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Intersubject Variability (intersubject + variability)
Selected AbstractsNormal cerebral perfusion measurements using arterial spin labeling: Reproducibility, stability, and age and gender effectsMAGNETIC RESONANCE IN MEDICINE, Issue 4 2004Laura M. Parkes Abstract Before meaningful conclusions can be drawn from clinical measures of cerebral blood perfusion, the precision of the measurement must be determined and set in the context of inter- and intrasubject sources of variability. This work establishes the reproducibility of perfusion measurements using the noninvasive MRI technique of continuous arterial spin labeling (CASL). Perfusion was measured in 34 healthy normal subjects. Intersubject variability was assessed, and age and gender contributions were estimated. Intersubject variation was found to be large, with up to 100% perfusion difference for subjects of the same age and gender. Repeated measurements in one subject showed that perfusion remains remarkably stable in the short term when compared with intersubject variation and the large capacity for perfusion change in the brain. A significant decrease in the ratio of gray-matter to white-matter perfusion was found with increasing age (0.79% per year (P < 0.0005)). This appears to be due mainly to a reduction in gray-matter perfusion, which was found to decrease by 0.45% per year (P = 0.04). Regional analysis suggested that the gray-matter age-related changes were predominantly localized in the frontal cortex. Whole-brain perfusion was 13% higher (P = 0.02) in females compared to males. Magn Reson Med 51:736,743, 2004. © 2004 Wiley-Liss, Inc. [source] Measurement delay associated with the Guardian® RT continuous glucose monitoring systemDIABETIC MEDICINE, Issue 1 2010C. Wei Diabet. Med. Abstract Aims, Using compartment modelling, we assessed the time delay between blood glucose and sensor glucose measured by the Guardian® RT continuous glucose monitoring system in young subjects with Type 1 diabetes (T1D). Methods, Twelve children and adolescents with T1D treated by continuous subcutaneous insulin infusion (male/female 7/5; age 13.1 ± 4.2 years; body mass index 21.9 ± 4.3 kg/m2; mean ± sd) were studied over 19 h in a Clinical Research Facility. Guardian® RT was calibrated every 6 h and sensor glucose measured every 5 min. Reference blood glucose was measured every 15 min using a YSI 2300 STAT Plus Analyser. A population compartment model of sensor glucose,blood glucose kinetics was adopted to estimate the time delay, the calibration scale and the calibration shift. Results, The population median of the time delay was 15.8 (interquartile range 15.2, 16.5) min, which was corroborated by correlation analysis between blood glucose and 15-min delayed sensor glucose. The delay has a relatively low intersubject variability, with 95% of individuals predicted to have delays between 10.4 and 24.3 min. Population medians (interquartile range) for the scale and shift are 0.800 (0.777, 0.823) (unitless) and 1.66 (1.47, 1.84) mmol/l, respectively. Conclusions, In young subjects with T1D, the total time delay associated with the Guardian® RT system was approximately 15 min. This is twice that expected on physiological grounds, suggesting a 5- to 10-min delay because of data processing. Delays above 25 min are rarely to be observed. [source] Monoamine variability in the chronic model of atypical absence seizuresEPILEPSIA, Issue 4 2009Eduard Bercovici Summary Purpose:, We studied the variability of the slow-spike-and-wave discharges (SSWDs) derived from AY-9944 (AY) treatment during brain development of Long-Evans hooded (LEh) rats. Methods:, Although all LEh rats received the standard dose of AY (7.5 mg/kg), we have observed an intersubject variability of the total SSWD duration at postnatal day (P) 55. Therefore, we set out to investigate the underlying brain levels of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and its metabolite (5-HIAA), as determined by high-performance liquid chromatography (HPLC) analyses from four different brain regions: thalamus (Th), frontoparietal cortex (Cx), hippocampus (Hp), and brainstem (Bs). Results:, All brains were obtained after two baseline electrocorticographic (ECoG) recordings with characteristic chronic, recurrent, bilaterally synchronous 4,6 Hz SSWD, at P 55 (336.25 ± 97.23 s/h) and P60 (494.50 ± 150.36 s) (r = 0.951, r2 = 0.904, p < 0.005, Pearson product). The thalamic NE levels and the brainstem NE, DA, and 5HT levels were all significantly correlated with baseline SSWD duration at P55 and P60 (p < 0.01, Pearson product). Conclusion:, Our data indicate that brain monoamine levels may determine the intersubject variability of SSWD duration in AY rats with chronic atypical absence seizures. [source] Groupwise registration based on hierarchical image clustering and atlas synthesisHUMAN BRAIN MAPPING, Issue 8 2010Qian Wang Abstract Groupwise registration has recently been proposed for simultaneous and consistent registration of all images in a group. Since many deformation parameters need to be optimized for each image under registration, the