Iterative Bayesian Learning for Crowdsourced Regression

Crowdsourcing platforms emerged as popular venues for purchasing human intelligence at low cost for large volume of tasks. As many low-paid workers are prone to give noisy answers, a common practice is to add redundancy by assigning multiple workers to each task and then simply average out these answers. However, to fully harness the wisdom of the crowd, one needs to learn the heterogeneous quality of each worker. We resolve this fundamental challenge in crowdsourced regression tasks, i.e., the answer takes continuous labels, where identifying good or bad workers becomes much more non-trivial compared to a classification setting of discrete labels. In particular, we introduce a Bayesian iterative scheme and show that it provably achieves the optimal mean squared error. Our evaluations on synthetic and real-world datasets support our theoretical results and show the superiority of the proposed scheme

Development of Prediction Method for Dimensional Stability of 3D-Printed Objects

Fused deposition modeling (FDM), as one of the additive manufacturing processes, is known for strong layer adhesion suitable for prototypes and end-use items. This study used a multiple regression model and statistical analysis to explore the dimensional accuracy of FDM objects. Factors such as inclination angle, layer thickness, support space, and raster angle were examined. Machine learning models (Gaussian process regression (GPR), support vector machines (SVM), and artificial neural network (ANN)) predicted dimensions using 81 datapoints. The mean squared dimensional error (MSDE) between the measured and designed surface profiles was selected as an output for the dimensional accuracy. Support spacing, layer thickness, and raster angle were determined to be statistically significant, and all factors were confirmed as significant predictors. The coefficients of determination for multiple linear regression, GPR, SVM, and ANN models were 76%, 98%, 93%, and 99%, respectively. The mean absolute errors (MAEs)—errors between the measured and the predicted MSDEs—were 0.020 mm and 0.034 mm, respectively, for GPR and SVM models. The MAEs for ANN models were 0.0055 mm for supporting cases and 2.1468 x 10 -5 mm for non-supporting cases

Early Growth Response Factor-1 Is Associated With Intraluminal Thrombus Formation in Human Abdominal Aortic Aneurysm

ObjectivesThe goal of this study was to investigate the expression of early growth response-1 (Egr-1), a vascular pathogenic transcription factor, and its potential relationship with tissue factor (TF), a key player during the thrombus formation in the abdominal aortic aneurysm (AAA) wall.BackgroundAlthough intraluminal thrombus is a common finding in human AAA, the molecular mechanism of the thrombus formation has not been studied.MethodsDuring the elective AAA repair, specimens were taken from the thrombus-covered and thrombus-free portions of the aneurysmal wall in each of 16 patients with AAA and analyzed to assess the differential expression of Egr-1 and TF. The proinflammatory and prothrombogenic activities of Egr-1 in vasculature were evaluated in vitro and in vivo by overexpressing it using adenovirus.ResultsThe expression of both Egr-1 and TF was significantly increased in the thrombus-covered wall compared with the thrombus-free wall, in which their up-regulation in the thrombus-covered wall was strongly correlated with each other (p < 0.005, r = 0.717). Adenoviral overexpression of Egr-1 in human vascular smooth muscle and endothelial cells was found to up-regulate the expression of TF and inflammation-related genes. Moreover, Egr-1 overexpression in endothelial cells increased their adhesiveness to monocytes and also substantially promoted the intravascular thrombus formation in vivo, as shown in the inferior vena cava ligation experiment of the rat.ConclusionsThe present study demonstrates the differential up-regulation of Egr-1 in the thrombus-covered wall of human AAA and also suggests its possible contribution to the thrombogenic and inflammatory pathogenesis in human AAA

Genetic Analysis of Three Korean Patients with Clinical Features of Ehlers-Danlos Syndrome Type IV

Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue. EDS type IV (EDS IV), the vascular type of the disease, is characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations in the gene for type III procollagen (COL3A1). However, recent studies suggest that the causative mutation of EDS IV is not homogeneous. We report our experience with three patients presenting with clinical features of type IV EDS. A 48-yr-old woman presented with acute aortic dissection (patient 1) and 36-yr-old and 21-yr-old women presented with carotid-cavernous fistula (patients 2 and 3, respectively). All three patients bruised easily. Two patients (patients 1 and 3) had thin transparent skin with visible veins. Genetic analysis of COL3A1 revealed a Gly732Val (c.2195G>T) mutation in patient 1 and a duplication of 15 base pairs (c.3221_3235dup) which resulted in an interposition of five amino acids (p.Gly1074_Pro1078dup) in patient 2. However, no mutations were observed in COL3A1 or transforming growth factor β receptors 1 and 2 in patients 3, which might be either due to a deletion of single or multiple exons in the COL3A1 gene or due to a genetic heterogeneity. This is the first report of genetically confirmed cases of EDS IV in Korea

Utility of Integrated Analysis of Pharmacogenomics and Pharmacometabolomics in Early Phase Clinical Trial: A Case Study of a New Molecular Entity

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials

The Reliability and Validity of the Korean Version of the Structured Interview for Prodromal Syndrome

OBJECTIVE: The Structured Interview for Prodromal Syndrome (SIPS) from Yale University is intended to diagnose prodromal syndrome of psychosis and to measure the severity of prodromal symptoms. Here, a Korean version of SIPS is presented, and its reliability, validity, and factor structures are examined using a representative Korean sample. METHODS: The Korean version of SIPS was administered to 40 participants over a period of 1 year. The inter-rater reliability and internal consistency of the SIPS were then evaluated. In addition, its factor structure was investigated using principal-axis factor analysis. Concurrent validity was explored using Pearson correlation coefficients with the Positive and Negative Syndrome Scale (PANSS). RESULTS: Of the 40 subjects, 12.5% developed psychotic disorders during the 1-year follow-up period. Inter-rater reliability was good (intra-class correlations=0.96), and internal consistency was acceptable (Cronbach's alpha=0.83). A three-factor resolution displayed the best simple structure and accounted for 52.6% of all item variance. Factors 1 and 2 showed strong correlations with negative symptoms and cognitive dysfunction, respectively, on the PANSS. Factor 3 was not correlated with any factor on the PANSS. CONCLUSION: The Korean version of SIPS is a reliable instrument for the assessment of prodromal symptoms in subjects and may be used to evaluate prodromal psychosis.ope

The Significance of Repetitive Ventricular Responses Induced by Radiofrequency Energy Application for Idiopathic Left Ventricular Tachycardia

In radiofrequency (RF) ablation for idiopathic left ventricular tachycardia (ILVT), the termination of tachycardia during RF ablation is considered a hallmark of success. However, in cases of patients with difficulty of induction of ventricular tachycardia (VT), the evaluation of procedural success can be problematic. We have observed thermal responses reflected as ventricular rhythm change to RF energy delivered on sinus rhythm for ILVT. We therefore describe the significance of repetitive ventricular responses. The study subjects were 11 ILVT patients for whom RF energy was delivered during sinus rhythm because of difficulty in re-induction of tachycardia. During each energy delivery, we focused on the occurrence of repetitive ventricular responses especially exhibiting a similar morphology to clinical VT. The repetitive ventricular responses were noted in 10 of 11 patients. Two patients received a second procedure due to the recurrence of ILVT. The mean follow-up period was 36.2±12.8 months. The clinical course of the remaining patients was favorable and without recurrence of ILVT. Based on the favorable clinical outcomes, ablation-induced repetitive ventricular responses with similar QRS morphology to clinical ILVT are useful markers for selecting an ablation site and could be used as an additional mapping method, termed as "thermal mapping"