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PubMed1996

Detection of hearing loss in young children and adults using otoacoustic emissions.

Measures of transient evoked otoacoustic emission (TEOAE) reproducibility were obtained for 506 ears of 260 children and young adults. Frequency-specific and whole reproducibility data were obtained using ILO88 hardware and software (version 3.92), and were analyzed with respect to pure tone threshold and emmittance data for the same ears. The 2,000-Hz reproducibility score was the most efficient of all measurements (0.85-0.91) in separating normal and hearing-impaired ears, regardless of the frequencies at which the hearing loss occurred. TEOAE reproducibility measures may be very useful in screening for hearing loss in babies, leading to the earliest identification of children with hearing loss.

Acoustic Stimulation↗
PubMedDate not supplied

Numerical grading of astrocytomas.

Ninety-three astrocytomas from biopsy material including glioblastomas ('astrocytomas grade 4') were graded according to Kernohan (1949) by light microscopy. Feulgen sections were subjected to an automated microscopic analysis to obtain morphometric-densitometric data of the tumour cell nuclei. These quantitative and reproducible data showed a significant correlation with malignancy expressed in terms of Kernohan and prove automated image analysis to be a valuable tool in the grading of gliomas. This is in particular true if the nuclear parameters determined by image analysis are completed by histologic features which were recorded semiquantitatively by subjective light microscopic evaluation as is usual in clinic pathologic diagnosis of brain tumours. A quadratic discriminant analysis of morphometric-densitometric data of tumour cell nuclei and semiquantitative microscopic data gave a 94% agreement with subjective grading.

Astrocytoma↗
PubMed2026

Community-driven advances in computational mass spectrometry: The perspective of EuBIC-MS members.

Advances in data acquisition, artificial intelligence, and integrative bioinformatics are driving the rapid evolution of computational mass spectrometry, and in turn, transforming modern proteomics, metabolomics, and lipidomics. These developments have greatly increased the scale and complexity of mass spectrometry data, underscoring the importance of evolving accurate, transparent, efficient and reproducible data processing workflows. Addressing these challenges requires collaborative innovation that brings together expertise in software engineering, statistics, and biology. The European Bioinformatics Community for Mass Spectrometry (EuBIC-MS), an initiative of the European Proteomics Association (EuPA), fosters a culture of open, community-driven development through its biennial Developers Meetings and Winter Schools. This commentary summarizes the scientific background and outcomes of the EuBIC-MS Developers Meeting 2025, which took place in Novacella, Italy. Three keynote presentations highlighted major frontiers in the field: deep proteome and phosphoproteome profiling, text mining for protein-protein interaction extraction, and scalable proteomics for AI-driven drug discovery. Seven community-selected hackathons addressed emerging challenges such as single-cell proteomics data analysis, FAIR metadata extraction, deep learning frameworks, R-Python interoperability, and DIA validation. Together, these efforts demonstrate the potential for scientific and technical innovation to arise from open collaboration, and highlight how community-driven initiatives can accelerate progress in computational mass spectrometry. SIGNIFICANCE: Modern proteomics increasingly depends on computational advances to translate complex, high-dimensional data into biological knowledge. The EuBIC-MS Developers Meeting 2025 exemplifies how community-driven collaboration can directly accelerate this process by bringing together experts from bioinformatics, statistics, and experimental proteomics to co-develop open, interoperable, and reproducible analytical tools. By fostering shared software frameworks, transparent benchmarking, and collaborative problem solving, the EuBIC-MS community helps ensure that technological innovation translates into reliable biological insights. This collaborative model strengthens the foundation for quantitative, system-level understanding of proteomes and establishes a sustainable path for integrating artificial intelligence and next-generation data acquisition into routine biological discovery. This commentary shows some current highlights in the field of computational mass spectrometry and community-based approaches undertaken during the most recent Developers Meeting to solve these challenges. The approaches discussed and initiated during the meeting - ranging from deep proteome profiling and phosphosite mapping to text mining, single-cell data analysis, and FAIR metadata extraction - address key bottlenecks that currently limit the biological interpretability and comparability of proteomics data.

Mass Spectrometry↗
PubMed1991

Tandem mass spectrometry of peptides using hybrid and four-sector instruments: a comparative study.

