bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolution of the reference value concept
Authors: Gräsbeck Ralph 
Published: August 2004

AbstractThis manuscript reviews the introduction of the concept of reference values, the corresponding philosophy, and subsequent recommendations reflecting the different subtopics of the field. The generally unrecognised phenomenon that laboratory results of the population tended to be lognormal instead of Gaussian attracted the attention of the author, who became sceptical of the concept of normal values because of its ambiguity. Together with N.-E. Saris a new concept of reference values was launched at a congress in 1969. Briefly, clinical measurements should be interpreted against values from proper control subjects. Subsequently international, regional and national societies established expert panels which produced recommendations covering the general principles and terminology of reference values, the concept of health, standardised specimen collection and preanalytical factors, statistical treatment of collected values, stratification of data, relating observed (patient) values to reference values, etc. The importance of using correct terminology, taking into consideration the aim of ordering the laboratory test and some neglected procedures (e.g., survival values) are emphasised. New developments such as reference changes are mentioned. The field has evolved largely as the result of constructive international teamwork.
Graphical interpretation of confidence curves in rankit plots
Authors: Petersen Per Hyltoft , Blaabjerg Ole , Andersen Marianne , Jørgensen Lone G. M. , Schousboe Karoline , Jensen Esther 
Published: August 2004

AbstractA well-known transformation from the bell-shaped Gaussian (normal) curve to a straight line in the rankit plot is investigated, and a tool for evaluation of the distribution of reference groups is presented. It is based on the confidence intervals for percentiles of the calculated Gaussian distribution and the percentage of cumulative points exceeding these limits.The process is to rank the reference values and plot the cumulative frequency points in a rankit plot with a logarithmic (ln=logThis is a conservative validation, which is more demanding than the Kolmogorov-Smirnov test. The graphical presentation, however, makes it easy to disclose deviations from ln-Gaussianity, and to make other interpretations of the distributions, e.g., comparison to non-Gaussian distributions in the same plot, where the cumulative frequency percentage can be read from the ordinate. A long list of examples of ln-Gaussian distributions of subgroups of reference values from healthy individuals is presented. In addition, distributions of values from well-defined diseased individuals may showup as ln-Gaussian.It is evident from the examples that the rankit transformation and simple graphical evaluation for non-Gaussianity is a useful tool for the description of sub-groups.
Partitioning biochemical reference data intosubgroups: comparison of existing methods
Authors: Lahti Ari 
Published: August 2004

AbstractFour existing methods for partitioning biochemical reference data into subgroups are compared. Two of these, the method of Sinton et al. and that of Ichihara and Kawai, are based on a quotient of a difference between the subgroups and the reference interval for the combined distribution. The criterion of Sinton et al. appears rather stringent and could lead to recommendations to apply a common reference interval in many cases where establishment of group-specific reference intervals would be more useful. The method of Ichihara and Kawai is similar to that of Sinton et al., but their criterion, based on a quantity derived from between-group and within-group variances, seems to lead to inconsistent results when applied to some model cases. These two methods have the common weakness of using gross differences between subgroup distributions as an indicator of differences between their reference limits, while distributions with different means can actually have equal reference limits and those with equal means can have different reference limits. The idea of Harris and Boyd to require that the proportions of the subgroup distributions outside the common reference limits be kept reasonably close to the ideal value of 2.5% as a prerequisite for using common reference limits seems to have been a major improvement. The other two methods considered, that of Harris and Boyd and the “new method” follow this idea. The partitioning criteria of Harris and Boyd have previously been shown to provide a poor correlation to those proportions, however, and the weaknesses of their method are summarized in a list of five drawbacks. Different versions of the new method offer improvements to these drawbacks.
Should we maintain the 95 percent reference intervals in the era of wellness testing? A concept paper
Authors: Jørgensen Lone G. M. , Brandslund Ivan , Petersen Per Hyltoft 
Published: August 2004

AbstractThe reference interval is probably the most widely used decision-making tool in clinical practice, with a modern use aiming at identifying wellness during health check and screening. Its use as a diagnostic tool is much less recognised and may be obsolete.The present study investigates the consequences of the newpractice for the interpretation of prospective value, negative vs. positive, the probability of confirming wellness, and number of false results based on selected strategy for reference interval establishment.Calculations assumed normalised Gaussian-distributed reference intervals with analytical variation set to zero and absolute accuracy. Also assumed is the independency of tests. Probability for no values outside reference intervals in healthy subjects was calculated from the formula pUse of the 99.9 centile for health checks will increase the probability for no false from 60% to 99% for 10 tests, and from 46% to 98% for 15 tests.The probability for one false-positive result in 10 tests in a panel can be reduced from 32% to 1% if the 99.9% centile is substituted for the 95% centile. For two in 10 tests, the probability can be reduced from 8% to below 0.1%. In both cases, selection of the 99.9% centile improves the diagnostic accuracy.Reference intervals are needed as a “true” negative reference for absence of disease, and should cover the 99.9% centile of the reference distribution of an analyte to avoid false positives. For this new use, it is critical that reference persons are absolutely normal without clinical, genetic and biochemical signs of the condition being investigated. However, reference intervals cannot substitute clinical decision limits for diagnosis and medical intervention.
Clinical interpretation of reference intervals and reference limits. A plea for assay harmonization
Authors: Klee George G. 
Published: August 2004

