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Assessment of image post-processing and of measuring assistance tools in computed radiography. Evaluation of the weight-bearing knee.

PURPOSE: A system for the examination and measurement of the weight-bearing knee was adapted to computed radiography (CR) and to a picture archiving and communication system (PACS). The examination and measurement system was developed on examination equipment used for QUESTOR precision radiography (QPR). For an easier and more standardised localisation of bony landmarks on the screen, 4 measuring assistance tools (MATs) were developed. The aim of this study was to evaluate the usefulness of the tools developed and of image post-processing, specifically as magnification (zoom) and filtering (edge enhancement), by determining intra-observer variation in the measurement of angles and distances. MATERIAL AND METHODS: The original QPR measurement program, generating 19 angles and distances corrected for parallax and magnification, was converted and installed on a multi-modality workstation (Imtec Image 1200). A CR system (Fuji AC-2) was used for the generation of the related images and the measurements were made on the workstation. Four unilateral examinations of weight-bearing knees were undertaken. These examinations were measured twice under 5 different measurement conditions by 4 viewers. RESULTS AND CONCLUSIONS: The most important factor in reducing intra-observer variation was the ability to magnify (zoom) the images. The MATs also reduced variation. Filtering (edge enhancement), however, did not affect precision.

Biomechanical Phenomena↗

Running economy and distance running performance of highly trained athletes.

The purpose of the study was to determine the relationship between running economy and distance running performance in highly trained and experienced distance runners of comparable ability. Oxygen uptake (Vo2) during steady-state and maximal aerobic power (Vo2max) were measured during treadmill running using the open-circuit method. Distance running performance was determined in a nationally prominent 10 km race; all subjects (12 males) placed among the top 19 finishers. The subjects averaged 32.1 min on the 10 km run, 71.7 ml.kg-1.min-1 for Vo2max, and 44.7, 50.3, and 55.9 ml.kg-1.min-1 for steady-state Vo2 at three running paces (241, 268, and 295 m.min-1). The relationship between Vo2max and distance running performance was r = -0.12 (p = 0.35). The relationship between steady-state Vo2 at 241, 268 and 295 m.min-1 and 10 km time were r = 0.83, 0.82, and 0.79 (p < 0.01), respectively. Within this elite cluster of finishers, 65.4% of the variation observed in race performance time on the 10 km run could be explained by variation in running economy. It was concluded that among highly trained and experienced runners of comparable ability and similar Vo2max, running economy accounts for a large and significant amount of the variation observed in performance on a 10 km race.

Adolescent↗

Socioeconomic influence on small area hospital utilization.

Health care policy makers, concerned with the rising cost of health care, have focused on the observed variation in the use of hospitals as a potential area in which to lower health care costs, i.e., if hospital utilization can be decreased, health care costs may also decline. However, it is crucial that the reasons for the observed variation in the current practice be understood or attempts to reduce costs may lead to policies that harm groups of patients and the providers and institutions currently delivering care. Using hospital discharge data from 59 hospital market communities in the lower peninsula of Michigan in 1984-86, the authors examined possible associations between socioeconomic characteristics and the observed small area variation in hospital discharge rates. First, a series of Poisson regressions was used for each of five covariates and 112 modified diagnosis-related groups (DRGs). Then, multiple regressions were examined, utilizing the five socioeconomic characteristics, after excluding statistically influential communities. The results indicate that community characteristics, including education, poverty, and unemployment, have a statistically significant association with the observed small area hospital discharge rate for many DRGs. Moreover, the direction of the effect is consistent across multiple disease categories. In multiple regressions, the five selected socioeconomic variables explained 48% of the variance for medical admissions and 19% for surgical admissions. For most DRGs, high educational levels were associated with lower hospitalization rates. The authors also identified statistically influential communities whose hospital utilization profile was different from that of most communities in Michigan.

Diagnosis-Related Groups↗

An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN).

The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter- and intra-observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n=30), koilocytosis (n=46), CIN 1 (n=52), CIN 2 (n=56), and CIN 3 (n=46). Intra- and inter-observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object-oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical biopsies using computerized image analysis is possible. Analysis of positional information enables quantitative evaluation of architectural features in CIN using Delaunay triangulation meshes, which is effective in the objective classification of CIN. This demonstrates the future potential of automated machine vision systems in diagnostic histopathology.

