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Effect of observer variability on glomerular filtration rate measurement by renal scintigraphy in dogs.

Observer variation in kidney depth measurement for correction of soft-tissue attenuation and kidney region of interest (ROI) drawing was evaluated using 60 clinical dogs with a wide range of glomerular filtration rate (GFR) for their effect on the calculated percentage uptake of 99mTc-diethylenetriamine pentaacetic acid (DTPA) and individual kidney GFR by scintigraphy. Kidney depth was measured separately on the lateral image using two color tables: a threshold and a continuous red-green-blue. Within-observer variability of the semi-automatic ROI drawing of the estimated total GFR was up to 10% for the right kidney (RK) and 9% for the left kidney (LK). The variability was lower between observers, 6% for RK and 8% for LK. Manual ROI drawing caused more within observer variation than semi-automatic: up to 14% for RK and 11% for LK. Continuous red-green-blue table caused more variation within and between observers than threshold table. Average within-observer variability from both observers of kidney depth measurement on different color tables could vary up to 5.5% and 6.5% variation of the GFR of RK and LK, respectively. Most variation affecting the DTPA percentage uptake came from the ROI drawing technique. Variations of the method because of the effects of both kidney depth and kidney ROI drawing were up to 8% and 10% for RK and LK, respectively. To minimize these variations a threshold scale should be used for the kidney depth measurement and an automatic or semi-automatic ROI should be used whenever possible. In sequential examinations the same person should make all the measurements.

Animals↗

3H-glucosamine and 3H-fucose incorporation by murine peritoneal macrophages "non-divided" during differentiation in vitro.

Normal murine peritoneal macrophages were maintained in culture for 24 hours and 6 days. These cells continuously incorporated 3H-glucosamine and 3H-fucose in their membrane components. For both precursors culture ages, these components may be considered to undergo turnover according to a given rhythm with a 24 hours doubling time. Treatment with neuraminidase did not modify the doubling time, although a slight increase of incorporation of radioactivity was observed. Variations of 3H-fucose and 3H-glucosamine incorporations were observed. Variations of 3H-fucose and 3H-glucosamine incorporations were observed between 24 hours old and 6 days old cultures: 6 days old cultures incorporated more glucosamine than 24 hours old cultures whereas no difference in fucose incorporation was observed between the two cultures.

Animals↗

The fetal heart rate trace is normal, isn't it? Observer agreement of categorical assessments.

The limitations of the kappa statistic method to measure inter-observer variation of categorical assessments are shown by means of a hypothetical example. Another method for assessing the inter-observer variation of categorical variables, the proportion of agreement, is used for the same example, and reasons why it is preferable to the kappa statistic are given. Since this method allows measurement of the inherent difficulty of carrying out a particular assessment, it has wide applicability in the introduction of new technology. If a proportion of agreement study shows poor inter-observer agreement for a new method, the technology must either be improved or abandoned.

Bias↗

Muscle fiber-type variation in lizards (Squamata) and phylogenetic reconstruction of hypothesized ancestral states.