AbstractReference intervals for healthy subjects and diseased populations are important benchmarks for the clinical interpretation of laboratory test values. It is important that the testing conditions used to collect the reference data be closely matched with the testing conditions used for patient data. Interlaboratory differences and intralaboratory changes, especially changes in analytic set-points, can markedly affect the clinical interpretation of tests. If laboratory testing methods could be harmonized, laboratories could potentially share reference data to make these data more reliable.This chapter illustrates the use of reference intervals for healthy subjects and reference data from diseased populations for medical decisions. One example illustrates the effects of age differences on test result interpretation. Other examples illustrate use of thyroid-stimulating hormone (TSH) and combinations of TSH with free thyroxine measurements for diagnosing thyroid diseases. Both univariate and multivariate reference intervals are discussed. Model systems for using disease prevalence and cost utility functions are provided to illustrate optimization of medical decisions.
Inherent biological variation and reference values
Authors: Fraser Callum G. 
Published: August 2004

AbstractThere is a need for revisiting theoretical concepts and practical applications of conventional population-based reference values to make for better clinical use of laboratory data. Knowledge of the underlying biological variation of quantities examined in medical laboratories is vital to understanding the proper generation and application of traditional population-based reference values. Appreciation of the biological changes that occur over the span of life is a necessary prerequisite to deciding whether stratification of reference values according to age is likely to be necessary. Knowledge of the detail of predictable biological cyclical rhythms is required for correct clinical interpretation of laboratory data and appropriate collection of specimens at times relevant to the clinical purpose. Quantitative data on inherent within- and between-subject biological components of variation have shown the marked individuality of most quantities of interest in laboratory medicine. This individuality casts light on why examinations are not generally very successfully applied in population screening or case-finding. Consideration of individuality demonstrates why stratification of reference values is often very advantageous. Individuality provides an indisputable argument for better use of individual specific reference values.
Intraindividual reference values
Authors: Queraltó Josep M. 
Published: August 2004

AbstractWhen a biological quantity examination exhibits a high degree of individuality, developing a strategy for interpreting these values in an individual context can be a useful alternative. Time-series analysis is the appropriate statistical framework to build a model for explanation of the behaviour of laboratory information and to forecast future values. The key concepts in this approach are autocorrelation and withinperson variance. Unfortunately, the powerful tools provided by time-series analysis require many observations, a requisite difficult to meet in every day practice. However, introducing some restrictions in the autocorrelation parameter of the most reliable model, the first order autocorrelation model, and using the average within-person variance from a selected population, it is possible to build predictive reference intervals for an individual, based on only few observations. The most common case is the minimum time series: when there are just two observations. The statistical significance of the change from a previous observation is a problem that arises from both quality control (delta checks) and the interpretative diagnostic fields (reference change limit). Applying the same restrictive criteria, it is possible to develop specific limits for a difference between consecutive observations based on a within-person variance selected from the distribution of variances found in a sample of similar individuals.
Proposal for guidelines to establish common biological reference intervals in large geographical areas for biochemical quantities measured frequently in serum and plasma
Authors: Rustad Pål , Felding Peter , Lahti Ari 
Published: August 2004

AbstractA suggestion for a standard procedure to establish biological reference intervals for biochemical quantities by a multicenter approach is presented. This procedure was developed for and used in the Nordic Reference Interval Project 2000 (NORIP). This project established biological reference intervals for 25 frequently requested biochemical quantities through cooperation of 102 Nordic laboratories. Each laboratory performed collection of reference samples and measurement using their routine methods. The bias of each routine method was eliminated by use of common reference materials measured in each of the participating laboratories.
Study of reference values and biological variation: a necessity and a model for Preventive Medicine Centers
Authors: Siest Gérard 
Published: August 2004

