• Title/Summary/Keyword: Diagnostic validation

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Different Real Time PCR Approaches for the Fine Quantification of SNP's Alleles in DNA Pools: Assays Development, Characterization and Pre-validation

  • Mattarucchi, Elia;Marsoni, Milena;Binelli, Giorgio;Passi, Alberto;Lo Curto, Francesco;Pasquali, Francesco;Porta, Giovanni
    • BMB Reports
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    • v.38 no.5
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    • pp.555-562
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    • 2005
  • Single nucleotide polymorphisms (SNPs) are becoming the most common type of markers used in genetic analysis. In the present report a SNP has been chosen to test the applicability of Real Time PCR to discriminate and quantify SNPs alleles on DNA pools. Amplification Refractory Mutation System (ARMS) and Mismatch Amplification Mutation Assay (MAMA) has been applied. Each assay has been pre-validated testing specificity and performances (linearity, PCR efficiency, interference limit, limit of detection, limit of quantification, precision and accuracy). Both the approaches achieve a precise and accurate estimation of the allele frequencies on pooled DNA samples in the range from 5% to 95% and don't require standard curves or calibrators. The lowest measurement that could be significantly distinguished from the background noise has been determined around the 1% for both the approaches, allowing to extend the range of quantifications from 1% to 99%. Furthermore applicability of Real Time PCR assays for general diagnostic purposes is discussed.

A water treatment case study for quantifying model performance with multilevel flow modeling

  • Nielsen, Emil K.;Bram, Mads V.;Frutiger, Jerome;Sin, Gurkan;Lind, Morten
    • Nuclear Engineering and Technology
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    • v.50 no.4
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    • pp.532-541
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    • 2018
  • Decision support systems are a key focus of research on developing control rooms to aid operators in making reliable decisions and reducing incidents caused by human errors. For this purpose, models of complex systems can be developed to diagnose causes or consequences for specific alarms. Models applied in safety systems of complex and safety-critical systems require rigorous and reliable model building and testing. Multilevel flow modeling is a qualitative and discrete method for diagnosing faults and has previously only been validated by subjective and qualitative means. To ensure reliability during operation, this work aims to synthesize a procedure to measure model performance according to diagnostic requirements. A simple procedure is proposed for validating and evaluating the concept of multilevel flow modeling. For this purpose, expert statements, dynamic process simulations, and pilot plant experiments are used for validation of simple multilevel flow modeling models of a hydrocyclone unit for oil removal from produced water.

Noninvasive molecular biomarkers for the detection of colorectal cancer

  • Kim, Hye-Jung;Yu, Myeong-Hee;Kim, Ho-Guen;Byun, Jong-Hoe;Lee, Cheolju
    • BMB Reports
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    • v.41 no.10
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    • pp.685-692
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    • 2008
  • Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, non-invasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussed.

A Design of Automated Contingency Management and Case Study for Monopropellant Propulsion System (단일추진시스템의 ACM 설계 및 사례연구)

  • Lee, Young-Jin;Lee, Kwon-Soon;Vachtsevanos, George
    • Journal of the Korean Society for Aviation and Aeronautics
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    • v.16 no.2
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    • pp.1-11
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    • 2008
  • Increasing demand for improved reliability and survivability of mission-critical systems is driving the development of health monitoring and Automated Contingency Management (ACM) systems. An ACM system is expected to adapt autonomously to fault conditions with the goal of still achieving mission objectives by allowing some degradation in system performance within permissible limits. ACM performance depends on supporting technologies like sensors and anomaly detection, diagnostic/prognostic and reasoning algorithms. This paper presents the development of a generic prototype test bench software framework for developing and validating ACM systems for advanced propulsion systems called the Propulsion ACM (PACM) Test Bench. The architecture has been implemented for a Monopropellant Propulsion System (MPS) to demonstrate the validity of the approach. A Simulink model of the MPS has been developed along with a fault injection module. It has been shown that the ACM system is capable of mitigating the failures by searching for an optimal strategy. Furthermore, the concepts of Validation and Verification (V&V) of such systems are introduced with relevant examples.

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Marine gas turbine monitoring and diagnostics by simulation and pattern recognition

  • Campora, Ugo;Cravero, Carlo;Zaccone, Raphael
    • International Journal of Naval Architecture and Ocean Engineering
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    • v.10 no.5
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    • pp.617-628
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    • 2018
  • Several techniques have been developed in the last years for energy conversion and aeronautic propulsion plants monitoring and diagnostics, to ensure non-stop availability and safety, mainly based on machine learning and pattern recognition methods, which need large databases of measures. This paper aims to describe a simulation based monitoring and diagnostic method to overcome the lack of data. An application on a gas turbine powered frigate is shown. A MATLAB-SIMULINK(R) model of the frigate propulsion system has been used to generate a database of different faulty conditions of the plant. A monitoring and diagnostic system, based on Mahalanobis distance and artificial neural networks have been developed. Experimental data measured during the sea trials have been used for model calibration and validation. Test runs of the procedure have been carried out in a number of simulated degradation cases: in all the considered cases, malfunctions have been successfully detected by the developed model.

