The application of more complex radiotherapy techniques using multileaf collimation (MLC), such as 3D conformal radiation therapy and intensity-modulated radiation therapy (IMRT), has increased the significance of verifying leaf position and motion. Due to thier reliability and empirical robustness, quality assurance (QA) of MLC. However easy use and the ability to provide digital data of electronic portal imaging devices (EPIDs) have attracted attention to portal films as an alternatives to films for routine qualify assurance, despite concerns about their clinical feasibility, efficacy, and the cost to benefit ratio. In this study, we developed method for daily QA of MLC using electronic portal images (EPIs). EPID availability for routine QA was verified by comparing of the portal films, which were simultaneously obtained when radiation was delivered and known prescription input to MLC controller. Specially designed two-test patterns of dynamic MLC were applied for image acquisition. Quantitative off-line analysis using an edge detection algorithm enhanced the verification procedure as well as on-line qualitative visual assessment. In conclusion, the availability of EPI was enough for daily QA of MLC leaf position with the accuracy of portal films.
A rapid, selective and sensitive reversed-phase HPLC method for the determination of glipizide in human serum was validated and applied to the pharmacokinetic study of glipizide. Glipizide and internal standard, tolbutamide, were extracted from human serum by liquid-liquid extraction with benzene and analyzed on a Nova Pak $C_{18}\;60{\AA}$ column with the mobile phase of acetonitrile-potassium dihydrogen phosphate (10 mM, pH 3.5) (4:6, v/v). Detection wavelength of 275 nm and flow rate of 0.7 ml/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed glipizide concentration (500 ng/ ml) with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 10-1000 ng/ml with correlation coefficient greater than 0.999. The lower limit of quantitation using 0.5 ml of serum was 10.0 ng/ml, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 82.6 to 105.0% for glipizide with overall precision (% C.V.) being 1.13-13.20%. The percent recovery for human serum was in the range of 85.2 93.5%. Stability studies showed that glipizide was stable during storage, or during the assay procedure in human serum. The peak area and retention time of glipizide were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of glipizide in human serum samples for the pharmacokinetic studies at three different laboratories, demonstrating the suitability of the method.
A rapid, selective and sensitive reversed-phase HPLC method for the determination of a major metabolite of terfenadine, fexofenadine, in human serum was developed, validated, and applied to the pharmacokinetic study of terfenadine. Fexofenadine and internal standard, haloperidol were extracted from human serum by liquid-liquid extraction with acetonitrile and analyzed on a $Symmetry^{TM}$ C8 column with the mobile phase of 1% triethylamine phosphate (pH 3.7)-acetonitrile (67:33, v/v, adjusted to pH 5.6 with triethylamine). Detection wavelength of 230 nm for excitation, 280 nm for emission and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed fexofenadine concentration (50 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 10-500 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 10 ng/mL, which was sensitive enough for the pharmacokinetic studies of terfenadine. The overall accuracy of the quality control samples ranged from 95.70 to 114.58% for fexofenadine with overall precision (% C.V.) being 3.53-14.39%. The relative mean recovery of fexofenadine for human serum was 90.17%. Stability studies (freeze-thaw, short-term, extracted serum sample and stock solution) showed that fexofenadine was stable during storage, or during the assay procedure in human serum. However, the storage at $-70^{\circ}C$ for 4 weeks showed that fexofenadine was not stable. The peak area and retention time of fexofenadine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of fexofenadine in human serum samples for the pharmacokinetic studies of orally administered Tafedine tablet (60 mg as terfenadine) at three different laboratories, demonstrating the suitability of the method.
