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PubMed1975

Some statistical characteristics of voice fundamental frequency.

Two experiments are reported in which the magnitude of sampling errors associated with estimates of the mean, median, and standard deviation of voice fundamental frequencies (fo) during oral reading is investigated as a function of sample size. In one experiment, voices are sampled with fixed time windows. In the other experiment, results of fo analysis are compared for single-sentence voice samples and paragraph voice samples. Overall shape of fo distributions as well as interrelationships among various distributional measures are discussed.

Adult↗

PubMed1993

Intraoperative frozen section diagnosis in skull base surgery.

During January 1990 through June 1992, we performed 39 surgeries for base of skull tumors with extracranial and intracranial involvement on 33 patients. Intraoperative frozen section was requested on 581 of 904 specimens submitted (64%). There was a discrepancy between the frozen section diagnosis and final diagnosis in 15 specimens for an error rate of 3%. There were two false-positive diagnoses of malignancy and 13 false-negative diagnoses. The discrepancies were a result of sampling error in ten cases and of interpretive error in five cases. Four of the five interpretive errors involved intradural tissues. Only two of the discrepancies were clinically significant. One involved the evaluation of adequacy of surgical margins and a second involved the misinterpretation of metastatic renal cell carcinoma for hemangioblastoma. We recommend careful attention to cryostat sectioning and interpretive experience in head and neck pathology and neuropathology. The importance of vigilant communications between surgeon and pathologist before, during, and after surgery cannot be overstated. We are utilizing a video-linked microscopic network that allows the surgeon to view the frozen section histologic sections in the operating room. Future trends may include the use of monoclonal antibodies and morphometry to improve accuracy in frozen section diagnosis.

Journal Article↗

PubMed1996

Detection of cytomegalovirus in blood donors by PCR using the digene SHARP signal system assay: effects of sample preparation and detection methodology.

Cytomegalovirus (CMV) is an important cause of transfusion-associated morbidity and mortality; however, only 0.4 to 12% of the blood products obtained from seropositive blood donors transmit infection. The effects of three commercially available whole-blood sample preparation kits on the detection of CMV PCR products by a semiquantitative adaptation of the Digene SHARP Signal System Assay (DSSSA) in samples from volunteer blood donors was assessed. Of 101 samples from seropositive blood donors, CMV was detected in 0 (0%) of the samples extracted with a QIAamp blood kit (QIAGEN), 1 (1%) of the samples extracted with an Amplicor whole-blood specimen preparation kit (Roche), and 8 (8%) of the samples extracted with an Isoquick nucleic acid extraction kit (modified by the addition of carrier tRNA) (Microprobe). CMV DNA was not detected in samples from seronegative blood donors (n = 13). Nested PCR of selected samples confirmed the detection of CMV in the sane eight samples extracted with the modified Isoquick nucleic acid extraction kit and detected an additional nine CMV-positive samples (n = 50). Samples from volunteer blood donors contain low copy numbers of CMV DNA. PCR amplification of such specimens can result in analytical sampling errors, giving results similar to the variations in titers recognized during determinations of the 50% tissue culture infective dose. The detection of CMV in blood samples from volunteer blood donors by PCR is a function of sample preparation, amplification conditions, and detection methodology. Accurate assessments of the clinical utility of CMV DNA detection by nucleic acid amplification for blood product screening and patients will require highly standardized and quantitative methodology.

Blood Donors↗

PubMed1999

Laboratory-based quality assurance programme for near-patient urine dipstick testing, 1990-1997: development, management and results.