number of images that can be effectively handled by conventional groupwise registration methods is limited. Moreover, the robustness of registration is at stake due to significant intersubject variability. To overcome these problems, we present a groupwise registration framework, which is based on a hierarchical image clustering and atlas synthesis strategy. The basic idea is to decompose a large-scale groupwise registration problem into a series of small-scale problems, each of which is relatively easy to solve using a general computer. In particular, we employ a method called affinity propagation, which is designed for fast and robust clustering, to hierarchically cluster images into a pyramid of classes. Intraclass registration is then performed to register all images within individual classes, resulting in a representative center image for each class. These center images of different classes are further registered, from the bottom to the top in the pyramid. Once the registration reaches the summit of the pyramid, a single center image, or an atlas, is synthesized. Utilizing this strategy, we can efficiently and effectively register a large image group, construct their atlas, and, at the same time, establish shape correspondences between each image and the atlas. We have evaluated our framework using real and simulated data, and the results indicate that our framework achieves better robustness and registration accuracy compared to conventional methods. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc. [source] Simplified intersubject averaging on the cortical surface using SUMAHUMAN BRAIN MAPPING, Issue 1 2006Brenna D. Argall Abstract Task and group comparisons in functional magnetic resonance imaging (fMRI) studies are often accomplished through the creation of intersubject average activation maps. Compared with traditional volume-based intersubject averages, averages made using computational models of the cortical surface have the potential to increase statistical power because they reduce intersubject variability in cortical folding patterns. We describe a two-step method for creating intersubject surface averages. In the first step cortical surface models are created for each subject and the locations of the anterior and posterior commissures (AC and PC) are aligned. In the second step each surface is standardized to contain the same number of nodes with identical indexing. An anatomical average from 28 subjects created using the AC,PC technique showed greater sulcal and gyral definition than the corresponding volume-based average. When applied to an fMRI dataset, the AC,PC method produced greater maximum, median, and mean t -statistics in the average activation map than did the volume average and gave a better approximation to the theoretical-ideal average calculated from individual subjects. The AC,PC method produced average activation maps equivalent to those produced with surface-averaging methods that use high-dimensional morphing. In comparison with morphing methods, the AC,PC technique does not require selection of a template brain and does not introduce deformations of sulcal and gyral patterns, allowing for group analysis within the original folded topology of each individual subject. The tools for performing AC,PC surface averaging are implemented and freely available in the SUMA software package. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [source] Appropriate dosing of antiarrhythmic drugs in Japan requires therapeutic drug monitoring,JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2005M. Takada PhD Summary Objective:, In general, drugs are used in accordance with an approved dosage regimen in expectation of an appropriate balance between efficacy and toxicity. However, dose control of drugs with a narrow therapeutic range and marked intersubject variability in pharmacokinetics should be established through individualization of dosing based on therapeutic drug monitoring (TDM). The purpose of this study was to examine differences between the approved dosage regimen and the doses of antiarrhythmic drugs and digoxin used in clinical practice and to examine the influence of TDM on dosing. Methods:, Prescription research of antiarrhythmic drugs was performed at five national hospitals in Japan. Prescriptions for antiarrhythmic drugs (cibenzoline, disopyramide, pirmenol, mexiletine, aprindine, flecainide, pilsicainide, amiodarone and digoxin) were counted for the study period. The mean dose and dose distribution of the drugs were determined in each hospital. Comparisons were made of mean dose obtained in the study with the dosage approved by the authority. In addition, the percentage of patients that received TDM was determined. Results:, A difference was seen between the approved dosage and the actual dose. For all drugs except flecainide, the mean dose was smaller than the approved dosage. For all drugs except digoxin, remarkable variations were seen in the dose distribution among the hospitals. Digoxin showed a similar dose distribution among the five hospitals. Overall, the percentage of patients that received TDM was low except for Hospital