Estimation of uncertainties in clinical analysis

 Owing to the importance of clinical analysis for human health, it is necessary to have reliable analytical information. Considering that the reliability of analytical information is a complex function of uncertainties of the sample, method, instrumentation, and data processing, it should be observed that the maximum reliability of analytical information is obtained by minimization of uncertainty values. Applying this concept to clinical analysis, the role of spectrometric and electrometric methods is highlighted.     

Some remarks on the information power and selectivity of analytical processes

The consistency of the equation given by Shannon for the transfer of maximum amount of information in one channel, and the equation deduced by Kaiser for the expression of the information power of analytical methods is shown. The fundamental difference between the maximum amount of information obtainable by an instrument and that by an analytical procedure is reported. In the second case the selectivity of the analytical procedure also has to be taken into consideration.     

Application of reference materials for quality assessment in neutron activation analysis-use of information theory

It is generally accepted that an analytical procedure can be regarded as an information production system yielding information on the composition of the analyzed sample. Thus, information theory can be useful and the quantities characterizing the information properties of an analytical method may be applied not only as evaluation criteria but also as objective functions in the optimization. The usability of information theory is demonstrated on the example of neutron activation analysis. Both precision and bias of NAA results are taken into account together with the possible use of reference materials for quality assessment. The influence of the above-mentioned parameters on information properties such as information gain and profitability of NAA results is discussed in detail. It has been proved that information theory is especially useful in choosing suitable reference materials for the quality assessment of routine analytical procedures not only with respect to matrix and analyte concentration in the sample but also to concentrations and uncertainties of certified values in the CRM used. In the extreme trace analysis, CRMs with relatively large uncertainties and very low certified concentrations can still yield rather high information gain of results.     

Estimation of the limit of detection using information theory measures

Definitions of the limit of detection (LOD) based on the probability of false positive and/or false negative errors have been proposed over the past years. Although such definitions are straightforward and valid for any kind of analytical system, proposed methodologies to estimate the LOD are usually simplified to signals with Gaussian noise. Additionally, there is a general misconception that two systems with the same LOD provide the same amount of information on the source regardless of the prior probability of presenting a blank/analyte sample. Based upon an analogy between an analytical system and a binary communication channel, in this paper we show that the amount of information that can be extracted from an analytical system depends on the probability of presenting the two different possible states. We propose a new definition of LOD utilizing information theory tools that deals with noise of any kind and allows the introduction of prior knowledge easily. Unlike most traditional LOD estimation approaches, the proposed definition is based on the amount of information that the chemical instrumentation system provides on the chemical information source. Our findings indicate that the benchmark of analytical systems based on the ability to provide information about the presence/absence of the analyte (our proposed approach) is a more general and proper framework, while converging to the usual values when dealing with Gaussian noise.     

Measurement uncertainty – a reliable concept in food analysis and for the use of recovery data?

 Steps which are taken to implement the concept of measurement uncertainty in analytical chemical laboratories should take full account of existing internationally agreed protocols for analytical quality assurance and reflect the needs of particular analytical sectors. For the food sector this may mean that for official purposes the use of the term measurement uncertainty is replaced by the term measurement reliability and that a quantitative estimation of this is made based on existing collaborative trial data. In many analytical sectors, the differing strategies currently followed for the determination and use of recovery information are an important cause of the non-comparability of analytical results. Guidelines which are being prepared for the estimation and use of recovery information in analytical measurement may provide a more unified approach which includes measurement uncertainty as a key concept in the use of recovery data. Received: 4 November 1997 · Accepted: 3 February 1998     

Informationsgewinn bei analytisch-chemischen Messungen

Summary The aim of every analytical experiment is to gain information about a particular chemical system. In order to design and carry out such an experiment it is necessary to take into consideration the chemical properties of the matter as well as the metrological rules inherent in the analytical method applied. In this aim (to obtain information) and in the manner of working (to regard chemical properties and metrological rules) analytical chemistry can be seen as being a uniform and independent scientific discipline. The different analytical methods and the numerous analytical problems can then be described in uniform manner. The different measuring parameters and steps in analytical work can all be reduced to uniform terms and processes. The treatment and evaluation of the signal produced in the analytical experiment is always at the centre of all discussions. The uniform theoretical interpretation of seemingly different methodological terms makes a standardized nomenclature possible. The aim of effectively obtained information explains the preference of certain analytical methods for trace analysis, structure analysis, multicomponent analysis or other analytical problems. Furthermore, it is possible to derive useful strategies for applying an analytical method or managing an analytical problem. Finally, tendencies can be shown for the development of analytical methods, which are particularly effective in obtaining information.     

