Traceable measurements in clinical laboratories

 Reliable, traceable and comparable measurements provide the rational basis for evaluation of the quality of a result and the starting point for recognized laboratory accreditation in any national area. Modern medical diagnostics and treatment involve rapidly rising numbers and types of clinical laboratory measurements, that are reliable. Therefore, the basic principles to be followed to assure the traceability of clinical measurements as required by the Romanian Laws of Metrology are reviewed. Main sources affecting the quality of the unbroken chain of calibrations that relate the measurements back to appropriate measurement standards are discussed. Examples of how to achieve traceable measurements in clinical laboratories are presented. Details of specific uses of reference materials, measuring instruments and standard measurement methods are also discussed. Received: 8 January 1998 · Accepted: 21 April 1998     

A statistical method to detect chromosomal regions with DNA copy number alterations using SNP-array-based CGH data

Single nucleotide polymorphism (SNP) arrays were used to detect chromosomal regions with DNA copy number alterations. Current statistical methods for microarray-based comparative genomic hybridization (array-CGH) analysis generally assume certain relationships among adjacent markers on the same chromosome, and these assumptions may be questionable. For an SNP-array-based CGH study, multiple normal reference SNP arrays were collected. In order to utilize these normal reference SNP arrays, we derived an empirical distribution of signal ratios for each SNP marker. With an assumed threshold value for the overall error rate control and the defined signal ratio ranges for chromosomal amplification and deletion, we proposed a procedure to identify chromosomal alteration regions based on several bootstrapped one-sample t-tests and the false discovery rate control. When we have multiple arrays for different individuals with the same disease, our method can also be used to detect SNP markers for chromosomal alteration regions that are common among these individuals. We applied our method to a published SNP array data set for breast carcinoma cell lines. For an individual with breast cancer, numerous chromosomal alteration regions were identified. Compared to results of previous studies, our method identified more chromosomal alteration regions, with some being implicated in the literature to harbor genes associated with breast cancer. For multiple cancer arrays, our results suggested the existence of common chromosomal alteration regions. However, a high proportion of false positives also indicated that genetic variations among different individuals with breast cancer can be present.     

The application of the measurement uncertainty concept to in-process control in pharmaceutical development

 Any analytical data is used to provide information about a sample. The "possible error" of the measurement can be of extreme importance in order to have complete information. The measurement uncertainty concept is a way to achieve quantitative information about this "possible error" using an estimation procedure. On the basis of the analytical result, the chemist makes a decision on the next step of the development process. If the uncertainty is unknown, the information is not complete; therefore this decision might be impossible. The major problem for the in-process control (IPC) procedure is that not only the repeatability but also the intermediate precision (which expresses the variations within laboratories related to different days, different analysts, different equipment, etc.) has to be good enough to make a decision. Unfortunately, the statistical information achieved from one single analytical run only gives information about the repeatability. This paper shows that the estimation of the measurement uncertainty for IPC is a way to solve the problem and gives the necessary information about the quality of the procedure. An example demonstrates that an estimate of uncertainty based on the standard deviations of an analytical method gives a value similar to one based on the standard deviations obtained from a control chart. Therefore, the estimation is both a very useful and also a very cost-effective tool. Though measurement uncertainty cannot replace validation in general, it is a viable alternative to validation for all methods that will never be used routinely. Received: 24 May 1996 Accepted: 10 August 1996     

丙酮中除虫脲溶液标准物质研制

采用重量-容量法制备丙酮中除虫脲溶液标准物质。准确称量国家二级标准物质除虫脲溶解到色谱纯丙酮中,通过A级容量瓶定容至500 mL,摇匀后分装到2 mL安瓿瓶内共460瓶,每瓶为1 mL,保持低温迅速封口,配制过程中室温保持在(20±2)℃。采用液相色谱法进行均匀性、稳定性检验和定值结果验证。从样品中随机抽取16瓶进行均匀性检验,经F检验表明,在95%的置信区间范围内该标准物质均匀性良好;采用t检验对标准物质稳定性进行检验,标准物质在12月内稳定性良好。对该标准物质的不确定度进行了评定,研制的丙酮中除虫脲溶液标准物质定值结果为100μg/mL,相对扩展不确定度为2%(k=2)。结果表明,该标准物质均匀性与稳定性良好,量值准确,可用于日常分析检测中的方法评价和仪器校准。     

