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PubMed2006

Auditing as part of the terminology design life cycle.

OBJECTIVE: To develop and test an auditing methodology for detecting errors in medical terminologies satisfying systematic inheritance. This methodology is based on various abstraction taxonomies that provide high-level views of a terminology and highlight potentially erroneous concepts. DESIGN: Our auditing methodology is based on dividing concepts of a terminology into smaller, more manageable units. First, we divide the terminology's concepts into areas according to their relationships/roles. Then each multi-rooted area is further divided into partial-areas (p-areas) that are singly-rooted. Each p-area contains a set of structurally and semantically uniform concepts. Two kinds of abstraction networks, called the area taxonomy and p-area taxonomy, are derived. These taxonomies form the basis for the auditing approach. Taxonomies tend to highlight potentially erroneous concepts in areas and p-areas. Human reviewers can focus their auditing efforts on the limited number of problematic concepts following two hypotheses on the probable concentration of errors. RESULTS: A sample of the area taxonomy and p-area taxonomy for the Biological Process (BP) hierarchy of the National Cancer Institute Thesaurus (NCIT) was derived from the application of our methodology to its concepts. These views led to the detection of a number of different kinds of errors that are reported, and to confirmation of the hypotheses on error concentration in this hierarchy. CONCLUSION: Our auditing methodology based on area and p-area taxonomies is an efficient tool for detecting errors in terminologies satisfying systematic inheritance of roles, and thus facilitates their maintenance. This methodology concentrates a domain expert's manual review on portions of the concepts with a high likelihood of errors.

Biology↗
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↗
PubMed1993

Measurement of water turnover using a stable isotope technique: calculation of error propagation.

Water turnover may be determined with stable isotope techniques from the product of tracer dilution space and tracer elimination rate. Tracer concentrations must be measured in two body fluid samples which are separated by a sampling interval. The tracer concentration of the first sample may be charged with an error which may be due to analytical errors, incomplete tracer dilution or because the necessary steady-state assumption (water influx equals water efflux) is violated at the moment of tracer loading. Error propagation shows that the influence of this error on the estimation of water turnover is partially compensated for. The goodness of compensation depends on the sampling interval and on the magnitude of the error of the first sample. The error is best compensated using sampling intervals of 1.5 tracer half life.

Body Water↗
PubMed2005

Detection of genotyping errors and pseudo-SNPs via deviations from Hardy-Weinberg equilibrium.

Genotype error can greatly reduce the power of a genetic study. For family data, genotype error can be assessed by examining marker data for non-Mendelian inconsistencies, closely linked markers for double recombination events, and consistency of duplicate genotypes. For case-control data, duplicate samples are genotyped, and controls are tested for deviations from Hardy-Weinberg equilibrium (HWE). Duplicate samples can provide accurate estimates of genotyping error rates, unless systematic genotyping errors have occurred. Although genotyping errors can cause deviations from HWE, these deviations are usually small, and the power to detect them is low except for high rates of genotyping error and/or large sample sizes. An additional problem is that even when deviations from HWE are detected for marker loci, without additional experimentation it is not possible to unequivocally implicate genotyping error as the cause. The power and sample sizes necessary to detect deviations from HWE for single-nucleotide polymorphism (SNP) data are examined for a variety of genotyping error and pseudo-SNP models. For the majority of genotyping models examined, the power is poor to detect deviations from HWE. For example, for 1,000 controls, if an allele with a frequency of 0.1 fails to amplify for 28% of the heterozygous genotypes producing a sample error rate of 0.05, the power is 0.51 to detect a deviation from HWE at an alpha level of 0.05. On the other hand, the detection of deviations from HWE for pseudo-SNPs (paralogous and ectopic sequence variants) for the majority of models examined produces a power of >0.8 for sample sizes as small as 50 individuals.

Gene Frequency↗
PubMedDate not supplied

Errors in plasma creatine kinase estimations on fetal blood samples resulting from contamination with amniotic fluid and maternal blood: relevance for the prenatal diagnosis of Duchenne muscular dystrophy.