Previously, we found that phrynosomatid lizards, a diverse group common in the southwestern USA, vary markedly in fiber-type composition of the iliofibularis (a hindlimb muscle important in locomotion). Phrynosomatidae comprises three subclades: the closely related sand and horned lizards, and their relatives the Sceloporus group. The variation in muscle fiber-type composition for 11 phrynosomatid species is attributable mainly to differences between the sand- and horned-lizard subclades. Here, we expand the phrynosomatid database with three additional species and compare these results with data collected for 10 outgroup (distantly related) species. Our goal was to determine if the patterns found in Phrynosomatidae hold across a broader phylogenetic range of the extant lizards and to elucidate the evolution of muscle fiber-type composition and related traits. To allow for meaningful comparisons, data were collected from species that are primarily terrestrial and relatively small in size (3.5-65 g body mass). Results indicate that the fiber-type variation observed within the Phrynosomatidae almost spans the range of variation observed in our sample of 24 species from eight families. However, one species of Acanthodactylus (Lacertidae) had a consistent region of large tonic fibers (that did not stain darkly for either succinic dehydrogenase or myosin ATPase activity), a fiber-type only occasionally seen in the other 23 species examined. Many species have a large proportion of either fast-twitch glycolytic (FG; e.g. sand lizards and Aspidoscelis) or fast-twitch oxidative-glycolytic (FOG) fibers (e.g. horned lizards), with the slow-oxidative proportion occupying only 1-17% of the iliofibularis. Importantly, the negative relationship between FG and FOG composition observed in Phrynosomatidae appears to be a characteristic of lizards in general, and could lead to functional trade-offs in aspects of locomotor performance, as has previously been reported for Lacertidae. Reconstruction of ancestral trait values by use of phylogenetically based statistical methods indicates especially large changes in fiber-type composition during the evolution of horned lizards.

Animals↗

Bone age assessment: a large scale comparison of the Greulich and Pyle, and Tanner and Whitehouse (TW2) methods.

PURPOSE: Comparison of bone age assessed using either the "atlas matching" method of Greulich and Pyle or the "point scoring system" of Tanner and Whitehouse (TW2). MATERIALS AND METHODS: 362 consecutive "bone age" radiographs of the left hand and distal radius performed in a large provincial teaching hospital. Data were analysed using the "method comparison" statistical technique. Ten per cent of the radiographs were re-analysed to assess intra-observer variation. RESULTS: The 95% confidence interval for the difference between the two methods was 2.28 to -1.52 years. Intra-observer variation was greater for the Greulich and Pyle method than for the TW2 method (95% confidence limit, -2.46 to 2.18 v -1.41 to 1.43). CONCLUSION: The two methods of bone age assessment as used in clinical practice do not give equivalent estimates of bone age and we suggest that one method only (preferably the TW2) should be used when performing serial measurements on an individual patient.

Adolescent↗

Reproducibility of goniometry of the wrist.

The wrist motion in 31 healthy probands was measured by four observers with a simple goniometer under standardized conditions. The INTRA-observer variation was calculated to 5 to 8 degrees and the INTER-observer variation to 6 to 10 degrees. No difference between experienced and non-experienced observers was found. The difference between the right and the left wrist was negligible, indicating that the opposite wrist can be used as reference when evaluating restrictions in motion.

Adult↗

Interobserver variability in the interpretation of contrast venography, technetium-99m red blood cell venography and impedance plethysmography for deep vein thrombosis.

Contrast venography (CV) is the standard technique for diagnosing deep vein thrombosis (DVT). Newer noninvasive tests have also proven efficacious. However, there is a lack of data on the level of agreement among observers in their interpretation of the results of the various tests. After agreeing on well-defined criteria, three experienced observers assessed, blindly, the results of tests performed over a 4-month period on 117 patients who were suspected clinically of having had a first episode of DVT. The kappa statistic was used to measure the level of agreement beyond chance for CV (69 patients), red blood cell venography (RBCV) (82 patients) and impedance plethysmography (76 patients). The results of CV were assigned to normal, abnormal or inadequate categories, and those of RBCV and IPG to normal, equivocal or abnormal categories. The kappa values for CV, RBCV and IPG ranged from 0.53 to 0.56, 0.42 to 0.56 and 0.90 to 0.91 respectively. Values greater than 0.75 represented excellent agreement beyond chance and those between 0.40 and 0.75 represented fair to good agreement. Excellent kappa values were obtained for IPG because interpretation of the results of this method is entirely objective. Although the values for CV and RBCV showed good to fair agreement, there was a greater degree of observer variation, despite the well-defined criteria, indicating the subjectivity of interpretation of these test results. It is concluded that the kappa statistic can be used to measure observer variation of the results of tests for diagnosing DVT and may serve as a quality control tool for studies in which more than one person interprets the results.

Contrast Media↗

An objective spinal motion imaging assessment (OSMIA): reliability, accuracy and exposure data.

BACKGROUND: Minimally-invasive measurement of continuous inter-vertebral motion in clinical settings is difficult to achieve. This paper describes the reliability, validity and radiation exposure levels in a new Objective Spinal Motion Imaging Assessment system (OSMIA) based on low-dose fluoroscopy and image processing. METHODS: Fluoroscopic sequences in coronal and sagittal planes were obtained from 2 calibration models using dry lumbar vertebrae, plus the lumbar spines of 30 asymptomatic volunteers. Calibration model 1 (mobile) was screened upright, in 7 inter-vertebral positions. The volunteers and calibration model 2 (fixed) were screened on a motorized table comprising 2 horizontal sections, one of which moved through 80 degrees. Model 2 was screened during motion 5 times and the L2-S1 levels of the volunteers twice. Images were digitised at 5fps. Inter-vertebral motion from model 1 was compared to its pre-settings to investigate accuracy. For volunteers and model 2, the first digitised image in each sequence was marked with templates. Vertebrae were tracked throughout the motion using automated frame-to-frame registration. For each frame, vertebral angles were subtracted giving inter-vertebral motion graphs. Volunteer data were acquired twice on the same day and analysed by two blinded observers. The root-mean-square (RMS) differences between paired data were used as the measure of reliability. RESULTS: RMS difference between reference and computed inter-vertebral angles in model 1 was 0.32 degrees for side-bending and 0.52 degrees for flexion-extension. For model 2, X-ray positioning contributed more to the variance of range measurement than did automated registration. For volunteer image sequences, RMS inter-observer variation in intervertebral motion range in the coronal plane was 1.86 degrees and intra-subject biological variation was between 2.75 degrees and 2.91 degrees. RMS inter-observer variation in the sagittal plane was 1.94 degrees. Radiation dosages in each view were below the levels recommended for a plain film. CONCLUSION: OSMIA can measure inter-vertebral angular motion patterns in routine clinical settings if modern image intensifier systems are used. It requires skillful radiography to achieve optimal positioning and dose limitation. Reliability in individual subjects can be judged from the variance of their averaged inter-vertebral angles and by observing automated image registration.

Adult↗

Leg length inequality measured by ultrasound and clinical methods.

Leg length inequality (LLI) was determined by ultrasound and two clinical methods in 100 subjects without previous disorders of the lower extremities. The mean LLI by ultrasound was 4.1 mm (range: 0-16 mm). An LLI of 10 mm or more was found in 4% of the subjects. The mean inter-observer variation by ultrasound was 0.9 mm (range: divided by 5-8 mm), which was significantly less than that obtained by clinical methods. The 95% confidence interval of inter-observer variation (+/- 2 SD) by ultrasound was +/- 5 mm and this interval is assumed to represent the accuracy of the method. Because LLI measurement by ultrasound is more reliable than clinical methods, ultrasound is recommended for routine use in clinical practice.

Adolescent↗

Computed radiography for characterisation of the weight-bearing knee.

PURPOSE: A new method for examining and measuring the weight-bearing knee in computed radiography (CR) and picture archiving and communication systems (PACS) has recently been developed on examination equipment used in QUESTOR Precision Radiography (QPR). QPR is a method for the standardised examination of the knee, and generates 9 angles (e.g. hip-knee-ankle (HKA) angle) and 10 distances, corrected for parallax and magnification. The aim of this present study was to evaluate the reproducibility of this newly developed method and to determine intra- and interobserver variation in its measurements. MATERIAL AND METHODS: The images were generated on a CR system, archived, and transferred to a multimodality work-station that had a monitor with a resolution of 1280x1024 (1kx1k). Photostimulable phosphor plates were used to generate images with a matrix of 1760x2140 pixels (pixel size 0.2 mm, corresponding resolution 2.5 1p/mm). Ten volunteers without knee problems were examined twice, bilaterally, by 2 different radiology technologists. RESULTS: The total reproducibility of the method was good, offering an HKA reproducibility of +/-2.64 degrees in slight flexion and +/-1.62 degrees in extension, at 95% confidence. The intra- and inter-observer variations were low with a reduction of the intra-observer variations in all measurements (except one) by a factor of 2.8 on average compared with the original QPR method for conventional film-screen radiography. CONCLUSION: When QPR is modified for CR, it fulfils the requirement of reproducibility in measurements of the weight-bearing knee.

Adult↗

A GIS model of subsurface water potential for aquatic resource inventory, assessment, and environmental management.

Biological, chemical, and physical attributes of aquatic ecosystems are often strongly influenced by groundwater sources. Nonetheless, widespread access to predictions of subsurface contributions to rivers, lakes, and wetlands at a scale useful to environmental managers is generally lacking. In this paper, we describe a "neighborhood analysis" approach for estimating topographic constraints on spatial patterns of recharge and discharge and discuss how this index has proven useful in research, management, and conservation contexts. The Michigan Rivers Inventory subsurface flux model (MRI-DARCY) used digital elevation and hydraulic conductivity inferred from mapped surficial geology to estimate spatial pattems of hydraulic potential. Model predictions were calculated in units of specific discharge (meters per day) for a 30-m-cell raster map and interpreted as an index of potential subsurface water flux (shallow groundwater and event through-flow). The model was evaluated by comparison with measurements of groundwater-related attributes at watershed, stream segment, and local spatial scales throughout Lower Michigan (USA). Map-based predictions using MRI-DARCY accounted for 85% of the observed variation in base flow from 128 USGS gauges, 69% of the observed variation in discharge accrual from 48 river segments, and 29% of the residual variation in local groundwater flux from 33 locations as measured by hyporheic temperature profiles after factoring out the effects of climate. Although it does not incorporate any information about the actual water table surface, by quantifying spatial variation of key constraints on groundwater-related attributes, the model provides strata for more intensive study, as well as a useful spatial tool for regional and local conservation planning, fisheries management, wetland characterization, and stream assessment.

Conservation of Natural Resources↗

Irradiation of paranasal sinus tumors, a delineation and dose comparison study.

PURPOSE: To determine the influence of observer variation and treatment planner variation on the dose delivered to the target and normal structures when irradiating paranasal sinus carcinomas. PATIENTS AND METHODS: Nine patients with paranasal sinus tumors underwent debulking surgery and subsequent radiation therapy. Two observers from two different institutions delineated the clinical target volumes (CTVs) for the elective and the boost volumes. These volumes were expanded in three dimensions with a 5-mm margin. At both institutions, a three-dimensional conformal treatment plan of 46 Gy to the elective volumes, plus 20 Gy to the boost target volumes, was designed. The delineated volumes and treatment plans were compared. RESULTS: The mean volume ratio between institutions of the elective CTVs was 0.9 (standard error = 0.05). The differences were located mainly at the bottom of the nasal cavity and at the frontal border of the target areas. The differences in boost CTVs were large; the mean volume ratio was 2.6 (standard error = 0.58). After expansion of the CTV, the mean distance between the planning target volume (PTV) and the chiasm differed by 0.5 cm between the two institutions. Cases with smaller distances between the PTV and the chiasm had more underdosage to the PTV. This effect was less pronounced for institution A (1 vol.%/cm) than for institution B (10 vol.%/cm) treatment plans, which were less conformal. When the treatment plan was designed for the PTV of institution B, 23 volume % of the PTV of institution A received <95% of the prescribed dose. If the treatment plan was designed for the (on average larger) PTV of institution A, the underdosed volume of PTV at institution B was 17%. The relative underdosage to the "other" PTV was larger when the original treatment plan was more conformal. CONCLUSION: In the irradiation of paranasal sinus cancer, both the treatment planner and the observer have a significant influence on the dose to the target and organs at risk. Both effects are similar in magnitude. The observer effect increases with more conformal treatment plans. Minimizing the observer variation is important for adequate irradiation of paranasal sinus cancer.

Carcinoma, Adenoid Cystic↗

Exteroceptive suppression periods in jaw-closing muscles. Variability and relation to experimental pain and sustained muscle contraction.

The duration of the late exteroceptive suppression period (ES2) of temporal muscle EMG activity has been reported to be reduced in patients suffering from chronic tension-type headache. Methods of recording and analysing ES2 have varied between centers and reproducibility of results within subjects, although insufficiently studied, has generally been poor. ES2 was investigated in 30 healthy subjects, using a computerized technique of recording, rectifying and averaging the EMG signals. Hour to hour and week to week variations of ES2 durations were calculated, and the influence of pain during a cold pressor test and of sustained muscle contraction on ES2 durations was investigated. The intra-individual variation of ES2 durations was 16.0% from hour to hour and 20.7% from week to week. The inter-individual variation was 36.7%. The present method for analysis of ES2 periods proved to be reliable, as the intra-observer variation was 4.2% and the inter-observer variation 4.6%. ES2 periods were significantly shorter on the first compared to the second day of examination (p = 0.006) and during experimental pain (p = 0.0005). We recommend the use of the computerized average technique in future studies and caution against the dependence of results upon factors such as conditioning and pain.

Adult↗

Reproducibility of microvessel counts in breast cancer specimens.

Assessment of tumour vascularity in core biopsy specimens may be a useful predictor of response to primary therapy. This study addresses practical methodological issues regarding accuracy of tumour vascularity assessments in different breast cancer specimens. Issues addressed in the study are variation caused by (i) inherent observer variation in the method, (ii) tumour heterogeneity and (iii) previous surgical manipulation of tumours. Microvessel counts were performed by two observers on separate occasions and by two different observers. Counts were performed on core biopsies and tumour sections taken simultaneously (n = 16) and with an intervening time interval (n = 21). In addition core biopsies were obtained from the same tumour on two separate occasions (n = 10). A highly significant correlation was found in counts performed by the same observers at different times and between two different observers. No significant correlation was found in counts of core biopsies and tumour sections taken either simultaneously or subsequently. No correlation was found between counts of sequential core biopsies. Study findings suggest that, although microvessel counts may be assessed reproducibly by the same and different observers, counts performed in core biopsies do not accurately reflect those of overall tumour, limiting their potential as predictive or prognostic markers.

Adult↗

Histometry and the H.O.M.E. concept: an aid to the grading of intra-cervical neoplasia?

The view has been expressed that few quantitative methods are of value to the pathologist in purely diagnostic work. Quantitative systems are perceived as too large for the average reporting room, too time consuming to learn, very expensive to buy and quick to become obsolete. Further, the software supplied usually cannot provide fully automated analysis, and user interaction is often tedious. If measurement techniques have little value in diagnosis they may have a role in assessing the prognosis of tumours. High levels of inter- and intra-observer variation in tumour grading have been reported and quantitative methods have been used to reduce this and more emphasis has been placed on the measurement of changes in tissue architecture, which may help to reduce observer variation. This paper describes such a method based on cell sociology, which has been implemented on a quantitative microscope specifically designed for use in the routine diagnostic pathology environment. The results of a preliminary study on grading cervical intraepithelial neoplasia show a significant difference between all groups (P less than 1 x 10(-5)) and a linear trend for the measurement of Area Disorder (P less than 1 x 10(-5)).

Female↗

(2)H- and (13)C-labelled tracers compared for kinetic studies of ascorbic acid metabolism in man: a factor analytical approach.