The need for quality assurance (QA) programmes covering near-patient testing technologies has been acknowledged since the mid-1980s. However, most effort has been directed towards capillary blood glucose monitoring techniques. The most common biochemical near-patient testing device is the dry reagent strip or 'dipstick' for urinalysis. This report describes a quality assurance programme for urinalysis, used in the wards and clinics of a district general hospital, and in some of the general practitioner surgeries within its catchment area. The project describes the preparation of an aqueous 'urine' sample, the design of a report form, the dispatch of the sample and report forms to the ward/clinic/health centre, the receipt and scoring of the returned results, and the assessment of the results, both in terms of management information and sources of error. Samples were spiked to give a target value midway between two colour blocks for each analyte. Results were scored as +/- 1 if adjacent colour block to the target, +/- 2 for results two colour blocks (error) and +/- 3 (gross error) for results three or more colour blocks from the target value. For urine glucose, results showed an overall 14.7% error and 2.6% gross error rate. Similar scoring gave the following error and gross error rates for the other analytes: bilirubin (1.0%, 3.3%); ketone (4.3%, 0.3%); specific gravity (13.4%, 3.1%); pH (11.2%, 6.5%); blood (7.7%, 2.9%); protein (9.7%, 2.3%); and nitrite (gross errors 4.9%). Investigation of the results of the programme showed four types of error in dipstick testing-timing, misalignment, misunderstanding and transcription. Analysis of the results showed a reduction in error rates when an electronic reader was used (errors 2.0%, gross errors 0.75%), compared to reading against the colour blocks on the side of the bottle (7.7%, 1.6%) or using the colour blocks on a flat card reader (7.4%, 1.7%). The report demonstrates the importance of a QA scheme in providing a reliable screening service. It gives confidence to the users of dipsticks, information on training needs to clinical managers, and an understanding of both types of error and how they can be reduced.

England↗

PubMed1991

Sources of diagnostic discrepancies in fine-needle aspiration of the breast.

Fine-needle aspiration (FNA) is a valuable technique to use in the evaluation of breast lesions; however, inadequate and discrepant diagnoses do occur. To identify the source and nature of inaccuracies related to the method we studied 39 cases in which FNA posed diagnostic problems. These problems could be attributed to sampling errors (71.8%), to the criteria of adequacy we use at our institution (25.6%), and to interpretation (2.6%). The nature of the breast lesion (68%) was the most common cause of inadequate sampling, followed by the experience of the aspirator (32%).

Biopsy, Needle↗

PubMed1992

Information, discrimination and divergence in cytology. VI. Biases and errors of measurement in small samples.

Total discrimination and total divergence have been shown to be useful measures of performance in diagnostic cytology. The sample size, Ns (observed number of cytology-histology pairs, essential components of a confusion matrix), may be small for the comparison of two or more laboratories or periodic quality control using observed values. From actual data from previous reports in this series, the best estimation of the confusion matrix of a population was obtained by fitting a Gaussian-type curve after pseudoscalar transform of ranks (row and column numbers). Small sample confusion matrices were generated by Monte Carlo simulation to 2.5 x 10(-7) resolution. To keep measurement biases within +/- 0.5 decits, we found that 100-200 samples of cytology-histology pairs were required in the best classifications of three, four and five category-states. At these sample sizes, measurement errors (standard errors) were also contained within +/- 0.5 decits. This study also confirmed that previously reported overestimated propagated errors in small samples were in fact overestimation and that their use for testing a null hypothesis was valid. The number of samples with indefinable statistics due to a zero denominator can be as high as 30% when the sample sizes are 500 for three, four and five category-state classifications. Biases due to small samples were positive for most category-states except for the optimum three category-states, in which bias changed to negative ("bias inversion"), and observed errors of discrimination and divergence paradoxically decreased as Ns decreased ("error-sample paradox") for a small sample size (Ns less than 700).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytodiagnosis↗

PubMed1990

The impact of dietary measurement error on planning sample size required in a cohort study.

Dietary measurement error has two consequences relevant to epidemiologic studies: first, a proportion of subjects are misclassified into the wrong groups, and second, the distribution of reported intakes is wider than the distribution of true intakes. While the first effect has been dealt with by several other authors, the second effect has not received as much attention. Using a simple errors-in-measurement model, the authors investigate the implications of measurement error for the distribution of fat intake. They then show how the inference of a more narrow distribution of true intakes affects the calculation of sample size for a cohort study. The authors give an example of the calculation for a cohort study investigating dietary fat and colorectal cancer. This shows that measurement error has a profound effect on sample size, requiring a six- to eightfold increase over the number required in the absence of error, if the correlation coefficient between reported and true intakes is 0.65. Reliable detection of a relative risk of 1.36 between a true intake of greater than 47.5% calories from fat and less than 25% calories from fat would require approximately one million subjects.

Bias↗

PubMed2000

Causes of unsatisfactory performance in proficiency testing.

