Percent Coefficient Of Variation Research Articles

Pediatric Brain Tumor Consortium Multisite Assessment of Apparent Diffusion Coefficient z-Axis Variation Assessed with an Ice–Water Phantom

Magnetic resonance diffusion imaging can characterize physiologic characteristics of pediatric brain tumors used to assess therapy response. The purpose of this study was to assess the variability of the apparent diffusion coefficient (ADC) along z-axis of scanners in the multicenter Pediatric Brain Tumor Consortium (PBTC). Ice-water diffusion phantoms for each PBTC site were distributed with a specific diffusion imaging protocol. The phantom was scanned four successive times to 1) confirm water in the tube reached thermal equilibrium and 2) allow for assessment of intra-examination ADC repeatability. ADC profiles across slice positions for each vendor and institution combination were characterized using linear regression modeling with a quadratic fit. Eleven sites collected data with a high degree of compliance to the diffusion protocol for each scanner. The mean ADC value at slice position zero for vendor A was 1.123×10(-3)mm(2)/s, vendor B was 1.0964×10(-3)mm(2)/s, and vendor C was 1.110×10(-3)mm(2)/s. The percentage coefficient of variation across all sites was 0.309% (standard deviation=0.322). The ADC values conformed well to a second-order polynomial along the z-axis, (ie, following a linear model pattern with quadratic fit) for vendor-institution combinations and across vendor-institution combinations as shown in the longitudinal model. Assessment of the variability of diffusion metrics is essential for establishing the validity of using these quantitative metrics in multicenter trials. The low variability in ADC values across vendors and institutions and validates the use of ADC as a quantitative tumor marker in pediatric multicenter trials.

Analysis of imprecision in incurred sample reanalysis for small molecules.

Over the years, incurred sample (IS) reanalysis (ISR) has become a tool to confirm the reliability of bioanalytical measurements. The recommendation for ISR acceptance criterion for small molecules is at least 67% of ISR samples that have reanalyzed concentrations within 20% of their original concentrations when normalized to their means. To understand the relevance of the ISR acceptance criterion and sample size requirements, simulated ISR studies evaluated the probability of ISR studies passing the acceptance criterion (ISR pass rate) as a function of IS imprecision and sample size. When IS imprecision (percent coefficient of variation: %CV) is low (≤ 10 or 1-10% CV), high ISR pass rate (≥ 99%) is attained with <50 samples. At intermediate IS imprecision (e.g., 12% CV or 7-12% CV range), 80-160 samples are required for a high ISR pass rate. When IS imprecision is at the higher end of the acceptance limit, ISR pass rate decreases significantly, and increasing sample size fails to achieve high ISR pass rate. The effect of systematic bias (e.g., instability, interconversion) on ISR pass rate is strongly dependent on sample size at intermediate IS imprecision. The results provide an understanding of the effect of IS imprecision on ISR pass rates and a framework for selection of ISR sample sizes.

Spatial-Temporal Variation and Prediction of Rainfall in Northeastern Nigeria

In Northeastern Nigeria seasonal rainfall is critical for the availability of water for domestic use through surface and sub-surface recharge and agricultural production, which is mostly rain fed. Variability in rainfall over the last 60 years is the main cause for crop failure and water scarcity in the region, particularly, due to late onset of rainfall, short dry spells and multi-annual droughts. In this study, we analyze 27 years (1980–2006) of gridded daily rainfall data obtained from a merged dataset by the National Centre for Environmental Prediction and Climate Research Unit reanalysis data (NCEP-CRU) for spatial-temporal variability of monthly amounts and frequency in rainfall and rainfall trends. Temporal variability was assessed using the percentage coefficient of variation and temporal trends in rainfall were assessed using maps of linear regression slopes for the months of May through October. These six months cover the period of the onset and cessation of the wet season throughout the region. Monthly rainfall amount and frequency were then predicted over a 24-month period using the Auto Regressive Integrated Moving Average (ARIMA) Model. The predictions were evaluated using NCEP-CRU data for the same period. Kolmogorov Smirnov test results suggest that despite there are some months during the wet season (May–October) when there is no significant agreement (p &lt; 0.05) between the monthly distribution of the values of the model and the corresponding 24-month NCEP-CRU data, the model did better than simply replicating the long term mean of the data used for the prediction. Overall, the model does well in areas and months with lower temporal rainfall variability. Maps of the coefficient of variation and regression slopes are presented to indicate areas of high rainfall variability and water deficit over the period under study. The implications of these results for future policies on Agriculture and Water Management in the region are highlighted.

