Determination of reference values

In order to construct a calibration model, the values of the parameters to be determined must be obtained by using a reference method. The optimum choice of reference method will be that providing the highest possible accuracy and precision. The quality of the results obtained with a multivariate calibration model can never exceed that of the method used to obtain the reference values, so the choice should be carefully made as the quality of the model will affect every subsequent prediction. The averaging of random errors inherent in regression methods can help construct models with a higher precision than the reference method. 

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The exclusion criteria may be relaxed. As already discussed, the set of relevant sources of biological variation differs among different analytes. One may define a minimum set of exclusion criteria for a given laboratory test. In the Kristianstad study, the complete group of individuals could probably be used for establishment of reference values (e.g., serum sodium), and most of the individuals would be acceptable for the determination of reference values for several other analytes. ... 

Reference values of a tumor marker are obtained from a healthy population, preferably with age- and sex-matched individuals. The determination of reference values is time-consuming and requires a large healthy population (n > 120 subjects). Statistical analysis using the mean 2 standard deviation (SD) for a population with a gaussian (normal) distribution is a frequently used method. For a nongaussian distribution, the percentile method is a simple approach and often used (for further discussion of reference values, see Chapter 16). 

Flachaire E, Beney C, Berthier A, Salandre J, Quincy C, Renaud B. Determination of reference values for serotonin concentration in platelets of healthy newborns, children, adults, and elderly subjects by HPLC with electrochemical detection. Clin Chem 1990 36 2117-20. 

Evaluation and interpretation of the DNT and comparative cholinesterase study data are conducted in accordance with agency risk assessment guidelines for developmental toxicity, reproductive toxicity, and neurotoxicity (EPA, 1991b, 1996, 1998e). Risk as.se.ssinents. including determination of reference values and application of traditional uncertainty factors in the calculations, are conducted ba.sed on historically established principles (NAS, 1983). 

The determination of AU values as well as the potential is effected by simple measurements of the difference in potential between two reference electrodes over the pipeline. To reduce possible electrode errors, partial sums can also be measured for a larger span, e.g., (a - O ) = 300 m ... 

For saturated hydrocarbons, exchange is too slow and reference points are so uncertain that direct determination of pAT values by exchange measurements is not feasible. The most useful proach to obtain pK data for such hydrocarbons involves making a measurement of the electrochemical potential for the reaction... 

Three types of the LFERs may be distinguished. The first group (A) includes expressions valid for a specific type of compound and certain processes. They are based on well-defined reference processes, which serve for the determination of the values of the constants These LFERs usually are named after the authors who have introduced them (Hammett, Taft, Brown, etc.), and special symbols for the parameters a and p are used (see Table I). The advantage of these established LFERs is the availability of... 

Bouman AA, Platenkamp AJ, Posma FD. 1986. Determination of aluminum in human tissues by flameless atomic absorption spectroscopy and comparison of references values. Ann Clin Biochem 23 91-101. 

A numerical analysis such as the one discussed above is best performed with a computer. Heat-transfer rates calculated from a variable-properties analysis can frequently differ by substantial amounts from a constant-properties analysis. The most difficult part of the analysis is, of course, a determination of the values of h. The interested reader is referred to the heat-transfer literature for additional information on this complicated but important subject. 

Establishment of reference values of general use requires general availability of a well-defined calibrator. The availability of such a calibrator also facilitates accreditation of procedures for quantitative determination of the corresponding analyte. Recombinant human cystatin C can easily be produced and isolated and used for establishing reliable calibrators (A2, Dl). A first step toward an international calibrator for cystatin C has been taken by the production of a solution of recombinant human cystatin C of high purity, determining the concentration of this... 

Optimal dietary intake is difficult to determine. Dietary Reference Intakes (DRIs) in the US are reference values that are quantitative estimates of nutrient intakes to be used for planning and assessing diets for apparently healthy people. DRIs are composed of reference values including Estimated Average Requirements (EARs), Recoimnended Dietary Allowances (RDAs), Adequate Intakes (AIs) and Tolerable Upper Intake Levels (ULs). Most nations have established the eqnivalent ofthe US DRIs. These are consensus and statistical valnes obtained from retrospective public health dietary studies, controlled experiments on metabolic wards, epidemiological surveys, isotopic tracer investigations, and extrapolation from animal models. 

Figure 50.9. Example of a non-spherical cell with directional dependence of diffusion. Primary laboratory frame of reference is given by X, y and z axes, while the primary axes of diffusion are given as Xjj (major), (intermediate) and (minor). Determination of the values of elements of the diffusion tensor allows determination of the magnitude and direction of the primary axes of diffusion (eigenvalues)...

