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At least 1,117 records · Page 62Linked to original sources
PubMed2004

Sampling times for monitoring tacrolimus in stable adult liver transplant recipients.

The aim of this study was to determine the most informative sampling time(s) providing a precise prediction of tacrolimus area under the concentration-time curve (AUC). Fifty-four concentration-time profiles of tacrolimus from 31 adult liver transplant recipients were analyzed. Each profile contained 5 tacrolimus whole-blood concentrations (predose and 1, 2, 4, and 6 or 8 hours postdose), measured using liquid chromatography-tandem mass spectrometry. The concentration at 6 hours was interpolated for each profile, and 54 values of AUC(0-6) were calculated using the trapezoidal rule. The best sampling times were then determined using limited sampling strategies and sensitivity analysis. Linear mixed-effects modeling was performed to estimate regression coefficients of equations incorporating each concentration-time point (C0, C1, C2, C4, interpolated C5, and interpolated C6) as a predictor of AUC(0-6). Predictive performance was evaluated by assessment of the mean error (ME) and root mean square error (RMSE). Limited sampling strategy (LSS) equations with C2, C4, and C5 provided similar results for prediction of AUC(0-6) (R2 = 0.869, 0.844, and 0.832, respectively). These 3 time points were superior to C0 in the prediction of AUC. The ME was similar for all time points; the RMSE was smallest for C2, C4, and C5. The highest sensitivity index was determined to be 4.9 hours postdose at steady state, suggesting that this time point provides the most information about the AUC(0-12). The results from limited sampling strategies and sensitivity analysis supported the use of a single blood sample at 5 hours postdose as a predictor of both AUC(0-6) and AUC(0-12). A jackknife procedure was used to evaluate the predictive performance of the model, and this demonstrated that collecting a sample at 5 hours after dosing could be considered as the optimal sampling time for predicting AUC(0-6).

Adult↗
PubMed2006

Cost-effectiveness analysis of sedation and analgesia regimens during fracture manipulation in the pediatric emergency department.

OBJECTIVE: To conduct a cost-effectiveness analysis, from a hospital's perspective, of 4 procedural sedation and analgesia (PSA) regimens to facilitate forearm fracture manipulation in the pediatric emergency department (ED): deep sedation with ketamine/midazolam (K/M) administration, propofol/fentanyl administration, fentanyl/midazolam (F/M) administration, and axillary block. DESIGN/METHODS: We constructed a decision analytic model using relevant probabilities from published studies of pediatric patients who underwent fracture manipulation in the EDs. Total costs were calculated by assessing ED resource utilization associated with uncomplicated PSA and with PSA complicated by adverse events. Costs of consumable equipment were considered to be fixed. Total sedation time, personnel time, and drug costs were considered variable. We assumed that all PSA regimens provided effective relief from procedural distress. Failure rates for axillary block were estimated based on reports in the literature. When patients experienced emesis, recovery agitation, respiratory depression, lidocaine toxicity, or regional block failure, we assumed that the patients would require 1 additional hour of ED stay. Sensitivity analyses of all key variables in the model were performed to identify those that may result in a change in the preferred option. Monte Carlo simulations were performed to assess model robustness. RESULTS: Under baseline assumptions, the propofol/fentanyl regimen was the most cost-effective choice (expected cost, 84.06 US dollars), followed by axillary block (88.18 US dollars), K/M (105.32 US dollars), and F/M (159.79 US dollars), respectively. Varying the fixed and variable costs by 50% to 200% of their baseline values did not alter the ranking. When ketamine and propofol were administered without adjunctive midazolam and fentanyl, respectively, propofol remained the optimum choice. With total PSA time as the outcome measure, the incremental cost-effectiveness ratios were 8.1 US dollars and 24.9 US dollars per hour of ED time saved, for propofol/fentanyl versus axillary block and for axillary block versus K/M, respectively. CONCLUSIONS: Among PSA regimens during forearm fracture manipulation in the pediatric ED, propofol/fentanyl is the most cost-effective regimen followed by axillary block, K/M, and F/M.

Analgesics↗
PubMed2000

Dynamic properties of hydrogen-bonded networks in supercritical water

Dynamic properties of supercritical water at temperatures between 573 and 773 K and densities between 0.49 and 0.83 g/cm(3) have been investigated by molecular dynamics simulation and compared to states located on the vapor-liquid coexistence curve. A flexible simple point charge potential has been assumed for interactions in the subcritical states, whereas a reparameterization of that model has been performed to model the supercritical states. The hydrogen bonding structure and the diffusion coefficients in an ensemble of simulated states were previously analyzed and a good agreement with available experimental data was found. Dynamic properties of hydrogen bonding like the bond lifetimes and the influence of hydrogen bonds in the vibrational spectra are discussed along a range of simulation conditions. A nonlinear behavior of the hydrogen-bond lifetime as a function of temperature is observed in subcritical water whereas a linear dependence is found in supercritical water. Special attention is paid to the intermolecular vibrational spectrum (10-400 cm(-1)). It has been observed that the mode centered at 200 cm(-1), attributed to the intermolecular O-O stretching vibration in the ambient state remains active in the supercritical states.