BACKGROUND: Proficiency testing (PT) provides a measure of the effectiveness of laboratory quality assurance programs. Test reports are released from processes that the laboratory judges to be in conformance with quality specifications; an evaluation of unsatisfactory performance (UNSAT) by a PT provider is an unexpected outcome for the laboratory. An understanding of the root cause(s) of testing errors provides an opportunity for the continuous improvement of laboratory services. METHODS: We used participant data from the New York State Department of Health PT program to characterize the quality of testing in the toxicology specialty. Outcomes from laboratory investigations into causes of UNSAT and information on quality control practices collected from all program participants were used to identify the root causes of error. RESULTS: Two classes of error were encountered: spurious test results caused by lapses in standard operating procedures and instrument malfunctions (300 per million assays) and common-cause analytic error (7000 per million assays or 0.7% rate of UNSAT). Causes of spurious results included inaccurate mathematical correction for specimen dilution, misinterpretation of instrument codes, and instrument sampling errors. Calibration drift was most frequently cited as the common-cause analytic error. Approximately one-half of the laboratories used an allowable error for the quality control of analytical systems that exceeded the threshold error specified by manufacturers for stable instrument performance. CONCLUSIONS: The causes of spurious results suggest the need for ongoing competency testing of analysts where analyst intervention is required in an otherwise automated process, and for continued diligence in mistake-proofing instrument design. The intrinsic quality of laboratory testing is unlikely to improve until the allowable error in quality control is consistent with manufacturer specifications for stable system performance.

Clinical Chemistry Tests↗

PubMed2003

[False negative Pap smears in a Danish material].

INTRODUCTION: The aims of screening against cervical cancer are: 1) to reduce the number of cervical cancer cases, 2) to diagnose the cervical carcinoma precursor lesions of which treatment is quite simple and 3) to use the available resources in the best possible way. The purposes of this study were firstly to get an impression of the false negative rate in the County of Funen, secondly to illustrate some of the causes, and thirdly to recommend some ways to reduce the false negative cases in the future. MATERIAL AND METHODS: All previously negative Pap smears in the period from April 1, 1989 to December 31, 1999 from women who had shown at least moderate dysplasia histologically in the period from Jan 1, 1996 to December 31, 2000 were reevaluated. RESULTS: A total of 551 Pap smears were rescreened. Eighty-one per cent were sampling errors and the rest was regarded as interpretation and screening errors. The false negative rate for a single year, 1991, was assessed at 22%. The false negative rate of interpretation and screening errors was 4.6%. DISCUSSION: The results are in accordance with other studies. We describe three characteristical cytological cell patterns as the main causes of the false negative samples. To prevent false negative samples a very important factor is thorough training and further education of the staff. Furthermore, a change into liquid-based cytology will raise the quality both of the cell sample and of the screening procedure.

Adenocarcinoma↗

PubMed1993

[Estimation of the sampling variance of co-heritability].

Formulae for the sampling variances of co-heritability and co-environment are developed from the one-fold and two-fold nested genetic analyses of variance and covariance with balanced and unbalanced data. Some potential roles of the co-heritability in breeding programs and the relationship with genetic correlation have also been investigated. The co-heritability has dual characteristics of both heritability and genetic correlation. Heritability is a special case of co-heritability with co-heritability an extended form of heritability. The use of co-heritability to express the genetic covariation between two characters will give smaller sampling errors than those of the genetic correlation (gamma A).

Analysis of Variance↗

PubMed2006

Long loop prediction using the protein local optimization program.

We have developed an improved sampling algorithm and energy model for protein loop prediction, the combination of which has yielded the first methodology capable of achieving good results for the prediction of loop backbone conformations of 11 residue length or greater. Applied to our newly constructed test suite of 104 loops ranging from 11 to 13 residues, our method obtains average/median global backbone root-mean-square deviations (RMSDs) to the native structure (superimposing the body of the protein, not the loop itself) of 1.00/0.62 A for 11 residue loops, 1.15/0.60 A for 12 residue loops, and 1.25/0.76 A for 13 residue loops. Sampling errors are virtually eliminated, while energy errors leading to large backbone RMSDs are very infrequent compared to any previously reported efforts, including our own previous study. We attribute this success to both an improved sampling algorithm and, more critically, the inclusion of a hydrophobic term, which appears to approximately fix a major flaw in SGB solvation model that we have been employing. A discussion of these results in the context of the general question of the accuracy of continuum solvation models is presented.

Algorithms↗

PubMed1984

The effect of numbers of noise events on people's reactions to noise: an analysis of existing survey data.

