Reproducibility and variation of morphometric analysis of carcinoembryonic antigen staining in histopathology. The influence of standardized microscopic fields

Using morphometric methods, five pathologists analyzed the positive staining for carcinoembryonic antigen (CEA) in sections from 17 ovarian tumors, with the intraclass correlation coefficient (ICC) and the mean values of the coefficients of variation (CV) used to assess reproducibility and variation. First, field and point scores for epithelium and mucin were estimated using 25 randomly selected square fields in sections from each of the tumors. The ICC range in the whole sample field was 0.53 to 0.81 (slight to substantial reproducibility) while the mean values of CV were 0.50 to 0.75. Second, the results of using random and standardized individual fields for the measurements were studied in three tumors. In random fields, the ICC was 0.57 to 0.71 (slight to moderate reproducibility) and the mean values of CV were 0.53 to 0.65. The corresponding values in standardized fields were 0.71 to 0.73 (moderate reproducibility) and 0.41 to 0.57, respectively. The results show that the variation is smaller and the degree of reproducibility higher in standardized fields. Considerable variation remains, however, revealing human factors as an important source of variation in practical morphometry.     

Measuring outcomes in primary care: a patient generated measure,MYMOP, compared with the SF-36 health survey.

OBJECTIVE--To assess the sensitivity to within person change over time of an outcome measure for practitioners in primary care that is applicable to a wide range of illness. DESIGN--Comparison of a new patient generated instrument, the measure yourself medical outcome profile (MYMOP), with the SF-36 health profile and a five point change score; all scales were completed during the consultation with'' practitioners and repeated after four weeks. 103 patients were followed up for 16 weeks and their results charted; seven practitioners were interviewed. SETTING--Established practice of the four NHS general practitioners and four of the private complementary practitioners working in one medical centre. SUBJECTS--Systematic sample of 218 patients from general practice and all 47 patients of complementary practitioners; patients had had symptoms for more than seven days. OUTCOME MEASURES--Standardised response mean and index of responsiveness; view of practitioners. RESULTS--The index of responsiveness, relating to the minimal clinically important difference, was high for MYMOP: 1.4 for the first symptom, 1.33 for activity, and 0.85 for the profile compared with < 0.45 for SF-36. MYMOP''s validity was supported by significant correlation between the change score and the change in the MYMOP score and the ability of this instrument to detect more improvement in acute than in chronic conditions. Practitioners found that MYMOP was practical and applicable to all patients with symptoms and that its use increased their awareness of patients'' priorities. CONCLUSION--MYMOP shows promise as an outcome measure for primary care and for complementary treatment. It is more sensitive to change than the SF-36 and has the added bonus of improving patient-practitioner communication.     

Estimating the responsiveness of an instrument using more than two repeated measures

The responsiveness of a measuring instrument is its ability to detect change over time. A commonly used index of responsiveness is the effect size for paired differences. This paper generalizes the effect size for paired differences to more than two repeated observations per subject. The sampling distribution of the generalized responsiveness statistic, Rt, is simulated for a range of plausible parameter values and for a range of sample sizes varying both the number of subjects (n) and the number of observations per subject (t). The coverage properties of confidence intervals constructed by four methods are compared. Confidence intervals based on jackknife estimates of the standard error and bias of Rt have good coverage properties even when n and t are small. The methods are used to determine which of two standard quality-of-life measures is more responsive to improvements in quality of life following surgery for early-stage breast cancer.     

Interobserver Reproducibility of Diffusion-Weighted MRI in Monitoring Tumor Response to Neoadjuvant Therapy in Esophageal Cancer

Objective

To investigate the reproducibility of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing tumor response early in the course of neoadjuvant chemoradiotherapy in patients with operable esophageal cancer.

Methods

Eleven male patients (mean age 54.8 years) with newly diagnosed esophageal cancer underwent DW-MRI before and 10 days after start of chemoradiotherapy. Reproducibility of apparent diffusion coefficient (ADC) measurements by manual (freehand) and semi-automated volumetric methods was assessed.

