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Transferability of clinical laboratory data within a health care region.

Analytical data for S-Creatinine and S-Urate are presented from seventeen laboratories in the Swedish Uppsala-Orebro regional quality assessment program. The bias and imprecision as well as the instability of the measurement procedures in the participating laboratories were estimated over three 14-week periods. Bias was estimated by a linear least squares fit of the difference between measured and assigned values vs. assigned values, and expressed in absolute and relative terms. Instability of the measurement procedures was estimated by comparing slope and intercept of regression lines of measured vs. assigned values from three fourteen week periods. According to our experiences we recommend regression analysis to describe the performance of the analytical methods of a laboratory over time. The results show that most laboratories fell within the limits of +/- 15% bias for S-Creatinine above 100 mumol l-1 and +/- 17% for S-Urate at concentrations above 250 mumol l-1. Various steps to reduce the inter-laboratory variability are suggested, including numerical correction of individual laboratory results using correction functions. In a few laboratories, instability was too high to allow for numerical corrections of analytical results.

Bias

EDMUS, a European database for multiple sclerosis.

EDMUS is a minimal descriptive record developed for research purposes to document clinical and laboratory data in patients with multiple sclerosis (MS). It has been designed by a committee of the European Concerted Action for MS, organised under the auspices of the Commission of the European Communities. The software is user-friendly and fast, with a minimal set of obligatory data. Priority has been given to analytical data and the system is capable of automatically generating data, such as diagnosis classification, using appropriate algorithms. This procedure saves time, ensures a uniform approach to individual cases and allows automatic updating of the classification whenever additional information becomes available. It is also compatible with future developments and requirements since new algorithms can be entered in the programme when necessary. This system is flexible and may be adapted to the users needs. It is run on Apple and IBM-PC personal microcomputers. Great care has been taken to preserve confidentiality of the data. It is anticipated that this "common" language will enable the collection of appropriate cases for specific purposes, including population-based studies of MS and will be particularly useful in projects where the collaboration of several centres is needed to recruit a critical number of patients.

Database Management Systems

[Central accounting as a model of laboratory diagnosis].

From the experiences in the field of scientific organisation of the last years results a laboratory-diagnostic model with an automatic laboratory, a district laboratory and larger central units, so-called coordination laboratories which work together with about 10 to 20 laboratories and guarantee an up-to-date diagnostic spectre for the whole territory. Apart from the increasing investigation frequency, a constant dilatation of the diagnostic spectre and improved quality control of structural conditions must be taken into consideration. The constructed model which demands the collaboration of all institutions meets these critical problems. A central balancing should also extend to the personal and technical apparative capacity. Apart from this the system is to be extended by further automation in the sense of a machine activity with improvement by control and regulation processes. An electronic data processing improves the functional capacity only when the analytic data processing has achieved a high level. The cooperation in the field of laboratory diagnostics is not only a task in scientific organisation, but in the same way also scientific problems are solved together. The requirements increasing in qualitative and quantitative respect may optimally be fulfilled only by the two partners, clinic and laboratory. With increasing independence the laboratories should in scientific and organizational respect remain a place of meeting for laboratory scientist and physician.

Clinical Laboratory Techniques

Medical economics survey-methods study: design, data collection, and analytical plan.

This paper describes the background, methodology, data collection, and analytical plan of a pilot investigation conducted under contract for the National Center for Health Statistics during 1975. The objective was to determine the cost effectiveness of a variety of strategies under consideration for national application to develop previously unavailable information on utilization of, and the costs and payments for, health care. Detailed data on health care utilization and expenditures were collected periodically from a panel of 691 Maryland households over a six-month interval. Issues to be tested through a random experimental design include whether periodicity (monthly vs bimonthly interviews) and type of contact (in-person vs telephone) are significant factors in the cost effectiveness of this type of survey. An extensive record check involving all providers and third-party payers identified in the household survey was carried out. Record information will be used to 1) provide a basis for measuring accuracy of household data, 2) fill gaps in household knowledge, and 3) determine whether a subset of the record sources can provide adequate information for correcting household data. The household survey resulted in an initial response rate of 77.5 per cent with a subsequent attrition rate over six months of 13.6 per cent. Signed permission to access record data was obtained for 84.9 per cent of the individuals completing the entire survey. The most intensive survey strategy, monthly, mostly in-person contact, resulted in the lowest participation. The analytical plan presents details of the approaches to be taken in making judgments on the relative accuracy and completeness of data obtained by the various survey strategies and the contribution made by availability of data from record sources.

Adolescent

Classification of fungi by means of pyrolysis-gas chromatography-pattern recognition.

