor (RPF) is not appropriate for the comparison of the dose response behavior of different dioxin-like congeners.

Animals↗
PubMed2004

Trends in occupational lead exposure since the 1978 OSHA lead standard.

BACKGROUND: The purpose of the study was to evaluate trends in occupational lead exposures throughout U.S. industry after the establishment of the general industry lead standard in 1978 and the construction industry standard in 1993. METHODS: Lead exposure measurements collected by the Occupational Safety and Health Administration (OSHA) under their compliance and consultation programs were analyzed. Time trends in the distributions of exposure levels were evaluated graphically. Trends in the proportion of exposures above the OSHA permissible exposure limit (PEL) were analyzed using logistic regression models. RESULTS: The distribution of lead exposure levels declined over the study time period for general industry, but not for construction. The median exposure levels for general industry facilities decreased five- to tenfold. Logistic regression models reveal statistically significant declines in the odds of a lead exposure exceeding the PEL. CONCLUSIONS: This study provides evidence for relatively large decreases in lead exposure levels in general industry facilities over time. The study does not provide similar evidence for the construction industry. Given the limited number of years of data available since the implementation of the revised construction standard for lead, re-analysis of lead exposure levels within this industry would be worthwhile when more data become available.

Environmental Monitoring↗
PubMed2004

The effect of rate denominator source on US fatal occupational injury rate estimates.

BACKGROUND: The Current Population Survey (CPS) is often used as a source of denominator information for analyses of US fatal occupational injury rates. However, given the relatively small sample size of the CPS, analyses that examine the cross-classification of occupation or industry with demographic or geographic characteristics will often produce highly imprecise rate estimates. The Decennial Census of Population provides an alternative source for rate denominator information. We investigate the comparability of fatal injury rates derived using these two sources of rate denominator information. METHODS: Information on fatal occupational injuries that occurred between January 1, 1983 and December 31, 1994 was obtained from the National Traumatic Occupational Fatality surveillance system. Annual estimates of employment by occupation, industry, age, and sex were derived from the CPS, and by linear interpolation and extrapolation from the 1980 and 1990 Census of Population. Fatal injury rates derived using these denominator data were compared. RESULTS: Fatal injury rates calculated using Census-based denominator data were within 10% of rates calculated using CPS data for all major occupation groups except farming/forestry/fishing, for which the fatal injury rate calculated using Census-based denominator data was 24.69/100,000 worker-years and the rate calculated using CPS data was 19.97/100,000 worker-years. The choice of denominator data source had minimal influence on estimates of trends over calendar time in the fatal injury rates for most major occupation and industry groups. CONCLUSIONS: The Census offers a reasonable source for deriving fatal injury rate denominator data in situations where the CPS does not provide sufficiently precise data, although the Census may underestimate the population-at-risk in some industries as a consequence of seasonal variation in employment.

Accidents, Occupational↗
PubMed2004

Effects of data limitations when modeling fatal occupational injury rates.

BACKGROUND: Occupational fatal injury rate studies are often based upon uncertain and variable data. The numerator in rate calculations is often obtained from surveillance systems that can understate the true number of deaths. Worker-years, the denominator in many occupational rate calculations, are frequently estimated from sources that exhibit different amounts of variability. METHODS: Effects of these data limitations on analyses of trends in occupational fatal injuries were studied using computer simulation. Fatality counts were generated assuming an undercount. Employment estimates were produced using two different strategies, reflecting either frequent but variable measurements or infrequent, precise estimates with interpolated estimates for intervening years. Poisson regression models were fit to the generated data. A range of empirically motivated fatality rate and employment parameters were studied. RESULTS: Undercounting fatalities resulted in biased estimation of the intercept in the Poisson regression model. Relative bias in the trend estimate was near zero for most situations, but increased when a change in fatality undercounting over time was present. Biases for both the intercept and trend were larger when small employment populations were present. Denominator options resulted in similar rate and trend estimates, except where the interpolated method did not capture true trends in employment. CONCLUSIONS: Data quality issues such as consistency of conditions throughout the study period and the size of population being studied affect the size of the bias in parameter estimation.

Accidents, Occupational↗
PubMed2004

A parametric model for studying organism fitness using step-stress experiments.