A recent report that a (13)C stable isotope method can be used to measure the kinetics of ascorbic acid uptake and distribution in man has raised some interesting questions with regard to the physiological interpretation of the data obtained, in particular the sizes of the ascorbate distribution spaces. In order to prove that this result is not a function of the label used we have compared the behaviour of two different tracers to see if they are likely to give comparable results for the kinetic parameters. Volunteers received an oral dose of ascorbic acid, half of which was labelled with (2)H, and half of which was labelled with (13)C. Blood samples were taken over the course of the next 48 h, and ascorbic acid mass spectra measured by gas chromatography/mass spectrometry (GC/MS). Principal component analysis was used to investigate the number of factors required to explain the total variations observed in the ratios of the molecular isotopomer cluster over the time course of the experiment. Theoretical cracking patterns were then used as test vectors in target transformation and as the basis for subsequent combination to determine tracer/tracee ratios. Two factors were found sufficient to account for the observed cracking pattern variations within experimental error. These were identified as (1) the spectrum of unlabelled (endogenous) ascorbic acid, and (2) a linear combination of the spectra of the two labelled species used. The absence of a third factor in the decomposition indicates that there is no difference in the behaviour of the (13)C- and (2)H-labelled tracers. Target testing allowed the tracer/tracee ratios to be determined using calculated cracking patterns, and produced equivalent results to conventional methods. Our experience in this work indicates that factor analysis has a useful place in many kinetic studies of this kind, either with one or many labelled species.

Administration, Oral↗

Two-hydronic-reactive states of acetylcholinesterase, mechanistically relevant acid-base catalyst of pKa 6.5 and a modulatory group of pKa 5.5.

Variation of experimentally observed pKa values in pH-dependent kinetic studies using acetylcholinesterase (AcChE) is rationalized by proposal of two-hydronic-reactive states, EH and EH2, of the free AcChE molecule. Two kinetically influential ionizations with pKa 6.5 for the general acid-base catalyst, possibly the imidazole group of histidine, and a modulatory group with pKa 5.5 residing at the juxtaposal modulatory site, provided fundamental bases for the observed variation in pK(app) values. Appropriate equations applicable to the proposed kinetic model in conjunction with pKa values (pKI 5.5, pKII 6.5) and relative varied values of the pH-independent rate constants, k'cat/K'm and kcat/Km, of the reactive states were used to generate computer simulation error-free pH-rate profiles. A series of theoretical apparently simple sigmoidal pH-rate profiles with characterizing parameters pK(app) varying between 5.5-6.5 were obtained. Ionization of a modulatory group with pKa 5.5 alone modifies the reaction mechanism of AcChE, and binding of substrates and inhibitors at this site provides modulation of catalysis/binding at the active center. Analysis of the relative magnitudes of pH-independent rate constants for the two reactive states revealed that in terms of the overall catalysis, the EH state shows favorable reactivity towards the cationic reagents with reactivity 1.0, as compared to the EH2 state with reactivities 0.25-0.55. Neutral reagents, in general, make use of the EH2 state more than cationic reagents, with reactivities 1.0 for the EH state and 0.3-1.0 for the EH2 state. Further analysis showed that this discrimination between the two reactive states, by both types of reagents, occurs predominantly through the difference in binding constants K'm and Km. Relative binding of a given cationic reagent to the respective reactive states ranges from K'm = 1.8 X Km to 4.0 X Km, and from K'm = 1.0 X Km to 2.0 X Km for the neutral reagents.

Acetylcholinesterase↗

Experimental study of wave dispersion and attenuation in concrete.

Results from an experimental study concerning wave propagation in cementitious materials are presented in this paper. Narrow band pulses at several frequencies were introduced into specimens of cement paste, mortar and concrete allowing direct measurement of longitudinal wave velocities and amplitude for each frequency. It is shown that aggregate content play an important role in wave propagation increasing considerably the wave velocity, while the aggregate size seems to control the attenuation observed. Slight velocity variations observed with frequency are discussed in relation to the degree of inhomogeneity of the materials.

Journal Article↗