Comparison of bacterial culture, polymerase chain reaction, and a mix-enzyme-linked immunosorbent assay for the detection of Salmonella status in grow-to-finish pigs in western Canada with a Bayesian approach

Among grow-to-finish pigs from 10 herds in Alberta and Saskatchewan, 23 (16%) of 144 fecal samples were culture-positive and 40 (28%) of 144 pigs were seropositive for Salmonella. With a Bayesian model specifying dependence between the 2 tests, the sensitivity (Se) of culture and real-time polymerase chain reaction (RT-PCR) was 79% to 86%, depending on the cut-off value for the enzyme-linked immunosorbent assay (ELISA). Culture specificity (Sp) was assumed to be 100%; RT-PCR Sp was found to be 94%. The ELISA Se was 76% and 51% at optical density cut-off values ≥ 20% and ≥ 40%, respectively; the Sp was 94% at each cut-off value. The model showed some sensitivity to ELISA prior information, the ELISA Se being approximately 8% lower when informative prior information was specified in the model. When there was no adjustment for dependence between culture and RT-PCR, the posterior estimates for both culture and RT-PCR Se were 11% higher than with the conditional-dependence model and had considerably narrower probability intervals, which suggests that correlation between culture and PCR is important and should be adjusted for in future studies.     

Influence of likelihood function choice for estimating crop model parameters using the generalized likelihood uncertainty estimation method

Proper estimation of model parameters is required for ensuring accurate model predictions and good model-based decisions. The generalized likelihood uncertainty estimation (GLUE) method is a Bayesian Monte Carlo parameter estimation technique that makes use of a likelihood function to measure the closeness-of-fit of modeled and observed data. Various likelihood functions and methods of combining likelihood values have been used in previous studies. This research was conducted to determine the effects of using previously reported likelihood functions in a GLUE procedure for estimating parameters in a widely-used crop simulation model. A factorial computer experiment was conducted with synthetic measurement data to compare four likelihood functions and three methods of combining likelihood values using the CERES-Maize model of the Decision Support System for Agrotechnology Transfer (DSSAT). The procedure used an arbitrarily-selected parameter set as the known “true parameter set” and the CERES-Maize model to generate true output values. Then synthetic observations of crop variables were randomly generated (four replicates) by using the simulated true output values (dry yield, anthesis date, maturity date, leaf nitrogen concentration, soil nitrate concentration, and soil moisture) and adding a random observation error based on the variances of corresponding field measurements. The environmental conditions were obtained from a sweet corn (Zea mays L.) experiment conducted in 2005 in northern Florida. Results showed that the method of combining likelihood values had a strong influence on parameter estimates. The combination method based on the product of the likelihoods associated with each set of observations reduced the uncertainties in posterior distributions of parameter estimates most significantly. It was also found that the likelihood function based on Gaussian probability density function was the best among those tested. This combination accurately estimated the true parameter values, suggesting that it can be used when estimating CERES-Maize model parameters for real experiments.     

Pharmacokinetics of carvedilol after intravenous and oral administration in conscious healthy dogs

OBJECTIVE: To determine the pharmacokinetics of carvedilol administered IV and orally and determine the dose of carvedilol required to maintain plasma concentrations associated with anticipated therapeutic efficacy when administered orally to dogs. ANIMALS: 8 healthy dogs. PROCEDURES: Blood samples were collected for 24 hours after single doses of carvedilol were administered IV (175 microg/kg) or PO (1.5 mg/kg) by use of a crossover nonrandomized design. Carvedilol concentrations were detected in plasma by use of high-performance liquid chromatography. Plasma drug concentration versus time curves were subjected to noncompartmental pharmacokinetic analysis. RESULTS: The median peak concentration (extrapolated) of carvedilol after IV administration was 476 ng/mL (range, 203 to 1,920 ng/mL), elimination half-life (t(1/2)) was 282 minutes (range, 19 to 1,021 minutes), and mean residence time (MRT) was 360 minutes (range, 19 to 819 minutes). Volume of distribution at steady state was 2.0 L/kg (range, 0.7 to 4.3 L/kg). After oral administration of carvedilol, the median peak concentration was 24 microg/mL (range, 9 to 173 microg/mL), time to maximum concentration was 90 minutes (range, 60 to 180 minutes), t(1/2) was 82 minutes (range, 64 to 138 minutes), and MRT was 182 minutes (range, 112 to 254 minutes). Median bioavailability after oral administration of carvedilol was 2.1% (range, 0.4% to 54%). CONCLUSIONS AND CLINICAL RELEVANCE: Although results suggested a 3-hour dosing interval on the basis of MRT, pharmacodynamic studies investigating the duration of beta-adrenoreceptor blockade provide a more accurate basis for determining the dosing interval of carvedilol.