We propose a method based on parametric survival analysis to analyze step-stress data. Step-stress studies are failure time studies in which the experimental stressor is increased at specified time intervals. While this protocol has been frequently employed in industrial reliability studies, it is less common in the life sciences. Possible biological applications include experiments on swimming performance of fish using a step function defining increasing water velocity over time, and treadmill tests on humans. A likelihood-ratio test is developed for comparing the failure times in two groups based on a piecewise constant hazard assumption. The test can be extended to other piecewise distributions and to include covariates. An example data set is used to illustrate the method and highlight experimental design issues. A small simulation study compares this analysis procedure to currently used methods with regard to type I error rate and power.

Analysis of Variance↗
PubMed2004

Fatal occupational injury rates in southern and non-southern States, by race and Hispanic ethnicity.

OBJECTIVES: We investigated fatal occupational injury rates in the United States by race and Hispanic ethnicity during the period 1990-1996. METHODS: Fatalities were identified by means of the national traumatic occupational fatalities surveillance system. Fatal occupational injury rates were calculated by race/ethnicity and region using US-census-based workforce estimates. RESULTS: Non-Hispanic Black men in the South had the highest fatal occupational injury rate (8.5 per 100000 worker-years), followed by Hispanic men in the South (7.9 per 100000 worker-years). Fatal injury rates for Hispanic men increased over the study period, exceeding rates for non-Hispanic Black men in the latter years of observation. CONCLUSIONS: These data suggest a change in the demographics of fatal occupational injuries in the United States. Hispanic men in the South appear to be emerging as the group with the nation's highest unintentional fatal occupational injury rate.

Accidents, Occupational↗
PubMed2003

External cause-specific summaries of occupational fatal injuries. Part I: an analysis of rates.

BACKGROUND: Industries and occupations vary with respect to the incidence of fatal injuries and their causes. METHODS: Fatalities from the National Traumatic Occupational Fatality database (years 1983-1994) serve as the basis for examining external cause of death code specific rates. Industries and occupations are compared with respect to rate and frequency of fatal injuries. In addition, external causes of injury (E-codes) are examined across all industries and occupations as well as within industries and occupations to evaluate which events would be identified by frequency ordered comparisons versus injury rate ordered comparisons. RESULTS: Machinery, electric current, homicide, falls, and transportation-related events are identified by high frequency and rate of occurrence. CONCLUSIONS: The external cause categories of homicide, machinery-related, motor-vehicle-related, electric current, and falls, account for over one-half of all occupational fatal injuries. Targeted interventions in homicide may be especially warranted in sales and service occupations and in the retail trade and services industries. In addition, younger workers might be targeted for special interventions designed to identify hazardous practices, procedures, and solutions to reduce fatalities associated with electrocution or falls from buildings.

Accidental Falls↗
PubMed2003

External cause-specific summaries of occupational fatal injuries. Part II: an analysis of years of potential life lost.

BACKGROUND: Fatal injury surveillance data provide an opportunity to assess the impact of occupational injuries and may indicate which industries or occupations are appreciably more hazardous than others, and thus should be given priority in public health intervention. METHODS: Fatalities from the National Traumatic Occupational Fatality surveillance system served as the basis for examining external cause (E-code) specific impact summaries. Years of potential life lost (YPLL) were calculated for fatal injuries in the years 1983-1994. Industries and occupations were compared with respect to frequency of fatal injuries. In addition, injuries in categories of external causes are examined across all industries and occupations. RESULTS: Machinery, electric current, homicide, falls, and transportation-related are the external cause groups highlighted by high frequency/rate of occurrence. Electric current event groups are also characterized by high average YPLL. Poisoning, conflagration, and lightning were also identified in several occupations as having high associated average YPLL. CONCLUSIONS: The external-cause-specific analysis of average YPLL identified industries and occupations where, on average, younger workers were dying in fatal injuries. Noteworthy in this assessment were homicides and falls. The YPLL measure coupled with more commonly employed indices (e.g., rates) may provide a fuller description of the impact of occupational fatal injuries.

Accidental Falls↗
PubMed2003

Toxicokinetics of sediment-sorbed benzo[a]pyrene and hexachlorobiphenyl using the freshwater invertebrates Hyalella azteca, Chironomus tentans, and Lumbriculus variegatus.