Results

Interobserver reproducibility for the assessment of mean tumor ADC by the manual measurement method was good, with an ICC of 0.69 (95% CI, 0.36 to 0.85; P = 0.001). Interobserver reproducibility for the assessment of mean tumor ADC by the semi-automated volumetric measurement method was very good, with an ICC of 0.96 (95% CI, 0.91 to 0.98; P<0.001).

Conclusion

Semi-automated volumetric ADC measurements have higher reproducibility than manual ADC measurements in assessing tumor response to chemoradiotherapy in patients with esophageal adenocarcinoma.     

Cognition after malignant media infarction and decompressive hemicraniectomy - a retrospective observational study

Background

The Multiple Sclerosis International Quality Of Life (MusiQoL) questionnaire, a 31-item, multidimensional, self-administrated questionnaire that is available in 14 languages including Spanish, has been validated using a large international sample. We investigated the validity and reliability of the Spanish version of MusiQoL in Spain.

Methods

Consecutive patients with different types and severities of multiple sclerosis (MS) were recruited from 22 centres across Spain. All patients completed the MusiQoL questionnaire, the 36-Item Short Form (SF-36) health survey, and a symptoms checklist at baseline and 21 days later. External validity, internal consistency, reliability and reproducibility were tested.

Results

A total of 224 Spanish patients were evaluated. Dimensions of MusiQoL generally demonstrated a high internal consistency (Cronbach's alpha: 0.70-0.92 for all but two MusiQoL domain scores). External validity testing revealed that the MusiQoL index score correlated significantly with all SF-36 dimension scores (Pearson's correlation: 0.46-0.76), reproducibility was satisfactory (intraclass correlation coefficient: 0.60-0.91), acceptability was high, and the time taken to complete the 31-item questionnaire was reasonable (mean [standard deviation]: 9.8 [11.8] minutes).

Conclusions

The Spanish version of the MusiQoL questionnaire appears to be a valid and reliable instrument for measuring quality of life in patients with MS in Spain and constitutes a useful instrument to measure health-related quality of life in the clinical setting.     

Reproducibility of surface EMG variables in isometric sub-maximal contractions of jaw elevator muscles.

The aims of this study were: (1) to develop and assess reproducibility of a new method for measuring masticatory force in the intercuspal position; (2) to test the reproducibility of surface EMG signal amplitude and spectral variables in constant force contractions of jaw elevator muscles and its dependency on inter-electrode distance. The study was performed on the masseter and temporalis anterior muscles of both sides of nine healthy volunteers. An intraoral compressive-force sensor was used to measure maximal voluntary contraction forces in the intercuspal position and to provide a visual feedback on sub-maximal forces to the subject. Three experimental sessions were performed in three days. In each session, three isometric contractions at 80% of the maximal force were sustained by the subjects for 30s. The intra-class correlation coefficient (ICC) of the maximal force measure was 71.9%. ICC of average rectified value and mean power spectral frequency of the EMG signal increased with inter-electrode distance, with values larger than 70% with 30 mm inter-electrode distance. It was concluded that surface EMG variables measured in isometric contractions of the jaw elevator muscles with the proposed force recording system show good reproducibility for clinical applications when a 30 mm inter-electrode distance is considered.     

A scanning inverted microfluorometer with electronic shutter control for automatic measurements in micro-test plates

A microfluorometer is described for automated measurements with a fixed excitation period in small volumes (5–10 μl) using standard Terasaki test plates. The Leitz inverted microfluorometer has been equipped with a scanning stage that has been linked electronically to electric shutters to control the excitation and measuring periods. The excitation of the sample takes place from below through the bottom of the test plate. The fluorescence signal is measured with an average value current meter which integrates the anode current of the photomultiplier during 1 sec. The result is printed on a digital recorder. The total measuring time for a 60-well Terasaki tray is about 135 s. The sensitivity of the instrument and the linearity and reproducibility of the measurements have been determined with samples of increasing concentrations of 4-methyl umbelliferone (4-MU). The coefficient of variation was smaller than 5%. The blank corresponded to 0.025 μm 4-MU (in 10 μl) which is equivalent to 0.25 pmol of 4-MU. The applicability of the instrument is illustrated by the measurements of β-hexosaminidase activity in diluted homogenates of cultured human fibroblasts.     