AbstractLaboratory tests were at the origin of the modern approach to the evaluation of the health status in many Preventive Medicine Centers.Guided by the theory of reference values and its applications, years of efforts have been devoted to defining the health status of people, and understanding the biological variation of the population.At the Nancy Center for Preventive Medicine, 40,000 people are invited every year for health examination; many coming with their families. French legislation authorized every citizen to have full health examination every five years. Annually, 600,000 people are seen at 70 centers.The visit includes answering questionnaires, physiological and biological testing modified for age, risks, and social criteria. The process concludes with consultation with a general practitioner.Data accumulated over 30 years have led to the identification of primary factors influencing biological variation of common laboratory tests. For example, body mass index (BMI) has to be considered, in addition to age and gender, for measurement of γ-glutamyltransferase, alanine aminotransferase, and other analytes.More recently, the familial Stanislas cohort has shown that apolipoprotein E (apoE) genetic polymorphism has to be considered as a factor for variation in some individuals. For example, there was greater than 100% difference in the mean concentration of apoE between
Difficulties in establishing reference intervals for special fluids: the example of 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluids
Authors: Dhondt Jean-Louis 
Published: August 2004

AbstractBiochemical measurements in “special fluids” are complicated with the problem of reference intervals. Reference intervals are difficult to establish for these types of samples since they are usually only collected in patients with clinical suspicion of disease. Determination of neurotransmitter metabolites in cerebrospinal fluid illustrates this difficulty. This paper will review the factors and circumstances that have been identified or are suspected to modifythe concentration of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid. In addition to obvious parameters such as age-related variation that can affect the concentration of 5-HIAA and HVA in cerebrospinal fluid, a varietyof other factors can explain the wide range of “control” group sizes reported in the literature. Reference intervals must take into account the purpose of cerebrospinal fluid examinations, whether they be prospective studies to explore physio-pathologic relationships or for diagnostic purposes. In the latter case, certain neurological disorders cannot be excluded if a single measured value is within the reference interval.
Creation of the necessary analytical quality for generating and using reference intervals
Authors: Klein Gerhard , Junge Wolfgang 
Published: August 2004

AbstractThis is a brief compilation of criteria on analytical quality that are prerequisites for the establishment and use of reference intervals in laboratory medicine. In this context, analytical quality is characterized by the precision, accuracy and long-term stability of laboratory methods performed with diagnostic kits, including their application on various instrument platforms. Systematically, analytical quality can be differentiated into quality of the method and its performance, and quality of long-term use. Factors influencing these types of quality in the development of diagnostic kits are discussed. The responsibility for maintaining analytical quality is shared by the two parties involved in the provision and use of reference intervals: The manufacturers of diagnostic kits are committed to providing complete description and traceability of their methods, whereas users must consider the effects of physiological, biometrical, preanalytical and analytical influences on the reference interval.
Analytical quality specifications for common reference intervals
Authors: Ricós Carmen , Doménech Maria Vicenta , Perich Carmen 
Published: August 2004

AbstractInterpretation oflaboratory test results requires comparison to some type of reference value or reference interval. These comparisons can be cross-sectional (population-based reference interval and cut-off values) or longitudinal (reference change value). Quality specifications for cross-sectional comparison have been established by determining the influence of analytical bias and imprecision on the percentage ofthe healthy population falling outside the reference limits, when sharing population-based reference intervals in a Gaussian distribution ofresults. Quality specifications for longitudinal comparisons are equally important and are often overlooked, since less work has been done in this area. Some criteria suggest that a difference between consecutive results designates a true change in a patient health status when the difference is higher than the within-subject biological variation plus the within-laboratory analytical variation. In this chapter we discuss the clinical considerations and laboratory-related factors that must be considered when quality specifications are applied to sharing reference comparisons. Real life experience shows that different analytical methods can produce comparable results when common quality goals are established, and quality can be achieved through a willingness to work together. Within the existing organization, the current specifications for analytical quality and a dedication to quality health care makes it possible to achieve transferability between laboratories within a geographic area.
Design of internal quality control for reference value studies
Authors: Westgard James O. 
Published: August 2004

AbstractInternal quality control should assure that the desired quality goals are achieved during reference value studies. Quality goals are often stated in the form of allowable limits of error, such as an allowable total error or an allowable bias. For reference value studies, it may be more appropriate to utilize a goal for allowable bias. In either case, it is possible to calculate a metric in the form of the critical systematic error that can be used to guide selection or design of the internal quality control procedure. A graphical tool, called the critical-error graph, facilitates the selection by superimposing the calculated critical systematic error on the power curves of different control rules and numbers of control measurements. Examples are provided to illustrate the calculation of the critical systematic error from both an allowable total error goal and an allowable bias goal, using figures from an extensive tabulation of available total error and bias goals.
Bonamia sp. (Haplosporidia) Found in Nonnative Oysters Crassostrea ariakensis in Bogue Sound, North Carolina
Authors: Burreson Eugene M. , Stokes Nancy A. , Carnegie Ryan B. , Bishop Melanie J. 
Published: August 2004