Female↗

Testing and implementing signal impact analysis in a regulatory setting: results of a pilot study.

BACKGROUND AND AIM: Statistical signal detection methods such as proportional reporting ratios (PRRs) detect many drug safety signals when applied to databases of spontaneous suspected adverse drug reactions (ADRs). Impact analysis is a tool that was developed as an aid to prioritisation of such signals. This paper describes a pilot project whereby impact analysis was simultaneously introduced into practice in a regulatory setting and tested in comparison with the existing approach. METHODS: Impact analysis was run on signals detected during a 26-week period from the UK Adverse Drug Reactions On-line Information Tracking (ADROIT) database of spontaneous ADRs that met minimum criteria (PRR>or=3.0, chi2>or=4.0 and >or=3 reported cases) and related to established drugs (i.e. those that have been available for at least 2 years and no longer carry the 'black triangle' symbol). The current method of signal prioritisation (i.e. the collective judgement at a weekly meeting) was initially performed without knowledge of the findings of impact analysis. Subsequently, the meeting was presented with the findings and, where appropriate, given the opportunity to reconsider the judgement made. The categories arising from the two methods were compared and the ultimate action recorded. Inter-observer variation between scientists performing impact analysis was also assessed. RESULTS: Eighty-six separate signals were analysed by impact analysis, of which 5% were categorised as high priority (A), 14% as requiring further information (B), 31% as low priority (C) and 50% as no action required (D). In general, the new method tended to give a higher level of priority to signals than the existing approach. Overall, there was 59% agreement between the impact analysis and the collective judgement at the meetings (kappa statistic=0.30). There was slightly greater agreement between impact analysis and the final action taken (kappa statistic=0.39), indicating that the findings of an impact analysis had an influence on the outcome. Assessment of inter-observer variation demonstrated that the method is repeatable (kappa statistic for overall category=0.77). Almost 70% of those who participated in the pilot study believed that impact analysis represented an improvement in how signals were prioritised. CONCLUSIONS: Impact analysis is a repeatable method of signal prioritisation that tended to give a higher level of priority to signals than the standard approach and which had an influence on the ultimate outcome.

Adverse Drug Reaction Reporting Systems↗

Hemolytic capacity of human monocytes in normal subjects.

The capacity of human monocytes to lyse human A1 erythrocytes in the presence of anti-A1 serum was determined in a group of normal subjects. It was found that monocyte hemolytic capacity varied widely, and that this variation was not accounted for by differences between the sexes or ages of the subjects. The intraassay variation was small compared with the variation observed between individual subjects and between assays of the same individual performed on different occasions. It is concluded that the variation observed is more likely to be due to differences in function of monocytes than to technical variation in assay performance. This variation limits the usefulness of the assay to those situations where there are large differences from control subjects or to studies where large numbers of patients are involved.

Age Factors↗

[Variations by canton in the use of medical observation centers of the disability-insurance in Switzerland].

The Medical Observation Centres of the state Disability Insurance (COMAI) are specialized agencies serving the cantonal commissions of the Disability Insurance in Switzerland. Using data collected for each case examined by the COMAI, utilisation rates and rankings were established for each canton. Utilisation rates varied by a factor of 40 from one canton to the next. This observed variation is independent of the number of new cases presenting to the Disability Insurance and of the number of disability pensions granted. Rankings were also independent of denominators used to define utilisation rates. These results suggest possible non-uniform application of state directives concerning the use of the COMAI, and unequal access to these specialized agencies. The reasons for these variations are the object of a study now underway.

Disability Evaluation↗

Evaluation of immunohistochemistry for the detection of Helicobacter pylori in gastric mucosal biopsies.

A reliable diagnosis of Helicobacter pylori is important in clinical practice and research. To evaluate sensitivity, specificity and inter-observer variation of three histological staining methods for the diagnosis of intragastric H. pylori bacterial flora, four observers assessed the presence of H. pylori in a test set of pairs of gastric biopsies taken from 40 patients during GI-endoscopy. Histological slides of one biopsy of each patient (formalin-fixed and paraffin-embedded) were stained with a Modified Giemsa (MG), the Warthin-Starry (WS), and an immunohistochemical method (IMM) using purified polyclonal H. pylori antiserum (DAKO B471). As a standard, bacterial culture was performed on the adjacent biopsy, using the four quadrants method. Special attention was paid to the presence of non-H. pylori bacterial flora. Twenty out of 40 specimens were H. pylori-positive by culture. Using culture as a standard, sensitivity for H. pylori was 90.0+/-10.0% with MG, 70.0+/-14.1% with WS, and 83.8+/-11.1% with IMM stain. Specificity was 53.8+/-19.3%, 82.5+/-9.6% and 90.0+/-0.0%, respectively. Of 37, 14 and eight false positive scores by all observers for MG, WS and IMM, respectively, non-H. pylori flora was cultured from 17, six, and four of the corresponding adjacent biopsies. Non-H. pylori flora may account for overdiagnosis of H. pylori in gastric biopsies. Kappa values for the variance between the four observers were 0.28 for MG, 0.57 for WS, and 0.83 for IMM. Immunohistochemical staining for H. pylori is highly specific and has a low inter-observer variation. We advise that in situations where gastric histology is the main diagnostic tool, IMM should be used for the detection of H. pylori.

Azure Stains↗

Pitfalls in the diagnosis of recurrent ulceration after surgery for peptic ulcer disease.

We have studied the accuracy of diagnostic methods in achieving a diagnosis in 75 patients with 81 proven episodes of recurrent ulceration. When the endoscopic findings did not permit an accurate diagnosis, radiology usually provided no additional information. The sensitivity of a combined diagnostic approach was not different from that of endoscopy alone, and so the routine use of upper GI radiographs in addition to endoscopy should, therefore, be abandoned. We also assessed observer variation among endoscopists prospectively in 38 patients investigated for dyspepsia after operation for peptic ulcer. Major observer variation in diagnosing suspected recurrent ulceration occurred in 11% of patients, with a sensitivity and specificity higher than 77 and 94%, respectively. As not all the postoperative gastroduodenojejunal mucosal breaches are peptic, we suggest that acid output and enterogastric reflux assessments are useful diagnostic adjuncts to endoscopy.

Deglutition Disorders↗

Systematic oserver variation in trachoma studies.

There has been increasing awareness in recent years among trachomatologists, as well as among workers in other fields of medical research, of the frequency and importance of observer variation in epidemiological studies and clinical trials. In trachoma, the lack of simple definitive laboratory diagnostic procedures suitable for wide application has placed the onus largely, and usually exclusively, on clinical observation.The study reported is based on the recorded observations of two skilled ophthalmologists in an epidemiological survey covering more than 35 000 persons in Taiwan. Observer differences were found to lie not only in deciding whether a case is trachomatous or not but also in assigning cases diagnosed as trachoma to the appropriate evolutive stage of the WHO trachoma classification.THE CONCLUSIONS REACHED ARE THAT: (a) inter- and intra-observer variations of some degree are inevitable if dependence is placed on clinical examination alone; (b) it is possible by preliminary testing of observers' interpretation of clinical signs to determine the nature of these differences, to assess their importance, and to reduce them; also to set base-lines for the detection of subsequent divergences over time; and (c) it is better to have two observers than one in any trachoma survey or clinical trial.

Adolescent↗

Observer variability in upper gastrointestinal endoscopy.

An analysis of the observer variation between 4 endoscopists was made assessing the frequency of visual interpretative discrepancies in the areas of the esophagus, stomach and duodenum. The observer variation in relation to the experience of the endoscopist was compared. The trial was carried out in 104 patients. Two observers were staff members with a minimum of 5 years experience in endoscopy. The other two were fellows with one year experience in endoscopy. The procedure was carried out by one endoscopist while the other observed the procedure through the teaching attachment. The findings were immediately recorded on a protocol. Discrepancies observed were classified in two categories: "Major" and "Minor" discrepancies. Results were evaluated in subgroups according to the different endoscopist's training (staff vs fellow, staff vs staff, fellow vs fellow). An analysis of the lesions where discrepancies occurred was made. The minor discrepancies per case was 2.18 +/- 1.32. Major discrepancies were reduced to 1.19 +/- 1.08. There was a significantly decreased incidence of minor and major discrepancies in the comparison of the staff vs staff as opposed to cases performed by fellow vs fellow (p less than 0.01 and p less than 0.005). The diagnoses where discrepancies occurred most often in order of decreasing frequency included. Esophagitis, hiatal hernia, gastritis, gastric ulcer, erosions and duodenal mucosal lesions.

Duodenal Diseases↗

Structural and functional differences in the promoter and 5' flanking region of Ldh-B within and between populations of the teleost Fundulus heteroclitus.

We have investigated the mechanisms underlying differences in the transcriptional regulation of lactate dehydrogenase-B (Ldh-B) between northern and southern populations of a teleost fish, Fundulus heteroclitus. A 1-kb region immediately 5' of the gene was sequenced from populations throughout the species range. There were two major allele classes in the sample, one containing alleles from Maine and another containing those from Florida. Populations from intermediate localities contained both allele classes. Some individuals from Georgia had sequences intermediate between the two classes, representing either ancestral alleles or recombinants. Tests of neutrality were applied to determine whether observed variation was consistent with neutral expectations. Significant deviations from neutral expectations were detected for the 5' flanking region, but not for other loci. The functional consequences of flanking sequence variation were assessed by transfection of reporter gene constructs into cultured cells and injection into living fish. Consistent with observed variation in Ldh-B transcription rate between populations, significant differences in reporter gene activity were driven by flanking regions from northern and southern populations both in cell culture and in vivo. This functional differentiation, coupled with departures from neutral expectations, suggests that selection may have acted on the regulation of Ldh-B in F. heteroclitus.

Animals↗

Sodium turnover rate determines sensitivity to acute copper and silver exposure in freshwater animals.

The mechanisms of acute copper and silver toxicity in freshwater organisms appear similar. Both result in inhibition of branchial sodium (and chloride) uptake initiating a cascade of effects leading to mortality. The inhibition of the branchial Na/K-ATPase in the basolateral membrane is generally accepted as the key component responsible for the reduced sodium uptake. We propose that branchial carbonic anhydrase and the apical sodium channel may also be important targets for both copper and silver exposure. Several attempts have been made to predict metal sensitivity. A prominent example is the geochemical-biotic ligand model. The geochemical-biotic ligand modeling approach has been successful in explaining variations in tolerance to metal exposure for specific groups of animals exposed at different water chemistries. This approach, however, cannot explain the large observed variation in tolerance to these metals amongst different groups of freshwater animals (i.e. Daphnia vs. fish). Based on the detailed knowledge of physiological responses to acute metal exposure, the present review offers an explanation for the observed variation in tolerance. Smaller animals are more sensitive than large animals because they exhibit higher sodium turnover rates. The same relative inhibition of sodium uptake results in faster depletion of internal sodium in animals with higher sodium turnover. We present a way to improve predictions of acute metal sensitivity, noting that sodium turnover rate is the key predictor for variation in acute copper and silver toxicity amongst groups of freshwater animals. We suggest that the presented sodium turnover model is used in conjunction with the Biotic Ligand Model for risk management decisions.

Animals↗

Tools for the identification of variable and potentially variable tandem repeats.

BACKGROUND: Tandem repeat arrays showing variation between sequences within a population, between strains or across species may have functional effects. The increasing availability of genomic sequence data makes routine description of observed variation possible, creating a need for tools to describe such variability. RESULTS: We present a set of programs that facilitate the identification of tandem repeats showing variation across multiple sequences or genomes, and the prediction of potentially polymorphic tandem repeats. The VNTRfinder (Variable Number of Tandem Repeats finder) program enables the detection of sequence length variation between arrays of inter-specific or intra-specific tandem repeats. In the absence of comparable sequences to explore observed variation, predictions are provided describing which tandem repeats are more likely to be variable, to help guide and focus further experimental evaluation. CONCLUSION: These tools represent a resource for researchers interested in tandem repeats in nucleotide sequences that are most likely to be of clinical and evolutionary interest. The tools are available at http://bioinformatics.rcsi.ie/vntrfinder/. Downloadable versions for UNIX/LINUX and WINDOWS which permit the consideration of longer and more numerous sequences are also available.

Algorithms↗

Observer bias in blood pressure studies.

Observer variation in blood pressure measurement following training with standard techniques has been investigated in a study of 7735 middle-aged men. The initial training produced consistent results between observers, but there were progressive deteriorations in the ensuing months. Subsequent re-training led to marked though inconsistent reductions in variation, but within 1 or 2 months, observers reverted back to an individual level of bias. The magnitude of observer variation is in line with the few other published accounts, and is sufficient to have important implications for group comparisons, clinical trials, and the clinical care of individual patients. Four methods of reducing observer variation are considered: regular re-training, self-measurement and ambulatory monitoring, automatic sphygmomanometers, and adjustment in the analysis. The adjustment procedure used in the British Regional Heart Study is described. Regular and frequent re-training with monitoring of performance, or the use of automatic machines are presently considered the two most practical methods of reducing observer variation.

Adult↗

Blood P50 calculated from a single measurement of pH, PO2, and SO2.

P50 was calculated from a single measurement of pH, Po2, and So2 at a known temperature in 135 blood samples from 21 normal nonsmokers and eight patients. In the 92 blood samples with So2 between 20 and 90 per cent, the standard deviation of repeated calculated P50's on the same sample of blood at different So2 was plus or minus 1.0 Torr. Below So2 of 20 per cent and above So2 of 90 per cent, the standard deviations were plus or minus 5.5 and plus or minus 2.4 Torr, respectively. Combined measurement errors of plus or minus 1 Torr in Po2, plus or minus 1 percent in So2, plus or minus 0.01 in pH, and plus or minus 0.1 degree C in temperature are sufficient to explain the observed variation in calculated P50 in 90 per cent of 135 blood samples from 29 subjects and account for the greater observed variation at So2 less than 20 per cent and greater than 90 per cent.

Carbon Dioxide↗

Clinical assessment of disease activity in rheumatoid arthritis.

A new experimental design was developed to study the value of clinical parameters of disease activity in patients with rheumatoid arthritis. Ten patients with classical rheumatoid arthritis were examined by five senior doctors in a department of medical rheumatology. In spite of an attempt to make the clinical examination as uniform as possible the inter-observer variation among the doctors was greater than the variation among the patients, for the following parameters: joint pain at rest, joint tenderness and joint swelling. An acceptable inter-observer variation in relation to patient variation was found for 1) a combined registration of joint pain at rest or on movement, 2) duration of morning stiffness, 3) grip strength, 4) subjective well-being as indicated on a visual analogue scale, 5) fingertip--palm distance, and 6) maximum flexion-extension in elbows, wrists and knees. The variation from morning to afternoon and from day to day was negligible. It is concluded that registration of elaborated articular scores is useless in the daily routine in rheumatological departments when different doctors examine the patients.

Adult↗

Comparison of egg excretion and serum pepsinogen levels as measures of nematode worm burdens in calves with limited pasture exposure.

Four- to 6-mo-old calves raised on clean pastures were allowed to graze for about 30 days on pastures naturally contaminated with Ostertagia ostertagi, Cooperia spp., Haemonchus placei, and Nematodirus helvetianus. The calves were then housed on concrete for 3 wk before slaughter. At necropsy the eggs per gram of feces (EPG) and the total worm burdens from the abomasum and small intestine were determined. Blood samples were also obtained for serum pepsinogen (PEP) assays. A total of 44 calves was sampled over 27 mo. Adult worm totals were distributed more normally after logarithmic transformation (LOGTOTAL), and EPG and PEP were distributed more normally after square root transformation (SQRT--EPG; SQRT--PEP). Correlation between LOGTOTAL and either SQRT--EPG or SQRT--PEP was about 0.7. These correlations were higher than those obtained with nontransformed data, suggesting that either EPG or PEP are easily measured variables that explain a significant amount of the variation observed in total worm burdens. Polynomial regression models of a cubic order using the SQRT--EPG accounted for 78% of the variation observed in the LOGTOTAL, whereas SQRT--PEP accounted for 58% of the variance. Within the range of worm burdens observed, these results indicate that EPG has value in estimating total worm burdens of naturally infected calves, and that pepsinogen levels are of less value for analysis of total worm burden in calves with a limited previous exposure to trichostrongyle nematodes.

Abomasum↗