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Saccades to moving targets.

The metrics and dynamics of saccades to stationary and moving targets were observed in monkeys (Macaca mulatta). To isolate the effects of target speed on the saccade from contributions of smooth pursuit, saccade velocity was corrected for intrasaccadic pursuit velocity on a trial-by-trial basis prior to analysis. The effects of presaccadic retinal error and target speed on the saccadic velocity profile were determined by analyzing the partial correlations computed as a function of time after saccade onset. The main results are: (1) Saccade amplitude is determined not only by the retinal error sampled before the saccade, but also by the speed of the target during the latency period. (2) The dynamics of saccades, even if compensated for smooth-pursuit components, differ between forward- and backward-moving targets. (3) Whereas the presaccadic retinal error affects the eye velocity throughout the saccade, target speed has no effect before peak velocity. These results are discussed in the context of current models of saccade generation and their physiological substrates, in particular the role of the cerebellum in the local feedback loop.

Animals↗

Renal vein renin in essential hypertension.

A frequency distribution curve and interval percentages of variations in right versus left renal vein renin (RVR) were calculated from 227 sets of renin data from patients with mild and moderate essential hypertension (EH). A renal vein renin ratio (RVRR), large/small, of approximately 2.0 or more falls beyond the 95 per cent confidence interval, and may therefore by considered to be abnormal. Although assay variability and sampling errors may contribute to artifactually large RVRR's in EH, they usually indicate true disparity, probably secondary to asymmetrical nephrosclerosis. Recent hypotheses regarding diagnostic value of RVR in hypertension are evaluated in light of data yielded by this investigation. Simultaneous and/or replicate sampling should reduced within-patient variability and improve clinical interpretation of test results.

Adult↗

Screening errors in cervical cytologic screening.

A total of 555 cervical smears, originally classified as Papanicolaou classes I and II, from women in whom three years later cytologic findings consistent with moderate dysplasia, severe dysplasia, carcinoma in situ and invasive cancer were diagnosed were reviewed in order to estimate the screening error. The initial diagnosis proved to be underestimated in 17.5% of the smears. The two diagnoses correlated in 70.2% of the smears while 12.3% of the smears that contained no abnormality were judged to be inadequate for making a diagnosis, probably representing sampling errors. Quality-control measures to reduce these errors are briefly summarized.

Adult↗

The quality of the fossil record and the accuracy of phylogenetic inferences about sampling and diversity.

Because phylogenies can be estimated without stratigraphic data and because estimated phylogenies also infer gaps in sampling, some workers have used phylogeny estimates as templates for evaluating sampling from the fossil record and for "correcting" historical diversity patterns. However, it is not known how sampling intensity (the probability of sampling taxa per unit time) and completeness (the proportion of taxa sampled) affect the accuracy of phylogenetic inferences, nor how phylogenetically inferred estimates of sampling and diversity respond to inaccurate estimates of phylogeny. Both issues are addressed with a series of simulations using simple models of character evolution, varying speciation patterns, and various rates of speciation, extinction, character change, and preservation. Parsimony estimates of simulated phylogenies become less accurate as sampling decreases, and inaccurate trees chronically underestimate sampling. Biotic factors such as rates of morphologic change and extinction both affect the accuracy of phylogenetic estimates and thus affect estimated gaps in sampling, indicating that differences in implied sampling need not reflect actual differences in sampling. Errors in inferred diversity are concentrated early in the history of a clade. This, coupled with failure to account for true extinction times (i.e., the Signor-Lipps effect), inflates relative diversity levels early in clade histories. Because factors other than differences in sampling predict differences in the numbers of gaps implied by phylogeny estimates, inferred phylogenies can be misleading templates for evaluating sampling or historical diversity patterns.

Fossils↗

Imaging of cyclooxygenase-2 (COX-2) expression: potential use in diagnosis and drug evaluation.

