Concept Of Reference Values Research Articles

The theory of reference values: an unfinished symphony

The history of the theory of reference values can be written as an unfinished symphony. The first movement, allegro con fuoco, played from 1960 to 1980: a mix of themes devoted to the study of biological variability (intra-, inter-individual, short- and long-term), preanalytical conditions, standardization of analytical methods, quality control, statistical tools for deriving reference limits, all of them complex variations developed on a central melody: the new concept of reference values that would replace the notion of normality whose definition was unclear. Additional contributions (multivariate reference values, use of reference limits from broad sets of patient data, drug interferences) conclude the movement on the variability of laboratory tests. The second movement, adagio, from 1980 to 2000, slowly develops and implements initial works. International and national recommendations were published by the IFCC-LM (International Federation of Clinical Chemistry and Laboratory Medicine) and scientific societies [French (SFBC), Spanish (SEQC), Scandinavian societies…]. Reference values are now topics of many textbooks and of several congresses, workshops, and round tables that are organized all over the world. Nowadays, reference values are part of current practice in all clinical laboratories, but not without difficulties, particularly for some laboratories to produce their own reference values and the unsuitability of the concept with respect to new technologies such as HPLC, GCMS, and PCR assays. Clinicians through consensus groups and practice guidelines have introduced their own tools, the decision limits, likelihood ratios and Reference Change Value (RCV), creating confusion among laboratorians and clinicians in substituting reference values and decision limits in laboratory reports. The rapid development of personalized medicine will eventually call for the use of individual reference values. The beginning of the second millennium is played allegro ma non-troppo from 2000 to 2012: the theory of reference values is back into fashion. The need to revise the concept is emerging. The manufacturers make a friendly pressure to facilitate the integration of Reference Intervals (RIs) in their technical documentation. Laboratorians are anxiously awaiting the solutions for what to do. The IFCC-LM creates Reference Intervals and Decision Limits Committee (C-RIDL) in 2005. Simultaneously, a joint working group IFCC-CLSI is created on the same topic. In 2008 the initial recommendations of IFCC-LM are revised and new guidelines are published by the Clinical and Laboratory Standards Institute (CLSI C28-A3). Fundamentals of the theory of reference values are not changed, but new avenues are explored: RIs transference, multicenter reference intervals, and a robust method for deriving RIs from small number of subjects. Concomitantly, other statistical methods are published such as bootstraps calculation and partitioning procedures. An alternative to recruiting healthy subjects proposes the use of biobanks conditional to the availability of controlled preanalytical conditions and of bioclinical data. The scope is also widening to include veterinary biology! During the early 2000s, several groups proposed the concept of 'Universal RIs' or 'Global RIs'. Still controversial, their applications await further investigations. The fourth movement, finale: beyond the methodological issues (statistical and analytical essentially), important questions remain unanswered. Do RIs intervene appropriately in medical decision-making? Are RIs really useful to the clinicians? Are evidence-based decision limits more appropriate? It should be appreciated that many laboratory tests represent a continuum that weakens the relevance of RIs. In addition, the boundaries between healthy and pathological states are shady areas influenced by many biological factors. In such a case the use of a single threshold is questionable. Wherever it will apply, individual reference values and reference change values have their place. A variation on an old theme! It is strange that in the period of personalized medicine (that is more stratified medicine), the concept of reference values which is based on stratification of homogeneous subgroups of healthy people could not be discussed and developed in conjunction with the stratification of sick patients. That is our message for the celebration of the 50th anniversary of Clinical Chemistry and Laboratory Medicine. Prospects are broad, enthusiasm is not lacking: much remains to be done, good luck for the new generations!

Construction and Operation Management of Children's Clothing Brand Community

With the development of the Internet and improvement of digital transmission technology, online communication is becoming a part of people's life. More and more people begin to communicate with each other and share valuable message in this digital space and virtual community based on the personal interest and specialized demand, which is playing a more important role in human society than the traditional community. In the context of this society, this research focused on researching the commercial brand community and the commercial nature of the brand with the community. The construction and operational issues were discussed to arrive at the concept of reference values and programs to solve the widespread problems in fashion brand community building, through studying children's clothing brand object. After a careful analysis of a plenty of famous children's wear brands on web sites such as Les Enphants, Wahaha, Balabala, the planning program about enhancing the participation and highlighting the effectiveness of community activities were put forward. The operation of section management and content updating, which will also be interspersed some practical operational and creative ideas, were mainly discussed. In order to promote the marketing, the significance of this research was mainly reflected by following two aspects: on the one hand, enriching the theory of the brand community; on the other hand, rationalizing the operation of brand community of Children's wear and maximizing the effective of the community by strengthening the interactive between consumers and retailers.

Drug Metabolizing Enzymes and Transporters mRNA in Peripheral Blood Mononuclear Cells of Healthy Subjects: Biological Variations and Importance of Preanalytical Steps

Quantification in peripheral blood mononuclear cells of mRNA of drug metabolizing enzymes or drug targets could give interesting, new information in the field of pharmacogenomics and molecular mechanisms. However, for the interpretation of these data, it is necessary to know mRNA biological variations. In this review, we propose a strategy based on the production and interpretation of clinical chemistry reference values. We discuss the concept of reference values; the necessity to master pre-analytical variations of CYP and ABC transporters; the choice of the analytical methods and of the reference genes; and finally the biological variations themselves. In particular, we focus on the importance of considering homogeneity for age, sex, degree of adiposity, tobacco and alcohol intake, food habits, and drug consumption, including their inductive effects, at the phase of subject recruitment. All this information is useful to define the partition and exclusion factors to obtain mRNA reference limits.

