Mean Within-subject Coefficient Of Variation Research Articles

Improved reproducibility of γ-aminobutyric acid measurement from short-echo-time proton MR spectroscopy by linewidth-matched basis sets in LCModel.

γ-Aminobutyric acid (GABA), as the primary inhibitory neurotransmitter, is extremely important for maintaining healthy brain function, and deviations from GABA homeostasis are related to various brain diseases. Short-echo-time (short-TE) proton MR spectroscopy (1 H-MRS) has been employed to measure GABA concentration from various human brain regions at high magnetic fields. The aim of this study was to investigate the effect of spectral linewidth on GABA quantification and explore the application of an optimized basis-set preparation approach using a spectral-linewidth-matched (LM) basis set in LCModel to improve the reproducibility of GABA quantification from short-TE 1 H-MRS. In contrast to the fixed-linewidth basis-set approach, the LM basis-set preparation approach, where all metabolite basis spectra were simulated with a linewidth 4 Hz narrower than that of water, showed a smaller standard deviation of estimated GABA concentration from synthetic spectra with varying linewidths and lineshapes. The test-retest reproducibility was assessed by the mean within-subject coefficient of variation, which improved from 19.2% to 12.0% in the thalamus, from 27.9% to 14.9% in the motor cortex, and from 9.7% to 2.8% in the medial prefrontal cortex using LM basis sets at 7 T. We conclude that spectral linewidth has a large effect on GABA quantification from short-TE 1 H-MRS data and that using LM basis sets in LCModel can improve the reproducibility of GABA quantification.

Transmission-Mode Ultrasound for Monitoring the Instantaneous Elastic Modulus of the Achilles Tendon During Unilateral Submaximal Vertical Hopping.

Submaximal vertical hopping capitalizes on the strain energy storage-recovery mechanism associated with the stretch-shortening cycle and is emerging as an important component of progressive rehabilitation protocols in Achilles tendon injury and a determinant of readiness to return to sport. This study explored the reliability of transmission mode ultrasound in quantifying the instantaneous modulus of elasticity of human Achilles tendon during repetitive submaximal hopping. A custom-built ultrasound transmission device, consisting of a 1 MHz broadband emitter and four regularly spaced receivers, was used to measure the axial velocity of ultrasound in the Achilles tendon of six healthy young adults (mean ± SD; age 26 ± 5 years; height 1.78 ± 0.11 m; weight 79.8 ± 13.6 kg) during steady-state unilateral hopping (2.5 Hz) on a piezoelectric force plate. Vertical ground reaction force and lower limb joint kinematics were simultaneously recorded. The potential sensitivity of the technique was further explored in subset of healthy participants (n = 3) that hopped at a slower rate (1.8 Hz) and a patient who had undergone Achilles tendon rupture-repair (2.5 Hz). Reliability was estimated using the mean-within subject coefficient of variation calculated at each point during the ground-contact phase of hopping, while cross-correlations were used to explore the coordination between lower limb kinematics ground reaction forces and ultrasound velocity in the Achilles tendon. Axial velocity of ultrasound in the Achilles tendon was highly reproducible during hopping, with the mean within-subject coefficient of variation ranging between 0.1 and 2.0% across participants. Ultrasound velocity decreased immediately following touch down (−19 ± 13 ms–1), before increasing by 197 ± 81 ms–1, on average, to peak at 2230 ± 87 ms–1 at 67 ± 3% of ground contact phase in healthy participants. Cross-correlation analysis revealed that ultrasound velocity in the Achilles tendon during hopping was strongly associated with knee (mean r = 0.98, range 0.95–1.00) rather than ankle (mean r = 0.67, range 0.35–0.79) joint motion. Ultrasound velocity was sensitive to changes in hopping frequency in healthy adults and in the surgically repaired Achilles tendon was characterized by a similar peak velocity (2283 ± 13 ms–1) but the change in ultrasound velocity (447 ± 21 ms–1) was approximately two fold that of healthy participants (197 ± 81 ms–1). Although further research is required, the technique can be used to reliably monitor ultrasound velocity in the Achilles tendon during hopping, can detect changes in the instantaneous elastic modulus of tendon with variation in hopping frequency and tendon pathology and ultimately may provide further insights into the stretch-shortening cycle and aid clinical decision concerning tendon rehabilitation protocols and readiness to return to sport.

A novel method for infant multiple breath washout: First report in clinical practice.

