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Biomedical subjects

C Brownie

Publications and source records attributed to C Brownie.

At least 19 recordsLinked to original sources

A likelihood-based approach to capture-recapture estimation of demographic parameters under the robust design.

The Jolly-Seber method has been the traditional approach to the estimation of demographic parameters in long-term capture-recapture studies of wildlife and fish species. This method involves restrictive assumptions about capture probabilities that can lead to biased estimates, especially of population size and recruitment. Pollock (1982, Journal of Wildlife Management 46, 752-757) proposed a sampling scheme in which a series of closely spaced samples were separated by longer intervals such as a year. For this "robust design," Pollock suggested a flexible ad hoc approach that combines the Jolly-Seber estimators with closed population estimators, to reduce bias caused by unequal catchability, and to provide estimates for parameters that are unidentifiable by the Jolly-Seber method alone. In this paper we provide a formal modelling framework for analysis of data obtained using the robust design. We develop likelihood functions for the complete data structure under a variety of models and examine the relationship among the models. We compute maximum likelihood estimates for the parameters by applying a conditional argument, and compare their performance against those of ad hoc and Jolly-Seber approaches using simulation.

Animals

Percutaneous absorption of topical parathion through porcine skin: in vitro studies on the effect of environmental perturbations.

Topical use of pesticides in domestic animals such as swine is a common practice; however, the effect of environmental factors on the extent of absorption has not received attention. Since no single factor can exert its effects alone in the natural environment, the interaction of environmental factors on the percutaneous absorption of pesticides must be understood before potential toxicity of dermal absorption of pesticides can be effectively estimated. In the present studies, the effects of air temperature (Ta), perfusate temperature (Tp), perfusate flow (F) and relative humidity (%RH) on absorption of parathion were studied in vitro in porcine skin. Parathion absorption was determined by measuring radiolabel appearing in the perfusate over time. Three main environmental parameters were found to have a significant effect on parathion penetration. Increasing Ta from 37 degrees C to 42 degrees C, %RH from 60% to 90% or F from 4 ml/h to 8 ml/h each produced a significant increase in penetration. The following significantly positive two-way interactions among test parameters were seen: Ta x F and %RH x F at the 4 micrograms dose, %RH x F at the 40 micrograms dose and Ta x %RH, Ta x F and %RH x F at the 400 micrograms dose. There were no three-way interactions at any of the three doses tested. These results suggest that the factors tested are not independent variables and must be considered interactive when used in assessing pesticide percutaneous absorption.

Animals

Fractional excretion of electrolytes in lactating dairy cows.

Samples of serum and urine were obtained simultaneously from 56 healthy lactating cows to determine ranges of fractional excretion (FE) of calcium (Ca), phosphate (PO4), magnesium (Mg), sodium (Na), potassium (K), and chloride (Cl). Samples were obtained at 3 stages of lactation: period 1 = 1 to 7 days, 2 = 83 to 112 days, and 3 = 175 to 197 days. The FE of electrolytes were significantly different among periods 1, 2, and 3 for Ca (P less than 0.001), PO4 (P less than 0.025) and Mg (P less than 0.025), but were not significantly different for Na, K, and Cl. Least squares mean FE of Ca was lowest in period 1 and not significantly different for periods 2 and 3, whereas mean FE values for PO4 and Mg were highest in period 2 and not significantly different for periods 1 and 3. The mean FE values of Na, K, and Cl did not change with stage of lactation. Age and category of milk production (high, medium, and low) did not influence the FE values of the electrolytes.

Animals

A rank-based mixed model approach to multisite clinical trials.

New rank-based methods for analyzing data from multisite clinical trials are presented in the context of "mixed" linear models. In contrast to current rank methods, the new procedures test for a drug main effect in the presence of a random drug by site interaction (or drug by investigator interaction when there is only one investigator per site). Analogous procedures are also provided for the "fixed-effects" situation, and comparisons are made with current methods. The rationale for an analysis that assumes random investigator effects is described.

