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Sample records for accuracy sensitivity specificity

  1. Assessment of the Sensitivity, Specificity, and Accuracy of Thermography in Identifying Patients with TMD

    PubMed Central

    Woźniak, Krzysztof; Szyszka-Sommerfeld, Liliana; Trybek, Grzegorz; Piątkowska, Dagmara

    2015-01-01

    Background The purpose of the present study was to evaluate the sensitivity, specificity, and accuracy of thermography in identifying patients with temporomandibular dysfunction (TMD). Material/Methods The study sample consisted of 50 patients (27 women and 23 men) ages 19.2 to 24.5 years (mean age 22.43±1.04) with subjective symptoms of TMD (Ai II–III) and 50 patients (25 women and 25 men) ages 19.3 to 25.1 years (mean age 22.21±1.18) with no subjective symptoms of TMD (Ai I). The anamnestic interviews were conducted according to the three-point anamnestic index of temporomandibular dysfunction (Ai). The thermography was performed using a ThermaCAM TMSC500 (FLIR Systems AB, Sweden) independent thermal vision system. Thermography was closely combined with a 10-min chewing test. Results The results of our study indicated that the absolute difference in temperature between the right and left side (ΔT) has the highest diagnostic value. The diagnostic effectiveness of this parameter increased after the chewing test. The cut-off points for values of temperature differences between the right and left side and identifying 95.5% of subjects with no functional disorders according to the temporomandibular dysfunction index Di (specificity 95.5%) were 0.26°C (AUC=0.7422, sensitivity 44.3%, accuracy 52.4%) before the chewing test and 0.52°C (AUC=0.7920, sensitivity 46.4%, accuracy 56.3%) after it. Conclusions The evaluation of thermography demonstrated its diagnostic usefulness in identifying patients with TMD with limited effectiveness. The chewing test helped in increasing the diagnostic efficiency of thermography in identifying patients with TMD. PMID:26002613

  2. Raman Spectroscopy: A Sensitive and Specific Technique for Determining the Accuracy of Compounded Pharmaceutical Formulations.

    PubMed

    Meek, Claudia; Hoe, Jihye; Evans, Jason; Thurman, Rosanne; Ashworth, Lisa; Leff, Richard

    2016-01-01

    OBJECTIVES: Raman spectroscopy is a widely used technology to identify chemical unknowns or confirm chemical identity. We have tested Raman spectrometry to identify compounded pharmaceutical formulations. In contrast to the commonly used application mentioned above, compounded pharmaceutical formulations contain a mixture of ingredients, and the Raman spectrometer is being used to correctly identify the composition of the complete pharmaceutical formulation, including the active pharmaceutical ingredient(s). The objective of this pilot study was to document the potential use of Raman spectroscopy as a tool to provide quality control to compounded pharmaceutical formulations. METHODS: "Testing a test" study design was used to prospectively determine whether Raman spectroscopy could verify the accuracy of compounded pharmaceutical formulations. A total of 9 formulations that are commonly compounded at Cook Children's Health Center were selected for testing. Each of the 9 formulations and 2 blank controls were randomly tested for compounding accuracy in replicate. A total of 110 tests were conducted. RESULTS: Raman spectroscopy was found to be a reliable test to determine the accuracy of compounded pharmaceutical formulations with a 100% positive predictive value. CONCLUSIONS: Raman spectroscopy promises to be an excellent tool for compounding pharmacies to provide an objective measure of compounding accuracy to their unique, compounded pharmaceutical formulations.

  3. Raman Spectroscopy: A Sensitive and Specific Technique for Determining the Accuracy of Compounded Pharmaceutical Formulations

    PubMed Central

    Meek, Claudia; Hoe, Jihye; Evans, Jason; Thurman, Rosanne; Ashworth, Lisa

    2016-01-01

    OBJECTIVES: Raman spectroscopy is a widely used technology to identify chemical unknowns or confirm chemical identity. We have tested Raman spectrometry to identify compounded pharmaceutical formulations. In contrast to the commonly used application mentioned above, compounded pharmaceutical formulations contain a mixture of ingredients, and the Raman spectrometer is being used to correctly identify the composition of the complete pharmaceutical formulation, including the active pharmaceutical ingredient(s). The objective of this pilot study was to document the potential use of Raman spectroscopy as a tool to provide quality control to compounded pharmaceutical formulations. METHODS: “Testing a test” study design was used to prospectively determine whether Raman spectroscopy could verify the accuracy of compounded pharmaceutical formulations. A total of 9 formulations that are commonly compounded at Cook Children's Health Center were selected for testing. Each of the 9 formulations and 2 blank controls were randomly tested for compounding accuracy in replicate. A total of 110 tests were conducted. RESULTS: Raman spectroscopy was found to be a reliable test to determine the accuracy of compounded pharmaceutical formulations with a 100% positive predictive value. CONCLUSIONS: Raman spectroscopy promises to be an excellent tool for compounding pharmacies to provide an objective measure of compounding accuracy to their unique, compounded pharmaceutical formulations. PMID:27877094

  4. Accuracy, Precision, Sensitivity, and Specificity of Noninvasive ICP Absolute Value Measurements.

    PubMed

    Krakauskaite, Solventa; Petkus, Vytautas; Bartusis, Laimonas; Zakelis, Rolandas; Chomskis, Romanas; Preiksaitis, Aidanas; Ragauskas, Arminas; Matijosaitis, Vaidas; Petrikonis, Kestutis; Rastenyte, Daiva

    2016-01-01

    An innovative absolute intracranial pressure (ICP) value measurement method has been validated by multicenter comparative clinical studies. The method is based on two-depth transcranial Doppler (TCD) technology and uses intracranial and extracranial segments of the ophthalmic artery as pressure sensors. The ophthalmic artery is used as a natural pair of "scales" that compares ICP with controlled pressure Pe, which is externally applied to the orbit. To balance the scales, ICP = Pe a special two-depth TCD device was used as a pressure balance indicator. The proposed method is the only noninvasive ICP measurement method that does not need patient-specific calibration.

  5. Accuracy of Pressure Sensitive Paint

    NASA Technical Reports Server (NTRS)

    Liu, Tianshu; Guille, M.; Sullivan, J. P.

    2001-01-01

    Uncertainty in pressure sensitive paint (PSP) measurement is investigated from a standpoint of system modeling. A functional relation between the imaging system output and luminescent emission from PSP is obtained based on studies of radiative energy transports in PSP and photodetector response to luminescence. This relation provides insights into physical origins of various elemental error sources and allows estimate of the total PSP measurement uncertainty contributed by the elemental errors. The elemental errors and their sensitivity coefficients in the error propagation equation are evaluated. Useful formulas are given for the minimum pressure uncertainty that PSP can possibly achieve and the upper bounds of the elemental errors to meet required pressure accuracy. An instructive example of a Joukowsky airfoil in subsonic flows is given to illustrate uncertainty estimates in PSP measurements.

  6. Comparison of the diagnostic accuracy, sensitivity and specificity of four odontological methods for age evaluation in Italian children at the age threshold of 14 years using ROC curves.

    PubMed

    Pinchi, Vilma; Pradella, Francesco; Vitale, Giulia; Rugo, Dario; Nieri, Michele; Norelli, Gian-Aristide

    2016-01-01

    The age threshold of 14 years is relevant in Italy as the minimum age for criminal responsibility. It is of utmost importance to evaluate the diagnostic accuracy of every odontological method for age evaluation considering the sensitivity, or the ability to estimate the true positive cases, and the specificity, or the ability to estimate the true negative cases. The research aims to compare the specificity and sensitivity of four commonly adopted methods of dental age estimation - Demirjian, Haavikko, Willems and Cameriere - in a sample of Italian children aged between 11 and 16 years, with an age threshold of 14 years, using receiver operating characteristic curves and the area under the curve (AUC). In addition, new decision criteria are developed to increase the accuracy of the methods. Among the four odontological methods for age estimation adopted in the research, the Cameriere method showed the highest AUC in both female and male cohorts. The Cameriere method shows a high degree of accuracy at the age threshold of 14 years. To adopt the Cameriere method to estimate the 14-year age threshold more accurately, however, it is suggested - according to the Youden index - that the decision criterion be set at the lower value of 12.928 for females and 13.258 years for males, obtaining a sensitivity of 85% and specificity of 88% in females, and a sensitivity of 77% and specificity of 92% in males. If a specificity level >90% is needed, the cut-off point should be set at 12.959 years (82% sensitivity) for females.

  7. Data mining methods in the prediction of Dementia: A real-data comparison of the accuracy, sensitivity and specificity of linear discriminant analysis, logistic regression, neural networks, support vector machines, classification trees and random forests

    PubMed Central

    2011-01-01

    Background Dementia and cognitive impairment associated with aging are a major medical and social concern. Neuropsychological testing is a key element in the diagnostic procedures of Mild Cognitive Impairment (MCI), but has presently a limited value in the prediction of progression to dementia. We advance the hypothesis that newer statistical classification methods derived from data mining and machine learning methods like Neural Networks, Support Vector Machines and Random Forests can improve accuracy, sensitivity and specificity of predictions obtained from neuropsychological testing. Seven non parametric classifiers derived from data mining methods (Multilayer Perceptrons Neural Networks, Radial Basis Function Neural Networks, Support Vector Machines, CART, CHAID and QUEST Classification Trees and Random Forests) were compared to three traditional classifiers (Linear Discriminant Analysis, Quadratic Discriminant Analysis and Logistic Regression) in terms of overall classification accuracy, specificity, sensitivity, Area under the ROC curve and Press'Q. Model predictors were 10 neuropsychological tests currently used in the diagnosis of dementia. Statistical distributions of classification parameters obtained from a 5-fold cross-validation were compared using the Friedman's nonparametric test. Results Press' Q test showed that all classifiers performed better than chance alone (p < 0.05). Support Vector Machines showed the larger overall classification accuracy (Median (Me) = 0.76) an area under the ROC (Me = 0.90). However this method showed high specificity (Me = 1.0) but low sensitivity (Me = 0.3). Random Forest ranked second in overall accuracy (Me = 0.73) with high area under the ROC (Me = 0.73) specificity (Me = 0.73) and sensitivity (Me = 0.64). Linear Discriminant Analysis also showed acceptable overall accuracy (Me = 0.66), with acceptable area under the ROC (Me = 0.72) specificity (Me = 0.66) and sensitivity (Me = 0.64). The remaining classifiers showed

  8. 40 CFR 91.305 - Dynamometer specifications and calibration accuracy.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... specifications. (1) The dynamometer test stand and other instruments for measurement of engine speed and torque... accuracy. (1) The dynamometer test stand and other instruments for measurement of engine torque and...

  9. 40 CFR 91.305 - Dynamometer specifications and calibration accuracy.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... specifications. (1) The dynamometer test stand and other instruments for measurement of engine speed and torque... accuracy. (1) The dynamometer test stand and other instruments for measurement of engine torque and...

  10. 40 CFR 91.305 - Dynamometer specifications and calibration accuracy.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... specifications. (1) The dynamometer test stand and other instruments for measurement of engine speed and torque... accuracy. (1) The dynamometer test stand and other instruments for measurement of engine torque and...

  11. 40 CFR 91.305 - Dynamometer specifications and calibration accuracy.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... specifications. (1) The dynamometer test stand and other instruments for measurement of engine speed and torque... accuracy. (1) The dynamometer test stand and other instruments for measurement of engine torque and...

  12. 40 CFR 90.305 - Dynamometer specifications and calibration accuracy.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Dynamometer specifications and... KILOWATTS Emission Test Equipment Provisions § 90.305 Dynamometer specifications and calibration accuracy. (a) Dynamometer specifications. The dynamometer test stand and other instruments for measurement...

  13. 40 CFR 91.305 - Dynamometer specifications and calibration accuracy.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Dynamometer specifications and... Equipment Provisions § 91.305 Dynamometer specifications and calibration accuracy. (a) Dynamometer specifications. (1) The dynamometer test stand and other instruments for measurement of engine speed and...

  14. Simultaneously improving the sensitivity and absolute accuracy of CPT magnetometer.

    PubMed

    Liang, Shang-Qing; Yang, Guo-Qing; Xu, Yun-Fei; Lin, Qiang; Liu, Zhi-Heng; Chen, Zheng-Xiang

    2014-03-24

    A new method to improve the sensitivity and absolute accuracy simultaneously for coherent population trapping (CPT) magnetometer based on the differential detection method is presented. Two modulated optical beams with orthogonal circular polarizations are applied, in one of which two magnetic resonances are excited simultaneously by modulating a 3.4GHz microwave with Larmor frequency. When a microwave frequency shift is introduced, the difference in the power transmitted through the cell in each beam shows a low noise resonance. The sensitivity of 2pT/Hz @ 10Hz is achieved. Meanwhile, the absolute accuracy of ± 0.5nT within the magnetic field ranging from 20000nT to 100000nT is realized.

  15. Specific Challenges in Conducting and Reporting Studies on the Diagnostic Accuracy of Ultrasonography in Bovine Medicine.

    PubMed

    Buczinski, Sébastien; O'Connor, Annette M

    2016-03-01

    Ultrasonography is used by bovine practitioners more for reproductive issues than as a diagnostic test for medical and surgical diseases. This article reviews the specific challenges and standards concerning reporting of studies on diagnostic accuracy of ultrasound in cattle for nonreproductive issues. Specific biases and applicability concerns in studies reporting ultrasonography as a diagnostic test are also reviewed. Better understanding of these challenges will help the practitioner to interpret and apply (or not) diagnostic accuracy study results depending on the field context. Examples of application of sensitivity and specificity results in a clinical context are given using the Bayes theorem.

  16. A systematic review on diagnostic procedures for specific language impairment: The sensitivity and specificity issues

    PubMed Central

    Shahmahmood, Toktam Maleki; Jalaie, Shohreh; Soleymani, Zahra; Haresabadi, Fatemeh; Nemati, Parvin

    2016-01-01

    Background: Identification of children with specific language impairment (SLI) has been viewed as both necessity and challenge. Investigators and clinicians use different tests and measures for this purpose. Some of these tests/measures have good psychometric properties, but it is not sufficient for diagnostic purposes. A diagnostic procedure can be used for identification a specific population with confidence only when its sensitivity and specificity are acceptable. In this study, we searched for tests/measures with predefined sensitivity and specificity for identification of preschool children with SLI from their typically developing peers. Materials and Methods: A computerized search in bibliographic databases from 2000 to August 2015 was performed with the following keywords: “specific language impairment” or SLI” and “primary language impairment” or ‘PLI’ with at least one of the followings: “diagnosis,” “identification,” “accuracy,” “sensitivity,” and “specificity.” In addition, the related citations and reference lists of the selected articles were considered. Results: The results of reviewing 23 included studies show that the index measures used in studies vary in accuracy with the sensitivity ranging from 16% to 100% and the specificity ranging from 14% to 100%. Conclusion: These varieties in sensitivity and specificity of different tests/measures confirm the necessity of attention to the diagnostic power of tests/measures before their use as diagnostic tool. Further, the results indicate there are some promising tests/measures that the available evidence supports their performances in the diagnosis of SLI in preschool-aged children, yet the place of a reference standard for the diagnosis of SLI is vacant among investigations. PMID:27904612

  17. Accuracy of critical-temperature sensitivity coefficients predicted by multilayered composite plate theories

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Burton, Scott

    1992-01-01

    An assessment is made of the accuracy of the critical-temperature sensitivity coefficients of multilayered plates predicted by different modeling approaches, based on two-dimensional shear-deformation theories. The sensitivity coefficients considered measure the sensitivity of the critical temperatures to variations in different lamination and material parameters of the plate. The standard of comparison is taken to be the sensitivity coefficients obtained by the three-dimensional theory of thermoelasticity. Numerical studies are presented showing the effects of variation in the geometric and lamination parameters of the plate on the accuracy of both the sensitivity coefficients and the critical temperatures predicted by the different modeling approaches.

  18. Sensitivity and specificity in Drosophila pheromone perception.

    PubMed

    Benton, Richard

    2007-10-01

    How the brain perceives volatile chemicals in the environment to evoke the appropriate behaviour is a fundamental question in sensory neuroscience. The olfactory system of the fruit fly, Drosophila melanogaster, has emerged as a powerful model system to address this problem. Recent analysis of the molecular, neuroanatomical and physiological properties of the olfactory circuits that detect the sex and social aggregation pheromone cis-vaccenyl acetate now provides one of the most comprehensive outlines for the neural basis of odour perception. This review describes these latest advances, discusses what they reveal about where stimulus sensitivity and specificity is encoded in olfactory circuits, and considers future questions.

  19. Accuracy of Specific BIVA for the Assessment of Body Composition in the United States Population

    PubMed Central

    Buffa, Roberto; Saragat, Bruno; Cabras, Stefano; Rinaldi, Andrea C.; Marini, Elisabetta

    2013-01-01

    Background Bioelectrical impedance vector analysis (BIVA) is a technique for the assessment of hydration and nutritional status, used in the clinical practice. Specific BIVA is an analytical variant, recently proposed for the Italian elderly population, that adjusts bioelectrical values for body geometry. Objective Evaluating the accuracy of specific BIVA in the adult U.S. population, compared to the ‘classic’ BIVA procedure, using DXA as the reference technique, in order to obtain an interpretative model of body composition. Design A cross-sectional sample of 1590 adult individuals (836 men and 754 women, 21–49 years old) derived from the NHANES 2003–2004 was considered. Classic and specific BIVA were applied. The sensitivity and specificity in recognizing individuals below the 5th and above the 95th percentiles of percent fat (FMDXA%) and extracellular/intracellular water (ECW/ICW) ratio were evaluated by receiver operating characteristic (ROC) curves. Classic and specific BIVA results were compared by a probit multiple-regression. Results Specific BIVA was significantly more accurate than classic BIVA in evaluating FMDXA% (ROC areas: 0.84–0.92 and 0.49–0.61 respectively; p = 0.002). The evaluation of ECW/ICW was accurate (ROC areas between 0.83 and 0.96) and similarly performed by the two procedures (p = 0.829). The accuracy of specific BIVA was similar in the two sexes (p = 0.144) and in FMDXA% and ECW/ICW (p = 0.869). Conclusions Specific BIVA showed to be an accurate technique. The tolerance ellipses of specific BIVA can be used for evaluating FM% and ECW/ICW in the U.S. adult population. PMID:23484033

  20. Sensitivity of Tumor Motion Simulation Accuracy to Lung Biomechanical Modeling Approaches and Parameters

    PubMed Central

    Tehrani, Joubin Nasehi; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu

    2015-01-01

    Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the Neo-Hookean compressible and uncoupled Mooney-Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney-Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney-Rivlin material model along left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation. PMID:26531324

  1. Sensitivity of tumor motion simulation accuracy to lung biomechanical modeling approaches and parameters.

    PubMed

    Tehrani, Joubin Nasehi; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu; Wang, Jing

    2015-11-21

    Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the neo-Hookean compressible and uncoupled Mooney-Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney-Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney-Rivlin material model along left-right, anterior-posterior, and superior-inferior directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation.

  2. Sensitivity of tumor motion simulation accuracy to lung biomechanical modeling approaches and parameters

    NASA Astrophysics Data System (ADS)

    Nasehi Tehrani, Joubin; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu; Wang, Jing

    2015-11-01

    Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the neo-Hookean compressible and uncoupled Mooney-Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney-Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney-Rivlin material model along left-right, anterior-posterior, and superior-inferior directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation.

  3. Linear polarization sensitivity specifications for space-borne instruments

    NASA Astrophysics Data System (ADS)

    Maymon, Peter W.; Chipman, Russell A.

    1992-12-01

    The radiometric accuracy of space-borne instruments such as radiometers and spectroradiometers which make measurements of the earth and other celestial objects can be compromised by the linear polarization sensitivity (LPS) induced by the optical system. Most of these optical systems contain optical elements whose reflectance or transmission is polarization dependent, such as diffraction gratings, folding and scanning mirrors, dichroic filters, and optical fibers. Optical system incorporating such elements generally display linear polarization sensitivity; different linear polarization states incident with equal radiometric power will be measured as different power levels. If the incident polarization state is unknown, the linear polarization sensitivity cannot be compensated during the data reduction. The light reflected from the earth and other planets and moons is usually partially linearly polarized, but in a random distribution. Thus, to make accurate radiometric measurements of these bodies, a radiometer or spectrometer should have a low level of linear polarization sensitivity. This paper contains a mathematical description of LPS, contains references to systems which have imposed a LPS specification, describes some of the sources of LPS, describes how to model LPS by polarization ray tracing, and discusses methods to reduce the LPS of an optical system.

  4. Sensitivity and accuracy analysis of CT image in PRISM autocontouring using confusion matrix and ROC/AUC curve methods

    NASA Astrophysics Data System (ADS)

    Yunisa, Regina; Haryanto, Freddy

    2015-09-01

    The research was conducted to evaluate and analyze the results of the CT image autocontouring Prism TPS using confusion matrix and ROC methods. This study begins by treating thoracic CT images using a grayscale format TPS Prism software. Autocontouring done in the area of spinal cord and right lung with appropriate parameter settings window. The average value of the sensitivity, specificity and accuracy for 23 slices of spinal cord are 0.93, 0.99, and 0.99. For two slices of the right lung, average value of sensitivity, specificity, and accuracy of 2 slices were 0.99, 0.99, and 0.99. These values are classified as `Excellent'.

  5. Sensitivity of grass and alfalfa reference evapotranspiration to weather station sensor accuracy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A sensitivity analysis was conducted to determine the relative effects of measurement errors in climate data input parameters on the accuracy of calculated reference crop evapotranspiration (ET) using the ASCE-EWRI Standardized Reference ET Equation. Data for the period of 1991 to 2008 from an autom...

  6. Enhancing detection sensitivity and accuracy on “Candidatus Liberibacter asiaticus” through next generation sequencing technology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    “Candidatus Liberibacter asiaticus” is associated with citrus Huanglongbing (HLB, yellow shoot disease). Detection of this unculturable bacterium exclusively depends on polymerase chain reaction (PCR). Appropriate primer design is key to assure detection sensitivity and accuracy, which depend on qua...

  7. The sensitivity and specificity of markers for event times.

    PubMed

    Cai, Tianxi; Pepe, Margaret Sullivan; Zheng, Yingye; Lumley, Thomas; Jenny, Nancy Swords

    2006-04-01

    The statistical literature on assessing the accuracy of risk factors or disease markers as diagnostic tests deals almost exclusively with settings where the test, Y, is measured concurrently with disease status D. In practice, however, disease status may vary over time and there is often a time lag between when the marker is measured and the occurrence of disease. One example concerns the Framingham risk score (FR-score) as a marker for the future risk of cardiovascular events, events that occur after the score is ascertained. To evaluate such a marker, one needs to take the time lag into account since the predictive accuracy may be higher when the marker is measured closer to the time of disease occurrence. We therefore consider inference for sensitivity and specificity functions that are defined as functions of time. Semiparametric regression models are proposed. Data from a cohort study are used to estimate model parameters. One issue that arises in practice is that event times may be censored. In this research, we extend in several respects the work by Leisenring et al. (1997) that dealt only with parametric models for binary tests and uncensored data. We propose semiparametric models that accommodate continuous tests and censoring. Asymptotic distribution theory for parameter estimates is developed and procedures for making statistical inference are evaluated with simulation studies. We illustrate our methods with data from the Cardiovascular Health Study, relating the FR-score measured at enrollment to subsequent risk of cardiovascular events.

  8. Decoding Accuracy in Supplementary Motor Cortex Correlates with Perceptual Sensitivity to Tactile Roughness

    PubMed Central

    Kim, Junsuk; Chung, Yoon Gi; Park, Jang-Yeon; Chung, Soon-Cheol; Wallraven, Christian; Bülthoff, Heinrich H.; Kim, Sung-Phil

    2015-01-01

    Perceptual sensitivity to tactile roughness varies across individuals for the same degree of roughness. A number of neurophysiological studies have investigated the neural substrates of tactile roughness perception, but the neural processing underlying the strong individual differences in perceptual roughness sensitivity remains unknown. In this study, we explored the human brain activation patterns associated with the behavioral discriminability of surface texture roughness using functional magnetic resonance imaging (fMRI). First, a whole-brain searchlight multi-voxel pattern analysis (MVPA) was used to find brain regions from which we could decode roughness information. The searchlight MVPA revealed four brain regions showing significant decoding results: the supplementary motor area (SMA), contralateral postcentral gyrus (S1), and superior portion of the bilateral temporal pole (STP). Next, we evaluated the behavioral roughness discrimination sensitivity of each individual using the just-noticeable difference (JND) and correlated this with the decoding accuracy in each of the four regions. We found that only the SMA showed a significant correlation between neuronal decoding accuracy and JND across individuals; Participants with a smaller JND (i.e., better discrimination ability) exhibited higher decoding accuracy from their voxel response patterns in the SMA. Our findings suggest that multivariate voxel response patterns presented in the SMA represent individual perceptual sensitivity to tactile roughness and people with greater perceptual sensitivity to tactile roughness are likely to have more distinct neural representations of different roughness levels in their SMA. PMID:26067832

  9. Variola virus-specific diagnostic assays: characterization, sensitivity, and specificity.

    PubMed

    Kondas, Ashley V; Olson, Victoria A; Li, Yu; Abel, Jason; Laker, Miriam; Rose, Laura; Wilkins, Kimberly; Turner, Jonathan; Kline, Richard; Damon, Inger K

    2015-04-01

    A public health response relies upon rapid and reliable confirmation of disease by diagnostic assays. Here, we detail the design and validation of two variola virus-specific real-time PCR assays, since previous assays cross-reacted with newly identified cowpox viruses. The assay specificity must continually be reassessed as other closely related viruses are identified.

  10. Accuracy and sensitivity analysis of the conical null-screen based corneal topographer

    NASA Astrophysics Data System (ADS)

    Cossio-Guerrero, Cesar; Campos-García, Manuel

    2016-09-01

    In every optical testing method, the time taken to process data, the precision of the results and the sensitivity are among the most relevant aspects to be taken into account when the viability of its implementation is been under consideration. An accuracy and sensitivity analysis of a topographer based on a conical null-screen with a semi-radial distribution of targets is presented. On the other hand, we proposed a custom evaluation algorithm in order to reduce the time in the calculation of the normal to the corneal surface. Finally, we perform some corneal topographical measurements.

  11. A simple modification to improve the accuracy of methylation-sensitive restriction enzyme quantitative polymerase chain reaction.

    PubMed

    Krygier, Magdalena; Podolak-Popinigis, Justyna; Limon, Janusz; Sachadyn, Paweł; Stanisławska-Sachadyn, Anna

    2016-05-01

    DNA digestion with endonucleases sensitive to CpG methylation such as HpaII followed by polymerase chain reaction (PCR) quantitation is commonly used in molecular studies as a simple and inexpensive solution for assessment of region-specific DNA methylation. We observed that the results of such analyses were highly overestimated if mock-digested samples were applied as the reference. We determined DNA methylation levels in several promoter regions in two setups implementing different references: mock-digested and treated with a restriction enzyme that has no recognition sites within examined amplicons. Fragmentation of reference templates allowed removing the overestimation effect, thereby improving measurement accuracy.

  12. The Kappa Statistic as a Function of Sensitivity and Specificity

    ERIC Educational Resources Information Center

    Feuerman, M.; Miller, A. R.

    2005-01-01

    This paper explores analytically the connections between three commonly used statistical measures of agreement: sensitivity, specificity, and Cohen's (unweighed) kappa, which are employed often in clinical studies. In particular, we show that if both sensitivity and specificity are below 7/8, then a kappa of 3/4 or greater (which is considered to…

  13. Integrated multi-ISE arrays with improved sensitivity, accuracy and precision

    PubMed Central

    Wang, Chunling; Yuan, Hongyan; Duan, Zhijuan; Xiao, Dan

    2017-01-01

    Increasing use of ion-selective electrodes (ISEs) in the biological and environmental fields has generated demand for high-sensitivity ISEs. However, improving the sensitivities of ISEs remains a challenge because of the limit of the Nernstian slope (59.2/n mV). Here, we present a universal ion detection method using an electronic integrated multi-electrode system (EIMES) that bypasses the Nernstian slope limit of 59.2/n mV, thereby enabling substantial enhancement of the sensitivity of ISEs. The results reveal that the response slope is greatly increased from 57.2 to 1711.3 mV, 57.3 to 564.7 mV and 57.7 to 576.2 mV by electronic integrated 30 Cl− electrodes, 10 F− electrodes and 10 glass pH electrodes, respectively. Thus, a tiny change in the ion concentration can be monitored, and correspondingly, the accuracy and precision are substantially improved. The EIMES is suited for all types of potentiometric sensors and may pave the way for monitoring of various ions with high accuracy and precision because of its high sensitivity. PMID:28303939

  14. Integrated multi-ISE arrays with improved sensitivity, accuracy and precision

    NASA Astrophysics Data System (ADS)

    Wang, Chunling; Yuan, Hongyan; Duan, Zhijuan; Xiao, Dan

    2017-03-01

    Increasing use of ion-selective electrodes (ISEs) in the biological and environmental fields has generated demand for high-sensitivity ISEs. However, improving the sensitivities of ISEs remains a challenge because of the limit of the Nernstian slope (59.2/n mV). Here, we present a universal ion detection method using an electronic integrated multi-electrode system (EIMES) that bypasses the Nernstian slope limit of 59.2/n mV, thereby enabling substantial enhancement of the sensitivity of ISEs. The results reveal that the response slope is greatly increased from 57.2 to 1711.3 mV, 57.3 to 564.7 mV and 57.7 to 576.2 mV by electronic integrated 30 Cl‑ electrodes, 10 F‑ electrodes and 10 glass pH electrodes, respectively. Thus, a tiny change in the ion concentration can be monitored, and correspondingly, the accuracy and precision are substantially improved. The EIMES is suited for all types of potentiometric sensors and may pave the way for monitoring of various ions with high accuracy and precision because of its high sensitivity.

  15. Integrated multi-ISE arrays with improved sensitivity, accuracy and precision.

    PubMed

    Wang, Chunling; Yuan, Hongyan; Duan, Zhijuan; Xiao, Dan

    2017-03-17

    Increasing use of ion-selective electrodes (ISEs) in the biological and environmental fields has generated demand for high-sensitivity ISEs. However, improving the sensitivities of ISEs remains a challenge because of the limit of the Nernstian slope (59.2/n mV). Here, we present a universal ion detection method using an electronic integrated multi-electrode system (EIMES) that bypasses the Nernstian slope limit of 59.2/n mV, thereby enabling substantial enhancement of the sensitivity of ISEs. The results reveal that the response slope is greatly increased from 57.2 to 1711.3 mV, 57.3 to 564.7 mV and 57.7 to 576.2 mV by electronic integrated 30 Cl(-) electrodes, 10 F(-) electrodes and 10 glass pH electrodes, respectively. Thus, a tiny change in the ion concentration can be monitored, and correspondingly, the accuracy and precision are substantially improved. The EIMES is suited for all types of potentiometric sensors and may pave the way for monitoring of various ions with high accuracy and precision because of its high sensitivity.

  16. The devil is in the specificity: the negative effect of prediction specificity on prediction accuracy.

    PubMed

    Yoon, Song-Oh; Suk, Kwanho; Goo, Jin Kyung; Lee, Jiheon; Lee, Seon Min

    2013-07-01

    In the research reported here, we proposed and demonstrated the prediction-specificity effect, which states that people's prediction of the general outcome of an event (e.g., the winner of a soccer match) is less accurate when the prediction question is framed in a more specific manner (e.g., guessing the score) rather than in a less specific manner (e.g., guessing the winner). We demonstrated this effect by examining people's predictions on actual sports games both in field and laboratory studies. In Study 1, the analysis of 19 billion bets from a commercial sports-betting business provided evidence for the effect of prediction specificity. This effect was replicated in three controlled laboratory studies, in which participants predicted the outcomes of a series of soccer matches. Furthermore, the negative effect of prediction specificity was mediated by participants' underweighting of important holistic information during decision making.

  17. Effects of domain-specific exercise load on speed and accuracy of a domain-specific perceptual-cognitive task.

    PubMed

    Schapschröer, M; Baker, J; Schorer, J

    2016-08-01

    In the context of perceptual-cognitive expertise it is important to know whether physiological loads influence perceptual-cognitive performance. This study examined whether a handball specific physical exercise load influenced participants' speed and accuracy in a flicker task. At rest and during a specific interval exercise of 86.5-90% HRmax, 35 participants (experts: n=8, advanced: n=13, novices, n=14) performed a handball specific flicker task with two types of patterns (structured and unstructured). For reaction time, results revealed moderate effect sizes for group, with experts reacting faster than advanced and advanced reacting faster than novices, and for structure, with structured videos being performed faster than unstructured ones. A significant interaction for structure×group was also found, with experts and advanced players faster for structured videos, and novices faster for unstructured videos. For accuracy, significant main effects were found for structure with structured videos solved more accurately. A significant interaction for structure×group was revealed, with experts and advanced more accurate for structured scenes and novices more accurate for unstructured scenes. A significant interaction was also found for condition×structure; at rest, unstructured and structured scenes were performed with the same accuracy while under physical exercise, structured scenes were solved more accurately. No other interactions were found. These results were somewhat surprising given previous work in this area, although the impact of a specific physical exercise on a specific perceptual-cognitive task may be different from those tested generally.

  18. Comparative assessment of thematic accuracy of GLC maps for specific applications using existing reference data

    NASA Astrophysics Data System (ADS)

    Tsendbazar, N. E.; de Bruin, S.; Mora, B.; Schouten, L.; Herold, M.

    2016-02-01

    Inputs to various applications and models, current global land cover (GLC) maps are based on different data sources and methods. Therefore, comparing GLC maps is challenging. Statistical comparison of GLC maps is further complicated by the lack of a reference dataset that is suitable for validating multiple maps. This study utilizes the existing Globcover-2005 reference dataset to compare thematic accuracies of three GLC maps for the year 2005 (Globcover, LC-CCI and MODIS). We translated and reinterpreted the LCCS (land cover classification system) classifier information of the reference dataset into the different map legends. The three maps were evaluated for a variety of applications, i.e., general circulation models, dynamic global vegetation models, agriculture assessments, carbon estimation and biodiversity assessments, using weighted accuracy assessment. Based on the impact of land cover confusions on the overall weighted accuracy of the GLC maps, we identified map improvement priorities. Overall accuracies were 70.8 ± 1.4%, 71.4 ± 1.3%, and 61.3 ± 1.5% for LC-CCI, MODIS, and Globcover, respectively. Weighted accuracy assessments produced increased overall accuracies (80-93%) since not all class confusion errors are important for specific applications. As a common denominator for all applications, the classes mixed trees, shrubs, grasses, and cropland were identified as improvement priorities. The results demonstrate the necessity of accounting for dissimilarities in the importance of map classification errors for different user application. To determine the fitness of use of GLC maps, accuracy of GLC maps should be assessed per application; there is no single-figure accuracy estimate expressing map fitness for all purposes.

  19. McNemar chi2 test revisited: comparing sensitivity and specificity of diagnostic examinations.

    PubMed

    Trajman, A; Luiz, R R

    2008-01-01

    When evaluating a novel diagnostic examination for clinical use, it should be compared with a reference standard, defined as the best available examination, which may include clinical and laboratory criteria. The novel examination and reference standard's results are usually presented in the form of a 2 x 2 table, which allows calculation of sensitivity, specificity and accuracy. It has been recommended that the measures of statistical uncertainty should be reported, such as the 95% confidence interval, when evaluating the accuracy of diagnostic examinations. Comparing the difference in sensitivity or specificity of a novel examination with the reference standard is important when evaluating its usefulness. The McNemar chi(2) test, used to compare discordance of two dichotomous responses, can be applied for this purpose. However, applying the McNemar test to a 2 x 2 table for comparing the accuracy of examinations is not recommended, since this test is sensitive to the proportion of positive versus negative subjects. Moreover, if the novel examination has higher sensitivity than the one considered as the reference standard, constructing a classic 2 x 2 table would result in low specificity of the novel examination. Thus, in order to compare sensitivities and specificities between examinations, this table is inappropriate and an independent reference standard is necessary. In this article, we propose the use of the McNemar chi(2) test to compare sensitivities between examinations using a 2 x 2 table exclusively among diseased patients, defined by a set of criteria and follow-up of patients. Likewise, specificities can be compared applying the McNemar test among healthy individuals.

  20. Site-specific DNA-antibody conjugates for specific and sensitive immuno-PCR

    PubMed Central

    Kazane, Stephanie A.; Sok, Devin; Cho, Edward H.; Uson, Maria Loressa; Kuhn, Peter; Schultz, Peter G.; Smider, Vaughn V.

    2012-01-01

    Antibody conjugates are widely used as diagnostics and imaging reagents. However, many such conjugates suffer losses in sensitivity and specificity due to nonspecific labeling techniques. We have developed methodology to site-specifically conjugate oligonucleotides to antibodies containing a genetically encoded unnatural amino acid with orthogonal chemical reactivity. These oligobody molecules were used in immuno-PCR assays to detect Her2+ cells with greater sensitivity and specificity than nonspecifically coupled fragments, and can detect extremely rare Her2+ cells in a complex cellular environment. Such designed antibody-oligonucleotide conjugates should provide sensitive and specific reagents for diagnostics, as well as enable other unique applications based on oligobody building blocks. PMID:22345566

  1. Confidence interval estimation for sensitivity at a fixed level of specificity for combined biomarkers.

    PubMed

    Tian, Lili

    2013-05-01

    In diagnostic studies, we often need to combine several biomarkers to increase the diagnostic accuracy. For continuous-scaled biomarkers or diagnostic tests, it is often of interest to estimate the confidence interval for sensitivity at a fixed level of specificity. Despite the fact that there exist many literature reports on confidence interval estimation of sensitivity at a fixed level of specificity for a single marker, the inference procedures for sensitivity at a fixed level of specificity for combined markers have rarely been addressed. This article fills this gap by investigating a generalized variable procedure for this purpose. The performance of the proposed generalized approach is numerically studied. For the optimal linear combination proposed by Su and Liu ( 1993 ), simulation study demonstrates that the proposed approach generally can provide confidence intervals with excellent coverage probabilities. The robustness of the proposed approach is investigated for categorical data. In the end, the proposed approach is applied to a real-life data set.

  2. Advancing the speed, sensitivity and accuracy of biomolecular detection using multi-length-scale engineering

    PubMed Central

    Kelley, Shana O.; Mirkin, Chad A.; Walt, David R.; Ismagilov, Rustem F.; Toner, Mehmet; Sargent, Edward H.

    2015-01-01

    Rapid progress in identifying disease biomarkers has increased the importance of creating high-performance detection technologies. Over the last decade, the design of many detection platforms has focused on either the nano or micro length scale. Here, we review recent strategies that combine nano- and microscale materials and devices to produce large improvements in detection sensitivity, speed and accuracy, allowing previously undetectable biomarkers to be identified in clinical samples. Microsensors that incorporate nanoscale features can now rapidly detect disease-related nucleic acids expressed in patient samples. New microdevices that separate large clinical samples into nanocompartments allow precise quantitation of analytes, and microfluidic systems that utilize nanoscale binding events can detect rare cancer cells in the bloodstream more accurately than before. These advances will lead to faster and more reliable clinical diagnostic devices. PMID:25466541

  3. Advancing the speed, sensitivity and accuracy of biomolecular detection using multi-length-scale engineering

    NASA Astrophysics Data System (ADS)

    Kelley, Shana O.; Mirkin, Chad A.; Walt, David R.; Ismagilov, Rustem F.; Toner, Mehmet; Sargent, Edward H.

    2014-12-01

    Rapid progress in identifying disease biomarkers has increased the importance of creating high-performance detection technologies. Over the last decade, the design of many detection platforms has focused on either the nano or micro length scale. Here, we review recent strategies that combine nano- and microscale materials and devices to produce large improvements in detection sensitivity, speed and accuracy, allowing previously undetectable biomarkers to be identified in clinical samples. Microsensors that incorporate nanoscale features can now rapidly detect disease-related nucleic acids expressed in patient samples. New microdevices that separate large clinical samples into nanocompartments allow precise quantitation of analytes, and microfluidic systems that utilize nanoscale binding events can detect rare cancer cells in the bloodstream more accurately than before. These advances will lead to faster and more reliable clinical diagnostic devices.

  4. High accuracy measurements of the intrapixel sensitivity of VIS to LWIR astronomical detectors: experimental demonstration

    NASA Astrophysics Data System (ADS)

    Viale, T.; Ketchazo, C.; Guérineau, N.; Boulade, O.; de la Barrière, F.; Moreau, V.; Mugnier, L.; Dubreuil, D.; Bonnefois, A.; Delisle, C.; Druart, G.; Mulet, P.

    2016-08-01

    The reduction of systematic effects is necessary to improve the accuracy in imaging and astrometry. For example, in Euclid Mission which aims at carrying out accurate measurements of dark energy and quantifying precisely its role in the evolution of the Universe, systematic effects need at be controlled to a level better than 10-7 (Euclid, Science Book). To achieve this goal, a high-level of knowledge of the system point spread function (PSF) is required. This paper follows the concept-paper presented at the last SPIE conference1 and gives the recent developments achieved in the design of the test bench for the intrapixel sensitivity measurements. The measurement technique we use is based on the projection of a high spatial resolution periodic pattern on the detector using the self-imaging property of a new class of diffractive objects named continuously self-imaging gratings (CSIG) and developed at ONERA. The principle combines the potential of global techniques, which make measurements at once on the whole FPA, and the accuracy of spot-scan-based techniques, which provide high local precision.

  5. Requirements for Minimum Sample Size for Sensitivity and Specificity Analysis

    PubMed Central

    Adnan, Tassha Hilda

    2016-01-01

    Sensitivity and specificity analysis is commonly used for screening and diagnostic tests. The main issue researchers face is to determine the sufficient sample sizes that are related with screening and diagnostic studies. Although the formula for sample size calculation is available but concerning majority of the researchers are not mathematicians or statisticians, hence, sample size calculation might not be easy for them. This review paper provides sample size tables with regards to sensitivity and specificity analysis. These tables were derived from formulation of sensitivity and specificity test using Power Analysis and Sample Size (PASS) software based on desired type I error, power and effect size. The approaches on how to use the tables were also discussed. PMID:27891446

  6. Travel-time source-specific station correction improves location accuracy

    NASA Astrophysics Data System (ADS)

    Giuntini, Alessandra; Materni, Valerio; Chiappini, Stefano; Carluccio, Roberto; Console, Rodolfo; Chiappini, Massimo

    2013-04-01

    Accurate earthquake locations are crucial for investigating seismogenic processes, as well as for applications like verifying compliance to the Comprehensive Test Ban Treaty (CTBT). Earthquake location accuracy is related to the degree of knowledge about the 3-D structure of seismic wave velocity in the Earth. It is well known that modeling errors of calculated travel times may have the effect of shifting the computed epicenters far from the real locations by a distance even larger than the size of the statistical error ellipses, regardless of the accuracy in picking seismic phase arrivals. The consequences of large mislocations of seismic events in the context of the CTBT verification is particularly critical in order to trigger a possible On Site Inspection (OSI). In fact, the Treaty establishes that an OSI area cannot be larger than 1000 km2, and its larger linear dimension cannot be larger than 50 km. Moreover, depth accuracy is crucial for the application of the depth event screening criterion. In the present study, we develop a method of source-specific travel times corrections based on a set of well located events recorded by dense national seismic networks in seismically active regions. The applications concern seismic sequences recorded in Japan, Iran and Italy. We show that mislocations of the order of 10-20 km affecting the epicenters, as well as larger mislocations in hypocentral depths, calculated from a global seismic network and using the standard IASPEI91 travel times can be effectively removed by applying source-specific station corrections.

  7. Soccer-specific accuracy and validity of the local position measurement (LPM) system.

    PubMed

    Frencken, Wouter G P; Lemmink, Koen A P M; Delleman, Nico J

    2010-11-01

    Limited data is available on accuracy and validity of video-based, GPS and electronic tracking systems, particularly with reference to curved courses and short high intensity running activities. The main goal of this study was to assess soccer-specific accuracy and validity of the radio-frequency based local position measurement (LPM) system (1000Hz) for measuring distance and speed during walking and sprinting. Three males walked and sprinted 4 soccer-specific courses 10 times each. Distance and speed recorded by LPM were compared to actual distance and speed measured by measuring tape and timing gates. In addition, accuracy was assessed. The static accuracy (SD of the mean) is 1cm for devices put on the pitch and 2-3 cm when worn by participants. LPM underestimates actual distance (mean difference at most -1.6%). Coefficient of variation becomes larger at higher speed and increased turning angle. With regard to speed, validity correlations are high (range: 0.71-0.97). The LPM speed is significantly and systematically lower, although absolute and relative differences are small, between -0.1 km h⁻¹ (-1.3%) and -0.6 km h⁻¹ (-3.9%). The typical error of the estimate increases with increased speed, but does not increase with increased turning angle. Because the reported differences are small, we conclude that the LPM-system produces highly accurate position and speed data in static and dynamic conditions and is a valid tool for player tracking in soccer and ball team sports in general.

  8. Sensitivity and Specificity of Histoplasma Antigen Detection by Enzyme Immunoassay.

    PubMed

    Cunningham, Lauren; Cook, Audrey; Hanzlicek, Andrew; Harkin, Kenneth; Wheat, Joseph; Goad, Carla; Kirsch, Emily

    2015-01-01

    The objective of this study was to evaluate the sensitivity and specificity of an antigen enzyme immunoassay (EIA) on urine samples for the diagnosis of histoplasmosis in dogs. This retrospective medical records review included canine cases with urine samples submitted for Histoplasma EIA antigen assay between 2007 and 2011 from three veterinary institutions. Cases for which urine samples were submitted for Histoplasma antigen testing were reviewed and compared to the gold standard of finding Histoplasma organisms or an alternative diagnosis on cytology or histopathology. Sensitivity, specificity, negative predictive value, positive predictive value, and the kappa coefficient and associated confidence interval were calculated for the EIA-based Histoplasma antigen assay. Sixty cases met the inclusion criteria. Seventeen cases were considered true positives based on identification of the organism, and 41 cases were considered true negatives with an alternative definitive diagnosis. Two cases were considered false negatives, and there were no false positives. Sensitivity was 89.47% and the negative predictive value was 95.35%. Specificity and the positive predictive value were both 100%. The kappa coefficient was 0.9207 (95% confidence interval, 0.8131-1). The Histoplasma antigen EIA test demonstrated high specificity and sensitivity for the diagnosis of histoplasmosis in dogs.

  9. A material sensitivity study on the accuracy of deformable organ registration using linear biomechanical models.

    PubMed

    Chi, Y; Liang, J; Yan, D

    2006-02-01

    Model-based deformable organ registration techniques using the finite element method (FEM) have recently been investigated intensively and applied to image-guided adaptive radiotherapy (IGART). These techniques assume that human organs are linearly elastic material, and their mechanical properties are predetermined. Unfortunately, the accurate measurement of the tissue material properties is challenging and the properties usually vary between patients. A common issue is therefore the achievable accuracy of the calculation due to the limited access to tissue elastic material constants. In this study, we performed a systematic investigation on this subject based on tissue biomechanics and computer simulations to establish the relationships between achievable registration accuracy and tissue mechanical and organ geometrical properties. Primarily we focused on image registration for three organs: rectal wall, bladder wall, and prostate. The tissue anisotropy due to orientation preference in tissue fiber alignment is captured by using an orthotropic or a transversely isotropic elastic model. First we developed biomechanical models for the rectal wall, bladder wall, and prostate using simplified geometries and investigated the effect of varying material parameters on the resulting organ deformation. Then computer models based on patient image data were constructed, and image registrations were performed. The sensitivity of registration errors was studied by perturbating the tissue material properties from their mean values while fixing the boundary conditions. The simulation results demonstrated that registration error for a subvolume increases as its distance from the boundary increases. Also, a variable associated with material stability was found to be a dominant factor in registration accuracy in the context of material uncertainty. For hollow thin organs such as rectal walls and bladder walls, the registration errors are limited. Given 30% in material uncertainty

  10. A material sensitivity study on the accuracy of deformable organ registration using linear biomechanical models

    SciTech Connect

    Chi, Y.; Liang, J.; Yan, D.