A. However, TDM of digoxin was relatively common at four of the hospitals. Conclusions:, It is concluded that, with the exception of digoxin, the appropriate dosing regimen for antiarrhythmic drugs is not yet established. The establishment of appropriate dosing regimens for antiarrhythmic drugs requires the more widespread adoption of TDM. [source] EFFECTS OF BITE SIZE ON THE SENSORY PROPERTIES OF VANILLA CUSTARD DESSERTSJOURNAL OF SENSORY STUDIES, Issue 3 2007JON F. PRINZ ABSTRACT A trained panel of 19 subjects were asked to rate a number of sensory attributes of commercially available vanilla custard desserts. Stimuli were placed in plastic cups and were sampled using 11-mm-diameter straws. In total, 304 samples were weighed before and after sampling and the volume ingested was calculated. The subjects were categorized into two groups on the basis of the mean volume ingested per sample (< and >10.6 mL). There were significant differences in the ratings between the two groups for temperature, creamy, astringent, melting and airy mouthfeels and rough and fatty after-feel. We suggest that in sensory testing, it is important to either control or measure bite size to reduce intersubject variability. Manufacturers and caterers may also be able to modify the perception of their products by providing cues to the appropriate bite size by controlling the size of the spoon or container provided. [source] Optimization of sigma amplitude threshold in sleep spindle detectionJOURNAL OF SLEEP RESEARCH, Issue 4 2000E. Huupponen Sleep spindles are transient EEG waveforms of non-rapid eye movement sleep. There is considerable intersubject variability in spindle amplitudes. The problem in automatic spindle detection has been that, despite this fact, a fixed amplitude threshold has been used. Selection of the spindle detection threshold value is critical with respect to the sensitivity of spindle detection. In this study a method was developed to estimate the optimal recording-specific threshold value for each all-night recording without any visual scorings. The performance of the proposed method was validated using four test recordings each having a very different number of visually scored spindles. The optimal threshold values for the test recordings could be estimated well. The presented method seems very promising in providing information about sleep spindle amplitudes of individual all-night recordings. [source] Individual Differences in Responses to Ethanol and d-Amphetamine: A Within-Subject StudyALCOHOLISM, Issue 4 2001Louis Holdstock Background: In some individuals, ethanol (EtOH) produces marked stimulant-like subjective effects resembling those of stimulant drugs, like d-amphetamine (AMP). In this study, we examined the neurochemical basis of these individual differences by examining the same subjects' responses to both EtOH and AMP. A positive correlation between subjects' responses to the two drugs may suggest that AMP and EtOH produce their stimulant-like subjective effects by a shared mechanism. Methods: Twenty-seven volunteers (17 male, 10 female), aged 21,35, received beverages or capsules containing EtOH 0.8 g/kg, AMP 10 or 20 mg, or placebo on four separate sessions in random order and under double-blind conditions. Various self-reported and objective drug effects were measured, including measures sensitive to subjective and cognitive stimulant-like effects. Results: EtOH and AMP produced their prototypical subjective and behavioral effects, including increased ratings of stimulant-like subjective effects, increased heart rate and blood pressure, and improved vigilance performance after AMP and increased ratings of sedative-like subjective effects, increased heart rate and blood pressure, and impaired vigilance performance after EtOH. Consistent with previous reports, there was substantial intersubject variability in subjective responses to EtOH: some subjects reported primarily stimulant-like effects, whereas others reported primarily sedative-like effects. To examine the relationship between these responses to EtOH and subjects' responses to AMP, correlations were examined between effects of EtOH and AMP. For all subjects together, there was a significant positive correlation between responses to EtOH and 20 mg AMP on the ARCI A scale (a measure of stimulant-like subjective effects;r= 0.41, p < 0.05). Among only those subjects who reported primarily stimulant-like effects from EtOH, the correlation between EtOH and AMP was 0.64 (p < 0.05). Conclusions: Subjects who experience pronounced stimulant-like effects from EtOH also report greater stimulant effects from AMP, suggesting that these effects may be mediated through similar mechanisms. These correlations between the drugs' effects were not observed on other measures, such as DSST or vigilance task performance or heart rate. This may indicate that these other effects are mediated by separate mechanisms. The study illustrates a novel approach to studying the neurochemical basis of drug effects. [source] Use of tissue water as a concentration reference for proton spectroscopic imagingMAGNETIC RESONANCE IN MEDICINE, Issue 6 