Normality: the unreachable star?

The concept of reference values is widely accepted, but their application has been quite lax over the years. This is due primarily to the difficulty of properly selecting and documenting samples from a reference population. In the absence of a clear description of reference individuals, reference values lose their meaning, are ambiguous at best, and are often confused with decision limits. The clinical medicine perspective of reference values is to rule out diseases and to define health, while that of preventive medicine is to appreciate the state of health. Defining reference limits and normality in this context is a great challenge. Advances in the fields of genomics and proteomics and the rapid pace of technological advances help highlight the biological diversity among individuals. However, there is a great need for reference values that are representative of healthy humans and presented in a manner that they can be utilized by all laboratories. In addition, as secure information technology becomes available, the goal of using an individual as their own reference during a lifetime is now possible, provided that consistency of databases is ensured.

Finding the “natural” vector bases for multidimensional reference values

The concept of reference values can be extended to multidimensional results. A probability function describes the relative density of the observations in the multivariate space. When the density of a given point is measured relative to all other points, we get an estimate of the density rank of a given point. If the rank of a point is lower than 95 per cent of all points, the multidimensional result is outside the multidimensional reference range. The single-dimensional case is a special case of this general concept. Many observations are needed to define multidimensional distributions. However, less points are needed if the dimensionality of the data matrix is reduced by statistical methods such as principal component analysis (PCA). Also other vector bases than the orthogonal solution produced by PCA are possible, and all of them compress data equally well. So the choice must be based on other criteria than compression. We propose using a vector basis that consists of positive numbers. The positive vectors can be found by direct methods such as Alternating Regression (AR) or they can be modified from the results of the PCA. Positive vectors resemble the spectra that are familiar in chemistry and physics. They are a "natural" way to describe multidimensional results. It is easier to name the positive vectors than the purely statistical vectors of PCA. To obtain a unique positive solution, additional constraints besides positivity are needed.

IFCC recommendation: The theory of reference values. Part 4. Control of analytical variation in the production, transfer and application of reference values

This paper is the fourth in a series of Recommendations on the Theory of Reference Values. The others cover: Part 1. The Concept of Reference Values [1]. Part 2. Selection of Individuals for the Production of Reference Values [2]. Part 3. Preparation of Individuals and Collection of Specimens for the Production of Reference Values [3]. Part 5. Statistical Treatment of Collected Reference Values. Determination of Reference Limits [4]. Part 6. Presentation of Observed Values Related to Reference Values [5]. A Guide to the Documents is currently in preparation. The Expert Panel of Theory of Reference Values (EPTRV) was created in 1970 by the Committee on Standards (at present: Scientific Division) of the International Federation of Clinical Chemistry (IFCC). Its task was to develop a nomenclature and recommend procedures for the production of reference values and their treatment, and presentation of observed values in relation to reference data. The first document in the above-mentioned series describes the subject of reference values and defines various terms. It would be best to read it for a thorough understanding of the present document.

Approved recommendation (1986) on the theory of reference values. Part 1. The concept of reference values.

The establishment of reference intervals (RIs) for complement 3 (C3) and complement 4 (C4) is rare, especially by indirect methods. Therefore, this study aims to establish regional RIs for C3 and C4 by an indirect method, using relevant statistical methods.Total of 12,313 data points for C3 and 12,125 data points for C4 were obtained from the First Hospital of Jilin University's database in China and standardised using the Tukey and Box–Cox statistical methods. The coefficients of the skewness-median-coefficient of variation curves (LMS) were used to determine the critical value for age, and a subsequent z test used to compare the differences. A non-parametric method was used to establish the RIs.The C3 and C4 concentrations showed no significant differences by sex, and a weak correlation with age. No significant difference was found after calculating the z value for the age points on the LMS curves. The RIs for C3 and C4 were 0.83–1.58 g/L and 0.15–0.40 g/L, respectively. The RIs all passed verification.Suitable RIs for C3 and C4 were established for the local population, and will benefit clinical diagnosis. The feasibility and practicability of the indirect method were demonstrated.

Provisional recommendation on the theory of reference values (1978). Part 1. The concept of reference values.

Journal Article Provisional recommendation on the theory of reference values (1978). Part 1. The concept of reference values. Get access R Gräsbeck, R Gräsbeck Search for other works by this author on: Oxford Academic Google Scholar G Siest, G Siest Search for other works by this author on: Oxford Academic Google Scholar P Wilding, P Wilding Search for other works by this author on: Oxford Academic Google Scholar G Z Williams, G Z Williams Search for other works by this author on: Oxford Academic Google Scholar T P Whitehead T P Whitehead Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 25, Issue 8, 1 August 1979, Pages 1506–1508, https://doi.org/10.1093/clinchem/25.8.1506 Published: 01 August 1979