Optimization of barrel temperature and kidney bean flour percentage based on various physical properties of extruded snacks.

The aim of the experiment was to optimize barrel temperature (122 to 178 ± 0.5°C) and red kidney bean flour percentage (KBF) (12 to 68 ± 0.5%) based on physical properties of extrudates like flash off percentage, water absorption index (WAI), water solubility index (WSI), bulk density (BD), radial expansion ratio (RER) and overall acceptability (OAA) using single screw extruder. The study was carried out by central composite rotatable design (CCRD) using Response surface methodology (RSM) and moisture content of feed was kept as constant 16.0 ± 0.5% throughout experiments. Mathematical models for various responses were found to fit significantly (P < 0.05) for prediction. Optimization of experimental conditions was carried out using numerical optimization technique and the optimum barrel temperature and kidney bean flour percentage were 120°C (T1) & 142.62°C (T2 = T3) and 20% respectively with desirability value of 0.909. Experiments were carried out using predicted values and verified using t-test and coefficient of variation percentage. Extruded snack prepared with rice flour (80%) and kidney bean flour (20%) at optimized conditions was accepted by the taste panellists and above 20%KB incorporation was found to decrease overall acceptability score.

Obesity Increases Precision Errors in Total Body Dual-Energy X-Ray Absorptiometry Measurements

Total body (TB) dual-energy X-ray absorptiometry (DXA) is increasingly being used to measure body composition in research and clinical settings. This study investigated the effect of body mass index (BMI) and body fat on precision errors for total and regional TB DXA measurements of bone mineral density, fat tissue, and lean tissue using the GE Lunar Prodigy (GE Healthcare, Bedford, UK). One hundred forty-four women with BMI's ranging from 18.5 to 45.9 kg/m2 were recruited. Participants had duplicate DXA scans of the TB with repositioning between examinations. Participants were divided into 3 groups based on their BMI, and the root mean square standard deviation and the percentage coefficient of variation were calculated for each group. The root mean square standard deviation (percentage coefficient of variation) for the normal (<25 kg/m2; n = 76), overweight (25–30 kg/m2; n = 36), and obese (>30 kg/m2; n = 32) BMI groups, respectively, were total BMD (g/cm2): 0.009 (0.77%), 0.009 (0.69%), 0.011 (0.91%); total fat (g): 545 (2.98%), 486 (1.72%), 677 (1.55%); total lean (g): 551 (1.42%), 540 (1.34%), and 781 (1.68%). These results suggest that serial measurements in obese subjects should be treated with caution because the least significant change may be larger than anticipated.

Effect of the Drip Flow Rate with Multiple Manifolds on the Homogeneity of the Delivered Volume

AbstractThe reliable volumetric distribution of fertigation is vital for sustainable precision agriculture because it not only evenly distributes water in the spatial region where it is needed but also ensures rhizosphere nutrient utilization efficiency, electrical conductivity, and pH, thus yielding better production and reduced environmental emissions. We evaluated the supply delivered by two and four manifolds from a self-compensating antidrain dripper-emitter with flow rates of 2, 3, 4, and 8 L/h. Spikes with regulators (T1) and without regulators (T0) were tested. Connecting multiple manifolds to a single dripper with T1 spikes is not recommended. Drippers with low flow rates of 2 and 3 L/h are not suitable for multiple distribution, but drippers with flow rates from 4–8 L/h having two or four manifolds with T1 spikes produce adequate fertigation distribution for precision agriculture (≤5%, coefficient of variation percentage). The combination of an 8 L/h dripper with four or two regulated manifo...

