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.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*
3.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*
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.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*
6.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
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.Biochemical Characteristics of Vibrios isolated from Cultured Shellfish, Ruditapes philippinarum, and Some Species of Wild Shellfish.
Hun Ku LEE ; Sang Seob LEE ; Young Hee YOON ; Kuk Hea HA
Journal of the Korean Society for Microbiology 1998;33(6):567-574
This study was conducted to investigate the vibrio flora in edible shellfish (Ruditapes philippinarum, Scapharca broughtonii, Batillus cornutus and Mytilus coruscus) which were purchased from seafood-market or collected from shellfish culture bed in Pusan and Masan Bay from May to October 1997. Sixty-three vibrio strains were identified among 438 collected strains. Five species of vibrios [V. alginolyticus (22 strains), V. parahaemolyticus (35 strains), V. costicola (2 strains), L. damsela (V. damsela 2 strains), and V. cholerae non-Ol (2 strains)] were identified by their phenotyfic and biochemical characteristics. Four groups (142 strains) were identified as genus Vibrio by their biological characteristics, but they could not be identified to the species level.
Bays
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Busan
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Cholera
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Mytilus
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Population Characteristics
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Scapharca
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Shellfish*
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Vibrio*
9.Influences of Geometric Configurations of Bypass Grafts on Hemodynamics in End-to-Side Anastomosis.
Jae Sung CHOI ; Sung Chul HONG ; Hyuck Moon KWON ; Sang Ho SUH ; Jeong Sang LEE
The Korean Journal of Thoracic and Cardiovascular Surgery 2011;44(2):89-98
BACKGROUND: Although considerable efforts have been made to improve the graft patency in coronary artery bypass surgery, the role of biomechanical factors remains underrecognized. The aim of this study is to investigate the influences of geometric configurations of the bypass graft on hemodynamic characteristics in relation to anastomosis. MATERIALS AND METHODS: The Numerical analysis focuses on understanding the flow patterns for different values of inlet and distal diameters and graft angles. The Blood flow field is treated as a two-dimensional incompressible laminar flow. A finite volume method is adopted for discretization of the governing equations. The Carreau model is employed as a constitutive equation for blood. In an attempt to obtain the optimal aorto-coronary bypass conditions, the blood flow characteristics are analyzed using in vitro models of the end-to-side anastomotic angles of 45degrees, 60degrees and 90degrees. To find the optimal graft configurations, the mass flow rates at the outlets of the four models are compared quantitatively. RESULTS: This study finds that Model 3, whose bypass diameter is the same as the inlet diameter of the stenosed coronary artery, delivers the largest amount of blood and the least pressure drop along the arteries. CONCLUSION: Biomechanical factors are speculated to contribute to the graft patency in coronary artery bypass grafting.
Bays
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Computer Simulation
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Coronary Artery Bypass
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Coronary Vessels
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Hemodynamics
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Transplants
10.Anterior Transcervical Approach to Superior Sulcus Tumor.
Ho CHOI ; Cheol Joo LEE ; Joon Wha HONG ; Joon Kyu KANG ; Jin Wook CHOI ; You Sang YOON
The Korean Journal of Thoracic and Cardiovascular Surgery 2001;34(5):426-429
Superior sulcus or pancoast tumor refers to any primary lung cancer locating in thoracic inlet and causing pain in the periscapular region or arm. These originate in peripheral, and involve the extrapulmonary structures more than arenchyma of the lung. We experienced 1 case of superior sulcus tumor radically resected via anterior transcervical approach, which provided more safe exposure of cervical structures of thoracic inlet than classic posterolateral thoracotomy. Therefore we report this case with review of literature.
Arm
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Bays
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Lung
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Lung Neoplasms
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Pancoast Syndrome
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Thoracotomy