A Ratio Estimator of the Kappa Index of Agreement Between Two Observers

The kappa index is usually used for measuring the agreement between two observers when the scale is nominal. A modification of Cohen's kappa index was given by Krauth. The new estimator was biased and its large sample variance was obtained. An alternative estimator is developed here It is a ratio estimator and its mean square error is derived. A comparison with Cohen's estimator and Krauth's one is given by the examples used in the paper of Krauth.     

Validation of the Chinese Version of the Quality of Nursing Work Life Scale

Quality of Nursing Work Life (QNWL) serves as a predictor of a nurse’s intent to leave and hospital nurse turnover. However, QNWL measurement tools that have been validated for use in China are lacking. The present study evaluated the construct validity of the QNWL scale in China. A cross-sectional study was conducted conveniently from June 2012 to January 2013 at five hospitals in Guangzhou, which employ 1938 nurses. The participants were asked to complete the QNWL scale and the World Health Organization Quality of Life abbreviated version (WHOQOL-BREF). A total of 1922 nurses provided the final data used for analyses. Sixty-five nurses from the first investigated division were re-measured two weeks later to assess the test-retest reliability of the scale. The internal consistency reliability of the QNWL scale was assessed using Cronbach’s α. Test-retest reliability was assessed using the intra-class correlation coefficient (ICC). Criterion-relation validity was assessed using the correlation of the total scores of the QNWL and the WHOQOL-BREF. Construct validity was assessed with the following indices: χ² statistics and degrees of freedom; relative mean square error of approximation (RMSEA); the Akaike information criterion (AIC); the consistent Akaike information criterion (CAIC); the goodness-of-fit index (GFI); the adjusted goodness of fit index; and the comparative fit index (CFI). The findings demonstrated high internal consistency (Cronbach’s α = 0.912) and test-retest reliability (interclass correlation coefficient = 0.74) for the QNWL scale. The chi-square test (χ² = 13879.60, df [degree of freedom] = 813 P = 0.0001) was significant. The RMSEA value was 0.091, and AIC = 1806.00, CAIC = 7730.69, CFI = 0.93, and GFI = 0.74. The correlation coefficient between the QNWL total scores and the WHOQOL-BREF total scores was 0.605 (p<0.01). The QNWL scale was reliable and valid in Chinese-speaking nurses and could be used as a clinical and research instrument for measuring work-related factors among nurses in China.     

Measuring disease-specific quality of life in clinical trials.

While measurement of quality of life is a vital part of assessing the effect of treatment in many clinical trials, a measure that is responsive to clinically important change is often unavailable. Investigators are therefore faced with the challenge of constructing an index for a specific condition or even for a single trial. There are several stages in the development and testing of a quality-of-life measure: selecting an initial item pool, choosing the "best" items from that pool, deciding on questionnaire format, pretesting the instrument, and demonstrating the responsiveness and validity of the instrument. At each stage the investigator must choose between a rigorous, time-consuming approach to questionnaire construction that will establish the clinical relevance, responsiveness and validity of the instrument and a more efficient, less costly strategy that leaves reproducibility, responsiveness and validity untested. This article describes these options and outlines a pragmatic approach that yields consistently satisfactory disease-specific measures of quality of life.     

Inconstancy of Taylor'sb: Simulated sampling with different quadrat sizes and spatial distributions

Taylor 's power law, s²=am^b, provides a precise summary of the relationship between sample variance (s²) and sample mean (m) for many organisms. The coefficient b has been interpreted as an index of aggregation, with a characteristic value for a given species in a particular environment, and has been thought to be independent of the sample unit. Simulation studies were conducted that demonstrate that the value of b may vary with the size of the sample unit in quadrat sampling, and this relationship, in turn, depends on the underlying spatial distribution of the population. For example, simulated populations with hierarchical aggregation on a large scale produced values of b that increased with the size of the sample unit. In contrast, for a simulated population with randomly distributed clusters of individuals, the value of b eventually decreased with increasing quadrat size, as sample counts became more uniform. A single value ofTaylor 's b, determined with a particular sample unit, provides neither a fixed index of aggregation nor a complete picture of a species' spatial distribution. Rather, it describes a consistent relationship between sample variance and sample mean over a range of densities, on a spatial scale related to the size of the sample unit. This relationship may reflect, but not uniquely define, density-dependent population and behavioral processes governing the spatial distribution of the organism. Interpretation ofTaylor 'sb for a particular organism should be qualified by reference to the sample unit, and comparisons should not be made between cases in which different sample units were used. Whenever possible, a range of sample units should be used to provide information about the pattern of distribution of a population on various spatial scales.     

Reliability and validity of the Ethiopian version of the hospital anxiety and depression scale (HADS) in HIV infected patients

Background

The hospital anxiety and depression scale (HADS) is a widely used instrument for evaluating psychological distress from anxiety and depression. HADS has not yet been validated in Ethiopia. The aim of this study was to evaluate the reliability and validity of the Amharic (Ethiopian language) version of HADs among HIV infected patients.

Methods

The translated scale was administered to 302 HIV/AIDS patients on follow up for and taking anti-retroviral treatment. Consistency assessment was conducted using Cronbach''s alpha, test-retest reliability using intra-class correlation coefficients (ICC). Construct validity was examined using principal components analysis (PCA). Parallel analysis, Kaiser''s criterion and the scree test were used for factor extraction.

Results

The internal consistency was 0.78 for the anxiety, 0.76 for depression subscales and 0.87 for the full scale of HADS. The intra-class correlation coefficient (ICC) was 80%, 86%, and 84% for the anxiety and depression subscales, and total score respectively. PCA revealed a one dimensional scale.

Conclusion

This preliminary validation study of the Ethiopian version of the HADs indicates that it has promising acceptability, reliability and validity. The adopted scale has a single underlying dimension as indicated by Razavi''s model. The HADS can be used to examine psychological distress in HIV infected patients. Findings are discussed and recommendations made.     

A differential heat-conduction microcalorimeter for heat-capacity measurements of fluids

A heat-conduction calorimeter has been developed for measuring small changes in heat capacity of milligram samples of membrane lipid dispersed in water as a function of temperature. The operation of the instrument is based on the principle that the thermal response of the sample to a short (10 s), electrically generated heat burst is a function of the diffusivity of the sample. Modeling studies of the instrument's performance have revealed that the output response after the heat burst is a function of only the heat capacity, ϱC_p. Calibration of the instrument experimentally confirmed this behavior. This feature obviated the need to measure the thermal conductivity in order to determine ϱC_p from the diffusivity equation, η = γ/ϱC_p. The calorimeter has the following characteristics: reproducibility of loading: ± 400 μJ/C° · cm³; baseline stability: ± 10 μJ/C° · cm³ per 36 h; resolution (± 1 S.D.): ± 50 μJ/C° · cm³; sample size 600 μl.     

Reproducibility of Frankfort Horizontal Plane on 3D Multi-Planar Reconstructed MR Images

Objective

The purpose of this study was to determine the accuracy and reliability of Frankfort horizontal plane identification using displays of multi-planar reconstructed MRI images, and propose it as a sufficiently stable and standardized reference plane for craniofacial structures.

Materials and Methods

MRI images of 43 subjects were obtained from the longitudinal population based cohort study SHIP-2 using a T1-weighted 3D sequence. Five examiners independently identified the three landmarks that form FH plane. Intra-examiner reproducibility and inter-examiner reliability, correlation coefficients (ICC), coefficient of variability and Bland-Altman plots were obtained for all landmarks coordinates to assess reproducibility. Intra-examiner reproducibility and inter-examiner reliability in terms of location and plane angulation were also assessed.

Results

Intra- and inter-examiner reliabilities for X, Y and Z coordinates of all three landmarks were excellent with ICC values ranging from 0.914 to 0.998. Differences among examiners were more in X and Z than in Y dimensions. The Bland–Altman analysis demonstrated excellent intra- as well as inter-examiner agreement between examiners in all coordinates for all landmarks. Intra-examiner reproducibility and inter-examiner reliability of the three landmarks in terms of distance showed mean differences between 1.3 to 2.9 mm, Mean differences in plane angulation were between 1.0° to 1.5° among examiners.

Conclusion

This study revealed excellent intra-examiner reproducibility and inter-examiner reliability of Frankfort Horizontal plane through 3D landmark identification in MRI. Sufficiently stable landmark-based reference plane could be used for different treatments and studies.     

Neurophysiological evaluation of healthy human anorectal sensation

Patients with functional gastrointestinal disorders often demonstrate abnormal visceral sensation. Currently, rectal sensation is assessed by manual balloon distension or barostat. However, neither test is adaptable for use in the neurophysiological characterization of visceral afferent pathways by sensory evoked potentials. The aim of this study was to assess the reproducibility and quality of sensation evoked by electrical stimulation (ES) and rapid balloon distension (RBD) in the anorectum and to apply the optimum stimulus to examine the visceral afferent pathway with rectal evoked potentials. Healthy subjects (n = 8, median age 33 yr) were studied on three separate occasions. Variability, tolerance, and stimulus characteristics were assessed with each technique. Overall ES consistently invoked pain and was chosen for measuring rectal evoked potential whereas RBD in all cases induced the strong urge to defecate. Rectal intraclass correlation coefficient (ICC) for ES and RBD (0.82 and 0.72, respectively) demonstrated good reproducibility at pain/maximum tolerated volume but not at sensory threshold. Only sphincter ICC for ES at pain showed acceptable between-study reproducibility (ICC 0.79). Within studies ICC was good (>0.6) for anorectal ES and RBD at both levels of sensation. All subjects reported significantly more unpleasantness during RBD than ES (P < 0.01). This study demonstrates that ES and RBD are similarly reproducible. However, the sensations experienced with each technique differed markedly, probably reflecting differences in peripheral and/or central processing of the sensory input. This is of relevance in interpreting findings of neuroimaging studies of anorectal sensation and may provide insight into the physiological characteristics of visceral afferent pathways in health and disease.     

Reproducibility of surface EMG variables and peak torque during three sets of ten dynamic contractions.

The interpretation of the electromyogram (EMG) of dynamic contractions might be difficult because the movement per se introduces additional factors that could affect its characteristics. There is a lack of studies concerning the reproducibility of surface EMG registrations during dynamic contractions. The aim was to investigate the during-the-day reproducibility (using intra-class correlation; ICC) of the peak torque (PT) and the EMG variables (without removing the electrodes) of dynamic contractions. Ten healthy subjects performed three sets of 10 dynamic maximum right-knee extensions with a one-hour interval in between, using an isokinetic dynamometer and the PT was determined. EMG signals were recorded from the right vastus lateralis, rectus femoris and vastus medialis muscles using surface electrodes and the mean frequency of the power spectrum (MNF [Hz]) and the signal amplitude (RMS [microV]), were computed. The ability to relax in-between the maximum extensions was calculated as a ratio of the RMS during the passive flexion phase and the RMS during the active extension phase of each contraction cycle: the signal amplitude ratio (SAR). Both PT (ICC = 0.99) and RMS (ICC = 0.83-0.98) had good reproducibility. The reproducibility of MNF was good for all muscles when the mean of contraction nos.: 1-10 was used. Vastus lateralis had the highest ICC among the three muscles. The reproducibility of SAR was generally poor (ICC < 0.60). The present study showed good reproducibility for common EMG variables (MNF and RMS) obtained during maximum isokinetic contractions.     

Finlay–Wilkinson's regression coefficient as a pre‐screening criterion for yield responsiveness to elevated atmospheric CO2 concentration in crops

The rising atmospheric CO₂ concentration ([CO₂]) can increase crop productivity, but there are likely to be intraspecific variations in the response. To meet future world food demand, screening for genotypes with high [CO₂] responsiveness will be a useful option, but there is no criterion for high [CO₂] responsiveness. We hypothesized that the Finlay–Wilkinson regression coefficient (RC) (for the relationship between a genotype's yield versus the mean yield of all genotypes in a specific environment) could serve as a pre‐screening criterion for identifying genotypes that respond strongly to elevated [CO₂]. We collected datasets on the yield of 6 rice and 10 soybean genotypes along environmental gradients and compared their responsiveness to elevated [CO₂] based on the regression coefficients (i.e. the increases of yield per 100 µmol mol^?1 [CO₂]) identified in previous reports. We found significant positive correlations between the RCs and the responsiveness of yield to elevated [CO₂] in both rice and soybean. This result raises the possibility that the coefficient of the Finlay–Wilkinson relationship could be used as a pre‐screening criterion for [CO₂] responsiveness.     

Test-retest reliability of three different countermovement jumping tests

In studies of physical performance comprising muscle strength and power, a vertical jump is a test method that frequently is used. It is important to have access to accurate measuring tools providing data with high reproducibility. Studies have shown that body composition also may play an important part in physical performance. The purpose of this study was to determine test-retest reliability for 3 different kinds of vertical jumps and to correlate jump height with body composition. Thirty-four normally trained subjects (women n = 17) between 18 and 25 years participated. Test-retest, on 3 kinds of vertical jumps, was performed with a median of 7 days between jumps. Methods used were a countermovement jump (CMJ) on a contact mat, with and without arm swing, and an Abalakow jump (AJ) using measuring tape, with arm swing. Body composition was assessed with the use of bioelectric impedance analysis. The results showed that high intraclass correlation coefficients (ICCs) were observed between testing occasions for all 3 vertical jumps (ICC between 0.48 and 0.88). The AJ in women presented the lowest ICC. Also the correlation between CMJ and AJ was high (rs = 0.88). Moderate-to-high correlations could be shown between body composition and CMJ in women (rs = -0.57-0.76). In conclusion, very high test-retest reliability for CMJ on a contact mat was found. For the AJ using a measuring tape, ICC were overall high, but a moderate nonsignificant ICC were found in women, indicating poor reproducibility. The data from the CMJ and AJ may be compared if approximately 25% of the AJ value is subtracted. In practice, this means that vertical jump tests have high reproducibility and can be used as measures of power development.     

Reproducibility of Middle Cerebral Artery Stenosis Measurements by DSA: Comparison of the NASCET and WASID Methods

Purpose

To evaluate the intra- and inter-observer variability of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) criteria for the evaluation of middle cerebral artery (MCA) stenosis using digital subtraction angiography (DSA).

Materials and Methods

DSA images of 114 cases with 131 stenotic MCAs were retrospectively analyzed. Two radiologists and a researcher measured the degree of MCA stenosis independently using both NASCET and WASID methods. To determine intra-observer agreement, all the observers reevaluated the degree of MCA stenosis 4 weeks later. The linear relation and coefficient of variation (CV) between the measurements made by the two methods were assessed by correlation coefficient and multi-factor analysis of variance (ANOVA), respectively. Intra- and inter-observer variability of the two methods was evaluated by intraclass correlation coefficient (ICC), Spearman’s R value, Pearson correlation coefficient and Bland-Altman plots.

Results

Despite the fact that the degree of MCA stenosis measured by NASCET was lower than measured using the WASID method, there was good linear correlation between the measurements made by the two methods (for the mean measurements of the 3 observers, NASCET% = 0.891 × WASID% - 1.89%; ICC, Spearman’s R value and Pearson correlation were 0.874, 0.855, and 0.874, respectively). The CVs of both intra- and inter-observer measurements of MCA stenosis using WASID were significantly lower than that using NASCET confirmed by the multi-factor ANOVA results, which showed only the measurement methods of MCA stenosis had significant effects on the CVs both in intra- and inter-observer measurements (both P values < 0.001). Intra-observer measurements showed good or excellent agreement with respect to WASID and NASCET evaluation (ICC, 0.656 to 0.817 and 0.635 to 0.761, respectively). Good agreement for the WASID evaluation (ICC, 0.592 to 0.628) and for the NASCET evaluation (ICC, 0.529 to 0.568) was observed for inter-observer measurements. Bland-Altman plots demonstrated that the WASID method had better reproducibility and intra-observer agreement than NASCET method for evaluating MCA stenosis.

Conclusion

Both NASCET and WASID methods have an acceptable level of agreement; however, the WASID method had better reproducibility for the evaluation of MCA stenosis, and thus the WASID method may serve as a standard for measuring the degree of MCA stenosis.