    2006-02-15

    Model-based deformable organ registration techniques using the finite element method (FEM) have recently been investigated intensively and applied to image-guided adaptive radiotherapy (IGART). These techniques assume that human organs are linearly elastic material, and their mechanical properties are predetermined. Unfortunately, the accurate measurement of the tissue material properties is challenging and the properties usually vary between patients. A common issue is therefore the achievable accuracy of the calculation due to the limited access to tissue elastic material constants. In this study, we performed a systematic investigation on this subject based on tissue biomechanics and computer simulations to establish the relationships between achievable registration accuracy and tissue mechanical and organ geometrical properties. Primarily we focused on image registration for three organs: rectal wall, bladder wall, and prostate. The tissue anisotropy due to orientation preference in tissue fiber alignment is captured by using an orthotropic or a transversely isotropic elastic model. First we developed biomechanical models for the rectal wall, bladder wall, and prostate using simplified geometries and investigated the effect of varying material parameters on the resulting organ deformation. Then computer models based on patient image data were constructed, and image registrations were performed. The sensitivity of registration errors was studied by perturbating the tissue material properties from their mean values while fixing the boundary conditions. The simulation results demonstrated that registration error for a subvolume increases as its distance from the boundary increases. Also, a variable associated with material stability was found to be a dominant factor in registration accuracy in the context of material uncertainty. For hollow thin organs such as rectal walls and bladder walls, the registration errors are limited. Given 30% in material uncertainty

  11. Detailed high-accuracy megavoltage transmission measurements: A sensitive experimental benchmark of EGSnrc

    SciTech Connect

    Ali, E. S. M.; McEwen, M. R.; Rogers, D. W. O.

    2012-10-15

    Purpose: There are three goals for this study: (a) to perform detailed megavoltage transmission measurements in order to identify the factors that affect the measurement accuracy, (b) to use the measured data as a benchmark for the EGSnrc system in order to identify the computational limiting factors, and (c) to provide data for others to benchmark Monte Carlo codes. Methods: Transmission measurements are performed at the National Research Council Canada on a research linac whose incident electron parameters are independently known. Automated transmission measurements are made on-axis, down to a transmission value of {approx}1.7%, for eight beams between 10 MV (the lowest stable MV beam on the linac) and 30 MV, using fully stopping Be, Al, and Pb bremsstrahlung targets and no fattening filters. To diversify energy differentiation, data are acquired for each beam using low-Z and high-Z attenuators (C and Pb) and Farmer chambers with low-Z and high-Z buildup caps. Experimental corrections are applied for beam drifts (2%), polarity (2.5% typical maximum, 6% extreme), ion recombination (0.2%), leakage (0.3%), and room scatter (0.8%)-the values in parentheses are the largest corrections applied. The experimental setup and the detectors are modeled using EGSnrc, with the newly added photonuclear attenuation included (up to a 5.6% effect). A detailed sensitivity analysis is carried out for the measured and calculated transmission data. Results: The developed experimental protocol allows for transmission measurements with 0.4% uncertainty on the smallest signals. Suggestions for accurate transmission measurements are provided. Measurements and EGSnrc calculations agree typically within 0.2% for the sensitivity of the transmission values to the detector details, to the bremsstrahlung target material, and to the incident electron energy. Direct comparison of the measured and calculated transmission data shows agreement better than 2% for C (3.4% for the 10 MV beam) and

  12. Accuracy and efficacy of osteotomy in total knee arthroplasty with patient-specific navigational template

    PubMed Central

    Gan, Yudong; Ding, Jing; Xu, Yongqing; Hou, Chunlin

    2015-01-01

    This study develops and validates a novel patient-specific navigational template for total knee arthroplasty (TKA). A total of 70 patients who underwent TKA were randomized and divided into conventional method group and navigational template group. In the navigational template group, the patient-specific navigational templates were designed and used intraoperatively to assist 35 patients with knee arthroplasty. Information on operation time and blood loss was recorded. After surgery, the positions of the prosthesis were evaluated using CT scan and X-rays. Analysis showed significant differences in errors between the two techniques. In addition, mean operation time and mean blood loss were statistically and significantly lower in the navigational template group than in the conventional group. Overall, the navigational template method showed a high degree of accuracy and efficacy. PMID:26550129

  13. Sensitivity and specificity of WAIS-III/WMS-III demographically corrected factor scores in neuropsychological assessment.

    PubMed

    Taylor, M J; Heaton, R K

    2001-11-01

    This study explored the neurodiagnostic utility of 6 factor scores identified by recent exploratory and confirmatory factor analyses of the WAIS-III and WMS-III: Verbal Comprehension, Perceptual Organization, Processing Speed, Working Memory, Auditory Memory and Visual Memory. Factor scores were corrected for age. education, sex and ethnicity to minimize their influences on diagnostic accuracy. Cut-offs at 1, 1.5 and 2 standard deviations (SDs) below the standardization sample mean were applied to data from the overlapping test normative samples (N = 1073) and 6 clinical samples described in the WAIS-III/WMS-III Technical Manual (N = 126). The analyses suggest that a I SD cut-off yields the most balanced levels of sensitivity and specificity; more strict (1.5 or 2 SD) cut-offs generally result in trading modest gains in specificity for larger losses in sensitivity. Finally, using combinations of WAIS-III/WMS-III factors together as test batteries, we explored the sensitivity and specificity implications of varying diagnostic decision rules (e.g.,1 vs. 2 impaired factors = "impairment"). For most of the disorders considered here, even a small (e.g., 3 factor) WAIS-III/WMS-III battery provides quite good overall diagnostic accuracy.

  14. Specific and sensitive radioimmunoassay for 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG)

    SciTech Connect

    Keeton, T.K.; Krutzsch, H.; Lovenberg, W.

    1981-02-06

    Antibodies that specifically bind the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG) were produced in rabbits after injection of a derivative of MOPEG conjugated with bovine thyroglobulin. A sensitive radioimmunoassay was devised with this antiserum, in which as little as 0.5 nanogram of MOPEG can be accurately measured with a final antibody dilution of 1:180. The antibody appears to be specific for MOPEG, since tritiated MOPEG was not displaced from the antibodies by norepinephrine, epinephrine, dopamine, serotonin, or their major metabolites, including MOPEG-sulfate (333 nanograms each).

  15. Size-specific sensitivity: Applying a new structured population model

    SciTech Connect

    Easterling, M.R.; Ellner, S.P.; Dixon, P.M.

    2000-03-01

    Matrix population models require the population to be divided into discrete stage classes. In many cases, especially when classes are defined by a continuous variable, such as length or mass, there are no natural breakpoints, and the division is artificial. The authors introduce the integral projection model, which eliminates the need for division into discrete classes, without requiring any additional biological assumptions. Like a traditional matrix model, the integral projection model provides estimates of the asymptotic growth rate, stable size distribution, reproductive values, and sensitivities of the growth rate to changes in vital rates. However, where the matrix model represents the size distributions, reproductive value, and sensitivities as step functions (constant within a stage class), the integral projection model yields smooth curves for each of these as a function of individual size. The authors describe a method for fitting the model to data, and they apply this method to data on an endangered plant species, northern monkshood (Aconitum noveboracense), with individuals classified by stem diameter. The matrix and integral models yield similar estimates of the asymptotic growth rate, but the reproductive values and sensitivities in the matrix model are sensitive to the choice of stage classes. The integral projection model avoids this problem and yields size-specific sensitivities that are not affected by stage duration. These general properties of the integral projection model will make it advantageous for other populations where there is no natural division of individuals into stage classes.

  16. Sensitivity and specificity of parallel or serial serological testing for detection of canine Leishmania infection.

    PubMed

    Arruda, Mauro Maciel de; Figueiredo, Fabiano Borges; Marcelino, Andreza Pain; Barbosa, José Ronaldo; Werneck, Guilherme Loureiro; Noronha, Elza Ferreira; Romero, Gustavo Adolfo Sierra

    2016-03-01

    In Brazil, human and canine visceral leishmaniasis (CVL) caused by Leishmania infantum has undergone urbanisation since 1980, constituting a public health problem, and serological tests are tools of choice for identifying infected dogs. Until recently, the Brazilian zoonoses control program recommended enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescence assays (IFA) as the screening and confirmatory methods, respectively, for the detection of canine infection. The purpose of this study was to estimate the accuracy of ELISA and IFA in parallel or serial combinations. The reference standard comprised the results of direct visualisation of parasites in histological sections, immunohistochemical test, or isolation of the parasite in culture. Samples from 98 cases and 1,327 noncases were included. Individually, both tests presented sensitivity of 91.8% and 90.8%, and specificity of 83.4 and 53.4%, for the ELISA and IFA, respectively. When tests were used in parallel combination, sensitivity attained 99.2%, while specificity dropped to 44.8%. When used in serial combination (ELISA followed by IFA), decreased sensitivity (83.3%) and increased specificity (92.5%) were observed. Serial testing approach improved specificity with moderate loss in sensitivity. This strategy could partially fulfill the needs of public health and dog owners for a more accurate diagnosis of CVL.

  17. Does McNemar's test compare the sensitivities and specificities of two diagnostic tests?

    PubMed

    Kim, Soeun; Lee, Woojoo

    2017-02-01

    McNemar's test is often used in practice to compare the sensitivities and specificities for the evaluation of two diagnostic tests. For correct evaluation of accuracy, an intuitive recommendation is to test the diseased and the non-diseased groups separately so that the sensitivities can be compared among the diseased, and specificities can be compared among the healthy group of people. This paper provides a rigorous theoretical framework for this argument and study the validity of McNemar's test regardless of the conditional independence assumption. We derive McNemar's test statistic under the null hypothesis considering both assumptions of conditional independence and conditional dependence. We then perform power analyses to show how the result is affected by the amount of the conditional dependence under alternative hypothesis.

  18. Spatial variability in sensitivity of reference crop ET to accuracy of climate data in the Texas High Plains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A detailed sensitivity analysis was conducted to determine the relative effects of measurement errors in climate data input parameters on the accuracy of calculated reference crop evapotranspiration (ET) using the ASCE-EWRI Standardized Reference ET Equation. Data for the period of 1995 to 2008, fro...

  19. Factors affecting sensitivity and specificity of a diagnostic test: the exercise thallium scintigram

    SciTech Connect

    Detrano, R.; Janosi, A.; Lyons, K.P.; Marcondes, G.; Abbassi, N.; Froelicher, V.F.

    1988-04-01

    Technical and methodological factors might affect the reported accuracies of diagnostic tests. To assess their influence on the accuracy of exercise thallium scintigraphy, the medical literature (1977 to 1986) was non-selectively searched and meta-analysis was applied to the 56 publications thus retrieved. These were analyzed for year of publication, sex and mean age of patients, percentage of patients with angina pectoris, percentage of patients with prior myocardial infarction, percentage of patients taking beta-blocking medications, and for angiographic referral (workup) bias, blinding of tests, and technical factors. The percentage of patients with myocardial infarction had the highest correlation with sensitivity (0.45, p = 0.0007). Only the inclusion of subjects with prior infarction and the percentage of men in the study group were independently and significantly (p less than 0.05) related to test sensitivity. Both the presence of workup bias and publication year adversely affected specificity (p less than 0.05). Of these two factors, publication year had the strongest association by stepwise linear regression. This analysis suggests that the reported sensitivity of thallium scintigraphy is higher and the specificity lower than that expected in clinical practice because of the presence of workup bias and the inappropriate inclusion of post-infarct patients.

  20. HPV 9G DNA chip: 100% clinical sensitivity and specificity.

    PubMed

    An, Heejung; Song, Keum-Soo; Nimse, Satish Balasaheb; Kim, Junghoon; Nguyen, Van-Thuan; Ta, Van-Thao; Sayyed, Danishmalik Rafiq; Kim, Taisun

    2012-03-01

    We describe a novel HPV 9G DNA chip test for the accurate and reliable genotyping of human papillomavirus (HPV). The HPV 9G DNA chip test established its efficiency in terms of a signal-to-background ratio (SBR) of 200, which is 50 times superior to commercial HPV DNA chips, and 100% target-specific hybridization at 25°C. We compared the genotyping results for the 439 clinical samples by the HPV 9G DNA chip test with the sequencing results for the MY11/GP6+ (M2) primer set-mediated PCR products. The discrimination of HPV genotypes in the 151 HPV-positive clinical samples by the HPV 9G DNA chip test were 100% identical with the sequencing analysis. The clinical sensitivities of HPV genotyping by the HPV 9G DNA chip test and a commercial HPV DNA chip test were 100% and 88%, respectively. However, the clinical specificities of HPV genotyping by the HPV 9G DNA chip test and the commercial HPV DNA chip test were 100% and 94%, respectively. The 100% clinical sensitivity and specificity of the HPV 9G DNA chip test make it a promising diagnostic tool for HPV genotyping.

  1. Accuracy of Computational Cerebral Aneurysm Hemodynamics Using Patient-Specific Endovascular Measurements

    NASA Astrophysics Data System (ADS)

    McGah, Patrick; Levitt, Michael; Barbour, Michael; Mourad, Pierre; Kim, Louis; Aliseda, Alberto

    2013-11-01

    We study the hemodynamic conditions in patients with cerebral aneurysms through endovascular measurements and computational fluid dynamics. Ten unruptured cerebral aneurysms were clinically assessed by three dimensional rotational angiography and an endovascular guidewire with dual Doppler ultrasound transducer and piezoresistive pressure sensor at multiple peri-aneurysmal locations. These measurements are used to define boundary conditions for flow simulations at and near the aneurysms. The additional in vivo measurements, which were not prescribed in the simulation, are used to assess the accuracy of the simulated flow velocity and pressure. We also performed simulations with stereotypical literature-derived boundary conditions. Simulated velocities using patient-specific boundary conditions showed good agreement with the guidewire measurements, with no systematic bias and a random scatter of about 25%. Simulated velocities using the literature-derived values showed a systematic over-prediction in velocity by 30% with a random scatter of about 40%. Computational hemodynamics using endovascularly-derived patient-specific boundary conditions have the potential to improve treatment predictions as they provide more accurate and precise results of the aneurysmal hemodynamics. Supported by an R03 grant from NIH/NINDS

  2. Accuracy of Optimized Branched Algorithms to Assess Activity-Specific PAEE

    PubMed Central

    Edwards, Andy G.; Hill, James O.; Byrnes, William C.; Browning, Raymond C.

    2009-01-01

    PURPOSE To assess the activity-specific accuracy achievable by branched algorithm (BA) analysis of simulated daily-living physical activity energy expenditure (PAEE) within a sedentary population. METHODS Sedentary men (n=8) and women (n=8) first performed a treadmill calibration protocol, during which heart rate (HR), accelerometry (ACC), and PAEE were measured in 1-minute epochs. From these data, HR-PAEE, and ACC-PAEE regressions were constructed and used in each of six analytic models to predict PAEE from ACC and HR data collected during a subsequent simulated daily-living protocol. Criterion PAEE was measured during both protocols via indirect calorimetry. The accuracy achieved by each model was assessed by the root mean square of the difference between model-predicted daily–living PAEE and the criterion daily-living PAEE (expressed here as % of mean daily living PAEE). RESULTS Across the range of activities an unconstrained post hoc optimized branched algorithm best predicted criterion PAEE. Estimates using individual calibration were generally more accurate than those using group calibration (14 vs. 16 % error, respectively). These analyses also performed well within each of the six daily-living activities, but systematic errors appeared for several of those activities, which may be explained by an inability of the algorithm to simultaneously accommodate a heterogeneous range of activities. Analyses of between mean square error by subject and activity suggest that optimization involving minimization of RMS for total daily-living PAEE is associated with decreased error between subjects but increased error between activities. CONCLUSION The performance of post hoc optimized branched algorithms may be limited by heterogeneity in the daily-living activities being performed. PMID:19952842

  3. Real-Word and Nonword Repetition in Italian-Speaking Children with Specific Language Impairment: A Study of Diagnostic Accuracy

    PubMed Central

    Dispaldro, Marco; Leonard, Laurence B.; Deevy, Patricia

    2013-01-01

    Purpose: Using two different scoring methods, we examined the diagnostic accuracy of both real-word and nonword repetition in identifying Italian-speaking children with and without specific language impairment (SLI). Method: A total of 34 children aged 3;11 to 5;8 participated – 17 children with SLI and 17 typically developing children matched for age (TD-A children). Children completed real-word and nonword repetition tasks. The capacity of real-word and nonword repetition tasks to discriminate children with SLI from TD-A was examined through binary logistic regression and response operating characteristics curves. Results: Both real-word and nonword repetition showed good (or excellent) sensitivity and specificity in distinguishing children with SLI from their typically developing peers. Conclusions: Nonword repetition appears to be a useful diagnostic indicator for Italian, as in other languages. In addition, real-word repetition also holds promise. The contributions of each type of measure are discussed. PMID:22761319

  4. Diagnosing synaesthesia with online colour pickers: maximising sensitivity and specificity.

    PubMed

    Rothen, Nicolas; Seth, Anil K; Witzel, Christoph; Ward, Jamie

    2013-04-30

    The most commonly used method for formally assessing grapheme-colour synaesthesia (i.e., experiencing colours in response to letter and/or number stimuli) involves selecting colours from a large colour palette on several occasions and measuring consistency of the colours selected. However, the ability to diagnose synaesthesia using this method depends on several factors that have not been directly contrasted. These include the type of colour space used (e.g., RGB, HSV, CIELUV, CIELAB) and different measures of consistency (e.g., city block and Euclidean distance in colour space). This study aims to find the most reliable way of diagnosing grapheme-colour synaesthesia based on maximising sensitivity (i.e., ability of a test to identify true synaesthetes) and specificity (i.e., ability of a test to identify true non-synaesthetes). We show, applying ROC (receiver operating characteristics) to binary classification of a large sample of self-declared synaesthetes and non-synaesthetes, that the consistency criterion (i.e., cut-off value) for diagnosing synaesthesia is considerably higher than the current standard in the field. We also show that methods based on perceptual CIELUV and CIELAB colour models (rather than RGB and HSV colour representations) and Euclidean distances offer an even greater sensitivity and specificity than most currently used measures. Together, these findings offer improved heuristics for the behavioural assessment of grapheme-colour synaesthesia.

  5. Sensitivity and Specificity of Hypnosis Effects on Gastric Myoelectrical Activity

    PubMed Central

    Enck, Paul; Weimer, Katja; Muth, Eric R.; Zipfel, Stephan; Martens, Ute

    2013-01-01

    Objectives The effects of hypnosis on physiological (gastrointestinal) functions are incompletely understood, and it is unknown whether they are hypnosis-specific and gut-specific, or simply unspecific effects of relaxation. Design Sixty-two healthy female volunteers were randomly assigned to either a single session of hypnotic suggestion of ingesting an appetizing meal and an unappetizing meal, or to relax and concentrate on having an appetizing or unappetizing meal, while the electrogastrogram (EGG) was recorded. At the end of the session, participants drank water until they felt full, in order to detect EGG-signal changes after ingestion of a true gastric load. During both conditions participants reported their subjective well-being, hunger and disgust at several time points. Results Imagining eating food induced subjective feelings of hunger and disgust as well as changes in the EGG similar to, but more pronounced than those seen with a real gastric water load during both hypnosis and relaxation conditions. These effects were more pronounced when imagining an appetizing meal than with an unappetizing meal. There was no significant difference between the hypnosis and relaxation conditions. Conclusion Imagination with and without hypnosis exhibits similar changes in subjective and objective measures in response to imagining an appetizing and an unappetizing food, indicating high sensitivity but low specificity. PMID:24358287

  6. Sensitivity and specificity of the Major Depression Inventory in outpatients

    PubMed Central

    Cuijpers, Pim; Dekker, Jack; Noteboom, Annemieke; Smits, Niels; Peen, Jaap

    2007-01-01

    Background The Major Depression Inventory (MDI) is a new, brief, self-report measure for depression based on the DSM-system, which allows clinicians to assess the presence of a depressive disorder according to the DSM-IV, but also to assess the severity of the depressive symptoms. Methods We examined the sensitivity, specificity, and psychometric qualities of the MDI in a consecutive sample of 258 psychiatric outpatients. Of these patients, 120 had a mood disorder (70 major depression, 49 dysthymia). A total of 139 subjects had a comorbid axis-I diagnosis, and 91 subjects had a comorbid personality disorder. Results Crohnbach's alpha of the MDI was a satisfactory 0.89, and the correlation between the MDI and the depression subscale of the SCL-90 was 0.79 (p < .001). Subjects with major depressive disorder (MDD) had a significantly higher MDI score than subjects with anxiety disorders (but no MDD), dysthymias, bipolar, psychotic, other neurotic disorders, and subjects with relational problems. In ROC analysis we found that the area under the curve was 0.68 for the MDI. A good cut-off point for the MDI seems to be 26, with a sensitivity of 0.66, and a specificity of 0.63. The indication of the presence of MDD based on the MDI had a moderate agreement with the diagnosis made by a psychiatrist (kappa: 0.26). Conclusion The MDI is an attractive, brief depression inventory, which seems to be a reliable tool for assessing depression in psychiatric outpatients. PMID:17688685

  7. Sensitivity of subject-specific models to errors in musculo-skeletal geometry.

    PubMed

    Carbone, V; van der Krogt, M M; Koopman, H F J M; Verdonschot, N

    2012-09-21

    Subject-specific musculo-skeletal models of the lower extremity are an important tool for investigating various biomechanical problems, for instance the results of surgery such as joint replacements and tendon transfers. The aim of this study was to assess the potential effects of errors in musculo-skeletal geometry on subject-specific model results. We performed an extensive sensitivity analysis to quantify the effect of the perturbation of origin, insertion and via points of each of the 56 musculo-tendon parts contained in the model. We used two metrics, namely a Local Sensitivity Index (LSI) and an Overall Sensitivity Index (OSI), to distinguish the effect of the perturbation on the predicted force produced by only the perturbed musculo-tendon parts and by all the remaining musculo-tendon parts, respectively, during a simulated gait cycle. Results indicated that, for each musculo-tendon part, only two points show a significant sensitivity: its origin, or pseudo-origin, point and its insertion, or pseudo-insertion, point. The most sensitive points belong to those musculo-tendon parts that act as prime movers in the walking movement (insertion point of the Achilles Tendon: LSI=15.56%, OSI=7.17%; origin points of the Rectus Femoris: LSI=13.89%, OSI=2.44%) and as hip stabilizers (insertion points of the Gluteus Medius Anterior: LSI=17.92%, OSI=2.79%; insertion point of the Gluteus Minimus: LSI=21.71%, OSI=2.41%). The proposed priority list provides quantitative information to improve the predictive accuracy of subject-specific musculo-skeletal models.

  8. Effect of mesh distortion on the accuracy of transverse shear stresses and their sensitivity coefficients in multilayered composites

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Kim, Yong H.

    1995-01-01

    A study is made of the effect of mesh distortion on the accuracy of transverse shear stresses and their first-order and second-order sensitivity coefficients in multilayered composite panels subjected to mechanical and thermal loads. The panels are discretized by using a two-field degenerate solid element, with the fundamental unknowns consisting of both displacement and strain components, and the displacement components having a linear variation throughout the thickness of the laminate. A two-step computational procedure is used for evaluating the transverse shear stresses. In the first step, the in-plane stresses in the different layers are calculated at the numerical quadrature points for each element. In the second step, the transverse shear stresses are evaluated by using piecewise integration, in the thickness direction, of the three-dimensional equilibrium equations. The same procedure is used for evaluating the sensitivity coefficients of transverse shear stresses. Numerical results are presented showing no noticeable degradation in the accuracy of the in-plane stresses and their sensitivity coefficients with mesh distortion. However, such degradation is observed for the transverse shear stresses and their sensitivity coefficients. The standard of comparison is taken to be the exact solution of the three-dimensional thermoelasticity equations of the panel.

  9. A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody-based tests for detection of dengue infection.

    PubMed

    Alagarasu, K; Walimbe, A M; Jadhav, S M; Deoshatwar, A R

    2016-03-01

    Immunoglobulin A (IgA)-based tests have been evaluated in different studies for their utility in diagnosing dengue infections. In most of the studies, the results were inconclusive because of a small sample size. Hence, a meta-analysis involving nine studies with 2096 samples was performed to assess the diagnostic accuracy of IgA-based tests in diagnosing dengue infections. The analysis was conducted using Meta-Disc software. The results revealed that IgA-based tests had an overall sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratios of 73·9%, 95·2%, 66·7, 22·0 and 0·25, respectively. Significant heterogeneity was observed between the studies. The type of test, infection status and day of sample collection influenced the diagnostic accuracy. The IgA-based diagnostic tests showed a greater accuracy when the samples were collected 4 days after onset of symptoms and for secondary infections. The results suggested that IgA-based tests had a moderate level of accuracy and are diagnostic of the disease. However, negative results cannot be used alone for dengue diagnosis. More prospective studies comparing the diagnostic accuracy of combinations of antigen-based tests with either IgA or IgM are needed and might be useful for suggesting the best strategy for dengue diagnosis.

  10. Strategies to Improve the Accuracy of Mars-GRAM Sensitivity Studies at Large Optical Depths

    NASA Technical Reports Server (NTRS)

    Justh, Hilary L.; Justus, Carl G.; Badger, Andrew M.

    2010-01-01

    The poster provides an overview of techniques to improve the Mars Global Reference Atmospheric Model (Mars-GRAM) sensitivity. It has been discovered during the Mars Science Laboratory (MSL) site selection process that the Mars Global Reference Atmospheric Model (Mars-GRAM) when used for sensitivity studies for TES MapYear = 0 and large optical depth values such as tau = 3 is less than realistic. A preliminary fix has been made to Mars-GRAM by adding a density factor value that was determined for tau = 0.3, 1 and 3.

  11. Analysis of reliability, accuracy, sensitivity and predictive value of a subjective method to classify facial pattern in adults

    PubMed Central

    Queiroz, Gilberto Vilanova; Rino, José; de Paiva, João Batista; Capelozza, Leopoldino

    2016-01-01

    ABSTRACT Introduction: Craniofacial pattern diagnosis is vital in Orthodontics, as it influences decision-making regarding treatment options and prognosis. Capelozza Filho proposed a subjective method for facial classification comprising five patterns: I, II, III, Long Face and Short Face. Objective: To investigate the accuracy of a subjective classification method of facial patterns applied to adults. Methods: A sample consisting of 52 adults was used for this study. Frontal and lateral view photographs were taken with subjects at rest position, including frontal smile. Lateral cephalometric radiographs were organized in a PowerPoint® presentation and submitted to 20 raters. Method performance was assessed by examining reproducibility with Kappa test and calculating accuracy, sensitivity and positive predictive values, for which 70% was set as critical value. The gold standard of the classification was personally set by the author of the method. Results: Reproducibility was considered moderate (Kappa = 0.501); while accuracy, sensitivity and positive predictive values yielded similar results, but below 70%. Conclusions: The subjective method of facial classification employed in the present study still needs to have its morphological criteria improved in order to be used to discriminate the five facial patterns. PMID:28125141

  12. Bayesian estimation of diagnostic sensitivity and specificity of a nervous necrosis virus antibody ELISA.

    PubMed

    Jaramillo, Diana; Dürr, Salome; Hick, Paul; Whittington, Richard

    2016-01-01

    Diagnosis of nervous necrosis virus (NNV) infection in susceptible fish species is mostly performed post-mortem due to the neurotropism of the causative agent and the only validated diagnostic assays require samples from brain and retinal tissue. However, a non-lethal alternative to test for exposure of fish to NNV is needed. An indirect ELISA for the detection of anti-NNV antibodies in was recently developed and evaluated to detect responses in the sera from immunized fish. For this study, we assessed the accuracy of the assay at detecting specific antibodies from naturally exposed fish using field samples from populations with differing infection status. We applied a Bayesian model, using RTqPCR as a second test. Median estimates of the diagnostic sensitivity and specificity of the VNN ELISA were 81.8% and 86.7%, respectively. We concluded that the assay was fit for the purpose of identifying animals in naturally exposed populations. With further evaluation in larger populations the test might be used to inform implementation of control measures, and for estimating infection prevalence to facilitate risk analysis. To our knowledge this is the first report on the diagnostic accuracy of an antibody ELISA for an infectious disease in finfish.

  13. Real-Word and Nonword Repetition in Italian-Speaking Children with Specific Language Impairment: A Study of Diagnostic Accuracy

    ERIC Educational Resources Information Center

    Dispaldro, Marco; Leonard, Laurence B.; Deevy, Patricia

    2013-01-01

    Purpose: Using 2 different scoring methods, the authors examined the diagnostic accuracy of both real-word and nonword repetition in identifying Italian-speaking children with and without specific language impairment (SLI). Method: A total of 34 children ages 3;11-5;8 (years;months) participated--17 children with SLI and 17 typically developing…

  14. Specific fungal exposures, allergic sensitization, and rhinitis in infants.

    PubMed

    Osborne, Melissa; Reponen, Tiina; Adhikari, Atin; Cho, Seung-Hyun; Grinshpun, Sergey A; Levin, Linda; Bernstein, David I; LeMasters, Grace

    2006-09-01

    Indoor air quality has become increasingly important as we live in a society where the majority of our time is spent indoors. Specific attention has been drawn to airborne fungal spores as a factor affecting indoor air quality. This study targeted shortcomings of other studies by utilizing long-term air sampling and total fungal spore enumeration to determine associations between health outcomes and fungal spore concentrations. Infants (n = 144) were clinically evaluated and had skin prick tests (SPT) for 17 allergens. Airborne fungal spores were collected using a Button Personal Inhalable Sampler (SKC Inc.) for 48 h at a flow rate of 4 l/min. Sampling was conducted in the spring (March-May) or fall (August-October) in 2003-2004. Fungal spores were analyzed using microscopy-based total counting and identified to the genus/group level. Total spore and individual genus concentrations were analyzed for associations with rhinitis and positive SPT results. Overall, concentrations varied widely, between <2 and 2294 spores/m(3). While no relationship was observed between SPT(+) and total fungal counts, several significant associations were found when analysis was conducted on the various fungal genera and health outcomes. Positive associations were obtained between: Basidiospores and rhinitis (p < 0.01), Penicillium/Aspergillus and SPT(+) to any allergen (p < 0.01), and Alternaria and SPT(+) to any allergen (p < 0.01). Inverse associations were found between: Cladosporium and SPT(+) to any allergen (p < 0.05), and Cladosporium and SPT(+) to aeroallergens (p < 0.05). This study indicates that health outcome may vary by fungal genera; some fungal types may have sensitizing effects while others may have a beneficial role.

  15. Statistically tested comparisons of the accuracy of forecasting methods for age-specific and sex-specific mortality and life expectancy.

    PubMed

    Shang, Han Lin

    2015-01-01

    Although there are continuing developments in the methods for forecasting mortality, there are few comparisons of the accuracy of the forecasts. The subject of the statistical validity of these comparisons, which is essential to demographic forecasting, has all but been ignored. We introduce Friedman's test statistics to examine whether the differences in point and interval forecast accuracies are statistically significant between methods. We introduce the Nemenyi test statistic to identify which methods give results that are statistically significantly different from others. Using sex-specific and age-specific data from 20 countries, we apply these two test statistics to examine the forecast accuracy obtained from several principal component methods, which can be categorized into coherent and non-coherent forecasting methods.

  16. Sensitivity of Magnetospheric Multi-Scale (MMS) Mission Navigation Accuracy to Major Error Sources

    NASA Technical Reports Server (NTRS)

    Olson, Corwin; Long, Anne; Car[emter. Russell

    2011-01-01

    The Magnetospheric Multiscale (MMS) mission consists of four satellites flying in formation in highly elliptical orbits about the Earth, with a primary objective of studying magnetic reconnection. The baseline navigation concept is independent estimation of each spacecraft state using GPS pseudorange measurements referenced to an Ultra Stable Oscillator (USO) with accelerometer measurements included during maneuvers. MMS state estimation is performed onboard each spacecraft using the Goddard Enhanced Onboard Navigation System (GEONS), which is embedded in the Navigator GPS receiver. This paper describes the sensitivity of MMS navigation performance to two major error sources: USO clock errors and thrust acceleration knowledge errors.

  17. Sensitive and specific liquid chromatographic-tandem mass spectrometric assay for barnidipine in human plasma.

    PubMed

    Pawula, M; Watson, D; Teramura, T; Watanabe, T; Higuchi, S; Cheng, K N

    1998-11-20

    A sensitive and specific LC-MS-MS assay has been developed and validated for barnidipine (1-benzyl-3-pyrrolidinyl)methyl-2,6-dimethyl-4(m-nitrophenyl)-1,4-dihydr opyridine-3,5-dicarboxylate). The assay involves a simple and rapid solid-phase extraction procedure. Sample analysis was on a Spherisorb S3ODS2 100 mmX2 mm I.D. column, with a Finnigan TSQ 7000 mass spectrometer, using an electrospray interface and selective reaction monitoring (SRM). The intra- and inter-day precision and accuracy, determined as the coefficient of variation and relative error, respectively, were 11.8% or less. The limit of quantitation was 0.03 ng/ml, and the calibration was linear between 0.03 and 3.0 ng/ml. The method has been used successfully for the measurement of over two thousand human plasma samples from pharmacokinetic clinical trials.

  18. Reaction cross sections for two direct simulation Monte Carlo models: Accuracy and sensitivity analysis

    NASA Astrophysics Data System (ADS)

    Wysong, Ingrid; Gimelshein, Sergey; Gimelshein, Natalia; McKeon, William; Esposito, Fabrizio

    2012-04-01

    The quantum kinetic chemical reaction model proposed by Bird for the direct simulation Monte Carlo method is based on collision kinetics with no assumed Arrhenius-related parameters. It demonstrates an excellent agreement with the best estimates for thermal reaction rates coefficients and with two-temperature nonequilibrium rate coefficients for high-temperature air reactions. This paper investigates this model further, concentrating on the non-thermal reaction cross sections as a function of collision energy, and compares its predictions with those of the earlier total collision energy model, also by Bird, as well as with available quasi-classical trajectory cross section predictions (this paper also publishes for the first time a table of these computed reaction cross sections). A rarefied hypersonic flow over a cylinder is used to examine the sensitivity of the number of exchange reactions to the differences in the two models under a strongly nonequilibrium velocity distribution.

  19. Updating Mars-GRAM to Increase the Accuracy of Sensitivity Studies at Large Optical Depths

    NASA Technical Reports Server (NTRS)

    Justh, Hiliary L.; Justus, C. G.; Badger, Andrew M.

    2010-01-01

    The Mars Global Reference Atmospheric Model (Mars-GRAM) is an engineering-level atmospheric model widely used for diverse mission applications. Mars-GRAM s perturbation modeling capability is commonly used, in a Monte-Carlo mode, to perform high fidelity engineering end-to-end simulations for entry, descent, and landing (EDL). During the Mars Science Laboratory (MSL) site selection process, it was discovered that Mars-GRAM, when used for sensitivity studies for MapYear=0 and large optical depth values such as tau=3, is less than realistic. From the surface to 80 km altitude, Mars-GRAM is based on the NASA Ames Mars General Circulation Model (MGCM). MGCM results that were used for Mars-GRAM with MapYear set to 0 were from a MGCM run with a fixed value of tau=3 for the entire year at all locations. This has resulted in an imprecise atmospheric density at all altitudes. As a preliminary fix to this pressure-density problem, density factor values were determined for tau=0.3, 1 and 3 that will adjust the input values of MGCM MapYear 0 pressure and density to achieve a better match of Mars-GRAM MapYear 0 with Thermal Emission Spectrometer (TES) observations for MapYears 1 and 2 at comparable dust loading. Currently, these density factors are fixed values for all latitudes and Ls. Results will be presented from work being done to derive better multipliers by including variation with latitude and/or Ls by comparison of MapYear 0 output directly against TES limb data. The addition of these more precise density factors to Mars-GRAM 2005 Release 1.4 will improve the results of the sensitivity studies done for large optical depths.

  20. Evidence mapping for decision making: feasibility versus accuracy - when to abandon high sensitivity in electronic searches.

    PubMed

    Buchberger, Barbara; Krabbe, Laura; Lux, Beate; Mattivi, Jessica Tajana

    2016-01-01

    Hintergrund: Evidence Mapping ist eine vergleichsweise neue methodische Herangehensweise, die für die Entwicklung von Forschungsfragen und Entscheidungen über deren Relevanz oder Priorität hilfreich sein kann. Allerdings stellt die Menge der heutzutage zur Verfügung stehenden Daten eine Herausforderung für Wissenschaftler dar, die zum Teil mit Ergebnissen von Datenbankrecherchen konfrontiert sind, die über 30.000 identifizierte Literaturstellen für ein erstes Screening umfassen.Ziele: Zur Überprüfung der Eignung des Themas „Diabetes und Fahrerlaubnis“ als Fragestellung für eine evidenzbasierte nationale klinische Leitlinie wurde ein Evidence Mapping durchgeführt. Darüber hinaus wurde eine hoch sensitive mit einer hoch spezifischen Suchstrategie verglichen.Methoden: Auf der Basis eines systematischen Reviews waren die Datenbankrecherchen auf den Zeitraum von 2002 bis heute begrenzt sowie auf deutsche und englische Publikationen.Ergebnisse: Aufgrund der stark fokussierten Fragestellung und der Begrenzungen ergab die hoch sensitive Recherche eine handhabbare Menge von Literaturstellen, die ausreichend Evidenz enthielten, um die Fragestellung nach der Eignung des Themas für eine evidenzbasierte Leitlinie positiv beantworten zu können. Unter Anwendung der hoch spezifischen Suchstrategie wurde eine Reduktion der Literaturstellen um 25% erreicht, mit der 88% der relevanten Literaturstellen identifiziert werden konnten.Schlussfolgerung: Um eine Übersicht über ein Forschungsgebiet zu erlangen, ist im Gegensatz zu systematischen Reviews, die zur Reduktion von Bias die Darstellung der vollständigen, identifizierbaren Evidenz enthalten müssen, keine Recherche von größter Genauigkeit erforderlich. Unter Berücksichtigung dieses methodischen Unterschieds kann unter Anwendung einer hoch spezifischen Recherche anstelle einer hoch sensitiven eine große Menge zu bearbeitender, aber überflüssiger Informationen vermieden werden.

  1. Roche DAT immunoassay: sensitivity and specificity testing for amphetamines, cocaine, and opiates in oral fluid.

    PubMed

    Crooks, C Richard; Brown, Sue

    2010-03-01

    Laboratory testing of oral fluid for drugs of abuse continues to expand in the workplace, legal, treatment, and health settings. In this study, we assessed recently developed homogeneous Roche DAT screening assays for amphetamines, cocaine metabolite [benzoylecgonine (BZE)], methamphetamines, and opiates in oral fluid. Precision and accuracy were assessed using control samples at +/-25% of cutoff. Sensitivity, specificity, and agreement compared to liquid chromatography-tandem mass spectrometry (LC-MS-MS) was assessed by analysis of oral fluid specimens collected from 994 subjects enrolled in a drug treatment or probation and parole drug-testing program. An additional 180 research specimens from Kroll Laboratories were analyzed for amphetamine and methamphetamine. Screening cutoff concentrations (ng/mL) were as follows: amphetamines, 40; cocaine metabolite, 3; methamphetamines, 40; and opiates, 10. LC-MS-MS analyses were performed with the following cutoff concentrations (ng/mL): amphetamine, 40; BZE, 2.0; methamphetamine, 40; and codeine or morphine, 10. The percent coefficient of variation ranged from 3.4% to 7.3%. Sensitivity and specificity of the Roche DAT assays compared to LC-MS-MS were > 94%, and agreement was > 96% for the four assays. The performance of the Roche DAT assays suggests these new homogeneous screening assays will be an attractive alternative to existing more labor-intensive enzyme immunoassays.

  2. Sensitivity and specificity of subgingival bacteria in predicting preterm birth- a pilot cohort study

    PubMed Central

    Hassan, Khalid S; El Tantawi, Maha M.; Alagl, Adel S; Alnimr, Amani M; Haseeb, Yasmeen A

    2016-01-01

    Objective Preterm birth (PTB) increases the risk of adverse outcomes for new born infants. Subgingival bacteria are implicated in causing PTB. The aim of the present study was to assess the accuracy of some subgingival gram positive and gram negative bacteria detected by routine lab procedures in predicting PTB. Methodology Pregnant Saudi women (n= 170) visiting King Fahad hospital, Dammam, Saudi Arabia, were included in a pilot cohort study. Plaque was collected in the 2nd trimester and screened for subgingival anaerobes using Vitek2. Pregnancy outcome (preterm/full term birth) was assessed at delivery. Sensitivity, specificity and positive and negative likelihood ratios were calculated for the identified bacteria to predict PTB. Results Data about time of delivery was available for 94 subjects and 22 (23.4%) had PTB. Three gram negative and 4 gram positive subgingival bacteria had sensitivity ≥ 95% with two of each having negative likelihood ratios ≤0.10. Three gram positive bacteria had specificity > 95% with only one having positive likelihood ratio >2. Conclusion Subgingival bacteria identified using readily available lab techniques in the plaque of pregnant Saudi women in their 2nd trimester have useful potential to rule out PTB. PMID:27833518

  3. Sensitivity and Specificity of a Novel Approach to Confirm the Depth of the Endotracheal Tube

    PubMed Central

    Li, Yansong; Xie, Ying; Hu, Bailong; Wang, Jing; Song, Haibo; Wei, Xinchuan

    2015-01-01

    Abstract This study aimed to explore the sensitivity and specificity an approach to confirm the depth of the endotracheal tube. It was a prospective, diagnostic study (Registration number: chiCTR-TRC-14005170) conducted in the Department of Anesthesiology of West China Hospital. A total of 100 patients underwent general anesthesia were included. The distance between the upper margin of the cuff and the manubriosternal joint (CM) and the distance between the upper margin of the cuff and the carina (CC) were measured. The accuracy of the confirmed approach against fiberoptic bronchoscopy (FOB) was evaluated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The correlation and agreement between CM and CC were explored. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined to be 94.74% (95% CI: 87.07–98.55%), 79.17% (95% CI: 57.85–92.87%), 93.51% (95% CI: 85.49–97.86%), 82.61% (95% CI: 61.22%–95.05%), respectively. The κ value was 0.75 (95% CI: 0.60–0.90). There was a significant correlation between CM and CC (P < 0.001) with a correlation coefficient of 0.91(95% CI: 0.87–0.94). Bland and Altman plots also demonstrated a good agreement between the CM and CC. This novel method may be used to confirm the depth of the endotracheal tubes. PMID:26313810

  4. Design and calibration of a high-sensitivity and high-accuracy polarimeter based on liquid crystal variable retarders

    NASA Astrophysics Data System (ADS)

    Guo, Jing; Ren, De-Qing; Liu, Cheng-Chao; Zhu, Yong-Tian; Dou, Jiang-Pei; Zhang, Xi; Beck, Christian

    2017-01-01

    Polarimetry plays an important role in the measurement of solar magnetic fields. We developed a high-sensitivity and high-accuracy polarimeter (HHP) based on nematic liquid crystal variable retarders (LCVRs), which has a compact setup and no mechanical moving parts. The system design and calibration methods are discussed in detail. The azimuth error of the transmission axis of the polarizer as well as the fast axes of the two LCVRs and the quarter-wave plate were determined using dedicated procedures. Linearly and circularly polarized light were employed to evaluate the performance of the HHP. The experimental results indicate that a polarimetric sensitivity of better than \\[5.7 × {10 - 3}\\] can be achieved by using a single short-exposure image, while an accuracy on the order of 10‑5 can be reached by using a large number of short-exposure images. This makes the HHP a high-performance system that can be used with a ground-based solar telescope for high-precision solar magnetic field investigations.

  5. Quantitative measurement of hypertrophic scar: intrarater reliability, sensitivity, and specificity.

    PubMed

    Nedelec, Bernadette; Correa, José A; Rachelska, Grazyna; Armour, Alexis; LaSalle, Léo

    2008-01-01

    The comparison of scar evaluation over time requires measurement tools with acceptable intrarater reliability and the ability to discriminate skin characteristics of interest. The objective of this study was to evaluate the intrarater reliability and sensitivity and specificity of the Cutometer, the Mexameter, and the DermaScan C relative to the modified Vancouver Scar Scale (mVSS) in patient-matched normal skin, normal scar (donor sites), and hypertrophic scar (HSc). A single investigator evaluated four tissue types (severe HSc, less severe HSc, donor site, and normal skin) in 30 burn survivors with all four measurement tools. The intraclass correlation coefficient (ICC) for the Cutometer was acceptable (> or =0.75) for the maximum deformation measure for the donor site and normal skin (>0.78) but was below the acceptable range for the HSc sites and all other parameters. The ICC for the Mexameter erythema (>0.75) and melanin index (>0.89) and the DermaScan C total thickness measurement (>0.82) were acceptable for all sites. The ICC for the total of the height, pliability, and vascularity subscales of the mVSS was acceptable (0.81) for normal scar but below the acceptable range for the scar sites. The DermaScan C was clearly able to discriminate HSc from normal scar and normal skin based on the total thickness measure. The Cutometer was less discriminating but was still able to discriminate HSc from normal scar and normal skin. The Mexameter erythema index was not a good discriminator of HSc and normal scar. Receiver operating characteristic curves were generated to establish the best cutoff point for the DermaScan C total thickness and the Cutometer maximum deformation, which were 2.034 and 0.387 mm, respectively. This study showed that although the Cutometer, the DermaScan C, and the Mexameter have measurement properties that make them attractive substitutes for the mVSS, caution must be used when interpreting results since the Cutometer has a ceiling effect when

  6. Improving Mars-GRAM: Increasing the Accuracy of Sensitivity Studies at Large Optical Depths

    NASA Technical Reports Server (NTRS)

    Justh, Hilary L.; Justus, C. G.; Badger, Andrew M.

    2010-01-01

    Extensively utilized for numerous mission applications, the Mars Global Reference Atmospheric Model (Mars-GRAM) is an engineering-level atmospheric model. In a Monte-Carlo mode, Mars-GRAM's perturbation modeling capability is used to perform high fidelity engineering end-to-end simulations for entry, descent, and landing (EDL). Mars-GRAM has been found to be inexact when used during the Mars Science Laboratory (MSL) site selection process for sensitivity studies for MapYear=0 and large optical depth values such as tau=3. Mars-GRAM is based on the NASA Ames Mars General Circulation Model (MGCM) from the surface to 80 km altitude. Mars-GRAM with the MapYear parameter set to 0 utilizes results from a MGCM run with a fixed value of tau=3 at all locations for the entire year. Imprecise atmospheric density and pressure at all altitudes is a consequence of this use of MGCM with tau=3. Density factor values have been determined for tau=0.3, 1 and 3 as a preliminary fix to this pressure-density problem. These factors adjust the input values of MGCM MapYear 0 pressure and density to achieve a better match of Mars-GRAM MapYear 0 with Thermal Emission Spectrometer (TES) observations for MapYears 1 and 2 at comparable dust loading. These density factors are fixed values for all latitudes and Ls and are included in Mars-GRAM Release 1.3. Work currently being done, to derive better multipliers by including variations with latitude and/or Ls by comparison of MapYear 0 output directly against TES limb data, will be highlighted in the presentation. The TES limb data utilized in this process has been validated by a comparison study between Mars atmospheric density estimates from Mars-GRAM and measurements by Mars Global Surveyor (MGS). This comparison study was undertaken for locations on Mars of varying latitudes, Ls, and LTST. The more precise density factors will be included in Mars-GRAM 2005 Release 1.4 and thus improve the results of future sensitivity studies done for large

  7. Accuracy and sensitivity analysis for 54 models of computing hourly diffuse solar irradiation on clear sky

    NASA Astrophysics Data System (ADS)

    Badescu, Viorel; Gueymard, Christian A.; Cheval, Sorin; Oprea, Cristian; Baciu, Madalina; Dumitrescu, Alexandru; Iacobescu, Flavius; Milos, Ioan; Rada, Costel

    2013-02-01

    Fifty-four broadband models for computation of solar diffuse irradiation on horizontal surface were tested in Romania (South-Eastern Europe). The input data consist of surface meteorological data, column integrated data, and data derived from satellite measurements. The testing procedure is performed in 21 stages intended to provide information about the sensitivity of the models to various sets of input data. There is no model to be ranked "the best" for all sets of input data. However, some of the models performed better than others, in the sense that they were ranked among the best for most of the testing stages. The best models for solar diffuse radiation computation are, on equal footing, ASHRAE 2005 model (ASHRAE 2005) and King model (King and Buckius, Solar Energy 22:297-301, 1979). The second best model is MAC model (Davies, Bound Layer Meteor 9:33-52, 1975). Details about the performance of each model in the 21 testing stages are found in the Electronic Supplementary Material.

  8. Strategies to Improve the Accuracy of Mars-GRAM Sensitivity Studies at Large Optical Depths

    NASA Technical Reports Server (NTRS)

    Justh, Hilary L.; Justus, Carl G.; Badger, Andrew M.

    2009-01-01

    The Mars Global Reference Atmospheric Model (Mars-GRAM) is an engineering-level atmospheric model widely used for diverse mission applications. Mars-GRAM s perturbation modeling capability is commonly used, in a Monte-Carlo mode, to perform high fidelity engineering end-to-end simulations for entry, descent, and landing (EDL). It has been discovered during the Mars Science Laboratory (MSL) site selection process that Mars-GRAM when used for sensitivity studies for MapYear=0 and large optical depth values such as tau=3 is less than realistic. A comparison study between Mars atmospheric density estimates from Mars- GRAM and measurements by Mars Global Surveyor (MGS) has been undertaken for locations of varying latitudes, Ls, and LTST on Mars. The preliminary results from this study have validated the Thermal Emission Spectrometer (TES) limb data. From the surface to 80 km altitude, Mars- GRAM is based on the NASA Ames Mars General Circulation Model (MGCM). MGCM results that were used for Mars-GRAM with MapYear=0 were from a MGCM run with a fixed value of tau=3 for the entire year at all locations. Unrealistic energy absorption by uniform atmospheric dust leads to an unrealistic thermal energy balance on the polar caps. The outcome is an inaccurate cycle of condensation/sublimation of the polar caps and, as a consequence, an inaccurate cycle of total atmospheric mass and global-average surface pressure. Under an assumption of unchanged temperature profile and hydrostatic equilibrium, a given percentage change in surface pressure would produce a corresponding percentage change in density at all altitudes. Consequently, the final result of a change in surface pressure is an imprecise atmospheric density at all altitudes. To solve this pressure-density problem, a density factor value was determined for tau=.3, 1 and 3 that will adjust the input values of MGCM MapYear 0 pressure and density to achieve a better match of Mars-GRAM MapYear=0 with MapYears 1 and 2 MGCM output

  9. Accuracy of diagnostic methods and surveillance sensitivity for human enterovirus, South Korea, 1999-2011.

    PubMed

    Hyeon, Ji-Yeon; Hwang, Seoyeon; Kim, Hyejin; Song, Jaehyoung; Ahn, Jeongbae; Kang, Byunghak; Kim, Kisoon; Choi, Wooyoung; Chung, Jae Keun; Kim, Cheon-Hyun; Cho, Kyungsoon; Jee, Youngmee; Kim, Jonghyun; Kim, Kisang; Kim, Sun-Hee; Kim, Min-Ji; Cheon, Doo-Sung

    2013-08-01

    The epidemiology of enteroviral infection in South Korea during 1999-2011 chronicles nationwide outbreaks and changing detection and subtyping methods used over the 13-year period. Of 14,657 patients whose samples were tested, 4,762 (32.5%) samples were positive for human enterovirus (human EV); as diagnostic methods improved, the rate of positive results increased. A seasonal trend of outbreaks was documented. Genotypes enterovirus 71, echovirus 30, coxsackievirus B5, enterovirus 6, and coxsackievirus B2 were the most common genotypes identified. Accurate test results correlated clinical syndromes to enterovirus genotypes: aseptic meningitis to echovirus 30, enterovirus 6, and coxsackievirus B5; hand, foot and mouth disease to coxsackievirus A16; and hand, foot and mouth disease with neurologic complications to enterovirus 71. There are currently no treatments specific to human EV infections; surveillance of enterovirus infections such as this study provides may assist with evaluating the need to research and develop treatments for infections caused by virulent human EV genotypes.

  10. Sensitivity and specificity of administrative mortality data for identifying prescription opioid–related deaths

    PubMed Central

    Gladstone, Emilie; Smolina, Kate; Morgan, Steven G.; Fernandes, Kimberly A.; Martins, Diana; Gomes, Tara

    2016-01-01

    Background: Comprehensive systems for surveilling prescription opioid–related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid–related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid–related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. Methods: We identified all prescription opioid–related deaths from Ontario coroners’ data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid–related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid–related deaths. Results: Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. Interpretation: In the absence of specific systems for monitoring prescription opioid–related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid–related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies. PMID:26622006

  11. Species-specific temperature sensitivity of TRPA1.

    PubMed

    Laursen, Willem J; Anderson, Evan O; Hoffstaetter, Lydia J; Bagriantsev, Sviatoslav N; Gracheva, Elena O

    2015-01-01

    Transient receptor potential ankyrin 1 (TRPA1) is a polymodal ion channel sensitive to temperature and chemical stimuli. The importance of temperature and aversive chemical detection for survival has driven the evolutionary diversity of TRPA1 sensitivity. This diversity can be observed in the various roles of TRPA1 in different species, where it is proposed to act as a temperature-insensitive chemosensor, a heat transducer, a noxious cold transducer, or a detector of low-intensity heat for prey localization. Exploring the variation of TRPA1 functions among species provides evolutionary insight into molecular mechanisms that fine-tune thermal and chemical sensitivity, and offers an opportunity to address basic principles of temperature gating in ion channels. A decade of research has yielded a number of hypotheses describing physiological roles of TRPA1, modulators of its activity, and biophysical principles of gating. This review surveys the diversity of TRPA1 adaptations across evolutionary taxa and explores possible mechanisms of TRPA1 activation.

  12. Species-specific temperature sensitivity of TRPA1

    PubMed Central

    Laursen, Willem J; Anderson, Evan O; Hoffstaetter, Lydia J; Bagriantsev, Sviatoslav N; Gracheva, Elena O

    2015-01-01

    Abstract Transient receptor potential ankyrin 1 (TRPA1) is a polymodal ion channel sensitive to temperature and chemical stimuli. The importance of temperature and aversive chemical detection for survival has driven the evolutionary diversity of TRPA1 sensitivity. This diversity can be observed in the various roles of TRPA1 in different species, where it is proposed to act as a temperature-insensitive chemosensor, a heat transducer, a noxious cold transducer, or a detector of low-intensity heat for prey localization. Exploring the variation of TRPA1 functions among species provides evolutionary insight into molecular mechanisms that fine-tune thermal and chemical sensitivity, and offers an opportunity to address basic principles of temperature gating in ion channels. A decade of research has yielded a number of hypotheses describing physiological roles of TRPA1, modulators of its activity, and biophysical principles of gating. This review surveys the diversity of TRPA1 adaptations across evolutionary taxa and explores possible mechanisms of TRPA1 activation. PMID:27227025

  13. Using Lunar Observations to Validate Pointing Accuracy and Geolocation, Detector Sensitivity Stability and Static Point Response of the CERES Instruments

    NASA Technical Reports Server (NTRS)

    Daniels, Janet L.; Smith, G. Louis; Priestley, Kory J.; Thomas, Susan

    2014-01-01

    Validation of in-orbit instrument performance is a function of stability in both instrument and calibration source. This paper describes a method using lunar observations scanning near full moon by the Clouds and Earth Radiant Energy System (CERES) instruments. The Moon offers an external source whose signal variance is predictable and non-degrading. From 2006 to present, these in-orbit observations have become standardized and compiled for the Flight Models -1 and -2 aboard the Terra satellite, for Flight Models-3 and -4 aboard the Aqua satellite, and beginning 2012, for Flight Model-5 aboard Suomi-NPP. Instrument performance measurements studied are detector sensitivity stability, pointing accuracy and static detector point response function. This validation method also shows trends per CERES data channel of 0.8% per decade or less for Flight Models 1-4. Using instrument gimbal data and computed lunar position, the pointing error of each detector telescope, the accuracy and consistency of the alignment between the detectors can be determined. The maximum pointing error was 0.2 Deg. in azimuth and 0.17 Deg. in elevation which corresponds to an error in geolocation near nadir of 2.09 km. With the exception of one detector, all instruments were found to have consistent detector alignment from 2006 to present. All alignment error was within 0.1o with most detector telescopes showing a consistent alignment offset of less than 0.02 Deg.

  14. Mapping Local Protein Electrostatics by EPR of pH-Sensitive Thiol-Specific Nitroxide† ¶

    PubMed Central

    Voinov, Maxim A.; Ruuge, Andres; Reznikov, Vladimir A.; Grigor’ev, Igor A.; Smirnov, Alex I.

    2013-01-01

    A first thiol-specific pH-sensitive nitroxide spin label of the imidazolidine series -methanethiosulfonic acid S-(1-oxyl-2,2,3,5,5-pentamethylimidazolidin-4-ylmethyl) ester (IMTSL) - has been synthesized and characterized. X- (9 GHz) and W-band (94 GHz) EPR spectral parameters of the new spin label in its free form and covalently attached to an amino acid cysteine and a tripeptide glutathione were studied as a function of pH and solvent polarity. pKa value of protonatable tertiary amino group of the spin label was found to be unaffected by other ionizable groups present in side chains of unstructured small peptides. The W-band EPR spectra were shown to allow for pKa determination from precise g-factor measurements. Is has been demonstrated that high accuracy of pKa determination for pH-sensitive nitroxides could be achieved regardless the frequency of measurements or the regime of spin exchange: fast at X-band and slow at W-band. IMTSL was found to react specifically with a model protein - iso-1-cytochrome c from yeast Saccharomyces cerevisiae - giving EPR spectra very similar to those of the most commonly employed cysteine-specific label MTSL. CD data indicated no perturbations to the overall protein structure upon IMTSL labeling. It was found that for IMTSL, giso correlates linearly with Aiso but the slopes are different for the neutral and charged forms of the nitroxide. This finding was attributed to the solvent effects on the spin density at the oxygen atom of the N–O group and on the excitation energy of the oxygen lone-pair orbital. PMID:18426227

  15. ICan: an optimized ion-current-based quantification procedure with enhanced quantitative accuracy and sensitivity in biomarker discovery.

    PubMed

    Tu, Chengjian; Sheng, Quanhu; Li, Jun; Shen, Xiaomeng; Zhang, Ming; Shyr, Yu; Qu, Jun

    2014-12-05

    The rapidly expanding availability of high-resolution mass spectrometry has substantially enhanced the ion-current-based relative quantification techniques. Despite the increasing interest in ion-current-based methods, quantitative sensitivity, accuracy, and false discovery rate remain the major concerns; consequently, comprehensive evaluation and development in these regards are urgently needed. Here we describe an integrated, new procedure for data normalization and protein ratio estimation, termed ICan, for improved ion-current-based analysis of data generated by high-resolution mass spectrometry (MS). ICan achieved significantly better accuracy and precision, and lower false-positive rate for discovering altered proteins, over current popular pipelines. A spiked-in experiment was used to evaluate the performance of ICan to detect small changes. In this study E. coli extracts were spiked with moderate-abundance proteins from human plasma (MAP, enriched by IgY14-SuperMix procedure) at two different levels to set a small change of 1.5-fold. Forty-five (92%, with an average ratio of 1.71 ± 0.13) of 49 identified MAP protein (i.e., the true positives) and none of the reference proteins (1.0-fold) were determined as significantly altered proteins, with cutoff thresholds of ≥ 1.3-fold change and p ≤ 0.05. This is the first study to evaluate and prove competitive performance of the ion-current-based approach for assigning significance to proteins with small changes. By comparison, other methods showed remarkably inferior performance. ICan can be broadly applicable to reliable and sensitive proteomic survey of multiple biological samples with the use of high-resolution MS. Moreover, many key features evaluated and optimized here such as normalization, protein ratio determination, and statistical analyses are also valuable for data analysis by isotope-labeling methods.

  16. Sensitivity and specificity of in situ hybridization for diagnosis of cutaneous infection by Leishmania infantum in dogs.

    PubMed

    Menezes, Rodrigo C; Figueiredo, Fabiano B; Wise, Annabel G; Madeira, Maria F; Oliveira, Raquel V C; Schubach, Tânia M P; Kiupel, Matti; Langohr, Ingeborg M

    2013-01-01

    An accurate diagnosis of infection by Leishmania infantum in dogs is fundamental for the control of zoonotic visceral leishmaniasis (VL). Histopathology (HP) and immunohistochemistry (IHC) are frequently used for the histological diagnosis of L. infantum in dogs but have shown limited accuracy. To improve the sensitivity and specificity of the histological diagnosis of VL, we evaluated automated in situ hybridization (ISH) using a generic probe for Leishmania and a specific probe for L. infantum in surgical skin biopsy specimens of dogs. The ISH results were compared with those of HP and IHC, using parasitological culture as the reference standard. Skin samples from 51 dogs with cutaneous L. infantum infection and 51 noninfected dogs were randomly selected from samples of dogs from various cities in Brazil where canine VL is endemic. These samples were processed for parasitological culture, HP, IHC, and ISH using both probes. The sensitivities of ISH using the specific probe, ISH using the generic probe, IHC, and HP were, respectively, 74.5%, 70.6%, 69.5%, and 57.6%. The specificity of both ISH probes tested was 100%, and there was no cross-hybridization of the generic and specific probes with selected pathogenic fungi and protozoa. The specific probe discriminated L. infantum from the other species of Leishmania that infect dogs in the New World. ISH is highly sensitive and specific for the diagnosis of L. infantum in histologic samples of skin from infected dogs and can be used on routine biopsy material to make a diagnosis of leishmaniasis.

  17. A first investigation of accuracy, precision and sensitivity of phase-based x-ray dark-field imaging

    NASA Astrophysics Data System (ADS)

    Astolfo, Alberto; Endrizzi, Marco; Kallon, Gibril; Millard, Thomas P.; Vittoria, Fabio A.; Olivo, Alessandro

    2016-12-01

    In the last two decades, x-ray phase contrast imaging (XPCI) has attracted attention as a potentially significant improvement over widespread and established x-ray imaging. The key is its capability to access a new physical quantity (the ‘phase shift’), which can be complementary to x-ray absorption. One additional advantage of XPCI is its sensitivity to micro structural details through the refraction induced dark-field (DF). While DF is extensively mentioned and used for several applications, predicting the capability of an XPCI system to retrieve DF quantitatively is not straightforward. In this article, we evaluate the impact of different design options and algorithms on DF retrieval for the edge-illumination (EI) XPCI technique. Monte Carlo simulations, supported by experimental data, are used to measure the accuracy, precision and sensitivity of DF retrieval performed with several EI systems based on conventional x-ray sources. The introduced tools are easy to implement, and general enough to assess the DF performance of systems based on alternative (i.e. non-EI) XPCI approaches.

  18. Quantification of Cooperativity in Heterodimer-DNA Binding Improves the Accuracy of Binding Specificity Models.

    PubMed

    Isakova, Alina; Berset, Yves; Hatzimanikatis, Vassily; Deplancke, Bart

    2016-05-06

    Many transcription factors (TFs) have the ability to cooperate on DNA elements as heterodimers. Despite the significance of TF heterodimerization for gene regulation, a quantitative understanding of cooperativity between various TF dimer partners and its impact on heterodimer DNA binding specificity models is still lacking. Here, we used a novel integrative approach, combining microfluidics-steered measurements of dimer-DNA assembly with mechanistic modeling of the implicated protein-protein-DNA interactions to quantitatively interrogate the cooperative DNA binding behavior of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ):retinoid X receptor α (RXRα) heterodimer. Using the high throughput MITOMI (mechanically induced trapping of molecular interactions) platform, we derived equilibrium DNA binding data for PPARγ, RXRα, as well as the PPARγ:RXRα heterodimer to more than 300 target DNA sites and variants thereof. We then quantified cooperativity underlying heterodimer-DNA binding and derived an integrative heterodimer DNA binding constant. Using this cooperativity-inclusive constant, we were able to build a heterodimer-DNA binding specificity model that has superior predictive power than the one based on a regular one-site equilibrium. Our data further revealed that individual nucleotide substitutions within the target site affect the extent of cooperativity in PPARγ:RXRα-DNA binding. Our study therefore emphasizes the importance of assessing cooperativity when generating DNA binding specificity models for heterodimers.

  19. Predictive models of lameness in dairy cows achieve high sensitivity and specificity with force measurements in three dimensions.

    PubMed

    Dunthorn, Jason; Dyer, Robert M; Neerchal, Nagaraj K; McHenry, Jonathan S; Rajkondawar, Parimal G; Steingraber, Gary; Tasch, Uri

    2015-11-01

    Lameness remains a significant cause of production losses, a growing welfare concern and may be a greater economic burden than clinical mastitis . A growing need for accurate, continuous automated detection systems continues because US prevalence of lameness is 12.5% while individual herds may experience prevalence's of 27.8-50.8%. To that end the first force-plate system restricted to the vertical dimension identified lame cows with 85% specificity and 52% sensitivity. These results lead to the hypothesis that addition of transverse and longitudinal dimensions could improve sensitivity of lameness detection. To address the hypothesis we upgraded the original force plate system to measure ground reaction forces (GRFs) across three directions. GRFs and locomotion scores were generated from randomly selected cows and logistic regression was used to develop a model that characterised relationships of locomotion scores to the GRFs. This preliminary study showed 76 variables across 3 dimensions produced a model with greater than 90% sensitivity, specificity, and area under the receiver operating curve (AUC). The result was a marked improvement on the 52% sensitivity, and 85% specificity previously observed with the 1 dimensional model or the 45% sensitivities reported with visual observations. Validation of model accuracy continues with the goal to finalise accurate automated methods of lameness detection.

  20. Particulate matter inflammation and receptor sensitivity are target cell specific.

    PubMed

    Veronesi, Bellina; de Haar, Colin; Roy, Josee; Oortgiesen, Marga

    2002-02-01

    The complexity of primary source particulate matter (PM) and the various cell types encountered by its inhalation raise the possibility that target cells are differentially activated. Since epithelial cells, which line the nasal-tracheal-bronchial airways, and sensory C fibers, which terminate throughout this epithelial layer, are initially targeted by inhaled PM, we compared their relative biological response in vitro to PM originating from volcanic (MSH), anthropogenic (diesel), residential (woodstove), urban ambient (St. Louis, Ottawa), and industrial emission (coal fly ash, CFA; residual oil fly ash, ROFA; oil fly ash, OFA) sources. Increases in intracellular calcium (i.e., [Ca(2+)](i)) are a second-messenger event that indicates cellular activation and signal transduction, in both nerve and epithelial cells. Single-cell calcium imaging recordings were taken of human bronchial epithelial cells (BEAS-2B) exposed to selected PM (50 microg/ml or 30 microg/cm(2)). These cells responded with variable increases in [Ca(2+)](i) ranging from abrupt increases, which returned to baseline upon washing of the cells, to oscillations of the [Ca(2+)](i) that did not wash out. Increases in [Ca(2+)](i) and inflammatory cytokine (i.e., interleukin 6, IL-6) release were measured in populations of BEAS-2B cells exposed to PM (50 microg/ml) and were shown to significantly correlate (r(2) =.80). BEAS-2B cells, stained histochemically with cobalt, displayed a concentration-dependent precipitation in response to acid pH and capsaicin, indicating the presence of acid-sensitive pathways (e.g., VR1 and acid-sensitive receptors). To demonstrate the relevance of these pathways to inflammatory cytokine (i.e., IL-6) release, BEAS-2B cells were pretreated (15 min) with antagonists to the vanilloid (VR1) receptor (i.e., capsazepine, CPZ) or acid-sensitive pathways (i.e., amiloride) before their exposure to the selected PM. A significant reduction of IL-6 release occurred in response to all PM

  1. Assessing the accuracy of an inter-institutional automated patient-specific health problem list

    PubMed Central

    2010-01-01

    Background Health problem lists are a key component of electronic health records and are instrumental in the development of decision-support systems that encourage best practices and optimal patient safety. Most health problem lists require initial clinical information to be entered manually and few integrate information across care providers and institutions. This study assesses the accuracy of a novel approach to create an inter-institutional automated health problem list in a computerized medical record (MOXXI) that integrates three sources of information for an individual patient: diagnostic codes from medical services claims from all treating physicians, therapeutic indications from electronic prescriptions, and single-indication drugs. Methods Data for this study were obtained from 121 general practitioners and all medical services provided for 22,248 of their patients. At the opening of a patient's file, all health problems detected through medical service utilization or single-indication drug use were flagged to the physician in the MOXXI system. Each new arising health problem were presented as 'potential' and physicians were prompted to specify if the health problem was valid (Y) or not (N) or if they preferred to reassess its validity at a later time. Results A total of 263,527 health problems, representing 891 unique problems, were identified for the group of 22,248 patients. Medical services claims contributed to the majority of problems identified (77%), followed by therapeutic indications from electronic prescriptions (14%), and single-indication drugs (9%). Physicians actively chose to assess 41.7% (n = 106,950) of health problems. Overall, 73% of the problems assessed were considered valid; 42% originated from medical service diagnostic codes, 11% from single indication drugs, and 47% from prescription indications. Twelve percent of problems identified through other treating physicians were considered valid compared to 28% identified through study

  2. Improved Sensitivity and Specificity for Detection of Prostate Cancer

    DTIC Science & Technology

    2007-11-01

    SUBJECT TERMS Prostate, spectroscopy, MRI 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...assessment of the correlation between MRI /MRSI and histopathology. Specific Aim 2: The development of a tumor index based on individual MRI /MRSI...Overall Status of the Project: The goal of the study is to diagnose prostate cancer more effectively using various MRI techniques, with the ultimate

  3. Sensitive, fast, and specific immunoassays for methyltestosterone detection.

    PubMed

    Kong, Na; Song, Shanshan; Peng, Juan; Liu, Liqiang; Kuang, Hua; Xu, Chuanlai

    2015-04-29

    An indirect competitive enzyme-linked immunosorbent assay (icELISA) and an immunochromatographic strip assay using a highly specific monoclonal antibody, were developed to detect methyltestosterone (MT) residues in animal feed. The optimized icELISA had a half-inhibition concentration value of 0.26 ng/mL and a limit of detection value of 0.045 ng/mL. There was no cross-reactivity with eight analogues, revealing high specificity for MT. Based on icELISA results, the recovery rate of MT in animal feed was 82.4%-100.6%. The results were in accordance with those obtained by gas chromatography-mass spectrometry. The developed immunochromatographic strip assay, as the first report for MT detection, had a visual cut-off value of 1 ng/mL in PBS, 2.5 ng/g in fish feed, and 2.5 ng/g in pig feed. Therefore, these immunoassays are useful and fast tools for MT residue detection in animal feed.

  4. Sensitive, Fast, and Specific Immunoassays for Methyltestosterone Detection

    PubMed Central

    Kong, Na; Song, Shanshan; Peng, Juan; Liu, Liqiang; Kuang, Hua; Xu, Chuanlai

    2015-01-01

    An indirect competitive enzyme-linked immunosorbent assay (icELISA) and an immunochromatographic strip assay using a highly specific monoclonal antibody, were developed to detect methyltestosterone (MT) residues in animal feed. The optimized icELISA had a half-inhibition concentration value of 0.26 ng/mL and a limit of detection value of 0.045 ng/mL. There was no cross-reactivity with eight analogues, revealing high specificity for MT. Based on icELISA results, the recovery rate of MT in animal feed was 82.4%–100.6%. The results were in accordance with those obtained by gas chromatography-mass spectrometry. The developed immunochromatographic strip assay, as the first report for MT detection, had a visual cut-off value of 1 ng/mL in PBS, 2.5 ng/g in fish feed, and 2.5 ng/g in pig feed. Therefore, these immunoassays are useful and fast tools for MT residue detection in animal feed. PMID:25938198

  5. Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures

    SciTech Connect

    Rettmann, Maryam E. Holmes, David R.; Camp, Jon J.; Cameron, Bruce M.; Robb, Richard A.; Kwartowitz, David M.; Gunawan, Mia; Johnson, Susan B.; Packer, Douglas L.; Dalegrave, Charles; Kolasa, Mark W.

    2014-02-15

    Purpose: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. Methods: Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamicin vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. Results: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved

  6. Tumor Specific Gene Expression and Tumor Specific Vector Replication for Systemic Chemotherapy Sensitization Treatment of Breast Cancer

    DTIC Science & Technology

    2002-07-01

    directed at the use of the L-plastin tumor-specific transcriptional promoter to control the expression of a chemotherapy sensitization gene ( cytosine ... deaminase ) and a viral replication gene (ElA) so that any toxic effect is tumor specific. These vectors have been shown to suppress the growth of human

  7. Individual density-elasticity relationships improve accuracy of subject-specific finite element models of human femurs.

    PubMed

    Eberle, Sebastian; Göttlinger, Michael; Augat, Peter

    2013-09-03

    In a previous study on subject-specific finite-element-models, we found that appropriate density-elasticity relationships to compute the mechanical behavior of femurs seem to be subject-specific. The purpose of this study was to test the hypothesis that the predictive error of a cohort of subject-specific finite element-models is lower with subject-specific density-elasticity relationships than with a cohort-specific density-elasticity relationship. Finite-element-analysis and inverse optimization based on response surface methodology were employed to test the hypothesis. Subject-specific FE-models of 17 human femurs and corresponding experimental data from biomechanical tests were taken from a previous study. A power function for the relation between radiological bone density and elastic modulus was set up with the optimization variables a and b: E(MPa)=aρqCT(b)(gK2HPO4/cm(3)). The goal of the optimization was to minimize the root-mean-square error in percent (RMSE%) between computational and experimental results. A Wilcoxon test (p=0.05) was performed on all absolute relative errors between the two groups (subject-specific functions vs. cohort-specific function). The subject-specific functions resulted in a 6% lower overall prediction error and a 6% lower RMSE% than the cohort-specific function (p<0.001). The determined subject-specific relations were mostly linear, with variable a ranging from 9307 to 15673 and variable b ranging from 0.68 to 1.40. For the cohort-specific relation, the following power law was obtained: E(MPa)=12486ρqCT(1.16)(gK2HPO4/cm(3)). We conclude that individual density-elasticity relationships improve the accuracy of subject-specific finite element models. Future subject-specific finite-element-analyses of bones should include the individuality of the elastic properties by a stochastic density-elasticity relationship with mean and standard deviation of a and b.

  8. High sensitivity and accuracy dissolved oxygen (DO) detection by using PtOEP/poly(MMA-co-TFEMA) sensing film.

    PubMed

    Zhang, Ke; Zhang, Honglin; Wang, Ying; Tian, Yanqing; Zhao, Jiupeng; Li, Yao

    2017-01-05

    Fluorinated acrylate polymer has received great interest in recent years due to its extraordinary characteristics such as high oxygen permeability, good stability, low surface energy and refractive index. In this work, platinum octaethylporphyrin/poly(methylmethacrylate-co-trifluoroethyl methacrylate) (PtOEP/poly(MMA-co-TFEMA)) oxygen sensing film was prepared by the immobilizing of PtOEP in a poly(MMA-co-TFEMA) matrix and the technological readiness of optical properties was established based on the principle of luminescence quenching. It was found that the oxygen-sensing performance could be improved by optimizing the monomer ratio (MMA/TFEMA=1:1), tributylphosphate(TBP, 0.05mL) and PtOEP (5μg) content. Under this condition, the maximum quenching ratio I0/I100 of the oxygen sensing film is obtained to be about 8.16, Stern-Volmer equation is I0/I=1.003+2.663[O2] (R(2)=0.999), exhibiting a linear relationship, good photo-stability, high sensitivity and accuracy. Finally, the synthesized PtOEP/poly(MMA-co-TFEMA) sensing film was used for DO detection in different water samples.

  9. High sensitivity and accuracy dissolved oxygen (DO) detection by using PtOEP/poly(MMA-co-TFEMA) sensing film

    NASA Astrophysics Data System (ADS)

    Zhang, Ke; Zhang, Honglin; Wang, Ying; Tian, Yanqing; Zhao, Jiupeng; Li, Yao

    2017-01-01

    Fluorinated acrylate polymer has received great interest in recent years due to its extraordinary characteristics such as high oxygen permeability, good stability, low surface energy and refractive index. In this work, platinum octaethylporphyrin/poly(methylmethacrylate-co-trifluoroethyl methacrylate) (PtOEP/poly(MMA-co-TFEMA)) oxygen sensing film was prepared by the immobilizing of PtOEP in a poly(MMA-co-TFEMA) matrix and the technological readiness of optical properties was established based on the principle of luminescence quenching. It was found that the oxygen-sensing performance could be improved by optimizing the monomer ratio (MMA/TFEMA = 1:1), tributylphosphate(TBP, 0.05 mL) and PtOEP (5 μg) content. Under this condition, the maximum quenching ratio I0/I100 of the oxygen sensing film is obtained to be about 8.16, Stern-Volmer equation is I0/I = 1.003 + 2.663[O2] (R2 = 0.999), exhibiting a linear relationship, good photo-stability, high sensitivity and accuracy. Finally, the synthesized PtOEP/poly(MMA-co-TFEMA) sensing film was used for DO detection in different water samples.

  10. The gastric/pancreatic amylase ratio predicts postoperative pancreatic fistula with high sensitivity and specificity.

    PubMed

    Jin, Shuo; Shi, Xiao-Ju; Sun, Xiao-Dong; Zhang, Ping; Lv, Guo-Yue; Du, Xiao-Hong; Wang, Si-Yuan; Wang, Guang-Yi

    2015-01-01

    This article aims to identify risk factors for postoperative pancreatic fistula (POPF) and evaluate the gastric/pancreatic amylase ratio (GPAR) on postoperative day (POD) 3 as a POPF predictor in patients who undergo pancreaticoduodenectomy (PD).POPF significantly contributes to mortality and morbidity in patients who undergo PD. Previously identified predictors for POPF often have low predictive accuracy. Therefore, accurate POPF predictors are needed.In this prospective cohort study, we measured the clinical and biochemical factors of 61 patients who underwent PD and diagnosed POPF according to the definition of the International Study Group of Pancreatic Fistula. We analyzed the association between POPF and various factors, identified POPF risk factors, and evaluated the predictive power of the GPAR on POD3 and the levels of serum and ascites amylase.Of the 61 patients, 21 developed POPF. The color of the pancreatic drain fluid, POD1 serum, POD1 median output of pancreatic drain fluid volume, and GPAR were significantly associated with POPF. The color of the pancreatic drain fluid and high GPAR were independent risk factors. Although serum and ascites amylase did not predict POPF accurately, the cutoff value was 1.24, and GPAR predicted POPF with high sensitivity and specificity.This is the first report demonstrating that high GPAR on POD3 is a risk factor for POPF and showing that GPAR is a more accurate predictor of POPF than the previously reported amylase markers.

  11. Interactive cervical motion kinematics: sensitivity, specificity and clinically significant values for identifying kinematic impairments in patients with chronic neck pain.

    PubMed

    Sarig Bahat, Hilla; Chen, Xiaoqi; Reznik, David; Kodesh, Einat; Treleaven, Julia

    2015-04-01

    Chronic neck pain has been consistently shown to be associated with impaired kinematic control including reduced range, velocity and smoothness of cervical motion, that seem relevant to daily function as in quick neck motion in response to surrounding stimuli. The objectives of this study were: to compare interactive cervical kinematics in patients with neck pain and controls; to explore the new measures of cervical motion accuracy; and to find the sensitivity, specificity, and optimal cutoff values for defining impaired kinematics in those with neck pain. In this cross-section study, 33 patients with chronic neck pain and 22 asymptomatic controls were assessed for their cervical kinematic control using interactive virtual reality hardware and customized software utilizing a head mounted display with built-in head tracking. Outcome measures included peak and mean velocity, smoothness (represented by number of velocity peaks (NVP)), symmetry (represented by time to peak velocity percentage (TTPP)), and accuracy of cervical motion. Results demonstrated significant and strong effect-size differences in peak and mean velocities, NVP and TTPP in all directions excluding TTPP in left rotation, and good effect-size group differences in 5/8 accuracy measures. Regression results emphasized the high clinical value of neck motion velocity, with very high sensitivity and specificity (85%-100%), followed by motion smoothness, symmetry and accuracy. These finding suggest cervical kinematics should be evaluated clinically, and screened by the provided cut off values for identification of relevant impairments in those with neck pain. Such identification of presence or absence of kinematic impairments may direct treatment strategies and additional evaluation when needed.

  12. Sensitivity and specificity of the safe driving behavior measure and the driving habits questionnaire for older self-drivers

    PubMed Central

    Kim, Kweon-Young; Song, Chiang-Soon; Lee, Hye-Sun

    2016-01-01

    [Purpose] To evaluate the sensitivity and specificity of the Safe Driving Behavior Measure and the Driving Habits Questionnaire in community-dwelling older self-drivers. [Subjects and Methods] Forty-five older participated in this study, to measure the Safe Driving Behavior Measure and the Driving Habits Questionnaire. Sensitivity and specificity were calculated along with cut-off values and overall accuracy of each measure as determined by the participants operating characteristic curve and the area under the curve. Multivariate logistic regression analysis was employed to identify predictors of driving abilities. [Results] The sensitivities were 0.538 for Safe Driving Behavior Measure, and 0.577, 0.423, and 0.615 for the difficulty, crash and citations, and driving space on domains of the Driving Habits Questionnaire, respectively. The specificities of the person-vehicle domain, person-environment domain, and person-vehicle-environment domain of the Safe Driving Behavior Measure were 0.474, 0.526, and 0.421, respectively, while the Driving Habits Questionnaire domains, the specificities of difficulty, crash and citations, and driving space were 0.526, 0.211, and 0.421, respectively. [Conclusion] The results of this study suggest that factors related to the accident history of older self-drivers were not well-explained, although the Safe Driving Behavior Measure and Driving Habits Questionnaire domains have the potential to determine driving-related accident history. PMID:27821942

  13. [Sensitivity and specificity of the ELISA Kit for the detection of antidobies to Junin virus].

    PubMed

    Pirozhkov, A P; Timofeev, M A; Borisevich, I V; Syromiatnikova, S I; Shatokhina, I V; Pantyukhov, V B; Kovalchuk, A V; Borisevich, S V

    2015-01-01

    The goal of this work was to describe methodological approaches to determination of sensitivity and specificity of the enzyme-linked immunosorbent assay kit (ELISA Kit) for detection of the specific anti-Junin virus (JV) antibody. Comparison of ELISA to plaque reduction neutralization test (PRNT) showed direct relationship between antibody titers in the samples of serum of immunized animals, determined by either PRNT or ELISA methods. The obtained results provided an opportunity to form the panels of positive and negative serum samples to determine the sensitivity and specificity of the ELISA Kit. Sensitivity of the ELISA Kit was at least 98% when studying the samples of serum of immunized guinea pigs and rabbits (determined as positive in PRNT). The sensitivity of the ELISA Kit was at least 68% when studying the samples determined by PNRT as uncertain positive. The specificity was 98%. The specificity of the ELISA Kit was 98%.

  14. Improving the diagnostic accuracy of acute myocardial infarction with the use of high-sensitive cardiac troponin T in different chronic kidney disease stages

    PubMed Central

    Yang, Hongliu; Liu, Jing; Luo, Han; Zeng, Xiaoxi; Tang, Xi; Ma, Liang; Mai, Hongxia; Gou, Shenju; Liu, Fang; Fu, Ping

    2017-01-01

    High-sensitive cardiac troponin T (hs-TnT) is a critical biomarker in diagnosis of acute myocardial infarction (AMI). However, CKD individuals usually have elevated hs-TnT even in the absence of AMI. Our study aimed to explore the optimal cutoff-value of hs-TnT and further to improve diagnostic accuracy of AMI in CKD patients. Clinical data of 489 patients were collected from the maintained database between September 2010 and June 2014. CKD patients with AMI were assigned to CKD+AMI group and CKD patients without AMI were assigned to CKD group. Receiver operating characteristic curves were utilized to derive the optimal cutoff-value. In CKD+STEMI and CKD group, hs-TnT was increased with descending eGFR. In CKD+NSTEMI group, hs-TnT showed an upward trend with increasing SYNTAX Score. In patients with CKD+STEMI, hs-TnT was significantly correlated with SYNTAX Score in CKD stage 2, stage 4 and in total. In CKD patients, the optimal cutoff-value of hs-TnT for diagnosis of AMI was 129.45 ng/l with 75.2% sensitivity and 83.2% specificity. The cutoff-value appeared to be hs-TnT level of 99.55ng/l in CKD stage 3, 129.45 ng/l in CKD stage 4, 105.50 ng/l in CKD stage 5 and 149.35 ng/l in dialysis patients, respectively. In different stages of CKD, eGFR-range-specific optimal cutoff-values should be considered. PMID:28145489

  15. Factors Affecting Accuracy of Past Tense Production in Children with Specific Language Impairment and Their Typically Developing Peers: The Influence of Verb Transitivity, Clause Location, and Sentence Type

    ERIC Educational Resources Information Center

    Owen, Amanda J.

    2010-01-01

    Purpose: The author examined the influence of sentence type, clause order, and verb transitivity on the accuracy of children's past tense productions. All groups of children, but especially children with specific language impairment (SLI), were predicted to decrease accuracy as linguistic complexity increased. Method: The author elicited past…

  16. Accuracy of specimen-specific nonlinear finite element analysis for evaluation of radial diaphysis strength in cadaver material.

    PubMed

    Matsuura, Yusuke; Kuniyoshi, Kazuki; Suzuki, Takane; Ogawa, Yasufumi; Sukegawa, Koji; Rokkaku, Tomoyuki; Thoreson, Andrew Ryan; An, Kai-Nan; Takahashi, Kazuhisa

    2015-01-01

    The feasibility of a user-specific finite element model for predicting the in situ strength of the radius after implantation of bone plates for open fracture reduction was established. The effect of metal artifact in CT imaging was characterized. The results were verified against biomechanical test data. Fourteen cadaveric radii were divided into two groups: (1) intact radii for evaluating the accuracy of radial diaphysis strength predictions with finite element analysis and (2) radii with a locking plate affixed for evaluating metal artifact. All bones were imaged with CT. In the plated group, radii were first imaged with the plates affixed (for simulating digital plate removal). They were then subsequently imaged with the locking plates and screws removed (actual plate removal). Fracture strength of the radius diaphysis under axial compression was predicted with a three-dimensional, specimen-specific, nonlinear finite element analysis for both the intact and plated bones (bones with and without the plate captured in the scan). Specimens were then loaded to failure using a universal testing machine to verify the actual fracture load. In the intact group, the physical and predicted fracture loads were strongly correlated. For radii with plates affixed, the physical and predicted (simulated plate removal and actual plate removal) fracture loads were strongly correlated. This study demonstrates that our specimen-specific finite element analysis can accurately predict the strength of the radial diaphysis. The metal artifact from CT imaging was shown to produce an overestimate of strength.

  17. Sensitivity and Specificity of In Situ Hybridization for Diagnosis of Cutaneous Infection by Leishmania infantum in Dogs

    PubMed Central

    Figueiredo, Fabiano B.; Wise, Annabel G.; Madeira, Maria F.; Oliveira, Raquel V. C.; Schubach, Tânia M. P.; Kiupel, Matti; Langohr, Ingeborg M.

    2013-01-01

    An accurate diagnosis of infection by Leishmania infantum in dogs is fundamental for the control of zoonotic visceral leishmaniasis (VL). Histopathology (HP) and immunohistochemistry (IHC) are frequently used for the histological diagnosis of L. infantum in dogs but have shown limited accuracy. To improve the sensitivity and specificity of the histological diagnosis of VL, we evaluated automated in situ hybridization (ISH) using a generic probe for Leishmania and a specific probe for L. infantum in surgical skin biopsy specimens of dogs. The ISH results were compared with those of HP and IHC, using parasitological culture as the reference standard. Skin samples from 51 dogs with cutaneous L. infantum infection and 51 noninfected dogs were randomly selected from samples of dogs from various cities in Brazil where canine VL is endemic. These samples were processed for parasitological culture, HP, IHC, and ISH using both probes. The sensitivities of ISH using the specific probe, ISH using the generic probe, IHC, and HP were, respectively, 74.5%, 70.6%, 69.5%, and 57.6%. The specificity of both ISH probes tested was 100%, and there was no cross-hybridization of the generic and specific probes with selected pathogenic fungi and protozoa. The specific probe discriminated L. infantum from the other species of Leishmania that infect dogs in the New World. ISH is highly sensitive and specific for the diagnosis of L. infantum in histologic samples of skin from infected dogs and can be used on routine biopsy material to make a diagnosis of leishmaniasis. PMID:23135932

  18. Control over structure-specific flexibility improves anatomical accuracy for point-based deformable registration in bladder cancer radiotherapy

    SciTech Connect

    Wognum, S.; Chai, X.; Hulshof, M. C. C. M.; Bel, A.; Bondar, L.; Zolnay, A. G.; Hoogeman, M. S.

    2013-02-15

    Purpose: Future developments in image guided adaptive radiotherapy (IGART) for bladder cancer require accurate deformable image registration techniques for the precise assessment of tumor and bladder motion and deformation that occur as a result of large bladder volume changes during the course of radiotherapy treatment. The aim was to employ an extended version of a point-based deformable registration algorithm that allows control over tissue-specific flexibility in combination with the authors' unique patient dataset, in order to overcome two major challenges of bladder cancer registration, i.e., the difficulty in accounting for the difference in flexibility between the bladder wall and tumor and the lack of visible anatomical landmarks for validation. Methods: The registration algorithm used in the current study is an extension of the symmetric-thin plate splines-robust point matching (S-TPS-RPM) algorithm, a symmetric feature-based registration method. The S-TPS-RPM algorithm has been previously extended to allow control over the degree of flexibility of different structures via a weight parameter. The extended weighted S-TPS-RPM algorithm was tested and validated on CT data (planning- and four to five repeat-CTs) of five urinary bladder cancer patients who received lipiodol injections before radiotherapy. The performance of the weighted S-TPS-RPM method, applied to bladder and tumor structures simultaneously, was compared with a previous version of the S-TPS-RPM algorithm applied to bladder wall structure alone and with a simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. Performance was assessed in terms of anatomical and geometric accuracy. The anatomical accuracy was calculated as the residual distance error (RDE) of the lipiodol markers and the geometric accuracy was determined by the surface distance, surface coverage, and inverse consistency errors. Optimal parameter values for the flexibility and bladder weight

  19. Sensitivity and specificity considerations for fMRI encoding, decoding, and mapping of auditory cortex at ultra-high field.

    PubMed

    Moerel, Michelle; De Martino, Federico; Kemper, Valentin G; Schmitter, Sebastian; Vu, An T; Uğurbil, Kâmil; Formisano, Elia; Yacoub, Essa

    2017-03-31

    Following rapid technological advances, ultra-high field functional MRI (fMRI) enables exploring correlates of neuronal population activity at an increasing spatial resolution. However, as the fMRI blood-oxygenation-level-dependent (BOLD) contrast is a vascular signal, the spatial specificity of fMRI data is ultimately determined by the characteristics of the underlying vasculature. At 7T, fMRI measurement parameters determine the relative contribution of the macro- and microvasculature to the acquired signal. Here we investigate how these parameters affect relevant high-end fMRI analyses such as encoding, decoding, and submillimeter mapping of voxel preferences in the human auditory cortex. Specifically, we compare a T2* weighted fMRI dataset, obtained with 2D gradient echo (GE) EPI, to a predominantly T2 weighted dataset obtained with 3D GRASE. We first investigated the decoding accuracy based on two encoding models that represented different hypotheses about auditory cortical processing. This encoding/decoding analysis profited from the large spatial coverage and sensitivity of the T2* weighted acquisitions, as evidenced by a significantly higher prediction accuracy in the GE-EPI dataset compared to the 3D GRASE dataset for both encoding models. The main disadvantage of the T2* weighted GE-EPI dataset for encoding/decoding analyses was that the prediction accuracy exhibited cortical depth dependent vascular biases. However, we propose that the comparison of prediction accuracy across the different encoding models may be used as a post processing technique to salvage the spatial interpretability of the GE-EPI cortical depth-dependent prediction accuracy. Second, we explored the mapping of voxel preferences. Large-scale maps of frequency preference (i.e., tonotopy) were similar across datasets, yet the GE-EPI dataset was preferable due to its larger spatial coverage and sensitivity. However, submillimeter tonotopy maps revealed biases in assigned frequency

  20. Specific Patterns of Allergic Sensitization in Early Childhood and Asthma & Rhinitis Risk

    PubMed Central

    Stoltz, Daniel J.; Jackson, Daniel J.; Evans, Michael D.; Gangnon, Ronald E.; Tisler, Christopher J.; Gern, James E.; Lemanske, Robert F.

    2012-01-01

    BACKGROUND Specific patterns of allergic sensitization as well as quantification of the in vitro IgE response in early life may provide relevant clinical insight into future rhinitis and asthma risk. OBJECTIVE To define relationships among established sensitization to particular aeroallergens, quantitative analyses of allergen-specific IgE levels, pet exposure and sensitization, and asthma and rhinitis risk. METHODS Children at high-risk for the development of asthma and allergic diseases were enrolled at birth into the Childhood Origins of ASThma (COAST) study. Allergen-specific IgE was assessed at ages 1, 3, 6, and 9 years by fluoroenzyme immunoassay (Unicap® 100, Pharmacia Diagnostics). Current asthma and rhinitis were diagnosed at age 6 and 8 years. RESULTS Sensitization to dog was strongly associated with increased asthma risk (p < 0.0001). Sensitization to perennial compared to seasonal allergens was more strongly associated with asthma risk, while sensitization to seasonal allergens was more closely associated with rhinitis risk. Increased levels of specific IgE to perennial allergens were associated with an increased asthma risk (p = 0.05), while any detectable level of IgE to seasonal allergens was associated with increased rhinitis risk (p = 0.0009). While dog and cat sensitization were both independently associated with increased asthma and rhinitis risk, dog exposure at birth was associated with a reduced risk of asthma, regardless of dog sensitization status during the first 6 years of life (p = 0.05). CONCLUSIONS & CLINICAL RELEVANCE Analyzing specific patterns of an individual’s allergic sensitization profile reveals additional relevant associations with asthma and rhinitis risk as opposed to the information gained from characterizing an individual as “atopic” by the presence of any demonstrable sensitization alone. Further, protective mechanisms of dog exposure with regards to asthma risk appear to be unrelated to the prevention of

  1. Efficient Noninferiority Testing Procedures for Simultaneously Assessing Sensitivity and Specificity of Two Diagnostic Tests.

    PubMed

    Shan, Guogen; Amei, Amei; Young, Daniel

    2015-01-01

    Sensitivity and specificity are often used to assess the performance of a diagnostic test with binary outcomes. Wald-type test statistics have been proposed for testing sensitivity and specificity individually. In the presence of a gold standard, simultaneous comparison between two diagnostic tests for noninferiority of sensitivity and specificity based on an asymptotic approach has been studied by Chen et al. (2003). However, the asymptotic approach may suffer from unsatisfactory type I error control as observed from many studies, especially in small to medium sample settings. In this paper, we compare three unconditional approaches for simultaneously testing sensitivity and specificity. They are approaches based on estimation, maximization, and a combination of estimation and maximization. Although the estimation approach does not guarantee type I error, it has satisfactory performance with regard to type I error control. The other two unconditional approaches are exact. The approach based on estimation and maximization is generally more powerful than the approach based on maximization.

  2. The sensitivity and specificity of F-DOPA PET in a movement disorder clinic

    PubMed Central

    Ibrahim, Nevein; Kusmirek, Joanna; Struck, Aaron F; Floberg, John M; Perlman, Scott B; Gallagher, Catherine; Hall, Lance T

    2016-01-01

    Idiopathic Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Early PD may present a diagnostic challenge with broad differential diagnoses that are not associated with nigral degeneration or striatal dopamine deficiency. Therefore, the early clinical diagnosis alone may not be accurate and this reinforces the importance of functional imaging targeting the pathophysiology of the disease process. 18F-DOPA L-6-[18F] fluoro-3,4-dihydroxyphenylalnine (18F-DOPA) is a positron emission tomography (PET) agent that measures the uptake of dopamine precursors for assessment of presynaptic dopaminergic integrity and has been shown to accurately reflect the monoaminergic disturbances in PD. In this study, we aim to illustrate our local experience to determine the accuracy of 18F-DOPA PET for diagnosis of PD. We studied a total of 27 patients. A retrospective analysis was carried out for all patients that underwent 18F-DOPA PET brain scan for motor symptoms suspicious for PD between 2001-2008. Both qualitative and semi-quantitative analyses of the scans were performed. The patient’s medical records were then assessed for length of follow-up, response to levodopa, clinical course of illness, and laterality of symptoms at time of 18F-DOPA PET. The eventual diagnosis by the referring neurologist, movement disorder specialist, was used as the reference standard for further analysis. Of the 28 scans, we found that one was a false negative, 20 were true positives, and 7 were true negatives. The resultant values are Sensitivity 95.4% (95% CI: 100%-75.3%), Specificity 100% (95% CI: 100%-59.0%), PPV 100% (95% CI 100%-80.7%), and NPV 87.5% (95% CI: 99.5%-50.5%). PMID:27069770

  3. Evaluation of deformation accuracy of a virtual pneumoperitoneum method based on clinical trials for patient-specific laparoscopic surgery simulator

    NASA Astrophysics Data System (ADS)

    Oda, Masahiro; Qu, Jia Di; Nimura, Yukitaka; Kitasaka, Takayuki; Misawa, Kazunari; Mori, Kensaku

    2012-02-01

    This paper evaluates deformation accuracy of a virtual pneumoperitoneum method by utilizing measurement data of real deformations of patient bodies. Laparoscopic surgery is an option of surgical operations that is less invasive technique as compared with traditional surgical operations. In laparoscopic surgery, the pneumoperitoneum process is performed to create a viewing and working space. Although a virtual pneumoperitoneum method based on 3D CT image deformation has been proposed for patient-specific laparoscopy simulators, quantitative evaluation based on measurements obtained in real surgery has not been performed. In this paper, we evaluate deformation accuracy of the virtual pneumoperitoneum method based on real deformation data of the abdominal wall measured in operating rooms (ORs.) The evaluation results are used to find optimal deformation parameters of the virtual pneumoperitoneum method. We measure landmark positions on the abdominal wall on a 3D CT image taken before performing a pneumoperitoneum process. The landmark positions are defined based on anatomical structure of a patient body. We also measure the landmark positions on a 3D CT image deformed by the virtual pneumoperitoneum method. To measure real deformations of the abdominal wall, we measure the landmark positions on the abdominal wall of a patient before and after the pneumoperitoneum process in the OR. We transform the landmark positions measured in the OR from the tracker coordinate system to the CT coordinate system. A positional error of the virtual pneumoperitoneum method is calculated based on positional differences between the landmark positions on the 3D CT image and the transformed landmark positions. Experimental results based on eight cases of surgeries showed that the minimal positional error was 13.8 mm. The positional error can be decreased from the previous method by calculating optimal deformation parameters of the virtual pneumoperitoneum method from the experimental

  4. A sensitive and specific hyperbranched rolling circle amplification assay and test strip for white spot syndrome virus.

    PubMed

    Zhao, Yu-Ran; Yin, Wei-Li; Yue, Zhi-Qin; Li, Ba-Fang

    2014-01-01

    White spot syndrome virus (WSSV) is a global threat to the prawn industry, and there is no simple method for field-based testing of this virus. We designed a padlock probe and primers to the capsid protein gene VP28 of WSSV, and established a hyperbranched rolling circle amplification (HRCA) assay and a corresponding strip-based test. The assay and the test strip both had similar high accuracy and specificity, and their sensitivity was about 10 copies/μL, which is 100 times higher than conventional PCR. In this study, 68 batches of prawns were tested for WSSV with the HRCA assay and test strip, and the results were compared with the PCR assay. The results indicated that both the assay and test strip had accuracy similar to each other and to the PCR results. However, the assay and strip were more sensitive and user-friendly than PCR. Establishment of this method will provide a rapid detection of WSSV and also a basis for field-based detection of animal disease.

  5. Accuracy and Sensitivity of Commercial PCR-Based Methods for Detection of Salmonella enterica in Feed ▿

    PubMed Central

    Koyuncu, Sevinc; Andersson, M. Gunnar; Häggblom, Per

    2010-01-01

    The present study compared the performance of commercial PCR-based Salmonella enterica detection methods (BAX System Q7, the iQ-Check Salmonella II kit, and the TaqMan Salmonella enterica detection kit) with culture-based methods (modified semisolid Rappaport-Vassiliadis [MSRV] and NMKL71) in spiked and naturally contaminated samples of feed mill scrapings (FMS), palm kernel meal (PKM), pelleted feed (PF), rape seed meal (RSM), soybean meal (SM), and wheat grain (WG). When results from the various feeds were compared, the number of Salmonella enterica CFU/25 g required to produce a positive were as follows: PKM > FMS = WG > RSM = SM = PF. These data are similar to those developed in earlier studies with culture-based Salmonella detection methods. PCR-based methods were performed similarly to culture-based methods, with respect to sensitivity and specificity. However, many PCR positives could not be confirmed by Salmonella isolation and for that reason the evaluated methods were found to be suitable only when rapid results were paramount. Nevertheless, PCR-based methods cannot presently replace culture-based methods when typing information is required for tracing studies or epidemiological investigations. The observed difference in detection levels is a potential problem when prevalence data are compared as well as when feed ingredients are tested for conformance with microbiological criteria. This paper also presents a statistical model that describes the detection probability when different levels (CFU) of Salmonella contamination are present in feed materials. PMID:20228106

  6. Luminescent analysis of lymphocytes of peripheral blood in definition of organism's sensitivity to specific antigene

    NASA Astrophysics Data System (ADS)

    Yusupova, Lira B.

    1994-01-01

    Possibility for definition of organism's sensitivity to specific allergen by means of luminescent analysis of peripheral blood lymphocytes was shown. The positive correlation dependence between luminescence intensity increase at 640 nm of acridine orange colored lymphocytes after simulation by specific allergene in vitro and the serum antiallergene antibodies level was detected.

  7. Specific and differential prediction of health anxiety by disgust sensitivity and propensity.

    PubMed

    Brady, Robert E; Cisler, Josh M; Lohr, Jeffrey M

    2014-01-01

    Current models of health anxiety suggest that fear resulting from false alarms to perceived threats to one's health results in the development of hypochondriasis and related disorders. Disgust has been proposed as an affective response that may function as an etiological and maintenance mechanism in health anxiety. Moreover, the way in which an individual perceives the disgust response (disgust sensitivity) may affect health anxiety, separately from their likelihood of experiencing disgust (disgust propensity). The present study utilized multiple hierarchical regression analysis to investigate the degree to which self-reported disgust sensitivity and disgust propensity differentially predict elevated health anxiety in a sample of 620 non-treatment-seeking undergraduates. Further, this effect is tested in comparison to that of anxiety sensitivity, a construct demonstrated to be strongly related to health anxiety. Analyses indicate that disgust sensitivity, rather than disgust propensity, is primarily responsible for this relation. An additional analysis tested the specificity of disgust sensitivity relative to anxiety sensitivity. Disgust sensitivity was no longer significant after including anxiety sensitivity in the model. Suggestions for further evaluation of this relation are provided. These results suggest that although disgust sensitivity may appear related to health anxiety, this relation may be confounded by anxiety sensitivity.

  8. Analyzing the tradeoff between electrical complexity and accuracy in patient-specific computational models of deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Howell, Bryan; McIntyre, Cameron C.

    2016-06-01

    Objective. Deep brain stimulation (DBS) is an adjunctive therapy that is effective in treating movement disorders and shows promise for treating psychiatric disorders. Computational models of DBS have begun to be utilized as tools to optimize the therapy. Despite advancements in the anatomical accuracy of these models, there is still uncertainty as to what level of electrical complexity is adequate for modeling the electric field in the brain and the subsequent neural response to the stimulation. Approach. We used magnetic resonance images to create an image-based computational model of subthalamic DBS. The complexity of the volume conductor model was increased by incrementally including heterogeneity, anisotropy, and dielectric dispersion in the electrical properties of the brain. We quantified changes in the load of the electrode, the electric potential distribution, and stimulation thresholds of descending corticofugal (DCF) axon models. Main results. Incorporation of heterogeneity altered the electric potentials and subsequent stimulation thresholds, but to a lesser degree than incorporation of anisotropy. Additionally, the results were sensitive to the choice of method for defining anisotropy, with stimulation thresholds of DCF axons changing by as much as 190%. Typical approaches for defining anisotropy underestimate the expected load of the stimulation electrode, which led to underestimation of the extent of stimulation. More accurate predictions of the electrode load were achieved with alternative approaches for defining anisotropy. The effects of dielectric dispersion were small compared to the effects of heterogeneity and anisotropy. Significance. The results of this study help delineate the level of detail that is required to accurately model electric fields generated by DBS electrodes.

  9. Verification of Accuracy of CyberKnife Tumor-tracking Radiation Therapy Using Patient-specific Lung Phantoms

    SciTech Connect

    Jung, Jinhong; Song, Si Yeol; Yoon, Sang Min; Kwak, Jungwon; Yoon, KyoungJun; Choi, Wonsik; Jeong, Seong-Yun; Choi, Eun Kyung; Cho, Byungchul

    2015-07-15

    Purpose: To investigate the accuracy of the CyberKnife Xsight Lung Tracking System (XLTS) compared with that of a fiducial-based target tracking system (FTTS) using patient-specific lung phantoms. Methods and Materials: Three-dimensional printing technology was used to make individualized lung phantoms that closely mimicked the lung anatomy of actual patients. Based on planning computed tomographic data from 6 lung cancer patients who underwent stereotactic ablative radiation therapy using the CyberKnife, the volume above a certain Hounsfield unit (HU) was assigned as the structure to be filled uniformly with polylactic acid material by a 3-dimensional printer (3D Edison, Lokit, Korea). We evaluated the discrepancies between the measured and modeled target positions, representing the total tracking error, using 3 log files that were generated during each treatment for both the FTTS and the XLTS. We also analyzed the γ index between the film dose measured under the FTTS and XLTS. Results: The overall mean values and standard deviations of total tracking errors for the FTTS were 0.36 ± 0.39 mm, 0.15 ± 0.64 mm, and 0.15 ± 0.62 mm for the craniocaudal (CC), left–right (LR), and anteroposterior (AP) components, respectively. Those for the XLTS were 0.38 ± 0.54 mm, 0.13 ± 0.18 mm, and 0.14 ± 0.37 mm for the CC, LR, and AP components, respectively. The average of γ passing rates was 100% for the criteria of 3%, 3 mm; 99.6% for the criteria of 2%, 2 mm; and 86.8% for the criteria of 1%, 1 mm. Conclusions: The XLTS has segmentation accuracy comparable with that of the FTTS and small total tracking errors.

  10. Intra- and inter-laboratory reproducibility and accuracy of the LuSens assay: A reporter gene-cell line to detect keratinocyte activation by skin sensitizers.

    PubMed

    Ramirez, Tzutzuy; Stein, Nadine; Aumann, Alexandra; Remus, Tina; Edwards, Amber; Norman, Kimberly G; Ryan, Cindy; Bader, Jackie E; Fehr, Markus; Burleson, Florence; Foertsch, Leslie; Wang, Xiaohong; Gerberick, Frank; Beilstein, Paul; Hoffmann, Sebastian; Mehling, Annette; van Ravenzwaay, Bennard; Landsiedel, Robert

    2016-04-01

    Several non-animal methods are now available to address the key events leading to skin sensitization as defined by the adverse outcome pathway. The KeratinoSens assay addresses the cellular event of keratinocyte activation and is a method accepted under OECD TG 442D. In this study, the results of an inter-laboratory evaluation of the "me-too" LuSens assay, a bioassay that uses a human keratinocyte cell line harboring a reporter gene construct composed of the rat antioxidant response element (ARE) of the NADPH:quinone oxidoreductase 1 gene and the luciferase gene, are described. Earlier in-house validation with 74 substances showed an accuracy of 82% in comparison to human data. When used in a battery of non-animal methods, even higher predictivity is achieved. To meet European validation criteria, a multicenter study was conducted in 5 laboratories. The study was divided into two phases, to assess 1) transferability of the method, and 2) reproducibility and accuracy. Phase I was performed by testing 8 non-coded test substances; the results showed a good transferability to naïve laboratories even without on-site training. Phase II was performed with 20 coded test substances (performance standards recommended by OECD, 2015). In this phase, the intra- and inter-laboratory reproducibility as well as accuracy of the method was evaluated. The data demonstrate a remarkable reproducibility of 100% and an accuracy of over 80% in identifying skin sensitizers, indicating a good concordance with in vivo data. These results demonstrate good transferability, reliability and accuracy of the method thereby achieving the standards necessary for use in a regulatory setting to detect skin sensitizers.

  11. High specificity but low sensitivity of mutation-specific antibodies against EGFR mutations in non-small-cell lung cancer.

    PubMed

    Bondgaard, Anna-Louise; Høgdall, Estrid; Mellemgaard, Anders; Skov, Birgit G

    2014-12-01

    Determination of epidermal growth factor receptor (EGFR) mutations has a pivotal impact on treatment of non-small-cell lung cancer (NSCLC). A standardized test has not yet been approved. So far, Sanger DNA sequencing has been widely used. Its rather low sensitivity has led to the development of more sensitive methods including real-time PCR (RT-PCR). Immunohistochemistry with mutation-specific antibodies might be a promising detection method. We evaluated 210 samples with NSCLC from an unselected Caucasian population. Extracted DNA was analyzed for EGFR mutations by RT-PCR (Therascreen EGFR PCR kit, Qiagen, UK; reference method). For immunohistochemistry, antibodies against exon19 deletions (clone 6B6), exon21 mutations (clone 43B2) from Cell Signaling Technology (Boston, USA) and EGFR variantIII (clone 218C9) from Dako (Copenhagen, DK) were applied. Protein expression was evaluated, and staining score (multipum of intensity (graded 0-3) and percentages (0-100%) of stained tumor cells) was calculated. Positivity was defined as staining score >0. Specificity of exon19 antibody was 98.8% (95% confidence interval=95.9-99.9%) and of exon21 antibody 97.8% (95% confidence interval=94.4-99.4%). Sensitivity of exon19 antibody was 63.2% (95% confidence interval=38.4-83.7%) and of exon21 antibody was 80.0% (95% confidence interval=44.4-97.5%). Seven exon19 and four exon21 mutations were false negatives (immunohistochemistry negative, RT-PCR positive). Two exon19 and three exon21 mutations were false positive (immunohistochemistry positive, RT-PCR negative). One false positive exon21 mutation had staining score 300. The EGFR variantIII antibody showed no correlation to EGFR mutation status determined by RT-PCR or to EGFR immunohistochemistry. High specificity of the mutation-specific antibodies was demonstrated. However, sensitivity was low, especially for exon19 deletions, and thus these antibodies cannot yet be used as screening method for EGFR mutations in NSCLC

  12. The sensitivity and specificity of postbreeding plasma progesterone levels as a pregnancy test for dairy cows.

    PubMed Central

    Montgomery, M E; Leslie, K E; Martin, S W

    1985-01-01

    Plasma progesterone levels on day 4 and day 8 postbreeding were measured for one hundred and eighty-four dairy cows. These two parameters (PPD4, PPD8), their absolute difference (PPDIFF) and their ratio (PPRATIO) were assessed for their ability to identify cows not conceiving, using the principles of sensitivity and specificity. PPD4 was significantly higher (p less than 0.10) and PPD8, PPDIFF and PPRATIO were significantly lower (p less than 0.01) in cows remaining open than in pregnant cows. Evaluating each parameter separately, PPDIFF greater than 3.00 units had the highest specificity, 85.7%, but a low sensitivity (27.0%). Combining two parameters using series interpretation to increase specificity resulted in the best combination of specificity (87%) and sensitivity (27%). Maximum specificity was 97% for PPD4 less than or equal to 1.00 units and PPD8 greater than 4.00 units, and also for PPD4 less than or equal to 1.00 units and PPDIFF greater than 3.00 units, but sensitivity was very low (7% and 10% respectively). Predictive values of the test results with the best specificity were evaluated; given the population pregnancy rate of 54%, none exceeded 50%, indicating that the plasma progesterone parameters were not very useful for identifying open dairy cows. PMID:4041979

  13. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity

    PubMed Central

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination. PMID:27110562

  14. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity.

    PubMed

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination.

  15. Issues of sample size in sensitivity and specificity analysis with special reference to oncology.

    PubMed

    Juneja, Atul; Sharma, Shashi

    2015-01-01

    Sample size is one of the basics issues, which medical researcher including oncologist faces with any research program. The current communication attempts to discuss the computation of sample size when sensitivity and specificity are being evaluated. The article intends to present the situation that the researcher could easily visualize for appropriate use of sample size techniques for sensitivity and specificity when any screening method for early detection of cancer is in question. Moreover, the researcher would be in a position to efficiently communicate with a statistician for sample size computation and most importantly applicability of the results under the conditions of the negotiated precision.

  16. Sample taking during orthopedic surgery: sensitivity and specificity using the BACTEC blood culture system.

    PubMed

    Podleska, L E; Lendemans, S; Schmid, E; Hussmann, B; Nast-Kolb, D; Taeger, G

    2012-02-01

    The use of blood culture systems for sterile body fluids other than blood has proven to be superior to routine culture methods. This study was conducted in order to assess the performance of the BACTEC blood culture system compared to swab/tissue sample collection for the detection of infection from intraoperative samples taken during surgical procedures. Sensitivity was determined by taking samples (BACTEC and swab/tissue samples) from patients with clinically evident infection (Infection group). Specificity was tested by taking the same sample sets from patients who had aseptic operations with no history of infection (Control group). The sensitivity was found to be much higher for the BACTEC group (50 isolates from 56 samples, sensitivity: 89%) compared to the swab/tissue samples (29 isolates out of 56 samples, sensitivity: 52%). The specificity was lower in the BACTEC group (32 isolates out of 44 samples, specificity: 27%) compared to the swab/tissue samples (1 isolate out of 44 samples, specificity: 98%). We conclude that BACTEC is useful for intraoperative sample collection in cases of low-grade infection. However, it is less specific and there is always the possibility for contamination. Therefore, it is advisable to use this technique in combination with regular tissue samples.

  17. Assessing the accuracy of subject-specific, muscle-model parameters determined by optimizing to match isometric strength.

    PubMed

    DeSmitt, Holly J; Domire, Zachary J

    2016-12-01

    Biomechanical models are sensitive to the choice of model parameters. Therefore, determination of accurate subject specific model parameters is important. One approach to generate these parameters is to optimize the values such that the model output will match experimentally measured strength curves. This approach is attractive as it is inexpensive and should provide an excellent match to experimentally measured strength. However, given the problem of muscle redundancy, it is not clear that this approach generates accurate individual muscle forces. The purpose of this investigation is to evaluate this approach using simulated data to enable a direct comparison. It is hypothesized that the optimization approach will be able to recreate accurate muscle model parameters when information from measurable parameters is given. A model of isometric knee extension was developed to simulate a strength curve across a range of knee angles. In order to realistically recreate experimentally measured strength, random noise was added to the modeled strength. Parameters were solved for using a genetic search algorithm. When noise was added to the measurements the strength curve was reasonably recreated. However, the individual muscle model parameters and force curves were far less accurate. Based upon this examination, it is clear that very different sets of model parameters can recreate similar strength curves. Therefore, experimental variation in strength measurements has a significant influence on the results. Given the difficulty in accurately recreating individual muscle parameters, it may be more appropriate to perform simulations with lumped actuators representing similar muscles.

  18. Sensitivity to general and specific numerical features in typical achievers and children with mathematics learning disability.

    PubMed

    Rotem, Avital; Henik, Avishai

    2015-01-01

    We examined the development of sensitivity to general and specific numerical features in typical achievers and in 6th and 8th graders with mathematics learning disability (MLD), using two effects in mental multiplication: operand-relatedness (i.e., difficulty in avoiding errors that are related to the operands via a shared multiplication row) and decade-consistency (i.e., difficulty in avoiding errors that are operand related and also share a decade with the true result). Responses to decade-consistent products were quick but erroneous. In line with the processing sequence in adults, children first became sensitive to the general numerical feature of operand-relatedness (typical achievers--from 3rd grade; children with MLD in 8th grade) and only later to the specific feature of decade-consistency (typical achievers--from 4th grade, but only from 6th grade in a mature pattern). Implications of the numerical sensitivity in children with MLD are discussed.

  19. California Verbal Learning Test Indicators of Malingered Neurocognitive Dysfunction: Sensitivity and Specificity in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Curtis, Kelly L.; Greve, Kevin W.; Bianchini, Kevin J.; Brennan, Adrianne

    2006-01-01

    The present study used well-defined traumatic brain injury (TBI) and mixed neurological (other than TBI) and psychiatric samples to examine the specificity and sensitivity to Malingered Neurocognitive Dysfunction (MND) of four individual California Verbal Learning Test (CVLT) variables and eight composite CVLT malingering indicators. Participants…

  20. Sensitivity and Specificity of the Montreal Cognitive Assessment Modified for Individuals Who Are Visually Impaired

    ERIC Educational Resources Information Center

    Wittich, Walter; Phillips, Natalie; Nasreddine, Ziad S.; Chertkow, Howard

    2010-01-01

    Evaluating the cognitive status of individuals who are visually impaired is limited by the design of the test that is used. This article presents data on the sensitivity and specificity of the version of the Montreal Cognitive Assessment for people who are visually impaired. The original validation data were reanalyzed, excluding the five visual…

  1. Highly sensitive and specific colorimetric detection of cancer cells via dual-aptamer target binding strategy.

    PubMed

    Wang, Kun; Fan, Daoqing; Liu, Yaqing; Wang, Erkang

    2015-11-15

    Simple, rapid, sensitive and specific detection of cancer cells is of great importance for early and accurate cancer diagnostics and therapy. By coupling nanotechnology and dual-aptamer target binding strategies, we developed a colorimetric assay for visually detecting cancer cells with high sensitivity and specificity. The nanotechnology including high catalytic activity of PtAuNP and magnetic separation & concentration plays a vital role on the signal amplification and improvement of detection sensitivity. The color change caused by small amount of target cancer cells (10 cells/mL) can be clearly distinguished by naked eyes. The dual-aptamer target binding strategy guarantees the detection specificity that large amount of non-cancer cells and different cancer cells (10(4) cells/mL) cannot cause obvious color change. A detection limit as low as 10 cells/mL with detection linear range from 10 to 10(5) cells/mL was reached according to the experimental detections in phosphate buffer solution as well as serum sample. The developed enzyme-free and cost effective colorimetric assay is simple and no need of instrument while still provides excellent sensitivity, specificity and repeatability, having potential application on point-of-care cancer diagnosis.

  2. Autism Spectrum Disorder in the DSM-5: Diagnostic Sensitivity and Specificity in Early Childhood

    ERIC Educational Resources Information Center

    Christiansz, Jessica A.; Gray, Kylie M.; Taffe, John; Tonge, Bruce J.

    2016-01-01

    Changes to the DSM-5 Autism Spectrum Disorder (ASD) criteria raised concerns among parents and practitioners that the criteria may exclude some children with Pervasive Developmental Disorder (PDD). Few studies have examined DSM-5 sensitivity and specificity in children less than 5 years of age. This study evaluated 185 children aged 20-55 months…

  3. Mesocosm Community Response Sensitivities to Specific Conductivity Comprised of Different Major Ions

    EPA Science Inventory

    Traditional toxicity test assays have been used to evaluate the relative sensitivity to different major ion mixtures as a proxy for understanding what the response of aquatic species growing in their natural environment would be during exposure to specific conductivity stress ema...

  4. The Sensitivity and Specificity of Depression Screening Tools among Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Ailey, Sarah H.

    2009-01-01

    This study describes the validity and the sensitivity and specificity of depression screening tools among adults with intellectual and disabilities (ID). Subjects (N = 75) were interviewed with the Beck Depression Inventory II (BDI-II) and the Glasgow Depression Scale for People with a Learning Disability (GDS-LD) and also completed a clinical…

  5. Sensitivity and Specificity of Depression Questionnaires in a College-Age Sample

    ERIC Educational Resources Information Center

    Shean, Glenn; Baldwin, Gretchen

    2008-01-01

    The authors evaluated the sensitivity and specificity of the Beck Depression Inventory-II (BDI-II; A. T. Beck, R. A. Steer, & G. K. Brown, 1996) and Center for Epidemiological Studies-Depression Scale (CESD; L. S. Radloff, 1977) questionnaires for a college-student sample. Results indicate that the BDI-II and CES-D evidenced satisfactory…

  6. Utility of the Spelling Sensitivity Score to Analyze Spellings of Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Werfel, Krystal L.; Krimm, Hannah

    2015-01-01

    The purpose of this study was to examine the utility of the Spelling Sensitivity Score (SSS) beyond percentage correct scoring in analyzing the spellings of children with specific language impairment (SLI). Participants were 31 children with SLI and 28 children with typical language in grades 2-4. Spellings of individual words were scored using…

  7. Comparison of specific versus literature species sensitivity distributions for herbicides risk assessment.

    PubMed

    Larras, Floriane; Gregorio, Vincent; Bouchez, Agnès; Montuelle, Bernard; Chèvre, Nathalie

    2016-02-01

    Species sensitivity distributions (SSDs) are an important predictive tool in risk assessment. Usually, literature data are used to build SSDs that are mostly based on planktonic species. But, to get adequate protective thresholds for environmental communities, one could argue that SSD should be built on ecotoxicological data obtained from species found in the ecosystem that should be protected. This is particularly true when benthic algae are of concern. Due to the lack of literature data, building SSD on benthic microalgae is difficult. This paper aims in comparing SSDs, and thus protective thresholds (hazardous concentration that affects 5% of the species of a community, HC5), built on ecotoxicological data obtained (1) from literature and (2) with specific bioassays on benthic diatoms from a lake. Thresholds were derived for protection against four herbicides separately and for a mixture of them. Sensitivity data obtained from literature were statistically lower than the specific data for all herbicides: Species tested in the literature were usually more sensitive (mainly chlorophytes), leading to more protective lower HC5. The HC5 thresholds (literature or specific) derived for protection against the mixture were also compared to the observed sensitivity of an assemblage of benthic diatom species exposed to an increasing range of herbicide mixture concentrations. We observed that one species within the assemblage (Fragilaria rumpens) was affected at a concentration below both the literature and the specific HC5 thresholds.

  8. Parenting Supports for Early Vocabulary Development: Specific Effects of Sensitivity and Stimulation through Infancy.

    PubMed

    Vallotton, Claire; Mastergeorge, Ann; Foster, Tricia; Decker, Kalli B; Ayoub, Catherine

    2017-01-01

    Growing recognition of disparities in early childhood language environments prompt examination of parent-child interactions which support vocabulary. Research links parental sensitivity and cognitive stimulation to child language, but has not explicitly contrasted their effects, nor examined how effects may change over time. We examined maternal sensitivity and stimulation throughout infancy using two observational methods - ratings of parents' interaction qualities, and coding of discrete parenting behaviors - to assess the relative importance of these qualities to child vocabulary over time, and determine whether mothers make related changes in response to children's development. Participants were 146 infants and mothers, assessed when infants were 14, 24, and 36 months. At 14 months, sensitivity had a stronger effect on vocabulary than did stimulation, but the effect of stimulation grew throughout toddlerhood. Mothers' cognitive stimulation grew over time, whereas sensitivity remained stable. While discrete parenting behaviors changed with child age, there was no evidence of trade-offs between sensitive and stimulating behaviors, and no evidence that sensitivity moderated the effect of stimulation on child vocabulary. Findings demonstrate specificity of timing in the link between parenting qualities and child vocabulary which could inform early parent interventions, and supports a reconceptualization of the nature and measurement of parental sensitivity.

  9. Development of Sensitive and Specific Analysis of Vildagliptin in Pharmaceutical Formulation by Gas Chromatography-Mass Spectrometry

    PubMed Central

    Uçaktürk, Ebru

    2015-01-01

    A sensitive and selective gas chromatography-mass spectrometry (GC-MS) method was developed and fully validated for the determination of vildagliptin (VIL) in pharmaceutical formulation. Prior to GC-MS analysis, VIL was efficiently derivatized with MSTFA/NH4I/β-mercaptoethanol at 60°C for 30 min. The obtained O-TMS derivative of VIL was detected by selected ion monitoring mode using the diagnostic ions m/z 223 and 252. Nandrolone was chosen as internal standard. The GC-MS method was fully validated by the following validation parameters: limit of detection (LOD) and quantitation (LOQ), linearity, precision, accuracy, specificity, stability, robustness, and ruggedness. LOD and LOQ were found to be 1.5 and 3.5 ng mL−1, respectively. The GC-MS method is linear in the range of 3.5–300 ng mL−1. The intra- and interday precision values were less than ≤3.62%. The intra- and interday accuracy values were found in the range of −0.26–2.06%. Finally, the GC-MS method was successfully applied to determine VIL in pharmaceutical formulation. PMID:26682085

  10. Giant magnetoresistive sensor array for sensitive and specific multiplexed food allergen detection.

    PubMed

    Ng, Elaine; Nadeau, Kari C; Wang, Shan X

    2016-06-15

    Current common allergen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and dip-stick methods, do not provide adequate levels of sensitivity and specificity for at-risk allergic patients. A method for performing highly sensitive and specific detection of multiple food allergens is thus imperative as food allergies are becoming increasingly recognized as a major healthcare concern, affecting an estimated 4% of the total population. We demonstrate first instance of sensitive and specific multiplexed detection of major peanut allergens Ara h 1 and Ara h 2, and wheat allergen Gliadin using giant magnetoresistive (GMR) sensor arrays. Commercialized ELISA kits for Ara h 1 and Ara h 2 report limits of detection (LODs) at 31.5 ng/mL and 0.2 ng/mL, respectively. In addition, the 96-well-based ELISA developed in-house for Gliadin was found to have a LOD of 40 ng/mL. Our multiplexed GMR-based assay demonstrates the ability to perform all three assays on the same chip specifically and with sensitivities at LODs about an order of magnitude lower than those of 96-well-based ELISAs. LODs of GMR-based assays developed for Ara h 1, Ara h 2, and Gliadin were 7.0 ng/mL, 0.2 ng/mL, and 1.5 ng/mL, respectively, with little to no cross-reactivity. These LODs are clinically important as some patients could react strongly against such low allergen levels. Given the limitations of current industrial detection technology, multiplexed GMR-based assays provide a method for highly sensitive and specific simultaneous detection of any combination of food-product allergens, thus protecting allergic patients from life-threatening events, including anaphylaxis, by unintentional consumption.

  11. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy

    PubMed Central

    Huang, Chao; Sachse, Frank B.; Hitchcock, Robert W.; Kaza, Aditya K.

    2016-01-01

    Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2±0.3% and 98.0±0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2±0.3% and 94.0±2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease. PMID:26808149

  12. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

    PubMed

    Huang, Chao; Sachse, Frank B; Hitchcock, Robert W; Kaza, Aditya K

    2016-01-01

    Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease.

  13. Aptamer capturing of enzymes on magnetic beads to enhance assay specificity and sensitivity.

    PubMed

    Zhao, Qiang; Li, Xing-Fang; Le, X Chris

    2011-12-15

    Activity and specificity of enzyme molecules are important to enzymatic reactions and enzyme assays. We describe an aptamer capturing approach that improves the specificity and the sensitivity of enzyme detection. An aptamer recognizing the target enzyme molecule is conjugated on a magnetic bead, increasing the local concentration, and serves as an affinity probe to capture and separate minute amounts of the enzyme. The captured enzymes catalyze the subsequent conversion of fluorogenic substrate to fluorescent products, enabling a sensitive measure of the active enzyme. The feasibility of this technique is demonstrated through assays for human alpha thrombin and human neutrophil elastase (HNE), two important enzymes. Thrombin (2 fM) and 100 fM HNE can be detected. The incorporation of two binding events, substrate recognition and aptamer binding, greatly improves assay specificity. With its simplicity, this approach is applicable to biosensing and detection of disease biomarkers.

  14. Reduced Accuracy and Sensitivity in the Perception of Emotional Facial Expressions in Individuals with High Autism Spectrum Traits

    ERIC Educational Resources Information Center

    Poljac, Ervin; Poljac, Edita; Wagemans, Johan

    2013-01-01

    Autism spectrum disorder (ASD) is among other things characterized by specific impairments in emotion processing. It is not clear, however, to what extent the typical decline in affective functioning is related to the specific autistic traits. We employed "The Autism Spectrum-Quotient" (AQ) to quantify autistic traits in a group of 500…

  15. Limitations of sensitivity, specificity, likelihood ratio, and bayes' theorem in assessing diagnostic probabilities: a clinical example.

    PubMed

    Moons, K G; van Es, G A; Deckers, J W; Habbema, J D; Grobbee, D E

    1997-01-01

    We evaluated the extent to which the sensitivity, specificity, and likelihood ratio of the exercise test to diagnose coronary artery disease vary across subgroups of a certain patient population. Among 295 patients suspected of coronary artery disease, as independently determined by coronary angiography, we assessed variation in sensitivity and specificity according to patient history, physical examination, exercise test results, and disease severity in 207 patients with and 88 patients without coronary artery disease, respectively. The sensitivity varied substantially according to sex (women 30% and men 64%), systolic blood pressure at baseline (53% to 65%), expected workload (50% to 64%), systolic blood pressure at peak exercise (50% to 67%), relative workload (33% to 68%), and number of diseased vessels (39% to 77%). The specificity varied across subgroups of sex (men 89% and women 97%) and relative workload (85% to 98%). The likelihood ratio varied (3.8 to 17.0) across the same patient subgroups, as did the sensitivity. As each population tends to be heterogeneous with respect to patient characteristics, no single level of these parameters can be given that is adequate for all subgroups. Use of these parameters as a basis for calculating diagnostic probabilities in individual patients using Bayes' theorem has serious limitations.

  16. Specific disgust sensitivities differentially predict interest in careers of varying procedural-intensity among medical students.

    PubMed

    Consedine, Nathan S; Windsor, John A

    2014-05-01

    Mismatches between the needs of public health systems and student interests have led to renewed study on the factors predicting career specializations among medical students. While most work examines career and lifestyle values, emotional proclivities may be important; disgust sensitivity may help explain preferences for careers with greater and lesser degrees of procedural content. In the study, 294 students completed measures assessing: (1) demographics, (2) career interest or intention regarding emergency medicine, internal medicine, obstetrics/gynecology, and pediatric medicine, (3) traditional determinants of career intention/interest, and (4) core/bodily product, animal reminder, contamination, and sexual/moral disgust sensitivity. As predicted, logistic regressions controlling for demographics and traditional career predictors, showed that greater animal reminder disgust predicted reduced interest in emergency medicine but greater interest in pediatric medicine. Conversely, greater core/bodily product disgust predicted lower interest in obstetrics/gynecology and pediatric medicine; greater contamination and sexual/moral disgust both predicted increased odds of interest in internal medicine. Overall, specific disgust sensitivities were the best predictors of specialization intention in multivariate models. Specific disgust sensitivities appear to differentially deter and/or predispose self-selection into specific trajectories varying in procedural content. Such findings may permit the early identification of specialty fit and provide guidance in career counseling.

  17. The sensitivity and specificity of clinical measures of sport concussion: three tests are better than one

    PubMed Central

    Resch, Jacob E; Brown, Cathleen N; Schmidt, Julianne; Macciocchi, Stephen N; Blueitt, Damond; Cullum, C Munro; Ferrara, Michael S

    2016-01-01

    Context A battery of clinical measures of neurocognition, balance and symptoms has been recommended for the management of sport concussion (SC) but is based on variable evidence. Objective To examine the sensitivity and specificity of a battery of tests to assess SC in college athletes. Design Cross-sectional. Setting Research laboratory. Patients or other participants Division 1 athletes diagnosed with a SC (n=40) who were 20.2±1.60 years of age and 180.5±11.12 cm tall and healthy athletes (n=40) who were 19.0±0.93 years of age and 179.1±11.39 cm tall were enrolled. Intervention(s) Participants were administered Immediate Postconcussion Assessment and Cognitive Test (ImPACT), the Sensory Organization Test (SOT) and the Revised Head Injury Scale (HIS-r) prior to and up to 24 h following injury between the 2004 and 2014 sport seasons. Sensitivity and specificity were calculated using predictive discriminant analyses (PDA) and clinical interpretation guidelines. Main outcome measures Outcome measures included baseline and postinjury ImPACT, SOT and HIS-r composite scores. Results Using PDA, each clinical measure's sensitivity ranged from 55.0% to 77.5% and specificity ranged from 52.5% to 100%. The test battery possessed a sensitivity and specificity of 80.0% and 100%, respectively. Using clinical interpretation guidelines, sensitivity ranged from 55% to 97.5% individually, and 100% when combined. Conclusions Our results support a multidimensional approach to assess SC in college athletes which correctly identified 80–100% of concussed participants as injured. When each test was evaluated separately, up to 47.5% of our sample was misclassified. Caution is warranted when using singular measures to manage SC. PMID:27900145

  18. The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations

    PubMed Central

    Alabdali, Majed; Alsulaiman, Abdulla; Albulaihe, Hana; Breiner, Ari; Katzberg, Hans D.; Aljaafari, Danah; Lovblom, Leif E.; Bril, Vera

    2017-01-01

    Introduction Polyneuropathy is one of the most prevalent neurologic disorders. Although several studies explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients and have not correlated examination findings with symptoms and electrophysiological results. Objectives To explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, find the most sensitive combination of examination components for polyneuropathy detection, and correlate examination findings with symptoms and electrophysiological results. Methods Patients with polyneuropathy attending the neuromuscular clinic from 01/2013 to 09/2015 were evaluated. Inclusion criteria included symptomatic polyneuropathy, which was confirmed by electrophysiological studies. 47 subjects with no symptoms or electrophysiological findings suggestive for polyneuropathy, served as controls. Results The total cohort included 312 polyneuropathy patients, with a mean age of 60±14 years. Abnormal examination was found in 95%, most commonly sensory findings (86%). The most common abnormal examination components were impaired ankle reflexes (74%), vibration (73%), and pinprick (72%) sensation. Combining ankle reflex examination with vibration or pinprick perception had the highest sensitivity, of 88%. The specificities of individual examination component were generally high, excluding ankle reflexes (62%), and vibration perception (77%). Abnormal examination findings were correlated with symptomatic weakness and worse electrophysiological parameters. Conclusion The neurological examination is a valid, sensitive and specific tool for diagnosing polyneuropathy, and findings correlate with polyneuropathy severity. Ankle reflex examination combined with either vibration or pinprick sensory testing is the most sensitive combination for diagnosing polyneuropathy, and should be

  19. Sensitivity and specificity of the FAMACHA(©) system in Suffolk sheep and crossbred Boer goats.

    PubMed

    Sotomaior, Cristina Santos; Rosalinski-Moraes, Fernanda; da Costa, Alane Rayana Barbosa; Maia, Dhéri; Monteiro, Alda Lúcia Gomes; van Wyk, Jan A

    2012-11-23

    Sheep and goats are the species of farm animal with the highest growth rate in Paraná State. The main problems facing Paraná State flocks are gastrointestinal parasites and anthelmintic resistance. One of the newest resources used to slow down the development of anthelmintic resistance is the FAMACHA(©) system, a selective method useful for controlling gastrointestinal verminosis in small ruminants. The purpose of the present research was to evaluate the sensitivity and specificity of the FAMACHA(©) system in sheep and goats and to compare the results for both species. The conjunctivae of 83 Suffolk ewes and 60 adult crossbred Boer does were evaluated by the same trained person using the FAMACHA(©) system. The packed cell value (PCV) served as the gold standard for clinical FAMACHA(©) evaluation. To calculate the sensitivity and specificity of the FAMACHA(©) system, different criteria were adopted in turn: animals classified as FAMACHA(©) (F(©)) 4 and 5, or 3, 4 and 5, were considered to be anemic (positive test), and animals classified as F(©)1, 2 and 3, or 1 and 2 were considered to be non-anemic (negative test). Three standard values of PCV, namely ≤19%, ≤18% or ≤15%, were used to confirm anemia. At all cut-off levels, the sensitivity increased if F(©)3 animals were included as being anemic. However, changes in levels of sensitivity were associated with reciprocal changes in specificity. The sensitivity was higher for sheep than for goats, excepting when the criteria included PCV≤18 and F(©)3, F(©)4 and F(©)5 were considered positive. In contrast, the specificity was always lower in sheep for any criteria adopted. Other than in goats, using the ≤15 cut-off level for sheep, it is possible to opt not to drench the animals that were shown to be F(©)3 because the sensitivity is still high, indicating that few animals that should have been drenched were overlooked. In goats, in contrast, the low sensitivity at all cut-off levels made it too

  20. HMX and HNS Shock Sensitivity Correlation with Specific Heat and Reactive Temperature Magnitudes

    NASA Astrophysics Data System (ADS)

    Billingsley, J. P.

    1999-06-01

    A paper in the 1995 SCCM Conference Proceedings(pages 429-432) documents that shock sensitivity of five explosives(TETRYL, PETN,TNT, RDX, and TATB) could be correlated with their specific heats and reactive temperature magnitudes. In fact, it was demonstrated that the shock sensitivity of these explosives was basically related to their reactive temperatures such as T(melt), T(phase change), and T(explode). Two additional explosives(HMX and HNS) have also been investigated and similar results are documented in this article. Thus, this concept has been affirmatively demonstrated via comparisons with experimental results for seven important explosive chemical compounds.

  1. Sensitivity, Reliability and Accuracy of the Instant Center of Rotation Calculation in the Cervical Spine During In Vivo Dynamic Flexion-Extension

    PubMed Central

    Baillargeon, Emma

    2013-01-01

    The instant center of rotation (ICR) has been proposed as an alternative to range of motion (ROM) for evaluating the quality, rather than the quantity, of cervical spine movement. The purpose of the present study was to assess the sensitivity, reliability and accuracy of cervical spine ICR path calculations obtained during dynamic in vivo movement. The reliability and sensitivity of in vivo cervical spine ICR calculations were assessed by evaluating the effects of movement direction (flexion versus extension), rotation step size, filter frequency, and motion tracking error. The accuracy of the ICR path calculations was assessed through a simulation experiment that replicated in vivo movement of cervical vertebrae. The in vivo assessment included 20 asymptomatic subjects who performed continuous head flexion-extension movements while biplane radiographs were collected at 30 frames/s. In vivo motion of C2 through C7 cervical vertebrae was tracked with sub-millimeter accuracy using a volumetric model-based tracking technique. The finite helical axis method was used to determine ICRs between each pair of adjacent vertebra. The in vivo results indicate ICR path is not different during the flexion movement and the extension movement. In vivo, the path of the ICR can reliably be characterized within 0.5 mm in the SI and 1.0 mm in the AP direction. The inter-subject variability in ICR location averaged ±1.2 mm in the SI direction and ±2.2 mm in the AP direction. The computational experiment estimated the in vivo accuracy in ICR location was between 1.1 mm and 3.1 mm. PMID:23317757

  2. Accuracy of a prey-specific DNA assay and a generic prey-immunomarking assay for detecting predation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    1. Predator gut examinations are useful for detecting arthropod predation events. Here, the accuracy and reproducibility of two different types of gut assays are tested on various predator species that consumed an immature lacewing, Chrysoperla carnea (Stephens), that was externally labelled with ra...

  3. Validation Test Report for NFLUX PRE: Validation of Specific Humidity, Surface Air Temperature, and Wind Speed Precision and Accuracy for Assimilation into Global and Regional Models

    DTIC Science & Technology

    2014-04-02

    Test Report for NFLUX PRE: Validation of Specific Humidity, Surface Air Temperature, and Wind Speed Precision and Accuracy for Assimilation into...THIS PAGE 18. NUMBER OF PAGES 17. LIMITATION OF ABSTRACT Validation Test Report for NFLUX PRE: Validation of Specific Humidity, Surface Air...The regional algorithm products overlay the existing global product estimate. The location of the observations is tested to see if it falls within one

  4. Cellular heterogeneity mediates inherent sensitivity-specificity tradeoff in cancer targeting by synthetic circuits.

    PubMed

    Morel, Mathieu; Shtrahman, Roman; Rotter, Varda; Nissim, Lior; Bar-Ziv, Roy H

    2016-07-19

    Synthetic gene circuits are emerging as a versatile means to target cancer with enhanced specificity by combinatorial integration of multiple expression markers. Such circuits must also be tuned to be highly sensitive because escape of even a few cells might be detrimental. However, the error rates of decision-making circuits in light of cellular variability in gene expression have so far remained unexplored. Here, we measure the single-cell response function of a tunable logic AND gate acting on two promoters in heterogeneous cell populations. Our analysis reveals an inherent tradeoff between specificity and sensitivity that is controlled by the AND gate amplification gain and activation threshold. We implement a tumor-mimicking cell-culture model of cancer cells emerging in a background of normal ones, and show that molecular parameters of the synthetic circuits control specificity and sensitivity in a killing assay. This suggests that, beyond the inherent tradeoff, synthetic circuits operating in a heterogeneous environment could be optimized to efficiently target malignant state with minimal loss of specificity.

  5. Sensitivity and specificity of a commercial BSE kit for the detection of ovine scrapie.

    PubMed

    Yamamoto, Takuji; Ushiki-Kaku, Yuko; Yokoyama, Takashi; Hattori, Shunji

    2013-06-01

    To examine the sensitivity of a commercially available bovine spongiform encephalopathy (BSE) kit (NippIBL) for the detection of ovine scrapie, 50 scrapie-positive ovine samples from the UK, and 54 scrapie-negative ovine samples from Japan were obtain and tested using this kit. The sensitivity and specificity of NippIBL for ovine samples were 96% and 100%, respectively. The detection limit of the abnormal isoform of prion protein (PrP(Sc) ) of NippIBL was examined using diluted scrapie-positive samples. The sensitivity of NippIBL to ovine scrapie was 3-10 times superior to that of another commercial BSE diagnosis kit. Thus, the NippIBL kit proved more effective for the detection of ovine scrapie.

  6. Sensitivity of a mesoscale model to initial specification of relative humidity, liquid water and vertical motion

    NASA Technical Reports Server (NTRS)

    Kalb, M. W.; Perkey, D. J.

    1985-01-01

    The influence of synoptic scale initial conditions on the accuracy of mesoscale precipitation modeling is investigated. Attention is focused on the relative importance of the water vapor, cloud water, rain water, and vertical motion, with the analysis carried out using the Limited Area Mesoscale Prediction System (LAMPS). The fully moist primitive equation model has 15 levels and a terrain-following sigma coordinate system. A K-theory approach was implemented to model the planetary boundary layer. A total of 15 sensitivity simulations were run to investigate the effects of the synoptic initial conditions of the four atmospheric variables. The absence of synoptic cloud and rain water amounts in the initialization caused a 2 hr delay in the onset of precipitation. The delay was increased if synoptic-scale vertical motion was used instead of mesoscale values. Both the delays and a choice of a smoothed moisture field resulted in underestimations of the total rainfall.

  7. Autism Spectrum Disorder in the DSM-5: Diagnostic Sensitivity and Specificity in Early Childhood.

    PubMed

    Christiansz, Jessica A; Gray, Kylie M; Taffe, John; Tonge, Bruce J

    2016-06-01

    Changes to the DSM-5 Autism Spectrum Disorder (ASD) criteria raised concerns among parents and practitioners that the criteria may exclude some children with Pervasive Developmental Disorder (PDD). Few studies have examined DSM-5 sensitivity and specificity in children less than 5 years of age. This study evaluated 185 children aged 20-55 months with DSM-IV PDD or developmental delay. Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) data was assigned to DSM-5 subdomains. Children displaying the required symptomatology were classified with DSM-5 ASD. DSM-IV clinical diagnoses were compared to DSM-5 classifications. Using combined ADI-R/ADOS information, sensitivity was .84 and specificity was .54. Comorbid behaviour and emotional problems were significantly lower in children with PDD that did not meet DSM-5 criteria.