Cyclooxygenase is an enzyme that catalyzes the first two steps in the biosynthesis of prostanoids. The constitutively expressed isoform COX-1 is regarded as a housekeeping enzyme that is responsible for the normal production of prostanoids. The inducible isoform COX-2, on the other hand, is transiently induced during inflammation by various stimuli. Increasing evidence has shown that COX-2 is not only implicated in inflammation but also in oncogenesis. Overexpression of COX-2 has been observed in a variety of tumors. Prostaglandins produced by COX-2 affect important processes in carcinogenesis, including angiogenesis, tissue invasion, metastasis and apoptosis. Several studies indicate that COX-2 is also involved in neurological disorders, like Alzheimer's disease, Parkinson's disease and ischemia, where COX-2 overexpression leads to neurotoxicity. Many aspects of the role of COX-2 in (patho)physiology, however, remain unclear. At present, COX-2 expression is determined by ex vivo laboratory analysis, but the results could be greatly affected by the instability of COX-2 mRNA and protein and by sampling errors. A noninvasive imaging method to monitor COX-2 expression, like positron emission tomography (PET) or single photon emission computed tomography (SPECT), could overcome this complication and may provide novel insights in the role of COX-2, especially in neurological disorders where repetitive sampling is not possible. Such a technique could also be applied to the in vivo evaluation of novel selective COX-2 inhibitors and in dose-escalation studies. This review will present an overview of the developments in the recently emerging field of COX-2 imaging.

Animals↗

Screening for thyroid malignancy: the role of fine-needle biopsy.

Cytological examination of the aspirate of fine-needle biopsy is becoming more widely accepted as a screening test for malignancy in thyroid nodules. However, it tends to be used in addition to, rather than instead of, more traditional methods. In this five-year prospective evaluation we performed fine-needle biopsy in 618 euthyroid patients with nodular thyroid enlargement, 86% of whom also underwent radionuclide scans and 55% of whom underwent ultrasound scans. In 19% of patients fine-needle biopsy yielded insufficient material for diagnosis, and in 14% of patients normal follicular cells were found (which indicated that the clinical lesion was not sampled). To date, a histological diagnosis has been obtained in 258 (42%) patients, 44 of whom had malignancies. The results of the radionuclide and ultrasound scans did not alter the odds in favour of the detection of malignancy. The cytological diagnosis of malignancy was falsely-positive in two patients and falsely-negative in four patients (three cases of which probably were sampling errors). If, in addition to overtly-malignant cells, atypical Hürthle cells and follicular neoplasms were considered to be potentially malignant, fine-needle biopsy alone had a sensitivity of 87% and a specificity of 72%. This good accuracy would be reduced by sampling failures, but a policy of operating on all patients with potentially-malignant cells, or on those in whom satisfactory aspirates could not be obtained, would yield high rates of the diagnosis of malignancy and would reduce the number of operations. Our data indicate that the most-appropriate method of screening thyroid nodules for malignancy is fine-needle biopsy without pertechnetate scanning or ultrasound examinations.

Australia↗

Negative bias in estimates of the correlation between children's weight-for-height and height-for-age.

Several analyses of cross-sectional anthropometric survey data have found weak correlations between children's weight-for-height and height-for-age. Random non-sampling error in height measurement can produce a significant negative bias in estimates of their correlation. The size of this bias is quantified here using Monte Carlo simulation techniques. Even when two-thirds of height measurements are within two centimeters of their true value, the median estimate of the correlation is .095 below its true value for the sample. There may be differences in the etiology of protein energy malnutrition, as represented by stunting (low height-for-age) and wasting (low weight-for-height), but inferences based on cross-sectional data alone may be misleading, unless random measurement error is negligeable.

Body Height↗

Urea breath tests for the detection of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori is recognized as an important human pathogen. The urea breath test, using either 13C or 14C, provides a noninvasive diagnostic method for the detection of active H. pylori infection. METHODS: We review the data regarding the utility of the urea breath test in the diagnosis and follow-up of patients with suspected H. pylori infection. RESULTS: Following its ingestion, labeled urea is hydrolyzed by H. pylori urease, producing ammonia and labeled CO2, which is absorbed and can be detected in expired breath. The urea breath test provides a semiquantitative assessment of the load of H. pylori and overcomes the problem of the sampling error due to the patchy distribution of the infection. 13C-urea breath test has an advantage over the 14C version, because the 13C isotope is a nonradioactive natural isotope; therefore, a user's license is unnecessary, making simple the handling and mailing of samples. The 13C-urea breath test is preferred in children and expectant mothers. CONCLUSION: The high sensitivity, and specificity of the 13C-urea breath test are such that it can be considered a clinical gold standard against which other diagnostic methods can be validated. This test can be used as the sole method for evaluating the effectiveness of treatment of H. pylori infection.