Product-ion spectra produced by high- and low-energy collisionally activated dissociation (CAD) of [M + H]+ ions of a series of peptides (Mr 550-2500) have been compared on four-sector and hybrid tandem mass spectrometers, respectively. The fast atom bombardment product-ion spectra obtained for the smallest peptide analyzed (methionine-enkephalin) were remarkably similar, but substantial differences in fragmentation were observed for the heavier analytes. For peptides with Mr greater than 1000, more complete sequence information was obtained from high-energy CAD on the four-sector instrument. Nevertheless, low-energy CAD on the hybrid mass spectrometer was able to produce partial sequence information even for the largest of the peptides compared. Limits of analysis, defined as the least quantities of analyte for which product-ion spectra of essentially uncompromised quality could be obtained, were similar (ca. 15 pmol) for small peptides, but lower limits were achieved for larger peptides (Mr greater than 1000) with the four-sector instrument. High-energy CAD spectra were found to be highly reproducible, with qualitatively similar spectra obtained over a wide range of operating conditions. In contrast, it was necessary to carefully control collision gas pressures and collision energies in order to obtain good reproducible data for low-energy CAD. Experimental procedures for obtaining reproducible spectra with good sensitivity for peptides on the hybrid instrument are presented.

Adrenocorticotropic Hormone↗
PubMed2002

Reproducibility of survey results from a study of occupation-related respiratory health in the aluminum industry.

Confidence in dose-response relationships arising from occupational studies is dependent upon the reliability and validity of relevant exposure and morbidity estimates. Often self-reported occupational histories are a surrogate for direct exposure measures, and self-report of symptoms serves a similar purpose in place of more objective measures of morbidity. Unfortunately, there are few methods for validating either of these sources of information. This study attempts to evaluate the reproducibility of a survey instrument, and resulting cumulative exposure estimates, utilized in a study of work-related respiratory morbidity in the aluminum industry. The survey instrument comprised measures of pulmonary function, atopic status, smoking, occupational history, and respiratory symptoms. A Task Exposure Matrix was used to estimate exposure categories and cumulative exposure scores. Two groups of employees were administered the survey instrument on two separate occasions. Group A (n = 74) completed their two surveys more than ten weeks apart and Group B (n = 43) completed their surveys less than two weeks apart. Reproducibility was assessed using Cohen's Kappa for categorically measured outcome measures and intraclass correlation coefficients for continuously measured outcomes. Agreement across most variables, for both groups, was generally high. Repeatability of self-reported respiratory symptoms ranged from 70 to 98 percent (Group A) and 88 to 100 percent (Group B). Cumulative exposure scores were highly reproducible, despite some discrepancies in the self-reported occupational histories across interviews, with most of the calculated intraclass r scores exceeding 0.8. These results give strength to studies reporting dose-response relationships derived from similarly collected data. Reproducibility of the survey data was enhanced by use of standardized questionnaire material, consistent interview structure, and calibrated equipment for objective observation. In particular the authors recommend use of a company job dictionary to optimize reproducibility of self-reported occupational information.

Adult↗
PubMed1984

Automated image analysis of gliomas an objective and reproducible method for tumor grading.

A system of automated microscopic picture analysis was used in an examination of 272 gliomas (70 glioblastomas, 91 astrocytomas, 56 pilocytic astrocytomas or spongioblastomas , and 55 oligodendrogliomas). The specimens were prepared as Feulgen sections, 4 microns in thickness. Thirteen morphometric-densitometric parameters of tumor cell nuclei were tested together with two mitotic parameters. Objective and reproducible data on numerical nuclear density ( KRNZ , AREA), nuclear size ( KOFL , KFRL , P250 ), nuclear shape ( FOFK , FOFR , P150), optical density ( EXTU , EXTS , EXSR , EXTM , EXMR ), and mitotic activity ( MITZ , VHMK ) of the gliomas were obtained from the morphometric-densitometric parameters. All gliomas but glioblastomas were subdivided by four tumor grades. The morphometric-densitometric and mitotic data recorded were statistically checked, depending on tumor grade (Student's t-test, Wilcoxon's test, alpha = 0.05). Numerical nuclear density, deformation of nuclei, and mitotic activity were found to grow with significance along with increasing tumor grade up to glioblastoma. The relative standard deviation (SD) of nuclear size ( KFRL ), relative SD of shape factors ( FOFR ), and relative SD of extinction sums ( EXSR ) are high-accuracy parameters for the pathologist to describe variability of sizes, polymorphism, and polychromasia of nuclei. These parameters show a significant increase of values in parallel with rising tumor grade, with maximum values being recordable from cases of glioblastomas. In cases of astrocytomas, optical values of nuclei decrease along with rising tumor grade. The data thus obtained were used as reference values for objective, reproducible automatic glioma grading. The classifier method, described in an earlier publication, proved to be more effective than the regression method.