This paper presents a detailed analysis of the calculation of fetal plasma CK activity in fetal blood samples contaminated with amniotic fluid and maternal blood. The seemingly simple formula for this calculation, first presented by Mahoney et al. (1977), is actually more complex than it appears; values for up to nine variables, two of which can only be assumed, are needed. Small variations in certain variables may result in very large errors in the final calculated value of fetal plasma CK activity. Examples of diluted blood samples are considered and the effects of allowing for reasonable errors in the variables is explored. The main source of error is in the measurement of CK activities in the diluted blood sample and in the amniotic fluid. Contamination by blood originating from the maternal circulation can also be a large source of error, especially if the mother is a carrier of DMD and maintains a high level of plasma CK activity during pregnancy. Fetal blood indices have to be assumed; these may be a source of significant error, depending on the difference between the actual and assumed values. The measurement of fetal plasma CK activity by the indirect calculation method is discussed in the context of the prenatal diagnosis of DMD.

Amniocentesis↗
PubMed2005

Post-choice information processing by pigeons.

In a conditional discrimination (matching-to-sample), a sample is followed by two comparison stimuli, one of which is correct, depending on the sample. Evidence from previous research suggests that if the stimulus display is maintained following an incorrect response (the so-called penalty-time procedure), acquisition by pigeons is facilitated. The present research tested the hypothesis that the penalty-time procedure allows the pigeons to review and learn from the maintained stimulus display following an incorrect choice. It did so by including a penalty-time group for which, following an incorrect choice, the sample changed to match the incorrect comparison, thus providing the pigeons with post-choice 'misinformation.' This misinformation group acquired the matching task significantly slower than the standard penalty-time group (that had no change in the sample following an error). Furthermore, acquisition of matching by a control group that received no penalty time fell midway between the other two groups, suggesting that the pigeons did not merely take more care in making choices because of the aversiveness of penalty-time. Thus, it appears that in the acquisition of matching-to-sample, when the stimulus display is maintained following an incorrect choice, the pigeons can review or acquire information from the display. This is the first time that such an effect has been reported for a nonhuman species.

Animals↗
PubMed1990

Effects of the NMDA antagonists CPP and MK-801 on radial arm maze performance in rats.

The dose- and time-dependent effects of N-methyl-D-aspartate receptor/channel antagonists on radial 8-arm maze performance were examined in rats. Both CPP (1.0-30 mg/kg), a competitive NMDA antagonist, and MK-801 (0.1-1.0 mg/kg), a noncompetitive NMDA antagonist, produced dose-dependent increases in the number of errors made to sample all 8 baited arms. The effective doses of both drugs produced maximal performance impairments 2 hr after IP injection, and no effects after 24 hr. In a second radial arm maze task where only 4 arms were baited, CPP (10 mg/kg) had a somewhat greater effect on the number of working memory errors than on reference memory errors. MK-801 (0.1, 0.33 mg/kg) had no effects on either this task or on a task involving a 1-hr delay between correct choices 4 and 5 on the 8 choice task. CPP (10 mg/kg), however, impaired performance on this latter task. These results indicate that doses of NMDA antagonists, sufficient to block hippocampal long-term potentiation, also disrupt radial arm maze performance.

Animals↗
PubMed2005

Raman and near-infrared spectroscopy for quantification of fat composition in a complex food model system.

Raman and near-infrared (NIR) spectroscopy have been evaluated for determining fatty acid composition and contents of main constituents in a complex food model system. A model system consisting of 70 different mixtures of protein, water, and oil blends was developed in order to create a rough chemical imitation of typical fish and meat samples, showing variation both in fatty acid composition and in contents of main constituents. The model samples as well as the pure oil mixtures were measured using Raman and NIR techniques. Partial least squares regression was utilized for prediction, and fatty acid features were expressed in terms of the iodine value and as contents of saturated, monounsaturated, and polyunsaturated fatty acids. Raman spectroscopy provided the best results for predicting iodine values of the model samples, giving validated estimation errors accounting for 2.8% of the total iodine value range. Both techniques provided good results for predicting the content of saturated, monounsaturated, and polyunsaturated fatty acids in the model samples, yielding validated estimation errors in the range of 2.4-6.1% of the total range of fatty acid content. Prediction results for determining fatty acid features of the pure oil mixtures were similar for the two techniques. NIR was clearly the best technique for modeling content of main constituents in the model samples.