Reliability and variability of diffusion tensor imaging (DTI) tractography in pediatric epilepsy

BackgroundDiffusion tensor imaging (DTI) tractography is useful for isolating white matter (WM) trajectories and exploring microstructural integrity. Tractography can be performed on atypical brain anatomy when landmarks are malformed or displaced but has been criticized for its subjectivity even when investigators have advanced anatomical knowledge. Also, little is known about the variability and reliability of tractography as a tool for assessing white matter damage in clinical populations such as children with pediatric epilepsy. MethodsChildren diagnosed with epilepsy [N=43, mean age=11.7years, standard deviation=3.7years, 53% male] underwent a DTI sequence (6 directions, 2×2×3mmvoxels). Tractography for six white matter tracts (anterior forceps, fornices, bilateral arcuate fasciculi, and bilateral anterior cingula) was conducted twice by two experienced tractographers. Percent coefficient of variation (CV; for measuring variability) and intraclass correlation coefficients (ICCs; for measuring reliability) were calculated for tract volume and diffusion variables (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD] and radial diffusivity [RD]). ResultsDiffusion variables showed low variability (CV=2.7–8.8%) and very high reliability (ICC=.97–.99) except for limbic tracts [fornix (ICC=.75–.94); cingulum (ICC=.71–.98)]. Tract volume measurements showed high variability (CV=21.9–62.0%) and moderate reliability (ICC=.54–.99). Overall, tract volume measurements were much more variable and less reliable than diffusion characteristics. Limbic structures showed more variability compared with others. ConclusionsThis suggests that DTI tractography and resulting diffusivity variables can reliably inform on the integrity of WM structures in a clinical sample with pediatric epilepsy and highlights the importance of reporting reliability information in studies that aim to answer clinical questions about WM integrity.

Precision of the iDXA for Visceral Adipose Tissue Measurement in Severely Obese Patients

A new measurement tool, the automated software CoreScan, for the GE Lunar iDXA, has been validated for measuring visceral adipose tissue (VAT) against computed tomography in normal-weight populations. However, no study has evaluated the precision of CoreScan in measuring VAT among severely obese patients. The purpose of the study was to evaluate the precision of CoreScan for VAT measurements in severely obese adults (body mass index > 40 kg·m(-2)). A total of 55 obese participants with a mean age of 46 ± 11 yr, body mass index of 49 ± 6 kg·m(-2), and body mass of 137.3 ± 21.3 kg took part in this study. Two consecutive iDXA scans with repositioning of the total body were conducted for each participant. The coefficient of variation, the root-mean-square averages of SD of repeated measurements, the corresponding 95% least significant change, and intraclass correlations were calculated. Precision error was 8.77% (percent coefficient of variation), with a root-mean-square SD of 0.294 kg and an intraclass correlation of 0.96. Bland-Altman plots demonstrated a mean precision bias of -0.08 ± 0.41 kg, giving a coefficient of repeatability of 0.82 kg and a bias range of -0.890 to 0.725 kg. When interpreting VAT results with the iDXA in severely obese populations, clinicians should be aware of the precision error for this important clinical parameter.

Glucose variability indices in type 1 diabetes: parsimonious set of indices revealed by sparse principal component analysis.

Continuous glucose monitoring (CGM) time-series are often analyzed, retrospectively, to investigate glucose variability (GV), a risk factor for the development of complications in type 1 diabetes (T1D). In the literature, several tens of different indices for GV quantification have been proposed, but many of them carry very similar information. The aim of this article is to select a relatively small subset of GV indices from a wider pool of metrics, to obtain a parsimonious but still comprehensive description of GV in T1D datasets. A pool of 25 GV indices was evaluated on two CGM time-series datasets of 17 and 16 T1D subjects, respectively, collected during the European Union Seventh Framework Programme project "Diadvisor" (2008-2012) in two different clinical research centers using the Dexcom(®) (San Diego, CA) SEVEN(®) Plus. After the indices were centered and scaled, the Sparse Principal Component Analysis (SPCA) technique was used to determine a reduced set of metrics that allows preserving a high percentage of the variance of the whole original set. In order to assess whether or not the selected subset of GV indices is dataset-dependent, the analysis was applied to both datasets, as well as to the one obtained by merging them. SPCA revealed that a subset of up to 10 different GV indices can be sufficient to preserve more than the 60% of the variance originally explained by all the 25 variables. It is remarkable that four of these GV indices (i.e., Index of Glycemic Control, percentage of Glycemic Risk Assessment Diabetes Equation score due to euglycemia, percentage Coefficient of Variation, and Low Blood Glucose Index) were selected for all the considered T1D datasets. The SPCA methodology appears a suitable candidate to identify, among the large number of literature GV indices, subsets that allow obtaining a parsimonious, but still comprehensive, description of GV.

Enantioselective analysis of tolvaptan in rat and dog sera by high-performance liquid chromatography and application to pharmacokinetic study.