An autonomous control framework for advanced reactors

  • Wood, Richard T.;Upadhyaya, Belle R.;Floyd, Dan C.
    • Nuclear Engineering and Technology
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    • v.49 no.5
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    • pp.896-904
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    • 2017
  • Several Generation IV nuclear reactor concepts have goals for optimizing investment recovery through phased introduction of multiple units on a common site with shared facilities and/or reconfigurable energy conversion systems. Additionally, small modular reactors are suitable for remote deployment to support highly localized microgrids in isolated, underdeveloped regions. The long-term economic viability of these advanced reactor plants depends on significant reductions in plant operations and maintenance costs. To accomplish these goals, intelligent control and diagnostic capabilities are needed to provide nearly autonomous operations with anticipatory maintenance. A nearly autonomous control system should enable automatic operation of a nuclear power plant while adapting to equipment faults and other upsets. It needs to have many intelligent capabilities, such as diagnosis, simulation, analysis, planning, reconfigurability, self-validation, and decision. These capabilities have been the subject of research for many years, but an autonomous control system for nuclear power generation remains as-yet an unrealized goal. This article describes a functional framework for intelligent, autonomous control that can facilitate the integration of control, diagnostic, and decision-making capabilities to satisfy the operational and performance goals of power plants based on multimodular advanced reactors.

A Validation Study of the Korean Child Behavior Checklist 1.5-5 in the Diagnosis of Autism Spectrum Disorder and Non-Autism Spectrum Disorder

  • Cho, Han Nah;Ha, Eun Hye
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.30 no.1
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    • pp.9-16
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    • 2019
  • Objectives: The purpose of this study was to analyze the discriminant validity and the clinical cut off scores of the Child Behavior Checklist 1.5-5 (CBCL 1.5-5) in the diagnosis of autism spectrum disorder (ASD) and non-ASD. Methods: In total, 104 ASD and 441 non-ASD infants were included in the study. T-test, discriminant analysis, receiver operating characteristic (ROC) curve analysis, and odds ratio analysis were performed on the data. Results: The discriminant validity was confirmed by mean differences and discriminant analysis on the subscales of Emotionally reactive, Somatic complaints, Withdrawn, Sleep problems, Attention problems, Aggressive behavior, Internalizing problems, Externalizing problems, and Total problems, along with the Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented scales between the two groups. ROC analysis showed that the following subscales significantly separated ASD from normal infants: Emotionally reactive, Somatic complaints, Withdrawn, Sleep problems, Attention problems, Aggressive behavior, Internalizing problems, Externalizing problems, Total problems, and DSM pervasive developmental problems. Moreover, the clinical cut off score criteria adopted in the Korean-CBCL 1.5-5 were shown to be valid for the subscales Withdrawn, Internalizing problems, Externalizing problems, Total problems, and DSM pervasive developmental problems. Conclusion: The subscales of Withdrawn, Internalizing problems, Externalizing problems, Total problems, and DSM pervasive developmental problems significantly discriminated infants with ASD.

Differentiating Uterine Sarcoma From Atypical Leiomyoma on Preoperative Magnetic Resonance Imaging Using Logistic Regression Classifier: Added Value of Diffusion-Weighted Imaging-Based Quantitative Parameters