Algorithms↗
PubMed1998

Temporal sampling requirements for the tracer kinetics modeling of breast disease.

The physiological parameters measured in the tracer kinetics modeling of data from a dynamic contrast-enhanced magnetic resonance (MR) breast exam (blood flow-extraction fraction product [FE], volume of the extracellular extravascular space [Ve], and blood volume [Vb]) may enable non-invasive diagnosis of breast cancer. One of the factors that compromises the accuracy and precision of the parameter estimates, and therefore their diagnostic potential, is the temporal resolution of the MR scans used to measure contrast agent (gadolinium-diethylenetriamine pentaacetic acid [Gd-DTPA]) concentration in an artery (arterial input function [AIF]) and in the tissue (tissue residue function [TRF]). Using computer simulations, we have examined, for several AIF widths, the errors introduced into estimates of tracer kinetic parameters in breast tissue due to insufficient temporal sampling. Temporal sampling errors can be viewed as uncertainties and biases in the parameter estimates introduced by the uncertainty in the relative alignments of the AIF, TRF, and sampling grid. These effects arise from the model's inherent sensitivity to error in either the AIF or TRF, which is dependent on the values of the tracer kinetic parameters and increases with AIF width. Based on the results of the simulations, to ensure that the error in FE and Ve will be under 10% of their true values, we recommend a rapid bolus injection of contrast agent (approximately 10 s), that the AIF be sampled every second, and that the TRF be sampled every 16 s or less. An accurate measurement of Vb requires that the TRF be sampled at least every 4 s. The results of these investigations can be used to set minimum dynamic imaging rates for tracer kinetics modeling of the breast.

Breast↗
PubMed2000

Dose uniformity and redispersibility of pharmaceutical suspensions 2: assessment of three commercial erythromycin ethyl succinate oral liquids.

The content of active ingredient of single doses of a suspension depends to a large extent upon the redispersibility of the product. Mathematical and technical aspects of a procedure to test this property have been discussed in a preceding article. Here, the method is applied to three commercial erythromycin ethylsuccinate suspensions obtained from community pharmacies in Germany. Three specimens of each product were tested in parallel. For approximately two weeks, samples were taken t.i.d. at 9 am, 1 pm and 5 pm after shaking the bottles on a prototype testing apparatus with an intensity of 134m(2)/s(3) per cycle corresponding to the 25th percentile of a group of 79 subjects, whose shaking habits had been assessed previously. In order to minimize volumetric errors, 2.5ml samples were drawn using a syringe. They were assayed by HPLC with electrochemical detection using oleandomycin as an internal standard. While one of the products performed satisfactorily and one showed moderate shortcomings, the dose uniformity of two specimens of the third product was clearly deficient. The problem seems to be associated with poor wetting behaviour of the solids.

Administration, Oral↗
PubMed2003

Development and validation of a capillary zone electrophoresis method for the quantitative determination of anthocyanins in wine.

A capillary zone electrophoresis (CZE) method is proposed for the quantitative determination of anthocyanins in wine as an alternative to high-performance liquid chromatography. The CZE separation was carried out using a 46 cm (effective length) x 75 microm I.D. fused-silica capillary at 10 degrees C and a 50 mM sodium tetraborate buffer at pH 8.4 with 15% of methanol as modifier. A voltage of 25 kV and a hydrodynamic injection of 300 mbar s were used. The electropherograms were recorded at 599 nm. It was found that SO2 (antibacterial and antioxidant agent added to wine during its production) increased the absorbance of anthocyanins at 599 nm in a basic medium. Therefore, a concentration of 250 mg/l of SO2 was added to the samples and the calibration solution before the analysis in order to avoid errors by this matrix effect. The analytical response was linear (R=0.998) between 10 and 700 microg/ml of malvidin-3-O-glucoside. The limit of detection and the reproducibility (as a relative standard deviation, n=11) were 1 microg/ml and 1.5%, respectively. Finally, the CZE method was validated by the analysis of synthetic wine samples (errors less than 8%) and by the comparison of the results obtained in the analysis of different monovarietal wines by CZE with those obtained by the standard HPLC method. In this comparison, a good correlation (R=0.998) with a slope of 1.005+/-0.044 and an intercept of -0.752+/-6.690 was obtained for malvidin-3-O-glucoside.