Tolvaptan is a competitive vasopressin V2-receptor antagonist that inhibits water reabsorption in the renal collecting ducts. A selective high-performance liquid chromatography method for determining tolvaptan enantiomers in rat and dog sera was developed and validated. Benzyl salicylate was used as an internal standard. Sample preparation involved liquid-liquid extraction with an n-hexane:diethyl ether (1:1, v/v) solution, followed by solid-phase extraction using a silica-gel cartridge. Chromatographic separation was performed on a cellulose-based chiral stationary phase in the reversed phase mode. The analytes were monitored with UV detection. The calibration curve showed linearity over the concentration range from 0.025 to 2.5 μg/mL for each analyte. Precision as the percentage coefficient of variation did not exceed 14.8%, and accuracy as relative error was within ±14.6% for the analytes. The validated method was successfully applied to evaluate the pharmacokinetics of oral tolvaptan enantiomers in rats and dogs, indicating gender and species differences in the systemic exposure to tolvaptan enantiomers.

Variability and heritability analysis in short duration and high yielding Brassica rapa L.

The experiment was carried out with 32 genotypes of Brassica rapa including two commercially cultivated varieties as checks to study their inter-genotypic variability, heritability, GCV, PCV, genetic advance, and CV percent considering 10 morphological characters at the experimental farm of SAU, Dhaka during November 2009 to February 2010. Significant variation was observed among the genotypes for all the characters studied except thousand seed weight. High GCV and PCV values were observed for number of secondary branches/plant. High heritability values along with low genetic advance in percentage of mean were obtained for 1000-seed weight, number of secondary branches/plant, seeds/siliquae, and siliquae length. Highly significant positive association of seed yield per plant was observed with number of primary branches/plant, number of secondary branches/plant and number of siliquae/plant. Considering variability among the genotypes, heritability, genetic advance, percent co-efficient of variance, and field performances, the genotypes G-15, G-19, G-1, G-3, G-4, G-10, G-18, G21, and G-24 were found suitable for future breeding programme. DOI: http://dx.doi.org/10.3329/bjar.v38i4.19020 Bangladesh J. Agril. Res. 38(4): 647-657, December 2013

Test-retest reliability of a continuous glucose monitoring system in individuals with type 2 diabetes.

This study determined the test-retest reliability of a continuous glucose monitoring system (CGMS) (iPro™2; Medtronic, Northridge, CA) under standardized conditions in individuals with type 2 diabetes (T2D). Fourteen individuals with T2D spent two nonconsecutive days in a calorimetry unit. On both days, meals, medication, and exercise were standardized. Glucose concentrations were measured continuously by CGMS, from which daily mean glucose concentration (GLU(mean)), time spent in hyperglycemia (t(>10.0 mmol/L)), and meal, exercise, and nocturnal mean glucose concentrations, as well as glycemic variability (SD(w), percentage coefficient of variation [%cv(w)], mean amplitude of glycemic excursions [MAGEc, MAGE(ave), and MAGE(abs.gos)], and continuous overlapping net glycemic action [CONGA(n)]) were estimated. Absolute and relative reliabilities were investigated using coefficient of variation (CV) and intraclass correlation, respectively. Relative reliability ranged from 0.77 to 0.95 (P<0.05) for GLU(mean) and meal, exercise, and nocturnal glycemia with CV ranging from 3.9% to 11.7%. Despite significant relative reliability (R=0.93; P<0.01), t(>10.0 mmol/L) showed larger CV (54.7%). Among the different glycemic variability measures, a significant between-day difference was observed in MAGEc, MAGE(ave), CONGA6, and CONGA12. The remaining measures (i.e., SD(w), %cv(w), MAGE(abs.gos), and CONGA1-4) indicated no between-day differences and significant relative reliability. In individuals with T2D, CGMS-estimated glycemic profiles were characterized by high relative and absolute reliability for both daily and shorter-term measurements as represented by GLUmean and meal, exercise, and nocturnal glycemia. Among the different methods to calculate glycemic variability, our results showed SD(w), %cv(w), MAGE(abs.gos), and CONGAn with n ≤ 4 were reliable measures. These results suggest the usefulness of CGMS in clinical trials utilizing repeated measured.

