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Use of dimensional analysis to reduce medication errors.

The purpose of this pilot study was to determine whether using dimensional analysis as the method of mathematical computation could reduce nursing medication calculation errors. The sample for this study consisted of second-year baccalaureate nursing students in a required clinical skills course. Students in the control group were taught medication calculations using the traditional math method during one semester, whereas students in the experimental group were taught the same material using dimensional analysis during the next semester. Analysis of the collected data from a medication dosage calculation examination revealed the dimensional analysis group scored with greater accuracy than the traditional math group.

Attitude of Health Personnel↗

High grade squamous cervical lesions following negative Papanicolaou smears: false-negative cervical cytology or rapid progression.

The cervical cytologic finding of a high grade squamous intraepithelial lesion (HGSIL) or carcinoma shortly following a negative smear is unusual. To determine if such cases are due to screening errors, inadequate sampling, or rapidly progressive lesions, a review of negative smears (immediately preceding a diagnosis of HGSIL or carcinoma by at most 2 yr) was performed on 17 patients (all such patients in our 1990-92 files, representing 6% (17/290) of such diagnoses). The time between negative smear and positive result averaged 9.3 mo. Eighty-eight percent of these patients had prior histories of a cytologic abnormality. Upon review, 16 of 17 "negative" smears contained a cytologic abnormality. Atypical immature squamous metaplastic type cells (AISMTs) were found in 11 of 16 cases, atypical squamous cells or slight dysplasia were found in 5 of 16, HGSIL was found in 5 of 16, and atypical cells of undetermined type and origin were noted in 1 of 16. Combinations of the above diagnoses were present in 6 of 16 cases. The number of abnormal cells per slide was estimated, with < 10 cells in 1 case, < 50 in 4 cases, 50-100 in 7 cases, 100-200 in 3 cases, and > 200 in 1 case. In this study, screening and/or evaluation errors were the dominant cause of false-negative cytologic diagnoses, with AISMTs accounting for the most commonly missed or misinterpreted cells. These cells are small and have hyperchromatic nuclei with elevated nucleus to cytoplasmic ratio and nuclear irregularities.

Adult↗

Sources of uncertainty in the quantification of genetically modified oilseed rape contamination in seed lots.

Testing of seed and grain lots is essential in the enforcement of GM labelling legislation and needs reliable procedures for which associated errors have been identified and minimised. In this paper we consider the testing of oilseed rape seed lots obtained from the harvest of a non-GM crop known to be contaminated by volunteer plants from a GM herbicide tolerant variety. The objective was to identify and quantify the error associated with the testing of these lots from the initial sampling to completion of the real-time PCR assay with which the level of GM contamination was quantified. The results showed that, under the controlled conditions of a single laboratory, the error associated with the real-time PCR assay to be negligible in comparison with sampling error, which was exacerbated by heterogeneity in the distribution of GM seeds, most notably at a small scale, i.e. 25 cm3. Sampling error was reduced by one to two thirds on the application of appropriate homogenisation procedures.

Base Sequence↗

Sensitivity of frozen section examination of pelvic lymph nodes for metastatic prostate carcinoma.

BACKGROUND: A Total Quality Improvement review of frozen section diagnoses yielded four sequential false-negative frozen section diagnoses in lymph nodes in the evaluation of metastases from prostate carcinoma. Because these results appeared to differ from the department's overall frozen section experience, frozen section diagnoses of pelvic lymph nodes in patients with prostate carcinoma were reviewed to benchmark the department's performance. METHODS: All 220 pelvic lymph node frozen section samples from 110 patients with prostate carcinoma from January, 1986 to July, 1993 at Bridgeport Hospital (BH) were reviewed, and the department's frozen section diagnostic efficiency was compared with: (1) all BH frozen section procedures performed during the same period; (2) pelvic lymph node frozen section analysis and (3) imaging techniques for prostate carcinoma from other institutions found in MEDLARS literature searches from 1973 to 1993. RESULTS: Frozen section diagnostic efficiency for patients with prostate carcinoma from BH was 93.6% (sensitivity 63.2%, specificity 100%) compared with (1) 98% for all BH frozen section analyses (sensitivity 99%, specificity 98%); (2) 90.1% for MEDLARS search pelvic lymph node frozen section prostate carcinoma analyses (sensitivity 66.5%, specificity 100%); and (3) 88% for MEDLARS search magnetic resonance imaging (MRI) pelvic lymph node prostate carcinoma (sensitivity 41%, specificity 97%). CONCLUSIONS: Frozen section diagnosis of pelvic lymph nodes approaches the overall diagnostic efficiency of frozen section analysis and is more sensitive for the diagnosis of prostate carcinoma in pelvic lymph nodes than is MRI because more than half of the metastases are smaller than the 1.0-cm resolution limit of the MRI. False-negative frozen section diagnoses (67% sensitivity) occur because of errors in sampling microscopic metastases.

