Comparison of central macular thickness (CMT) measurement between time domain and spectral domain (SD) optical coherence tomography (OCT) and reproducibility of SD OCT in active neovascular AMD

Purpose: To evaluate the reproducibility of Cirrus-SD OCT measurements and to compare central macular thickness (CMT) measurements between TD-Stratus and SD-Cirrus OCT in patients with active exudative AMD. Methods: Consecutive case series of patients with active exudative AMD seen in the Medical Retina Department. Patients underwent 1 scan with Stratus (macular thickness map protocol) and 5 scans with Cirrus (Macular Cube protocol) at the same visit by the same experienced examiner. To be included, patients best-corrected visual acuity (BCVA) had to be >20/200 while all scans had to be of sufficient quality, well-centered and at least one Cirrus scan with CMT >300 microns. The repeatability of the SD Cirrus was estimated by using all 5 CMT measurements and the mean of the Cirrus measurements was compared with the CMT obtained by TD Stratus. Results: Cirrus OCT demonstrated high intraobserver repeatability at the central foveal region (ICC 96%). The mean of the CMT measurements was 321microns for Stratus and 387 microns for Cirrus. The average difference was 65m (SD=30). The coefficient of concordance between Stratus and Cirrus CMT measurements was rho=0,749 with a high precision and a moderate accuracy. The equation of the line of regression between Stratus and meanCirrus is given by the following: M_stratus = 0,848 x m_cirrus - 4,496 (1).Conclusions: The Cirrus macular cube protocol allows reproducible CMT measurements in patients with active exudative AMD. In cases of upgrading from TD to SD use and vice versa, there is the possibility to predict the measurements by using the equation (1). These real life data and conclusions can help in improving our clinical management of patients with neovascular AMD.

Reproducibility of diabetes quality of care indicators as reported by patients and physicians.

INTRODUCTION: Self-report of diabetes care has moderate validity and is prone to under- and over-reporting. We assessed reproducibility of a range of processes and outcomes of diabetes care as reported by patients and physicians. METHODS: In a Swiss community-based survey, patients with diabetes and physicians independently reported past 12 months processes of care (HbA1c, lipids, microalbuminuria, blood pressure, weight, foot and eye examinations) and last measured values of HbA1c, height, weight and blood pressure. For dichotomous variables, we assessed reliability by Cohen's kappa and agreement by uniform kappa. For continuous measures, we used Lin's concordance correlation coefficient and limits of agreement, respectively. RESULTS: Mean age of the 210 patients was 65 years; 40% were women, and 51% had diabetes for >10 years. Agreement was good for recommended processes of care such as blood pressure (uniform kappa = 0.94), HbA1c (0.93), weight (0.88) and lipid (0.78), but lower for microalbuminuria, foot and eye examinations (all <0.50). Cohen's kappa values were all low (<0.25). Comparisons of reported continuous variables showed large limits of agreement for height (±6 cm) and weight (8-10 kg) despite high concordance correlation coefficients (0.93 and 0.97). Concordance correlation coefficients were smaller for HbA1c (0.72) and blood pressure (0.5-0.6), with large limits of agreement (±2% and ±25 mmHg). CONCLUSION: While agreement of routine processes of care was good, agreement was less satisfactory for microalbuminuria, foot and eye examinations. Reports of continuous outcomes yielded good reliability but too wide limits of agreement. Quality of care evaluation relying on self-report only should be made cautiously.