2006Charles Gasparovic Abstract A strategy for using tissue water as a concentration standard in 1H magnetic resonance spectroscopic imaging studies on the brain is presented, and the potential errors that may arise when the method is used are examined. The sensitivity of the method to errors in estimates of the different water compartment relaxation times is shown to be small at short echo times (TEs). Using data from healthy human subjects, it is shown that different image segmentation approaches that are commonly used to account for partial volume effects (SPM2, FSL's FAST, and K-means) lead to different estimates of metabolite levels, particularly in gray matter (GM), owing primarily to variability in the estimates of the cerebrospinal fluid (CSF) fraction. While consistency does not necessarily validate a method, a multispectral segmentation approach using FAST yielded the lowest intersubject variability in the estimates of GM metabolites. The mean GM and white matter (WM) levels of N-acetyl groups (NAc, primarily N-acetylaspartate), choline (Ch), and creatine (Cr) obtained in these subjects using the described method with FAST multispectral segmentation are reported: GM [NAc] = 17.16 ± 1.19 mM; WM [NAc] = 14.26 ± 1.38 mM; GM [Ch] = 3.27 ± 0.47 mM; WM [Ch] = 2.65 ± 0.25 mM; GM [Cr] = 13.98 ± 1.20 mM; and WM [Cr] = 7.10 ± 0.67 mM. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] Automatic Extraction of ECG Strips from Continuous 12-lead Holter Recordings for QT Analysis at Prescheduled versus Optimized Time PointsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2009Fabio Badilini Ph.D. Background: Continuous 12-lead ECG monitoring (Holter) in early-phase pharmaceutical studies is today widely used as an ideal platform to extract discrete ECGs for analysis. The extraction process is typically performed manually by trained readers using commercial Holter processing systems. Methods: Antares, a novel method for automatic 12-lead extraction from continuous Holter recordings applying minimal noise criteria and heart-rate stability conditions is presented. A set of 12-lead Holter recordings from healthy subjects administered with sotalol is used to compare ECG extractions at fixed time points with ECG extractions generated by Antares optimizing noise and heart rate inside 5 minute windows centered around each expected time point of interest. Results: Global, low- and high-frequency noise content of extracted ECGs was significantly reduced via optimized approach by Antares. Heart rate was also slightly reduced (from 69 ± 13 to 64 ± 13 bpm, P < 0.05). Similarly, the corrected QT interval from optimized extractions was significantly reduced (QTcB from 414 ± 32 to 402 ± 30 ms, P < 0.05). Using only baseline data, and after adjusting for intersubject variability, the standard deviation (SD) of QT intervals was highly reduced with optimized extraction (SD of QTcF from 11 ± 8 to 7 ± 2 ms, P < 0.05). Conclusions: Extraction of discrete 12-lead ECG strips from continuous Holter generates less noisy and more stable ECGs leading to more robust QTc data, thereby potentially facilitating the assessment of ECG effects on clinical trials. [source] Population pharmacokinetic and pharmacodynamic modelling of the antimalarial chemotherapy chlorproguanil/dapsoneBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2006Julie A. Simpson Aims To determine the population pharmacokinetics of chlorproguanil, dapsone and the active metabolite of chlorproguanil, chlorcycloguanil; and to estimate the duration of parasitocidal activity for chlorpoguanil/dapsone against Plasmodium falciparum isolates of varying sensitivity. Methods Rich and sparse pharmacokinetic data were collected prospectively from: healthy volunteers (n = 48) and adults (n = 65) and children (n = 68) suffering from P. falciparum malaria. All subjects received 2.0 mg kg,1 of chlorproguanil and 2.5 mg kg,1 of dapsone. Results The population pharmacokinetic parameter estimates for chlorproguanil were ka = 00.09 h,1 (intersubject variability was 44%), CL/F = 51.53 l h,1 (57%), CLD/F = 54.67 l h,1, V1/F = 234.40 l (50%) and V2/F = 1612.75 l; for dapsone were ka = 00.93 h,1, CL/F = 1.99 l h,1 (72%) and V/F = 76.96 l (48%); and for chlorcycloguanil were CLm/Fm = 3.72 l h,1 kg,1 (67%) and Vm/Fm = 12.76 l kg,1 (64%). For dapsone, CL/F and V/F were both significantly positively correlated with body weight. For a 10-kg child, the mean duration of parasitocidal activity for chlorproguanil/dapsone against the three most susceptible P. falciparum strains was 4.5 days [5th and 95th percentiles 2.4, 7.3] for W282; 5.9 days (3.6, 9.7) for ItG2F6; and 6.1 days (3.7, 10.1) for K39. For an isolate with the ile-164-leu mutation, V1/S, activity ranged from 0.8 days (0.0, 3.3) for a 10-kg child to 1.8 days (0.0, 4.0) for a 60-kg adult. Conclusions Plasmodium falciparum malaria has no effect on the pharmacokinetic parameters for chlorproguanil, dapsone or chlorcycloguanil. Chlorproguanil/dapsone will probably prove to be ineffective against parasite strains with the mutation ile-164-leu, were these to become prevalent in Africa. [source] | |||||||||||||||||||