Adenocarcinoma↗

An empirical assessment of long-branch attraction artefacts in deep eukaryotic phylogenomics.

In the context of exponential growing molecular databases, it becomes increasingly easy to assemble large multigene data sets for phylogenomic studies. The expected increase of resolution due to the reduction of the sampling (stochastic) error is becoming a reality. However, the impact of systematic biases will also become more apparent or even dominant. We have chosen to study the case of the long-branch attraction artefact (LBA) using real instead of simulated sequences. Two fast-evolving eukaryotic lineages, whose evolutionary positions are well established, microsporidia and the nucleomorph of cryptophytes, were chosen as model species. A large data set was assembled (44 species, 133 genes, and 24,294 amino acid positions) and the resulting rooted eukaryotic phylogeny (using a distant archaeal outgroup) is positively misled by an LBA artefact despite the use of a maximum likelihood-based tree reconstruction method with a complex model of sequence evolution. When the fastest evolving proteins from the fast lineages are progressively removed (up to 90%), the bootstrap support for the apparently artefactual basal placement decreases to virtually 0%, and conversely only the expected placement, among all the possible locations of the fast-evolving species, receives increasing support that eventually converges to 100%. The percentage of removal of the fastest evolving proteins constitutes a reliable estimate of the sensitivity of phylogenetic inference to LBA. This protocol confirms that both a rich species sampling (especially the presence of a species that is closely related to the fast-evolving lineage) and a probabilistic method with a complex model are important to overcome the LBA artefact. Finally, we observed that phylogenetic inference methods perform strikingly better with simulated as opposed to real data, and suggest that testing the reliability of phylogenetic inference methods with simulated data leads to overconfidence in their performance. Although phylogenomic studies can be affected by systematic biases, the possibility of discarding a large amount of data containing most of the nonphylogenetic signal allows recovering a phylogeny that is less affected by systematic biases, while maintaining a high statistical support.

Animals↗

[Pre-analytic errors in the determination of arterial O(2)-partial pressure under hyperoxic conditions].

OBJECTIVE: A variety of influences reduce the validity of the measured oxygen partial pressure (paO(2)). Most errors occur when obtaining the blood sample and preparing it for analysis. Unfortunately, there is great controversy concerning the relevance and extent of these pre-analytic errors. Apart from this, the exact estimation of influencing factors under hyperoxic conditions has been neglected. Therefore, the objective of this study was to assess pre-analytic measuring errors for paO(2) under the condition of hyperoxia as completely as possible and to work out solutions to eliminate these errors. METHODS: paO(2) analysis was performed on more than 2000 blood samples. Errors analyzed were the technique of sample taking (direct puncture or from an indwelling catheter), aspirated air bubbles (0.05-0.35 ml), time and temperature of sample storage, and the material, size and manufacturer of the analyzing syringe. RESULTS: The paO(2) was on average 41 mmHg lower in samples taken from the indwelling catheter than by direct puncture. An air bubble size of 0.1-0.25 ml caused a decrease of 17-41 mmHg. Storage time of 2 min accounted for an paO(2) reduction of 6-67 mmHg depending on the type of syringe used. Glass syringes turned out to be more accurate than plastic syringes. The best results were obtained not from commercial "blood gas syringes" but from a simple plastic injection syringe. For all pre-analytic errors correction factors were established. CONCLUSION: All pre-analytic errors investigated caused a significant paO(2) decrease. Even an ideal procedure (almost no air bubble, short storage on ice) contributes a significant error. Only the appropriate correction factors as calculated from this study for routine use lead to the correct results. If they are not taken into account the paO(2) values will be falsely low, potentially leading to misinterpretation and misjudgement of a patient's condition.

Humans↗

Screening for clinical laboratory errors with Medicare claims data: results for digoxin.

A statistical model is demonstrated for finding outpatient clinical laboratories having high frequencies of bad patient outcomes, after testing, that may indicate testing errors. A sample of Medicare Part A and Part B claims for 30,685 digoxin tests for 1985 through 1987 was analyzed. Deaths or digoxin-related hospitalizations within 14 days of digoxin testing are defined as "adverse events" potentially influenced by test information. Approximately 3.3% of digoxin tests were followed by adverse events with two-thirds resulting in hospitalization or death. Adverse events were (a) lower in states with stronger laboratory regulations, (b) 15% higher whenever the site of testing switched, (c) unrelated to testing in low volume physician office laboratories, and (d) unrelated to frequency of digoxin testing in previous 6 months. Results a and b are consistent with findings for prothrombin testing but c and d are not. Differences are consistent with technical characteristics of the tests.

Anti-Arrhythmia Agents↗

A community survey of ptosis of the eyelid and pupil size of elderly people.

A randomly selected, age-stratified sample of subjects 50 years of age and older, living in the Salford Health District area of Greater Manchester was drawn from the age-sex register of a four-doctor group practice and invited by post to enter a study of ptosis. Of 851 subjects approached, 499 (59%) replied. Of these, 99 refused to participate. The remaining 400 were visited at home and underwent a standardized protocol of ophthalmic history, and examination including a photograph of the eyes in the primary position. Forty-six (11.5%) of the subjects had ptosis and its prevalence increased with age. Ptosis was bilateral in 18 (39%) and unilateral in 28 (61%). In all but four cases, the ptosis was acquired. The cause was evident in 23 (50%), with 11 cases being due to mechanical ptosis and 12 to aponeurotic disinsertion secondary to a known pathology. A further 22 cases had primary aponeurotic disinsertion and there was one case of probable myasthenia gravis. The prevalence of pupillary diameter of 1 mm or less increased significantly with age.

Aged↗

High affinity binding of fluorescein isothiocyanate to eosinophils detected by laser scanning cytometry: a potential source of error in analysis of blood samples utilizing fluorescein-conjugated reagents in flow cytometry.

BACKGROUND: In samples of peripheral blood cells processed using the commercial kits for detection of apoptosis based on DNA strand break labeling, a subpopulation of cells characterized by high green fluorescence, similar in intensity to that of apoptotic cells but more uniform, was consistently observed by flow cytometry. The labeled cells had no other features of apoptosis. The labeling was observed regardless of the fixative used and was evident in control samples lacking terminal deoxynucleotidyltransferase. Common to all the kits that generated this labeling pattern was the presence of fluorescein (f) conjugated reagents, f-dUTP, f-avidin, or f-antibody. METHODS: Laser scanning cytometry was used to identify the labeled cells and study the mechanism of labeling. Because it was suspected that the traces of unconjugated f-isothiocyanate (FITC) that may contaminate the reagents were responsible for the labeling, FITC binding affinity to white blood cells was studied. Gel electrophoresis was used to detect the presence of unconjugated FITC in the reagents. RESULTS: After staining with Giemsa, the strongly fluorescent objects were identified as eosinophils with normal morphology and no evidence of apoptosis. The fluorescence was localized exclusively within the cytoplasmic granules. Labeling of eosinophils was observed at 2 nM concentration of FITC, which was over three orders of magnitude lower than that needed to label neutrophils, monocytes, or lymphocytes. Gel electrophoresis of the f-conjugated reagents revealed only minor contamination with FITC. CONCLUSIONS: (1) Trace amounts of unconjugated FITC contaminating the reagents are adequate to strongly label eosinophils thereby introducing experimental bias in analysis of apoptosis and in other studies on blood cells utilizing f-labeled antibodies, e.g., in detecting cytokines. (2) FITC at concentration 2-500 nM can be used as a marker of eosinophiles; (3) Because of high affinity to FITC, eosinophiles (or the protein from these cells) may serve as a means of removing traces of unconjugated FITC from the reagents during their manufacture or prior to use.