Application of a medium-energy collimator for I-131 imaging after ablation treatment of differentiated thyroid cancer

High-energy (HE) collimators are usually applied for I-131 imaging after ablation treatment of differentiated thyroid cancer (DTC). However, purchase of HE collimators has been avoided in many nuclear medicine departments because the HE collimators are more expensive than other collimators. In this study, we compared the I-131 imaging using HE- and medium-energy (ME) collimators, which is more versatile than HE collimators. To simulate DTC patients with extra-thyroid beds, a phantom of acrylic containers containing I-131 was used. To simulate patients with thyroid beds, four phantoms representing extra-thyroid beds were arranged around the phantom representing normal thyroid tissues. Patients administered 1.11 or 3.70GBq NaI-131 were also evaluated. Whole-body imaging and SPECT imaging of the phantoms and patients performed using HE-general-purpose (HEGP) and ME-low-penetration (MELP) collimators, and full-width at half maximum (FWHM) and percent coefficient of variation (%CV) were measured. In the extra-thyroid beds, FWHM and%CV with MELP were negligibly different from those with HEGP in whole-body imaging. Although FWHM with MELP was a little different from that with HEGP in SPECT imaging,%CV with MELP was significantly higher than that with HEGP. In the thyroid beds, only an extra-thyroid bed including higher radioactivity was identified in whole-body imaging with both collimators. Although SPECT images with MELP could not clarify extra-thyroid beds with low radioactivity, HEGP could identify them. In patients, although some whole-body images with MELP could not detect extra-thyroid beds, whole-body imaging with HEGP and SPECT imaging with both collimators could detect them. Although HEGP is the best collimator for I-131 imaging, MELP is applicable for not only whole-body imaging but also SPECT imaging.

Does consistent piperacillin dosing result in consistent therapeutic concentrations in critically ill patients? A longitudinal study over an entire antibiotic course

Piperacillin plasma concentrations are known to vary between critically ill patients. However, there are no comprehensive data on the variability of antibiotic concentrations within the same patient. The purpose of this study was to investigate the adequacy of dosing during an entire 7-day antibiotic course and to investigate the variability in antibiotic trough concentrations both between patients and within the same patient. Piperacillin trough concentrations were measured daily in critically ill patients with normal renal function. The drug assay was performed using UPLC–MS/MS. The pharmacokinetic/pharmacodynamic target was 100% fT>MIC of the Pseudomonas aeruginosa EUCAST breakpoint. Within- and between-patient variability were calculated as percent coefficient of variation (CV). Eleven patients treated for pneumonia were included in this nested prospective observational cohort study. The median (range) age was 67 (18–79) years, weight was 75 (57–90)kg and BMI was 23.5 (22.3–26.4). The median (range) creatinine clearance on Day 1 of antibiotic treatment was 102 (62–154)mL/min. Trough concentrations were variable, ranging from 4.9mg/L to 98.0mg/L. A median CV of 40% for within-patient variability and 57% for between-patient variability was found. Within-patient variability was inversely correlated with SOFA score (R=0.65, P=0.027) and APACHE II score on admission (R=0.73, P=0.009). In conclusion, piperacillin concentrations varied widely both between patients and within the same patient. Within-patient variability was inversely correlated with disease severity. Consistent dosing of piperacillin/tazobactam does not result in consistent piperacillin concentrations throughout the entire treatment period.

Strong correlation between glycaemic variability and total glucose exposure in type 2 diabetes is limited to subjects with satisfactory glycaemic control

AimsThis study investigated the relationship between markers of overall glucose exposure, postprandial glucose excursions and glycaemic variability in patients with type 2 diabetes mellitus (T2DM). MethodsA total of 63 patients with T2DM (mean age 56 years) were enrolled. All wore a continuous glucose monitoring system (CGMS) device for 72h to collect data on markers of overall glucose exposure, postprandial glucose excursions and glycaemic variability parameters. ResultsSpearman's correlation analysis revealed significant correlations between all markers of overall glucose exposure and various parameters related to glucose excursions. The percent coefficient of variation (CV) showed the strongest correlation with glycated albumin (r=0.470, P<0.01). In participants with HbA1c levels<7.5% (n=33), almost all glycaemic markers and glycaemic variability parameters were significantly correlated with each other. Also, all postprandial glucose excursion parameters showed significant correlation with other glycaemic markers, and all markers of overall glucose exposure were significantly related to mean glucose, postprandial glucose excursions and glycaemic variability parameters (except CV). In contrast, in participants with HbA1c levels≥7.5% (n=30), no parameters of postprandial glucose excursions and glycaemic variability were related to any markers of chronic glycaemia. ConclusionPostprandial glucose excursions may explain glycaemic variability and total glucose exposures in well-controlled T2DM patients.