Helicobacter Infections↗

The T allele of a single-nucleotide polymorphism 13.9 kb upstream of the lactase gene (LCT) (C-13.9kbT) does not predict or cause the lactase-persistence phenotype in Africans.

The ability to digest the milk sugar lactose as an adult (lactase persistence) is a variable genetic trait in human populations. The lactase-persistence phenotype is found at low frequencies in the majority of populations in sub-Saharan Africa that have been tested, but, in some populations, particularly pastoral groups, it is significantly more frequent. Recently, a CT polymorphism located 13.9 kb upstream of exon 1 of the lactase gene (LCT) was shown in a Finnish population to be closely associated with the lactase-persistence phenotype (Enattah et al. 2002). We typed this polymorphism in 1,671 individuals from 20 distinct cultural groups in seven African countries. It was possible to match seven of the groups tested with groups from the literature for whom phenotypic information is available. In five of these groups, the published frequencies of lactase persistence are >/=25%. We found the T allele to be so rare that it cannot explain the frequency of the lactase-persistence phenotype throughout Africa. By use of a statistical procedure to take phenotyping and sampling errors into account, the T-allele frequency was shown to be significantly different from that predicted in five of the African groups. Only the Fulbe and Hausa from Cameroon possessed the T allele at a level consistent with phenotypic observations (as well as an Irish sample used for comparison). We conclude that the C-13.9kbT polymorphism is not a predictor of lactase persistence in sub-Saharan Africans. We also present Y-chromosome data that are consistent with previously reported evidence for a back-migration event into Cameroon, and we comment on the implications for the introgression of the -13.9kb*T allele.

Alleles↗

Forecasting the number of soil samples required to reduce remediation cost uncertainty.

Sampling scheme design is an important step in the management of polluted sites. It largely controls the accuracy of remediation cost estimates. In practice, however, sampling is seldom designed to comply with a given level of remediation cost uncertainty. In this paper, we present a new technique that allows one to estimate of the number of samples that should be taken at a given stage of investigation to reach a forecasted level of accuracy. The uncertainty is expressed both in terms of volume of polluted soil and overall cost of remediation. This technique provides a flexible tool for decision makers to define the amount of investigation worth conducting from an environmental and financial perspective. The technique is based on nonlinear geostatistics (conditional simulations) to estimate the volume of soil that requires remediation and excavation and on a function allowing estimation of the total cost of remediation (including investigations). The geostatistical estimation accounts for support effect, information effect, and sampling errors. The cost calculation includes mainly investigation, excavation, remediation, and transportation. The application of the technique on a former smelting work site (lead pollution) demonstrates how the tool can be used. In this example, the forecasted volumetric uncertainty decreases rapidly for a relatively small number of samples (20-50) and then reaches a plateau (after 100 samples). The uncertainty related to the total remediation cost decreases while the expected total cost increases. Based on these forecasts, we show how a risk-prone decision maker would probably decide to take 50 additional samples while a risk-averse decision maker would take 100 samples.

Forecasting↗

Serum markers detect the presence of liver fibrosis: a cohort study.

BACKGROUND & AIMS: Histologic examination of a liver biopsy specimen is regarded as the reference standard for detecting liver fibrosis. Biopsy can be painful and hazardous, and assessment is subjective and prone to sampling error. We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis. METHODS: In an international multicenter cohort study, serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease. Discriminant analysis of a test set of samples was used to identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum samples. RESULTS: The algorithm detected fibrosis (sensitivity, 90%) and accurately detected the absence of fibrosis (negative predictive value for significant fibrosis, 92%; area under the curve of a receiver operating characteristic plot, .804; standard error, .02; P < .0001; 95% confidence interval, .758-.851). Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease. The algorithm performed equally well in comparison with each of the pathologists. In contrast, pathologists' agreement over histologic scores ranged from very good to moderate (kappa = .97-.46). CONCLUSIONS: Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases.

Adult↗

Cognitive interviewing: verbal data in the design and pretesting of questionnaires.