Anthocyanins↗
PubMed2005

Pharmacodynamic parameter estimation: population size versus number of samples.

The purpose of this study was to evaluate the effects of population size, number of samples per individual, and level of interindividual variability (IIV) on the accuracy and precision of pharmacodynamic (PD) parameter estimates. Response data were simulated from concentration input data for an inhibitory sigmoid drug efficacy (E(max)) model using Nonlinear Mixed Effect Modeling, version 5 (NONMEM). Seven designs were investigated using different concentration sampling windows ranging from 0 to 3 EC(50) (EC(50) is the drug concentration at 50% of the E(max)) units. The response data were used to estimate the PD and variability parameters in NONMEM. The accuracy and precision of parameter estimates after 100 replications were assessed using the mean and SD of percent prediction error, respectively. Four samples per individual were sufficient to provide accurate and precise estimate of almost all of the PD and variability parameters, with 100 individuals and IIV of 30%. Reduction of sample size resulted in imprecise estimates of the variability parameters; however, the PD parameter estimates were still precise. At 45% IIV, designs with 5 samples per individual behaved better than those designs with 4 samples per individual. For a moderately variable drug with a high Hill coefficient, sampling from the 0.1 to 1, 1 to 2, 2 to 2.5, and 2.5 to 3 EC(50) window is sufficient to estimate the parameters reliably in a PD study.

Humans↗
PubMed1985

Controlled clinical trials in emergency medicine.

In this first article of a series on controlled clinical trials in emergency medicine, an overview of the structure of such studies and the relevant issues related to study design, data generation, statistical analysis, and reporting are presented. The importance of precise patient selection, randomization and stratification, blinding, and equivalent therapeutic intervention in study design has been discussed. In addition, precise outcome and measurement criteria, assessor qualifications, deficiencies in data, appropriate sample-size selection, and reporting are also presented. Although an idealized framework for the conduct and analysis of a controlled clinical trial is provided, it should be appreciated that design and analytical compromises may at times be difficult to avoid in clinical research. Future articles in this series will discuss randomization in clinical trials, alternatives to randomization, beta error and sample-size determination, the statistical and analytical issues related to imperfections in the execution of a trial, and issues related to the reporting of clinical trials.

Clinical Trials as Topic↗
PubMed1991

Forage quality analyses and interpretation.

The minimum analyses needed to determine the quality or nutritive composition of forages are DM, CP, ADF, NDF, Ca, and P. The accuracy of these and other analyses are affected by the sampling and analysis methods. Improper sampling is probably one of the largest but most overlooked sources of variation in analysis. Analysis methods must be both accurate and precise. New techniques like NIRS can be just as accurate and have better precision than conventional chemistry methods if correctly calibrated. Finally, understanding variations associated with the analysis and discerning sources of the variation as to errors in analysis, sampling, or natural variation caused by environmental growing conditions, plant species, or harvest practices is the biggest challenge for nutritionists. Forages cannot be fully and efficiently utilized in the diets of dairy cattle until their composition is accurately determined and interpreted for animal performance.

Animal Feed↗
PubMed2006

A linear feature extraction for multiclass classification problems based on class mean and covariance discriminant information.

A parametric linear feature extraction method is proposed for multiclass classification. The skeleton of the proposed method consists of two types of schemes that are complementary to each other with regard to the discriminant information used. The approximate pairwise accuracy criterion (aPAC) and the common-mean feature extraction (CMFE) are chosen to exploit the discriminant information about class mean and about class covariance, respectively. Choosing aPAC rather than the linear discriminant analysis (LDA) can also resolve the problem of overemphasized large distances introduced by LDA, while maintaining other decent properties of LDA. To alleviate the suboptimum problem caused by a direct cascading of the two different types of schemes, there should be a mechanism for sorting and merging features based on their effectiveness. Usage of a sample-based classification error estimation for evaluation of effectiveness of features usually costs a lot of computational time. Therefore, we develop a fast spanning-tree-based parametric classification accuracy estimator as an intermediary for the aPAC and CMFE combination. The entire framework is parametric-based. This avoids paying a costly price in computation, which normally happens to the sample-based approach. Our experiments have shown that the proposed method can achieve a satisfactory performance on real data as well as simulated data.