Analysis of Variance

Clinical and metabolic findings in dogs with chronic renal failure fed two diets.

Exogenous creatinine clearance, urinary electrolyte excretions, calcium and phosphorus balance, serum cholesterol concentration, arterial blood pressure, and body weight were evaluated in dogs with chronic renal failure that were fed 2 commercial diets. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF, exogenous creatinine clearance = 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal controls were fed a diet containing 31% protein for 8 weeks at which time hematologic and biochemical evaluations and clearance studies were performed. All dogs then were fed a phosphorus-restricted diet containing 16% protein and then reevaluated after 8 weeks. The dogs in this study had hematologic and biochemical abnormalities typical of CRF. Urine absolute and fractional excretion of electrolytes was higher in dogs with CRF than in controls and was affected by diet. Serum cholesterol concentration was higher in dogs with CRF and increased in those dogs after feeding the low protein diet. Changes in dietary sodium intake did not affect arterial blood pressure. The phosphorus-restricted diet did not affect serum amino terminal parathyroid hormone concentration in either group. Control dogs lost body weight, whereas dogs with CRF gained weight when fed the low protein diet. We concluded that dogs with mild to moderately severe CRF have the same biochemical abnormalities and response to dietary restriction of protein and phosphorus as has been previously reported in dogs with experimentally induced CRF. Restriction of dietary sodium may not decrease arterial blood pressure in some dogs with CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed

Amino acid profiles in dogs with chronic renal failure fed two diets.

Amino acid profiles and serum albumin and serum total protein concentrations were evaluated in dogs with renal disease. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF; exogenous creatinine clearance, 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal control dogs were fed a diet containing 31% protein for 8 weeks, at which time serum and urine amino acid assays and clearance studies were performed. All dogs then were fed a diet containing 16% protein for 8 weeks and then reevaluated. Chronic renal failure was associated with mild abnormalities in serum concentrations of amino acids. When fed the higher protein diet, dogs with CRF had lower serum concentrations of glutamine, leucine, proline, and serine and higher serum concentrations of cystathionine and 3-methylhistidine than clinically normal control dogs. When fed the low protein diet, dogs with CRF had lower serum serine concentrations and higher serum concentrations of cystathionine, phenylalanine, and 3-methylhistidine. Urine excretion of amino acids in all dogs on both diets was low, and dogs with CRF had lower renal clearances of 3-methylhistidine than control dogs. There were no significant differences in concentrations of serum albumin and total solids between either group, regardless of diet. We concluded that dogs with mild to moderately severe CRF have mild abnormalities of serum free amino acid concentrations, but renal conservation of essential amino acids is not impaired.

Amino Acids

Impact of menstrual periodicity on serum lipid levels and estimates of dietary intakes.

Nine eumenorrheic women were studied at five separate times each month for a minimum of 2 months. Fasting bloods and 1-day food records were obtained from all women at these times to describe the pattern and magnitude of within-person variation in selected nutrient and lipid indicators attributable to menstrual cyclicity. Serum cholesterol, beta-carotene, 17 beta-estradiol (E2), and dietary selenium intakes exhibited significant periodic regressions against time. For the group as a whole, however, only serum cholesterol and E2 measures exhibited significantly strong consistent periodicities. Future studies with a larger sample of women are warranted to confirm these findings. Unless strict blood sampling protocols are followed, variation attributable to menstrual cyclicity may mitigate the reliability of the serum cholesterol screenings advocated in the past few years.

Adult

Mixture models for continuous data in dose-response studies when some animals are unaffected by treatment.

A mixture model is described for dose-response studies where measurements on a continuous variable suggest that some animals are not affected by treatment. The model combines a logistic regression on dose for the probability an animal will "respond" to treatment with a linear regression on dose for the mean of the responders. Maximum likelihood estimation via the EM algorithm is described and likelihood ratio tests are used to distinguish between the full model and meaningful reduced-parameter versions. Use of the model is illustrated with three real-data examples.