The effect of the number of noise events on noise annoyance has been examined in an analysis of data from large-scale social surveys. The relative impact of noise level and number on human reactions is measured by the decibel equivalent number effect (k) expressed as the number of decibels which have an effect equivalent to that of a tenfold increase in number of events. Values of k differ between surveys but none is significantly greater (p greater than 0.05) than the value of k = 10 which is implicit in Leq or Ldn. The mean of the existing data provide a best estimate of k = 5. Although there are some surveys in which annoyance decreases as numbers of events increase above about 150 a day, the available evidence is not strong enough to reject the conventional assumption that reactions are related to the logarithm of the number of events. The conventional assumption that the effects of number and peak noise level are additive cannot be rejected with these data. Differences between the surveys' estimates of the effect of number of events remained large even when equivalent questionnaire items and definitions of noise events could be used. The most likely explanations for inconsistent estimates are (1) errors in specifying the values of noise parameters, (2) the effects of unmeasured acoustical and area characteristics which are correlated with noise level or number, and (3) large sampling errors which are due to community differences in response to noise. Multipoint annoyance scales give more reliable estimates than do dichotomous "very annoyed" measures. It is concluded that significant improvements in the knowledge about the effects of numbers of noise events will only occur if surveys include large numbers of study areas, a requirement which can only be met if economical noise measurement techniques are developed which have known levels of precision.

Aircraft↗

PubMed1999

Quantification of inositol phosphates using (31)P nuclear magnetic resonance spectroscopy in animal nutrition.

A (31)P NMR method for quantitative determination of inositol phosphates in simple incubation samples of sodium phytate and Aspergillus niger phytase and in different types of complex samples, such as diets, digesta, and feces, is described. The inositol phosphates in complex samples were extracted with HCl, concentrated, and purified using freeze-drying and filtration and subsequently determined at pH 12.6 in aqueous solution using a (31)P NMR method. The (31)P NMR technique has as its main advantages over the HPLC techniques that it does not necessitate standards that may cause background matrix effects and that the spectra of inositol phosphates and orthophosphate appear in the same run without further sampling errors. The results of inositol hexaphosphate analysis with HPLC can be confirmed by this (31)P NMR method. Contents of inositol tetra-, tri-, di-, and monophosphate in the biological samples appear to be quantitatively not important. The (31)P NMR method can be applied for use in animal nutrition in general and studies of using phytase in diets for farm animals in particular, by measuring the content of inositol phosphates in feed ingredients, complete feeds, ileal contents, and feces of pigs and poultry.

Animal Feed↗

PubMedDate not supplied

Cytomorphologic spectrum of carcinoma ex pleomorphic adenoma.

OBJECTIVE: To delineate the cytomorphologic features of carcinoma ex pleomorphic adenoma (CPA) and identify the diagnostic pitfalls. STUDY DESIGN: Smears of 14 cases suspected as CPA on fine needle aspiration over a period of 15 years were reviewed. Cytohistologic correlation was done in 10 cases. RESULTS: All cases had a salivary gland mass of 1-16 years' duration, with a rapid increase in size in 10 cases. Epithelial cells predominated over stroma in 11 of 14 cases. Group I showed unequivocal malignant cells admixed with benign epithelial and stromal components of pleomorphic adenoma (PA), which were considered diagnostic of CPA on review. The cytologic differential diagnosis in these cases included mucoepidermoid carcinoma, carcinosarcoma and metastatic adenocarcinoma. Group II comprised 7 cases suspected to be cellular PA with atypia or CPA. These showed mild to moderate degrees of pleomorphism, absence of unequivocal malignant cells, and a variable proportion of benign epithelial and stromal components. Four of them were histologically confirmed as CPA. CONCLUSION: Sampling error is an important cause of diagnostic pitfalls. Correlation with clinical data is essential in diagnosis of CPA on cytology. In a proper clinical setting, extensive fine needle aspiration sampling should be done initially. Any degree of nuclear atypia in PA should be documented, alerting the clinician and histopathologist to the possibility of CPA.

Adenocarcinoma↗

PubMed1996

Reliability and validity of the physical disector method for estimating neuron number.

The physical disector was proposed as an unbiased and efficient means to estimate neuron number; however, the validity and reliability of this method have been examined only infrequently. Estimates of neuron number in the dorsal root ganglia (DRG) of bullfrogs (Rana catesbeiana) were compared to nucleolar counts based on 3-dimensional reconstructions. Accuracy of disector estimates were not affected by size of the animal. Similarly, disector estimates were not systematically altered when area measurements were limited to cellular regions of the DRG versus inclusion of the entire cross-sectional area. However, the recommended protocol for applying the disector resulted in sampling errors that introduced considerable variability in repeated estimates of neuron number from a single ganglion. In addition to this lack of reliability, disector estimates were consistently lower than those obtained by means of a nucleolar counting method that was calibrated against 3-dimensional reconstructions of neuronal profiles. The systematic error of the disector method was greater when ganglia were cut parallel to the long axis of the DR than when they were cut perpendicular to this axis. Increasing the sample size beyond what was recommended increased the reliability of estimates obtained with the disector; however, the bias associated with the plane of section was not reduced. These results emphasize the need for empirical validation of methods used to estimate neuron number in the tissue to which they are to be applied.

Animals↗

PubMed1954

The use of sampling methods for ascertaining total morbidity in the Canadian sickness survey.

In 1948, the Canadian Federal Government launched a programme of annual grants to the provinces to expand and improve their health services. However, if there was to be a sound basis for planning and expenditure, much more had to be known about the incidence and prevalence of illness and injury; about the amount of medical, nursing, and similar care needed; and about the volume of family expenditure on health. Accordingly, an agreement was reached in 1950 to conduct a nation-wide survey to determine these matters. The Dominion Bureau of Statistics and the federal Department of National Health would be responsible for planning the survey, designing and setting up the sample, co-ordinating provincial activities, and analysing and publishing the results. The provinces would select, train, and pay enumerators; collect the data; verify diagnoses; and edit completed returns.The survey was conducted over a period of 14 months, each household in the random sample being visited monthly. The size of the sample (sampling error: 20%) was calculated to ensure that results would be within the margin of error 95 times out of 100. While certain areas of Canada had to be excluded from the survey for various reasons, 98% of the 1941 population was covered by the sample, which was composed of a random selection of households in the metropolitan areas and of primary sampling units of 2,000 people elsewhere.When the results were in, the Detailed List of the International Statistical Classification of Diseases, Injuries, and Causes of Death was tabulated for analysis, and it was found that only 19 categories occurred with the minimum frequency needed for a valid estimate. Of the family expenditure on health, 24% was for prepayment plans, 54% for direct services, and 22% for drugs, appliances, etc. The estimated total cost of the survey amounts to Can. $600,000.

Canada↗

PubMed1998

Urea breath tests in the management of Helicobacter pylori infection.

The 13/14C-Urea breath test (UBT) is based on the simple principle that a solution of isotopically labelled urea will be rapidly hydrolysed by the abundantly expressed urease of H pylori. The released 13/14CO2 is absorbed across the mucus layer to the gastric mucosa and hence, via the systemic circulation, excreted in the expired breath. Distribution of urea throughout the stomach prevents sampling error and allows semiquantitative assessments of the extent of H pylori infection. Originally the 13C-UBT was complex, cumbersome and costly but, by simplifying the protocol and reducing the number of samples to be analysed, is now a much easier, quicker and cheaper test for detecting H pylori. Although mass spectrometry is needed for analysis of exhaled 13CO2, the use of the stable isotope, which is completely safe, provides advantages over the 14C-UBT using radioactive 14C-urea, such that it can be used in women and children and a user's licence is not required. The widespread availability of scintigraphy for 14CO2 analysis may make the 14C-UBT seem an attractive alternative to the 13C-UBT. However, there are no standard protocols for the 14C-UBT and although the methods are similar, several different cut off values are used which makes formal validation studies still necessary. Both tests are easy to perform with minimum opportunity for observer variation or methodological error; they are very sensitive and specific tests and provide a clinical "gold standard" against which the accuracy of other tests can be validated. The 13/14C-UBT detects only current infection and can be used to screen for H pylori infection and as the sole method for assessing eradication. In addition, because the 13C-UBT can be performed repeatedly in the same subject, it can be used to monitor the effects of novel anti-H pylori therapies and for epidemiological studies in children.

Breath Tests↗

PubMed2002

Theory of a systematic computational error in free energy differences.

Systematic inaccuracy is inherent in any computational estimate of a nonlinear average, due to the availability of only a finite number of data values, N. Free energy differences (Delta)F between two states or systems are critically important examples of such averages. Previous work has demonstrated, empirically, that the "finite-sampling error" can be very large--many times k(B)T--in (Delta)F estimates for simple molecular systems. Here we present a theoretical description of the inaccuracy, including the exact solution of a sample problem, the precise asymptotic behavior in terms of 1/N for large N, the identification of a universal law, and numerical illustrations. The theory relies on corrections to the central and other limit theorems.

Energy Transfer↗