Population Pharmacokinetics of Intranasal Dexmedetomidine in Infants and Young Children.

BACKGROUND: Intranasal dexmedetomidine provides noninvasive, effective procedural sedation for pediatric patients, and has been widely used in clinical practice. However, the dosage applied has varied fourfold in pediatric clinical studies. To validate an appropriate dosing regimen, this study investigated the pharmacokinetics of intranasal dexmedetomidine in Chinese children under 3 yr old. METHODS: Intranasal dexmedetomidine 2 µg · kg-1 was administered to children with simple vascular malformations undergoing interventional radiological procedures. A population pharmacokinetic analysis with data from an optimized sparse-sampling design was performed using nonlinear mixed-effects modeling. Clearance was modeled using allometric scaling and a sigmoid postmenstrual age maturation model. Monte Carlo simulations were performed to assess the different dosing regimens. RESULTS: A total of 586 samples from 137 children aged 3 to 36 months were included in the trial. The data were adequately described by a two-compartment model with first-order elimination. Body weight with allometric scaling and maturation function were significant covariates of dexmedetomidine clearance. The pharmacokinetic parameters for the median subjects (weight 10 kg and postmenstrual age 101 weeks) in the authors' study were apparent central volume of distribution 7.55 l, apparent clearance of central compartment 9.92 l · h-1, apparent peripheral volume of distribution 7.80 l, and apparent intercompartmental clearance 61.7 l · h-1. The simulation indicated that at the dose of 2 µg · kg-1, 95% of simulated individuals could achieve a target therapeutic concentration of 0.3 ng · ml-1 within 20 min, and the average peak concentration of 0.563 ng · ml-1 could be attained at 61 min. CONCLUSIONS: The pharmacokinetic characteristics of intranasal dexmedetomidine were evaluated in Chinese pediatric patients aged between 3 and 36 months. An evidence-based dosing regimen at 2 µg · kg-1 could achieve a preset therapeutic threshold of mild to moderate sedation that lasted for up to 2 h.

Accuracies of genomic prediction for twenty economically important traits in Chinese Simmental beef cattle.

Genomic prediction has been widely utilized to estimate genomic breeding values (GEBVs) in farm animals. In this study, we conducted genomic prediction for 20 economically important traits including growth, carcass and meat quality traits in Chinese Simmental beef cattle. Five approaches (GBLUP, BayesA, BayesB, BayesCπ and BayesR) were used to estimate the genomic breeding values. The predictive accuracies ranged from 0.159 (lean meat percentage estimated by BayesCπ) to 0.518 (striploin weight estimated by BayesR). Moreover, we found that the average predictive accuracies across 20 traits were 0.361, 0.361, 0.367, 0.367 and 0.378, and the averaged regression coefficients were 0.89, 0.86, 0.89, 0.94 and 0.95 for GBLUP, BayesA, BayesB, BayesCπ and BayesR respectively. The genomic prediction accuracies were mostly moderate and high for growth and carcass traits, whereas meat quality traits showed relatively low accuracies. We concluded that Bayesian regression approaches, especially for BayesR and BayesCπ, were slightly superior to GBLUP for most traits. Increasing with the sizes of reference population, these two approaches are feasible for future application of genomic selection in Chinese beef cattle.

PCDD/Fs formation catalyzed by the copper chloride in the fly ash.

The secondary formation of dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) in the flue gas and ash from the municipal solid waste incinerator (MSWI) systems has attracted considerable public concern. The objective of our research was thus to examine reactions in fly ash from an MSWI operated with different precursors with similar chemical compositions, such as dibenzofurans (DFs), and metal chlorides, such as copper chloride (CuCl(2)). We observed that the concentrations of PCDD/Fs in CuCl(2) and in a mixture of CuCl(2) and DFs were 369.5 and 5307.8 ng/g, respectively, and thus significantly higher in the latter. Due to the catalytic effect of copper ions and the similar structure of dibenzofurans for PCDFs, the effect of the additive in forming PCDD/Fs were obvious. The concentrations of PCDD/Fs in CuCl(2) and copper oxide (CuO) were 369.5 and 97.05 ng/g, respectively. The results also show that the PCDD/Fs concentration when copper chloride was added was four times higher than when copper oxide was added. In addition, the level of activity of the chlorine atoms is greater than that of the oxygen atoms during the formation of PCDD/Fs. This study suggests that the use of metal-containing substances (such as Cu, Cl, Zn) or chlorination precursors (such as DF, chlorobenzene) should be avoided in the combustion process.