PURPOSE: The purpose of this paper is to discuss problems that occur in questionnaire responses and how cognitive interviewing can be used to identify problematic questions prior to using the questionnaire in the field. BACKGROUND: Questionnaire design involves developing wording that is clear, unambiguous and permits respondents successfully to answer the question that is asked. However, a number of problems in relation to respondents' understanding and successfully completing questionnaires have been identified. Cognitive interviewing, an amalgamation of cognitive psychology and survey methodology, has been developed to identify problematic questions that may elicit response error. The overall aim is to use cognitive theory to understand how respondents perceive and interpret questions and to identify potential problems that may arise in prospective survey questionnaires. METHODS: A literature review is used to examine the process of questionnaire design and how cognitive interviewing can be used to reduce sampling error and increase questionnaire response rates. FINDINGS: Cognitive interviewing involves interviewers asking survey respondents to think out loud as they go through a survey questionnaire and tell them everything they are thinking. This allows understanding of the questionnaire from the respondents' perspective rather than that of the researchers. Cognitive interviews have been used in a number of areas in health care research to pretest and validate questionnaires and to ensure high response rates. Interviewing has been found to be highly effective in developing questionnaires for age specific groups (children and adolescents) and in ascertaining respondents' understanding in health surveys prior to distribution. However, cognitive interviews have been criticized for being overly subjective and artificial. CONCLUSION: Cognitive interviews are a positive addition to current methods of pretesting questionnaires prior to distribution to the sample. They are most valuable in pretesting questions that are complex, where questions are sensitive and intrusive and for specific groups for whom questionnaire completion may pose particular difficulties.

Cognitive Science↗

Morphologic evaluation of stereotactic brain tumour biopsies.

The validity of morphologic diagnosis of stereotactic brain tumour biopsies was evaluated in a series of 600 patients treated since 1977 at the University Hospital, Freiburg. Combined cytological (smear preparations) and histological examination of paraffin-embedded samples revealed the tumour type and approximate grading in 492 (82%) of cases. In 66 patients a clinically suspected neoplasm could be ruled out. In the remaining 42 cases (7%), the presence of a tumour was confirmed but the available samples did not allow an unequivocal classification of the neoplasm. Inaccurate diagnoses were most frequently due to sampling errors in non-homogeneous tumours, i.e. biopsies taken from sites not representative for the entire neoplasm (tumour necroses, infiltration zone). In the future, the use of immunohistochemical methods for the identification of tumour markers and cytoskeleton proteins may partially compensate for the limited size of stereotactic biopsy samples.

Brain↗

Fine-needle aspiration cytology findings in 214 cases of nonparotid lesions of the head.

The use and limitations of fine-needle aspiration (FNA) of lesions of the parotid gland are known, but those of nonparotid lesions of the head have been described only sporadically. We conducted this study to evaluate the utility of FNA and to analyze the causes of diagnostic discrepancies for these lesions. A total of 6,898 FNAs of different sites was performed at our institutions between January 1991-August 1998, and 214 (3.1%) of the cases were FNAs of nonparotid lesions of the head. The most common diagnosis of nonparotid lesions was squamous-cell carcinoma, in 22% (n = 48), and the most common site aspirated was the scalp, in 34% (n = 73). Lipomas and keratinous cysts comprised 5% (n = 9) of the total. A statistical analysis was conducted on 98 paired cytology and histology (n = 83) and cytology and flow cytometry (n = 15) specimens (70 malignant and 28 benign). FNA recognized the malignant and benign nature of the lesion in 60 and 26 cases, respectively with 86% sensitivity 93% specificity and 88% accuracy. Causes of false-negative FNA diagnoses (n = 10) included sampling error (n = 6), bloody smears with scant cellularity (n = 3), and bland cytomorphology (n = 1). Florid granulation tissue and a mucocele of the tongue accounted for the two false-positive cases. We conclude that FNA is an effective tool for triage of surgery candidates with nonparotid lesions of the head. Adequate samples with sufficient cellularity are required for avoiding false-negative diagnoses. Occasionally, tissue biopsy is needed for diagnosis of equivocal cases.

Adult↗

The dominant class of somatosensory neurone recorded in the spinal dorsal horn of awake sheep has wide dynamic range properties.