Astrocytoma↗
PubMed1996

Determination of extracellular methotrexate tissue levels by microdialysis in a rat model.

We used a microdialysis technique to determine tissue methotrexate (MTX) levels during steady state in a rodent model. Two different approaches were employed to measure the actual extracellular MTX concentrations in muscle, liver, and kidney tissues of anesthetized Wistar rats. With the reduced-perfusion-rate technique, the flow in the microdialysis perfusate was gradually decreased toward zero to permit calculation of zero-flow intercepts. Using the net change technique, microdialysis probes were perfused with different MTX concentrations to allow an assessment of equilibrium drug levels. For these two methods to be used, drug concentrations in the matrix to be analyzed must remain unchanged during the experimental procedure. In the animal model, steady state was attained after 1.5 h and maintained throughout the rest of the experiments by the administration of MTX as continuous infusions through a venous catheter. In vitro and in vivo, both the reduced-perfusion-rate and net change techniques gave reproducible data that permitted the estimation of extracellular drug concentrations in the dialyzed tissue compartments.The data suggest that the level of unbound MTX in the circulation is fairly similar to the extracellular concentrations in the muscle and liver. In the kidney, MTX levels were measured to be 3-8 times higher than those of unbound, circulating MTX, and a considerable discrepancy between the two methods used for estimations was apparent. These results demonstrate that both the net change and reduced-flow microdialysis techniques can produce reproducible and precise data. The results may constitute a basis for determining recoveries and, thus, true extracellular drug levels during in vivo microdialysis of MTX. This may be of importance in delineation of the relationship between tissue MTX levels and outcome in a variety of normally inaccessible compartments during cancer pharmacotherapy.

Animals↗
PubMed1978

A scheme for the evaluation of methods in clinical chemistry with particular application to those measuring enzyme activities. Part II: analysis of data and performance assessment.

Recommendations are made concerning the editing of day-to-day reproducibility data for establishment of precision in the evaluation of a clinical chemistry method. The concept of diagnostic and equalized diagnostic indices is introduced together with formulae for their generation from the usual precision and accuracy data acquired in method evaluations. These indices allow direct comparison of data obtained from procedures for measuring enzyme activities which employ a variety of experimental conditions and units in their protocols. The equalized diagnostic index permits assessment of the suitability of the normal range assignment. Permissible limits of variation (PLV) and permissible limits of discrepancy (PLD) have been developed empirically from detailed examination of data from method evaluations and proficiency testing surveys in the published literature. The application of the diagnostic indices and the two permissible limits of criteria have been illustrated using data from the assessment of 19 kits measuring CPK activity. The inconsistency of the correlation coefficient in method comparisons is confirmed.

Canada↗
PubMed2002

Reproducibility and feasibility of neurophysiological assessment of the sensory trigeminal system for future application to paroxysmal headaches.

As the distribution of pain in primary headaches suggests involvement of the trigeminal sensory pathways, trigeminal somatosensory evoked potentials (TSEP) and blink reflexes (BR) may provide important information about their functional integrity. Functional differences between symptomatic and non-symptomatic sides and between measurements during and outside attacks may be particularly informative. These tests should therefore be reproducible and should require a suitable number of patients for future studies in patients with primary, paroxysmal headaches. We performed TSEP and BR twice in 22 healthy volunteers, in order to calculate sample sizes based on reproducibility data. This is, to our knowledge, the first study investigating the reproducibility of TSEP and BR measurements. Latencies of TSEP and BR are appropriate for future studies, as their reproducibility allows practical sample sizes (less than 25 subjects). Duration, amplitude and area parameters of the BR responses were less appropriate for longitudinal studies.

Adult↗
PubMed1998

Reproducibility of spirometrically controlled CT lung densitometry in a clinical setting.

The aim of this study was to assess the reproducibility of quantitative, spirometrically gated computed tomographic (CT) lung densitometry at defined levels of inspiration in hospitalized patients. On two consecutive days, spirometrically gated CT sections were obtained from 20 hospitalized patients at 5 cm above and 5 cm below the carina, and at 90 and 10% of the vital capacity (VC). The mean, modal and median lung densities were calculated, the cut-off points of the frequency distribution of Hounsfield units (HU) defining the lowest and the highest 10th percentile, as well as the histogram full width at half maximum. The lung density parameters of corresponding CT sections of both studies were compared. Reproducibility was expressed as the standard deviation of the signed difference between the results of Day 1 and Day 2 divided by the square root of 2. Reproducibility data were correlated with results of airflow limitation. At 90% VC, reproducibility was of the order of 3-14 HU in both lung zones. At 10% VC, reproducibility was worse by approximately a factor of three. No relationship was found between reproducibility and results of airflow limitation. In conclusion, objective measurement of lung density at spirometrically controlled levels of inspiration is a reproducible method in assessing pulmonary density. Reproducibility of lung density measurements is not influenced by severe respiratory insufficiency. The most reproducible computed tomographic lung density measurements can be obtained at 90% vital capacity.