Short-term Precision Error in Dual Energy X-Ray Absorptiometry, Bone Mineral Density and Trabecular Bone Score Measurements; and Effects of Obesity on Precision Error

Introduction: Bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA) is the primary screening tool for diagnosis of osteopenia and osteoporosis. BMD alone does not provide information regarding the structural characteristics of bone and this limitation has been a driver for the development of techniques, including trabecular bone score (TBS) software, to assess bone microarchitecture. Precision error in DXA is important for accurately monitoring changes in BMD and it has been demonstrated that BMD precision error increases with increasing body mass index (BMI). Information on in vivo precision error for TBS is very limited. This study evaluated short-term precision error (STPE) of lumbar spine BMD & TBS measurement, and investigated the effect of obesity on DXA precision error. Method: DXA lumbar spine scans (L1-L4) were performed using GE Lunar Prodigy. STPE was measured in ninety-one women at a single visit by duplicating scans with repositioning in-between. Precision error was calculated as the percentage coefficient of variation. Participants were sub-divided into four groups based on BMI to assess the effect of obesity on STPE. Results: STPE is poorer for TBS than for BMD. STPE is adversely affected for both BMD and TBS measurements by increasing BMI but this effect is mitigated for TBS in the highest BMI category where use of the thick scanning mode improves signal to noise ratio. Conclusion: Results from serial BMD and TBS measurements should take account of differences in precision error in the two techniques and in different BMI categories.

Normal corneal endothelial morphology of healthy Saudi children aged 7-12 years

PurposeThe aim of this study was to describe the corneal endothelial morphology of healthy Saudi children aged 7-12 years and investigate variations on the basis of age and sex.Participants and methodsIn this prospective study of 412 healthy children, one eye was examined of each child. The endothelial cell density (ECD), percentage coefficient of variation (CV), and cell hexagonality (Hex) were determined using a noncontact Nidek CEM 530 specular microscope. An unpaired t-test was used to compare ECD measurements between boys and girls. Descriptive statistics of endothelial characteristics (ECD, CV, Hex) of the right eyes of the children at each age were analyzed for the entire sample using Kruskal-Wallis and Spearman's correlation tests.ResultsThe Kruskal-Wallis test showed statistically significant differences in ECD on the basis of age (P = 0.01) and Spearman's correlation test detected a weak negative correlation between ECD and age (−0.20, P = 0.0001). Analysis of the CV did not indicate any statistically significant differences with age (P = 0.98), but a weak positive correlation was detected between CV and age (r = 0.02, P = 0.69). No significant differences in Hex were observed at each age (P = 0.10), but a weak negative correlation was detected between Hex and age (r = −0.14, P = 0.001).ConclusionIn children, ECD decreases with increasing age whereas CV and Hex do not change significantly with age.

Statistical analysis of nematode counts from interlaboratory proficiency tests

A series of proficiency tests on potato cyst nematode (PCN; ) and free-living stages of Meloidogyne and Pratylenchus () were investigated to determine the accuracy and precision of the nematode counts and to gain insights into possible trends and potential improvements. In each test, each participating laboratory received ten samples of soil collected from naturally infested fields and well mixed before distribution. The variance between the counts from the ten samples, estimated per test and laboratory, was constant for PCN cysts and free-living stages of Meloidogyne spp. and Pratylenchus spp. during the period monitored. However, during the initial years, the variance between the samples showed a downward trend for PCN living juveniles. The variance between the laboratories, estimated per test, was constant for PCN cysts over the period 1994-2010. For PCN living juveniles the variance between laboratory means declined from 1994-2000 and from 2000 it was more or less constant, which coincided with the introduction of a well-described new methodology. For Meloidogyne spp. and Pratylenchus spp., from 1998-2005 the variance between laboratory means was more or less constant or increased. From 2006, all participating laboratories incubated the organic matter and the variance between the laboratories was stable and below the levels observed during 2003-2005. After discarding data from initial years with unstable variances of the nematode counts, a meta-analysis was carried out on the remaining data using HGLMs to model the mean and variance of the counts simultaneously. The within-laboratory variance for the ten samples and the interaction variance of test and laboratory were estimated and combined to percentage coefficient of variation (%CV) per laboratory. For PCN cysts, %CV per laboratory ranged from 12.6 to 41.6 and for PCN juveniles in sandy soil from 24.4 to 67.4 and in loamy soil from 37.9 to 102.0. For Meloidogyne spp., %CV ranged from 53.2 to 84.4 and for Pratylenchus spp. from 24.3 to 90.6. The quality of a proficiency test is largely defined by random distribution of the nematodes over the samples allocated, statistical analysis of the data and communication of the results to participating laboratories. This study provides insights into the accuracy and precision at laboratories in recent years and the effect of concerted actions during the period in which the proficiency tests were conducted.