Algorithms

Preliminary study on serum enzyme changes in Long Evans rats given parenteral ochratoxin A, aflatoxin B1 and their combination.

Long Evans rats of both sexes were each administered a total of 250 micrograms aflatoxin B1 (AFB1), ochratoxin-A (OCH-A) or 500 micrograms AFB1 + OCH-A (1:1 ratio) in corn oil over 5 equal daily intraperitoneal (IP) injections of 50 micrograms/rat/day. Control rats were given a total of 1.25 ml corn oil over 5 equal daily IP injections of 0.25 ml/rat. All rats were observed daily for clinical signs of toxicity. Twenty-four hr following the last injection all rats were weighed, killed, examined for gross pathologic lesions and blood samples collected for routine hematologic and serum chemistry evaluation. All rats gained weight over the treatment period. Though not significantly different among the treatment groups, weight gain was significantly greater for males (54.0 g) than females (33.8 g). Routine hematology showed no difference among treatment groups. Serum enzyme aspartate aminotransferase (AST = SGOT) activities were indicative of hepatoxicity. Lactate dehydrogenase (LDH) activity was significantly increased in the AFB1 and AFB1 + OCH-A treatment groups, signifying a possible interaction between these 2 mycotoxins. LDH isoenzyme fractionation studies would be helpful in delineating the organ system(s) involved and the possible diagnostic value of this interaction.

Aflatoxin B1

Teratogenic effect of calcium edetate (CaEDTA) in rats and the protective effect of zinc.

The calcium chelate of EDTA (CaEDTA) currently is the drug of choice in the treatment of lead intoxication. This study investigated the teratogenic potential of CaEDTA, administered parenterally during periods of organogenesis and determined if incorporating zinc into EDTA would protect against teratogenic effects. Four doses (2, 4, 6, and 8 mmol/m2/day) of CaEDTA, two concentrations (8 and 20 mmol/m2/day) of ZnEDTA and ZnCaEDTA (molar ratio 0.5:0.5:1) were used, and a saline control (0.9% NaCl). Timed-pregnant Long-Evans rats were assigned at random to the treatment groups, 20 per dose for each chelate and 30 to the saline control. Rats were injected with the chelate or saline solution sc, twice daily during the 11th through 15th days of gestation. Pups removed by cesarean section on the 21st day were processed for osseous and visceral examination. Additional animals per treatment group were used for maternal plasma and liver and fetal zinc determinations. Results showed increases in several abnormalities (submucous cleft, cleft palate, adactyly-syndactyly, curly tail, abnormal rib and vertebrae) with increasing amounts of CaEDTA. No malformations were seen with ZnEDTA at either dose or with ZnCaEDTA at 8 mmol/m2/day. However, submucous cleft was seen in 6 of 20 litters from the dams receiving the higher dose of ZnCaEDTA. It was concluded that CaEDTA is teratogenic in rats at concentrations which, except for decreased weight gain, produce no discernible toxicity to the dam, and which are comparable to the recommended therapeutic dosage in humans (1500 mg/m2/day corresponding to 4 mmol/m2/day). Protection is afforded by incorporating zinc in the chelate.

Abnormalities, Drug-Induced

The effects of exposure misclassification on estimates of relative risk.

In epidemiologic studies, individuals may be misclassified with respect to exposure to a risk factor for disease. Such misclassification causes the relative risk of disease associated with the exposure in the population to be biased toward the null value. Here, a formula is derived for the apparent relative risk under misclassification (R) as a function of the sensitivity (U) and specificity (V) of the test for exposure and of the true relative risk (R) and true prevalence of exposure (P(E] in the population. The relative influence of U and V on the bias in R depends both on R and on P(E), with U tending to be more influential at higher values of P(E). When there is misclassification of exposure, variation in P(E) may bias comparisons of relative risk between groups or exposures, either by producing spurious differences or by masking true differences, and may generate spurious trends associated with a third variable such as age. Because the possible effects of misclassification of exposure on relative risk are complex and not easily generalized, the potential degree of bias should be evaluated individually in each situation.