Molecular spectroscopy in forensic residue analysis: a general overview of reliability, applicability and cost effectiveness

Classification of an analytical result for forensic purposes is briefly discussed, in addition to mandatory specificity and limits of appropriate analytical methods. Direct information on the molecular structure of the analyte is in general more reliable than indirect information. Direct information is obtained from molecular spectroscopic methods, in contrasts to chromatographic or immunochemical methods, which provide only indirect information. The cost effectiveness ratio as calculated per analyte is indicated for various analytical techniques.     

Analytical chemical methods as systems producing chemical information by inference

Summary Analytical chemical methods as systems produce chemical information about the material to be analyzed. Analytical chemical systems as semiosis consist of analytical signal production and analytical chemical signal interpretation and produce chemical information by inference in an indirect way through analytical information. From the logical point of view the chemical information produced by analytical chemical systems is only credible. Generalizing the results the idea of diagnostic systems can be introduced and the analytical chemical methods as systems are a special type of diagnostic systems.

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Chemisch-analytische Systeme zur Erlangung chemischer Informationen

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Presented at the First International Symposium on History and Philosophy in Analytical Chemistry, Vienna, November 22–23, 1985     

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     

Evaluation of the analytical method performance for incurred samples

A methodology for the evaluation of the performance of an analytical method for incurred samples is presented. Since this methodology is based on intra-laboratory information, it is suitable for analytical fields that lack reference materials with incurred analytes and it can be used to evaluate the analytical steps prior to the analytical portion, which are usually excluded in proficiency tests or at the certification of reference materials. This methodology can be based on tests performed on routine samples allowing the collection of information on the more relevant combinations analyte/matrix; therefore, this approach is particularly useful for analytical fields that involve a high number of analyte/matrix combinations, which are difficult to cover even considering the frequent participation in expensive proficiency tests.This approach is based on the development of a model of the performance of the analytical method based on the differential approach for the quantification of measurement uncertainty and on the comparison of recovery associated with each one of the analytical steps whose performance can vary with the analyte origin, for spiked and incurred samples.This approach was applied to the determination of pesticide residues in apples. For the analytes covered, no evidence was found that the studied sample processing and extraction steps performance for this matrix varies with the analyte origins.     

Evaluation of the Information Content of Solid-Sampling Spectrochemistry Methods Using the Theory of Information

The evaluation of analytical procedures is based on the determination of so-called primary “figures of merit” (metrological characteristics) of individual analytical elements (X) of the excitation procedures tested. Based on these experimental results, the information theory parameters, i.e., the information content and the related measures of information content, were depending on the relevance calculated. The final critical evaluation of the tested analytical procedures was realized by comparison of the given parameters.     

信息论与化学计量学

本文讨论了信息论在发展分析化学计量学中的意义和作用以及信息论在化学计量学中应用的一般规律和关系，总结了信息科学对化学计量学发展的贡献。     

Combined Analysis of NMR and MS Spectra (CANMS)

Cellular metabolism in mammalian cells represents a challenge for analytical chemistry in the context of current biomedical research. Mass spectrometry and NMR spectroscopy together with computational tools have been used to study metabolism in cells. Compartmentalization of metabolism complicates the interpretation of stable isotope patterns in mammalian cells owing to the superimposition of different pathways contributing to the same pool of analytes. This indicates a need for a model‐free approach to interpret such data. Mass spectrometry and NMR spectroscopy provide complementary analytical information on metabolites. Herein an approach that simulates ¹³C multiplets in NMR spectra and utilizes mass increments to obtain long‐range information is presented. The combined information is then utilized to derive isotopomer distributions. This is a first rigorous analytical and computational approach for a model‐free analysis of metabolic data applicable to mammalian cells.     