Repetitive samples of three strains of the mould Penicillium were subjected to pyrolysis-gas chromatography (Py-GC). From the chromatograms, 26 peak heights were used in a subsequent SIMCA pattern recognition analysis. This data analysis gives a marked improvement in the classification of the samples (100% correct, 85% unique) in comparison with the traditional analysis based on the average chromatogram of each class (92% correct, 45% unique). The data analytical method is described in detail using the Py-GC data as an illustration.

Analysis of Variance

Clinical pathology: preanalytical variation in preclinical safety assessment studies--effect on predictive value of analyte tests.

Significant differences in concentrations of analytes in samples may be introduced before samples enter analyzers. These differences are known as preanalytical variation and are part of the overall variation in analytical data. Preanalytical variation is caused by factors that operate during animal preparation prior to sampling, sample collection, sample processing, and sample storage prior to measurement. Preanalytical variation is important because it detracts from the predictive value of analyte measurements. Preanalytical variation may permanently damage data. Because its effects are difficult to quantitate it should be minimized in safety assessment studies. Sources of preanalytical variation are actions performed on animals prior to sample collection and actions performed on the specimen prior to analysis. Preanalytical variation produces a range of artefacts in experimental data. Consequences of preanalytical variation are loss of confidence in the data, obfuscation of real test article effects, false effects, and possibly the expense of repeating a study. To limit preanalytical variation, its sources must be identified, the effects documented, and measures devised to eliminate its sources. Predictive value (likelihood of actual disease) of appropriate clinical pathology tests in toxicology is inversely dependent on preanalytical variation: uncontrolled variation produces data with low predictive values, and controlled variation produces data with high predictive values.

Animals

Evaluation of sequencing reads at scale using rdeval.

MOTIVATION: Large sequencing datasets are being produced and deposited into public archives at unprecedented rates. The availability of tools that can reliably and efficiently generate and store sequencing read summary statistics has become critical. RESULTS: As part of the effort by the Vertebrate Genomes Project (VGP) to generate high-quality reference genomes at scale, we sought to address the community's need for efficient sequence data evaluation by developing rdeval, a standalone tool to quickly compute and interactively display sequencing read metrics. Rdeval can either run on the fly or store key sequence data metrics in tiny read 'snapshot' files. Statistics can then be efficiently recalled from snapshots for additional processing. Rdeval can convert fa*[.gz] files to and from other popular formats including BAM and CRAM for better compression. Overall, while CRAM achieves the best compression, the gain compared to BAM is marginal, and BAM achieves the best compromise between data compression and access speed. Rdeval also generates a detailed visual report with multiple data analytics that can be exported in various formats. We showcase rdeval's functionalities using long-read data from different sequencing platforms and species, including human. For PacBio long-read sequencing, our analysis shows dramatic improvements in both read length and quality over time, as well as the benefit of increased coverage for genome assembly, though the magnitude varies by taxa. AVAILABILITY AND IMPLEMENTATION: Rdeval is implemented in C++ for data processing and in R for data visualization. Precompiled releases (Linux, MacOS, Windows) and commented source code for rdeval are available under MIT license at https://github.com/vgl-hub/rdeval. Documentation is available on ReadTheDocs (https://rdeval-documentation.readthedocs.io). Rdeval is also available in Bioconda and in Galaxy (https://usegalaxy.org). An automated test workflow ensures the consistency of software updates.

Software

Thomas: building Bayesian statistical expert systems to aid in clinical decision making.

Knowledge-based system for classical statistical analysis must separate the task of analyzing data from that of using the results of the analysis. In contrast, a Bayesian framework for building biostatistical expert system allows for the integration of the data-analytic and decision-making tasks. The architecture of such a framework entails enabling the system (1) to make its recommendations on decision-analytic grounds; (2) to construct statistical models dynamically; (3) to update a statistical model based on the user's prior beliefs and on data from, the methodological concerns evinced by, the study. This architecture permits the knowledge engineer to represent a variety of types of statistical and domain knowledge. Construction of such systems requires that the knowledge engineer reinterpret traditional statistical concerns, such as by replacing the notion of statistical significance with that of a pragmatic clinical threshold. The clinical user of such a system can interact with the system at a semantic level appropriate to her fund of methodological knowledge, rather than at the level of statistical details. We demonstrate these issues with a prototype system called THOMAS which helps a physician decision maker interpret the results of a published randomized clinical trial.

Artificial Intelligence

A pattern classification system for automated cervical cytologic screening based on flow microfluorometric analysis.