Estimation of uncertainty in routine pH measurement

A procedure for estimation of measurement uncertainty of routine pH measurement (pH meter with two-point calibration, with or without automatic temperature compensation, combination glass electrode) based on the ISO method is presented. It is based on a mathematical model of pH measurement that involves nine input parameters. Altogether 14 components of uncertainty are identified and quantified. No single uncertainty estimate can be ascribed to a pH measurement procedure: the uncertainty of pH strongly depends on changes in experimental details and on the pH value itself. The uncertainty is the lowest near the isopotential point and in the center of the calibration line and can increase by a factor of 2 (depending on the details of the measurement procedure) when moving from around pH 7 to around pH 2 or 11. Therefore it is necessary to estimate the uncertainty separately for each measurement. For routine pH measurement the uncertainty cannot be significantly reduced by using more accurate standard solutions than ±0.02 pH units – the uncertainty improvement is small. A major problem in estimating the uncertainty of pH is the residual junction potential, which is almost impossible to take rigorously into account in the framework of a routine pH measurement.¹ Received: 11 August 2001 Accepted: 22 February 2002     

基于不确定指数O-U过程带有浮动利率模型的亚式期权定价

不确定金融是不确定理论在现代金融领域的一种应用,在解决金融问题中发挥着越来越重要的作用。而利率是一个重要的经济指标,经常受到一些不确定因素的影响,在研究期权定价时,有必要考虑浮动利率。本文提出了一种新的不确定指数Ornstein-Uhlenbeck过程模型,假设利率服从不确定均值回复过程,研究了期权定价问题,运用α-轨道方法,分别推导了亚式看涨期权和看跌期权定价公式。最后,设计了计算期权价格的数值算法,并给出数值算例。     

Including correlation effects in an improved spreadsheet calculation of combined standard uncertainties

A spreadsheet method allowing rapid calculation of combined standard uncertainties is described. The model used allows explicitly for correlation effects, and requires a user to enter only the parameters, the calculation used to obtain the final result (including relevant influence factors), the individual standard uncertainties for the parameters, and estimates of correlation coefficients where necessary. The estimation of correlation coefficients in common cases is discussed, and it is shown that correlation is likely to be practically significant only when the correlated contribution to individual standard uncertainties is significantly over about 30% of the relevant standard uncertainty, leading to correlation coefficients |r| greater than 0.1. The implementation includes a more robust differentiation algorithm than previously reported for spreadsheet use, and initial preparation of the spreadsheets has been automated. The principle is illustrated with a simple example. Electronic Supplementary Material  Supplementary material is available in the online version of this article at and is accessible for authorized users.

Uncertainty of the Thermal Conductivity Measurement Using the Transient Hot Wire Method

This work deals with uncertainty analysis of the thermal conductivity measurement using the transient hot wire method. The characterization is made from a sample of low-density, polyethylene BRALEN SA 200-22. The utilized experimental data are obtained from the test measurements performed on the air at room temperature. The sources of measurement errors are analyzed and the uncertainty of the measured value of the thermal conductivity is evaluated. The analysis shows that in the present case the uncertainty of the thermal conductivity measurement is about ±3.3% for 68% confidence level.This revised version was published online in November 2005 with corrections to the Cover Date.     

Evaluation of the limit of performance of an analytical method based on a statistical calculation of its critical concentrations according to ISO standard 11843: Application to routine control of banned veterinary drug residues in food according to European Decision 657/2002/EC

Traceability of the measurement of analytical parameters capable of evaluating the performance of methods is an important concept for the assessment of quality for the routine control, especially for residue monitoring of non-authorized medicinal substances in food from animal origin. The European Decision no. 657/2002/EC recommends to calculate two statistical limits, CCα and CCβ, which allow to evaluate the critical concentrations above which the method reliably distinguish and quantify a substance taking into account the variability of the method and the statistical risk to take a wrong decision. The calculation, which can be derived from the ISO standard no. 11843 is applied on a routine basis. An example displays a very simple way for evaluating the performance of an LC-MSMS method which has been validated a few years ago and is qualified onto a Micromass Quattro LCZ tandem mass spectrometer to monitor and confirm the nitrofuran metabolite residues in food from animal origin. Community Reference Laboratory for Antimicrobial Veterinary Drug Residue Control in Food from Animal Origin     

关于铀同位素标准物质的几个问题

讨论了铀同位素标准物质(UIRM)研制中的一些技术问题,如IRM中同位素丰度的定值,IRM不确定度的影响因素等,并介绍了国内外UIRM研制情况。