  8. Knowing your own mate value: sex-specific personality effects on the accuracy of expected mate choices.

    PubMed

    Back, Mitja D; Penke, Lars; Schmukle, Stefan C; Asendorpf, Jens B

    2011-08-01

    Knowing one's mate value (mate-value accuracy) is an important element in reproductive success. We investigated within- and between-sex differences in this ability in a real-life speed-dating event. A total of 190 men and 192 women filled out a personality questionnaire and participated in speed-dating sessions. Immediately after each date, participants recorded who they would choose as mates and who they expected would choose them. In line with evolutionarily informed hypotheses, results indicated that sociosexually unrestricted men and more agreeable women showed greater mate-value accuracy than sociosexually restricted men and less agreeable women, respectively. These results have important implications for understanding mating behavior and perhaps the origin of sex differences in personality.

  9. Development of a Sensitive and Specific Antigen-Detection System for Strongyloides Stercoralis and Hookworm Infections

    DTIC Science & Technology

    1997-06-01

    Development of a Sensitive and Specific Antigen-Detection System for Strongyloides Stercoralis and Hookworm Infections PRINCIPAL INVESTIGATOR: Helene...Stercoralis and Hookworm Infections 6. AUTHOR(S) Helene Paxton 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION Integrated...of S. stercoralis and human hookworms . Using commercial immunoreagents that were available during the time line of phase I, antibody capture DS

  10. Impact Shock Sensitivity of a TATB Based Explosive Relevant to Specific Heat Properties

    DTIC Science & Technology

    2006-02-01

    specific heat (CP) variation with temperature, was demonstrated in References [1] and [2] for RDX, TETRYL, PETN , TNT, and TATB, which are basic...secondary reactive compounds. In References [3] and [4], the Δ (v.e.)TR ideas were demonstrated for HMX and HNS which are also important basic...Report RD-SS-99-8, June 1999, U.S. Army Missile Command, Redstone Arsenal, Alabama, 35898. 4. Billingsley, J. P., “HMX and HNS Shock Sensitivity

  11. Sensitivity and specificity of cytodiagnosis of body fluids in a laboratory of urgencies.

    PubMed

    Rocher, A E; Guerra, F; Rofrano, J; Angeleri, A; Canessa, O E; Mendeluk, G R; Palaoro, L A

    2011-10-01

    The main purpose for studying cytological body fluids is confirmation of a benign or malignant effusion. Our cytology laboratory analyzes body fluids and results are requested urgently. The samples are stained by the Giemsa and Papanicolaou methods to give a preliminary report, then they are examined by other complementary techniques. Three hundred thirty samples of pleural and peritoneal fluids were studied to compare the sensitivity of Papanicolaou and Giemsa stains. AgNOR assay, immunocytochemistry and assessment of ploidy were used to improve the sensitivity of the cytodiagnosis. Two hundred one samples were positive, 84 negative and 45 inconclusive using the Papanicolaou stain, while 135 samples were positive, 72 negative and 123 inconclusive using Giemsa stain. The sensitivity was 79%, 53% and 83% for Papanicolaou, Giemsa, and both techniques together, respectively. Using complementary techniques, the sensitivity reached 95% for AgNOR, 87% for tumor markers (panel), and 92% for Ploidy. There were no false positive in our series; therefore specificity was 100%. The use of both Papanicolaou and Giemsa in conjunction increased the sensitivity of the cytodiagnosis in body fluids. The complementary methods, especially AgNOR assay and assessment of ploidy, diminished the number of inconclusive cases.

  12. Drugs of abuse specifically sensitize noradrenergic and serotonergic neurons via a non-dopaminergic mechanism.

    PubMed

    Lanteri, Christophe; Salomon, Lucas; Torrens, Yvette; Glowinski, Jacques; Tassin, Jean-Pol

    2008-06-01

    A challenge in drug dependence is to delineate long-term neurochemical modifications induced by drugs of abuse. Repeated d-amphetamine was recently shown to disrupt a mutual regulatory link between noradrenergic and serotonergic neurons, thus inducing long-term increased responses to d-amphetamine and para-chloroamphetamine, respectively. We show here that such a sensitization of noradrenergic and serotonergic neurons also occurs following repeated treatment with cocaine, morphine, or alcohol, three compounds belonging to main groups of addictive substances. In all cases, this sensitization is prevented by alpha 1b-adrenergic and 5-HT2A receptors blockade, indicating the critical role of these receptors on long-term effects of drugs of abuse. However, repeated treatments with two non-addictive antidepressants, venlafaxine, and clorimipramine, which nevertheless inhibit noradrenergic and serotonergic reuptake, do not induce noradrenergic and serotonergic neurons sensitization. Similarly, this sensitization does not occur following repeated treatments with a specific inhibitor of dopamine (DA) reuptake, GBR12783. Moreover, we show that the effects of SCH23390, a D1 receptor antagonist known to inhibit development of d-amphetamine behavioral sensitization, are due to its 5-HT2C receptor agonist property. SCH23390 blocks amphetamine-induced release of norepinephrine and RS102221, a 5-HT2C antagonist, can reverse this inhibition as well as inhibition of noradrenergic sensitization and development of behavioral sensitization induced by repeated d-amphetamine. We propose that noradrenergic/serotonergic uncoupling is a common neurochemical consequence of repeated consumption of drugs of abuse, unrelated with DA release. Our data also suggest that compounds able to restore the link between noradrenergic and serotonergic modulatory systems could represent important therapeutic targets for investigation.

  13. Sensitivity and specificity of Ankara University Cerebral Dominance Inventory in comparison with the Wada test.

    PubMed

    Yılmaz, Nesrin Helvacı; Bingol, Ayse Petek

    2014-03-01

    We aimed to examine the sensitivity and specificity of the Ankara University Cerebral Dominance Inventory (AUCDI) in determining left cerebral dominance compared with the Wada test. The AUCDI and Wada test were applied to 49 patients referred to Ankara University for epilepsy surgery. Hand, foot and 'total' preference scores were specified according to the results of the inventory. Thirty-eight of the patients had left cerebral dominance and 11 had atypical cerebral dominance for language. 86 % of the patients were right-handed and 43 % were right-footed. When compared with the results of the Wada test, the sensitivity of the AUCDI for each 'total preference', and hand and foot preference was 90, 95 and 50 % and specificity was 46, 46 and 82 %, respectively. The percentage of right-footed patients was low when compared with the other studies. This difference might result from the method used for assessing foot preference by the actual demonstration of the task rather than just asking about the performance. The AUCDI was found to be sensitive in terms of 'total preference' and hand preference, and specific in terms of foot preference for determining the left hemisphere dominance in patients preferring the right side. It was a cheap and noninvasive alternative to the Wada test, appropriate for clinical bedside evaluation.

  14. From specificity to sensitivity: affective states modulate visual working memory for emotional expressive faces

    PubMed Central

    Maran, Thomas; Sachse, Pierre; Furtner, Marco

    2015-01-01

    Previous findings suggest that visual working memory (VWM) preferentially remembers angry looking faces. However, the meaning of facial actions is construed in relation to context. To date, there are no studies investigating the role of perceiver-based context when processing emotional cues in VWM. To explore the influence of affective context on VWM for faces, we conducted two experiments using both a VWM task for emotionally expressive faces and a mood induction procedure. Affective context was manipulated by unpleasant (Experiment 1) and pleasant (Experiment 2) IAPS pictures in order to induce an affect high in motivational intensity (defensive or appetitive, respectively) compared to a low arousal control condition. Results indicated specifically increased sensitivity of VWM for angry looking faces in the neutral condition. Enhanced VWM for angry faces was prevented by inducing affects of high motivational intensity. In both experiments, affective states led to a switch from specific enhancement of angry expressions in VWM to an equally sensitive representation of all emotional expressions. Our findings demonstrate that emotional expressions are of different behavioral relevance for the receiver depending on the affective context, supporting a functional organization of VWM along with flexible resource allocation. In VWM, stimulus processing adjusts to situational requirements and transitions from a specifically prioritizing default mode in predictable environments to a sensitive, hypervigilant mode in exposure to emotional events. PMID:26379609

  15. Living cell dry mass measurement using quantitative phase imaging with quadriwave lateral shearing interferometry: an accuracy and sensitivity discussion

    NASA Astrophysics Data System (ADS)

    Aknoun, Sherazade; Savatier, Julien; Bon, Pierre; Galland, Frédéric; Abdeladim, Lamiae; Wattellier, Benoit; Monneret, Serge

    2015-12-01

    Single-cell dry mass measurement is used in biology to follow cell cycle, to address effects of drugs, or to investigate cell metabolism. Quantitative phase imaging technique with quadriwave lateral shearing interferometry (QWLSI) allows measuring cell dry mass. The technique is very simple to set up, as it is integrated in a camera-like instrument. It simply plugs onto a standard microscope and uses a white light illumination source. Its working principle is first explained, from image acquisition to automated segmentation algorithm and dry mass quantification. Metrology of the whole process, including its sensitivity, repeatability, reliability, sources of error, over different kinds of samples and under different experimental conditions, is developed. We show that there is no influence of magnification or spatial light coherence on dry mass measurement; effect of defocus is more critical but can be calibrated. As a consequence, QWLSI is a well-suited technique for fast, simple, and reliable cell dry mass study, especially for live cells.

  16. Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia

    PubMed Central

    Rofes, L; Arreola, V; Mukherjee, R; Clavé, P

    2014-01-01

    Background Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. Methods We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallow (cough, voice changes, and oxygen desaturation ≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. Key Results According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations. Conclusions & Inferences Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia. PMID:24909661

  17. Sensitivity and specificity of an abbreviated 13C-mixed triglyceride breath test for measurement of pancreatic exocrine function

    PubMed Central

    Meier, Viola; Wolfram, Kristina U; Rosien, Ulrich; Layer, Peter

    2014-01-01

    Background A modified 13C-mixed triglyceride breath test (13C -MTGT) detects moderate pancreatic exocrine insufficiency noninvasively and reliably, but it requires prolonged breath sampling (6 hours (hr)). Objective We aimed to investigate whether 13C -MTGT can be abbreviated, to optimize clinical usability. Methods We analyzed the 13C-MTGT of 200 consecutive patients, retrospectively. Cumulative 1–5 hr 13C-exhalation values were compared with the standard parameter (6-hr cumulative 13C-exhalation). We determined the sensitivity and specificity of shortened breath sampling periods, by comparison with the normal values from 10 healthy volunteers, whom also underwent a secretin test to quantitate pancreatic secretion. Moreover, we evaluated the influence of gastric emptying (GE), using a 13C-octanoic acid breath test in a subset (N = 117). Results The 1–5 hr cumulative 13C-exhalation tests correlated highly and significantly with the standard parameter (p < 0.0001). Sensitivity for detection of impaired lipolysis was high (≥77%), but the specificity was low (≥38%) for the early measurements. Both parameters were high after 4 hrs (88% and 94%, respectively) and 5 hrs (98% and 91%, respectively). Multivariate linear correlation analysis confirmed that GE strongly influenced early postprandial 13C-exhalation during the 13C-MTGT. Conclusion Shortening of the 13C -MTGT from 6 to 4 hrs of duration was associated with similar diagnostic accuracy, yet increased clinical usability. The influence of GE on early postprandial results of the 13C-MTGT precluded further abbreviation of the test. PMID:25083286

  18. Specific and sensitive detection of the conifer pathogen Gremmeniella abietina by nested PCR

    PubMed Central

    Zeng, Qing-Yin; Hansson, Per; Wang, Xiao-Ru

    2005-01-01

    Background Gremmeniella abietina (Lagerb.) Morelet is an ascomycete fungus that causes stem canker and shoot dieback in many conifer species. The fungus is widespread and causes severe damage to forest plantations in Europe, North America and Asia. To facilitate early diagnosis and improve measures to control the spread of the disease, rapid, specific and sensitive detection methods for G. abietina in conifer hosts are needed. Results We designed two pairs of specific primers for G. abietina based on the 18S rDNA sequence variation pattern. These primers were validated against a wide range of fungi and 14 potential conifer hosts. Based on these specific primers, two nested PCR systems were developed. The first system employed universal fungal primers to enrich the fungal DNA targets in the first round, followed by a second round selective amplification of the pathogen. The other system employed G. abietina-specific primers in both PCR steps. Both approaches can detect the presence of G. abietina in composite samples with high sensitivity, as little as 7.5 fg G. abietina DNA in the host genomic background. Conclusion The methods described here are rapid and can be applied directly to a wide range of conifer species, without the need for fungal isolation and cultivation. Therefore, it represents a promising alternative to disease inspection in forest nurseries, plantations and quarantine control facilities. PMID:16280082

  19. Immuno-PCR: Very sensitive antigen detection by means of specific antibody-DNA conjugates

    SciTech Connect

    Sano, T.; Smith, C.L.; Cantor, C.R. )

    1992-10-02

    An antigen detection system, termed immuno-polymerase chain reaction (immuno-PCR), was developed in which a specific DNA molecule is used as the marker. A streptavidin-protein A chimera that possesses tight and specific binding affinity both for biotin and immunoglobulin G was used to attach a biotinylated DNA specifically to antigen-monoclonal antibody complexes that had been immobilized on microtiter plate wells. Then, a segment of the attached DNA was amplified by PCR. Analysis of the PCR products by agarose gel electrophoresis after staining with ethidium bromide allowed as few as 580 antigen molecules to be readily and reproducibly detected. Direct comparison with enzyme-linked immunosorbent assay with the use of a chimera-alkaline phosphatase conjugate demonstrates that enhancement in detection sensitivity was obtained with the use of immuno-PCR. Given the enormous amplification capability and specificity of PCR, this immuno-PCR technology has a sensitivity greater than any existing antigen detection system and, in principle, could be applied to the detection of single antigen molecules.

  20. Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity

    NASA Astrophysics Data System (ADS)

    Ning, Xinghai; Lee, Seungjun; Wang, Zhirui; Kim, Dongin; Stubblefield, Bryan; Gilbert, Eric; Murthy, Niren

    2011-08-01

    The diagnosis of bacterial infections remains a major challenge in medicine. Although numerous contrast agents have been developed to image bacteria, their clinical impact has been minimal because they are unable to detect small numbers of bacteria in vivo, and cannot distinguish infections from other pathologies such as cancer and inflammation. Here, we present a family of contrast agents, termed maltodextrin-based imaging probes (MDPs), which can detect bacteria in vivo with a sensitivity two orders of magnitude higher than previously reported, and can detect bacteria using a bacteria-specific mechanism that is independent of host response and secondary pathologies. MDPs are composed of a fluorescent dye conjugated to maltohexaose, and are rapidly internalized through the bacteria-specific maltodextrin transport pathway, endowing the MDPs with a unique combination of high sensitivity and specificity for bacteria. Here, we show that MDPs selectively accumulate within bacteria at millimolar concentrations, and are a thousand-fold more specific for bacteria than mammalian cells. Furthermore, we demonstrate that MDPs can image as few as 105 colony-forming units in vivo and can discriminate between active bacteria and inflammation induced by either lipopolysaccharides or metabolically inactive bacteria.

  1. Highly specific and sensitive electrochemical genotyping via gap ligation reaction and surface hybridization detection.

    PubMed

    Huang, Yong; Zhang, Yan-Li; Xu, Xiangmin; Jiang, Jian-Hui; Shen, Guo-Li; Yu, Ru-Qin

    2009-02-25

    This paper developed a novel electrochemical genotyping strategy based on gap ligation reaction with surface hybridization detection. This strategy utilized homogeneous enzymatic reactions to generate molecular beacon-structured allele-specific products that could be cooperatively annealed to capture probes stably immobilized on the surface via disulfide anchors, thus allowing ultrasensitive surface hybridization detection of the allele-specific products through redox tags in close proximity to the electrode. Such a unique biphasic architecture provided a universal methodology for incorporating enzymatic discrimination reactions in electrochemical genotyping with desirable reproducibility, high efficiency and no interferences from interficial steric hindrance. The developed technique was demonstrated to show intrinsic high sensitivity for direct genomic analysis, and excellent specificity with discriminativity of single nucleotide variations.

  2. Higher sensitivity secondary ion mass spectrometry of biological molecules for high resolution, chemically specific imaging.

    PubMed

    McDonnell, Liam A; Heeren, Ron M A; de Lange, Robert P J; Fletcher, Ian W

    2006-09-01

    To expand the role of high spatial resolution secondary ion mass spectrometry (SIMS) in biological studies, numerous developments have been reported in recent years for enhancing the molecular ion yield of high mass molecules. These include both surface modification, including matrix-enhanced SIMS and metal-assisted SIMS, and polyatomic primary ions. Using rat brain tissue sections and a bismuth primary ion gun able to produce atomic and polyatomic primary ions, we report here how the sensitivity enhancements provided by these developments are additive. Combined surface modification and polyatomic primary ions provided approximately 15.8 times more signal than using atomic primary ions on the raw sample, whereas surface modification and polyatomic primary ions yield approximately 3.8 and approximately 8.4 times more signal. This higher sensitivity is used to generate chemically specific images of higher mass biomolecules using a single molecular ion peak.

  3. The optimization of low specific speed centrifugal pump based on incomplete sensitivities

    NASA Astrophysics Data System (ADS)

    Zhang, R. H.; Zheng, K.; Yao, L. H.; Shi, F. X.

    2012-11-01

    In this research, the optimization method for low specific speed centrifugal pump impeller based on incomplete sensitivities was proposed. The main feature of the algorithm is that it avoids solving the flow field repeatedly in one optimization cycle in finite difference method and it avoids solving the adjoint equation in adjoint method. The blade meridional plan is considered as constant, and the blade camber line was parameterize by Taylor function. The coefficients in the Taylor function were taken as the control variable. The moment acting on the blade was considered as the objective function. With the incomplete sensitivities we can get the gradient of the objective function with respect to the control variable easily, and the blade shape can be renewed according to the inverse direction of the gradient. We will find the optimum design when the objective function is minimized. The computational cost is greatly reduced. The calculation cases show that the proposed theory and method is rotational.

  4. Comparing sensitivity and specificity of screening mammography in the United States and Denmark.

    PubMed

    Kemp Jacobsen, Katja; O'Meara, Ellen S; Key, Dustin; S M Buist, Diana; Kerlikowske, Karla; Vejborg, Ilse; Sprague, Brian L; Lynge, Elsebeth; von Euler-Chelpin, My

    2015-11-01

    Delivery of screening mammography differs substantially between the United States (US) and Denmark. We evaluated whether there are differences in screening sensitivity and specificity. We included screens from women screened at age 50-69 years during 1996-2008/2009 in the US Breast Cancer Surveillance Consortium (BCSC) (n = 2,872,791), and from two population-based mammography screening programs in Denmark (Copenhagen, n = 148,156 and Funen, n = 275,553). Women were followed-up for 1 year. For initial screens, recall rate was significantly higher in BCSC (17.6%) than in Copenhagen (4.3%) and Funen (3.1%). Sensitivity was fairly similar in BCSC (91.8%) and Copenhagen (90.5%) and Funen (92.5%). At subsequent screens, recall rates were 8.8%, 1.8% and 1.4% in BCSC, Copenhagen and Funen, respectively. The BCSC sensitivity (82.3%) was lower compared with that in Copenhagen (88.9%) and Funen (86.9%), but when stratified by time since last screen, the sensitivity was similar. For both initial and subsequent screenings, the specificity of screening in BCSC (83.2% and 91.6%) was significantly lower than that in Copenhagen (96.6% and 98.8%) and Funen (97.9% and 99.2%). By taking time since last screen into account, it was found that American and Danish women had the same probability of having their asymptomatic cancers detected at screening. However, the majority of women free of asymptomatic cancers experienced more harms in terms of false-positive findings in the US than in Denmark.

  5. Inter- and intra-specific variation on sensitivity of larval amphibians to nitrite.

    PubMed

    Shinn, C; Marco, A; Serrano, L

    2008-03-01

    Several authors have suggested that nitrogen-based fertilizers may be contributing to the global amphibian decline. We have studied the impact of sodium nitrite on early aquatic stages of Epidalea calamita, Pelophylax perezi and Hyla meridionalis larvae from Doñana National Park (coastal wetland) and P. perezi from Gredos Mountain (high mountain ponds), exposed during 10 to 16 days. After 8 days of exposure all P. perezi larvae from Doñana presented 100% mortality at 5 mg l(-1)N-NO2(-) while E. calamita larvae mortality rates were significantly lower at that concentration after 15 days. However, for H. meridionalis at day 15 no deaths were registered at 5 mg l(-1)N-NO2(-) and at 20 mg l(-1)N-NO2(-) presented intermediate mortality rates. In Doñana the 10 d LC50 of older H. meridionalis larvae was between 20 and 30 mg l(-1)N-NO2(-) whilst for P. perezi it was below 5 mg l(-1)N-NO2(-). These results indicate inter-specific variation of the sensitivity of larval amphibians to nitrite. Gredos Mountain P. perezi larvae exposed since the egg stage were highly sensitive to nitrite, with a 16 d LC50 below 0.5 mg l(-1)N-NO2(-). The same species in Doñana had a 15 d LC50 between 5 and mg l(-1)N-NO2(-). These results suggest that there is also intra-specific variation in sensitivity of amphibian larvae to nitrite: mountain amphibian populations appear to be more sensitive to polluted environments than coastal populations. Geographic and genetic variation and evolutionary adaptation of tolerance may also be the keys to variation amongst populations of the same species.

  6. A shorter and more specific oral sensitization-based experimental model of food allergy in mice.

    PubMed

    Bailón, Elvira; Cueto-Sola, Margarita; Utrilla, Pilar; Rodríguez-Ruiz, Judith; Garrido-Mesa, Natividad; Zarzuelo, Antonio; Xaus, Jordi; Gálvez, Julio; Comalada, Mònica

    2012-07-31

    Cow's milk protein allergy (CMPA) is one of the most prevalent human food-borne allergies, particularly in children. Experimental animal models have become critical tools with which to perform research on new therapeutic approaches and on the molecular mechanisms involved. However, oral food allergen sensitization in mice requires several weeks and is usually associated with unspecific immune responses. To overcome these inconveniences, we have developed a new food allergy model that takes only two weeks while retaining the main characters of allergic response to food antigens. The new model is characterized by oral sensitization of weaned Balb/c mice with 5 doses of purified cow's milk protein (CMP) plus cholera toxin (CT) for only two weeks and posterior challenge with an intraperitoneal administration of the allergen at the end of the sensitization period. In parallel, we studied a conventional protocol that lasts for seven weeks, and also the non-specific effects exerted by CT in both protocols. The shorter protocol achieves a similar clinical score as the original food allergy model without macroscopically affecting gut morphology or physiology. Moreover, the shorter protocol caused an increased IL-4 production and a more selective antigen-specific IgG1 response. Finally, the extended CT administration during the sensitization period of the conventional protocol is responsible for the exacerbated immune response observed in that model. Therefore, the new model presented here allows a reduction not only in experimental time but also in the number of animals required per experiment while maintaining the features of conventional allergy models. We propose that the new protocol reported will contribute to advancing allergy research.

  7. Sensitive and Specific In-Situ Sensor for Monitoring Contaminated Water

    SciTech Connect

    Du, Yongzhai; Watson, David B; Whitten, William B; Li, Haiyang; Nazarov, Erkinjun; Xu, Jun

    2010-01-01

    We report on the development of a high-sensitivity and high-specificity sensor, combining membrane extraction, pre-concentration, and gas-chromatographic differential mobility spectrometry (GC/DMS), for in situ detection of chlorinated hydrocarbons in water. Direct in-situ detection was achieved by membrane conversion of aqueous analyte to vapor, followed by vapor spectroscopy using GC/DMS analyzer. The limit of detection (LOD) reaches 0.37 parts per billion in volume (ppbv), or 0.54 ug/L, for aqueous trichloroethylene (TCE) and 1.6 ug/L for perchloroethylene (PCE) by incorporating a preconcentrator between the membrane extraction and GC/DMS detection systems. The high specificity was achieved using two-dimensional separation parameters of GC retention time and DMS compensation voltage. The presence of co-contaminants and foreign contaminants, such as benzene, toluene, CCl4, and CHCl3 did not interfere with the identification of chlorinated hydrocarbons. This highly-sensitive and -specific sensor paves the way for developing field-deployable sensors for in-situ and real-time monitoring of chlorinated hydrocarbons in groundwater and surface water.

  8. Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas

    PubMed Central

    2011-01-01

    Background The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas. Methods Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel. Results Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa. Conclusions The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection. PMID:21777459

  9. Profiling single-guide RNA specificity reveals a mismatch sensitive core sequence

    PubMed Central

    Zheng, Ting; Hou, Yingzi; Zhang, Pingjing; Zhang, Zhenxi; Xu, Ying; Zhang, Letian; Niu, Leilei; Yang, Yi; Liang, Da; Yi, Fan; Peng, Wei; Feng, Wenjian; Yang, Ying; Chen, Jianxin; Zhu, York Yuanyuan; Zhang, Li-He; Du, Quan

    2017-01-01

    Targeting specificity is an essential issue in the development of CRISPR-Cas technology. Using a luciferase activation assay, off-target cleavage activity of sgRNA was systematically investigated on single nucleotide-mismatched targets. In addition to confirming that PAM-proximal mismatches are less tolerated than PAM-distal mismatches, our study further identified a “core” sequence that is highly sensitive to target-mismatch. This sequence is of 4-nucleotide long, located at +4 to +7 position upstream of PAM, and positioned in a steric restriction region when assembled into Cas9 endonuclease. Our study also found that, single or multiple target mismatches at this region abolished off-target cleavage mediated by active sgRNAs, thus proposing a principle for gene-specific sgRNA design. Characterization of a mismatch sensitive “core” sequence not only enhances our understanding of how this elegant system functions, but also facilitates our efforts to improve targeting specificity of a sgRNA. PMID:28098181

  10. Sensitivity and specificity of mu-capture ELISA for detection of enterovirus IgM.

    PubMed

    Bendig, J W; Molyneaux, P

    1996-05-01

    The sensitivity and specificity of an in-house mu-capture enzyme linked immunosorbent assay (ELISA) for enterovirus IgM in routine use was determined by analysing the results of 77 serum samples from 55 enterovirus culture-positive patients with aseptic meningitis and single serum samples from 140 patients with other infections. In addition, sera from 10 laboratory staff pre- and post-polio virus vaccination and 20 rheumatoid factor positive sera were tested for specificity. On testing the first serum specimen received, only 21 of 55 patients (38%) with aseptic meningitis yielded a positive result, rising to 33 of 55 (60%) on testing a second sample, where available. Out of 14 patients from whom multiple serum samples were tested and negative results obtained with the first serum, 12 were positive with the second sample (86%). Only patients with acute hepatitis A produced a significant number of false positives by the enterovirus ELISA (12 out of 20), but the reverse was not true: patients with enterovirus IgM did not produce false positive results in tests for hepatitis A IgM. Excluding samples positive for hepatitis A IgM, the number of non-enterovirus infections correctly reported as negative was 118 out of 120--a specificity of 98%. This test is probably the most useful serological test available at present for diagnosing recent enterovirus infection, although the limited sensitivity needs to be borne in mind.

  11. Specification for USAF Standard Form, Fit, and Function (F3) Medium Accuracy Inertial Navigation Unit, Revision D.

    DTIC Science & Technology

    2007-11-02

    and produced hardware can be used interchangeably at the Line Replaceable Unit (LRU) level in any given vehicle. The unique CDU interface is no longer part of this specification, and is now covered in SNU 84.1/F-16.

  12. Sensitive and specific miRNA detection method using SplintR Ligase

    PubMed Central

    Jin, Jingmin; Vaud, Sophie; Zhelkovsky, Alexander M.; Posfai, Janos; McReynolds, Larry A.

    2016-01-01

    We describe a simple, specific and sensitive microRNA (miRNA) detection method that utilizes Chlorella virus DNA ligase (SplintR® Ligase). This two-step method involves ligation of adjacent DNA oligonucleotides hybridized to a miRNA followed by real-time quantitative PCR (qPCR). SplintR Ligase is 100X faster than either T4 DNA Ligase or T4 RNA Ligase 2 for RNA splinted DNA ligation. Only a 4–6 bp overlap between a DNA probe and miRNA was required for efficient ligation by SplintR Ligase. This property allows more flexibility in designing miRNA-specific ligation probes than methods that use reverse transcriptase for cDNA synthesis of miRNA. The qPCR SplintR ligation assay is sensitive; it can detect a few thousand molecules of miR-122. For miR-122 detection the SplintR qPCR assay, using a FAM labeled double quenched DNA probe, was at least 40× more sensitive than the TaqMan assay. The SplintR method, when coupled with NextGen sequencing, allowed multiplex detection of miRNAs from brain, kidney, testis and liver. The SplintR qPCR assay is specific; individual let-7 miRNAs that differ by one nucleotide are detected. The rapid kinetics and ability to ligate DNA probes hybridized to RNA with short complementary sequences makes SplintR Ligase a useful enzyme for miRNA detection. PMID:27154271

  13. Sensitivity and specificity of the amer dizziness diagnostic scale (adds) for patients with vestibular disorders.

    PubMed

    Al Saif, Amer; Alsenany, Samira

    2015-01-01

    [Purpose] To investigate the sensitivity and specificity of a newly developed diagnostic tool, the Amer Dizziness Diagnostic Scale (ADDS), to evaluate and differentially diagnose vestibular disorder and to identify the strengths and weaknesses of the scale and its usefulness in clinical practice. [Subjects and Methods] Two hundred subjects of both genders (72 males, 128 females) aged between 18 to 60 (49.5±7.8) who had a history of vertigo and/or dizziness symptoms for this previous two weeks or less were recruited for the study. All subjects were referred by otolaryngologists, neurologists or family physicians in and around Jeddah, Kingdom of Saudi Arabia. On the first clinic visit, all the patients were evaluated once using the ADDS, following which they underwent routine testing of clinical signs and symptoms, audiometry, and a neurological examination, coupled with tests of Vestibulo-Ocular Reflex function, which often serves as the "gold standard" for determining the probability of a vestibular deficit. [Results] The results show that the ADDS strongly correlated with "true-positive" and "true-negative" responses for determining the probability of a vestibular disorder (r =0.95). A stepwise linear regression was conducted and the results indicate that the ADDS was a significant predictor of "true-positive" and "true-negative" responses in vestibular disorders (R(2) =0.90). Approximately 90% of the variability in the vestibular gold standard test was explained by its relationship to the ADDS. Moreover, the ADDS was found to have a sensitivity of 96% and a specificity of 96%. [Conclusion] This study showed that the Amer Dizziness Diagnostic Scale has high sensitivity and specificity and that it can be used as a method of differential diagnosis for patients with vestibular disorders.

  14. Label-Free Isothermal Amplification Assay for Specific and Highly Sensitive Colorimetric miRNA Detection

    PubMed Central

    2016-01-01

    We describe a new method for the detection of miRNA in biological samples. This technology is based on the isothermal nicking enzyme amplification reaction and subsequent hybridization of the amplification product with gold nanoparticles and magnetic microparticles (barcode system) to achieve naked-eye colorimetric detection. This platform was used to detect a specific miRNA (miRNA-10b) associated with breast cancer, and attomolar sensitivity was demonstrated. The assay was validated in cell culture lysates from breast cancer cells and in serum from a mouse model of breast cancer. PMID:27713932

  15. Site specific chemoselective labelling of proteins with robust and highly sensitive Ru(II) bathophenanthroline complexes.

    PubMed

    Uzagare, Matthew C; Claussnitzer, Iris; Gerrits, Michael; Bannwarth, Willi

    2012-03-21

    The bioorthogonal and chemoselective fluorescence labelling of several cell-free synthesized proteins containing a site-specifically incorporated azido amino acid was possible using different alkyne-functionalized Ru(II) bathophenanthroline complexes. We were able to achieve a selective labelling even in complex mixtures of proteins despite the fact that ruthenium dyes normally show a high tendency for unspecific interactions with proteins and are commonly used for total staining of proteins. Since the employed Ru complexes are extremely robust, photo-stable and highly sensitive, the approach should be applicable to the production of labelled proteins for single molecule spectroscopy and fluorescence-based interaction studies.

  16. Sensitivity, Specificity, and Receiver Operating Characteristics: A Primer for Neuroscience Nurses.

    PubMed

    McNett, Molly; Amato, Shelly; Olson, DaiWai M

    2017-04-01

    It is important for neuroscience nurses to have a solid understanding of the instruments they use in clinical practice. Specifically, when reviewing reports of research instruments, nurses should be knowledgeable of analytical terms when determining the applicability of instruments for use in clinical practice. The purpose of this article is to review 3 such analytical terms: sensitivity, specificity, and receiver operating characteristic curves. Examples of how these terms are used in the neuroscience literature highlight the relevance of these terms to neuroscience nursing practice. As the role of the nurse continues to expand, it is important not to simply accept all instruments as valid but to be able to critically evaluate their properties for applicability to nursing practice and evidence-based care of our patients.

  17. Sensitivity and Specificity of a Urine Circulating Anodic Antigen Test for the Diagnosis of Schistosoma haematobium in Low Endemic Settings

    PubMed Central

    Knopp, Stefanie; Corstjens, Paul L. A. M.; Koukounari, Artemis; Cercamondi, Colin I.; Ame, Shaali M.; Ali, Said M.; de Dood, Claudia J.; Mohammed, Khalfan A.; Utzinger, Jürg; Rollinson, David; van Dam, Govert J.

    2015-01-01

    Background Elimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are key goals of the World Health Organization for 2025. Conventional parasitological methods are insensitive for the detection of light-intensity infections. Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings and verification of elimination. We determined the accuracy of a urine-based up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay for Schistosoma haematobium diagnosis in low-prevalence settings in Zanzibar, Tanzania. Methodology A total of 1,740 urine samples were collected in 2013 from children on Pemba Island, from schools where the S. haematobium prevalence was <2%, 2–5%, and 5–10%, based on a single urine filtration. On the day of collection, all samples were tested for microhematuria with reagent strips and for the presence of S. haematobium eggs with microscopy. Eight months later, 1.5 ml of urine from each of 1,200 samples stored at -20°C were analyzed by UCP-LF CAA assay, while urine filtration slides were subjected to quality control (QCUF). In the absence of a true ‘gold’ standard, the diagnostic performance was calculated using latent class analyses (LCA). Principal Findings The ‘empirical’ S. haematobium prevalence revealed by UCP-LF CAA, QCUF, and reagent strips was 14%, 5%, and 4%, respectively. LCA revealed a sensitivity of the UCP-LF CAA, QCUF, and reagent strips of 97% (95% confidence interval (CI): 91–100%), 86% (95% CI: 72–99%), and 67% (95% CI: 52–81%), respectively. Test specificities were consistently above 90%. Conclusions/Significance The UCP-LF CAA assay shows high sensitivity for the diagnosis of S. haematobium in low-endemicity settings. Empirically, it detects a considerably higher number of infections than microscopy. Hence, the UCP-LF CAA employed in combination with QCUF, is a promising tool for

  18. Accuracy, sensitivity and robustness of five different methods for the estimation of gait temporal parameters using a single inertial sensor mounted on the lower trunk.

    PubMed

    Trojaniello, Diana; Cereatti, Andrea; Della Croce, Ugo

    2014-09-01

    In the last decade, various methods for the estimation of gait events and temporal parameters from the acceleration signals of a single inertial measurement unit (IMU) mounted at waist level have been proposed. Despite the growing interest for such methodologies, a thorough comparative analysis of methods with regards to number of extra and missed events, accuracy and robustness to IMU location is still missing in the literature. The aim of this work was to fill this gap. Five methods have been tested on single IMU data acquired from fourteen healthy subjects walking while being recorded by a stereo-photogrammetric system and two force platforms. The sensitivity in detecting initial and final contacts varied between 81% and 100% across methods, whereas the positive predictive values ranged between 94% and 100%. For all tested methods, stride and step time estimates were obtained; three of the selected methods also allowed estimation of stance, swing and double support time. Results showed that the accuracy in estimating step and stride durations was acceptable for all methods. Conversely, a statistical difference was found in the error in estimating stance, swing and double support time, due to the larger errors in the final contact determination. Except for one method, the IMU positioning on the lower trunk did not represent a critical factor for the estimation of gait temporal parameters. Results obtained in this study may not be applicable to pathologic gait.

  19. Sensitivity requirements of assisted BDS and GPS in specification 3GPP TS 36.171

    NASA Astrophysics Data System (ADS)

    Jin, Xiaoxi; Chen, Xin; Ying, Rendong; Yang, Genke

    2016-01-01

    With the needs of growing location-based service, a more high-performance satellite positioning technology - assisted global navigation satellite system (A-GNSS assisted-GNSS) becomes a new hotspot in area of navigation and positioning. Now, 3GPP has already provided supports for GPS, Galileo, GLONASS and QZSS, SBAS, so standardization work of introduction BDS into 3GPP organization is very imperative. In this paper, we first analysis the performance of GPS L1 C/A with assistant information, then by taking into account the difference between BDS and GPS, including the unique nature of GEO/NGEO satellites' navigation message data length and format, we design the sensitivity requirements of BDS B1 following A-GPS. The results between A-GPS and A-BDS of typical sensitivity test cases are shown in this paper, which show that the suggested sensitivity requirements satisfy the minimum performance requirements under technical specification of 3GPP TS 36.171.

  20. Integrating Domain Specific Knowledge and Network Analysis to Predict Drug Sensitivity of Cancer Cell Lines

    PubMed Central

    Kim, Sebo; Sundaresan, Varsha; Zhou, Lei; Kahveci, Tamer

    2016-01-01

    One of fundamental challenges in cancer studies is that varying molecular characteristics of different tumor types may lead to resistance to certain drugs. As a result, the same drug can lead to significantly different results in different types of cancer thus emphasizing the need for individualized medicine. Individual prediction of drug response has great potential to aid in improving the clinical outcome and reduce the financial costs associated with prescribing chemotherapy drugs to which the patient’s tumor might be resistant. In this paper we develop a network based classifier (NBC) method for predicting sensitivity of cell lines to anticancer drugs from transcriptome data. In the literature, this strategy has been used for predicting cancer types. Here, we extend it to estimate sensitivity of cells from different tumor types to various anticancer drugs. Furthermore, we incorporate domain specific knowledge such as the use of apoptotic gene list and clinical dose information in our method to impart biological significance to the prediction. Our experimental results suggest that our network based classifier (NBC) method outperforms existing classifiers in estimating sensitivity of cell lines for different drugs. PMID:27607242

  1. Flower Visitors of Campanula: Are Oligoleges More Sensitive to Host-Specific Floral Scents Than Polyleges?

    PubMed

    Brandt, Katharina; Dötterl, Stefan; Francke, Wittko; Ayasse, Manfred; Milet-Pinheiro, Paulo

    2017-01-01

    The pollen diet provided by adult bees to their offspring varies immensely. While some species collect pollen on several plants irrespective of their phylogenetic relatedness (polyleges), others collect only on plants within a genus or family (oligoleges). Floral scents play a central role in bee-plant interactions. To locate flowers, polyleges are assumed to rely on compounds commonly found as floral scent constituents, whereas oligoleges rely on unusual compounds to recognize host flowers unambiguously. Campanula flowers are visited by both polylectic and oligolectic species, and their scent bouquets consist of common and unusual (e.g., spiroacetals) volatiles. In a comparative approach, we performed electroantennographic analyses to investigate the antennal responses of three polyleges and three oligoleges to three common volatiles and four spiroacetals. We hypothesized that: 1) oligoleges and polyleges should respond similarly to common flower volatiles, and 2) Campanula oligoleges should be more sensitive to spiroacetals than are polyleges. In corroboration, we found that antennal sensitivity to common volatiles was similar among bees irrespective of pollen diet, whereas oligoleges of Campanula were more sensitive to spiroacetals than polyleges. Newly emerged bees of the Campanula oligolege Chelostoma rapunculi rely on spiroacetals for recognizing host-flowers, and our results suggest that this might also be true for other Campanula oligoleges, since Chelostoma campanularum and Hoplitis mitis also were able to perceive these specific volatiles at very low concentrations. Together, our results provide interesting insights into the significance of olfactory adaptations in oligolectic and polylectic bee species.

  2. Use of Sensitive and Specific Biomolecular and Mass Spectrometric Techniques to Monitor the Performance of In-Situ Hydrocarbon Biodegradation

    NASA Astrophysics Data System (ADS)

    Beller, H. R.; Kane, S. R.; Legler, T. C.

    2008-12-01

    Monitored natural attenuation (MNA) can be a cost-effective and viable approach for remediation of hydrocarbon-contaminated groundwater. However, regulatory acceptance of the approach is often contingent on monitoring that can convincingly demonstrate the role of microbial degradation. Recent advances in anaerobic hydrocarbon biochemistry, analytical chemistry, and molecular biology have fostered the development of powerful techniques that can be applied to MNA of BTEX (benzene, toluene, ethylbenzene, and xylenes). Here, I discuss two independent methods that have been developed to monitor in situ, anaerobic biodegradation of toluene and xylenes. A method has been developed for rapid, sensitive, and highly selective detection of distinctive indicators of anaerobic alkylbenzene metabolism. The target metabolites, benzylsuccinic acid and methylbenzylsuccinic acid isomers, have no known sources other than anaerobic toluene or xylene degradation; thus, their mere presence in groundwater provides definitive evidence of in situ metabolism. The method, which involves small sample size (<1 mL) and no extraction/concentration steps, relies on isotope dilution liquid chromatography/tandem mass spectrometry (LC/MS/MS) with selected reaction monitoring. Detection limits for benzylsuccinates were determined to be ca. 0.3 μg/L and accuracy and precision were favorable in a groundwater matrix. A monitoring method based on quantitative Polymerase Chain Reaction (qPCR) analysis has been developed to specifically quantify populations of anaerobic methylbenzene-degrading bacteria in aquifer sediment. The method targets a catabolic gene (bssA) associated with the first step of anaerobic toluene and xylene degradation. The method has proven to be sensitive (detection limit ca. 5 gene copies) and has a linear range of > 7 orders of magnitude. Application of these two methods in field studies will be discussed in the context of the methods' strengths and limitations. Field data will

  3. Hematoxylin and eosin stain shows a high sensitivity but sub-optimal specificity in demonstrating iron pigment in liver biopsies

    PubMed Central

    Alwahaibi, Nasar Yousuf; Alkhatri, Azza Sarhan; Kumar, Johanes Selva

    2015-01-01

    Background: Perls’ stain is routinely used to demonstrate iron in liver biopsies. We tested the hypothesis that it may be unnecessary in cases, where no iron or another similar pigment was seen on the routine hematoxylin and eosin (H and E) stained section. Aim: The aim of this study was to evaluate the efficiency of H and E stain in demonstrating iron in liver biopsies as well as to determine the possibility of replacing Perls’ stain with H and E stain. Materials and Methods: Two hundred pairs of slides of liver biopsies were taken from the archival files of the Department of Pathology from 2006 to 2011. Perls’ and H and E slides were independently reviewed for the presence of iron. Results: Hundred and one cases showed the presence of iron using H and E stain. 84 of 86 cases showed positive iron using both Perls’ and H and E stains. Seventeen cases were positive using H and E stain but negative with Perls’. Only two cases did not show the presence of iron using H and E stain. Ninety-seven cases were negative using both Perls’ and H and E stains. H and E stain showed a sensitivity, specificity, accuracy, positive predictive valve, and negative predictive value of 97.67%, 85.08%, 90.5%, 83.16%, and 97.98%, respectively. Conclusion: We demonstrate that the H and E stain is a sensitive method to detect iron pigment in liver biopsies, particularly when present in large quantities. A negative H and E stain might obviate the need for extra Perls’ staining, thus saving costs and shortening report turn-around times. PMID:26539364

  4. Determination of an optimally sensitive and specific chemical exchange saturation transfer MRI quantification metric in relevant biological phantoms

    PubMed Central

    Ray, Kevin J.; Larkin, James R.; Tee, Yee K.; Khrapitchev, Alexandre A.; Karunanithy, Gogulan; Barber, Michael; Baldwin, Andrew J.; Chappell, Michael A.

    2016-01-01

    The purpose of this study was to develop realistic phantom models of the intracellular environment of metastatic breast tumour and naïve brain, and using these models determine an analysis metric for quantification of CEST MRI data that is sensitive to only labile proton exchange rate and concentration. The ability of the optimal metric to quantify pH differences in the phantoms was also evaluated. Novel phantom models were produced, by adding perchloric acid extracts of either metastatic mouse breast carcinoma cells or healthy mouse brain to bovine serum albumin. The phantom model was validated using 1H NMR spectroscopy, then utilized to determine the sensitivity of CEST MRI to changes in pH, labile proton concentration, T 1 time and T 2 time; six different CEST MRI analysis metrics (MTRasym, APT*, MTRRex, AREX and CESTR* with and without T 1/T 2 compensation) were compared. The new phantom models were highly representative of the in vivo intracellular environment of both tumour and brain tissue. Of the analysis methods compared, CESTR* with T 1 and T 2 time compensation was optimally specific to changes in the CEST effect (i.e. minimal contamination from T 1 or T 2 variation). In phantoms with identical protein concentrations, pH differences between phantoms could be quantified with a mean accuracy of 0.6 pH units. We propose that CESTR* with T 1 and T 2 time compensation is the optimal analysis method for these phantoms. Analysis of CEST MRI data with T 1/T 2 time compensated CESTR* is reproducible between phantoms, and its application in vivo may resolve the intracellular alkalosis associated with breast cancer brain metastases without the need for exogenous contrast agents. PMID:27686882

  5. A dipstick test combined with urine specific gravity improved the accuracy of proteinuria determination in pregnancy screening.

    PubMed

    Makihara, Natsuko; Yamasaki, Mineo; Morita, Hiroki; Yamada, Hideto

    2011-01-21

    Proteinuria screening using a semi-quantitative dipstick test of the spot urine in antenatal clinic is known to have high false-positive rates. The aim of this study was to assess availability of a dipstick test combined with the urine specific gravity for the determination of pathological proteinuria. A dipstick test was performed on 582 urine samples obtained from 283 pregnant women comprising 260 with normal blood pressure and 23 with pregnancy-induced hypertension. The urine protein (P) and creatinine (C) concentrations, specific gravity (SG), P/C ratio were determined, and compared with dipstick test results. The P concentration increased along the stepwise augmentations in dipstick test result. Frequencies of the urine samples with 0.265 or more P/C ratio were 0.7% with - dipstick test result, 0.7% with the ± result, 3.3% with the 1+ result, and 88.9% with the ≥2+ result. However, if the urine specific gravity was low, frequencies of the high P/C ratio were 5.0% with ± dipstick test result and 9.3% with the 1+ result. A dipstick test result of ≥2+ seems appropriate for a criterion of positive screening for pathological proteinuria in antenatal care. A dipstick test combined with the urine specific gravity may be useful for outpatient clinic screening.

  6. Screening of depression in adolescents through the Internet : sensitivity and specificity of two screening questionnaires.

    PubMed

    Cuijpers, Pim; Boluijt, Petra; van Straten, Annemieke

    2008-02-01

    The Internet may offer new opportunities for treating depressed adolescents. However, before such treatments are possible, well-validated screening instruments are needed. In the current study, we validate two Internet-based screening instruments for depression among adolescents, the major depression inventory (MDI), and the Center for Epidemiological Studies-Depression scale (CES-D). A total of 1,392 adolescents, recruited through high schools and the Internet, filled in the online questionnaires. Of these, 243 (17%) were interviewed with the MINI diagnostic interview to assess the presence of a mood disorder. Cronbach's alpha was high for both the CES-D (0.93) and the MDI (0.88), and both correlated highly with each other (0.88; P < .001). The scores on both instruments were significantly increased in all subjects with a mood disorder, whether current or lifetime, except for lifetime minor depression. In the ROC analyses, high areas under the curve were found for the MDI (0.89) and CES-D (0.90). The best cut-off point for the MDI was 19 (sensitivity: 90.48; specificity: 71.53), and for the CES-D it was 22 (sensitivity: 90.48; specificity: 74.31). We conclude that the MDI and CES-D are reliable and valid instruments that can be used for this screening.

  7. Developmentally Sensitive Markers of Personality Functioning in Adolescents: Age-Specific and Age-Neutral Expressions.

