Use of Pseudo-observations in the Goodness-of-Fit Test for Gray\u27s Time-Varying Coefficients Model

Background The Cox proportional hazards (PH) regression model is the most common method to estimate underlying survival or failure probabilities and to estimate the effects of covariates on survival times. In Cox PH models, the regression coefficients are assumed constant over time. However, if covariate effects vary over time, alternative models which do not necessarily assume proportionality are needed. Method We proposed the Gray’s time-varying coefficient (TVC) method based on pseudo-observation. By using pseudo-observations, pseudo-residuals were calculated and plotted against the estimated survival rates at each of the nine selected time points, then were used to evaluate the goodness-of-fit of the Gray’s model. We applied this method to assess the fit for a model that predicts post-transplant survival probability among children who were under the age of 12 years, had end-stage liver disease, and underwent liver transplantation between January 2005 and June 2010. Result For Gray’s TVC model, through the first time point and the sixth time point, pseudo residual plots are around zero, while pseudo residual plots show slight departure at small values of estimated survival rate through the seventh time point and the ninth time point. Since the pseudo residual plots stay around zero at each time point without any significant departure or tendency, we can conclude that Gray’s model shows a good fit in estimating survival function at each time point. The results from this real liver transplantation data demonstrate that the final Gray’s model shows a good fit in estimating post-transplant survival. Conclusion When data violate the PH assumption, the Gray TVC model or an alternative should be used to obtain unbiased estimates on survival function and give correct inference on the relationship between potential covariates and survival. The proposed goodness-of-fit test offers a tool to investigate how well the model fits the data

The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma

AbstractTo test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity

A Simple and Facile Glucose Biosensor Based on Prussian Blue Modified Graphite String

This work describes the string sensor for the simple and sensitive detection of glucose which is based on Prussian blue (PB) modified graphite utilizing dipping. First, PB modified graphite (PB-G) strings are characterized by physical and electrochemical techniques to optimize the PB-G layer thickness. Then, glucose oxidase (GOx) is immobilized on PB-G string electrode with biocompatible chitosan overlayer (Chi/GOx/PB-G). The Chi/GOx/PB-G string electrode exhibits a sensitivity of 641.3 μA·mM−1·cm−2 to glucose with a linear range of 0.03 to 1.0 mM (R2=0.9957) and a rapid response time (<3 s). Moreover, the Chi/GOx/PB-G string electrodes are less sensitive to common interference materials such as ascorbic acid, uric acid, galactose, and acetaminophen than to glucose. The Chi/GOx/PB-G string electrodes also show excellent reproducibility (<5% RSD). Therefore, our Chi/GOx/PB-G string electrodes can be simple, robust, and reliable tools for glucose sensing which can avoid complicated and difficult multistep fabrication processes. In addition, we expect that they have many potential applications in fields ranging from health care to food analysis, in particular where single use is favorable

Microbial Ecology of Watery Kimchi

© 2015 Institute of Food Technologists®. This article has been contributed by US Government employees and their work is in the public domain in the USA. The biochemistry and microbial ecology of 2 similar types of watery (mul) kimchi, containing sliced and unsliced radish and vegetables (nabak and dongchimi, respectively), were investigated. Samples from kimchi were fermented at 4, 10, and 20 °C were analyzed by plating on differential and selective media, high-performance liquid chromatography, and high-throughput DNA sequencing of 16S rDNA. Nabak kimchi showed similar trends as dongchimi, with increasing lactic and acetic acids and decreasing pH for each temperature, but differences in microbiota were apparent. Interestingly, bacteria from the Proteobacterium phylum, including Enterobacteriaceae, decreased more rapidly during fermentation at 4 °C in nabak cabbage fermentations compared with dongchimi. Although changes for Proteobacterium and Enterobacteriaceae populations were similar during fermentation at 10 and 20 °C, the homolactic stage of fermentation did not develop for the 4 and 10 °C samples of both nabak and dongchimi during the experiment. These data show the differences in biochemistry and microbial ecology that can result from preparation method and fermentation conditions of the kimchi, which may impact safety (Enterobacteriaceae populations may include pathogenic bacteria) and quality (homolactic fermentation can be undesirable, if too much acid is produced) of the product. In addition, the data also illustrate the need for improved methods for identifying and differentiating closely related lactic acid bacteria species using high-throughput sequencing methods.This work was carried out as part of the international collaborative R&D program funded by the Agency for Korea Natl. Food Cluster (2013), and supported in part by a grant from Pickle Packers Intl. Inc., Washington, D.C., U.S.A. The authors thank the Spanish Government (MECD) for the postdoctoral fellowship support for Dr. E. Medina-Pradas.Peer Reviewe