Reproducibility of heart rate variability parameters measured in healthy subjects at rest and after a postural change maneuver

Heart rate variability (HRV) provides important information about cardiac autonomic modulation. Since it is a noninvasive and inexpensive method, HRV has been used to evaluate several parameters of cardiovascular health. However, the internal reproducibility of this method has been challenged in some studies. Our aim was to determine the intra-individual reproducibility of HRV parameters in short-term recordings obtained in supine and orthostatic positions. Electrocardiographic (ECG) recordings were obtained from 30 healthy subjects (20-49 years, 14 men) using a digital apparatus (sampling ratio = 250 Hz). ECG was recorded for 10 min in the supine position and for 10 min in the orthostatic position. The procedure was repeated 2-3 h later. Time and frequency domain analyses were performed. Frequency domain included low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) bands. Power spectral analysis was performed by the autoregressive method and model order was set at 16. Intra-subject agreement was assessed by linear regression analysis, test of difference in variances and limits of agreement. Most HRV measures (pNN50, RMSSD, LF, HF, and LF/HF ratio) were reproducible independent of body position. Better correlation indexes (r > 0.6) were obtained in the orthostatic position. Bland-Altman plots revealed that most values were inside the agreement limits, indicating concordance between measures. Only SDNN and NNv in the supine position were not reproducible. Our results showed reproducibility of HRV parameters when recorded in the same individual with a short time between two exams. The increased sympathetic activity occurring in the orthostatic position probably facilitates reproducibility of the HRV indexes.

Assessing the Reproducibility of Clustering of Molecular Dynamics Conformations on Self-Organizing Maps

The goal of most clustering algorithms is to find the optimal number of clusters (i.e. fewest number of clusters). However, analysis of molecular conformations of biological macromolecules obtained from computer simulations may benefit from a larger array of clusters. The Self-Organizing Map (SOM) clustering method has the advantage of generating large numbers of clusters, but often gives ambiguous results. In this work, SOMs have been shown to be reproducible when the same conformational dataset is independently clustered multiple times (~100), with the help of the Cramérs V-index (C_v). The ability of C_v to determine which SOMs are reproduced is generalizable across different SOM source codes. The conformational ensembles produced from MD (molecular dynamics) and REMD (replica exchange molecular dynamics) simulations of the penta peptide Met-enkephalin (MET) and the 34 amino acid protein human Parathyroid Hormone (hPTH) were used to evaluate SOM reproducibility. The training length for the SOM has a huge impact on the reproducibility. Analysis of MET conformational data definitively determined that toroidal SOMs cluster data better than bordered maps due to the fact that toroidal maps do not have an edge effect. For the source code from MATLAB, it was determined that the learning rate function should be LINEAR with an initial learning rate factor of 0.05 and the SOM should be trained by a sequential algorithm. The trained SOMs can be used as a supervised classification for another dataset. The toroidal 10×10 hexagonal SOMs produced from the MATLAB program for hPTH conformational data produced three sets of reproducible clusters (27%, 15%, and 13% of 100 independent runs) which find similar partitionings to those of smaller 6×6 SOMs. The χ^2 values produced as part of the C_v calculation were used to locate clusters with identical conformational memberships on independently trained SOMs, even those with different dimensions. The χ^2 values could relate the different SOM partitionings to each other.

Reproducibility of a short semi-quantitative food group questionnaire and its performance in estimating nutrient intake compared with a 7-day diet diary in the Million Women Study

Objectives: To assess the short- and long-term reproducibility of a short food group questionnaire, and to compare its performance for estimating nutrient intakes in comparison with a 7-day diet diary. Design: Participants for the reproducibility study completed the food group questionnaire at two time points, up to 2 years apart. Participants for the performance study completed both the food group questionnaire and a 7-day diet diary a few months apart. Reproducibility was assessed by kappa statistics and percentage change between the two questionnaires; performance was assessed by kappa statistics, rank correlations and percentages of participants classified into the same and opposite thirds of intake. Setting: A random sample of participants in the Million Women Study, a population-based prospective study in the UK. Subjects: In total, 12 221 women aged 50-64 years. Results: in the reproducibility study, 75% of the food group items showed at least moderate agreement for all four time-point comparisons. Items showing fair agreement or worse tended to be those where few respondents reported eating them more than once a week, those consumed in small amounts and those relating to types of fat consumed. Compared with the diet diary, the food group questionnaire showed consistently reasonable performance for the nutrients carbohydrate, saturated fat, cholesterol, total sugars, alcohol, fibre, calcium, riboflavin, folate and vitamin C. Conclusions: The short food group questionnaire used in this study has been shown to be reproducible over time and to perform reasonably well for the assessment of a number of dietary nutrients.

Reproducibility of the online Food4Me food-frequency questionnaire for estimating dietary intakes across Europe

Background: Accurate dietary assessment is key to understanding nutrition-related outcomes and is essential for estimating dietary change in nutrition-based interventions. Objective: The objective of this study was to assess the pan-European reproducibility of the Food4Me food-frequency questionnaire (FFQ) in assessing the habitual diet of adults. Methods: Participantsfromthe Food4Me study, a 6-mo,Internet-based, randomizedcontrolled trial of personalized nutrition conducted in the United Kingdom, Ireland, Spain, Netherlands, Germany, Greece, and Poland were included. Screening and baseline data (both collected before commencement of the intervention) were used in the present analyses, and participants were includedonly iftheycompleted FFQs at screeningand at baselinewithin a 1-mo timeframebeforethe commencement oftheintervention. Sociodemographic (e.g., sex andcountry) andlifestyle[e.g.,bodymass index(BMI,inkg/m2)and physical activity] characteristics were collected. Linear regression, correlation coefficients, concordance (percentage) in quartile classification, and Bland-Altman plots for daily intakes were used to assess reproducibility. Results: In total, 567 participants (59% female), with a mean 6 SD age of 38.7 6 13.4 y and BMI of 25.4 6 4.8, completed bothFFQswithin 1 mo(mean 6 SD: 19.26 6.2d).Exact plus adjacent classification oftotal energy intakeinparticipants was highest in Ireland (94%) and lowest in Poland (81%). Spearman correlation coefficients (r) in total energy intake between FFQs ranged from 0.50 for obese participants to 0.68 and 0.60 in normal-weight and overweight participants, respectively. Bland-Altman plots showed a mean difference between FFQs of 210 kcal/d, with the agreement deteriorating as energy intakes increased. There was little variation in reproducibility of total energy intakes between sex and age groups. Conclusions: The online Food4Me FFQ was shown to be reproducible across 7 European countries when administered within a 1-mo period to a large number of participants. The results support the utility of the online Food4Me FFQ as a reproducible tool across multiple European populations. This trial was registered at clinicaltrials.gov as NCT01530139.

Influence of image filters on the reproducibility of measurements of alveolar bone loss

The reproducibility of measurements of alveolar bone loss on radiographs may be a problem on epidemiologic studies, as they are based on comparisons of the diagnosis of various examiners. The aim of the present research paper was to assess the inter- and intra-examiner reproducibility of measurements of the interproximal alveolar bone loss on non-manipulated digital radiographs and after the application of image filters. Five Oral Radiologists measured the distance between the cementoenamel junction (CEJ) to the alveolar crest or to the deepest point of the bony defect on 12 interproximal digital radiographs of molars and bicuspids of a dry human skull. The digital manipulation and the linear measurements were obtained with the Trophy Windows software (Throphy®). For each image, six different versions were created: 1) non-manipulated; 2) bright-contrast adjustment; 3) negative; 4) negative with brightness-contrast adjustment; 5) pseudo-colored; 6) pseudo-colored with brightness-contrast adjustment. In order to prevent interpretation bias because of the repetition of measurements, the examiners measured the radiographs in a random sequence. The two-way ANOVA test at 5% level of significance to compare the means of readings of the same operator with each filter indicated p<0.05 for the majority of operators, while the comparison between the mean values of operators using the same filter indicated p>0.05 for all filters. Based on the results, we concluded that linear measurements of interproximal alveolar bone loss on digital radiographs are highly reproducible among examiners. Nevertheless, the application of image filters significantly influenced the degree of intra-examiner reproducibility. Some filters even reduced the reproducibility of intra-examiner readings.

Reproducibility of heart rate and rating of perceived exertion values obtained from different incremental treadmill tests

Objective The present study aimed to examine the reproducibility of heart rate (HR) and rating of perceived exertion (RPE) values obtained during different incremental treadmill tests. Equipment and methods Twenty male, recreational, endurance-trained runners (10-km running pace: 10–15 km·h−1) performed, in a counterbalanced order, three continuous incremental exercise tests with different speed increments (0.5 km·h−1, 1 km·h−1 and 2 km·h−1). Thereafter, each participant performed the three tests again, maintaining the same order as before. The reproducibility of the HR and RPE values were analyzed for all protocols during submaximal intensities (8, 10, 12, and 14 km·h−1). In addition, it was examined the reproducibility of maximal HR (HRmax) and peak RPE (RPEpeak). Results The variability of both the HR and RPE values showed a tendency to decrease over the stages during the incremental test and was not or slightly influenced by the incremental test design. The HR at 14 km·h−1 and HRmax presented the highest reproducibility (CV < 2%). In contrast, the submaximal RPE values showed higher variability indices (i.e., CV > 5.0%). In conclusion, the HR values were highly reproducible during the stages of the incremental test, in contrast to the RPE values that presented limited reproducibility.

Reproducibility of South American precipitation due to subtropical South Atlantic SSTs

This work investigates the eproducibility of precipitation simulated with an atmospheric general circulation model (AGCM) forced by subtropical South Atlantic sea surface temperature (SST) anomalies. This represents an important test of the model prior to investigating the impact of SSTs on regional climate. A five-member ensemble run was performed using the National Center for Atmospheric Research (NCAR) Community Climate Model, version 3 (CCM3). The CCM3 was forced by observed monthly SST over the South Atlantic from 20 to 60 S. The SST dataset used is from the Hadley Centre covering the period of September 1949-October 2001; this covers more than 50 yr of simulation. A statistical technique is used to determine the reproducibility in the CCM3 runs and to assess potential predictability in precipitation. Empirical orthogonal function analysis is used to reconstruct the ensemble using the most reproducible forced modes in order to separate the atmospheric response to local SST forcing from its internal variability. Results for reproducibility show a seasonal dependence, with higher values during austral autumn and spring. The spatial distribution of reproducibility shows that the tropical atmosphere is dominated by the underlying SSTs while variations in the subtropical-extratropical regions are primarily driven by internal variability. As such, changes in the South Atlantic convergence zone (SACZ) region are mainly dominated by internal atmospheric variability while the ITCZ has greater external dependence, making it more predictable. The reproducibility distribution reveals increased values after the reconstruction of the ensemble.

Effect of Population Heterogenization on the Reproducibility of Mouse Behavior: A Multi-Laboratory Study

In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions. Here, we examined whether a simple form of heterogenization effectively improves reproducibility of test results in a multi-laboratory situation. Each of six laboratories independently ordered 64 female mice of two inbred strains (C57BL/6NCrl, DBA/2NCrl) and examined them for strain differences in five commonly used behavioral tests under two different experimental designs. In the standardized design, experimental conditions were standardized as much as possible in each laboratory, while they were systematically varied with respect to the animals' test age and cage enrichment in the heterogenized design. Although heterogenization tended to improve reproducibility by increasing within-experiment variation relative to between-experiment variation, the effect was too weak to account for the large variation between laboratories. However, our findings confirm the potential of systematic heterogenization for improving reproducibility of animal experiments and highlight the need for effective and practicable heterogenization strategies.

Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy

Puppa G, Senore C, Sheahan K, Vieth M, Lugli A, Zlobec I, Pecori S, Wang L M, Langner C, Mitomi H, Nakamura T, Watanabe M, Ueno H, Chasle J, Conley S A, Herlin P, Lauwers G Y & Risio M (2012) Histopathology Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy Aims:  Despite the established prognostic relevance of tumour budding in colorectal cancer, the reproducibility of the methods reported for its assessment has not yet been determined, limiting its use and reporting in routine pathology practice. Methods and results:  A morphometric system within telepathology was devised to evaluate the reproducibility of the various methods published for the assessment of tumour budding in colorectal cancer. Five methods were selected to evaluate the diagnostic reproducibility among 10 investigators, using haematoxylin and eosin (H&E) and AE1-3 cytokeratin-immunostained, whole-slide digital scans from 50 pT1-pT4 colorectal cancers. The overall interobserver agreement was fair for all methods, and increased to moderate for pT1 cancers. The intraobserver agreement was also fair for all methods and moderate for pT1 cancers. Agreement was dependent on the participants' experience with tumour budding reporting and performance time. Cytokeratin immunohistochemistry detected a higher percentage of tumour budding-positive cases with all methods compared to H&E-stained slides, but did not influence agreement levels. Conclusions:  An overall fair level of diagnostic agreement for tumour budding in colorectal cancer was demonstrated, which was significantly higher in early cancer and among experienced gastrointestinal pathologists. Cytokeratin immunostaining facilitated detection of budding cancer cells, but did not result in improved interobserver agreement.

Intrapatient reproducibility of the BISxp monitor

BACKGROUND: The Bispectral Index (BIS) reportedly reflects anesthetic depth. It is recommended that anesthetic agents should be titrated to maintain the BIS between 40 and 60 arbitrary BIS units during anesthesia. For anesthesia providers to follow this recommendation, the monitor should be predictably affected by different anesthetic agents and have good interpatient and intrapatient reproducibility. The authors hypothesized that when two BISxp devices (Aspect Medical Systems, Newton, MA) are placed concurrently on the same patient, their readings are concordant throughout the anesthetic period. METHODS: Simultaneous BIS recordings from two BISxp monitors were obtained during anesthesia at 5-s intervals from 12 participants. RESULTS: In total 22,860 concurrent paired BIS readings were obtained. For 10.7% of the time, there were sustained periods of 30 s or greater where the readings suggested a different depth of anesthesia. For 6% of the time, there were sustained periods of 30 s or greater where the readings differed by 10 or more arbitrary BIS units. The regression coefficient (R) for the two devices was 0.65 (range, 0.35-0.92). There was zero bias between the devices, and the 95% limits of agreement ranged between -18 and +17. CONCLUSION: A conflicting anesthetic management was suggested by the simultaneous BIS readings 10.7% of the time. These results suggest that BISxp does not always provide a reproducible single number. Anesthesia providers should not rely exclusively on the BIS reading when assessing depth of anesthesia.

Reproducibility of dGEMRIC in assessment of hip joint cartilage: a prospective study

PURPOSE: To investigate the reproducibility of dGEMRIC in the assessment of cartilage health of the adult asymptomatic hip joint. MATERIALS AND METHODS: Fifteen asymptomatic volunteers (mean age, 26.3 years +/- 3.0) were preliminarily studied. Any volunteer that was incidentally diagnosed with damaged cartilage on MRI (n = 5) was excluded. Ten patients that had no evidence of prior cartilage damage (mean age, 26.2 years +/- 3.4) were evaluated further in this study. The reproducibility of dGEMRIC was assessed with two T1(Gd) exams performed 4 weeks apart in these volunteers. The protocol involved an initial standard MRI to confirm healthy cartilage, which was then followed by dGEMRIC. The second scan included only the repeat dGEMRIC. Region of interest (ROI) analyses for T1(Gd)-measurement was performed in seven radial reformats. Statistical analysis included the student's t-test and intra-class correlation (ICC) measurement to assess reproducibility. RESULTS: Overall 70 ROIs were studied. Mean cartilage T1(Gd) values at various loci ranged from 560.9 ms to 684.4 ms at the first set of readings and 551.5 ms to 662.2 ms in the second one. The mean difference per region of interest between the two T1(Gd)-measurements ranged from 21.4 ms (3.7%) to 45.0 ms (6.8%), which was not found to be statistically significant (P = 0.153). There was a high reproducibility detected (ICC range, 0.667-0.915). Intra- and Inter-observer analyses proved a high agreement for T1(Gd) assessment (0.973 and 0.932). CONCLUSION: We found dGEMRIC to be a reliable tool in the assessment of cartilage health status in adult hip joints.

Variability of anti-PF4/heparin antibody results obtained by the rapid testing system ID-H/PF4-PaGIA

BACKGROUND: Recent studies have shown that a low clinical pretest probability may be adequate for excluding heparin-induced thrombocytopenia. However, for patients with intermediate or high pretest probability, laboratory testing is essential for confirming or refuting the diagnosis. Rapid assessment of anti-PF4/heparin-antibodies may assist clinical decision-making. OBJECTIVES: To evaluate the performance of rapid ID-H/PF4-PaGIA. In particular, we verified reproducibility of results between plasma and serum specimens, between fresh and frozen samples, and between different ID-H/PF4-polymer lots (polystyrene beads coated with heparin/PF4-complexes). PATIENTS/METHODS: The samples studied were 1376 plasma and 914 corresponding serum samples from patients investigated for suspected heparin-induced thrombocytopenia between January 2000 and October 2008. Anti-PF4/heparin-antibodies were assessed by ID-H/PF4-PaGIA, commercially available ELISAs and heparin-induced platelet aggregation test. RESULTS: Among 914 paired plasma/serum samples we noted discordant results (negative vs. low-titre positive) in nine instances (1%; 95%CI, 0.4-1.6%). Overall, agreement between titres assessed in plasma vs. serum was highly significant (Spearman correlation coefficient, 0.975; P < 0.0001). Forty-seven samples tested both fresh and after freezing/thawing showed a good agreement, with one discordant positive/negative result (Spearman correlation coefficient, 0.970; P < 0.0001). Among 1376 plasma samples we noted a strikingly variable incidence of false negative results (none - 82%; 95%CI, 66-98%), depending on the employed ID-H/PF4-polymer lot. Faulty lots can be recognized by titrating commercial positive controls and stored samples of HIT-patients. CONCLUSION: Laboratories performing the assay should implement stringent internal quality controls in order to recognize potentially faulty ID-H/PF4-polymer lots, thus avoiding false negative results.

Reproducibility of cerebral phenylalanine levels in patients with phenylketonuria determined by 1H-MR spectroscopy

The reproducibility of metabolite content determined by MR spectroscopy (MRS) is usually at best a few percent for the prominent singlets. When studying low-concentration metabolites, like phenylalanine (Phe), where tissue content can be <100 micromol/kg, better reproducibility is paramount-particularly in view of using MRS results for potential individual treatment advice. An optimized, targeted spectroscopy method was established at 1.5T and reproducibility was established in 21 patients with phenylketonuria (PKU) where three spectra were recorded in each of three independent sessions, two of which were in immediate succession to minimize physiologic variation. Intersession variation was found to be only 7 micromol/kg Phe for back-to-back repetition of sessions, in close agreement with the variation of 16 micromol/kg observed for single spectra within a session. Analysis of variance proved the individuality of the blood/brain Phe ratio-though this ratio seems to be influenced by physiologic factors that are not stable in time. The excellent reproducibility was achieved through optimization of various factors, including signal-to-noise ratio, repositioning, and prescan calibrations, but also by enforcing as much prior information as possible (e.g., lineshape and phase from reference scans, constant prior-knowledge-locked baseline). While the application of maximum general prior knowledge is a general method to reduce fluctuations, one should remember that it may introduce systematic errors.