Lung clearance index (LCI), measured using multiple breath inert gas washout (MBW) is a potentially useful test in infants with respiratory disease, particularly cystic fibrosis (CF). Clinical use is limited however by the need for specialist staff and equipment. We have previously described a novel method for infant MBW suitable for use outside of specialist laboratories. This study describes its performance in vivo in infants with CF and healthy controls, including a limited comparison with the respiratory mass spectrometer. Children aged less than 2 years with CF and controls underwent MBW testing on a single occasion. The practical applicability of the system was determined by the number of successful duplicate tests and within-subject repeatability. Twenty-five children (seven with CF, 18 healthy controls, all sedated with chloral hydrate) attempted MBW. Twenty patients (seven with CF) successfully underwent duplicate testing (80% success rate). Mean within-subject coefficient of variation for functional residual capacity (FRC) was 7.2% and for LCI 5.9%. Comparison of LCI with the mass spectrometer was limited but gave very similar values for LCI and FRC in those patients who underwent technically adequate tests with both methods. We have described a new MBW method that is feasible and reproducible in sedated infants. Results fall within the expected range, and well within accuracy limits set by international guidelines. This could provide a more accessible alternative to previously described systems for infant MBW, and overcomes many of the technical challenges inherent in conventional MBW.

Achilles tendon loading patterns during barefoot walking and slow running on a treadmill: An ultrasonic propagation study.

Measurement of tendon loading patterns during gait is important for understanding the pathogenesis of tendon "overuse" injury. Given that the speed of propagation of ultrasound in tendon is proportional to the applied load, this study used a noninvasive ultrasonic transmission technique to measure axial ultrasonic velocity in the right Achilles tendon of 27 healthy adults (11 females and 16 males; age, 26 ± 9 years; height, 1.73 ± 0.07 m; weight, 70.6 ± 21.2 kg), walking at self-selected speed (1.1 ± 0.1 m/s), and running at fixed slow speed (2 m/s) on a treadmill. Synchronous measures of ankle kinematics, spatiotemporal gait parameters, and vertical ground reaction forces were simultaneously measured. Slow running was associated with significantly higher cadence, shorter step length, but greater range of ankle movement, higher magnitude and rate of vertical ground reaction force, and higher ultrasonic velocity in the tendon than walking (P < 0.05). Ultrasonic velocity in the Achilles tendon was highly reproducible during walking and slow running (mean within-subject coefficient of variation < 2%). Ultrasonic maxima (P1, P2) and minima (M1, M2) were significantly higher and occurred earlier in the gait cycle (P1, M1, and M2) during running than walking (P < 0.05). Slow running was associated with higher and earlier peaks in loading of the Achilles tendon than walking.

Reproducibility of Magnetic Resonance Perfusion Imaging

Dynamic MR biomarkers (T2*-weighted or susceptibility-based and T1-weighted or relaxivity-enhanced) have been applied to assess tumor perfusion and its response to therapies. A significant challenge in the development of reliable biomarkers is a rigorous assessment and optimization of reproducibility. The purpose of this study was to determine the measurement reproducibility of T1-weighted dynamic contrast-enhanced (DCE)-MRI and T2*-weighted dynamic susceptibility contrast (DSC)-MRI with two contrast agents (CA) of different molecular weight (MW): gadopentetate (Gd-DTPA, 0.5 kDa) and Gadomelitol (P792, 6.5 kDa). Each contrast agent was tested with eight mice that had subcutaneous MDA-MB-231 breast xenograft tumors. Each mouse was imaged with a combined DSC-DCE protocol three times within one week to achieve measures of reproducibility. DSC-MRI results were evaluated with a contrast to noise ratio (CNR) efficiency threshold. There was a clear signal drop (>95% probability threshold) in the DSC of normal tissue, while signal changes were minimal or non-existent (<95% probability threshold) in tumors. Mean within-subject coefficient of variation (wCV) of relative blood volume (rBV) in normal tissue was 11.78% for Gd-DTPA and 6.64% for P792. The intra-class correlation coefficient (ICC) of rBV in normal tissue was 0.940 for Gd-DTPA and 0.978 for P792. The inter-subject correlation coefficient was 0.092. Calculated Ktrans from DCE-MRI showed comparable reproducibility (mean wCV, 5.13% for Gd-DTPA, 8.06% for P792). ICC of Ktrans showed high intra-subject reproducibility (ICC = 0.999/0.995) and inter-subject heterogeneity (ICC = 0.774). Histograms of Ktrans distributions for three measurements had high degrees of overlap (sum of difference of the normalized histograms <0.01). These results represent homogeneous intra-subject measurement and heterogeneous inter-subject character of biological population, suggesting that perfusion MRI could be an imaging biomarker to monitor or predict response of disease.

Variability and typical error in the kinematics and kinetics of the maximal instep kick in soccer

The purpose of this paper was to establish the variability and typical error of kinematic and kinetic variables representing the maximal instep kick in soccer for both the kicking and support legs. Ten skilled (good amateur or semi-professional) soccer players performed 20 maximal instep kicks of a stationary ball into a goal mouth. Motion of the kicking and support legs was recorded by an optoelectronic motion analysis system, and a six degrees of freedom model was used to compute kinematic and kinetic variables. Participants repeated the kicks on a second day at least 1 week later. The mean within-subject coefficient of variation across the kinematic and kinetic variables, trials, and days was 16% and did not change substantially as trial number increased or between day of test. Increasing trial number reduced the typical error (as determined by the standard error of the mean) such that for 20 trials 75% of the variables were below an arbitrary 5% threshold. It was concluded that for kicking investigations, 10–15 trials could be used and typical errors of 5% should be expected.

Variability of Semen Parameters with Time in Placebo Treated Men

We describe the variability of semen parameters with time in normal men receiving placebo. We also report the impact of season and geographic region, among other variables, on these parameters. Data from the placebo arms of 5 randomized, controlled trials were pooled. All trials set minimum standards for semen parameters as an eligibility criterion for entry. Semen parameters examined include volume, density, motility, total count, total motile count and morphology. Mixed model repeated measure analysis was used for statistical analysis. Coefficients of variation for each semen parameter and the percent change from baseline were calculated. The mean within-subject coefficient of variation for each semen parameter ranged from a low of 10% to a high of almost 50%. The contribution of season and region to variability was negligible. The reduction in variability with an increasing number of samples per time point had decreasing returns beyond 2 samples. There was considerable variation in semen parameters with time in subjects who received placebo. Variation could not be attributed to season or region. We observed a general negative trend in semen parameters in this population selected for normal baseline semen parameters, which was likely due to the placebo response or to regression toward the mean.

Reproducibility of Maximal Exercise Ergometer Testing in Patients With Cystic Fibrosis

Exercise testing in patients with cystic fibrosis (CF) has become an important tool in assessing disease severity and predicting overall outcome. The reproducibility of maximal exercise testing was examined in adult subjects with stable CF. Nine subjects with CF underwent a total of three maximal exercise tests carried out under identical circumstances over a 28-day period. Oxygen uptake (VO2), minute ventilation (VE), respiratory frequency (f), heart rate (HR), and arterial oxygen saturation (SaO2) were measured at rest, at end exercise, and at 40% and 70% of maximum workload. There were no significant differences in these measurements among the three tests. Reproducibility of exercise performance was assessed using the coefficient of variation. The mean within-subject coefficient of variation for test variables at end exercise are as follows: VO2, 6.9%; VE, 6.2%; f, 5.8%; IIR, 3.0%; and SaO2, 1.1%. The mean within-subject coefficient of variation for test variables at 40% and 70% of maximal work rates are as follows: VO2, 5.2% and 4.6%; SaO2, 0.3% and 0.9%; HR, 4.0% and 3%; VE, 5.7% and 6.5%; and f, 5.8% and 7.2%, respectively. Variables measured during clinical cycle ergometer exercise testing in adult patients with stable CF are reproducible. No learning effect was found on repeated testing.

Is the short insulin tolerance test safe and reproducible?

The short insulin tolerance test (SITT) is described as a simple method to measure insulin sensitivity. To investigate the safety and reproducibility of the SITT, 16 healthy volunteers underwent two SITTs within 1 week. Intravenous insulin (0.05 U kg(-1) body weight) was injected into an antecubital vein. Blood samples were collected from the contralateral antecubital vein. The insulin-induced glucose disposal rate (Kitt) was calculated from the slope of the regression line of the logarithm of blood glucose against time during the first 3-15 min. Plasma glucose concentrations fell below 2.8 mmol l(-1) in 4 of the 32 tests and below 2.2 mmol I(-1) in 1 of these 4. Five subjects had mild hypoglycaemic symptoms, three of whom had plasma glucose concentrations below 2.8 mmol l(-1) in at least one SITT. The mean Kitt was 4.2% min(-1) (range 0.8-8.4) for the first test and 3.4% min(-1) (range 0.1-6.8) for the second test. The mean within-subject coefficient of variation was 30.7%. We conclude that SITT should be applied with caution especially on insulin sensitive subjects and has poor reproducibility using 0.05 U kg(-1) body weight of insulin injection, venous sampling, uncontrolled physical activity and uncontrolled dietary composition. Whether 0.1 U kg(-1) body weight of insulin injection and arterialized venous blood sampling as in the original description of this test can improve the reproducibility of the SITT needs further investigation.

Reproducibility of antipyrine half-lives in elderly subjects.

Antipyrine half-life determined on three to five separate occasions over a period ranging from 3 weeks to 1 year was highly reproducible in each of 20 elderly subjects (12 women and 8 men; mean age, 83 years). The mean within-subject coefficient of variation for antipyrine half-life was 9.6%, whereas the between-subject coefficient of variation was 33.3%. These findings indicate high reproducibility of individual rates of drug metabolism in medically stable elderly subjects.