Apoptosis↗

Instrumentation for positron emission tomography.

Positron emission tomography with a spatial resolution of 2 mm full width at half maximum for quantitation in regions of interest 4 mm in diameter will become possible with the development of detectors that achieve ultrahigh resolution. Improved resolution will be possible using solid-state photodetectors for crystal identification or photomultiplier tubes with many small electron multipliers . Temporal resolution of 2 seconds and gating of cyclic events can be accomplished if statistical requirements are met. The major physical considerations in achieving high-resolution positron emission tomography are the degradation in resolution resulting from positron range, emission angle, parallax error, detector sampling density, the sensitivity of various detector materials and packing schemes, and the trade off between temporal resolution and statistical accuracy. The accuracy of data required for physiological models depends primarily on the fidelity of spatial sampling independent of statistical constraints.

Humans↗

Simple method to measure power density entering a plane biological sample at millimeter wavelengths.

A simple method for measuring microwave power density is described. It is applicable to situations where exposure of samples in the near field of a horn is necessary. A transmitted power method is used to calibrate the power density entering the surface of the sample. Once the calibration is available, the power density is known in terms of the incident and reflected powers within the waveguide. The calibration has been carried out for liquid samples in a quartz cell. Formulas for calculating specific absorption rate (SAR) are derived in terms of the power density and the complex dielectric constant of the sample. An error analysis is also given.

Calibration↗

Evaluation of two oximeters for use in cardiac catheterization laboratories.

We evaluated two whole-blood oximeters designed for use in the cardiac catheterization laboratory: the Oxicom 3000 and the AVOXimeter 1000. Unlike the larger CO-Oximeters, which hemolyze a blood sample before analysis, these simple instruments use disposable cuvettes to allow determination of oxyhemoglobin saturation of whole blood. Thus they eliminate the need for cleaning solutions and considerable maintenance. We evaluated the accuracy of these instruments in comparison with a Radiometer OSM3 and found them both to work well on routine samples. Of note, the AVOXimeter performed better than the Oxicom when the sample was hemolyzed and when green dye was present. In addition, the AVOXimeter measures the total hemoglobin concentration and the oxygen content of each sample, eliminating errors that hemodilution introduces into the determination of cardiac output by the Fick principle. We conclude that whole-blood oximeters are accurate and useful instruments for use in the cardiac catheterization laboratory.

Calibration↗

Count-dependent filter for smoothing bivariate FCM histograms.

A data-smoothing filter has been developed that permits the improvement in accuracy of individual elements of a bivariate flow cytometry (FCM) histogram by making use of data from adjacent elements, a knowledge of the two-dimensional measurement system point spread function (PSF), and the local count density. For FCM data, the PSF is assumed to be a set of two-dimensional Gaussian functions with a constant coefficient of variation for each axis. A set of space variant smoothing kernels are developed from the basic PSF by adjusting the orthogonal standard deviations of each Gaussian smoothing kernel according to the local count density. This adjustment in kernel size matches the degree of smoothing to the local reliability of the data. When the count density is high, a small kernel is sufficient. When the density is low, however, a broader kernel should be used. The local count density is taken from a region defined by the measurement PSF. The smoothing algorithm permits the reduction in statistical fluctuations present in bivariate FCM histograms due to the low count densities often encountered in some elements. This reduction in high-frequency spatial noise aids in the visual interpretation of the data. Additionally, by making more efficient use of smaller samples, systematic errors due to system drift may be minimized.