The analytical laboratory computer as a management aid

Intelligent use of the data available in the store of the analytical laboratory computer can provide much of the information necessary for the optimization of laboratory resources. The research manager can use such information to monitor the activity of various projects and the cost effectiveness of the analytical service.     

Integration of analytical measurements and wireless communications--current issues and future strategies

Rapid developments in wireless communications are opening up opportunities for new ways to perform many types of analytical measurements that up to now have been restricted in scope due to the need to have access to centralised facilities. This paper will address both the potential for new applications and the challenges that currently inhibit more widespread integration of wireless communications with autonomous sensors and analytical devices. Key issues are identified and strategies for closer integration of analytical information and wireless communications systems discussed.     

Informationstheorie in der Analytik

Summary The information amount characterizing multicomponent analyses is derived for the qualitative and quantitative evaluation of independent and correlated analytical signals, respectively. It must be distinguished between detection and determination of certain selected components on the one hand and the identification of unknown components on the other hand. Selectivity, relevance and redundance of instrumental analytical methods are evaluated in connection with their potential information capacity. The information performance and effectivity are specified with regard to practical analytical problem solving.

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Teil I: Fresenius Z Anal Chem (1987) 327:312     

Artefacts and facts about metal(loid)s and their species from analytical procedures in environmental biomonitoring

Critical components of the total analytical process for the trace determination of metals, metalloids and their species in environmental biological specimens are highlighted. Examples are given of phenomena that may accompany “established” monitoring techniques but cause problems in the transformation of the original chemical composition of the bioindicators into scientifically sound analytical data and environmental information. It turns out that more problem-specific analytical developments are necessary in the field of environmental biomonitoring, in particular for the introduction of rigorously validated procedures of speciation analysis.     

Information theory and systematic toxicological analysis in “general unknown” poisoning cases

If qualitative analysis is aimed to detect large, imprecisely confined groups comprising hundreds or thousands of compounds – like during the analysis of questionable poisoning cases without direct hints, the so called “general unknowns”–, the evaluation of the identification certainty becomes equally important like the associated estimation of the necessary information capacity of the analytical procedures to be applied [1–4]. On this basis, the authors have outlined factors, which influence the usable information provided by analytical principles or procedures depending of the number and types (analytical categories, differences and similarities, detectability) of the analytes to be detected or included. A correlation between the usable information (excess or deficiency) and the probability of failing identifications is defined, and the information loss by interfering analytical signals is discussed. The concepts of discrimination power DP, identification power IP, and mean list length MLL [4–7] are associated with these considerations. Examples of analytical tasks in this “general unknown” environment of toxicological analysis are presented.     

Informationstheorie in der Analytik

Zusammenfassung Ausgehend von der Systematik analytischer Informationen und vom analytischen Prozeß als Informationsverarbeitungsprozeß wird ein Überblick gegeben über die informationstheoretischen Grundlagen der Analytik. Die Ermittlung des Informationsgehaltes von Analysenverfahren und -ergebnissen für qualitative und quantitative Einkomponentenanalysen wird unter Berücksichtigung realer analytischer Bedingungen abgeleitet und der Einfluß des Erwartungsbereiches, der Genauigkeit und Richtigkeit von Analysenergebnissen untersucht. Probleme der Kalibrierung quantitativer Analysenverfahren und der Zusammenhang zwischen Nachweisvermögen und Informationsgehalt von Spurenanalysen werden betrachtet.

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Information theory in analytical chemistryI. Principles and application to single-component analyses

Summary Starting from the system of analytical informations and from the analytical process as information processing technique a review is given about the information-theoretical fundamentals of analytical chemistry. The determination of information contents of analytical procedures and results in the cases of qualitative and quantitative single-component analyses is derived under the assumption of really existing analytical conditions. The influence of such properties as expectation range, precision and accuracy is discussed. Furthermore, the problems of calibration of quantitative analytical procedures and the relation between information content and detection limit in trace analysis are considered.