    PubMed

    Debast, Inge; Rossi, Gina; Feenstra, Dineke; Hutsebaut, Joost

    2016-05-23

    Criterion D of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association [APA], 2013) refers to a possible onset of personality disorders (PDs) in adolescence and in Section II the development/course in adolescence is described by some typical characteristics for several PDs. Yet, age-specific expressions of PDs are lacking in Section III. We urgently need a developmentally sensitive assessment instrument that differentiates developmental and contextual changes on the one hand from expressions of personality pathology on the other hand. Therefore we investigated which items of the Severity Indices for Personality Problems-118 (SIPP-118) were developmentally sensitive throughout adolescence and adulthood and which could be considered more age-specific markers requiring other content or thresholds over age groups. Applying item response theory (IRT) we detected differential item functioning (DIF) in 36% of the items in matched samples of 639 adolescents versus 639 adults. The DIF across age groups mainly reflected a different degree of symptom expressions for the same underlying level of functioning. The threshold for exhibiting symptoms given a certain degree of personality dysfunction was lower in adolescence for areas of personality functioning related to the Self and Interpersonal domains. Some items also measured a latent construct of personality functioning differently across adolescents and adults. This suggests that several facets of the SIPP-118 do not solely measure aspects of personality pathology in adolescents, but likely include more developmental issues. (PsycINFO Database Record

  8. Sensitivity and Specificity of a Novel Classifier for the Early Diagnosis of Dengue

    PubMed Central

    Tuan, Nguyen Minh; Nhan, Ho Thi; Chau, Nguyen Van Vinh; Hung, Nguyen Thanh; Tuan, Ha Manh; Tram, Ta Van; Ha, Nguyen Le Da; Loi, Phan; Quang, Han Khoi; Kien, Duong Thi Hue; Hubbard, Sonya; Chau, Tran Nguyen Bich; Wills, Bridget; Wolbers, Marcel; Simmons, Cameron P.

    2015-01-01

    Background Dengue is the commonest arboviral disease of humans. An early and accurate diagnosis of dengue can support clinical management, surveillance and disease control and is central to achieving the World Health Organisation target of a 50% reduction in dengue case mortality by 2020. Methods 5729 children with fever of <72hrs duration were enrolled into this multicenter prospective study in southern Vietnam between 2010-2012. A composite of gold standard diagnostic tests identified 1692 dengue cases. Using statistical methods, a novel Early Dengue Classifier (EDC) was developed that used patient age, white blood cell count and platelet count to discriminate dengue cases from non-dengue cases. Results The EDC had a sensitivity of 74.8% (95%CI: 73.0-76.8%) and specificity of 76.3% (95%CI: 75.2-77.6%) for the diagnosis of dengue. As an adjunctive test alongside NS1 rapid testing, sensitivity of the composite test was 91.6% (95%CI: 90.4-92.9%). Conclusions We demonstrate that the early diagnosis of dengue can be enhanced beyond the current standard of care using a simple evidence-based algorithm. The results should support patient management and clinical trials of specific therapies. PMID:25836753

  9. Comparison of the sensitivity and specificity of six immunoassays for the detection of amphetamines in urine.

    PubMed

    Verstraete, Alain G; Heyden, Fien V

    2005-01-01

    We analyzed 225 urine samples with FPIA (Abbott Amphetamine/Methamphetamine II on ADx and AxSYM), EMIT (Emit II Plus Monoclonal Amphetamine/Metamphetamine assay and EMIT II Plus Amphetamines assay, EMIT N), and KIMS (standard protocol and MDMA protocol, KIMS and KIMS X, respectively) immunoassays and compared their sensitivity and specificity. All assays were calibrated and used semi-quantitatively. All samples that screened positive by any amphetamine screening method and 15% of the negative samples were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). A sample was considered positive for amphetamines if amphetamine, methamphetamine, methylenedioxymethamphetamine, methylenedio-xyethylamphetamine, or methylenedioxyamphetamine was present at 250 ng/mL. Ninety (40%) of the samples were positive by LC-MS-MS. The areas under the receiver operating characteristic curve varied between 0.972 (KIMS X) and 1.000 (ADx). The optimal cut-off concentrations varied between 271 ng/mL (EMIT N) and 723 ng/mL (AxSYM). The sensitivity was 100% for ADx and between 93 and 95% for the other assays. The specificity varied between 88% (KIMS) and 100% (EMIT N). Use of a 500 ng/mL screening cut-off would have resulted in identical or very similar results for ADx and KIMS X and large increases in the false positives for AxSYM and EMIT and the false negatives for EMIT N and KIMS.

  10. Rapid, sensitive, and specific detection of Clostridium tetani by loop-mediated isothermal amplification assay.

    PubMed

    Jiang, Dongneng; Pu, Xiaoyun; Wu, Jiehong; Li, Meng; Liu, Ping

    2013-01-01

    Tetanus is a specific infectious disease, which is often associated with catastrophic events such as earthquakes, traumas, and war wounds. The obligate anaerobe Clostridium tetani is the pathogen that causes tetanus. Once the infection of tetanus progresses to an advanced stage within the wounds of limbs, the rates of amputation and mortality increase manifold. Therefore, it is necessary to devise a rapid and sensitive point-of-care detection method for C. tetani so as to ensure an early diagnosis and clinical treatment of tetanus. In this study, we developed a detection method for C. tetani using loop-mediated isothermal amplification (LAMP) assay, wherein the C. tetani tetanus toxin gene was used as the target gene. The method was highly specific and sensitive, with a detection limit of 10 colony forming units (CFU)/ml, and allowed quantitative analysis. While detecting C. tetani in clinical samples, it was found that the LAMP results completely agreed with those of the traditional API 20A anaerobic bacteria identification test. As compared with the traditional API test and PCR assay, LAMP detection of C. tetani is simple and rapid, and the results can be identified through naked-eye observation. Therefore, it is an ideal and rapid point-of-care testing method for tetanus.

  11. Partially hydrolyzed guar gum characterization and sensitive quantification in food matrices by high performance anion exchange chromatography with pulsed amperometric detection--validation using accuracy profile.

    PubMed

    Mercier, G; Campargue, C

    2012-11-02

    Interest concerning functional ingredients and especially dietary fibres has been growing in recent years. At the same time, the variety of ingredient accepted as dietary fibres and their mixing at low level in complex matrices have considerably complicated their quantitative analysis by approved AOAC methods. These reasons have led to the specific development of an innovative analytical method performed by high-performance anion-exchange chromatography (HPAEC) with pulsed amperometric detection (PAD) to detect and quantify partially hydrolyzed guar gum (PHGG) in fruit preparation and dairy matrices. The analytical methodology was divided in two steps which could be deployed separately or in conjunction. The first, consists in a complete characterization of PHGG by size exclusion chromatography (SEC) with multi-angle light scattering and refractive index detection and HPAEC-PAD to determine its physico-chemical properties and galactomannans content, and the second step is the development of a new HPAEC-PAD method for PHGG direct quantification in complex matrices (dairy product). Validation in terms of detection and quantification limits, linearity of the analytical range, average accuracy (recovery, trueness) and average uncertainty were statistically carried out with accuracy profile. Overall, this new chromatographic method has considerably improved the possibility to quantify without fractionation treatment, low level of dietary fibres emerging from specific galactomannans, in complex matrices and many foodstuffs.

  12. Application of a normalized Nash-Sutcliffe efficiency to improve the accuracy of the Sobol' sensitivity analysis of a hydrological model

    NASA Astrophysics Data System (ADS)

    Nossent, J.; Bauwens, W.

    2012-04-01

    Sensitivity analysis (SA) has become a main practice in hydrological modelling, since it allows to identify the influential and non-influential parameters of a model and can give insights on the model processes and their relation with the system. A very robust SA technique that is becoming popular in hydrology is the Sobol' method (Sobol', 1990). This method quantifies the amount of variance that each parameter contributes to the unconditional variance of the model output. This variance contribution is expressed with sensitivity indices, which are assessed by means of Monte Carlo integrals. Hereto, a large number of random points are sampled in the parameter hyperspace to evaluate the model. When the Sobol' method is applied to assess the influence of the model parameters on simulated time series, an objective function is required to transform the vector output of the model into a scalar input for the SA. Since the accuracy of the variance estimation with the numerical integrals may decrease when the mean value of the scalar inputs for the SA is large (Sobol', 2001), the Nash-Sutcliffe efficiency (NSE) is assumed to yield more accurate results than e.g. the also commonly used Sum of Squared Residuals (SSR). In our application on a SWAT model of the Kleine Nete catchment (Belgium) (Nossent et al., 2011), this is indeed valid for flow predictions, as the mean NSE for all model evaluations is -0.73. However, for water quality simulations with the same model, the mean NSE values become highly negative (even an extreme value of -4E6 is obtained for nitrate concentration simulations). In such cases, the Nash-Sutcliffe efficiency is not suitable for the Sobol' sensitivity analysis. We therefore introduce a normalized version of the Nash-Sutcliffe efficiency (NNSE) that yields values between 0 and 1, but preserves the main characteristics of the regular NSE: Σ (oi - o)2 N NSE = --1--= Σ--i------- 2- N SE (oi - si)2 + (oi - o)2 i where si is the simulated value on day i

  13. Strategy for Sensitive and Specific Detection of Yersinia pestis in Skeletons of the Black Death Pandemic

    PubMed Central

    Seifert, Lisa; Harbeck, Michaela; Thomas, Astrid; Hoke, Nadja; Zöller, Lothar; Wiechmann, Ingrid; Grupe, Gisela; Scholz, Holger C.; Riehm, Julia M.

    2013-01-01

    Yersinia pestis has been identified as the causative agent of the Black Death pandemic in the 14th century. However, retrospective diagnostics in human skeletons after more than 600 years are critical. We describe a strategy following a modern diagnostic algorithm and working under strict ancient DNA regime for the identification of medieval human plague victims. An initial screening and DNA quantification assay detected the Y. pestis specific pla gene of the high copy number plasmid pPCP1. Results were confirmed by conventional PCR and sequence analysis targeting both Y. pestis specific virulence plasmids pPCP1 and pMT1. All assays were meticulously validated according to human clinical diagnostics requirements (ISO 15189) regarding efficiency, sensitivity, specificity, and limit of detection (LOD). Assay specificity was 100% tested on 41 clinically relevant bacteria and 29 Y. pseudotuberculosis strains as well as for DNA of 22 Y. pestis strains and 30 previously confirmed clinical human plague samples. The optimized LOD was down to 4 gene copies. 29 individuals from three different multiple inhumations were initially assessed as possible victims of the Black Death pandemic. 7 samples (24%) were positive in the pPCP1 specific screening assay. Confirmation through second target pMT1 specific PCR was successful for 4 of the positive individuals (14%). A maximum of 700 and 560 copies per µl aDNA were quantified in two of the samples. Those were positive in all assays including all repetitions, and are candidates for future continuative investigations such as whole genome sequencing. We discuss that all precautions taken here for the work with aDNA are sufficient to prevent external sample contamination and fulfill the criteria of authenticity. With regard to retrospective diagnostics of a human pathogen and the uniqueness of ancient material we strongly recommend using a careful strategy and validated assays as presented in our study. PMID:24069445

  14. Strategy for sensitive and specific detection of Yersinia pestis in skeletons of the black death pandemic.

    PubMed

    Seifert, Lisa; Harbeck, Michaela; Thomas, Astrid; Hoke, Nadja; Zöller, Lothar; Wiechmann, Ingrid; Grupe, Gisela; Scholz, Holger C; Riehm, Julia M

    2013-01-01

    Yersinia pestis has been identified as the causative agent of the Black Death pandemic in the 14(th) century. However, retrospective diagnostics in human skeletons after more than 600 years are critical. We describe a strategy following a modern diagnostic algorithm and working under strict ancient DNA regime for the identification of medieval human plague victims. An initial screening and DNA quantification assay detected the Y. pestis specific pla gene of the high copy number plasmid pPCP1. Results were confirmed by conventional PCR and sequence analysis targeting both Y. pestis specific virulence plasmids pPCP1 and pMT1. All assays were meticulously validated according to human clinical diagnostics requirements (ISO 15189) regarding efficiency, sensitivity, specificity, and limit of detection (LOD). Assay specificity was 100% tested on 41 clinically relevant bacteria and 29 Y. pseudotuberculosis strains as well as for DNA of 22 Y. pestis strains and 30 previously confirmed clinical human plague samples. The optimized LOD was down to 4 gene copies. 29 individuals from three different multiple inhumations were initially assessed as possible victims of the Black Death pandemic. 7 samples (24%) were positive in the pPCP1 specific screening assay. Confirmation through second target pMT1 specific PCR was successful for 4 of the positive individuals (14%). A maximum of 700 and 560 copies per µl aDNA were quantified in two of the samples. Those were positive in all assays including all repetitions, and are candidates for future continuative investigations such as whole genome sequencing. We discuss that all precautions taken here for the work with aDNA are sufficient to prevent external sample contamination and fulfill the criteria of authenticity. With regard to retrospective diagnostics of a human pathogen and the uniqueness of ancient material we strongly recommend using a careful strategy and validated assays as presented in our study.

  15. Charts of operational process specifications ("OPSpecs charts") for assessing the precision, accuracy, and quality control needed to satisfy proficiency testing performance criteria.

    PubMed

    Westgard, J O

    1992-07-01

    "Operational process specifications" have been derived from an analytical quality-planning model to assess the precision, accuracy, and quality control (QC) needed to satisfy Proficiency Testing (PT) criteria. These routine operating specifications are presented in the form of an "OPSpecs chart," which describes the operational limits for imprecision and inaccuracy when a desired level of quality assurance is provided by a specific QC procedure. OPSpecs charts can be used to compare the operational limits for different QC procedures and to select a QC procedure that is appropriate for the precision and accuracy of a specific measurement procedure. To select a QC procedure, one plots the inaccuracy and imprecision observed for a measurement procedure on the OPSpecs chart to define the current operating point, which is then compared with the operational limits of candidate QC procedures. Any QC procedure whose operational limits are greater than the measurement procedure's operating point will provide a known assurance, with the percent chance specified by the OPSpecs chart, that critical analytical errors will be detected. OPSpecs charts for a 10% PT criterion are presented to illustrate the selection of QC procedures for measurement procedures with different amounts of imprecision and inaccuracy. Normalized OPSpecs charts are presented to permit a more general assessment of the analytical performance required with commonly used QC procedures.

  16. Influence of Geometry and Mechanical Properties on the Accuracy of Patient-Specific Simulation of Women Pelvic Floor.

    PubMed

    Mayeur, Olivier; Witz, Jean-François; Lecomte, Pauline; Brieu, Mathias; Cosson, Michel; Miller, Karol

    2016-01-01

    The woman pelvic system involves multiple organs, muscles, ligaments, and fasciae where different pathologies may occur. Here we are most interested in abnormal mobility, often caused by complex and not fully understood mechanisms. Computer simulation and modeling using the finite element (FE) method are the tools helping to better understand the pathological mobility, but of course patient-specific models are required to make contribution to patient care. These models require a good representation of the pelvic system geometry, information on the material properties, boundary conditions and loading. In this contribution we focus on the relative influence of the inaccuracies in geometry description and of uncertainty of patient-specific material properties of soft connective tissues. We conducted a comparative study using several constitutive behavior laws and variations in geometry description resulting from the imprecision of clinical imaging and image analysis. We find that geometry seems to have the dominant effect on the pelvic organ mobility simulation results. Provided that proper finite deformation non-linear FE solution procedures are used, the influence of the functional form of the constitutive law might be for practical purposes negligible. These last findings confirm similar results from the fields of modeling neurosurgery and abdominal aortic aneurysms.

  17. Estimation of normalized point-source sensitivity of segment surface specifications for extremely large telescopes.

    PubMed

    Seo, Byoung-Joon; Nissly, Carl; Troy, Mitchell; Angeli, George; Bernier, Robert; Stepp, Larry; Williams, Eric

    2013-06-20

    We present a method which estimates the normalized point-source sensitivity (PSSN) of a segmented telescope when only information from a single segment surface is known. The estimation principle is based on a statistical approach with an assumption that all segment surfaces have the same power spectral density (PSD) as the given segment surface. As presented in this paper, the PSSN based on this statistical approach represents a worst-case scenario among statistical random realizations of telescopes when all segment surfaces have the same PSD. Therefore, this method, which we call the vendor table, is expected to be useful for individual segment specification such as the segment polishing specification. The specification based on the vendor table can be directly related to a science metric such as PSSN and provides the mirror vendors significant flexibility by specifying a single overall PSSN value for them to meet. We build a vendor table for the Thirty Meter Telescope (TMT) and test it using multiple mirror samples from various mirror vendors to prove its practical utility. Accordingly, TMT has a plan to adopt this vendor table for its M1 segment final mirror polishing requirement.

  18. Validating Antibodies to the Cannabinoid CB2 Receptor: Antibody Sensitivity Is Not Evidence of Antibody Specificity.

    PubMed

    Marchalant, Yannick; Brownjohn, Philip W; Bonnet, Amandine; Kleffmann, Torsten; Ashton, John C

    2014-06-01

    Antibody-based methods for the detection and quantification of membrane integral proteins, in particular, the G protein-coupled receptors (GPCRs), have been plagued with issues of primary antibody specificity. In this report, we investigate one of the most commonly utilized commercial antibodies for the cannabinoid CB2 receptor, a GPCR, using immunoblotting in combination with mass spectrometry. In this way, we were able to develop powerful negative and novel positive controls. By doing this, we are able to demonstrate that it is possible for an antibody to be sensitive for a protein of interest-in this case CB2-but still cross-react with other proteins and therefore lack specificity. Specifically, we were able to use western blotting combined with mass spectrometry to unequivocally identify CB2 protein in over-expressing cell lines. This shows that a common practice of validating antibodies with positive controls only is insufficient to ensure antibody reliability. In addition, our work is the first to develop a label-free method of protein detection using mass spectrometry that, with further refinement, could provide unequivocal identification of CB2 receptor protein in native tissues.

  19. Nasometric sensitivity and specificity: a cross-dialect and cross-culture study.

    PubMed

    Dalston, R M; Neiman, G S; Gonzalez-Landa, G

    1993-05-01

    A series of 514 patients seen at three clinics in the United States and Spain were evaluated using clinical judgments of hypernasality, and nasometric assessment of oral-nasal resonance balance. Data from the nasometer were obtained while patients read a passage devoid of nasal consonants. Across all subjects, the Pearson correlation coefficient between the clinical and instrumental measures was 0.78. Prediction analyses revealed that maximum efficiency was obtained using a somewhat different threshold nasalance value for each of the three patient samples. When all 514 subjects were investigated as a single group, a threshold nasalance score of 28 was found to optimize identification of patients with and without clinically significant hypernasality. In that analysis, a sensitivity of 0.87, a specificity of 0.86 and an overall efficiency of 0.87 was obtained. The clinical relevance of these findings is discussed.

  20. Specific and sensitive detection of Alcaligenes species from an agricultural environment.

    PubMed

    Nakano, Miyo; Niwa, Masumi; Nishimura, Norihiro

    2013-03-01

    A quantitative real-time PCR assay to specifically detect and quantify the genus Alcaligenes in samples from the agricultural environment, such as vegetables and farming soils, was developed. The minimum detection sensitivity was 106 fg of pure culture DNA, corresponding to DNA extracted from two cells of Alcaligenes faecalis. To evaluate the detection limit of A. faecalis, serially diluted genomic DNA from this organism was mixed with DNA extracted from soil and vegetables and then a standard curve was constructed. It was found that Alcaligenes species are present in the plant phytosphere at levels 10(2)-10(4) times lower than those in soil. The approach presented here will be useful for tracking or quantifying species of the genus Alcaligenes in the agricultural environment.

  1. Aspects of grammar sensitive to procedural memory deficits in children with specific language impairment.

    PubMed

    Sengottuvel, Kuppuraj; Rao, Prema K S

    2013-10-01

    Procedural deficit hypothesis claims that language deficit in children with specific language impairment is affiliated to sequence learning problems. However, studies did not explore on aspects of grammar vulnerable to sequence learning deficits. The present study makes predictions for aspects of grammar that could be sensitive to procedural deficits based on core ideas of procedural deficit hypothesis. The hypothesis for the present study was that the grammatical operations that require greater sequencing abilities (such as inflectional operations) would be more affected in children with language impairment. Further, the influence of sequencing difficulties would be even greater in agglutinating inflectional languages. An adapted serial reaction time task for sequence learning measurements along with grammatical tasks on derivation, inflection, and sentence complexity were examined on typically developing and language impaired children. Results were in favor of procedural deficit hypothesis and its close relation to non-adjacent grammatical operations. The findings were discussed using procedural deficits, declarative compensatory mechanism, and statistical learning deficits.

  2. The sensitivity and specificity of a diagnostic test of sequence-space synesthesia.

    PubMed

    Rothen, Nicolas; Jünemann, Kristin; Mealor, Andy D; Burckhardt, Vera; Ward, Jamie

    2016-12-01

    People with sequence-space synesthesia (SSS) report stable visuo-spatial forms corresponding to numbers, days, and months (amongst others). This type of synesthesia has intrigued scientists for over 130 years but the lack of an agreed upon tool for assessing it has held back research on this phenomenon. The present study builds on previous tests by measuring the consistency of spatial locations that is known to discriminate controls from synesthetes. We document, for the first time, the sensitivity and specificity of such a test and suggest a diagnostic cut-off point for discriminating between the groups based on the area bounded by different placement attempts with the same item.

  3. Molecular basis for species-specific sensitivity to "hot" chili peppers.

    PubMed

    Jordt, Sven-Eric; Julius, David

    2002-02-08

    Chili peppers produce the pungent vanilloid compound capsaicin, which offers protection from predatory mammals. Birds are indifferent to the pain-producing effects of capsaicin and therefore serve as vectors for seed dispersal. Here, we determine the molecular basis for this species-specific behavioral response by identifying a domain of the rat vanilloid receptor that confers sensitivity to capsaicin to the normally insensitive chicken ortholog. Like its mammalian counterpart, the chicken receptor is activated by heat or protons, consistent with the fact that both mammals and birds detect noxious heat and experience thermal hypersensitivity. Our findings provide a molecular basis for the ecological phenomenon of directed deterence and suggest that the capacity to detect capsaicin-like inflammatory substances is a recent acquisition of mammalian vanilloid receptors.

  4. Photoperiod sensitivity of the Arabidopsis circadian clock is tissue-specific.

    PubMed

    Shimizu, Hanako; Araki, Takashi; Endo, Motomu

    2015-01-01

    Tissue-specific functions of the circadian clock in Arabidopsis have recently been revealed. The vasculature clock shows distinctive gene expression profiles compared to the clock in other tissues under light-dark cycles. However, it has not yet been established whether the vasculature clock also shows unique gene expression patterns that correlate with temperature cycles, another important environmental cue. Here, we detected diel phase of TIMING OF CAB EXPRESSION 1 (TOC1) expression in the vasculature and whole leaf under long-day light-dark cycles and temperature cycles. We found that the vasculature clock had advanced TOC1 phase under light-dark cycles but not under temperature cycles, suggesting that the vasculature clock has lower sensitivity against temperature signals. Furthermore, the phase advancement of TOC1 was seen only under long-day condition but not under short-day condition. These results support our previous conclusion that the circadian clock in vasculature preferentially senses photoperiodic signals.

  5. TRPV1 temperature activation is specifically sensitive to strong decreases in amino acid hydrophobicity.

    PubMed

    Sosa-Pagán, Jason O; Iversen, Edwin S; Grandl, Jörg

    2017-04-03

    Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. One hypothesized mechanism assumes that temperature activation is driven by the exposure of hydrophobic residues to solvent. This mechanism further predicts that residues are exposed to solvent in a coordinated fashion, but without necessarily being located in close proximity to each other. However, there is little experimental evidence supporting this mechanism in TRP channels. Here, we combined high-throughput mutagenesis, functional screening, and deep sequencing to identify mutations from a total of ~7,300 TRPV1 random mutant clones. We found that strong decreases in hydrophobicity of amino acids are better tolerated for activation by capsaicin than for activation by hot temperature, suggesting that strong hydrophobicity might be specifically required for temperature activation. Altogether, our work provides initial correlative support for a previously hypothesized temperature mechanism in TRP ion channels.

  6. Renaturation of blotted allergens increases the sensitivity of specific IgE detection.

    PubMed

    Muro, M D; Fernández, C; Moneo, I

    1996-01-01

    Several authors have demonstrated that renaturation is an essential step for the appropriate recognition of blotted proteins. The use of nonionic detergents has been described as a useful alternative to enhance the antigenicity in immunoblotting, although elution from proteins by detergents has been observed. To measure the influence of different factors on the sensitivity of specific IgE by immunoblotting, we used twenty human sera from atopic patients who were allergic or nonallergic to a common, reliable allergen (grass pollen mixture). The use of Nonidet-P40 was found to be a useful alternative for the renaturation of the allergens. No elution from the membrane was found when employing this detergent, even at high concentrations (3%), and its use gave better sensitivity than methanol. On the other hand, we detected that methanol possessed renaturing properties. A transfer method using diffusion instead of electric transfer gave the best results and two membranes could be obtained from each gel. Using this method, we found that after NP-40 incubation of the membrane, the use of bovine albumin could be omitted as blocking agent and that its use had even deleterious effects.

  7. An extremely sensitive species-specific ARMS PCR test for the presence of tiger bone DNA.

    PubMed

    Wetton, Jon H; Tsang, Carol S F; Roney, Chris A; Spriggs, Adrian C

    2002-04-18

    The survival of the tiger (Panthera tigris) is seriously threatened by poaching to provide raw materials for traditional Chinese medicines (TCMs). Most highly prized are the tiger's bones, which are used in combination with other animal and plant derivatives in pills and plasters for the treatment of rheumatism and other ailments. Hundreds of patent remedies have been produced which claim to contain tiger bone, but proof of its presence is needed if legislation prohibiting the trade in endangered species is to be enforced.A highly sensitive tiger-specific real-time PCR assay has been developed to address this problem. Using primers specific to the tiger mitochondrial cytochrome b gene, successful amplification has been reliably achieved from blood, hair and bone as well as from a range of TCMs spiked with 0.5% tiger bone. Although capable of detecting fewer than 10 substrate molecules, the seven varieties of TCM pills and plasters tested showed no detectable trace of tiger DNA before spiking. Furthermore, sequencing several "tiger bone" fragments seized from TCM shops has shown that they actually originated from cattle and pigs. The potential effects of traditional bone preparation methods, evidence that much lower concentrations are used than alleged on TCM packaging, and substitution of bones from other species all suggest a low likelihood of detecting tiger DNA in patent medicines. Despite this, the basic methods have been thoroughly proven and can be readily applied to derivatives from other Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) protected species, providing a rapid and highly sensitive forensic test for species of origin. Potential applications to the monitoring of wild populations are demonstrated by the successful identification of shed hairs and faecal samples.

  8. Triple sensitivity amplification for ultrasensitive electrochemical detection of prostate specific antigen.

    PubMed

    Tang, Zhongxue; Wang, Liyuan; Ma, Zhanfang

    2017-06-15

    In general, current difference (ΔI) due to immunoreactions is significant in determining biosensor sensitivity. In this work, a new strategy of triple sensitivity amplification for ultrasensitive electrochemical detection of prostate specific antigen (PSA) was developed. Au-poly(methylene blue) (Au-PMB) was implemented as a redox species with strong current signal at -0.144V and used to fabricate the substrate of the biosensor. Conductive reduced graphene oxide-Au nanocomposites (Au-rGO) were coated on the Au-PMB modified glassy carbon electrode (GCE) to amplify current signal. After peptides (CEHSSKLQLAK-NH2) were fixed on the Au-rGO/Au-PMB/GCE, the fixed peptides reacted with glutaraldehyde to immobilize polydopamine-Au-horse radish peroxidase nanocomposites (PDA-Au-HRP). The electrochemical sensing interface for PSA was realized. Due to smaller resistance compared to antibodies, the peptides which can be cleaved specifically by PSA were employed. After the incubation of PSA, a large ΔI was obtained and behaved as the decrease of current signal. Then the remaining PDA-Au-HRP accelerated an enzyme-catalyzed precipitation reaction between 4-chloro-1-naphthol and H2O2. A further decrease in current signal (namely the increase in ΔI) resulted from the poorly conductive precipitation adhering onto the biosensor. The designed biosensor presented a wide linear range from 1.0fgmL(-1) to 100ngmL(-1) with an ultralow detection limit of 0.11fgmL(-1).

  9. Liver-specific deletion of Ppp2cα enhances glucose metabolism and insulin sensitivity.

    PubMed

    Xian, Li; Hou, Siyuan; Huang, Zan; Tang, An; Shi, Peiliang; Wang, Qinghua; Song, Anying; Jiang, Shujun; Lin, Zhaoyu; Guo, Shiying; Gao, Xiang

    2015-04-01

    Protein phosphatase 2A (PP2A) is a key negative regulator of phosphatidylinositol 3-kinase/Akt pathway. Previous study showed that, in the liver, the catalytic subunit of PP2A (PP2Ac) is closely associated with insulin resistance syndrome, which is characterized by glucose intolerance and dyslipidemia. Here we studied the role of liver PP2Ac in glucose metabolism and evaluated whether PP2Ac is a suitable therapeutic target for treating insulin resistance syndrome. Liver-specific Ppp2cα knockout mice (Ppp2cα(loxp/loxp): Alb) exhibited improved glucose homeostasis compared with littermate controls in both normal and high-fat diet conditions, despite no significant changes in body weight and liver weight under chow diet. Ppp2cα(loxp/loxp): Alb mice showed enhanced glycogen deposition, serum triglyceride, cholesterol, low density lipoprotein and high density lipoprotein, activated insulin signaling, decreased expressions of gluconeogenic genes G6P and PEPCK, and lower liver triglyceride. Liver-specific Ppp2cα knockout mice showed enhanced glucose homeostasis and increased insulin sensitivity by activation of insulin signaling through Akt. These findings suggest that inhibition of hepatic Ppp2cα may be a useful strategy for the treatment of insulin resistance syndrome.

  10. Specific Elimination of Latently HIV-1 Infected Cells Using HIV-1 Protease-Sensitive Toxin Nanocapsules

    PubMed Central

    Wen, Jing; Yan, Ming; Liu, Yang; Li, Jie; Xie, Yiming; Lu, Yunfeng; Kamata, Masakazu; Chen, Irvin S. Y.

    2016-01-01

    Anti-retroviral drugs suppress HIV-1 plasma viremia to undetectable levels; however, latent HIV-1 persists in reservoirs within HIV-1-infected patients. The silent provirus can be activated through the use of drugs, including protein kinase C activators and histone deacetylase inhibitors. This “shock” approach is then followed by “kill” of the producing cells either through direct HIV-1-induced cell death or natural immune mechanisms. However, these mechanisms are relatively slow and effectiveness is unclear. Here, we develop an approach to specifically target and kill cells that are activated early in the process of virus production. We utilize a novel nanocapsule technology whereby the ricin A chain is encapsulated in an inactive form within a polymer shell. Specificity for release of the ricin A toxin is conferred by peptide crosslinkers that are sensitive to cleavage by HIV-1 protease. By using well-established latent infection models, J-Lat and U1 cells, we demonstrate that only within an HIV-1-producing cell expressing functional HIV-1 protease will the nanocapsule release its ricin A cargo, shutting down viral and cellular protein synthesis, and ultimately leading to rapid death of the producer cell. Thus, we provide proof of principle for a novel technology to kill HIV-1-producing cells without effects on non-target cells. PMID:27049645

  11. Sensitive and specific immunoradiometric assay (IRMA) for human thyroid stimulating hormone

    SciTech Connect

    Piaditis, G.P.; Hodgkinson, S.C.; McLean, C.; Lowry, P.J.

    1985-01-01

    A liquid phase ''two-site'' immunoradiometric assay (IRMA) specific for human thyroid stimulating hormone (hTSH) is described. The assay is based on the simultaneous addition of affinity purified sheep anti hTSH IgG- SVI and rabbit anti hTSH antiserum to standards and unknowns followed by 4h incubation at room temperature. The separation of free labelled sheep IgG- SVI from that bound to hTSH is achieved by the addition of sheep anti-rabbit IgG Fc fragment antiserum. The radiolabelled sheep anti-hTSH IgG- SVI was pretreated with solid phase urinary postmenopausal gonadotropins to remove cross reaction with FSH and LH. The assay is specific for hTSH and no cross reaction with the other anterior pituitary glycoproteins or protein hormones has been found. In addition it is characterized by a wide operating range, rapid equilibration of reactants and high sensitivity. The precision of dose estimates was less than 10% between 0.25-2.5 microU/ml and less than 2.5% over the range 2.5-60 microU/ml.

  12. Highly Sensitive, Highly Specific Whole-Cell Bioreporters for the Detection of Chromate in Environmental Samples

    PubMed Central

    Branco, Rita; Cristóvão, Armando; Morais, Paula V.

    2013-01-01

    Microbial bioreporters offer excellent potentialities for the detection of the bioavailable portion of pollutants in contaminated environments, which currently cannot be easily measured. This paper describes the construction and evaluation of two microbial bioreporters designed to detect the bioavailable chromate in contaminated water samples. The developed bioreporters are based on the expression of gfp under the control of the chr promoter and the chrB regulator gene of TnOtChr determinant from Ochrobactrum tritici 5bvl1. pCHRGFP1 Escherichia coli reporter proved to be specific and sensitive, with minimum detectable concentration of 100 nM chromate and did not react with other heavy metals or chemical compounds analysed. In order to have a bioreporter able to be used under different environmental toxics, O. tritici type strain was also engineered to fluoresce in the presence of micromolar levels of chromate and showed to be as specific as the first reporter. Their applicability on environmental samples (spiked Portuguese river water) was also demonstrated using either freshly grown or cryo-preserved cells, a treatment which constitutes an operational advantage. These reporter strains can provide on-demand usability in the field and in a near future may become a powerful tool in identification of chromate-contaminated sites. PMID:23326558

  13. Identification of specific gravity sensitive signal transduction pathways in human A431 carcinoma cells

    NASA Astrophysics Data System (ADS)

    Rijken, P. J.; de Groot, R. P.; Kruijer, W.; de Laat, S. W.; Verkleij, A. J.; Boonstra, J.

    Epidermal growth factor (EGF) activates a well characterized signal transduction cascade in human A431 epidermoid carcinoma cells. The influence of gravity on EGF-induced EGF-receptor clustering and early gene expression as well as on actin polymerization and actin organization have been investigated. Different signalling pathways induced by the agents TPA, forskolin and A23187 that activate gene expression were tested for sensitivity to gravity. EGF-induced c-fos and c-jun expression were decreased in microgravity. However, constitutive β-2 microglobulin expression remained unaltered. Under simulated weightlessness conditions EGF- and TPA-induced c-fos expression was decreased, while forskolin- and A23187-induced c-fos expression was independent of the gravity conditions. These results suggest that gravity affects specific signalling pathways. Preliminary results indicate that EGF-induced EGF-receptor clustering remained unaltered irrespective of the gravity conditions. Furthermore, the relative filamentous actin content of steady state A431 cells was enhanced under microgravity conditions and actin filament organization was altered. Under simulated weightlessness actin filament organization in steady state cells as well as in EGF-treated cells was altered as compared to the 1 G reference experiment. Interestingly the microtubule and keratin organization in untreated cells showed no difference with the normal gravity samples. This indicates that gravity may affect specific components of the signal transduction circuitry.

  14. A species-specific polymerase chain reaction assay for rapid and sensitive detection of Colletotrichum capsici.

    PubMed

    Torres-Calzada, C; Tapia-Tussell, R; Quijano-Ramayo, A; Martin-Mex, R; Rojas-Herrera, R; Higuera-Ciapara, I; Perez-Brito, D

    2011-09-01

    Colletotrichum capsici is an important fungal species that causes anthracnose in many genera of plants causing severe economic losses worldwide. A primer set was designed based on the sequences of the ribosomal internal transcribed spacer (ITS1 and ITS2) regions for use in a conventional PCR assay. The primer set (CcapF/CcapR) amplified a single product of 394 bp with DNA extracted from 20 Mexican isolates of C. capsici. The specificity of primers was confirmed by the absence of amplified product with DNA of four other Colletotrichum species and eleven different fungal genera. This primer set is capable of amplifying only C. capsici from different contaminated tissues or fungal structures, thereby facilitating rapid diagnoses as there is no need to isolate and cultivate the fungus in order to identify it. The sensitivity of detection with this PCR method was 10 pg of genomic DNA from the pathogen. This is the first report of a C. capsici-specific primer set. It allows rapid pathogen detection and provides growers with a powerful tool for a rational selection of fungicides to control anthracnose in different crops and in the post-harvest stage.

  15. Specific Elimination of Latently HIV-1 Infected Cells Using HIV-1 Protease-Sensitive Toxin Nanocapsules.

    PubMed

    Wen, Jing; Yan, Ming; Liu, Yang; Li, Jie; Xie, Yiming; Lu, Yunfeng; Kamata, Masakazu; Chen, Irvin S Y

    2016-01-01

    Anti-retroviral drugs suppress HIV-1 plasma viremia to undetectable levels; however, latent HIV-1 persists in reservoirs within HIV-1-infected patients. The silent provirus can be activated through the use of drugs, including protein kinase C activators and histone deacetylase inhibitors. This "shock" approach is then followed by "kill" of the producing cells either through direct HIV-1-induced cell death or natural immune mechanisms. However, these mechanisms are relatively slow and effectiveness is unclear. Here, we develop an approach to specifically target and kill cells that are activated early in the process of virus production. We utilize a novel nanocapsule technology whereby the ricin A chain is encapsulated in an inactive form within a polymer shell. Specificity for release of the ricin A toxin is conferred by peptide crosslinkers that are sensitive to cleavage by HIV-1 protease. By using well-established latent infection models, J-Lat and U1 cells, we demonstrate that only within an HIV-1-producing cell expressing functional HIV-1 protease will the nanocapsule release its ricin A cargo, shutting down viral and cellular protein synthesis, and ultimately leading to rapid death of the producer cell. Thus, we provide proof of principle for a novel technology to kill HIV-1-producing cells without effects on non-target cells.

  16. Dose Calculation on KV Cone Beam CT Images: An Investigation of the Hu-Density Conversion Stability and Dose Accuracy Using the Site-Specific Calibration

    SciTech Connect

    Rong Yi

    2010-10-01

    Precise calibration of Hounsfield units (HU) to electron density (HU-density) is essential to dose calculation. On-board kV cone beam computed tomography (CBCT) imaging is used predominantly for patients' positioning, but will potentially be used for dose calculation. The impacts of varying 3 imaging parameters (mAs, source-imager distance [SID], and cone angle) and phantom size on the HU number accuracy and HU-density calibrations for CBCT imaging were studied. We proposed a site-specific calibration method to achieve higher accuracy in CBCT image-based dose calculation. Three configurations of the Computerized Imaging Reference Systems (CIRS) water equivalent electron density phantom were used to simulate sites including head, lungs, and lower body (abdomen/pelvis). The planning computed tomography (CT) scan was used as the baseline for comparisons. CBCT scans of these phantom configurations were performed using Varian Trilogy{sup TM} system in a precalibrated mode with fixed tube voltage (125 kVp), but varied mAs, SID, and cone angle. An HU-density curve was generated and evaluated for each set of scan parameters. Three HU-density tables generated using different phantom configurations with the same imaging parameter settings were selected for dose calculation on CBCT images for an accuracy comparison. Changing mAs or SID had small impact on HU numbers. For adipose tissue, the HU discrepancy from the baseline was 20 HU in a small phantom, but 5 times lager in a large phantom. Yet, reducing the cone angle significantly decreases the HU discrepancy. The HU-density table was also affected accordingly. By performing dose comparison between CT and CBCT image-based plans, results showed that using the site-specific HU-density tables to calibrate CBCT images of different sites improves the dose accuracy to {approx}2%. Our phantom study showed that CBCT imaging can be a feasible option for dose computation in adaptive radiotherapy approach if the site-specific

  17. Exploring a Three-Level Model of Calibration Accuracy

    ERIC Educational Resources Information Center

    Schraw, Gregory; Kuch, Fred; Gutierrez, Antonio P.; Richmond, Aaron S.

    2014-01-01

    We compared 5 different statistics (i.e., G index, gamma, "d'", sensitivity, specificity) used in the social sciences and medical diagnosis literatures to assess calibration accuracy in order to examine the relationship among them and to explore whether one statistic provided a best fitting general measure of accuracy. College…

  18. Time-dependent effects of prazosin on the development of methamphetamine conditioned hyperactivity and context-specific sensitization in mice.

    PubMed

    White, André O; Rauhut, Anthony S

    2014-04-15

    The present experiments examined the effects of prazosin, a selective α₁-adrenergic receptor antagonist, on the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Mice received an injection of vehicle (distilled water) or prazosin (0.5, 1.0 or 2.0 mg/kg) 30 min prior to a second injection of vehicle (saline) or methamphetamine (1.0 mg/kg) during the conditioning sessions (Experiment 1). Following the conditioning sessions, mice were tested for conditioned hyperactivity and then tested for context-specific sensitization. In subsequent experiments, mice received an injection of vehicle (distilled water) or prazosin (2.0 mg/kg) immediately (Experiment 2) or 24 h (Experiment 3) after the conditioning sessions and then tested for conditioned hyperactivity and context-specific sensitization. Prazosin dose-dependently blocked the development of methamphetamine conditioned hyperactivity and context-specific sensitization when administered prior to the methamphetamine during the conditioning phase; however nonspecific motor impairments also were observed (Experiment 1). Immediate (Experiment 2), but not the 24-h delay (Experiment 3), post-session administration of prazosin attenuated the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Nonspecific motor impairments were not observed in these latter experiments. Collectively, these results suggest that the α₁-adrenergic receptor mediates the development of methamphetamine-conditioned hyperactivity and context-specific sensitization, perhaps by altering memory consolidation and/or reconsolidation processes.

  19. Accuracy of genotyping using the TaqMan PCR assay for single nucleotide polymorphisms responsible for thiopurine sensitivity in Japanese patients with inflammatory bowel disease.

    PubMed

    Osaki, Rie; Imaeda, Hirotsugu; Ban, Hiromitsu; Aomatsu, Tomoki; Bamba, Shigeki; Tsujikawa, Tomoyuki; Sasaki, Masaya; Fujiyama, Yoshihide; Andoh, Akira

    2011-09-01

    Thiopurine drugs are the most common drugs used to maintain clinical remission in inflammatory bowel disease (IBD). Three single-nucleotide polymorphisms (SNPs), TPMT A719G (rs1142345), inosine triphosphate pyrophosphatase (ITPase) C94A (rs1127354) and multidrug resistance protein 4 MRP4 G2269A (rs3765534), have been reported to account for heightened sensitivity to thiopurine drugs in the Japanese population. We investigated the usefulness of the TaqMan(®) PCR assay (Applied Biosystems) for the rapid detection of these SNPs to improve the safety of thiopurine therapy. We enrolled 44 healthy volunteers and 235 IBD patients. Genotyping of the SNPs was performed using Custom TaqMan SNP genotyping assays, direct sequencing and PCR-RFLP. Genotyping for MRP4 G2269A by the TaqMan PCR assay was successfully achieved in all samples. Comparison with our previous data using direct sequencing indicated one discordant result, and re-sequencing showed that the TaqMan PCR assay was correct. The overall accuracy of the TaqMan assay for MRP4 G2269A was 100%. The TaqMan PCR genotyping for TPMT A719G and ITPase C94A was successfully performed in all samples. The results of TPMT A719G by the TaqMan assay were identical with those of PCR-RFLP. In ITPase C94A, a comparison of the TaqMan assay and PCR-RFLP yielded 12 discordant results, and direct sequencing showed that the TaqMan PCR assay was correct. The allelic frequency determined by the TaqMan assay was 0.145 for MRP4 G2269A, 0.009 for TPMT A719G and 0.121 for ITPase C94A, respectively. In conclusion, the TaqMan(®) PCR assay is useful for genotyping of SNPs responsible for thiopurine sensitivity in Japanese IBD patients.

  20. A new sensitive and specific enzyme-linked immunosorbent assay for IgD.

    PubMed

    Mosedale, David E; Sandhu, Manjinder S; Luan, Jian'an; Goodall, Margaret; Grainger, David J

    2006-06-30

    We have developed a new highly specific ELISA for IgD, and then used it to measure levels of circulating IgD in the serum of 480 un-selected patients from the East Anglia region of UK. The assay is both extremely sensitive and specific, with a minimum detected IgD concentration of 30 pg/ml and more than 10,000-fold specificity for IgD over all other human immunoglobulins. The assay shows linear dilution characteristics with both purified IgD and human serum, and spiking of purified IgD into either purified immunoglobulins or human serum shows c. 100% recovery. Furthermore, intra-assay and inter-assay coefficients of variation for repeated measurements of the same samples are below 10% and 15% respectively. Measurement of IgD levels on the un-selected patient population showed levels to range from <300 pg/ml to over 100 microg/ml, with a geometric mean of 8 microg/ml. The distribution is approximately normal after log transformation. Levels of circulating IgD were higher in men than in women. There was a significant negative correlation between levels of IgD and age in women, but not in men. Moreover, after adjustment for age and sex, there were statistically significantly higher levels of circulating IgD in male (but not female) smokers, compared to their non-smoking counterparts. These results highlight the care that needs to be taken to control for age, sex and cigarette smoking when examining levels of circulating IgD in future studies.

  1. Sensitivity and Specificity of the Minimum Data Set 3.0 Discharge Data Relative to Medicare Claims

    PubMed Central

    Rahman, Momotazur; Tyler, Denise; Acquah, Joseph Kofi; Lima, Julie; Mor, Vincent

    2016-01-01

    Objective The objective of this study was to determine whether the Minimum Data Set (MDS) 3.0 discharge record accurately identifies hospitalizations and deaths of nursing home residents. Design We merged date of death from Medicare enrollment data and hospital inpatient claims with MDS discharge records to check whether the same information can be verified from both the sources. We examined the association of 30-day rehospitalization rates from nursing homes calculated only from MDS and only from claims. We also examined how correspondence between these 2 data sources varies across nursing homes. Settings All fee-for-service (FFS) Medicare beneficiaries admitted for Medicare-paid (with prospective payment system) skilled nursing facility (SNF) care in 2011. Results Some 94% of hospitalization events in Medicare claims can be identified using MDS discharge records and 87% of hospitalization events detected in MDS data can be verified by Medicare hospital claims. Death can be identified almost perfectly from MDS discharge records. More than 99% of the variation in nursing home–level 30-day rehospitalization rate calculated using claims data can be explained by the same rates calculated using MDS. Nursing home structural characteristics explain only 5% of the variation in nursing home–level sensitivity and 3% of the variation in nursing home–level specificity. Conclusion The new MDS 3.0 discharge record matches Medicare enrollment and hospitalization claims events with a high degree of accuracy, meaning that hospitalization rates calculated based on MDS offer a good proxy for the “gold standard” Medicare data. PMID:25179533

  2. [Sensitivity and specificity of flicker perimetry with Pulsar. Comparison with achromatic (white-on-white) perimetry in glaucoma patients].

    PubMed

    Göbel, K; Erb, C

    2013-02-01

    The early detection of functional glaucoma damage plays an increasingly more central role in the diagnosis and treatment of glaucoma disease. Using selective perimetry detection of early glaucomatous defects is more likely and one of these methods is flicker perimetry with Pulsar. Flicker perimetry is used to analyze the temporal visual function in combination with spatial resolution and contrast sensitivity as opposed to standard automated perimetry which measures the differential light sensitivity with a non-specific stimulus. This study showed a higher sensitivity and specificity of Pulsar perimetry in comparison to achromatic perimetry in glaucoma patients.

  3. A systems toxicology approach to elucidate the mechanisms involved in RDX species-specific sensitivity.

    PubMed

    Warner, Christopher M; Gust, Kurt A; Stanley, Jacob K; Habib, Tanwir; Wilbanks, Mitchell S; Garcia-Reyero, Natàlia; Perkins, Edward J

    2012-07-17

    Interspecies uncertainty factors in ecological risk assessment provide conservative estimates of risk where limited or no toxicity data is available. We quantitatively examined the validity of interspecies uncertainty factors by comparing the responses of zebrafish (Danio rerio) and fathead minnow (Pimephales promelas) to the energetic compound 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), a known neurotoxicant. Relative toxicity was measured through transcriptional, morphological, and behavioral end points in zebrafish and fathead minnow fry exposed for 96 h to RDX concentrations ranging from 0.9 to 27.7 mg/L. Spinal deformities and lethality occurred at 1.8 and 3.5 mg/L RDX respectively for fathead minnow and at 13.8 and 27.7 mg/L for zebrafish, indicating that zebrafish have an 8-fold greater tolerance for RDX than fathead minnow fry. The number and magnitude of differentially expressed transcripts increased with increasing RDX concentration for both species. Differentially expressed genes were enriched in functions related to neurological disease, oxidative-stress, acute-phase response, vitamin/mineral metabolism and skeletal/muscular disorders. Decreased expression of collagen-coding transcripts were associated with spinal deformity and likely involved in sensitivity to RDX. Our work provides a mechanistic explanation for species-specific sensitivity to RDX where zebrafish responded at lower concentrations with greater numbers of functions related to RDX tolerance than fathead minnow. While the 10-fold interspecies uncertainty factor does provide a reasonable cross-species estimate of toxicity in the present study, the observation that the responses between ZF and FHM are markedly different does initiate a call for concern regarding establishment of broad ecotoxicological conclusions based on model species such as zebrafish.