Cell Count↗

Fumonisin B1 analysis with capillary electrophoresis-electrospray ionization mass spectrometry.

Fumonisin B1, a mycotoxin produced by a common fungal contaminant of corn, Fusarium moniliforme, was analyzed by capillary electrophoresis-electrospray ionization mass spectrometry. System performance was maximal with uncoated columns. System efficiencies of approximately 44,000 plates/m and reproducible analysis times of about 13 min were obtained. System efficiency with methyl-coated columns was approximately 24,000 plates/m. Reproducible analysis times of about 3.5 min were obtained with these columns. With uncoated columns, the concentration limit of detection was 156 ppb with a s/n ratio of approximately 10. The estimated injected mass at 156 ppb was 1.1 pg. Repeated injections of extracts containing constant fumonisin B1 concentrations showed that peak areas were slightly inconsistent, although generally similar to variations encountered with liquid chromatography-electrospray ionization mass spectrometry. The source of this inconsistency was traced to sample solubility, errors inherent in electrophoresis injections, and electrospray instability. Minimizing these problem areas will produce a technique with peak area reproducibilities comparable to liquid chromatography-electrospray ionization mass spectrometry, but with potentially greater resolving power.

Carcinogens, Environmental↗

Method for the simultaneous determination of retinol and beta-carotene concentrations in human tissues and plasma.

To understand differential tissue distribution of retinoids and carotenoids, as it might influence biological processes in humans, we developed and demonstrated a method for measuring them in selected human tissues. The method includes internal standards and a secondary reference standard to eliminate the need for external standard calibration and to minimize sample-handling errors. Tissues were digested (saponified) in ethanolic KOH. Retinol and beta-carotene were extracted with organic solvent containing internal standards. Analytes were separated using isocratic liquid chromatography and quantified at 325 nm for retinol and 450 nm for beta-carotene. Plasma was analyzed in a similar way but without saponification. Retinal-O-ethyloxime and beta-apo-12'-carotenal-O-t-butyloxime served as internal standards. Plasma, breast, and fat from breast surgery patients and colon, liver, muscle, and fat from colon surgery patients were analyzed. Within-day relative standard deviations (RSDs) for plasma were <0.04 for beta-carotene and <0.03 for retinol, between-day RSDs were <0.05 for beta-carotene and <0.04 for retinol. Saponification ensured complete extraction of retinol and beta-carotene and removal of triglycerides that "foul" chromatographic columns. It seems retinol and beta-carotene concentrations in tissues and blood of cancer patients are the same or higher than those in corresponding tissues of patients without these cancers.

Adult↗

Atomic force microscopy imaging of the human trigeminal ganglion.

This paper describes an investigation of gangliocytes via imaging semithin sections of two human trigeminal ganglia with an atomic force microscope (AFM). Whereas semithin sections are usually employed for transmission electron microscopy, we adopted this special type of sample preparation for our AFM studies to extract topographical data from the gangliocyte itself and from the nucleus, the nucleolus, the crystal-arranged lipofuscin granules, and the cell-surrounding mantle cells; simultaneously we characterized the samples with error signal mode. This AFM-related technique revealed no information concerning friction force and elasticity due to the presence of the embedding material (epoxy), but it gave additional topographical contrast. These are the first images of the human trigeminal ganglion by AFM.

Adult↗

Unexpectedly high peak expiratory flow rates in normal Greek children.

Peak expiratory flow rate (PEFR) and standing height (Ht) were measured in 522 healthy Greek children aged 7-16 years. The regression equation of PEFR on height in centimetres was PEFR = 5.34 Ht--380.8. This demonstrated markedly higher values for PEFR in Greek children compared to previously published data from other countries. A sample of 339 British children was examined similarly. The regression equation of PEFR on height in centimetres was PEFR = 5.64 Ht--472.5. This was similar to previously published data. No cause for this discrepancy was found after close examination of population sampling, measurement error or calibration error in the Greek study. It is therefore concluded that Greek children appear to have an unexpectedly high PEFR for height.

Adolescent↗