Association between polymorphisms of arachidonate 12-lipoxygenase (ALOX12) and schizophrenia in a Korean population

Arachidonic acid (AA), an essential polyunsaturated fatty acid, is one of the major components of neural membranes, which show an altered phospholipid composition in schizophrenia. Arachidonate 12-lipoxygenase (ALOX12), an important enzyme, metabolizes AA to 12-HPETE, which affects catecholamine synthesis. However, research has yet to show the genetic association between ALOX12 and schizophrenia. Therefore, we investigated single nucleotide polymorphisms (SNP) of the ALOX12 gene in schizophrenia, recruiting patients with schizophrenia (n = 289) and normal controls (n = 306) from a Korean population. We selected three SNPs (rs1126667, rs434473, and rs1042357) of the ALOX12 gene and genotyped them by direct sequencing. We reviewed the schizophrenic patients' medical records and assessed them clinically using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Operational Criteria Checklist (OPCRIT). Then we statistically analyzed the genetic associations between the SNPs and schizophrenia, finding a genetic association between both rs1126667 and rs1042357 and schizophrenia, in the recessive model (p = 0.015 and 0.015, respectively). We also found an association between rs434473 and negative symptoms, defined through a factor analysis of the OPCRIT data (p = 0.040). Consequently, we suggest that SNPs of the ALOX12 gene might be associated with schizophrenia and negative symptoms in this Korean population. These weak positives require additional study

Recurrent Lower Gastrointestinal Bleeding from Congenital Arteriovenous Malformation in the Terminal Ileum Mimicking Intestinal Varicosis: A Case Report

We report on an exceptional vascular cause of gastrointestinal hemorrhage. A 30-yr-old man was admitted because of recurrent hematochezia. Colonoscopy showed circumferential, erythematous, and nodular vascular distensions with hematocystic spots in the terminal ileum resembling varicosis and subsequent computed tomography with 3-dimensional angiographic reconstruction revealed a vascular architecture around the terminal ileum. No other potential source of bleeding was identified. The patient was treated by ileocecectomy and the final diagnosis was of an arteriovenous malformation confined to the terminal ileum. He has been followed-up without a further hemorrhagic episode

Association Study of FOS-Like Antigen-2 Promoter Polymorphisms With Papillary Thyroid Cancer in Korean Population

ObjectivesFOS-like antigen-2 (FOSL-2), a member of the FOS gene family, encode leucine zipper proteins that can heterodimerize with proteins of Jun family. Thus, activating protein (AP)-1 transcription factor is formed, has a crucial role in proliferation, differentiation and apoptosis of normal tissue as well as oncogenic transformation and progression. We performed an association study of single nucleotide polymorphisms (SNPs) in the FOSL-2 with papillary thyroid cancer (PTC). We also estimated the relationships between the SNPs and the clinicopathologic characteristics of PTC.MethodsOne promoter SNPs (rs925255) of FOSL-2 gene were genotyped with direct sequencing method in 94 PTC and 213 controls. PTC patients were dichotomized and compared with respect to clinical parameters of PTC. Genetic data were analyzed using Helixtree, SNPAnalyzer, SNPStats. Multivariate logistic regression analysis was fulfilled to evaluate the genetic effect with adjustment for age and sex.ResultsSNP (rs925255) in FOSL-2 showed a significant association (codominant 1 model [G/G vs. A/G]: odds ratio [OR], 0.531, 95% confidence interval [CI], 0.293 to 0.96, P=0.036; dominant model: OR, 0.50, 95% CI, 0.28 to 0.89, P=0.015) with PTC. The frequency of allele G in rs925255 was also significantly associated with PTC (OR, 0.59; 95% CI, 0.34 to 0.91; P=0.02). But we fail to prove significant association between this polymorphism (rs925255) and clinico-pathological parameters.ConclusionOur findings suggest that the rs925255 SNP and its allele G show significant association with the PTC in Korean population

Imaging findings in coronavirus infections : SARS-CoV, MERS-CoV, and SARS-CoV-2

During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and non-specific, the most common initial chest radiograph (CXR) and CT findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks