1.Standard Error of Empirical Bayes Estimate in NONMEM(R) VI.
Dongwoo KANG ; Kyun Seop BAE ; Brett E HOUK ; Radojka M SAVIC ; Mats O KARLSSON
The Korean Journal of Physiology and Pharmacology 2012;16(2):97-106
The pharmacokinetics/pharmacodynamics analysis software NONMEM(R) output provides model parameter estimates and associated standard errors. However, the standard error of empirical Bayes estimates of inter-subject variability is not available. A simple and direct method for estimating standard error of the empirical Bayes estimates of inter-subject variability using the NONMEM(R) VI internal matrix POSTV is developed and applied to several pharmacokinetic models using intensively or sparsely sampled data for demonstration and to evaluate performance. The computed standard error is in general similar to the results from other post-processing methods and the degree of difference, if any, depends on the employed estimation options.
Bays
2.A Case of Perineal Testis.
Young Lae CHO ; Dong Hwan LEE ; Hong Jin SUH ; Woong Ki CHOI ; Myung Sik SHIN ; Byeong San KWON
Korean Journal of Urology 1997;38(8):894-896
The ectopy of testis may be due to an abnormal connection of the distal end of the gubernaculum testis and fibrous obstruction of scrotal inlet that lead the gonad to an abnormal position. We observed a case of perineal testis that is known to be rare form of ectopic testis and report it with review of literatures.
Bays
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Gonads
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Testis*
3.R-based reproduction of the estimation process hidden behind NONMEM® Part 2: First-order conditional estimation.
Translational and Clinical Pharmacology 2016;24(4):161-168
The first-order conditional estimation (FOCE) method is more complex than the first-order (FO) approximation method because it estimates the empirical Bayes estimate (EBE) for each iteration. By contrast, it is a further approximation of the Laplacian (LAPL) method, which uses second-order expansion terms. FOCE without INTERACTION can only be used for an additive error model, while FOCE with INTERACTION (FOCEI) can be used for any error model. The formula for FOCE without INTERACTION can be derived directly from the extension of the FO method, while the FOCE with INTERACTION method is a slight simplification of the LAPL method. Detailed formulas and R scripts are presented here for the reproduction of objective function values by NONMEM.
Bays
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Methods
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Reproduction*
4.Clincal Experience of the Median Mandibular Facial Cleft.
Hee Dong SON ; Kyoung OH ; Keun Cheol LEE ; Jung Min PARK ; Jeong Tae KIM ; Seok Kwun KIM
Journal of the Korean Cleft Palate-Craniofacial Association 2001;2(2):139-142
A median mandibular facial cleft(Tessier 30) is a rare congenital anomaly. It was first described by Couronne' in 1819, and classified by Tessier as a type 30 craniofacial cleft in 1976. Recently, Oostrom et al have reported a new embryologic hypothesis and subdivision. They reported that the hypoplasia of the mandibular processes during the early embryonic period will lead to the severest cleft of mandible which extends into the neck, whereas during the late embryonic period, the less severe median cleft will develop. The authors have experienced one case of the median cleft of the lower lip and mandible with associated bifid tongue and ankyloglossia. And the double inlet single ventricle at heart lesion was also present. She was operated at 3 month of age. Our procedure consisted of a one-stage correction of the clefts of the lip, tongue, and mandible(repair a cleft of lower lip using w-plasty and a cleft of mandible by manual reduction and internal fixation with 6-hole plate and screws).
Bays
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Heart
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Lip
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Mandible
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Neck
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Tongue
5.Context-Dependent Classification of Multi-Echo MRI Using Bayes Compound Decision Model.
Journal of the Korean Society of Magnetic Resonance in Medicine 1999;3(2):179-187
PURPOSE: This paper introduces a computationally inexpensive context-dependent classification of multi-echo MRI with Bayes compound decision model. In order to produce accurate region segmentation especially in homogeneous area and along boundaries of the regions, we propose a classification method that uses contextual information of local neighborhood system in the image. MATERIAL AND METHOD: The performance of the context free classifier over a statistically heterogeneous image can be improved if the local stationary regions in the image are disassociated from each other through the mechanism of the interaction parameters defined at the local neighborhood level. In order to improve the classification accuracy, we use the contextual information which resolves ambiguities in the class assignment of a pattern based on the labels of the neighboring patterns in classifying the image. Since the data immediately surrounding a given pixel is intimately associated with this given pixel, then if the true nature of the surrounding pixel is known this can be used to extract the true nature of the given pixel. The proposed context-dependent compound decision model uses the compound Bayes decision rule with the contextual information. As for the contextual information in the model, the directional transition probabilities estimated from the local neighborhood system are used for the interaction parameters. RESULTS: The context-dependent classification paradigm with compound Bayesian model for multi-echo MR images is developed. Compared to context free classification which does not consider contextual information, context-dependent classifier show improved classification results especially in homogeneous and along boundaries of regions since contextual information is used during the classification. CONCLUSION: We introduce a new paradigm to classify multi-echo MRI using clustering analysis and Bayesian compound decision model to improve the classification results.
Bays*
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Classification*
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Magnetic Resonance Imaging*
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Residence Characteristics
6.An imputation-based method to reduce bias in model parameter estimates due to non-random censoring in oncology trials.
Translational and Clinical Pharmacology 2016;24(4):189-193
In oncology trials, patients are withdrawn from study at the time when progressive disease (PD) is diagnosed, which is defined as 20% increase of tumor size from the minimum. Such informative censoring can lead to biased parameter estimates when nonlinear mixed effects models are fitted using NONMEM. In this work, we investigated how empirical Bayes estimates (EBE) could be exploited to impute missing tumor size observations and partially correct biases in the parameter estimates. 50 simulated datasets, each consisting of 100 patients, were generated based on the published model. From the simulated dataset, censoring due to PD diagnosis has been implemented. Using the post-hoc EBEs acquired from fitting the censored datasets using NONMEM, imputed values were generated from the tumor size model. Model fitting was carried out using censored and imputed datasets. Parameter estimates using both datasets were compared with true values. Tumor growth rate and cell kill rate were approximately 28% and 16% underestimated when fitted using the censored dataset, respectively. With the imputed datasets, relative biases of tumor growth rate and cell kill rate decreased to about 6% and 0%, respectively. Our work demonstrates that using EBEs acquired from fitting the model to the censored dataset and imputing the unknown tumor size observations with individual predictions beyond the PD time point is a viable option to solve the bias associated with structural parameter estimates. This approach, however, would not be helpful in getting better estimates of variance parameters.
Bays
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Bias (Epidemiology)*
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Dataset
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Diagnosis
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Humans
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Methods*
7.Considerations of Blood Properties, Outlet Boundary Conditions and Energy Loss Approaches in Computational Fluid Dynamics Modeling.
Ji Young MOON ; Dae Chul SUH ; Yong Sang LEE ; Young Woo KIM ; Joon Sang LEE
Neurointervention 2014;9(1):1-8
Despite recent development of computational fluid dynamics (CFD) research, analysis of computational fluid dynamics of cerebral vessels has several limitations. Although blood is a non-Newtonian fluid, velocity and pressure fields were computed under the assumptions of incompressible, laminar, steady-state flows and Newtonian fluid dynamics. The pulsatile nature of blood flow is not properly applied in inlet and outlet boundaries. Therefore, we present these technical limitations and discuss the possible solution by comparing the theoretical and computational studies.
Bays
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Cerebral Arteries
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Computer Simulation
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Hydrodynamics*
8.Effects of Oxygen Flow and the Length of Corrugate Tube as a Reservoir on the Resuscitation Bag.