Absorptiometry, Photon↗
PubMed2003

Incorporation of gene-specific variability improves expression analysis using high-density DNA microarrays.

BACKGROUND: The assessment of data reproducibility is essential for application of microarray technology to exploration of biological pathways and disease states. Technical variability in data analysis largely depends on signal intensity. Within that context, the reproducibility of individual probe sets has not been hitherto addressed. RESULTS: We used an extraordinarily large replicate data set derived from human placental trophoblast to analyze probe-specific contribution to variability of gene expression. We found that signal variability, in addition to being signal-intensity dependant, is probe set-specific. Importantly, we developed a novel method to quantify the contribution of this probe set-specific variability. Furthermore, we devised a formula that incorporates a priori-computed, replicate-based information on probe set- and intensity-specific variability in determination of expression changes even without technical replicates. CONCLUSION: The strategy of incorporating probe set-specific variability is superior to analysis based on arbitrary fold-change thresholds. We recommend its incorporation to any computation of gene expression changes using high-density DNA microarrays. A Java application implementing our T-score is available at http://www.sadovsky.wustl.edu/tscore.html.

Algorithms↗
PubMed2006

Physiological analysis of Methylobacterium extorquens AM1 grown in continuous and batch cultures.

Chemostat cultures of Methylobacterium extorquens AM1 grown on methanol or succinate at a range of dilution rates were compared to batch cultures in terms of enzyme levels, poly-beta-hydroxybutyrate content, and intracellular concentrations of adenine and pyridine nucleotides. In both chemostat and batch cultures, enzymes specific to C1 metabolism were up-regulated during growth on methanol and down-regulated during growth on succinate, polyhydroxybutyrate levels were higher on succinate, intracellular ATP levels and the energy charge were higher during growth on methanol, while the pools of reducing equivalents were higher during growth on succinate. For most of the tested parameters, little alteration occurred in response to growth rate. Overall, we conclude that the chemostat cultivation conditions developed in this study roughly mimic the growth in batch cultures, but provide a better control over the culturing conditions and a better data reproducibility, which are important for integrative functional studies. This study provides baseline data for future work using chemostat cultures, defining key similarities and differences in the physiology compared to existing batch culture data.

Adenine Nucleotides↗
PubMed1981

[Quality control in acid-base and gas analysis of the blood].

The data from the intra-laboratory qualitative control art analyzed--accuracy and reproducibility of the results from the determinations of pH, pCO2 and pO2. Reproducibility is followed day by day and the accuracy of the results from the determinations of pH, pCO2, and pO2. The determinations were performed as follows: pH--by micro-electrode, pCO2--by equilibrium and by selective electrode, pO2--by electrode, Clark type with apparatuses VME 22, VME 32 and automatic analyser for blood-gas analysis ABL 2 (Radiometer). Acidbasol and Versatol Acid-Base were used as control materials in the three ranges: normal, acid and alkaline. Reproducibility of the results as regards time, presented by variation coefficient (VC), followed up for a period of 9 months by the control materials Acidbasol with ABL 2 apparatus proved to be very good in the three ranges tested for pH and pCO2. Results dispersion is higher with pO2 determinations, even higher with the low values. The accuracy of the results from pH and pCO2, determinations for the same period was within the allowable limits. A very good reproducibility of pH and pCO2 was indicated by the reproducibility data in time of the results from pH and pCO2 determinations from one year with the three apparatuses, making use of the control serum Versatol Acid-Base for the three ranges. Better variation coefficients by equilibrium method were established for the higher values of pCO2 with its automatic determination. High reliability of the investigation methods was established be the results from the systematic qualitative control of acid-base and blood-gas parameters.

Acid-Base Equilibrium↗
PubMed2003

Radiation-induced gene expression in MCF-7 cells.