Journal Article↗
PubMed2004

Proof of concept: performance testing in models.

Pharmacokinetic (PK) and pharmacodynamic (PD) principles that predict antimicrobial efficacy can be used to set targets for antimicrobial design and optimisation. Although current formulations of amoxicillin and amoxicillin/clavulanate have retained their efficacy against many, but not all, penicillin-nonsusceptible Streptococcus pneumoniae, additional coverage is required to address the growing problem of drug-resistant strains. Accordingly, two new oral formulations of amoxicillin/clavulanate, a paediatric formulation at 90/6.4 mg/kg/day and a pharmacokinetically enhanced formulation at 2000/125 mg twice daily for adults, were designed using PK/PD principles. These principles indicate that for amoxicillin and amoxicillin/clavulanate, a time above MIC of 35-40% of the dosing interval is predictive of high bacterial efficacy. In line with PK/PD predictions, simulation of human pharmacokinetics in in-vitro kinetic models and in a rat model of pneumonia, amoxicillin/clavulanate 2000/125 mg twice daily was highly effective against S. pneumoniae strains with amoxicillin MICs of 4 or 8 mg/L. Against strains with amoxicillin MICs of 4 mg/L, amoxicillin/clavulanate 2000/125 mg twice daily was significantly more effective than the conventional 875/125 mg twice daily formulation, azithromycin and levofloxacin, even though all levofloxacin MICs were < or = 1 mg/L. Following infection with S. pneumoniae strains with amoxicillin MICs of 8 mg/L, the amoxicillin/clavulanate 2000/125 mg twice daily formulation was more effective than the conventional amoxicillin/clavulanate formulations of 875/125 mg twice daily and three times daily and 1000/125 mg three times daily, and had similar or better efficacy than azithromycin and levofloxacin, depending on the strain. These data indicate the potential benefit of therapy with amoxicillin/clavulanate 2000/125 mg twice daily compared with conventional formulations and other marketed antimicrobials in the treatment of respiratory tract infection.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2005

The performance of mixture models in heterogeneous closed population capture-recapture.

Dorazio and Royle (2003, Biometrics 59, 351-364) investigated the behavior of three mixture models for closed population capture-recapture analysis in the presence of individual heterogeneity of capture probability. Their simulations were from the beta-binomial distribution, with analyses from the beta-binomial, the logit-normal, and the finite mixture (latent class) models. In this response, simulations from many different distributions give a broader picture of the relative value of the beta-binomial and the finite mixture models, and provide some preliminary insights into the situations in which these models are useful.

Animal Identification Systems↗
PubMed1987

Two-mass models of the vocal cords for natural sounding voice synthesis.

Three new two-mass models of the vocal cords are treated. First, the features, structure, and differential equations of motion are described for each of the new models and compared with those of previous models. Second, performances of the models are discussed in terms of glottal volume flow, glottal area, radiated sound pressure, trajectories of mass movement, running spectra of the output sound pressure, and perceptual naturalness of the output sound. Finally, the major effects of glottal source-vocal tract interaction including skewing, truncation, and superposition are investigated, using one of the simplest types of two-mass models and two types of load representing the vocal tract.

Communication Devices for People with Disabilities↗
PubMed1988

Flexibility of DNA.

Both microscopic and macroscopic models of DNA flexibility should lead to the same quantitative description of the elastic properties of the DNA helix. This belief is reinforced by the fact that essentially all experimental (solution) studies to date support the macroscopic, elastic model. The performance of microscopic models can therefore be checked by their ability to produce the correct macroscopic quantities (P and C). To most carefully address the influence of such factors as base sequence, DNA damage, and drug or protein interaction on the flexibility of DNA, methods are required that are most sensitive for DNA molecules of less than 500-1000 bp. The use of molecules in this size range will maximize the signal due to the structural alteration as well as facilitate the construction of DNA sequences of any desired arrangement. I have emphasized three such methods and summarized their strengths and weaknesses; however, their concurrent application to the determination of DNA flexibility provides an important check of self-consistency. These studies have indicated that the persistence length of DNA in buffers of moderate salt concentration is 450-500 A. Synthetic DNA is now readily available, and many procedures for the construction and cloning of DNA molecules of defined length and sequence (107-108a) are in common use. The availability of restriction fragments of precisely defined length has transformed the study of the physical (particularly hydrodynamic) properties of such molecules, since the hitherto pervasive problem of length polydispersity has been eliminated. Sheared, sonicated, or otherwise abused calf thymus (or other) DNAs should no longer be considered acceptable materials for physical studies. Many studies of bending and torsional fluctuations in DNA have been excluded from this discussion because the DNA samples used were not precisely defined. The torsional elastic constant of DNA has been fairly well established as approximately 3.0 x 10(-19) erg-cm, mainly through a combination of elegant theoretical and experimental studies of topoisomer distributions in circular DNA molecules. The other general approach to the determination of the torsional elastic constant, luminescence decay, is still burdened by the poor characterization of the DNA used in many of the experimental studies as well as by some continued theoretical uncertainties.(ABSTRACT TRUNCATED AT 400 WORDS)

DNA↗
PubMed2006

Performance of statistical models to predict mental health and substance abuse cost.