Algorithms↗
PubMed1993

Zero and first moment area estimation from microdialysis data.

The calculation of classical pharmacokinetic parameters from microdialysis data has been described in a previous paper. In this paper I have derived methods for calculating AUMC and AUC from the time-integral type of data that are generated in microdialysis pharmacokinetics experiments. The method derived to estimate AUC is elementary, but is given a theoretical basis using principles of mathematical real analysis, clearly stating ths assumptions. The method derived to estimate AUMC is a numerical approximation method based on the linear trapezoidal method. A simulation study was performed to evaluate the precision of the methods and to compare them with corresponding methods for analysis of blood sample data. The estimates from the presently derived methods have a small bias and a small variance. In the simulation study I investigated the influence of model parameters, number of samples, size of statistical error, and the size of the AUC beyond the last sample. Finally, I have given numerical examples from real data to illustrate the use of the method.

Humans↗
PubMed2005

Early diagnosis of pancreatobiliary duct malignancies by brush cytology and biopsy.

Two hundred and five preoperative intraductal samplings (brushing and biopsy) were evaluated from 113 patients with biliary or Wirsung duct strictures. One hundred and three strictures could be specified by histology of the operative specimens, autopsy, or by the patients' clinical course. Preoperative diagnostic efficacy depended on the tumor location (it was the best for ampullary and para-papillary tumors), but the average quantitative indices for sensitivity, absolute sensitivity, specificity, positive and negative predictive values, diagnostic accuracy of cytology were 53%, 20%, 100%, 100%, 25%, 59%, respectively. The same values for biopsy were 43%, 34%, 100%, 100%, 36% and 56%. These figures improved after simultaneous cytology and biopsy. Close cooperation with the endoscopist was necessary in cases of negative, inconclusive and dysplastic (27%) samples. Repetition of sampling improved the results by 8%. Among the 26 preoperative false negative cases, sampling-, technical- and interpretative errors occurred in 84%, 4% and 12%, respectively. Revision of samples revealed 4 malignant cases among the false negative cytologic brushings. Reclassification of specimens considering the latest criteria - primary and secondary malignant features, pancreatic intraepithelial neoplasia (PanINs), etc. - resulted in improvement of the diagnostic efficiency.

Bile Duct Neoplasms↗
PubMed2005

Body mass index in elementary school children, metropolitan area food prices and food outlet density.

OBJECTIVE: The aim of this study was to examine the association between food prices and food outlet density and changes in the body mass index (BMI) among elementary school children in the USA. METHODS: The Early Childhood Longitudinal Study followed a nationally representative sample of kindergarten children over 4 years. We merged individual-level data to (a) metropolitan data on food prices and (b) per capita number of restaurants, grocery stores and convenience stores in the child's home and school zip code. The dependent variables were BMI changes over 1 and 3 years. We analysed mean changes with least-squares regression, and median changes and 85th percentile changes with quantile regression. We controlled for baseline BMI, age, real family income and sociodemographic characteristics. RESULTS: Lower real prices for vegetables and fruits were found to predict a significantly lower gain in BMI between kindergarten and third grade; half of that effect was found between kindergarten and first grade. Lower meat prices had the opposite effect, although this effect was generally smaller in magnitude and was insignificant for BMI gain over 3 years. Differences across subgroups were not statistically significant due to smaller sample sizes in subgroup analyses, but the estimated effects were meaningfully larger for children in poverty, children already at risk for overweight or overweight in kindergarten, and Asian and Hispanic children. There were no significant effects for dairy or fast-food prices, nor for outlet density, once we had controlled for individual characteristics and random intercepts to adjust standard errors for the sampling design. DISCUSSION: The geographic variation in fruit and vegetable prices is large enough to explain a meaningful amount of the differential gain in BMI among elementary school children across metropolitan areas. However, as consumption information was not available, we cannot confirm that this is the actual pathway. We found no effects of food outlet density at the neighbourhood level, possibly because availability is not an issue in metropolitan areas.

Body Mass Index↗