A data analytic technique is described for use in automated cervical cytology. The method entails the application of a two-dimensional Fourier transform to histogram data obtained by flow microfluorometry and the subsequent use of the Fourier coefficients as parameters for pattern classification. Analyses were performed on 186 samples including material from 62 positive and 124 negative cases. Cell suspensions were stained with propidium iodide and fluorescein isothiocyanate, and red and green cytofluoresence were measured simultaneously. The two-dimensional histogram data were normalized, the Fourier transform was applied, and a multivariate classifier based on 30 coefficients was assembled using a training set of half the original series. Performance was then assessed on the remaining cases. Overall accuracy was 79.6%, with a false-positive rate of 14.8% and a false-negative rate of 31.2%. The potential applicability of this approach as the basis of a practical screening system is discussed.

Adolescent

[Problems with standardization of the radioimmunologic determination].

Radioimmunoassay is an analytical procedure in which a radioactive tracer acts as an indicator and a specific antibody acts as a reagent. The requirements which have to be met to guarantee the validity of the assay are the essential characteristics of each microanalytical procedure, namely the sensitivity, specificity, precision and accuracy. The optimization of the assay demands than a careful examination of these factors, which first depend on the properties of the reagents. The consistency of the results is based on the identity, as far as the immunoreactivity is concerned, between the substance to be assayed in the biological sample and the substance used as a standard to build up the calibration curve. The immunoreactivity of the tracer can instead be lower than that shown by the standard, although it must not be too different. The features of all the reagents are reviewed and discussed, mainly those of the antiserum which affect the specificity of the assay. The most diffuse RIA techniques are reviewed and divided in gross categories, according to the methods used for the separation of the free and antibody-bound hormone. The different steps of the analytical procedure are investigated, taking into consideration the most important parameters which affect the assay, mainly the time and temperature of the incubation step. The practical ease of the analysis is definitely an essential factor of choice, provided that it could be associated to reproducible and accurate results. A severe quality control of each reagent and of the assembled set must be carried out to assure the consistency of the analytical data. In the particular case of radioimmunoassay the quality control must be extended to all the steps of the assay both before and after the analytical procedure itself, in order to assure the maximal clinical validity of the diagnostic determination.

Aldosterone

Cardiac function and Fourier phase data from simulated Wolff-Parkinson-White syndrome in a baboon model.

The diagnostic value of Fourier phase analysis and planar scintigraphy in Wolff-Parkinson-White (WPW) syndrome has been suspect. This study investigates phase analytical data from planar radionuclide ventriculography of six baboons with simulated WPW syndrome by means of implanted electrodes. An electrode in the atrium controlled the heart rate and a subsequent stimulation was delivered by electrodes placed at different sites on the ventricles, delayed to cause the characteristic delta wave of the WPW syndrome. Sensitivity for accurately-localizing variously-situated first points of activation (FPAs) from the Fourier phase images was found highest for premature right ventricular (RV) activation, and for atrioventricular (AV) delays around 125 msec. Other sites were subject to artifacts. Changes in cardiac function, phase delay, and histogram parameters were not statistically meaningful.

Animals

Quality assurance in pathology. Cytologic and histologic correlation.

In this study we used a computerized program to compare the cytologic and histologic diagnoses made in a three-year period with the aim of evaluating the data obtained as an index of the diagnostic accuracy of cytology in a pathology quality assurance program. Concordance between the cytologic and histologic diagnoses was observed in 83.2% of the cases. In 1.2% the cytologic diagnosis was suspected malignancy, and 78.4% of these cases were positive for tumor at histologic examination. Analysis of the data must be performed in accordance with the anatomic site involved, and discordance must be investigated by a pathologist, especially in view of the different modalities of cytologic and histologic sampling. Analytic data on the breast, bladder and lung are presented.

Cell Biology

Inactivation of Bacillus subtilis glutamine synthetase by metal-catalyzed oxidation.

Instability of Bacillus subtilis glutamine synthetase in crude extracts was attributed to site-specific oxidation by a mixed-function oxidation, and not to limited proteolysis by intracellular serine proteases (ISP). The crude extract from B. subtilis KN2, which is deficient in three intracellular proteases, inactivated glutamine synthetase similarly to the wild-type strain extract. To understand the structural basis of the functional change, oxidative modification of B. subtilis glutamine synthetase was studied utilizing a model system consisting of ascorbate, oxygen, and iron salts. The inactivation reaction appeared to be first order with respect to the concentration of unmodified enzyme. The loss of catalytic activity was proportional to the weakening of subunit interactions. B. subtilis glutamine synthetase was protected from oxidative modification by either 5 mM Mn2+ or 5 mM Mn2+ plus 5 mM ATP, but not by Mg2+. The CD-spectra and electron microscopic data showed that oxidative modification induced relatively subtle changes in the dodecameric enzyme molecules, but did not denature the protein. These limited changes are consistent with a site-specific free radical mechanism occurring at the metal binding site of the enzyme. Analytical data of the inactivated enzyme showed that loss of catalytic activity occurred faster than the appearance of carbonyl groups in amino acid side chains of the protein. In B. subtilis glutamine synthetase, the catalytic activity was highly sensitive to minute deviations of conformation in the dodecameric molecules and these subtle changes in the molecules could be regarded as markers for susceptibility to proteolysis.