  • Hokun Kim;Sung Eun Rha;Yu Ri Shin;Eu Hyun Kim;Soo Youn Park;Su-Lim Lee;Ahwon Lee;Mee-Ran Kim
    • Korean Journal of Radiology
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    • v.25 no.1
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    • pp.43-54
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    • 2024
  • Objective: To evaluate the added value of diffusion-weighted imaging (DWI)-based quantitative parameters to distinguish uterine sarcomas from atypical leiomyomas on preoperative magnetic resonance imaging (MRI). Materials and Methods: A total of 138 patients (age, 43.7 ± 10.3 years) with uterine sarcoma (n = 44) and atypical leiomyoma (n = 94) were retrospectively collected from four institutions. The cohort was randomly divided into training (84/138, 60.0%) and validation (54/138, 40.0%) sets. Two independent readers evaluated six qualitative MRI features and two DWI-based quantitative parameters for each index tumor. Multivariable logistic regression was used to identify the relevant qualitative MRI features. Diagnostic classifiers based on qualitative MRI features alone and in combination with DWI-based quantitative parameters were developed using a logistic regression algorithm. The diagnostic performance of the classifiers was evaluated using a cross-table analysis and calculation of the area under the receiver operating characteristic curve (AUC). Results: Mean apparent diffusion coefficient value of uterine sarcoma was lower than that of atypical leiomyoma (mean ± standard deviation, 0.94 ± 0.30 10-3 mm2/s vs. 1.23 ± 0.25 10-3 mm2/s; P < 0.001), and the relative contrast ratio was higher in the uterine sarcoma (8.16 ± 2.94 vs. 4.19 ± 2.66; P < 0.001). Selected qualitative MRI features included ill-defined margin (adjusted odds ratio [aOR], 17.9; 95% confidence interval [CI], 1.41-503, P = 0.040), intratumoral hemorrhage (aOR, 27.3; 95% CI, 3.74-596, P = 0.006), and absence of T2 dark area (aOR, 83.5; 95% CI, 12.4-1916, P < 0.001). The classifier that combined qualitative MRI features and DWI-based quantitative parameters showed significantly better performance than without DWI-based parameters in the validation set (AUC, 0.92 vs. 0.78; P < 0.001). Conclusion: The addition of DWI-based quantitative parameters to qualitative MRI features improved the diagnostic performance of the logistic regression classifier in differentiating uterine sarcomas from atypical leiomyomas on preoperative MRI.

Comparative Serum Proteomic Analysis of Serum Diagnosis Proteins of Colorectal Cancer Based on Magnetic Bead Separation and MALDI-TOF Mass Spectrometry

  • Deng, Bao-Guo;Yao, Jin-Hua;Liu, Qing-Yin;Feng, Xian-Jun;Liu, Dong;Zhao, Li;Tu, Bin;Yang, Fan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6069-6075
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    • 2013
  • Background: At present, the diagnosis of colorectal cancer (CRC) requires a colorectal biopsy which is an invasive procedure. We undertook this pilot study to develop an alternative method and potential new biomarkers for diagnosis, and validated a set of well-integrated tools called ClinProt to investigate the serum peptidome in CRC patients. Methods: Fasting blood samples from 67 patients diagnosed with CRC by histological diagnosis, 55 patients diagnosed with colorectal adenoma by biopsy, and 65 healthy volunteers were collected. Division was into a model construction group and an external validation group randomly. The present work focused on serum proteomic analysis of model construction group by ClinProt Kit combined with mass spectrometry. This approach allowed construction of a peptide pattern able to differentiate the studied populations. An external validation group was used to verify the diagnostic capability of the peptidome pattern blindly. An immunoassay method was used to determine serum CEA of CRC and controls. Results: The results showed 59 differential peptide peaks in CRC, colorectal adenoma and health volunteers. A genetic algorithm was used to set up the classification models. Four of the identified peaks at m/z 797, 810, 4078 and 5343 were used to construct peptidome patterns, achieving an accuracy of 100% (> CEA, P<0.05). Furthermore, the peptidome patterns could differentiate the validation group with high accuracy close to 100%. Conclusions: Our results showed that proteomic analysis of serum with MALDI-TOF MS is a fast and reproducible approach, which may provide a novel approach to screening for CRC.

Cell-Free miR-27a, a Potential Diagnostic and Prognostic Biomarker for Gastric Cancer

  • Park, Jong-Lyul;Kim, Mirang;Song, Kyu-Sang;Kim, Seon-Young;Kim, Yong Sung
    • Genomics & Informatics
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    • v.13 no.3
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    • pp.70-75
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    • 2015
  • MicroRNAs (miRNAs) have been demonstrated to play an important role in carcinogenesis. Previous studies revealed that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. In this study, we measured the plasma expression levels of three miRNAs (miR-21, miR-27a, and miR-155) to investigate the usefulness of miRNAs for gastric cancer detection. We initially examined plasma miRNA expression levels in a screening cohort consisting of 15 patients with gastric cancer and 15 healthy controls from Korean population, using TaqMan quantitative real-time polymerase chain reaction. We observed that the expression level of miR-27a was significantly higher in patients with gastric cancer than in healthy controls, whereas the miR-21 and miR-155a expression levels were not significantly higher in the patients with gastric cancer. Therefore, we further validated the miR-27a expression level in 73 paired gastric cancer tissues and in a validation plasma cohort from 35 patients with gastric cancer and 35 healthy controls. In both the gastric cancer tissues and the validation plasma cohort, the miR-27a expression levels were significantly higher in patients with gastric cancer. Receiver-operator characteristic (ROC) analysis of the validation cohort, revealed an area under the ROC curve value of 0.70 with 75% sensitivity and 56% specificity in discriminating gastric cancer. Thus, the miR-27a expression level in plasma could be a useful biomarker for the diagnosis and/or prognosis of gastric cancer.