  4. High-Sensitivity Monoclonal Antibodies Specific for Homoserine Lactones Protect Mice from Lethal Pseudomonas aeruginosa Infections

    PubMed Central

    Downham, Christina; Broadbent, Ian; Charlton, Keith; Porter, Andrew J.

    2014-01-01

    A number of bacteria, including pathogens like Pseudomonas aeruginosa, utilize homoserine lactones (HSLs) as quorum sensing (QS) signaling compounds and engage in cell-to-cell communication to coordinate their behavior. Blocking this bacterial communication may be an attractive strategy for infection control as QS takes a central role in P. aeruginosa biology. In this study, immunomodulation of HSL molecules by monoclonal antibodies (MAbs) was used as a novel approach to prevent P. aeruginosa infections and as tools to detect HSLs in bodily fluids as a possible first clue to an undiagnosed Gram-negative infection. Using sheep immunization and recombinant antibody technology, a panel of sheep-mouse chimeric MAbs were generated which recognized HSL compounds with high sensitivity (nanomolar range) and cross-reactivity. These MAbs retained their nanomolar sensitivity in complex matrices and were able to recognize HSLs in P. aeruginosa cultures grown in the presence of urine. In a nematode slow-killing assay, HSL MAbs significantly increased the survival of worms fed on the antibiotic-resistant strain PA058. The therapeutic benefit of these MAbs was further studied using a mouse model of Pseudomonas infection in which groups of mice treated with HSL-2 and HSL-4 MAbs survived, 7 days after pathogen challenge, in significantly greater numbers (83 and 67%, respectively) compared with the control groups. This body of work has provided early proof-of-concept data to demonstrate the potential of HSL-specific, monoclonal antibodies as theranostic clinical leads suitable for the diagnosis, prevention, and treatment of life-threatening bacterial infections. PMID:24185854

  5. Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block.

    PubMed

    Dravid, Shashank M; Erreger, Kevin; Yuan, Hongjie; Nicholson, Katherine; Le, Phuong; Lyuboslavsky, Polina; Almonte, Antoine; Murray, Ernest; Mosely, Cara; Barber, Jeremy; French, Adam; Balster, Robert; Murray, Thomas F; Traynelis, Stephen F

    2007-05-15

    We have compared the potencies of structurally distinct channel blockers at recombinant NR1/NR2A, NR1/NR2B, NR1/NR2C and NR1/NR2D receptors. The IC50 values varied with stereochemistry and subunit composition, suggesting that it may be possible to design subunit-selective channel blockers. For dizocilpine (MK-801), the differential potency of MK-801 stereoisomers determined at recombinant NMDA receptors was confirmed at native receptors in vitro and in vivo. Since the proton sensor is tightly linked both structurally and functionally to channel gating, we examined whether blocking molecules that interact in the channel pore with the gating machinery can differentially sense protonation of the receptor. Blockers capable of remaining trapped in the pore during agonist unbinding showed the strongest dependence on extracellular pH, appearing more potent at acidic pH values that promote channel closure. Determination of pK(a) values for channel blockers suggests that the ionization of ketamine but not of other blockers can influence its pH-dependent potency. Kinetic modelling and single channel studies suggest that the pH-dependent block of NR1/NR2A by (-)MK-801 but not (+)MK-801 reflects an increase in the MK-801 association rate even though protons reduce channel open probability and thus MK-801 access to its binding site. Allosteric modulators that alter pH sensitivity alter the potency of MK-801, supporting the interpretation that the pH sensitivity of MK-801 binding reflects the changes at the proton sensor rather than a secondary effect of pH. These data suggest a tight coupling between the proton sensor and the ion channel gate as well as unique subunit-specific mechanisms of channel block.

  6. Effects of ovariectomy and intrinsic aerobic capacity on tissue-specific insulin sensitivity

    PubMed Central

    Park, Young-Min; Rector, R. Scott; Thyfault, John P.; Zidon, Terese M.; Padilla, Jaume; Welly, Rebecca J.; Meers, Grace M.; Morris, Matthew E.; Britton, Steven L.; Koch, Lauren G.; Booth, Frank W.; Kanaley, Jill A.

    2015-01-01

    High-capacity running (HCR) rats are protected against the early (i.e., ∼11 wk postsurgery) development of ovariectomy (OVX)-induced insulin resistance (IR) compared with low-capacity running (LCR) rats. The purpose of this study was to utilize the hyperinsulinemic euglycemic clamp to determine whether 1) HCR rats remain protected from OVX-induced IR when the time following OVX is extended to 27 wk and 2) tissue-specific glucose uptake differences are responsible for the protection in HCR rats under sedentary conditions. Female HCR and LCR rats (n = 40; aged ∼22 wk) randomly received either OVX or sham (SHM) surgeries and then underwent the clamp 27 wk following surgeries. [3-3H]glucose was used to determine glucose clearance, whereas 2-[14C]deoxyglucose (2-DG) was used to assess glucose uptake in skeletal muscle, brown adipose tissue (BAT), subcutaneous white adipose tissue (WAT), and visceral WAT. OVX decreased the glucose infusion rate and glucose clearance in both lines, but HCR had better insulin sensitivity than LCR (P < 0.05). In both lines, OVX significantly reduced glucose uptake in soleus and gastrocnemius muscles; however, HCR showed ∼40% greater gastrocnemius glucose uptake compared with LCR (P < 0.05). HCR also exhibited greater glucose uptake in BAT and visceral WAT compared with LCR (P < 0.05), yet these tissues were not affected by OVX in either line. In conclusion, OVX impairs insulin sensitivity in both HCR and LCR rats, likely driven by impairments in insulin-mediated skeletal muscle glucose uptake. HCR rats have greater skeletal muscle, BAT, and WAT insulin-mediated glucose uptake, which may aid in protection against OVX-associated insulin resistance. PMID:26646101

  7. Sensitivity and specificity of 3-D texture analysis of lung parenchyma is better than 2-D for discrimination of lung pathology in stage 0 COPD

    NASA Astrophysics Data System (ADS)

    Xu, Ye; Sonka, Milan; McLennan, Geoffrey; Guo, Junfeng; Hoffman, Eric

    2005-04-01

    Lung parenchyma evaluation via multidetector-row CT (MDCT), has significantly altered clinical practice in the early detection of lung disease. Our goal is to enhance our texture-based tissue classification ability to differentiate early pathologic processes by extending our 2-D Adaptive Multiple Feature Method (AMFM) to 3-D AMFM. We performed MDCT on 34 human volunteers in five categories: emphysema in severe Chronic Obstructive Pulmonary Disease (COPD) as EC, emphysema in mild COPD (MC), normal appearing lung in COPD (NC), non-smokers with normal lung function (NN), smokers with normal function (NS). We volumetrically excluded the airway and vessel regions, calculated 24 volumetric texture features for each Volume of Interest (VOI); and used Bayesian rules for discrimination. Leave-one-out and half-half methods were used for testing. Sensitivity, specificity and accuracy were calculated. The accuracy of the leave-one-out method for the four-class classification in the form of 3-D/2-D is: EC: 84.9%/70.7%, MC: 89.8%/82.7%; NC: 87.5.0%/49.6%; NN: 100.0%/60.0%. The accuracy of the leave-one-out method for the two-class classification in the form of 3-D/2-D is: NN: 99.3%/71.6%; NS: 99.7%/74.5%. We conclude that 3-D AMFM analysis of the lung parenchyma improves discrimination compared to 2-D analysis of the same images.

  8. Specific and sensitive mRNA biomarkers for the identification of skin in 'touch DNA' evidence.

    PubMed

    Hanson, E; Haas, C; Jucker, R; Ballantyne, J

    2012-09-01

    In forensic casework analysis it is often necessary to attempt to obtain DNA profiles from microscopic amounts of biological material left behind by perpetrators of crime. The ability to obtain profiles from trace biological evidence is routinely demonstrated with so-called 'touch DNA' evidence, which is generally perceived to be the result of DNA obtained from shed skin cells transferred from donor to an object or person during physical contact. Although a genetic profile from trace biological evidence is routinely obtained, the tissue source of the profile is rarely known. This merely perpetuates the 'mystery' of the nature of 'touch DNA' evidence allowing the significance or meaningfulness of genetic profiles obtained from these samples to be challenged. Numerous reports state that the tissue source of origin of 'touch DNA' evidence cannot be determined due to the small amount of biological material present, while others conclude that the DNA profiles are obtained from shed skin cells (as opposed to, say, buccal epithelial cells present in saliva traces) without any scientific basis for this assertion. Proper identification of the biological material present might be crucial to the investigation and prosecution of a criminal offense and a misrepresentation of the nature of the evidence can have undue influence on the perception of the circumstance of the crime. Thus far, research has failed to provide forensic scientists with feasible, definitive methods to identify the tissue origin of 'touch DNA'. In the present work, we sought to identify novel highly specific and sensitive messenger RNA (mRNA) biomarkers for the identification of skin. Gene candidates were identified using both literature searches and whole transcriptome deep sequencing (RNA-Seq). Utilizing this dual approach, we identified and evaluated over 100 gene candidates. Five mRNA markers were identified that demonstrated a high degree of specificity for skin. Using these markers, we have been able

  9. Tissue-Specific and Genetic Regulation of Insulin Sensitivity-Associated Transcripts in African Americans

    PubMed Central

    Sharma, Neeraj K.; Sajuthi, Satria P.; Chou, Jeff W.; Calles-Escandon, Jorge; Demons, Jamehl; Rogers, Samantha; Ma, Lijun; Palmer, Nicholette D.; McWilliams, David R.; Beal, John; Comeau, Mary E.; Cherry, Kristina; Hawkins, Gregory A.; Menon, Lata; Kouba, Ethel; Davis, Donna; Burris, Marcie; Byerly, Sara J.; Easter, Linda; Bowden, Donald W.; Freedman, Barry I.; Langefeld, Carl D.

    2016-01-01

    Context: Compared with European Americans, African Americans (AAs) are more insulin resistant, have a higher insulin secretion response to glucose, and develop type 2 diabetes more often. Molecular processes and/or genetic variations contributing to altered glucose homeostasis in high-risk AAs remain uncharacterized. Objective: Adipose and muscle transcript expression profiling and genotyping were performed in 260 AAs to identify genetic regulatory mechanisms associated with insulin sensitivity (SI). We hypothesized that: 1) transcription profiles would reveal tissue-specific modulation of physiologic pathways with SI, and 2) a subset of SI-associated transcripts would be controlled by DNA sequence variants as expression quantitative traits, and these variants in turn would be associated with SI. Design and Settings: The cross-sectional research study was performed in a clinical research unit. Participants: Unrelated nondiabetic AAs were recruited for the study. Main Outcome Measures: SI was measured by frequently sampled iv glucose tolerance test. Results: The expression levels of 2212 transcripts in adipose and 145 transcripts in muscle were associated with SI. Genes involved in eIF2, eIF4-p70S6K, and mTOR signaling were modulated with SI in both tissues. Genes involved in leukocyte extravasation signaling showed adipose-specific regulation, and genes involved in oxidative phosphorylation had discordant regulation between tissues. Intersecting cis-expression quantitative trait loci results with data from transcript-SI association analysis identified cis-regulatory single nucleotide polymorphisms for 363 and 42 SI-associated transcripts in adipose and muscle, respectively. Cis-eSNPs for three SI-associated adipose transcripts, NINJ1, AGA, and CLEC10A were associated with SI. Abrogation of NINJ1 induction in THP1 macrophages modulated expression of genes in chemokine signaling, cell adhesion, and angiogenesis pathways. Conclusion: This study identified multiple

  10. Reinforcement Sensitivity and Risk for Psychopathology Following Exposure to Violence: A Vulnerability-Specificity Model in Latino Youth

    ERIC Educational Resources Information Center

    Gudino, Omar G.; Nadeem, Erum; Kataoka, Sheryl H.; Lau, Anna S.

    2012-01-01

    Urban Latino youth are exposed to high rates of violence, which increases risk for diverse forms of psychopathology. The current study aims to increase specificity in predicting responses by testing the hypothesis that youths' reinforcement sensitivity--behavioral inhibition (BIS) and behavioral approach (BAS)--is associated with specific clinical…

  11. Exercise thallium-201 myocardial imaging in left main coronary artery disease: sensitive but not specific

    SciTech Connect

    Rehn, T.; Griffith, L.S.; Achuff, S.C.; Bailey, I.K.; Bulkley, B.H.; Burow, R.; Pitt, B.; Becker, L.C.

    1981-08-01

    To determine the usefulness of thallium-201 scintigraphy for identifying left main coronary artery disease, the results of scintigraphy at rest and during exercise were compared in 24 patients with 50 percent or greater narrowing of the left main coronary artery and 80 patients with 50 percent or greater narrowing of one or more of the major coronary arteries but without left main coronary involvement. By segmental analysis of the scintigrams, perfusion defects were assigned to the left anterior descending, left circumflex or right coronary artery, singly or in combination, and the pattern of simultaneous left anterior descending and circumflex arterial defects was used to identify left main coronary artery disease. Of the 24 patients with left main coronary artery disease, 22 (92 percent) had abnormal exercise scintigrams. Despite this high sensitivity, the pattern of perfusion defects was not specific; the ''left main pattern'' was found in 3 patients (13 percent) with left main coronary artery disease but also in 3 (33 percent) of 9 patients with combined left anterior descending and left circumflex arterial disease, 4 (19 percent) of 21 patients with three vessel disease and 3 (6 percent) of 50 patients with one or two vessel disease but excluding the group with left anterior descending plus left circumflex arterial disease. The pattern of perfusion defects in the patients with left main coronary artery disease was determined by the location and severity of narrowings in the coronary arteries downstream from the left main arterial lesion. Concomitant lesions in other arteries were found in all patients with left main coronary disease (one vessel in 1 patient, two vessels in 7 patients and three vessels in 16). For this reason, it is unlikely that even with improvements in radiopharmaceutical agents and imaging techniques, myocardial perfusion scintigraphy will be sufficiently specific for definitive identification of left main coronary artery disease.

  12. Combining two serological assays optimises sensitivity and specificity for the identification of Streptococcus equi subsp. equi exposure.

    PubMed

    Robinson, Carl; Steward, Karen F; Potts, Nicola; Barker, Colin; Hammond, Toni-ann; Pierce, Karen; Gunnarsson, Eggert; Svansson, Vilhjálmur; Slater, Josh; Newton, J Richard; Waller, Andrew S

    2013-08-01

    The detection of anti-Streptococcus equi antibodies in the blood serum of horses can assist with the identification of apparently healthy persistently infected carriers and the prevention of strangles outbreaks. The aim of the current study was to use genome sequencing data to develop an indirect enzyme linked immunosorbent assay (iELISA) that targets two S. equi-specific protein fragments. The sensitivity and specificity of the antigen A and antigen C iELISAs were compared to an SeM-based iELISA marketed by IDvet - diagnostic Vétérinaire (IDvet). Individually, each assay compromised specificity in order to achieve sufficient sensitivity (SeM iELISA had a sensitivity of 89.9%, but a specificity of only 77.0%) or sensitivity to achieve high specificity. However, combining the results of the antigen A and antigen C iELISAs permitted optimisation of both sensitivity (93.3%) and specificity (99.3%), providing a robust assay for the identification of horses exposed to S. equi.

  13. Impact of test sensitivity and specificity on pig producer incentives to control Mycobacterium avium infections in finishing pigs.

    PubMed

    van Wagenberg, Coen P A; Backus, Gé B C; Wisselink, Henk J; van der Vorst, Jack G A J; Urlings, Bert A P

    2013-09-01

    In this paper we analyze the impact of the sensitivity and specificity of a Mycobacterium avium (Ma) test on pig producer incentives to control Ma in finishing pigs. A possible Ma control system which includes a serodiagnostic test and a penalty on finishing pigs in herds detected with Ma infection was modelled. Using a dynamic optimization model and a grid search of deliveries of herds from pig producers to slaughterhouse, optimal control measures for pig producers and optimal penalty values for deliveries with increased Ma risk were identified for different sensitivity and specificity values. Results showed that higher sensitivity and lower specificity induced use of more intense control measures and resulted in higher pig producer costs and lower Ma seroprevalence. The minimal penalty value needed to comply with a threshold for Ma seroprevalence in finishing pigs at slaughter was lower at higher sensitivity and lower specificity. With imperfect specificity a larger sample size decreased pig producer incentives to control Ma seroprevalence, because the higher number of false positives resulted in an increased probability of rejecting a batch of finishing pigs irrespective of whether the pig producer applied control measures. We conclude that test sensitivity and specificity must be considered in incentive system design to induce pig producers to control Ma in finishing pigs with minimum negative effects.

  14. The interaction of extraversion and anxiety sensitivity on social anxiety: evidence of specificity relative to depression.

    PubMed

    Naragon-Gainey, Kristin; Rutter, Lauren A; Brown, Timothy A

    2014-05-01

    Neuroticism and extraversion have been linked to the etiologies and course of anxiety and mood disorders, such that neuroticism is broadly associated with numerous disorders and extraversion is most strongly associated with social anxiety and depression. While previous research has established the broad associations between temperament and emotional disorders, less is known about the specific, proximal factors that are associated with them, and very few studies have situated these risk factors into a larger etiological model that specifies how they may relate to one another. The current study examined the interaction of extraversion and anxiety sensitivity (AS) in predicting social anxiety symptoms in a large, diagnostically diverse clinical sample (N=826). Symptoms were assessed with self-report and dimensional interview measures, and regression analyses were performed examining the main effects and interaction of extraversion and AS (examining both total and lower-order components) on social anxiety. Results showed that at higher levels of AS, the inverse relationship between extraversion and social anxiety was stronger, and the social concerns component of AS is responsible for this effect. This interaction was also observed with regard to depression symptoms, but the interaction was not present after accounting for shared variance (i.e., comorbidity) between depression and social anxiety symptoms. Clinical and theoretical implications of the results are discussed.

  15. Development of a Sensitive and Specific Polyclonal Antibody for Serological Detection of Clavibacter michiganensis subsp. sepedonicus

    PubMed Central

    Przewodowska, Agnieszka

    2017-01-01

    The quarantine bacterium Clavibacter michiganensis subsp. sepedonicus (Cms) causes bacterial ring rot (BRR) in potato but is difficult to detect, hampering the diagnosis of this disease. ELISA immunoassays have not been widely used to detect Cms because commercially available anti-Cms antibodies detect mainly EPS-producing bacteria and can fail to detect strains that do not produce EPS. In the current study, we developed a new type of polyclonal antibody that specifically detects Clavibacter michiganensis subsp. sepedonicus bacteria irrespective of their EPS level. We first found that the presence of bacterial EPS precluded quantitative measurement of bacteria by currently available immunoenzymatic methods, but that washing Cms cells with acidic and basic buffers to remove EPS before analysis successfully standardized ELISA results. We used a mix of three strains of Cms with diverse EPS levels to generate antigen for production of antibodies recognizing Cms cells with and without an EPS layer (IgG-EPS and IgG-N-EPS, respectively). The resulting IgG-N-EPS recognized almost all Cms strains tested in this work regardless of their mucoidal level. The availability of this new antibody renders immunological diagnostics of Cms more sensitive and reliable, as our newly developed antibodies can be used in many type of immunoassays. This work represents an important step forward in efforts to diagnose and prevent the spread of BRR, and the methods and solutions developed in this work are covered by six Polish, one European and one US patents. PMID:28068400

  16. Sensitivity of New Zealand mudsnail Potamopyrgus antipodarum (Gray) to a specific aromatase inhibitor.

    PubMed

    Gust, M; Garric, J; Giamberini, L; Mons, R; Abbaci, K; Garnier, F; Buronfosse, T

    2010-03-01

    The freshwater prosobranch Potamopyrgus antipodarum (Molluska, Hydrobiidea, Smith 1889) has been proposed as a suitable species to assess the impact of endocrine disrupting compounds (EDC) in aquatic ecosystems. Steroid hormone biosynthesis pathway is potentially an important target for EDC, and vertebrate-like sex steroids seem to play a functional role in the control of mollusk reproduction. To assess the response and the sensitivity of P. antipodarum to disrupters of the steroid hormone biosynthesis pathway, we have experienced the action of a specific vertebrate aromatase inhibitor, fadrozole, acting on 17beta-estradiol synthesis in two separate 28 and 42d exposures. Fadrozole had effects consistent with the expected mechanism of action. A decrease of the reproduction parameters (such as on the number of neonates and number of embryos in the brood pouch) in a dose-dependant manner was observed. The steroids levels were also impaired with the ratio 17beta-estradiol/testosterone decreased by half in exposed snails. This shift of the steroids balance was accompanied by some alteration in the gonads histology and immunohistochemistry in fadrozole-exposed snails. This study highlights the value role of P. antipodarum as a test species for assessing EDC effects in aquatic wildlife.

  17. Substrate specificity and inhibitor sensitivity of rabbit 20α-hydroxysteroid dehydrogenase.

    PubMed

    Endo, Satoshi; Arai, Yuki; Hara, Akira; Kitade, Yukio; Bunai, Yasuo; El-Kabbani, Ossama; Matsunaga, Toshiyuki

    2013-01-01

    In this study, we examined the substrate specificity and inhibitor sensitivity of rabbit 20α-hydroxysteroid dehydrogenase (AKR1C5), which plays a role in the termination of pregnancy by progesterone inactivation. AKR1C5 moderately reduced the 3-keto group of only 5α-dihydrosteroids with 17β- or 20α/β-hydroxy group among 3-ketosteroids. In contrast, the enzyme reversibly and efficiently catalyzed the reduction of various 17- and 20-ketosteroids, including estrogen precursors (dehydroepiandrosterone, estrone and 5α-androstan-3β-ol-17-one) and tocolytic 5β-pregnane-3,20-dione. In addition to the progesterone inactivation, the formation of estrogens and metabolism of the tocolytic steroid by AKR1C5 may be related to its role in rabbit parturition. AKR1C5 also reduced various non-steroidal carbonyl compounds, including isatin, an antagonist of the C-type natriuretic peptide receptor, and 4-oxo-2-nonenal, suggesting its roles in controlling the bioactive isatin and detoxification of cytotoxic aldehydes. AKR1C5 was potently and competitively inhibited by flavonoids such as kaempferol and quercetin, suggesting that its activity is affected by ingested flavonoids.

  18. Bactrian camel nanobody-based immunoassay for specific and sensitive detection of Cry1Fa toxin.

    PubMed

    Wang, Pingyan; Li, Guanghui; Yan, Junrong; Hu, Yonghong; Zhang, Cunzheng; Liu, Xianjin; Wan, Yakun

    2014-12-15

    The variable domain of the heavy-chain-only antibody (VHH) or nanobody (Nb), derived from camelids, begins to play an important role on the detection of protein markers. In this study, we constructed a phage-displayed library of VHHs against Cry1Fa by immunizing a healthy Bactrian camel with Cry1Fa toxin. After a series of bio-panning and screening by phage display technology, three anti-Cry1Fa nanobodies (Nbs) with great difference in complementarity determining region 3 (CDR3) were obtained and they were highly specific to Cry1Fa as well as showed full of activity when exposed to 70 °C for 3 h. Through modifying Nbs with Horseradish Peroxidase (HRP) and biotin, two Nbs which can recognize the different epitopes of Cry1Fa were determined and they were used to establish a novel sandwich immune ELISA based on biotin-SA interaction for Cry1Fa detection. The immunoassay exhibited a linear range from 1 to 100 ng/mL with a detection limit of 0.88 ng/mL. The recoveries from spiked corn and soybean samples were ranged from 83.33 to 117.17%, with a coefficient of variation (C.V) less than 6.0%. All together, the proposed immunoassay will be a promising way for sensitive and accurate determination of Cry1Fa toxin.

  19. Imaging Non-Specific Wrist Pain: Interobserver Agreement and Diagnostic Accuracy of SPECT/CT, MRI, CT, Bone Scan and Plain Radiographs

    PubMed Central

    Huellner, Martin W.; Bürkert, Alexander; Strobel, Klaus; Pérez Lago, María del Sol; Werner, Lennart; Hug, Urs; von Wartburg, Urs; Seifert, Burkhardt; Veit-Haibach, Patrick

    2013-01-01

    Purpose Chronic hand and wrist pain is a common clinical issue for orthopaedic surgeons and rheumatologists. The purpose of this study was 1. To analyze the interobserver agreement of SPECT/CT, MRI, CT, bone scan and plain radiographs in patients with non-specific pain of the hand and wrist, and 2. to assess the diagnostic accuracy of these imaging methods in this selected patient population. Materials and Methods Thirty-two consecutive patients with non-specific pain of the hand or wrist were evaluated retrospectively. All patients had been imaged by plain radiographs, planar early-phase imaging (bone scan), late-phase imaging (SPECT/CT including bone scan and CT), and MRI. Two experienced and two inexperienced readers analyzed the images with a standardized read-out protocol. Reading criteria were lesion detection and localisation, type and etiology of the underlying pathology. Diagnostic accuracy and interobserver agreement were determined for all readers and imaging modalities. Results The most accurate modality for experienced readers was SPECT/CT (accuracy 77%), followed by MRI (56%). The best performing, though little accurate modality for inexperienced readers was also SPECT/CT (44%), followed by MRI and bone scan (38% each). The interobserver agreement of experienced readers was generally high in SPECT/CT concerning lesion detection (kappa 0.93, MRI 0.72), localisation (kappa 0.91, MRI 0.75) and etiology (kappa 0.85, MRI 0.74), while MRI yielded better results on typification of lesions (kappa 0.75, SPECT/CT 0.69). There was poor agreement between experienced and inexperienced readers in SPECT/CT and MRI. Conclusions SPECT/CT proved to be the most helpful imaging modality in patients with non-specific wrist pain. The method was found reliable, providing high interobserver agreement, being outperformed by MRI only concerning the typification of lesions. We believe it is beneficial to integrate SPECT/CT into the diagnostic imaging algorithm of chronic wrist

  20. Dual Recognition Strategy for Specific and Sensitive Detection of Bacteria Using Aptamer-Coated Magnetic Beads and Antibiotic-Capped Gold Nanoclusters.

    PubMed

    Cheng, Dan; Yu, Mengqun; Fu, Fei; Han, Weiye; Li, Gan; Xie, Jianping; Song, Yang; Swihart, Mark T; Song, Erqun

    2016-01-05

    Food poisoning and infectious diseases caused by pathogenic bacteria such as Staphylococcus aureus (SA) are serious public health concerns. A method of specific, sensitive, and rapid detection of such bacteria is essential and important. This study presents a strategy that combines aptamer and antibiotic-based dual recognition units with magnetic enrichment and fluorescent detection to achieve specific and sensitive quantification of SA in authentic specimens and in the presence of much higher concentrations of other bacteria. Aptamer-coated magnetic beads (Apt-MB) were employed for specific capture of SA. Vancomycin-stabilized fluorescent gold nanoclusters (AuNCs@Van) were prepared by a simple one-step process and used for sensitive quantification of SA in the range of 32-10(8) cfu/mL with the detection limit of 16 cfu/mL via a fluorescence intensity measurement. And using this strategy, about 70 cfu/mL of SA in complex samples (containing 3 × 10(8) cfu/mL of other different contaminated bacteria) could be successfully detected. In comparison to prior studies, the developed strategy here not only simplifies the preparation procedure of the fluorescent probes (AuNCs@Van) to a great extent but also could sensitively quantify SA in the presence of much higher concentrations of other bacteria directly with good accuracy. Moreover, the aptamer and antibiotic used in this strategy are much less expensive and widely available compared to common-used antibodies, making it cost-effective. This general aptamer- and antibiotic-based dual recognition strategy, combined with magnetic enrichment and fluorescent detection of trace bacteria, shows great potential application in monitoring bacterial food contamination and infectious diseases.

  1. Hemisphere-Specific Effects of Subthalamic Nucleus Deep Brain Stimulation on Speaking Rate and Articulatory Accuracy of Syllable Repetitions in Parkinson's Disease.

    PubMed

    Wang, Emily Q; Metman, Leo Verhagen; Bakay, Roy A E; Arzbaecher, Jean; Bernard, Bryan; Corcos, Daniel M

    2006-01-01

    This study tested the hypothesis that left versus right deep brain stimulation (DBS) of the subthalamic nucleus (STN) would have differential effects on speech. Twenty right-handed individuals with advanced Parkinson's disease (PD) underwent unilateral STN DBS. Ten were operated on the right and 10 on the left hemisphere as indicated by severity of nonspeech motor function. Speech was evaluated before surgery and 3 to 6 months after surgery with stimulator-off and with stimulator-on, with all participants off anti-parkinsonian medication for 12 hours before evaluation. Evaluators and patient speakers were blinded to the stimulator status at the postsurgery evaluations. Motor performance was assessed with UPDRS-III. Each participant produced three samples of diadochokinetic syllables. Syllable rate, syllable and vowel duration, VOT, and F0 were obtained. The diadochokinetic syllables were rated for articulatory accuracy and speaking rate. Twenty graduate clinicians served as judges. The samples were randomly presented via headphones. A mixed ANOVA with repeated measures was used to assess the significance of the changes in UPRS-III scores and speech measures. The results indicated that unilateral STN DBS produced improvement in nonspeech motor function regardless of the side of stimulation. In contrast, the changes in articulatory accuracy and syllable rate associated with the STN DBS were hemisphere specific.

  2. Antigen-Specific Priming is Dispensable in Depletion of Apoptosis-Sensitive T Cells for GvHD Prophylaxis.

    PubMed

    Yarkoni, Shai; Stein, Jerry; Yaniv, Isaac; Askenasy, Nadir

    2014-01-01

    Prophylactic approaches to graft versus host disease (GvHD) have employed both phenotypic reduction of T cells and selective elimination of host-primed donor T cells in vitro and in vivo. An additional approach to GvHD prophylaxis by functional depletion of apoptosis-sensitive donor T cells without host-specific sensitization ex vivo showed remarkable reduction in GHD incidence and severity. We address the role and significance of antigen-specific sensitization of donor T cells and discuss the mechanisms of functional T cell purging by apoptosis for GvHD prevention. Host-specific sensitization is dispensable because migration is antigen-independent and donor T cell sensitization is mediated by multiple and redundant mechanisms of presentation of major and minor histocompatibility complex and tissue antigens by donor and host antigen-presenting cells. Our data suggest that potential murine and human GvH effectors reside within subsets of preactivated T cells susceptible to negative regulation by apoptosis prior to encounter of and sensitization to specific antigens.

  3. Antigen-Specific Priming is Dispensable in Depletion of Apoptosis-Sensitive T Cells for GvHD Prophylaxis

    PubMed Central

    Yarkoni, Shai; Stein, Jerry; Yaniv, Isaac; Askenasy, Nadir

    2014-01-01

    Prophylactic approaches to graft versus host disease (GvHD) have employed both phenotypic reduction of T cells and selective elimination of host-primed donor T cells in vitro and in vivo. An additional approach to GvHD prophylaxis by functional depletion of apoptosis-sensitive donor T cells without host-specific sensitization ex vivo showed remarkable reduction in GHD incidence and severity. We address the role and significance of antigen-specific sensitization of donor T cells and discuss the mechanisms of functional T cell purging by apoptosis for GvHD prevention. Host-specific sensitization is dispensable because migration is antigen-independent and donor T cell sensitization is mediated by multiple and redundant mechanisms of presentation of major and minor histocompatibility complex and tissue antigens by donor and host antigen-presenting cells. Our data suggest that potential murine and human GvH effectors reside within subsets of preactivated T cells susceptible to negative regulation by apoptosis prior to encounter of and sensitization to specific antigens. PMID:24904571

  4. Estimation of the sensitivity and specificity of a Leptospira spp. in-house ELISA through Bayesian modelling.

    PubMed

    Schlichting, Daniela; Nöckler, Karsten; Bahn, Peter; Luge, Enno; Greiner, Matthias; Müller-Graf, Christine; Mayer-Scholl, Anne

    2015-10-01

    The microscopic agglutination test (MAT) is still considered the gold standard for the diagnosis of leptospirosis, although studies have shown that the test is an imperfect gold standard for clinical samples and unsuitable for epidemiological studies. Here, test characteristics of an in-house ELISA were identified for both subclinical and clinical populations by Bayesian latent class models. A conditional dependence model for two diagnostic tests and two populations was adapted to analyse a clinical and a subclinical scenario, respectively. These Bayesian models were used to estimate the sensitivity and specificity of the in-house ELISA and the MAT as well as the prevalences. The Bayesian estimates of the in-house ELISA were: clinical sensitivity=83.0%, clinical specificity=98.5%, subclinical sensitivity=85.7% and subclinical specificity=99.1%. In contrast, the estimates of the MAT were: clinical sensitivity=65.6%, clinical specificity=97.7%, subclinical sensitivity 54.9% and subclinical specificity=97.3%. The results show the suitability of the in-house ELISA for both clinical investigations and epidemiological studies in mildly endemic areas.

  5. Advancing the prediction accuracy of protein-protein interactions by utilizing evolutionary information from position-specific scoring matrix and ensemble classifier.

    PubMed

    Wang, Lei; You, Zhu-Hong; Xia, Shi-Xiong; Liu, Feng; Chen, Xing; Yan, Xin; Zhou, Yong

    2017-04-07

    Protein-Protein Interactions (PPIs) are essential to most biological processes and play a critical role in most cellular functions. With the development of high-throughput biological techniques and in silico methods, a large number of PPI data have been generated for various organisms, but many problems remain unsolved. These factors promoted the development of the in silico methods based on machine learning to predict PPIs. In this study, we propose a novel method by combining ensemble Rotation Forest (RF) classifier and Discrete Cosine Transform (DCT) algorithm to predict the interactions among proteins. Specifically, the protein amino acids sequence is transformed into Position-Specific Scoring Matrix (PSSM) containing biological evolution information, and then the feature vector is extracted to present protein evolutionary information using DCT algorithm; finally, the ensemble rotation forest model is used to predict whether a given protein pair is interacting or not. When performed on Yeast and H. pylori data sets, the proposed method achieved excellent results with an average accuracy of 98.54% and 88.27%. In addition, we achieved good prediction accuracy of 98.08%, 92.75%, 98.87% and 98.72% on independent data sets (C.elegans, E.coli, H.sapiens and M.musculus). In order to further evaluate the performance of our method, we compare it with the state-of-the-art Support Vector Machine (SVM) classifier and get good results. As a web server, the source code and Yeast data sets used in this article are freely available at http://202.119.201.126:8888/DCTRF/.

  6. Sensitivity and Specificity of Interictal EEG-fMRI for Detecting the Ictal Onset Zone at Different Statistical Thresholds.

    PubMed

    Tousseyn, Simon; Dupont, Patrick; Goffin, Karolien; Sunaert, Stefan; Van Paesschen, Wim

    2014-01-01

    There is currently a lack of knowledge about electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) specificity. Our aim was to define sensitivity and specificity of blood oxygen level dependent (BOLD) responses to interictal epileptic spikes during EEG-fMRI for detecting the ictal onset zone (IOZ). We studied 21 refractory focal epilepsy patients who had a well-defined IOZ after a full presurgical evaluation and interictal spikes during EEG-fMRI. Areas of spike-related BOLD changes overlapping the IOZ in patients were considered as true positives; if no overlap was found, they were treated as false-negatives. Matched healthy case-controls had undergone similar EEG-fMRI in order to determine true-negative and false-positive fractions. The spike-related regressor of the patient was used in the design matrix of the healthy case-control. Suprathreshold BOLD changes in the brain of controls were considered as false positives, absence of these changes as true negatives. Sensitivity and specificity were calculated for different statistical thresholds at the voxel level combined with different cluster size thresholds and represented in receiver operating characteristic (ROC)-curves. Additionally, we calculated the ROC-curves based on the cluster containing the maximal significant activation. We achieved a combination of 100% specificity and 62% sensitivity, using a Z-threshold in the interval 3.4-3.5 and cluster size threshold of 350 voxels. We could obtain higher sensitivity at the expense of specificity. Similar performance was found when using the cluster containing the maximal significant activation. Our data provide a guideline for different EEG-fMRI settings with their respective sensitivity and specificity for detecting the IOZ. The unique cluster containing the maximal significant BOLD activation was a sensitive and specific marker of the IOZ.

  7. [A sensitive and specific radioimmunoassay for arginine vasopressin and its validation].

    PubMed

    Oki, Y; Ohgo, S; Yoshimi, T

    1984-03-20

    A sensitive and specific radioimmunoassay (RIA) for arginine vasopressin (AVP) has been developed and validated. Synthetic AVP was coupled to bovine serum albumin (BSA) with glutaraldehyde. Antisera against AVP were raised in three rabbits immunized with AVP-BSA complex. After 6 months, at the 16th injection, one of the antisera had a titer high enough to be utilizable for RIA at a final dilution of 1:400,000. The labeling of AVP with 125I Na was performed with the modified chloramine T method, and the purification of iodinated AVP was done with gel filtration chromatography on a Sephadex G-25 fine column (1 X 20 cm) with an elution buffer of 0.01 M acetic acid containing 0.1% BSA. Radioactivities from the Sephadex G-25 were eluted in three peaks. 125I-AVP, which was reactive to the antiserum, was contained in the third peak, and 125I-AVP in the fractions on the down slope of the peak was used for the radioligand in the amount of 1000 cpm. The specific activity of purified 125I-AVP was about 400 muCi/microgram. Diluted antiserum and samples, unlabeled AVP or related peptides were preincubated at 4 degrees C for 24 hr, and then 125I-AVP was added to the mixture and incubated for a further 72 hr. Separation of B and F was done with polyethyleneglycol. The minimal detection limit of AVP, which was 95% of the confidence limit of the mean value of B0, was 0.4 pg/tube. The cross-reactivities with lysine vasopressin, arginine vasotocin, DDAVP and oxytocin were 0.1%, 30%, 1% and 0%, respectively. AVP in plasma was extracted with cold acetone and petroleum ether. The recoveries of synthetic AVP from plasma which was added (2-16 pg) were more than 94%. The intra and inter-assay coefficients of variation determined by plasma of AVP concentration of about 4.8 pg/ml were 8.7% and 11.3%, respectively. The RIA detected AVP of concentration as low as 1 pg/ml following the extraction procedure. AVP immunoreactivity was detected without extraction in urine, and the lyophilized

  8. Sensitivity and specificity of Cobas TaqMan MTB real-time polymerase chain reaction for culture-proven Mycobacterium tuberculosis: meta-analysis of 26999 specimens from 17 Studies.

    PubMed

    Horita, Nobuyuki; Yamamoto, Masaki; Sato, Takashi; Tsukahara, Toshinori; Nagakura, Hideyuki; Tashiro, Ken; Shibata, Yuji; Watanabe, Hiroki; Nagai, Kenjiro; Nakashima, Kentaro; Ushio, Ryota; Ikeda, Misako; Sakamaki, Kentaro; Yoshiyama, Takashi; Kaneko, Takeshi

    2015-12-09

    Since 2010, studies on the diagnostic accuracy of COBAS TaqMan MTB (CTM) have been frequently reported with an unignorable discrepancy. The key inclusion criterion for this systematic review was original studies that could provide sufficient data for calculating the sensitivity and the specificity of CTM for M tuberculosis (TB) or M tuberculosis complex. The reference test was Mycobacterium culture. We used bivariate model for meta-analyses. Of the 201 candidate articles, we finally identified 17 eligible articles.Concerning the respiratory specimens, 1900 culture positive specimens and 20983 culture negative specimens from 15 studies were assessed. This provided the summary estimate sensitivity of 0.808 (95% CI 0.758-0.850) and the summary estimate specificity of 0.990 (95% CI 0.981-0.994). The area under curve was 0.956. The diagnostic odds ratio was 459 (95% CI 261-805, I(2) 26%). For the smear positive respiratory specimens, the sensitivity was 0.952 (95% CI 0.926-0.969) and the specificity was 0.916 (95% CI 0.797-0.968). For the smear negative respiratory specimens, the sensitivity and the specificity were 0.600 (95% CI 0.459-0.726) and 0.989 (95% CI 0.981-0.993), respectively. The diagnostic accuracy was poorer for the non-respiratory specimens, than for the respiratory specimens, but was acceptable. We believe that the information obtained from this study will aid physicians' decision making.

  9. Applicability, reliability, sensitivity, and specificity of six Brighton Collaboration standardized case definitions for adverse events following immunization.

    PubMed

    Kohl, Katrin S; Magnus, Manya; Ball, Robert; Halsey, Neal; Shadomy, Sean; Farley, Thomas A

    2008-11-25

    We evaluated the applicability, reliability, sensitivity, and specificity of six standardized case definitions for adverse events following immunization (AEFI) (for fever, generalized convulsive seizure, hypotonic-hyporesponsive episode, intussusception, nodule, and persistent crying) developed by the Brighton Collaboration using the U.S. Vaccine Adverse Event Reporting System (VAERS). The evaluation included: (a) the development of codified search strings using standardized coding terminology, and (b) for sensitivity and specificity analyses, the development of a "gold standard" for case determination by clinical expert reviews, and its comparison against the application of the definitions to VAERS reports by nonclinicians. Application of the case definitions in an automated approach proved to be valid, feasible, and unlikely to miss confirmed cases of the reported clinical event. The definitions had variable but generally high sensitivity and specificity compared to clinician review, which in itself yielded inconsistent case determination. The study demonstrated the need for the developed standardized definitions for AEFI and their usefulness in passive surveillance.

  10. Bayesian estimation of sensitivity and specificity of Coxiella burnetii antibody ELISA tests in bovine blood and milk.

    PubMed

    Paul, Suman; Toft, Nils; Agerholm, Jørgen S; Christoffersen, Anna-Bodil; Agger, Jens F

    2013-05-01

    Serological tests for Coxiella burnetii (the causative agent of Q fever) antibodies are usually based on enzyme linked immunosorbent assay (ELISA) although this method is not thoroughly evaluated. The objective of this study was to determine the sensitivity and specificity of an ELISA for detection of C. burnetii antibodies in milk and blood samples, using latent class models in a Bayesian analysis. Blood and milk samples of 568 lactating cows from 17 Danish dairy cattle herds collected in 2008 were used. The best combination of sensitivity and specificity estimates was revealed at a sample to positive (S/P) cut-off of 40 for both blood and milk ELISAs. At this cut-off, sensitivity of milk ELISA was 0.86 (95% posterior credibility interval [PCI] [0.76; 0.96]). This was slightly but insignificantly higher than sensitivity of blood ELISA (0.84; 95% PCI [0.75; 0.93]). The specificity estimates of the ELISA methods on milk and blood were equal at 0.99. No conditional dependence was observed between the specificity estimates of the two test methods. However, the sensitivity estimates of both tests were significantly reduced when conditional covariances ≥ 40 were used. Collection of milk samples from lactating cows is relatively easy, non-invasive and inexpensive and hence milk ELISA may be a better option for screening lactating cows. But, blood ELISA is an option for screening non-lactating cattle.

  11. Sensitivity of subject-specific models to Hill muscle-tendon model parameters in simulations of gait.

    PubMed

    Carbone, V; van der Krogt, M M; Koopman, H F J M; Verdonschot, N

    2016-06-14

    Subject-specific musculoskeletal (MS) models of the lower extremity are essential for applications such as predicting the effects of orthopedic surgery. We performed an extensive sensitivity analysis to assess the effects of potential errors in Hill muscle-tendon (MT) model parameters for each of the 56 MT parts contained in a state-of-the-art MS model. We used two metrics, namely a Local Sensitivity Index (LSI) and an Overall Sensitivity Index (OSI), to distinguish the effect of the perturbation on the predicted force produced by the perturbed MT parts and by all the remaining MT parts, respectively, during a simulated gait cycle. Results indicated that sensitivity of the model depended on the specific role of each MT part during gait, and not merely on its size and length. Tendon slack length was the most sensitive parameter, followed by maximal isometric muscle force and optimal muscle fiber length, while nominal pennation angle showed very low sensitivity. The highest sensitivity values were found for the MT parts that act as prime movers of gait (Soleus: average OSI=5.27%, Rectus Femoris: average OSI=4.47%, Gastrocnemius: average OSI=3.77%, Vastus Lateralis: average OSI=1.36%, Biceps Femoris Caput Longum: average OSI=1.06%) and hip stabilizers (Gluteus Medius: average OSI=3.10%, Obturator Internus: average OSI=1.96%, Gluteus Minimus: average OSI=1.40%, Piriformis: average OSI=0.98%), followed by the Peroneal muscles (average OSI=2.20%) and Tibialis Anterior (average OSI=1.78%) some of which were not included in previous sensitivity studies. Finally, the proposed priority list provides quantitative information to indicate which MT parts and which MT parameters should be estimated most accurately to create detailed and reliable subject-specific MS models.

  12. Sensitivity and specificity of waist circumference as a single screening tool for identification of overweight and obesity among Malaysian adults.

    PubMed

    Kee, C C; Jamaiyah, H; Geeta, A; Ali, Z Ahmad; Safiza, M N Noor; Suzana, S; Khor, G L; Rahmah, R; Jamalludin, A R; Sumarni, M G; Lim, K H; Faudzi, Y Ahmad; Amal, N M

    2011-12-01

    Generalised obesity and central obesity are risk factors for Type II diabetes mellitus and cardiovascular diseases. Waist circumference (WC) has been suggested as a single screening tool for identification of overweight or obese subjects in lieu of the body mass index (BMI) for weight management in public health program. Currently, the recommended waist circumference cut-off points of > or = 94cm for men and > or =80cm for women (waist action level 1) and > or = 102cm for men and > or = 88cm for women (waist action level 2) used for identification of overweight and obesity are based on studies in Caucasian populations. The objective of this study was to assess the sensitivity and specificity of the recommended waist action levels, and to determine optimal WC cut-off points for identification of overweight or obesity with central fat distribution based on BMI for Malaysian adults. Data from 32,773 subjects (14,982 men and 17,791 women) aged 18 and above who participated in the Third National Health Morbidity Survey in 2006 were analysed. Sensitivity and specificity of WC at waist action level 1 were 48.3% and 97.5% for men; and 84.2% and 80.6% for women when compared to the cut-off points based on BMI > or = 25kg/m2. At waist action level 2, sensitivity and specificity were 52.4% and 98.0% for men, and 79.2% and 85.4% for women when compared with the cut-off points based on BMI (> or = 30 kg/m2). Receiver operating characteristic analyses showed that the appropriatescreening cut-off points for WC to identify subjects with overweight (> or = 25kg/m2) was 86.0cm (sensitivity=83.6%, specificity=82.5%) for men, and 79.1cm (sensitivity=85.0%, specificity=79.5%) for women. Waist circumference cut-off points to identify obese subjects (BMI > or = 30 kg/m2) was 93.2cm (sensitivity=86.5%, specificity=85.7%) for men and 85.2cm (sensitivity=77.9%, specificity=78.0%) for women. Our findings demonstrated that the current recommended waist circumference cut-off points have low

  13. PI3 kinase is involved in cocaine behavioral sensitization and its reversal with brain area specificity

    SciTech Connect

    Zhang Xiuwu . E-mail: xwzhang@duke.edu; Mi Jing; Wetsel, William C.; Davidson, Colin; Xiong Xieying; Chen Qiang; Ellinwood, Everett H.; Lee, Tong H.