PURPOSE: Detection of gene targets applicable to biological dosimetry and early detection of radiation-induced cell damage. MATERIALS AND METHODS: MCF-7 human mammary carcinoma cells were exposed to 2 and 6 Gy X-rays. Expression of 1176 genes was traced with the Atlas Human 1.2 Array (Clontech). RESULTS: (1) Based on data reproducibility (about 98%), a new and improved analysis was employed. (2) Normalization of data using ubiquitin or total gene expression led to the same results. (3) Dose-dependent gene expression was shown for six genes, which were constantly expressed over 1 day (three genes), 2 days (two) and 3 days (one). Differential gene expression was confirmed by RTQ-PCR. Three of the six genes were novel radiation-induced gene targets. (4) When analysing the expression of all genes, the processes of cell degradation (e.g. cell death and protein catabolism) were activated. Simultaneously, inhibition not only of cell proliferation, but also of other cellular functions (e.g. cell repair) was found. Hence, cell death appears a process of 'active silencing'. CONCLUSIONS: With the screening method applied, six radiation-induced gene targets were found, three of which were novel genes. Their applicability in other cell models remains to be tested. Different sets of genes have to be considered for dose assessment, owing to their changes in gene expression with time after irradiation. Furthermore, it has to be investigated whether 'active silencing' represents a general principle of radiation-induced cell death.

Base Sequence↗
PubMed2006

DNA separations.

The use of two types of commercialized microfluidic chips for separation of double-stranded DNA (dsDNA), suitable for personal scale and high throughput use, is described. Compared with conventional approaches such as slab-gel and capillary electrophoresis (CE), these devices offer the advantages of faster separation times, better data reproducibility, greater ease of use, labor savings in quantitative analysis, and ease in data archiving and data sharing owing to the digital data format. With some simple precautions taken in keeping bubbles and particulates out of the microchannels, Lab-on-a-Chip devices have been adopted by many researchers in molecular biology and genomics laboratories to increase their productivity.

DNA↗
PubMed2006

Protein separations.

This chapter describes the use of two types of commercialized microfluidic chips for protein separation, suitable for personal scale and high-throughput use. Compared with conventional approaches, such as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and capillary electrophoresis (CE), these devices offer the advantages of faster separation times, better data reproducibility, greater ease of use, labor savings in quantitative analysis, and ease in data archiving and data sharing owing to the digital data format. With some simple precautions taken to keep bubbles and particulates out of the microchannels, Lab-on-a-Chip devices have been adopted by many researchers in protein processing, protein engineering, and proteomics research laboratories to increase their productivity.

Electrophoresis, Microchip↗
PubMed1997

A novel highly reproducible quantitative competitve RT PCR system.

Small changes in plasma fibrinogen concentration are often clinically important. To detect changes in fibrinogen mRNA level, we have designed a novel quantitative competitive reverse transcriptase (RT) PCR system, based on our recent understanding that an important factor causing imprecision with RT PCR is a change in the initial ratio of target to standard RNA templates during reverse transcription. The system comprises: (1) titration of a fixed amount of standard RNA with four different amounts of total RNA in each tube during cDNA synthesis; (2) amplification of each of the four cDNAs with four consecutive PCR cycles; and (3) quality control reactions in which synthesised quality control RNA (rather than total RNA) is added to the standard RNA under the same RT PCR conditions as the assay reaction. To obtain reproducible data, we suggest three criteria for analysis of RT PCR results. Employing these criteria, reproducibility of RT PCR was markedly improved with an inter-assay CV of 6.5% (n=5). Using this system, we are able to detect reduction in mRNA levels of all fibrinogen genes caused by dietary protein restriction in rats after weaning (alpha 39%, p= 0. 028; beta 55%, p = 0.017; gamma 35 %, p= 0.038), with a parallel reduction of plasma fibrinogen concentration (mean (+/-SD), 157(+/-19) versus 130(+/-14) mg/dl, p=0.006).

Analysis of Variance↗
PubMed1998

Reproducibility of optic disk topographic measurements with the Topcon ImageNet and the Heidelberg Retina Tomograph.

OBJECTIVE: To compare the reproducibility of optic disk measurements provided by an image analyzer and a scanning laser tomograph. METHODS: Ten images of the same eye of 10 normal volunteers were taken with the Heidelberg Retina Tomograph and with the Topcon ImageNet. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) were used to evaluate the reproducibility of the measurements. RESULTS: Eleven parameters were analyzed with the Topcon ImageNet. Six parameters (55%) had ICC greater than 90%. Four parameters (36%) had CV less than 10%. Twelve parameters were evaluated with the Heidelberg Retina Tomograph. Nine parameters (75%) had ICC over 90%. Nine parameters (75%) had CV less than 10%. CONCLUSION: Both systems provided reproducible data. The optic disk parameters provided by the Heidelberg Retina Tomograph had a better reproducibility than those obtained from the Topcon ImageNet.

Adult↗