Bacillus subtilis

Advances in tumor subclone formation and mechanisms of growth and invasion.

Tumor subclones refer to distinct cell populations within the same tumor that possess different genetic characteristics. They play a crucial role in understanding tumor heterogeneity, evolution, and therapeutic resistance. The formation of tumor subclones is driven by several key mechanisms, including the inherent genetic instability of tumor cells, which facilitates the accumulation of novel mutations; selective pressures from the tumor microenvironment and therapeutic interventions, which promote the expansion of certain subclones; and epigenetic modifications, such as DNA methylation and histone modifications, which alter gene expression patterns. Major methodologies for studying tumor subclones include single-cell sequencing, liquid biopsy, and spatial transcriptomics, which provide insights into clonal architecture and dynamic evolution. Beyond their direct involvement in tumor growth and invasion, subclones significantly contribute to tumor heterogeneity, immune evasion, and treatment resistance. Thus, an in-depth investigation of tumor subclones not only aids in guiding personalized precision therapy, overcoming drug resistance, and identifying novel therapeutic targets, but also enhances our ability to predict recurrence and metastasis risks while elucidating the mechanisms underlying tumor heterogeneity. The integration of artificial intelligence, big data analytics, and multi-omics technologies is expected to further advance research in tumor subclones, paving the way for novel strategies in cancer diagnosis and treatment. This review aims to provide a comprehensive overview of tumor subclone formation mechanisms, evolutionary models, analytical methods, and clinical implications, offering insights into precision oncology and future translational research.

Humans

The amelogenin problem: a comparison of purified enamel matrix proteins.

Using a combination of gel filtration and DEAE-cellulose chromatography, together with small-scale preparative polyacrylamide gel electrophoresis, we isolated five proteins (amelogenins) from demineralized bovine fetal dental enamel matrix. These purified proteins were characterized by amino acid analysis and gel electrophoresis. Comparisons of these data with those of other workers suggest that, although there are similarities in the published data between components of comparable electrophoretic mobility, there are gross differences in the reported amino acid compositions. It is suggested that these differences are due not to separative problems arising from reversible aggregations, but to inadequate comparisons of the electrophoretic and amino acid analytical data.

Amelogenesis

Alveolar phospholipids in pulmonary alveolar proteinosis.

The biochemical compositions of lung lavage fluid from three patients and that of the lung tissue obtained by a biopsy from a patient with alveolar proteinosis were analyzed. The lung lavage fluid was separated to the supernatant and the insoluble precipitate fractions by a brief centrifugation and the lung tissue was separated to surfactant and residual fractions by sucrose density gradient centrifugation. The supernatant of lung washing contained larger quantities of protein and less lipid which was mainly composed of lecithin and sphingomyelin. In contrast, the insoluble material of lung washing contained 4--8 fold of lipid as compared with the supernatant, and lecithin was a predominant phospholipid. From the analysis of fatty acid and individual molecular species of major phospholipids, the higher contents of dipalmitoyllecithin and sphingomyelin containing palmitate were found in the insoluble material. The phospholipid composition and fatty acid composition of lecithin were similar between the precipitate fraction of lung washing and the surfactant fraction of lung tissue. The ratio of protein to phospholipid in the precipitate fraction was similar to that of lung washing. These analytical data suggest that the materials accumulated in the alveoli of the patients may be derived mainly from the lung surfactant fraction. The metabolic studies showed that lecithin synthesis through de novo and lysolecithin pathways works in human lung with this disease as actively as in rat lung. The secretion of lung lecithin to the surfactant fraction also appeared to be normal. From these analytical and metabolic findings, the causes for the accumulation of the materials which cover alveolar surface and impair gaseous exchange in the alveoli of pulmonary alveolar proteinosis, were discussed.

Animals

Application of the official AOAC chloresterol Method to a wide variety of food products.

This paper presents analytical data on the cholesterol content of selected consumer food products including some fats and oils. The cholesterol data are grouped by food products. To determine the reproducibility of cholesterol values, recovery data were obtained from samples of pure vegetable shortening spiked at 40 and 20 mg cholesterol (as cholesteryl palmitate)/100 g fat. Average recoveries were 97.1% and 95.5% with coefficients of variation of 1.27 and 3.24%, respectively.

Chemistry Techniques, Analytical