Abstract
The Suminoe oyster Crassostrea ariakensis is being considered for introduction into the middle Atlantic coast region of the United States, where diseases have decimated native stocks of the eastern oyster C. virginica. Triploid C. ariakensis produced at the Virginia Institute of Marine Science (VIMS) and transferred to Bogue Sound, North Carolina, experienced high mortality in the summer of 2003. Histopathological examination of oysters collected 9 d after peak mortality in August revealed the presence of intrahemocytic inclusions, suggesting a Bonamia-like parasite infecting hemocytes in 9.1% (2/22) of the oysters. November sampling of a subsequent October 2003 deployment to Bogue Sound revealed that 47% were infected by Bonamia-like microcells. Diagnosis of a second sample from this group by Bonamia-specific polymerase chain reaction primers revealed 60% prevalence, and subsequent DNA sequence data confirmed that the parasite was a Bonamia. Two samples collected during the peak mortality and archived in North Carolina were received by VIMS in January 2004. These samples revealed 90.9% and 100% prevalence of Bonamia sp., 10 of the 14 infections being heavy in intensity. No infections were detected in C. ariakensis from Pamlico Sound, North Carolina, or from the York River, Virginia, which had originated from the same hatchery cohort, suggesting that the parasite originated in Bogue Sound and was not present in the seed transferred from VIMS. Additionally, no Bonamia sp. infections were detected in C. virginica from Bogue Sound, indicating specific susceptibility of C. ariakensis to the parasite. The natural host for this Bonamia sp. is unknown. How, or if, this parasite will affect the suitability of C. ariakensis for resource restoration or aquaculture in the middle Atlantic region must await studies on the temperature and salinity tolerance, transmission, and distribution of the natural host. Nonetheless, C. ariakensis appears to be highly susceptible to a previously unknown local pathogen.
Swimming Endurance of Bull Trout, Lake Trout, Arctic Char, and Rainbow Trout following Challenge with Renibacterium salmoninarum
Authors: Jones Darin T. , Moffitt Christine M. 
Published: August 2004

Abstract
We tested the swimming endurance of juvenile bull trout Salvelinus confluentus, lake trout S. namaycush, Arctic char S. alpinus, and rainbow trout Oncorhynchus mykiss at 9°C and 15°C to determine whether sublethal infection from a moderate challenge of Renibacterium salmoninarum administered months before testing affected the length of time fish could maintain a swimming speed of 5–6 body lengths per second in an experimental flume. Rainbow trout and Arctic char swam longer in trials than did bull trout or lake trout, regardless of challenge treatment. When we tested fish 14–23 weeks postchallenge, we found no measurable effect of R. salmoninarum on the swimming endurance of the study species except for bull trout, which showed a mixed response. We conducted additional trials with bull trout 5–8 weeks postchallenge to determine whether increasing the challenge dose would affect swimming endurance and hematocrit. In those tests, bull trout with clinical signs of disease and those exposed to the highest challenge doses had significantly reduced swimming endurance compared with unchallenged control fish. Fish hematocrit levels measured at the end of all swimming endurance tests varied among species and between test temperatures, and patterns were not always consistent between challenged and control fish.
Vascular Endothelial Growth Factor in Human Colon Cancer: Biology and Therapeutic Implications
Authors: Ellis Lee M. , Takahashi Yutaka , Liu Wenbiao , Shaheen Raymond M. 
Published: August 2004

Abstract
Tumor growth and metastasis are dependent on angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in the angiogenesis of numerous solid malignancies including colon cancer. Evidence from preclinical and clinical studies indicates VEGF is the predominant angiogenic factor in human colon cancer and is associated with formation of metastases and poor prognosis. Based on these results, it was hypothesized that inhibition of VEGF receptor activity could inhibit colon cancer liver metastasis. To test this hypothesis, the authors evaluated the ability of a small molecule inhibitor specific for the tyrosine kinase VEGF receptor Flk-1/KDR (SU5416) or multiple tyrosine kinase receptors (SU6668) to inhibit tumor angiogenesis and metastasis in a model of colon cancer hepatic metastasis. Both SU5416 and SU6668 inhibited metastases, microvessel formation, and cell proliferation while increasing tumor cell and endothelial cell apoptosis. These results showed that targeting the VEGF receptor/ligand system is a rational approach to inhibiting tumor growth and prolonging survival.