A rapid, selective and sensitive reversed-phase HPLC method for the determination of etodolac in human serum was developed, validated, and applied to the pharmacokinetic study of etodolac. Etodolac and internal standard, ibuprofen were extracted from human serum by liquid-liquid extraction with hexane/isopropanol (95:5, v/v) and analyzed on a Luna C18(2) column with the mobile phase of 1% aqueous acetic acid-acetonitrile (4:6, v/v). Detection wavelength of 227 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed etodolac concentration $(1\;{\mu}g/mL)$ with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of $0.05-40\;{\mu}g/mL$ with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 0.05 ${\mu}g/mL$, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.00 to 110.00% for etodolac with overall precision (% C.V.) being 1.08-10.11%. The percent recovery for human serum was in the range of 76.73-115.30%. Stability studies showed that etodolac was stable during storage, or during the assay procedure in human serum. The peak area and retention time of etodolac were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of etodolac in human serum samples for the pharmacokinetic studies of orally administered Lodin XL tablet (400 mg as etodolac) at three different laboratories, demonstrating the suitability of the method.
Journal of the Institute of Electronics Engineers of Korea SD
/
v.47
no.4
/
pp.75-87
/
2010
For two input-protection schemes suitable for RF ICs utilizing the thyristor and diode protection devices, which can be fabricated in standard CMOS processes, we attempt an in-depth comparison on HBM ESD robustness in terms of lattice heating inside protection devices and peak voltages developed across gate oxides in input buffers, based on DC, mixed-mode transient, and AC analyses utilizing a 2-dimensional device simulator. For this purpose, we construct an equivalent circuit for an input HBM test environment of a CMOS chip equipped with the input ESD protection circuits, which allows mixed-mode transient simulations for various HBM test modes. By executing mixed-mode simulations including up to six active protection devices in a circuit, we attempt a detailed analysis on the problems, which can occur in real tests. In the procedure, we suggest to a recipe to ease the bipolar trigger in the protection devices and figure out that oxide failure in internal circuits is determined by the junction breakdown voltage of the NMOS structure residing in the protection devices. We explain the characteristic differences of two protection schemes as an input ESD protection circuit for RF ICs, and suggest valuable guidelines relating design of the protection devices and circuits.
A quicker method was developed for foliar analysis in diagnosis of nitrogen in apple trees based on multivariate calibration procedure using partial least squares regression (PLSR) and principal component regression (PCR) to establish the relationship between reflectance spectra in the near infrared region and nitrogen content of fresh- and dry-leaf. Several spectral pre-processing methods such as smoothing, mean normalization, multiplicative scatter correction (MSC) and derivatives were used to improve the robustness and performance of the calibration models. Norris first derivative with a seven point segment and a gap of six points on MSC gave the best result of partial least squares-1 PLS-1) model for dry-leaf samples with root mean square error of prediction (RMSEP) equal to $0.699g\;kg^{-1}$, and that the Savitzky-Golay first derivate with a seven point convolution and a quadratic polynomial on MSC gave the best results of PLS-1 model for fresh-samples with RMSEP of $1.202g\;kg^{-1}$. The best PCR model was obtained with Savitzky-Golay first derivative using a seven point convolution and a quadratic polynomial on mean normalization for dry leaf samples with RMSEP of $0.553g\;kg^{-1}$, and obtained with the Savitzky-Golay first derivate using a seven point convolution and a quadratic polynomial for fresh samples with RMSEP of $1.047g\;kg^{-1}$. The results indicate that nitrogen can be determined by the near infrared reflectance (NIR) technology for fresh- and dry-leaf of apple.
A rapid, selective and sensitive reversed-phase HPLC method for the determination of dipyridamole in human serum was developed, validated, and applied to the pharmacokinetic study of dipyridamole. Dipyridamole and internal standard, loxapine, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Nova Pak $C_{I8}$ column with the mobile phase of 40 mM ammonium acetate:methanol:acetonitrile (35:35:30)(v/v/v, pH 7.8). Detection wavelength of 280 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed dipyridamole concentration (50 ng/mL) with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 2-2000 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 2 ng/mL, which was sensitive enough for pharmacokinetic studies of dipyridamole. The overall accuracy of the quality control samples ranged from 103.94 to 105.86% for dipyridamole with overall precision (% C.V.) being 4.60-11.49%. The relative mean recovery of dipyridamole for human serum was 97.64%. Stability studies showed that dipyridamole was stable during storage, or during the assay procedure in human serum. The peak area and retention time of dipyridamole were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of dipyridamole in human serum samples for the pharmacokinetic studies of orally administered Dimor tablet (75 mg as dipyridamole) at three different laboratories, demonstrating the suitability of the method.