Diagnostic Errors

Comparing indicators of health or nutritional status.

The performance of an indicator of health or nutritional status depends on its sensitivity and specificity properties over a range of cut-offs. Frequently, it is of interest to compare indicators to pick the best for a given purpose, such as screening for disease or monitoring to detect changes in prevalence of inadequate nutriture. Relative operating characteristic (ROC) analysis provides an objective method for making this comparison, but the application of this methodology as described for epidemiologists in this Journal is now outdated for most indicators. Recent developments are noted and an alternative analysis for use with continuous Gaussian data is presented here. The estimators and statistical test procedures proposed here are compared with the previously described methods, by means of a computer simulation study. The new procedures are found to be superior for continuous Gaussian data, and have the practical advantage that they do not require use of a specialized computer program. The implications of these results for comparing indicators to be used to monitor population prevalences are discussed.

Computers

Constant-parameter capture-recapture models.

Jolly (1982, Biometrics 38, 301-321) presented modifications of the Jolly-Seber model for capture-recapture data, which assume constant survival and/or capture rates. Where appropriate, because of the reduced number of parameters, these models lead to more efficient estimators than the Jolly-Seber model. The tests to compare models given by Jolly do not make complete use of the data, and we present here the appropriate modifications, and also indicate how to carry out goodness-of-fit tests which utilize individual capture history information. We also describe analogous models for the case where young and adult animals are tagged. The availability of computer programs to perform the analysis is noted, and examples are given using output from these programs.

Aging

Testing for a treatment effect in the presence of nonresponders.

Good (1979, Biometrics 35, 483-489) introduced a new randomization test for the two-sample problem where a proportion 1 - p of the treatment group does not respond to the treatment, and suggested that the Wilcoxon test is not effective for this situation. We show to the contrary that the Wilcoxon test is quite useful when p greater than or equal to .6 and point out an error in his definition of a one-tailed randomization test.

Animals

Selecting a screening cut-off point or diagnostic criterion for comparing prevalences of disease.

Comparisons of population prevalences of disease or of inadequate nutriture, across locations or over time (as in monitoring to detect a change in prevalence) are important activities in epidemiology and public health. The data collected are often counts based on a dichotomy of a continuous indicator variable, and performance of the test procedure depends on the cut-off point used. This cut-off may be chosen to optimize performance, on the assumption that the indicator has a mixed normal distribution with unknown mixing proportion corresponding to the unknown prevalence of disease. Results of James (1978, Biometrics 34, 265-275) are applied and extended to the context of monitoring. Charts are presented to facilitate determination of the optimal cut-off, and examples are given for several indicators of nutritional status.

Biometry

Prevalences of anemia and iron deficiency anemia in Black and White women in the United States estimated by two methods.

Prevalences of anemia were estimated by two methods for 742 Black and 3,074 White nonpregnant women of childbearing age drawn from a large probability sample of the United States civilian noninstitutionalized population (NHANES I). One method defines the prevalence of anemia as the proportion of women with hemoglobin levels below a 12 g/dl "cut-off". The second method defines the prevalence of anemia as the proportion of women whose hemoglobin values are shifted downwards relative to a distribution of hemoglobin values of non-anemic women. Estimates produced by both methods suggest a higher prevalence of anemia in Black than in White women. Estimates produced by the "cut-off" method, however, are higher than those from the "distribution" method for both racial groups, probably because the "cut-off" method results in large overestimates in populations where anemia prevalence is low. The "distribution" method is further used to estimate the contribution of iron deficiency to anemia. Essentially all anemia in White women and a high proportion of anemia in Black women is associated with iron deficiency in the US civilian noninstitutionalized population. Iron supplementation trials are needed in order to define the magnitude of the problem accurately and plan appropriate public health programs.

Adolescent