This study investigated the effect of long-term sediment aging on the toxicokinetics of benzo[a]pyrene (BaP) and hexachlorobiphenyl (HCBP) using three freshwater benthic invertebrates. Hyalella azteca, Chironomus tentans, and Lumbriculus variegatus were exposed to BaP- and HCBP-spiked sediments that were aged for 7 d or 1.5 years. The toxicokinetics of the two compounds were determined for each test organism using a two-compartment model. The modeling of BaP was more complex because biotransformation was included within the model. The results of this study showed that the HCBP uptake clearance rates (k(s)) for each species were generally an order of magnitude greater than those determined for BaP and this difference was most likely due to preferential and rapid binding of BaP to sediment particles. Overall, the bioavailability of HCBP in spiked sediments tended to decrease with duration of aging, based on k(s) values and bioaccumulation factors (BAFs). However, the decreases in bioavailability appear to be species specific. Benzo[a]pyrene did not decline in bioavailability for the species tested because it may resist movement into the micropores of the sediment due to its large size. In addition to the bioassays, this article outlines a method for toxicokinetic modeling of biotransformed compounds and methods for statistical comparisons of kinetic parameters (i.e., k(s), k(d)...) and BAF values.

Adsorption↗
PubMed2003

A simulation study of methods for constructing confidence intervals for bioaccumulation factors.

Toxicokinetics describe the time course of xenobiotics in an exposed organism. The steady state concentration of the xenobiotic is a characteristic of frequent concern, often summarized in terms of bioaccumulation factors (BAFs). Two experimental protocols are commonly used when estimating BAFs: a continuous exposure experiment and a start-stop exposure experiment. Nonlinear regression is then used for estimating components of the BAF. A variety of methods are available for constructing confidence intervals (CI) for the BAF, including the delta method and Fieller's method. The properties of these CI methods are explored through a simulation study. In particular, the coverage properties of the two CI methods along with their interval widths are examined for a variety of time-course patterns, error distributions, experimental protocols, and sampling designs. Fieller's method is observed to exceed nominal coverage probabilities for all conditions considered (the coverage probability being the probability that a confidence interval contains a parameter it estimates over repeated experiments). The delta method exhibited observed coverage probabilities lower than nominally specified for a number of conditions. For sampling designs in which more of the sampling times are prior to steady state or the stop exposure time, the delta method is observed to provide nominal coverage probabilities with interval widths much narrower than observed with the Fieller's method. Thus, the delta method is preferable when the above sampling time condition is met; however, in all other cases, Fieller's method should be used.

Animals↗
PubMed2002

An alternate characterization of hazard in occupational epidemiology: years of life lost per years worked.

BACKGROUND: Standardized mortality ratios (SMRs) and other measures of relative risk by themselves may not suffice as descriptors of occupational hazards for many audiences including decision-makers and those at direct risk from hazardous work. To explore other approaches, we calculated excess years of potential life lost and excess lifetime risk for both lung diseases and fatal injuries in a cohort of uranium miners with historical records of exposure to radon gas. METHODS: We used relatively simple life table (SMR) methods and also analyzed lung cancer mortality with Poisson regression methods permitting control for smoking. RESULTS: Among uranium miners hired after 1950, whose all-cause SMR was 1.5, 28 percent would experience premature death from lung diseases or injury in a lifetime of uranium mining. On average, each miner lost 1.5 yr of potential life due to mining-related lung cancer, or almost 3 months of life for each year employed in uranium mining. As a consequence of all excess lung disease and injury risks combined, a year of mining was associated with 5.9 months loss of potential life. For each year actually working underground, miners lost more than 8 months of potential life. When controlled for smoking (and healthy worker effect) with Poisson regression, the estimates for radon-related lung cancer effects were slightly larger. Although chronic disease deaths dominated in excess years of life lost (due to radon, silica and possibly other exposures), more years were lost on average per individual injury death (38 yr), than per excess lung cancer (20 yr) or other lung disease death (18 yr). Fatal-injury dominated the potential years of life lost up to about age 40. CONCLUSIONS: Years of life lost per years employed provides another, more intuitive summary of occupational mortality risk.

Accidents, Occupational↗