A rapid, selective and sensitive reversed-phase HPLC method for the determination of promethazine in human serum was developed, validated, and applied to the pharmacokinetic study of promethazine. Promethazine and internal standard, chlorpromazine, were extracted from human serum by liquid-liquid extraction with n-hexane containing 0.8% isopropanol and analyzed on a Capcell Pak CN column with the mobile phase of acetonitrile-0.2 M potassium dihydrogen phosphate (42:58, v/v, adjusted to pH 6.0 with 1 M NaOH). Detection wavelength of 251 nm and flow rate of 0.9 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed promethazine concentration (10 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 1-40 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was 1 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 96.15 to 105.40% for promethazine with overall precision (% C.V.) being 6.70-11.22%. The relative mean recovery of promethazine for human serum was 63.54%. Stability (freeze-thaw and short-term) studies showed that promethazine was stable during storage, or during the assay procedure in human serum. However, the storage at $-80^{\circ}C$ for 4 weeks showed that promethazine was not stable. Extracted serum sample and stock solution were not allowed to stand at ambient temperature for 12 hr prior to injection. The peak area and retention time of promethazine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of promethazine in human serum samples for the pharmacokinetic studies of orally administered Himazin tablet (25 mg as promethazine hydrochloride) at three different laboratories, demonstrating the suitability of the method.
Jung Hyun, Kim;Jong-Min, Lee;Uicheul, Yoon;Hyun-Pil, Kim;Bang Bon, Koo;In Young, Kim;Dong Soo, Lee;Jun Soo, Kwon;Sun I., Kim
Journal of Biomedical Engineering Research
/
v.25
no.5
/
pp.323-328
/
2004
The development of group-specific tissue probability maps (TPM) provides a priori knowledge for better result of cerebral tissue classification with regard to the inter-ethnic differences of inter-subject variability. We present sequential procedures of group-specific TPM and evaluate the age effects in the structural differences of TPM. We investigated 100 healthy volunteers with high resolution MRI scalming. The subjects were classified into young (60, 25.92+4.58) and old groups (40, 58.83${\pm}$8.10) according to the age. To avoid any bias from random selected single subject and improve registration robustness, average atlas as target for TPM was constructed from skull-stripped whole data using linear and nonlinear registration of AIR. Each subject was segmented into binary images of gray matter, white matter, and cerebrospinal fluid using fuzzy clustering and normalized into the space of average atlas. The probability images were the means of these binary images, and contained values in the range of zero to one. A TPM of a given tissue is a spatial probability distribution representing a certain subject population. In the spatial distribution of tissue probability according to the threshold of probability, the old group exhibited enlarged ventricles and overall GM atrophy as age-specific changes, compared to the young group. Our results are generally consistent with the few published studies on age differences in the brain morphology. The more similar the morphology of the subject is to the average of the population represented by the TPM, the better the entire classification procedure should work. Therefore, we suggest that group-specific TPM should be used as a priori information for the cerebral tissue classification.
This study investigated any possible financial attributes of the CDS spreads of a firm belonging to financial industries headquartered in the Republic of Korea. There were few studies on this issue, especially for the firms located in emerging capital markets. Coupled with the models such as a multiple regression and a principal component analysis(PCA), this research has identified that only two explanatory variables such as SLOPE and INTER3 (i.e. interaction effect between the BETA and the SLOPE) consistently showed their statistically significant influence on the CDS spreads through the 'selected' model without and with applying a stepwise regression procedure for the robustness. Given the rapid developments of sophisticated financial derivatives, this study may suggest a valuable insight to foreign and domestic investors to identify the possible determinants of CDS spreads at the firm- and/or the industry-level.
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