In order to investigate the properties of dorsal horn neurones in the absence of the distorting influences of anaesthesia, preparative surgery, prior training or excessive restraint, recordings have been made in sheep chronically prepared for single-cell recording. Within the limitations of sampling error of dorsal horn neurones with cutaneous receptive fields, the cell type most frequently encountered had wide dynamic range (WDR; convergent; multireceptive) properties; these accounted for 59% of the 46 neurones that were examined in detail. High-threshold mechanoreceptive (nocispecific) and low-threshold mechanoreceptive neurones formed 11% and 30% of the sample, respectively. These and other data indicate that under normal physiological conditions in the awake state, many spinal neurones do indeed have WDR properties, implying that these cells have an important function in nociceptive processing.

Animals↗

Hepatoblastoma: assessment of criteria for histologic classification.

BACKGROUND: Comparison of outcomes in different clinicopathologic studies of hepatoblastoma requires reproducible histologic classification. This review examines the diagnostic criteria employed by different pathologists for the classification of subtypes of hepatoblastoma and identifies specific problem areas. PROCEDURE: A selected review of published literature is provided. RESULTS: Published studies demonstrate that uniform criteria have not been applied in the classification of hepatoblastoma. These discrepancies hinder attempts to compare outcome data from different studies. Sampling error and potential treatment effects further complicate analysis of the published literature on the relationship between morphologic classification and outcome. CONCLUSIONS: Standardized criteria are essential to allow reproducible histologic classification of hepatoblastoma. There is significant variation in diagnostic criteria used to define the major subtypes of hepatoblastoma in published studies. Additional potential problems are identified in sampling methods and treatment effects.

Child↗

Use of meta-analysis to combine candidate gene association studies: application to study the relationship between the ESR PvuII polymorphism and sow litter size.

This article investigates the application of meta-analysis on livestock candidate gene effects. The PvuII polymorphism of the ESR gene is used as an example. The association among ESR PvuII alleles with the number of piglets born alive and total born in the first (NBA1, TNB1) and later parities (NBA, TNB) is reviewed by conducting a meta-analysis of 15 published studies including 9329 sows. Under a fixed effects model, litter size values were significantly lower in the "AA" genotype groups when compared with "AB" and "BB" homozygotes. Under the random effects model, the results were similar although differences between "AA" and "AB" genotype groups were not clearly significant for NBA and TNB. Nevertheless, the most noticeable result was the high and significant heterogeneity estimated among studies. This heterogeneity could be assigned to error sampling, genotype by environment interaction, linkage or epistasis, as referred to in the literature, but also to the hypothesis of population admixture/stratification. It is concluded that meta-analysis can be considered as a helpful analytical tool to synthesise and discuss livestock candidate gene effects. The main difficulty found was the insufficient information on the standard errors of the estimated genotype effects in several publications. Consequently, the convenience of publishing the standard errors or the concrete P-values instead of the test significance level should be recommended to guarantee the quality of candidate gene effect meta-analyses.

Animals↗

[Fine needle puncture of prostatic cancer].

Before commencing treatment for prostatic cancer the diagnosis must be confirmed by microscopic examination of prostatic tissue. Fine-needle aspiration biopsy by an experienced clinician is as accurate as the more invasive Tru-cut or Vim-Silverman needle biopsies. It involves fewer complications such as hemorrhage or infection, and does not require anesthesia. From 1971 to 1981 we performed more than 2300 fine needle biopsies including 2209 in outpatients. Only 4 patients (0.18%) needed hospitalizing for severe complications. Where the clinical examination prompts suspicion of prostatic cancer and the first fine needle biopsy is negative, the procedure should be repeated. When repeated aspirations were performed only 4 (2%) false negative cytologies were found out of 195 patients in whom prostatic cancer was clinically evident and confirmed by either cytology or histology. False negative cytological results are usually due to sampling errors by the physician rather than interpretation by the cytologist. The histology was false negative in 11.5% of 200 cases and this was due to failure of transurethral resection to reach a focal carcinoma situated in the capsule or sphincter region. Identical histological and cytological grading was found in 66% of the 168 cases where both investigations were positive. If a difference of one grade was accepted, the concurrence is 99%. The results of fine needle biopsy depend on the skill of the clinician in obtaining the right sample, and especially on the experience of the cytologist in its interpretation.

Adenoma↗