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Minimizing interlaboratory variation in routine assays of serum cholesterol through the use of serum calibrators.

A cholesterol standardization program was developed in The Netherlands for clinical laboratories that use their analytical results as indicators of cardiovascular risk. Participants with sufficient precision but inaccurate results are encouraged to use serum-based calibrators as a means to decrease bias. A regional pilot survey and thereafter a national one were carried out in 31 and 138 laboratories, respectively, to investigate whether use of the serum-calibration procedure could improve routinely performed cholesterol measurements. To participants in our national quality-control surveys were mailed three calibrators (pooled human serum) and five human-serum controls, for analysis of cholesterol on four different days. Reference method values had been assigned to the calibrators by the Netherlands Reference Laboratory, applying the U.S. Centers for Disease Control modification of the Abell-Kendall procedure. Using the calibration curves based on results for the serum calibrators decreased the between-laboratory variation (SD) by at least 50%, with improved accuracy for non-enzymatic methods. The initial within-laboratory precision was generally good, and improvements in it were small. To our knowledge, standardization results involving so many routine hospital laboratory procedures have not been previously reported.

Calibration↗

Results of calibration by the Dutch National Reference Laboratory of the thromboplastins included in the ICTH/ICSH collaborative study of prothrombin time standardization.

Results obtained with the original calibration procedure of Biggs and Denson obtained by one expert laboratory compare well with those obtained from the ICTH/ICSH collaborative study. The simplified calibration procedure described in 1975 should only be used for the assessment of inter-batch variability of a given brand of thromboplastin; for the calibration of unlike thromboplastins, the simplified procedure should be revised by using more than two abnormal plasmas, e.g. different plasmas representing seven levels of anticoagulation between international calibrated ratios (ICRs) from 1.5 to 4.5. The formula for the calculation for the proposed ICRs based on the calibration constant should be modified to allow for instances where the calibration line for dissimilar thromboplastins, fitted in the therapeutic range, does not pass through the origin of ratio 1,1.

Blood Preservation↗

Assay of cortisol with a radioimmunoassay method calibrated by isotope dilution-mass spectrometry. A Nordic collaborative study.

A reference method for serum cortisol, based on isotope dilution-mass spectrometry (ID-MS), was compared with a modified commercial RIA method. The modification solely concerned the calibration standards used in the RIA method. These were replaced by a series of human serum samples, in which the concentration of cortisol had been determined by the reference ID-MS method. The samples were selected so as to cover the whole range of the standard curve. Serum samples from healthy, untreated subjects with cortisol concentrations 270-1134 nmol/l were analysed with the ID-MS calibrated RIA method in four laboratories, one in each of the four Nordic countries. The results from two of the four laboratories did not differ significantly from the ID-MS values (P less than 0.05), whereas the results from the other two laboratories differed slightly. The mean values based on results from all four laboratories were almost identical with the values obtained with the reference method. In addition, serum samples from 11 patients with endocrine disorders with cortisol concentrations 31-916 nmol/l were analysed in three of the four laboratories. In three of the samples significant differences were observed between the values obtained with the ID-MS and the ID-MS calibrated RIA method. The value obtained with the ID-MS calibrated RIA was however always more accurate than the corresponding value obtained with RIA with the use of a commercial calibration standard. Advantages of the present model in increasing the accuracy of routine analysis by RIA are discussed. The possibility is further discussed that the ID-MS calibrated RIA method may be used as a 'secondary reference method'.

Adult↗

The usefulness of calibration verification and linearity surveys in predicting acceptable performance in graded proficiency tests.

OBJECTIVE: To assess the association between performance on graded chemistry surveys and evaluation of linearity and calibration in Linearity surveys. DESIGN: Data from Linearity Surveys (LN series) and from routine comprehensive College of American Pathologists chemistry surveys (all series) were used to evaluate the hypothesis that laboratories with nonlinear or univerified calibration would have a greater likelihood of unacceptable performance on comprehensive chemistry surveys. RESULTS: This study found that acceptable calibration verification evaluation is significantly related to acceptable rates for most analytes, including albumin, calcium, chloride, glucose, iron, magnesium, sodium, total bilirubin, uric acid, high-density lipoprotein cholesterol, triglycerides, alkaline phosphatase, alanine and aspartate aminotransferase, digoxin, gentamicin, phenobarbital, procainamide, and thyroxine. CONCLUSION: There is a consistent and strong relationship between calibration verification problems in the Linearity Surveys and failure rates in the College of American Pathologists chemistry surveys. Laboratories with poor calibration evaluations on Linearity Surveys have higher unacceptable rates on proficiency tests. Individual laboratories who were rated linear and whose calibration was verified by Linearity Surveys have lower unacceptable rates.

Calibration↗

[Physical technical calibration of a new self-tonometer].

The microprocessor-controlled applanation tonometer was calibrated in force measurement and area detection by using weights and silicon calibration pistons. This makes it possible to compare the technical precision of the instrument under standardized conditions and the results of previous clinical examinations. With the instrument in a vertical position, the force measurements meets the official calibration requirement. Force measurements in a horizontal position will follow in order to demonstrate that exact measurements can be taken with the instrument irrespective of position. A suitable method for calibrating the optical sensor by using the silicone pistons for area detection is shown. This method is to be extended by using calibration pistons of different diameters, which are within the permitted calibration tolerances.

Calibration↗

Accurate measurement of copper-67 in the presence of copper-64 contaminant using a dose calibrator.

UNLABELLED: The use of 67Cu-labeled antibodies for the treatment of cancer has advanced to the clinical trial phase. Quantitation of 67Cu radiopharmaceuticals is complicated by the presence of the radioimpurity of 64Cu in 67Cu supplies. Here we report a method to assay 67Cu and 64Cu in a mixed sample with a commonly available instrument, the ionization chamber dose calibrator. METHODS: The activities of 67Cu and 64Cu in a mixed sample can be calculated from a single-dose calibrator measurement. The calculation requires (1) instrument-specific response coefficients D67 and D64, generated by gauging the instrument for the efficiency of measurement of 67Cu and 64Cu, and (2) a value for the ratio of 67Cu to 64Cu in the sample, routinely provided by major suppliers of 67Cu. D67 and D64 were empirically determined by measuring samples containing known amounts of 67Cu and 64Cu. The samples were also assayed by gamma ray spectroscopy to verify the isotope ratios given by the suppliers. RESULTS: This method generated accurate response coefficients. At the recommended dose calibrator setting for the measurement of 67Cu, at which D67 = 1.0, the measurement for D67 with this method was 1.02 (+/- 0.04). Isotope ratios provided by the radionuclide suppliers were corroborated by gamma ray spectroscopy. CONCLUSION: A method is presented by which 67Cu and 64Cu in a mixed sample can be assayed using a dose calibrator. Although the derived numeric constants are only correct for a specific dose calibrator and setting, the method can be adapted for use with any dose calibrator.

Calibration↗

A simplified procedure for thromboplastin calibration--the usefulness of lyophilized plasmas assessed in a collaborative study.

The International Sensitivity Index (ISI) of thromboplastins is determined by calibration using fresh plasmas from 60 patients stabilized on oral anticoagulants and 20 healthy subjects. This procedure is demanding, particularly for those who have no easy access to patients. The alternative use of a smaller number of lyophilized plasmas has already been considered, but one important issue, the number of repeated measurements to be carried out, has never been addressed. Two commercial rabbit thromboplastins, A and B, were calibrated in 3 laboratories against CRM 149R. On each of 10 working days, prothrombin times were measured for a different set of 8 fresh plasmas and for the same set of 8 lyophilized plasmas. The ISI values for both thromboplastins were estimated by orthogonal regression on fresh and lyophilized plasmas. The between- and within-laboratory CV values of the estimated ISI were taken as measures of precision of the calibration. In addition, ISI and CV were calculated daily on cumulative results obtained with lyophilized plasmas from day 1 to day 10. The ISI values for both thromboplastins calculated with lyophilized plasmas were not significantly different from those with fresh plasmas (mean of 3 laboratories: 1.42 vs 1.48 for A and 1.22 vs 1.20 for B). The between-laboratory precision of the calibration with lyophilized plasmas was not considerably different from that with fresh plasmas (CV for 3 labs: 5.2% vs 6.8% for A and 0.9% vs 2.2% for B). The ISI estimated with lyophilized plasmas on results of day 1 were not different from those of days 2 through 10. Good within-laboratory precision of the calibration (CV around 2%) was already achieved on day 3. In conclusion, this study shows that lyophilized plasmas pooled from normals and patients on oral anticoagulants can be used as substitutes for individual fresh plasmas to simplify the existing procedure for thromboplastin calibration.

Anticoagulants↗

In-situ calibration of the implantable force transducer.

Recently, an implantable force transducer (IFT) has been introduced [Xu et al. (1992, J. Biomech. Engng 114, 170-177)] which can be used in tight spaces where force recordings with established transducers, such as the buckle-type transducers, are not possible because of impingement artifacts. The IFT is easily implanted in chronic animal preparations; however, calibration of the IFT in terminal experiments has produced unreliable results. The problems of IFT calibration are that minute movements of the transducer within the tendon, slight misalignments of the tendon, or slight errors in the line of pull cause dramatic changes in the IFT voltage output for a given applied calibration load. Here, we propose a method that eliminates the above calibration problems primarily because the target tendon is left in situ, the calibration loads are applied by the muscles which insert into the target tendon, and the transducer is implanted into the target tendon about two weeks prior to calibration. The theoretical and experimental approaches are demonstrated for the cat patellar tendon, but in principle can be performed with any tendon. The results are repeatable, lie within expected values, and reproduce some of the basic properties which have been observed in prior IFT testing.

Algorithms↗

Index of Orthodontic Treatment Need, its use in a dental epidemiology survey calibration exercise.

The Index of Orthodontic Treatment Need (IOTN) was included in a pre-survey calibration exercise of 18 dental epidemiologists. Nine months later 16 of the epidemiologists were re-calibrated in the IOTN. The Index was readily accepted by the experienced dental epidemiological examiners and each examination was estimated to be extended by, on average, less than two minutes. The inter-examiner agreement of the dental health component using the weighted kappa statistic improved from a mean of 0.53 (moderate agreement) for the first calibration to 0.66 (good agreement) at the second calibration. The mean inter-examiner agreement on the aesthetic component using the weighted kappa statistic reduced from 0.52 for the first calibration to 0.49 at the second. Using sensitivity and specificity to measure agreement on the dichotomous decision of those defined as having a definite treatment need, mean sensitivity rose from 0.72 to 0.79 and specificity from 0.90 to 0.97. It is concluded that dental examiners for epidemiological surveys can be trained to use the IOTN by using a pre-calibration exercise and that agreement on the dental health component improves after the index has been used for some months.

Adolescent↗

Consistency in calibrated backscattered electron images of calcified tissues and minerals analyzed in multiple imaging sessions.

Pure metal standards have been used to calibrate the operating envionment in quatitative backscattered electron (BSE) imaging of mineralized tissue, allowing comparisons to be made between various mineralization states of bone at the microscopic level. It has not previuously been documented that calibration procedures produce consistent, reliable results over multiple imaging sessions. In this study, BSE images were obtained from bones, pure metals, and a naturally occurring mineral in multiple imaging sessions over a six day period. The graylevel histogram profile (GHP) from each specimen was analyzed for changes in the shape and relative placement on the graylevel spectrum. Computer controlled calibration and a restrospective calibration method using pure aluminum and pure magnesium-aluminum-zinc demonstrated consistency between imaging sessions. Calibrated weighted mean graylevels (WMGLs) for biological meterials had an average standard deviation of 5.9 graylevels (2.4% variation) during the course of the study. WMGLs for inorganic materials had an average standard deviation of 0.9 graylevels (0.4% variation). A trend towards increased image brightness, due to specimen and/or embedding media degradation, was observed in the biological tissues. No increase in rightness was observed for the inorgtanic specimens. Kurtosis and skewness tests revealed a slight deviation from normality in all specimens, which remained consistent between multiple imaging sessions. These results demonstrate the BSE image analysis of bones and mineral can be calibrated with negligible precision error allowing comparisons between data within and between multiple imaging sessions.

Aluminum↗

Calibration of force-field dependency in free energy landscapes of peptide conformations by quantum chemical calculations.

The free energy landscapes of peptide conformations were calibrated by ab initio quantum chemical calculations, after the enhanced conformational diversity search using the multicanonical molecular dynamics simulations. Three different potentials of mean force for an isolated dipeptide were individually obtained by the multicanonical molecular dynamics simulations using the conventional force fields, AMBER parm94, AMBER parm96, and CHARMm22. Each potential of mean force was then calibrated based upon the umbrella sampling algorithm from the adiabatic energy map that was calculated separately by the ab initio molecular orbital method, and all of the calibrated potentials of mean force coincided well. The calibration method was also applied to the simulations of a peptide dimer in explicit water models, and it was shown that the calibrated free energy landscapes did not depend on the force field used in the classical simulations, as far as the conformational space was sampled well. The current calibration method fuses the classical free energy calculation with the quantum chemical calculation, and it should generally make simulations for biomolecular systems much more reliable when combining with enhanced conformational sampling.

Models, Molecular↗

Calibrated magnetic resonance hydrometry: an in vitro study.

PURPOSE: To demonstrate a quantitative approach to measuring fluid volumes with standard single shot RARE sequences. MATERIALS AND METHODS: In phantom experiments, magnetic resonance hydrometry (MRH), in combination with various calibration phantoms (5 mL up to 500 mL) as internal standards, was used to quantify fluid volumes. In total, 16 volume phantoms were investigated with six different calibration phantoms. In addition, noise correction was implemented to correct the quantification results and to avoid the influence of random noise in the image. RESULTS: All MR measurements show significant correlations of up to r = 0.99 (P <.05) with the real applied volume in the investigated phantoms. However, measurements of large volumes were more precise with large calibration phantoms. Noise reduction did not change the correlation between measured and real applied volumes, but did reduce the error of the measured volumes. Calibrated magnetic resonance hydrometry (cMRH) is able to quantify volumes of fluid fast and noninvasively. The volumes of the used calibration phantoms have to be at least in the order of magnitude of the volumes that are to be measured. CONCLUSION: In vitro, cMRH using a single-shot rapid acquisition with refocused echoes (ssRARE) sequence and calibration phantoms is a fast and accurate method of quantifying steady amounts of fluid.

Algorithms↗

Calibration of Comprehension: Research and Implications for Education and Instruction.

The ability to accurately evaluate one's understanding of text information is critical for optimum learning to take place. One widely used paradigm for examining the accuracy of individuals' self-assessed comprehension has been termed calibration of comprehension. In this paradigm, students read a passage and are asked to make predictions about their future performance on a comprehension test. Calibration of comprehension is the relation between students' confidence and performance or between predicted and actual performance. In the present paper we review research on calibration of comprehension, examining a number of variables that have been found to influence calibration ability. In the first three sections of our paper we focus on the effects of individual, task, and text variables on students' calibration of comprehension. In the final section, we discuss implications of research on calibration for education and instruction. Copyright 1998 Academic Press.

Journal Article↗

Children and chess expertise: the role of calibration.

Three studies of calibration are reported. Calibration refers to the accuracy with which one can predict one's own performance. In the first study child chess players, non-chess playing parents, and statistics students were asked to predict chances of winning chess games against hypothetical opponents. These subjective probabilities were compared to the actual probabilities, based on the Elo rating system. Better players' predictions were better calibrated. Confidence and ratings are negatively correlated, indicating that with lower ratings, players re overconfident. Skilled child players' predictions were better calibrated than any of the adults'. In the second study subjects were asked to estimate chances of winning in conjunctive situations, e.g., winning all the rounds in a tournament. Again, better child players were more accurate in their predictions and more accurate than adults. In the third study, child players were asked to predict their chances of winning in a non-chess domain after hearing a hypothetical win/loss history. Higher-rated players' predictions were again better calibrated, even though the domain was outside their expertise. The motivational and cognitive implications of calibration are discussed.

Achievement↗

Application of glow discharge mass spectrometry to multielement ultra-trace determination in ultrahigh-purity copper and iron: a calibration approach achieving quantification and traceability.

A new approach was developed for quantitative calibration in GD-MS which can afford reliable and metrologically traceable results for many trace elements and was exemplified for pure copper and pure iron. It can be assumed that the technique can be further improved and applied to the analysis of other pure metals. Pressed copper and iron powder samples were used to calibrate the glow discharge mass spectrometry applied to the analysis of pure copper and iron. The new type of glow discharge mass spectrometer--the Element GD (Thermo Electron Corporation)--was used with a Grimm-type discharge cell for flat samples. Two series of powder samples were prepared for each of the copper and iron matrixes. The powders were quantitatively doped with solutions of graduated and defined concentrations of 40 or 20 analytes, respectively. The mass fractions of the analytes in the dried and homogenized metal powder samples ranged from microg/kg levels up to 10 mg/kg levels. A special technique was developed to press the samples and to form mechanically stable pellets with low risk of contamination. Ion beam ratios of analyte ions to matrix ions were used as measurands. The calibration curves were determined and the linear correlation coefficients were calculated for different intervals of the curves. The linear correlation coefficients are very satisfactory for most of the calibration curves, which include the higher segments of mass fractions; however, they are less satisfactory for the lower segments of the calibration curves. Nevertheless, in many cases rather acceptable and rather promising values were achieved even for these lower segments, representing mass fractions of analytes at ultra-trace level. The comparison of the certified values of different reference materials with the measured values based on calibrations with the pressed powder samples led to deviations less than 30% for most of the considered examples.

Journal Article↗

[Coronary risk estimation in Spain using a calibrated Framingham function].

INTRODUCTION AND OBJECTIVES: The Framingham coronary heart disease (CHD) functions overestimate the risk of CHD in countries with a low incidence. Consequently, these functions should be calibrated for the purpose of primary prevention. Calibrated Framingham function charts of overall CHD risk for the Spanish population are presented. Patients and methods. The Framingham functions were calibrated by substituting the prevalence of CHD risk factors and incidence found in Framingham with the same values for Spain. The Framingham function that included high-density lipoprotein (HDL) cholesterol was used. The 10-year probability of developing a CHD event was estimated for several combinations of risk factors and HDL levels ranging from 35 to 59 mg/dl. Color-coded charts were prepared that show the exact probability of CHD corresponding to each combination of risk factors, shown in separate cells on the chart. RESULTS: The event rate and prevalence of CHD risk factors differed considerably between Girona and Framingham. HDL < 35 mg/dL increased risk by approximately 50% and HDL > 60 mg/dL reduced it by 50%. The proportion of cells in which the 10-year probability of developing a CHD event was > 9% was 2.3 times higher and that of cells with a probability > 19% was 13 times lower in the chart calibrated for Spain than in the original Framingham charts. CONCLUSIONS: The calibrated Framingham function may help to more accurately estimate the overall risk of CHD in the Spanish population for primary prevention purposes. The calibrated function should be validated, and the development of functions for the Spanish population should be promoted.

Algorithms↗

Experimental determinations of commercial 'dose calibrator' settings for nuclides used in nuclear medicine.

Commercial reentrant ionization chambers ('dose calibrators') have become the de facto standard instrument for making radioactivity measurements in the radiopharmaceutical industry. Accurate activity measurements, however, depend on the application of the correct calibration factor (dial setting) for the radionuclide in the exact measurement geometry for that particular instrument. Two methods are described for the experimental determination of dial settings for the Capintec CRC-12 dose calibrator. Using these methods, we have determined new calibration factors for 18F, 62Cu, 186Re and 188Re in several geometries. These new factors are presented, along with previously determined settings, for nuclides commonly used in nuclear medicine. The differences between the calibration factors for the different geometries, as well as the differences between the manufacturer's recommended setting underscore the need for empirically determined dose calibrator settings.

Radioisotopes↗

Determination of total sulfur in diesel fuel employing NIR spectroscopy and multivariate calibration.

A method for sulfur determination in diesel fuel employing near infrared spectroscopy, variable selection and multivariate calibration is described. The performances of principal component regression (PCR) and partial least square (PLS) chemometric methods were compared with those shown by multiple linear regression (MLR), performed after variable selection based on the genetic algorithm (GA) or the successive projection algorithm (SPA). Ninety seven diesel samples were divided into three sets (41 for calibration, 30 for internal validation and 26 for external validation), each of them covering the full range of sulfur concentrations (from 0.07 to 0.33% w/w). Transflectance measurements were performed from 850 to 1800 nm. Although principal component analysis identified the presence of three groups, PLS, PCR and MLR provided models whose predicting capabilities were independent of the diesel type. Calibration with PLS and PCR employing all the 454 wavelengths provided root mean square errors of prediction (RMSEP) of 0.036% and 0.043% for the validation set, respectively. The use of GA and SPA for variable selection provided calibration models based on 19 and 9 wavelengths, with a RMSEP of 0.031% (PLS-GA), 0.022% (MLR-SPA) and 0.034% (MLR-GA). As the ASTM 4294 method allows a reproducibility of 0.05%, it can be concluded that a method based on NIR spectroscopy and multivariate calibration can be employed for the determination of sulfur in diesel fuels. Furthermore, the selection of variables can provide more robust calibration models and SPA provided more parsimonious models than GA.

Journal Article↗