Thienpont, L.M. Van Nieuwenhove, B. Reinuer, H. De Leenheer, A.P. Determination of reference method values by isotope dilution-gas chromatography-mass spectrometry A five years experience of two European reference laboratories. Eur. J. Clin. Chem. Clin. Biochem. 1996, 34, 853-860. 

Titration The determination of assay values for reference standards, counter-ions, or impurities can often be independently determined via titration. While titration assays generally have less selectivity in comparison to chromatographic methods, the advantages of a broad spectrum of classical titration techniques that exist for organic functional groups is often overlooked. The methodologies include not only classical potentiometric acid/base titrations but also nonaqueous, redox, indirect, precipitation, and derivatization titrations.76-79... 

The initial process in the application of toxicity (dose-response) data in risk assessment is the extrapolation of findings to establish acceptable levels (AL) of human exposure. These levels may be reference values (inhalation reference concentrations, RfC or oral reference doses, RfD), minimal risk levels (MRL) values, occupational exposure limits, and so on. When the toxicity data are derived from animals, the lowest dose representing the NOAEL (preferably) or the LOAEL defines the point of departure (POD). In setting human RfD, RfC, or MRL values, the POD requires several extrapolations (see [13] and revisions). Extrapolations are often made for interspecies differences, intraspecies variability, duration of exposure, and effect level. Each area is generally addressed by applying a respective uncertainty factor having a default value of 10 their multiplicative value is called the composite uncertainty factor (UF). The UF is mathematically combined with the dose at the POD to determine the reference value ... 

International Federation of Clinical Chemistry. Approved recommendation (1987) on the theory of reference values. Part 5. Statistical treatment of collected reference values. Determination of reference limits. J Clin Chem Clin Biochem 1987 25 645-56. 

It is often claimed that the analytical quality should be better when determining reference values than when producing routine values. This may be true for accuracy aU measures should be taken to eliminate bias. The question of imprecision is more difficult because it depends partly on the intended use of the reference values. Increases in analytical random variation result in widening of the reference intervals For some special uses of reference values, the narrower reference interval obtained by a more precise analytical method may be appropriate. However, this is usually not true... 

This section deals with two main topics the partitioning of reference values into more homogeneous classes and the determination of reference limits and intervals. The subject matter is presented in the order in which data often are treated. Figure 16-2 gives an outline and refers to the corresponding sections in the text. Before the presentation of the... 

ADDITIONAL TOPICS Transferability of Reference Values The determination of refiable reference values for each test in the laboratory s repertoire is a major task and is often far beyond the capabilities of the individual laboratory. It would therefore be convenient if reference values generated in another laboratory could be used. This is especially important when ethical considerations limit the number of available individuals (e.g., when producing pediatric reference values). Then, cooperative establishment of reference values may be necessary. 

International Federation of Clinical Chemistry, Expert Panel on Theory of Reference Values. Approved recommendation on the theory of reference values. Part 1. The concept of reference values. J CUn Chem Clin Biochem 1987 25 337-42 Part 2. Selection of individuals for the production of reference values. J Clin Chem Clin Biochem 1987 25 639-44 Part 3. Preparation of individuals and collection of specimens for the production of reference values. J Clin Chem Clin Biochem 1988 26 593-8 Part 4. Control of analytical variation in the production transfer and application of reference values. Eur J CUn Chem Clin. Biochem 1991 29 531-5 Part 5. Statistical treatment of collected reference values Determination of reference limits. J Clin Chem... 

The deconvolution methods are multi-wavelength procedures which can be classified with regard to the selection procedure of reference spectra. These spectra can be chosen from specific compounds (Maier, 1981), from independent spectra of real samples (Thomas et al., 1993), statistically selected (Gallot and Thomas, 1993) or from a mixed choice of spectra of specific compounds and of real samples. Reference spectra are not universal recently, according to the complexity of the composition of wastewater, SECOMAM has developed UVPro software based on advanced UV spectral deconvolution (Patent 00402038-4, 17 July 2000) which allows creating dedicated models and determination of reference spectra from a set of studied water and wastewater UV spectra an automatic calibration step is carried using parameters values obtained by standard or reference method. Deconvolution is used in order to find a linear relation between measured and UV estimated values for any parameter. 

Ibid, 37, 635-42 (1948). Determination of industrial value of detergents, with 31 refer-... 

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