Seo Young CHOI ; Sung Su CHUNG ; Chang Young JEONG ; Chan Jin PARK
Korean Journal of Anesthesiology 1994;27(6):543-548
Resuscitation bag (RB) is widely used for artificial ventilation and adequate ventilation during resuscitation, or for patient transport, when high concentration of inspired oxygen (70-100%) must be supplied. The purpose of this study was to investigate the effect of oxygen flow and the length of corrugated tube as a reservoir on the oxygen concentration in the adult type and pediatric type resuseitation bag. Each 24 mm corrugated tube (0, 20,40, 60, 80, 100 cm) was attached to the inlet valve, oxygen flow of 1, 3, 5, 7, 9, 11, 13 or 15 L/min was delivered to oxygen inlet site of RB. and oxygen concentration was measured for 10 times. To eliminate the possibility that ventilatory pattern affect the oxygen concentration, RB was manually handled with normal ventilatory pattern ; in advlt type, tidal volume was 800 cc, respiratory rate was 10/min and 1:E ratio was 1:2, in pediatric type, tidal volume was 100 cc, respiratory rate was 20/min and 1:E ratio was 1:2. In adult RB, a 15 L oxygen flow without reservoir delivered less than 50% oxygen. To get more than 70% oxygen, one must administer more than a 15 L oxygen flow with reservoir of 60 cm corrugated tube, oxygen flow of 9 L/min with 80 cm corrugated tube or a 7 L flow of oxygen with 100 cm corrugated tube. And to provide more than 80%, oxygen of more than a 11 L flow with reservoir of 100 cm should be delivered. In pediatric RB, a 15 L oxygen flow without reservoir get more than 70% oxygen. A 20 cm corrugated tube as a reservoir increased abruptly oxygen concentration, and A 40 cm tube with more than a 7 L flow delivered more than 95% oxygen, but above 60cm tube there is little increase in the oxygen concentration. These results indicated that to get more than 70% oxygen, 60 cm and 40 cm corrugated tube is required in adult type RB and pediatric type RB respectively as an oxygen reservoir.
Adult
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Bays
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Humans
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Oxygen*
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Respiratory Rate
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Resuscitation*
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Tidal Volume
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Ventilation
9.The Effects of Patterns of AMBU bag Ventilation on the Inspiratory Oxygen Concentration.
Young Kyun CHUNG ; Jong Ho BAE ; Ju Tae SON
Korean Journal of Anesthesiology 1994;27(10):1361-1367
The AMBU bag is a useful equipment at the cardiopulmonary resuscitation (CPR) or the respiratory therapy. The AMBU bag eonsists simply of a self-reflating bag, a patient valve and a inlet valve. The patient valve is a non-rebreathing valve and the self-inflating bag is a recoiled rubber bag. The inlet valve on the posterior site of self-inflstion bag is closed during the bag is squeezed, and opened during the bag is released. During reflation of bag, fresh room air through the one-way valve and fresh oxygen through the orifice for oxygen supply will mix. Therefore the inspiratory oxygen concentration is decided by a speed of re- flation of the self-reflating bag. We measured inspiratory oxygen concentration during AMBU bag ventilation under different inspiration : expiration (I:E) ratio, frequency of venti- lation, ventilatory volume and flow rate of oxygen. The results were that factors increase a inspirstory oxygen concentration are 1) decrease of I:E ratio, 2) decrease of frequency of ventilation, 3) decrease of ventilatory volume, 4) inerease of flow rate. We found that haste of physician makes frequent squeezing of AMBU bag and the haste results a decrease of inspiratory oxygen concentration.
Bays
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Cardiopulmonary Resuscitation
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Humans
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Oxygen*
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Respiratory Therapy
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Rubber
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Ventilation*
10.Real-Time Visualization of Ultrasonography Guided Cubital Tunnel Injection: A Cadaveric Study.
Jae Min KIM ; Hyun Mi OH ; Min Wook KIM
Annals of Rehabilitation Medicine 2012;36(4):496-500
OBJECTIVE: To describe an ultrasonography-guided technique for cubital tunnel injection. METHOD: The ulnar nerves from 12 elbows of 6 adult cadavers were scanned, and the cross-sectional areas of the ulnar nerves, cubital tunnel inlets and outlets were measured by using ultrasonography. All elbows were dissected after an ultrasonography-guided dye injection at the inlet of the cubital tunnel. The dissectors evaluated the spread of dye and the coloration of the nerve and remeasured the cross-sectional areas of the cubital tunnel inlets and outlets. RESULTS: After a real-time visualization of an ultrasonography-guided injection, the ulnar nerves were seperated from the medial groove for the ulnar nerve. All the ulnar nerves of the cadavers were successfully colored with the dye, from the inlet to oulet of the cubital tunnel. The post-injection cross-sectional areas were significantly larger than the pre-injection cross-sectional areas. No significant differences were detected in the post-injection cross-sectional areas of the cubital tunnel outlet and the ulnar nerve as compared with the pre-injection areas. CONCLUSION: Clinicians should consider real-time visualization of ultrasonography for guided injection around the ulnar nerve at the inlet of the cubital tunnel.
Adult
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Bays
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Cadaver
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Elbow
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Humans
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Ulnar Nerve
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Ulnar Neuropathies