A quantitative LC–MS/MS method for determination of thiazolidinedione mitoNEET ligand NL-1 in mouse serum suitable for pharmacokinetic studies

Thiazolidinedione (TZD) compounds have shown promise as antidiabetic, antibiotics, antifungal and neuroprotective agents. The mitochondrial effect of a novel mitoNEET ligand, NL-1 {5-[(3,5-di-tert-butyl-4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione}, and other TZD compounds, is a newly proposed mechanism for the neuroprotective action of these TZD compounds. In this work, a sensitive LC-MS/MS assay has been developed and validated for quantification of NL-1 in mouse serum. Sample preparation involved an acetonitrile protein precipitation procedure with addition of an internal standard NL-2 {5-[(4-hydroxy-3,5-dimethyl-phenyl)methyl]thiazolidine-2,4-dione}. LC-MS/MS analysis utilized a Columbus C-18 HPLC column (2mm×50mm, 5μm). Chromatography employed a multiple step gradient program that featured a steep linear gradient (25-95% in 0.5min) of 15μM ammonium acetate (additive for eliminating carry-over) in 2% methanol mixing with increasing proportions of 100% methanol. The HPLC was interfaced to a QTrap 5500 mass spectrometer (AB Sciex) equipped with an electrospray ionization source used in a negative ionization mode. Multiple reaction monitoring (MRM) of m/z 334→263 for NL-1 and m/z 250→179 for NL-2 was done. The method had a linear range of at least 1-100ng/mL in serum. The intra-assay and inter-assay percent coefficient of variation (%CV) were less than 4% and accuracies (%RE) ranged from -2.7% to 2.0%. The analytical procedure gave 96-115% absolute extraction recovery of NL-1. The relative matrix effect was measured and found to be insignificant. The analyte in serum was confirmed to be stable during storage and treatment. The method is suitable for pharmacokinetic (PK) studies of the parent drug NL-1 based on the preliminary serum results from dosed NL-1 mouse studies.

Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Belatacept in Adult Kidney Transplant Recipients

Background and ObjectivesBelatacept is a first-in-class, selective co-stimulation blocker recently approved for the prophylaxis of organ rejection in adult kidney transplant recipients. The objective of this study was to report the pharmacokinetics, pharmacodynamics, and immunogenicity of belatacept.MethodsThe pharmacokinetics, pharmacodynamics (CD86 receptor occupancy), and immunogenicity of belatacept were studied in de novo adult kidney transplant recipients in phase II and III clinical studies.ResultsFollowing multiple doses of 5 or 10 mg/kg, the geometric mean (percentage coefficient of variation) maximum serum concentration and area under the serum concentration–time curve over one dosing interval of belatacept were 136 (20 %) and 238 (27 %) μg/mL, and 13,587 (27 %) and 21,241 (35 %) μg·h/mL, respectively. The median belatacept elimination half-life was 8–9 days. Belatacept exhibited concentration-dependent binding to CD86 receptors. The pre-dose CD86 receptor occupancy by belatacept decreased from 94 to 65 % between day 5 and 1 year post-transplant, with corresponding pre-dose trough serum concentrations of belatacept decreasing from ~35 to 4 μg/mL during this period. The cumulative incidence of developing anti-belatacept antibodies was 5.3 % up to 3 years post-transplant and had no impact on belatacept exposure.ConclusionsBelatacept in adult kidney transplant demonstrated linear pharmacokinetics with low variability, concentration-dependent pharmacodynamics, and a low incidence of anti-drug antibodies.