Interval-parameter semi-infinite fuzzy-stochastic mixed-integer programming approach for environmental management under multiple uncertainties.

In this study, an interval-parameter semi-infinite fuzzy-chance-constrained mixed-integer linear programming (ISIFCIP) approach is developed for supporting long-term planning of waste-management systems under multiple uncertainties in the City of Regina, Canada. The method improves upon the existing interval-parameter semi-infinite programming (ISIP) and fuzzy-chance-constrained programming (FCCP) by incorporating uncertainties expressed as dual uncertainties of functional intervals and multiple uncertainties of distributions with fuzzy-interval admissible probability of violating constraint within a general optimization framework. The binary-variable solutions represent the decisions of waste-management-facility expansion, and the continuous ones are related to decisions of waste-flow allocation. The interval solutions can help decision-makers to obtain multiple decision alternatives, as well as provide bases for further analyses of tradeoffs between waste-management cost and system-failure risk. In the application to the City of Regina, Canada, two scenarios are considered. In Scenario 1, the City's waste-management practices would be based on the existing policy over the next 25 years. The total diversion rate for the residential waste would be approximately 14%. Scenario 2 is associated with a policy for waste minimization and diversion, where 35% diversion of residential waste should be achieved within 15 years, and 50% diversion over 25 years. In this scenario, not only landfill would be expanded, but also CF and MRF would be expanded. Through the scenario analyses, useful decision support for the City's solid-waste managers and decision-makers has been generated. Three special characteristics of the proposed method make it unique compared with other optimization techniques that deal with uncertainties. Firstly, it is useful for tackling multiple uncertainties expressed as intervals, functional intervals, probability distributions, fuzzy sets, and their combinations; secondly, it has capability in addressing the temporal variations of the functional intervals; thirdly, it can facilitate dynamic analysis for decisions of facility-expansion planning and waste-flow allocation within a multi-facility, multi-period and multi-option context.

Black box radiation gauges and analyzers: dream or reality?

This paper describes our attempts to make radiation gauges and analyzers operate in more of a 'black box' manner-being more independent of or at least more insensitive to changes in such things as sample composition and position. Our overall approach relies heavily on Monte Carlo simulation and that is discussed first in relation to radiation gauge and analyzer design and usage. Then the principles and applications of radiation gauges and analyzers including the Measurement Chi-Square and Monte Carlo Library Least-Squares, respectively, are treated. Finally, future work in this area is discussed.

Serum hyaluronate in the assessment of liver endothelial cell function after orthotopic liver transplantation in the rat.

This study was designed to evaluate the use of serum hyaluronate as a marker of liver endothelial cell function after liver transplantation. We performed orthotopic liver transplantation in both isogeneic and allogeneic rejector models. After transplantation, hepatocyte function was assessed on the basis of serum ALT and total bilirubin levels, and liver endothelial cell function was judged on the basis of serum hyaluronate levels. Significant increase of hyaluronate in the rejector model, compared with the isogeneic model, was seen before any significant results could be obtained from conventional liver function tests. The impaired metabolism of hyaluronate in the rejector model was observed after intravenous injection of trace amounts of radioactive material. Serial studies demonstrate that the endothelial cell is a more susceptible target for the immune response than the hepatocyte. Serum hyaluronate concentration may be a better indicator in the early assessment of graft function. We also examined serum hyaluronate levels to evaluate cold ischemia-reperfusion injury to the liver endothelial cells in the isogeneic model. At 2 hr after reperfusion, hyaluronate levels in the 6-hr cold ischemia (nonviable allograft) group were significantly higher than in the 1-hr and 3-hr cold ischemia (viable allograft) groups. However, there was little difference between the viable allograft groups. After an intravenous injection of 1 mg/kg hyaluronate, the hyaluronate elimination rate in the 3-hr group was distinctly slower than that in the 1-hr group. These data indicate that the hyaluronate elimination rate may be a more sensitive marker of liver endothelial cell function in viable liver after a short period of ischemia.