BACKGROUND: Providers use risk-adjustment systems to help manage healthcare costs. Typically, ordinary least squares (OLS) models on either untransformed or log-transformed cost are used. We examine the predictive ability of several statistical models, demonstrate how model choice depends on the goal for the predictive model, and examine whether building models on samples of the data affects model choice. METHODS: Our sample consisted of 525,620 Veterans Health Administration patients with mental health (MH) or substance abuse (SA) diagnoses who incurred costs during fiscal year 1999. We tested two models on a transformation of cost: a Log Normal model and a Square-root Normal model, and three generalized linear models on untransformed cost, defined by distributional assumption and link function: Normal with identity link (OLS); Gamma with log link; and Gamma with square-root link. Risk-adjusters included age, sex, and 12 MH/SA categories. To determine the best model among the entire dataset, predictive ability was evaluated using root mean square error (RMSE), mean absolute prediction error (MAPE), and predictive ratios of predicted to observed cost (PR) among deciles of predicted cost, by comparing point estimates and 95% bias-corrected bootstrap confidence intervals. To study the effect of analyzing a random sample of the population on model choice, we re-computed these statistics using random samples beginning with 5,000 patients and ending with the entire sample. RESULTS: The Square-root Normal model had the lowest estimates of the RMSE and MAPE, with bootstrap confidence intervals that were always lower than those for the other models. The Gamma with square-root link was best as measured by the PRs. The choice of best model could vary if smaller samples were used and the Gamma with square-root link model had convergence problems with small samples. CONCLUSION: Models with square-root transformation or link fit the data best. This function (whether used as transformation or as a link) seems to help deal with the high comorbidity of this population by introducing a form of interaction. The Gamma distribution helps with the long tail of the distribution. However, the Normal distribution is suitable if the correct transformation of the outcome is used.

Aged↗
PubMed2006

Physics-based multiplicative scatter correction approaches for improving the performance of calibration models.

Light scattering effects pose a major problem in the estimation of chemical properties of particulate systems such as blood, tissue, and pharmaceutical solids. Recently, Martens et al. proposed an extended multiplicative signal correction (EMSC) approach where light-scattering effects were taken into account in an empirical manner. It is possible to include causal, first-principles mathematical models based on the physics of light scattering into the EMSC framework. This could lead to significant improvements in the separation of absorption and scattering effects. A preconditioning step prior to application of EMSC, whereby a transformation based on the physics of light scattering is used to convert the spectra into a form where the absorption and scattering effects are separable (an underlying assumption of EMSC), is proposed. Results indicate that the transformation followed by EMSC gives better calibration models than the direct application of EMSC to the absorbance spectra.

Calibration↗
PubMed2002

Evaluation of the AgDISP aerial spray algorithms in the AgDRIFT model.

A systematic evaluation of the AgDISP algorithms, which simulate off-site drift and deposition of aerially applied pesticides, contained in the AgDRIFT model was performed by comparing model simulations to field-trial data collected by the Spray Drift Task Force. Field-trial data used for model evaluation included 161 separate trials of typical agriculture aerial applications under a wide range of application and meteorological conditions. Input for model simulations included information on the aircraft and spray equipment, spray material, meteorology, and site geometry. The model input datasets were generated independently of the field deposition results, i.e., model inputs were in no way altered or selected to improve the fit of model output to field results. AgDRIFT shows a response similar to that of the field observations for many application variables (e.g., droplet size, application height, wind speed). However, AgDRIFT is sensitive to evaporative effects, and modeled deposition in the far-field responds to wet bulb depression whereas the field observations did not. The model tended to overpredict deposition rates relative to the field data for far-field distances, particularly under evaporative conditions. AgDRIFT was in good agreement with field results for estimating near-field buffer zones needed to manage human, crop, livestock, and ecological exposure.

Agriculture↗
PubMed1989

A causal model of mathematics performance in early adolescence: the role of sex.

Using path analysis, the present investigation was done to clarify possible causal linkages among general scholastic aptitude, academic achievement in mathematics, self-concept of ability, and performance on a mathematics examination. Subjects were 122 eighth-grade students who completed a mathematics examination as well as a measure of self-concept of ability. Aptitude and achievement measures were obtained from school records. Analysis showed sex differences in prediction of performance on the mathematics examination. For boys, this performance could be predicted from scholastic aptitude and previous achievement in mathematics. For girls, performance only could be predicted from previous achievement in mathematics. These results indicate that the direction, strength, and magnitude of relations among these variables differed for boys and girls, while mean levels of performance did not.

Achievement↗
PubMed2000

[The method of time series modeling and its application in the spectral analysis of lubricating oil].

In this paper, we discuss the applications of time series modeling method in the analysis of lubricating oil of mechanical equipment. We obtained satisfactory results by applying AR model to perform time series modeling and forecasting analysis to the collected spectral analysis data of the air engine. So we have built a practical method for state monitoring and trouble forecasting of mechanical equipment.

English Abstract↗