    2006-02-24

    Phosphatidylinositol 3-kinase (PI3K) is an important signaling molecule involved in cell differentiation, proliferation, survival, and phagocytosis, and may participate in various brain functions. To determine whether it is also involved in cocaine sensitization, we measured the p85{alpha}/p110 PI3K activity in the nuclear accumbens (NAc) shell, NAc core, and prefrontal cortex (PFC) following establishment of cocaine sensitization and its subsequent reversal. Naive rats were rank-ordered and split into either daily cocaine or saline pretreatment group based on their locomotor responses to an acute cocaine injection (7.5 mg/kg, i.p.). These two groups were then injected with cocaine (40 mg/kg, s.c.) or saline for 4 consecutive days followed by 9-day withdrawal. Cocaine sensitization was subsequently reversed by 5 daily injections of the D{sub 1}/D{sub 2} agonist pergolide (0.1 mg/kg, s.c.) in combination with the 5-HT{sub 3} antagonist ondansetron (0.2 mg/kg, s.c., 3.5 h after pergolide injection). After another 9-day withdrawal, behavioral cocaine sensitization and its reversal were confirmed with an acute cocaine challenge (7.5 mg/kg, i.p.), and animals were sacrificed the next day for measurement of p85{alpha}/p110 PI3K activity. Cocaine-sensitized animals exhibited increased PI3K activity in the NAc shell, and this increase was reversed by combined pergolide/ondansetron treatment, which also reversed behavioral sensitization. In the NAc core and PFC, cocaine sensitization decreased and increased the PI3K activity, respectively. These changes, in contrast to that in the NAc shell, were not normalized following the reversal of cocaine-sensitization. Interestingly, daily injections of pergolide alone in saline-pretreated animals induced PI3K changes that were similar to the cocaine sensitization-associated changes in the NAc core and PFC but not the NAc shell; furthermore, these changes in saline-pretreated animals were prevented by ondansetron given 3.5 h after

  14. Assessing the Sensitivity and Specificity of the MAYSI-2 for Detecting Trauma among Youth in Juvenile Detention

    ERIC Educational Resources Information Center

    Kerig, Patricia K.; Moeddel, Melissa Arnzen; Becker, Stephen P.

    2011-01-01

    This study investigated the sensitivity and specificity of the most widely used mental health screening instrument in juvenile detention, the Massachusetts Youth Screening Instrument (MAYSI-2), for detecting trauma and symptoms of posttraumatic stress disorder (PTSD) among detained youth. The MAYSI-2 scales measuring Substance Use,…

  15. Assessment of Relationship-Specific Incentive and Threat Sensitivities: Predicting Satisfaction and Affect in Adult Intimate Relationships

    ERIC Educational Resources Information Center

    Laurenceau, Jean-Philippe; Kleinman, Brighid M.; Kaczynski, Karen J.; Carver, Charles S.

    2010-01-01

    Self-report scales assessing relationship-specific incentive and threat sensitivity were created. Initial tests of factor structure and associations with relationship quality were conducted in a sample of persons in intimate relationships (Study 1). Associations with conceptually related measures were examined to determine convergent and…

  16. Sensitivity and Specificity of the Screen for Child Anxiety Related Emotional Disorders (SCARED): A Community-Based Study

    ERIC Educational Resources Information Center

    DeSousa, Diogo Araujo; Salum, Giovanni Abrahao; Isolan, Luciano Rassier; Manfro, Gisele Gus

    2013-01-01

    The aim of this cross-sectional community-based study was to examine the sensitivity and specificity of the Screen for Child Anxiety Related Emotional Disorders (SCARED) to the diagnosis of anxiety disorders (AD). Participants were 119 students aged 9-18. Psychiatric diagnoses were assessed by a psychiatrist throughout a structural clinical…

  17. Analysis of the Sensitivity and Specificity of Noninvasive Imaging Tests for the Diagnosis of Renal Artery Stenosis

    PubMed Central

    Borelli, Flavio Antonio de Oliveira; Pinto, Ibraim M. F.; Amodeo, Celso; Smanio, Paola E. P.; Kambara, Antonio M.; Petisco, Ana Claudia G.; Moreira, Samuel M.; Paiva, Ricardo Calil; Lopes, Hugo Belotti; Sousa, Amanda G. M. R.

    2013-01-01

    Background Aging and atherosclerosis are related to renovascular hypertension in elderly individuals. Regardless of comorbidities, renal artery stenosis is itself an important cause of cardiovascular morbidity and mortality. Objective To define the sensitivity, specificity, positive predictive value, and negative predictive value of noninvasive imaging tests used in the diagnosis of renal artery stenosis. Methods In a group of 61 patients recruited, 122 arteries were analized, thus permitting the definition of sensitivity, specificity, and the relative contribution of each imaging study performed (Doppler, scintigraphy and computed tomographic angiography in comparison to renal arteriography). Results The mean age was 65.43 years (standard deviation: 8.7). Of the variables related to the study population that were compared to arteriography, two correlated with renal artery stenosis, renal dysfunction and triglycerides. The median glomerular filtration rate was 52.8 mL/min/m2. Doppler showed sensitivity of 82.90%, specificity of 70%, a positive predictive value of 85% and negative predictive value of 66.70%. For tomography, sensitivity was 66.70%, specificity 80%, positive predictive value 87.50% and negative predictive value 55.20%. With these findings, we could identify the imaging tests that best detected stenosis. Conclusion Tomography and Doppler showed good quality and efficacy in the diagnosis of renal artery stenosis, with Doppler having the advantage of not requiring the use of contrast medium for the assessment of a disease that is common in diabetics and is associated with renal dysfunction and severe left ventricular dysfunction. PMID:24061685

  18. Theory of Planned Behavior: Sensitivity and Specificity in Predicting Graduation and Drop-Out among College and University Students?

    ERIC Educational Resources Information Center

    Fichten, Catherine S.; Amsel, Rhonda; Jorgensen, Mary; Nguyen, Mai Nhu; Budd, Jillian; King, Laura; Jorgensen, Shirley; Asuncion, Jennison

    2016-01-01

    We examined sensitivity and specificity when using the three theory of planned behavior (TPB) scales (Perceived Behavioral Control, Subjective Norms, Attitude) to predict graduation and drop-out in a longitudinal study of 252 college and university students with disabilities and in a separate cross-sectional study of a random sample of 1380…

  19. Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection.

    PubMed

    Hoff, Soren T; Peter, Jonathan G; Theron, Grant; Pascoe, Mellissa; Tingskov, Pernille N; Aggerbeck, Henrik; Kolbus, Daniel; Ruhwald, Morten; Andersen, Peter; Dheda, Keertan

    2016-03-01

    C-Tb, a novel Mycobacterium tuberculosis and 6-kDa early secretory antigenic target/10-kDa culture filtrate protein (ESAT-6/CFP-10)-specific skin test, has high specificity in bacille Calmette-Guerin-vaccinated healthy controls. However, the sensitivity of C-Tb has hitherto not been determined. The objective was to determine the sensitivity of C-Tb in patients with active tuberculosis (TB) in comparison with the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT).C-Tb and TST were randomly administered in a double-blinded fashion to one or the other forearm in 253 patients with active TB with or without HIV co-infection. QFT-GIT testing was performed prior to skin testing.Using a receiver operating characteristic curve-derived cut-point of 5 mm, C-Tb sensitivity was similar to QFT-GIT (73.9 (95% CI 67.8-79.3) versus 75.1 (95% CI 69.3-80.2)), and similar in HIV-infected and HIV-uninfected patients (76.7 (95% CI 69.0-83.3) versus 69.5 (95% CI 59.2-78.5)). However, sensitivity was significantly diminished in HIV-infected patients with CD4 counts <100 cells·mm(-3). C-Tb and QFT-GIT combined had significantly higher sensitivity than C-Tb alone (p<0.0001). C-Tb was safe with no significant adverse events. The 5 mm cut-point corresponded to that found in the previously published specificity study (TESEC-04).C-Tb has similar sensitivity compared with QFT-GIT for the diagnosis of M. tuberculosis infection. Sensitivity was reduced only in HIV-infected patients with severe immunosuppression. Further studies in different settings are required to validate the proposed 5 mm cut-point.

  20. Enhancing and evaluating diagnostic accuracy.

    PubMed

    Swets, J A; Getty, D J; Pickett, R M; D'Orsi, C J; Seltzer, S E; McNeil, B J

    1991-01-01

    Techniques that may enhance diagnostic accuracy in clinical settings were tested in the context of mammography. Statistical information about the relevant features among those visible in a mammogram and about their relative importances in the diagnosis of breast cancer was the basis of two decision aids for radiologists: a checklist that guides the radiologist in assigning a scale value to each significant feature of the images of a particular case, and a computer program that merges those scale values optimally to estimate a probability of malignancy. A test set of approximately 150 proven cases (including normals and benign and malignant lesions) was interpreted by six radiologists, first in their usual manner and later with the decision aids. The enhancing effect of these feature-analytic techniques was analyzed across subsets of cases that were restricted progressively to more and more difficult cases, where difficulty was defined in terms of the radiologists' judgements in the standard reading condition. Accuracy in both standard and enhanced conditions decreased regularly and substantially as case difficulty increased, but differentially, such that the enhancement effect grew regularly and substantially. For the most difficult case sets, the observed increases in accuracy translated into an increase of about 0.15 in sensitivity (true-positive proportion) for a selected specificity (true-negative proportion) of 0.85 or a similar increase in specificity for a selected sensitivity of 0.85. That measured accuracy can depend on case-set difficulty to different degrees for two diagnostic approaches has general implications for evaluation in clinical medicine. Comparative, as well as absolute, assessments of diagnostic performances--for example, of alternative imaging techniques--may be distorted by inadequate treatments of this experimental variable. Subset analysis, as defined and illustrated here, can be useful in alleviating the problem.

  1. Children's school-breakfast reports and school-lunch reports (in 24-h dietary recalls): conventional and reporting-error-sensitive measures show inconsistent accuracy results for retention interval and breakfast location.

    PubMed

    Baxter, Suzanne D; Guinn, Caroline H; Smith, Albert F; Hitchcock, David B; Royer, Julie A; Puryear, Megan P; Collins, Kathleen L; Smith, Alyssa L

    2016-04-14

    Validation-study data were analysed to investigate retention interval (RI) and prompt effects on the accuracy of fourth-grade children's reports of school-breakfast and school-lunch (in 24-h recalls), and the accuracy of school-breakfast reports by breakfast location (classroom; cafeteria). Randomly selected fourth-grade children at ten schools in four districts were observed eating school-provided breakfast and lunch, and were interviewed under one of eight conditions created by crossing two RIs ('short'--prior-24-hour recall obtained in the afternoon and 'long'--previous-day recall obtained in the morning) with four prompts ('forward'--distant to recent, 'meal name'--breakfast, etc., 'open'--no instructions, and 'reverse'--recent to distant). Each condition had sixty children (half were girls). Of 480 children, 355 and 409 reported meals satisfying criteria for reports of school-breakfast and school-lunch, respectively. For breakfast and lunch separately, a conventional measure--report rate--and reporting-error-sensitive measures--correspondence rate and inflation ratio--were calculated for energy per meal-reporting child. Correspondence rate and inflation ratio--but not report rate--showed better accuracy for school-breakfast and school-lunch reports with the short RI than with the long RI; this pattern was not found for some prompts for each sex. Correspondence rate and inflation ratio showed better school-breakfast report accuracy for the classroom than for cafeteria location for each prompt, but report rate showed the opposite. For each RI, correspondence rate and inflation ratio showed better accuracy for lunch than for breakfast, but report rate showed the opposite. When choosing RI and prompts for recalls, researchers and practitioners should select a short RI to maximise accuracy. Recommendations for prompt selections are less clear. As report rates distort validation-study accuracy conclusions, reporting-error-sensitive measures are recommended.

  2. Aquaporin-4 Autoantibodies in Neuromyelitis Optica: AQP4 Isoform-Dependent Sensitivity and Specificity

    PubMed Central

    Pisani, Francesco; Sparaneo, Angelo; Tortorella, Carla; Ruggieri, Maddalena; Trojano, Maria; Mola, Maria Grazia; Nicchia, Grazia Paola; Frigeri, Antonio; Svelto, Maria

    2013-01-01

    Neuromyelitis Optica (NMO) is an autoimmune demyelinating disease, characterized by the presence of autoantibody (NMO-IgG) to Aquaporin-4 (AQP4). NMO-IgG identification supports NMO diagnosis and several diagnostic tests have been developed, but their sensitivity is too variable, and some assay show low sensitivity. This impairs correct diagnosis of NMO. By cell based assay (CBA) we here evaluate the efficacy of different strategies to express AQP4 in mammalian cells in terms of: a) AQP4 translation initiation signals; b) AQP4 isoforms (M1 and M23) and fluorescent tag position; c) NMO serum concentration and AQP4 degradation. Our results demonstrate that when using AQP4-M1, the nucleotide in position −3 of the AUG greatly affects the AQP4-M1/M23 protein ratio, NMO-IgG binding, and consequently test sensitivity. Test sensitivity was highest with M23 expressing cells (97.5%) and only 27.5% with AQP4-M1. The fluorescent tag added to the N-terminus of AQP4-M23 considerably affected the NMO-IgG binding, and test sensitivity, due to disruption of AQP4 suprastructures. Furthermore, sera used at high concentration resulted in AQP4 degradation which affected test sensitivity. To further evaluate the reliability of the M23 based CBA test, samples of one NMO patient collected during about 2 years clinical follow-up were tested. The results of serum titer correlated with disease activity and treatment response. In conclusion, we provide a molecular explanation for the contrasting CBA test data reported and suggest the use of M23 with a C-terminus fluorescent tag as the proper test for NMO diagnosis. PMID:24260168

  3. Aquaporin-4 autoantibodies in Neuromyelitis Optica: AQP4 isoform-dependent sensitivity and specificity.

    PubMed

    Pisani, Francesco; Sparaneo, Angelo; Tortorella, Carla; Ruggieri, Maddalena; Trojano, Maria; Mola, Maria Grazia; Nicchia, Grazia Paola; Frigeri, Antonio; Svelto, Maria

    2013-01-01

    Neuromyelitis Optica (NMO) is an autoimmune demyelinating disease, characterized by the presence of autoantibody (NMO-IgG) to Aquaporin-4 (AQP4). NMO-IgG identification supports NMO diagnosis and several diagnostic tests have been developed, but their sensitivity is too variable, and some assay show low sensitivity. This impairs correct diagnosis of NMO. By cell based assay (CBA) we here evaluate the efficacy of different strategies to express AQP4 in mammalian cells in terms of: a) AQP4 translation initiation signals; b) AQP4 isoforms (M1 and M23) and fluorescent tag position; c) NMO serum concentration and AQP4 degradation. Our results demonstrate that when using AQP4-M1, the nucleotide in position -3 of the AUG greatly affects the AQP4-M1/M23 protein ratio, NMO-IgG binding, and consequently test sensitivity. Test sensitivity was highest with M23 expressing cells (97.5%) and only 27.5% with AQP4-M1. The fluorescent tag added to the N-terminus of AQP4-M23 considerably affected the NMO-IgG binding, and test sensitivity, due to disruption of AQP4 suprastructures. Furthermore, sera used at high concentration resulted in AQP4 degradation which affected test sensitivity. To further evaluate the reliability of the M23 based CBA test, samples of one NMO patient collected during about 2 years clinical follow-up were tested. The results of serum titer correlated with disease activity and treatment response. In conclusion, we provide a molecular explanation for the contrasting CBA test data reported and suggest the use of M23 with a C-terminus fluorescent tag as the proper test for NMO diagnosis.

  4. Construction and Accuracy Assessment of Patient-Specific Biocompatible Drill Template for Cervical Anterior Transpedicular Screw (ATPS) Insertion: An In Vitro Study

    PubMed Central

    Kong, Xiangxue; Zhao, Weidong; Tang, Lei; Li, Jianyi; Ouyang, Jun

    2013-01-01

    Background With the properties of three-column fixation and anterior-approach-only procedure, anterior transpedicular screw (ATPS) is ideal for severe multilevel traumatic cervical instabilities. However, the accurate insertion of ATPS remains challenging. Here we constructed a patient-specific biocompatible drill template and evaluated its accuracy in assisting ATPS insertion. Methods After ethical approval, 24 formalin-preserved cervical vertebrae (C2–C7) were CT scanned. 3D reconstruction models of cervical vertebra were obtained with 2-mm-diameter virtual pin tracts at the central pedicles. The 3D models were used for rapid prototyping (RP) printing. A 2-mm-diameter Kirschner wire was then inserted into the pin tract of the RP model before polymethylmethacrylate was used to construct the patient-specific biocompatible drill template. After removal of the anterior soft tissue, a 2-mm-diameter Kirschner wire was inserted into the cervical pedicle with the assistance of drill template. Cadaveric cervical spines with pin tracts were subsequently scanned using the same CT scanner. A 3D reconstruction was performed of the scanned spines to get 3D models of the vertebrae containing the actual pin tracts. The deviations were calculated between 3D models with virtual and actual pin tracts at the middle point of the cervical pedicle. 3D models of 3.5 mm-diameter screws were used in simulated insertion to grade the screw positions. Findings The patient-specific biocompatible drill template was constructed to assist ATPS insertion successfully. There were no significant differences between medial/lateral deviations (P = 0.797) or between superior/inferior deviations (P = 0.741). The absolute deviation values were 0.82±0.75 mm and 1.10±0.96 mm in axial and sagittal planes, respectively. In the simulated insertion, the screws in non-critical position were 44/48 (91.7%). Conclusions The patient-specific drill template is biocompatible, easy-to-apply and accurate

  5. Sensitivity and Specificity of Proposed "DSM-5" Diagnostic Criteria for Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    McPartland, James C.; Reichow, Brian; Volkmar, Fred R.

    2012-01-01

    Objective: This study evaluated the potential impact of proposed "DSM-5" diagnostic criteria for autism spectrum disorder (ASD). Method: The study focused on a sample of 933 participants evaluated during the "DSM-IV" field trial; 657 carried a clinical diagnosis of an ASD, and 276 were diagnosed with a non-autistic disorder. Sensitivity and…

  6. Spinal Manipulative Therapy Specific Changes In Pain Sensitivity In Individuals With Low Back Pain (NCT01168999)

    PubMed Central

    Bialosky, Joel E; George, Steven Z; Horn, Maggie E; Price, Donald D; Staud, Roland; Robinson, Michael E

    2013-01-01

    Spinal Manipulative Therapy (SMT) is effective for some individuals experiencing low back pain (LBP); however, the mechanisms are not established regarding the role of placebo. SMT is associated with changes in pain sensitivity suggesting related altered central nervous system response or processing of afferent nociceptive input. Placebo is also associated with changes in pain sensitivity and the efficacy of SMT for changes in pain sensitivity beyond placebo has not been adequately considered. We randomly assigned 110 participants with LBP to receive SMT, placebo SMT, placebo SMT with the instructional set, “The manual therapy technique you will receive has been shown to significantly reduce low back pain in some people”, or no intervention. Participants receiving the SMT and placebo SMT received their assigned intervention 6 times over two weeks. Pain sensitivity was assessed prior to and immediately following the assigned intervention during the first session. Clinical outcomes were assessed at baseline and following two weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (p= 0.05, partial η2= 0.07). Group dependent differences were not observed for changes in pain intensity and disability at two week. Participant satisfaction was greatest following the enhanced placebo SMT. PMID:24361109

  7. Specific Disgust Sensitivities Differentially Predict Interest in Careers of Varying Procedural-Intensity among Medical Students

    ERIC Educational Resources Information Center

    Consedine, Nathan S.; Windsor, John A.

    2014-01-01

    Mismatches between the needs of public health systems and student interests have led to renewed study on the factors predicting career specializations among medical students. While most work examines career and lifestyle values, emotional proclivities may be important; disgust sensitivity may help explain preferences for careers with greater and…

  8. Probe-Specific Procedure to Estimate Sensitivity and Detection Limits for 19F Magnetic Resonance Imaging

    PubMed Central

    Taylor, Alexander J.; Granwehr, Josef; Lesbats, Clémentine; Krupa, James L.; Six, Joseph S.; Pavlovskaya, Galina E.; Thomas, Neil R.; Auer, Dorothee P.; Meersmann, Thomas; Faas, Henryk M.

    2016-01-01

    Due to low fluorine background signal in vivo, 19F is a good marker to study the fate of exogenous molecules by magnetic resonance imaging (MRI) using equilibrium nuclear spin polarization schemes. Since 19F MRI applications require high sensitivity, it can be important to assess experimental feasibility during the design stage already by estimating the minimum detectable fluorine concentration. Here we propose a simple method for the calibration of MRI hardware, providing sensitivity estimates for a given scanner and coil configuration. An experimental “calibration factor” to account for variations in coil configuration and hardware set-up is specified. Once it has been determined in a calibration experiment, the sensitivity of an experiment or, alternatively, the minimum number of required spins or the minimum marker concentration can be estimated without the need for a pilot experiment. The definition of this calibration factor is derived based on standard equations for the sensitivity in magnetic resonance, yet the method is not restricted by the limited validity of these equations, since additional instrument-dependent factors are implicitly included during calibration. The method is demonstrated using MR spectroscopy and imaging experiments with different 19F samples, both paramagnetically and susceptibility broadened, to approximate a range of realistic environments. PMID:27727294

  9. Linear and Logarithmic Speed-Accuracy Trade-Offs in Reciprocal Aiming Result from Task-Specific Parameterization of an Invariant Underlying Dynamics

    ERIC Educational Resources Information Center

    Bongers, Raoul M.; Fernandez, Laure; Bootsma, Reinoud J.

    2009-01-01

    The authors examined the origins of linear and logarithmic speed-accuracy trade-offs from a dynamic systems perspective on motor control. In each experiment, participants performed 2 reciprocal aiming tasks: (a) a velocity-constrained task in which movement time was imposed and accuracy had to be maximized, and (b) a distance-constrained task in…

  10. Adaptive smoothing based on Gaussian processes regression increases the sensitivity and specificity of fMRI data.

    PubMed

    Strappini, Francesca; Gilboa, Elad; Pitzalis, Sabrina; Kay, Kendrick; McAvoy, Mark; Nehorai, Arye; Snyder, Abraham Z

    2017-03-01

    Temporal and spatial filtering of fMRI data is often used to improve statistical power. However, conventional methods, such as smoothing with fixed-width Gaussian filters, remove fine-scale structure in the data, necessitating a tradeoff between sensitivity and specificity. Specifically, smoothing may increase sensitivity (reduce noise and increase statistical power) but at the cost loss of specificity in that fine-scale structure in neural activity patterns is lost. Here, we propose an alternative smoothing method based on Gaussian processes (GP) regression for single subjects fMRI experiments. This method adapts the level of smoothing on a voxel by voxel basis according to the characteristics of the local neural activity patterns. GP-based fMRI analysis has been heretofore impractical owing to computational demands. Here, we demonstrate a new implementation of GP that makes it possible to handle the massive data dimensionality of the typical fMRI experiment. We demonstrate how GP can be used as a drop-in replacement to conventional preprocessing steps for temporal and spatial smoothing in a standard fMRI pipeline. We present simulated and experimental results that show the increased sensitivity and specificity compared to conventional smoothing strategies. Hum Brain Mapp 38:1438-1459, 2017. © 2016 Wiley Periodicals, Inc.

  11. Viral immunoblotting: a sensitive method for detecting viral-specific oliogoclonal bands in unconcentrated cerebrospinal fluid.

    PubMed

    Moyle, S; Keir, G; Thompson, E J

    1984-06-01

    A new method for detecting viral antibodies in cerebrospinal fluid is described. The technique has many advantages over previously published methods in that it is highly sensitive eliminating the need to concentrate the CSF, takes 5 h to complete, avoids the use of radionucleides, and most importantly circumvents problems associated with prozone effects which occur in immunoprecipitation reaction since the viral antigen is immobilized on nitrocellulose membranes.

  12. Overlay accuracy fundamentals

    NASA Astrophysics Data System (ADS)

    Kandel, Daniel; Levinski, Vladimir; Sapiens, Noam; Cohen, Guy; Amit, Eran; Klein, Dana; Vakshtein, Irina

    2012-03-01

    Currently, the performance of overlay metrology is evaluated mainly based on random error contributions such as precision and TIS variability. With the expected shrinkage of the overlay metrology budget to < 0.5nm, it becomes crucial to include also systematic error contributions which affect the accuracy of the metrology. Here we discuss fundamental aspects of overlay accuracy and a methodology to improve accuracy significantly. We identify overlay mark imperfections and their interaction with the metrology technology, as the main source of overlay inaccuracy. The most important type of mark imperfection is mark asymmetry. Overlay mark asymmetry leads to a geometrical ambiguity in the definition of overlay, which can be ~1nm or less. It is shown theoretically and in simulations that the metrology may enhance the effect of overlay mark asymmetry significantly and lead to metrology inaccuracy ~10nm, much larger than the geometrical ambiguity. The analysis is carried out for two different overlay metrology technologies: Imaging overlay and DBO (1st order diffraction based overlay). It is demonstrated that the sensitivity of DBO to overlay mark asymmetry is larger than the sensitivity of imaging overlay. Finally, we show that a recently developed measurement quality metric serves as a valuable tool for improving overlay metrology accuracy. Simulation results demonstrate that the accuracy of imaging overlay can be improved significantly by recipe setup optimized using the quality metric. We conclude that imaging overlay metrology, complemented by appropriate use of measurement quality metric, results in optimal overlay accuracy.

  13. From "five" to 5 for 5 minutes: Arabic number transcoding as a short, specific, and sensitive screening tool for mathematics learning difficulties.

    PubMed

    Moura, Ricardo; Lopes-Silva, Júlia Beatriz; Vieira, Laura Rodrigues; Paiva, Giulia Moreira; Prado, Ana Carolina de Almeida; Wood, Guilherme; Haase, Vitor Geraldi

    2015-02-01

    Number transcoding (e.g., writing 29 when hearing "twenty-nine") is one of the most basic numerical abilities required in daily life and is paramount for mathematics achievement. The aim of this study is to investigate psychometric properties of an Arabic number-writing task and its capacity to identify children with mathematics difficulties. We assessed 786 children (55% girls) from first to fourth grades, who were classified as children with mathematics difficulties (n = 103) or controls (n = 683). Although error rates were low, the task presented adequate internal consistency (0.91). Analyses revealed effective diagnostic accuracy in first and second school grades (specificity equals to 0.67 and 0.76 respectively, and sensitivity equals to 0.70 and 0.88 respectively). Moreover, items tapping the understanding of place-value syntax were the most sensitive to mathematics achievement. Overall, we propose that number transcoding is a useful tool for the assessment of mathematics abilities in early elementary school.

  14. Exercise transcutaneous oxygen pressure measurement has good sensitivity and specificity to detect lower extremity arterial stenosis assessed by computed tomography angiography.

    PubMed

    Koch, Caroline; Chauve, Emmanuel; Chaudru, Ségolène; Le Faucheur, Alexis; Jaquinandi, Vincent; Mahé, Guillaume

    2016-09-01

    Peripheral artery disease (PAD) is a highly prevalent disease diagnosed by the use of ankle-brachial index (ABI) at rest. In some clinical conditions (diabetes, renal insufficiency, advanced age), ABI can be falsely normal and other tests are required for the PAD diagnosis (American Heart Association statement). This study was conducted to determine the accuracy of exercise transcutaneous oxygen pressure measurement (exercise-TcPo2) in detection of arterial stenosis ≥50% using computed tomography angiography (CTA) as the gold standard.We retrospectively analyzed consecutive patients referred to our vascular unit (University Hospital, Rennes, France) for exercise-TcPo2 testing from 2014 to 2015. All included patients had a CTA performed within 3 months of the exercise-TcPo2 test. Exercise-TcPo2 was performed on treadmill (10% slope; 2 mph speed). We calculated the Delta from Resting Oxygen Pressure (DROP) index (expressed in mm Hg) at the proximal and distal levels. Two blinded physicians performed stenosis quantification on CTA. The receiver operating characteristic (ROC) curve was used to define a cutoff point to detect arterial stenosis ≥50%, stenosis ≥60%, and stenosis ≥70%.A total of 34 patients (mean age 64 ± 2 years old; 74% men) were analyzed. The highest areas under the curve (AUC) were found for 60% stenosis at both proximal and distal levels. For stenosis ≥50%, sensitivity and specificity of proximal minimal DROP were 80.9% [67.1-89.7], 81.0% [59.3-92.7] respectively. For stenosis ≥50%, sensitivity and specificity of distal minimal DROP were 73.2% [60.3-83.1], 83.3% [53.8-96.2], respectively. For stenosis ≥60%, sensitivity and specificity of proximal minimal DROP were 82.5% [67.6-91.5] and 85.7% [67.7-94.8] respectively. For stenosis ≥60%, sensitivity and specificity of distal minimal DROP were 80.4% [67.3-89.1] and 88.2% [64.2-97.7], respectively. For stenosis ≥70%, sensitivity and specificity of proximal minimal DROP were 85

  15. Achilles tendon stress is more sensitive to subject-specific geometry than subject-specific material properties: A finite element analysis.

    PubMed

    Hansen, Wencke; Shim, Vickie B; Obst, Steven; Lloyd, David G; Newsham-West, Richard; Barrett, Rod S

    2017-03-04

    This study used subject-specific measures of three-dimensional (3D) free Achilles tendon geometry in conjunction with a finite element method to investigate the effect of variation in subject-specific geometry and subject-specific material properties on tendon stress during submaximal isometric loading. Achilles tendons of eight participants (Aged 25-35years) were scanned with freehand 3D ultrasound at rest and during a 70% maximum voluntary isometric contraction. Ultrasound images were segmented, volume rendered and transformed into subject-specific 3D finite element meshes. The mean (±SD) lengths, volumes and cross-sectional areas of the tendons at rest were 62±13mm, 3617±984mm(3) and 58±11mm(2) respectively. The measured tendon strain at 70% MVIC was 5.9±1.3%. Subject-specific material properties were obtained using an optimisation approach that minimised the difference between measured and modelled longitudinal free tendon strain. Generic geometry was represented by the average mesh and generic material properties were taken from the literature. Local stresses were subsequently computed for combinations of subject-specific and generic geometry and material properties. For a given geometry, changing from generic to subject-specific material properties had little effect on the stress distribution in the tendon. In contrast, changing from generic to subject-specific geometry had a 26-fold greater effect on tendon stress distribution. Overall, these findings indicate that the stress distribution experienced by the living free Achilles tendon of a young and healthy population during voluntary loading are more sensitive to variation in tendon geometry than variation in tendon material properties.

  16. Preliminary Observations on Sensitivity and Specificity of Magnetization Transfer Asymmetry for Imaging Myelin of Rat Brain at High Field

    PubMed Central

    Kim, Jae-Woong; Choi, Jiye; Cho, Janggeun; Lee, Chulhyun; Jeon, Daejong; Park, Sung-Hong

    2015-01-01

    Magnetization transfer ratio (MTR) has been often used for imaging myelination. Despite its high sensitivity, the specificity of MTR to myelination is not high because tissues with no myelin such as muscle can also show high MTR. In this study, we propose a new magnetization transfer (MT) indicator, MT asymmetry (MTA), as a new method of myelin imaging. The experiments were performed on rat brain at 9.4 T. MTA revealed high signals in white matter and significantly low signals in gray matter and muscle, indicating that MTA has higher specificity than MTR. Demyelination and remyelination studies demonstrated that the sensitivity of MTA to myelination was as high as that of MTR. These experimental results indicate that MTA can be a good biomarker for imaging myelination. In addition, MTA images can be efficiently acquired with an interslice MTA method, which may accelerate clinical application of myelin imaging. PMID:26413534

  17. HPV Genotyping of Modified General Primer-Amplicons Is More Analytically Sensitive and Specific by Sequencing than by Hybridization

    PubMed Central

    Meisal, Roger; Rounge, Trine Ballestad; Christiansen, Irene Kraus; Eieland, Alexander Kirkeby; Worren, Merete Molton; Molden, Tor Faksvaag; Kommedal, Øyvind; Hovig, Eivind; Leegaard, Truls Michael

    2017-01-01

    Sensitive and specific genotyping of human papillomaviruses (HPVs) is important for population-based surveillance of carcinogenic HPV types and for monitoring vaccine effectiveness. Here we compare HPV genotyping by Next Generation Sequencing (NGS) to an established DNA hybridization method. In DNA isolated from urine, the overall analytical sensitivity of NGS was found to be 22% higher than that of hybridization. NGS was also found to be the most specific method and expanded the detection repertoire beyond the 37 types of the DNA hybridization assay. Furthermore, NGS provided an increased resolution by identifying genetic variants of individual HPV types. The same Modified General Primers (MGP)-amplicon was used in both methods. The NGS method is described in detail to facilitate implementation in the clinical microbiology laboratory and includes suggestions for new standards for detection and calling of types and variants with improved resolution. PMID:28045981

  18. Preliminary Observations on Sensitivity and Specificity of Magnetization Transfer Asymmetry for Imaging Myelin of Rat Brain at High Field.

    PubMed

    Kim, Jae-Woong; Choi, Jiye; Cho, Janggeun; Lee, Chulhyun; Jeon, Daejong; Park, Sung-Hong

    2015-01-01

    Magnetization transfer ratio (MTR) has been often used for imaging myelination. Despite its high sensitivity, the specificity of MTR to myelination is not high because tissues with no myelin such as muscle can also show high MTR. In this study, we propose a new magnetization transfer (MT) indicator, MT asymmetry (MTA), as a new method of myelin imaging. The experiments were performed on rat brain at 9.4 T. MTA revealed high signals in white matter and significantly low signals in gray matter and muscle, indicating that MTA has higher specificity than MTR. Demyelination and remyelination studies demonstrated that the sensitivity of MTA to myelination was as high as that of MTR. These experimental results indicate that MTA can be a good biomarker for imaging myelination. In addition, MTA images can be efficiently acquired with an interslice MTA method, which may accelerate clinical application of myelin imaging.

  19. Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments

    NASA Astrophysics Data System (ADS)

    Loo, Lit-Hsin; Bougen-Zhukov, Nicola Michelle; Tan, Wei-Ling Cecilia

    2017-03-01

    Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent.

  20. Label-Free Electrical Immunosensor for Highly Sensitive and Specific Detection of Microcystin-LR in Water Samples.

    PubMed

    Tan, Feng; Saucedo, Nuvia Maria; Ramnani, Pankaj; Mulchandani, Ashok

    2015-08-04

    Microcystin-LR (MCLR) is one of the most commonly detected and toxic cyclic heptapeptide cyanotoxins released by cyanobacterial blooms in surface waters, for which sensitive and specific detection methods are necessary to carry out its recognition and quantification. Here, we present a single-walled carbon nanotube (SWCNTs)-based label-free chemiresistive immunosensor for highly sensitive and specific detection of MCLR in different source waters. MCLR was initially immobilized on SWCNTs modified interdigitated electrode, followed by incubation with monoclonal anti-MCLR antibody. The competitive binding of MCLR in sample solutions induced departure of the antibody from the antibody-antigen complexes formed on SWCNTs, resulting in change in the conductivity between source and drain of the sensor. The displacement assay greatly improved the sensitivity of the sensor compared with direct immunoassay on the same device. The immunosensor exhibited a wide linear response to log value of MCLR concentration ranging from 1 to 1000 ng/L, with a detection limit of 0.6 ng/L. This method showed good reproducibility, stability and recovery. The proposed method provides a powerful tool for rapid and sensitive monitoring of MCLR in environmental samples.

  1. Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments

    PubMed Central

    Loo, Lit-Hsin; Bougen-Zhukov, Nicola Michelle; Tan, Wei-Ling Cecilia

    2017-01-01

    Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent. PMID:28272488

  2. Development of a highly sensitive and specific blastomycosis antibody enzyme immunoassay using Blastomyces dermatitidis surface protein BAD-1.

    PubMed

    Richer, Sarah M; Smedema, Melinda L; Durkin, Michelle M; Brandhorst, T Tristan; Hage, Chadi A; Connolly, Patricia A; Leland, Diane S; Davis, Thomas E; Klein, Bruce S; Wheat, L Joseph

    2014-02-01

    Serologic tests for antibodies to Blastomyces dermatitidis are not thought to be useful for the diagnosis of blastomycosis, in part due to the low sensitivity of immunodiffusion and complement fixation. Earlier studies have shown that the enzyme immunoassay improves the sensitivity of antibody detection for the diagnosis of blastomycosis. Microplates coated with the B. dermatitidis surface protein BAD-1 were used for testing sera from patients with proven blastomycosis or histoplasmosis and controls. Semiquantification was accomplished by using standards containing human anti-B. dermatitidis antibodies. The antibodies were detected in 87.8% of the patients with blastomycosis by the enzyme immunoassay compared to 15.0% by immunodiffusion. The specificities were 99.2% for patients with nonfungal infections and healthy subjects and 94.0% for patients with histoplasmosis. The results were highly reproducible on repeat testing. When combined with antigen testing, antibody testing improved the sensitivity from 87.8% to 97.6%. Enzyme immunoassay detection of antibodies against BAD-1 is highly specific, has greatly improved sensitivity over immunodiffusion, and may identify cases with negative results by antigen testing. This assay has the potential to aid in the diagnosis of blastomycosis.

  3. Sensitive and specific detection of Xanthomonas axonopodis pv. citri by PCR using pathovar specific primers based on hrpW gene sequences.

    PubMed

    Park, Dong Suk; Hyun, Jae Wook; Park, Young Jin; Kim, Jung Sun; Kang, Hee Wan; Hahn, Jang Ho; Go, Seung Joo

    2006-01-01

    A sensitive and specific assay was developed to detect citrus bacterial canker caused by Xanthomonas axonopodis pv. citri, in leaves and fruits of citrus. Primers XACF and XACR from hrpW homologous to pectate lyase, modifying the structure of pectin in plants, were used to amplify a 561 bp DNA fragment. PCR technique was applied to detect the pathogen in naturally or artificially infected leaves of citrus. The PCR product was only produced from X. axonopodis pv. citri among 26 isolates of Xanthomonas strains, Escherichia coli (O157:H7), Pectobacterium carotovorum subsp. carotovorum, and other reference microbes.

  4. Differential Sensitivity of Specific Neuronal Populations of the Rat Hypothalamus to Prolactin Action

    PubMed Central

    Sapsford, Tony J.; Kokay, Ilona C.; Östberg, Lovisa; Bridges, Robert S.; Grattan, David R.

    2014-01-01

    Prolactin stimulates dopamine release from neuroendocrine dopaminergic (NEDA) neurons in the hypothalamic arcuate nucleus (ARC) to maintain low levels of serum prolactin. Elevated prolactin levels during pregnancy and lactation may mediate actions in other hypothalamic regions such as the paraventricular nucleus (PVN) and rostral preoptic area (rPOA). We predicted that NEDA neurons would be more sensitive prolactin targets than neurons in other regions because they are required to regulate basal prolactin secretion. Moreover, differences in the accessibility of the ARC to prolactin in blood may influence the responsiveness of this population. Therefore, we compared prolactin-induced signaling in different hypothalamic neuronal populations following either systemic or intracerebroventricular (icv) prolactin administration. Phosphorylation of the signal transduction factor, STAT5 (pSTAT5), was used to identify prolactin-responsive neurons. In response to systemic prolactin, pSTAT5-labeled cells were widely observed in the ARC but absent from the rPOA and PVN. Many of these responsive cells in the ARC were identified as NEDA neurons. The lowest icv prolactin dose (10 ng) induced pSTAT5 in the ARC, but with higher doses (>500 ng) pSTAT5 was detected in numerous regions, including the rPOA and PVN. NEDA neurons were maximally labeled with nuclear pSTAT5 in response to 500 ng prolactin and appeared to be more sensitive than dopaminergic neurons in the rPOA. Subpopulations of oxytocin neurons in the hypothalamus were also found to be differentially sensitive to prolactin. These data suggest that differences in the accessibility of the arcuate nucleus to prolactin, together with intrinsic differences in the NEDA neurons, may facilitate homeostatic feedback regulation of prolactin release. PMID:21953590

  5. Patient-specific geometrical modeling of orthopedic structures with high efficiency and accuracy for finite element modeling and 3D printing.

    PubMed

    Huang, Huajun; Xiang, Chunling; Zeng, Canjun; Ouyang, Hanbin; Wong, Kelvin Kian Loong; Huang, Wenhua

    2015-12-01

    We improved the geometrical modeling procedure for fast and accurate reconstruction of orthopedic structures. This procedure consists of medical image segmentation, three-dimensional geometrical reconstruction, and assignment of material properties. The patient-specific orthopedic structures reconstructed by this improved procedure can be used in the virtual surgical planning, 3D printing of real orthopedic structures and finite element analysis. A conventional modeling consists of: image segmentation, geometrical reconstruction, mesh generation, and assignment of material properties. The present study modified the conventional method to enhance software operating procedures. Patient's CT images of different bones were acquired and subsequently reconstructed to give models. The reconstruction procedures were three-dimensional image segmentation, modification of the edge length and quantity of meshes, and the assignment of material properties according to the intensity of gravy value. We compared the performance of our procedures to the conventional procedures modeling in terms of software operating time, success rate and mesh quality. Our proposed framework has the following improvements in the geometrical modeling: (1) processing time: (femur: 87.16 ± 5.90 %; pelvis: 80.16 ± 7.67 %; thoracic vertebra: 17.81 ± 4.36 %; P < 0.05); (2) least volume reduction (femur: 0.26 ± 0.06 %; pelvis: 0.70 ± 0.47, thoracic vertebra: 3.70 ± 1.75 %; P < 0.01) and (3) mesh quality in terms of aspect ratio (femur: 8.00 ± 7.38 %; pelvis: 17.70 ± 9.82 %; thoracic vertebra: 13.93 ± 9.79 %; P < 0.05) and maximum angle (femur: 4.90 ± 5.28 %; pelvis: 17.20 ± 19.29 %; thoracic vertebra: 3.86 ± 3.82 %; P < 0.05). Our proposed patient-specific geometrical modeling requires less operating time and workload, but the orthopedic structures were generated at a higher rate of success as compared with the conventional method. It is expected to benefit the surgical planning of orthopedic

  6. Species-Specific Antimonial Sensitivity in Leishmania Is Driven by Post-Transcriptional Regulation of AQP1

    PubMed Central

    Mandal, Goutam; Mandal, Srotoswati; Sharma, Mansi; Charret, Karen Santos; Papadopoulou, Barbara; Bhattacharjee, Hiranmoy; Mukhopadhyay, Rita

    2015-01-01

    Leishmania is a digenetic protozoan parasite causing leishmaniasis in humans. The different clinical forms of leishmaniasis are caused by more than twenty species of Leishmania that are transmitted by nearly thirty species of phlebotomine sand flies. Pentavalent antimonials (such as Pentostam or Glucantime) are the first line drugs for treating leishmaniasis. Recent studies suggest that pentavalent antimony (Sb(V)) acts as a pro-drug, which is converted to the more active trivalent form (Sb(III)). However, sensitivity to trivalent antimony varies among different Leishmania species. In general, Leishmania species causing cutaneous leishmaniasis (CL) are more sensitive to Sb(III) than the species responsible for visceral leishmaniasis (VL). Leishmania aquaglyceroporin (AQP1) facilitates the adventitious passage of antimonite down a concentration gradient. In this study, we show that Leishmania species causing CL accumulate more antimonite, and therefore exhibit higher sensitivity to antimonials, than the species responsible for VL. This species-specific differential sensitivity to antimonite is directly proportional to the expression levels of AQP1 mRNA. We show that the stability of AQP1 mRNA in different Leishmania species is regulated by their respective 3’-untranslated regions. The differential regulation of AQP1 mRNA explains the distinct antimonial sensitivity of each species. PMID:25714343

  7. Highly sensitive and adaptable fluorescence-quenched pair discloses the substrate specificity profiles in diverse protease families.

    PubMed

    Poreba, Marcin; Szalek, Aleksandra; Rut, Wioletta; Kasperkiewicz, Paulina; Rutkowska-Wlodarczyk, Izabela; Snipas, Scott J; Itoh, Yoshifumi; Turk, Dusan; Turk, Boris; Overall, Christopher M; Kaczmarek, Leszek; Salvesen, Guy S; Drag, Marcin

    2017-02-23

    Internally quenched fluorescent (IQF) peptide substrates originating from FRET (Förster Resonance Energy Transfer) are powerful tool for examining the activity and specificity of proteases, and a variety of donor/acceptor pairs are extensively used to design individual substrates and combinatorial libraries. We developed a highly sensitive and adaptable donor/acceptor pair that can be used to investigate the substrate specificity of cysteine proteases, serine proteases and metalloproteinases. This novel pair comprises 7-amino-4-carbamoylmethylcoumarin (ACC) as the fluorophore and 2,4-dinitrophenyl-lysine (Lys(DNP)) as the quencher. Using caspase-3, caspase-7, caspase-8, neutrophil elastase, legumain, and two matrix metalloproteinases (MMP2 and MMP9), we demonstrated that substrates containing ACC/Lys(DNP) exhibit 7 to 10 times higher sensitivity than conventional 7-methoxy-coumarin-4-yl acetic acid (MCA)/Lys(DNP) substrates; thus, substantially lower amounts of substrate and enzyme can be used for each assay. We therefore propose that the ACC/Lys(DNP) pair can be considered a novel and sensitive scaffold for designing substrates for any group of endopeptidases. We further demonstrate that IQF substrates containing unnatural amino acids can be used to investigate protease activities/specificities for peptides containing post-translationally modified amino acids. Finally, we used IQF substrates to re-investigate the P1-Asp characteristic of caspases, thus demonstrating that some human caspases can also hydrolyze substrates after glutamic acid.

  8. Sensitivity and specificity of the pictorial Pediatric Symptom Checklist for psychosocial problem detection in a Mexican sample.

    PubMed

    Leiner, Marie A; Puertas, Héctor; Caratachea, Raúl; Pérez, Héctor; Jiménez, Patricia

    2010-01-01

    Written questionnaires have been developed to assess children's risks of psychosocial problems based on parents' responses. However, the effectiveness of these questionnaires is limited in populations with low literacy rates, which are also among the most in need of improved mental health screening and care. The present study compared the sensitivity and specificity of a version of the Pediatric Symptom Checklist (PSC)--which contained pictorial descriptions in addition to written text--against the "gold standard" Child Behavior Checklist. We retrospectively analyzed 240 sets of questionnaires completed by the mothers or stepmothers of children who visited clinics in a Community Center in Ciudad Juarez, Mexico, between May and December 2007, under the Seguro Popular insurance program provided to Mexicans with the lowest socioeconomic status. Over 95% of the parental participants had less than a high school level of education. The pictorial PSC was a useful tool for screening for psychosocial impairment, with improved sensitivity and specificity in comparison to previous assessments of the written PSC in similar populations within the U.S. Optimal sensitivity and specificity were achieved when the threshold for clinical follow-up was lowered from 28 to 22 points. Questionnaires that include pictorial descriptions may be valuable for improvements of health screening in communities with low education levels.

  9. Good sensitivity and specificity of ultrasound for detecting pseudotumors in 83 failed metal-on-metal hip replacements

    PubMed Central

    Lainiala, Olli; Elo, Petra; Reito, Aleksi; Pajamäki, Jorma; Puolakka, Timo; Eskelinen, Antti

    2015-01-01

    Background and purpose Ultrasound is used for imaging of pseudotumors associated with metal-on-metal (MoM) hips. Ultrasound has been compared with magnetic resonance imaging, but to date there have been no studies comparing ultrasound findings and revision findings. Methods We evaluated the sensitivity and specificity of preoperative ultrasound for detecting pseudotumors in 82 patients with MoM hip replacement (82 hips). Ultrasound examinations were performed by 1 of 3 musculoskeletal radiologists, and pseudotumors seen by ultrasound were retrospectively classified as fluid-filled, mixed-type, or solid. Findings at revision surgery were retrieved from surgical notes and graded according to the same system as used for ultrasound findings. Results Ultrasound had a sensitivity of 83% (95% CI: 63–93) and a specificity of 92% (CI: 82–96) for detecting trochanteric region pseudotumors, and a sensitivity of 79% (CI: 62–89) and a specificity of 94% (CI: 83–98) for detecting iliopsoas-region pseudotumors. Type misclassification of pseudotumors found at revision occurred in 8 of 23 hips in the trochanteric region and in 19 of 33 hips in the iliopsoas region. Interpretation Despite the discrepancy in type classification between ultrasound and revision findings, the presence of pseudotumors was predicted well with ultrasound in our cohort of failed MoM hip replacements. PMID:25582840

  10. Highly sensitive and adaptable fluorescence-quenched pair discloses the substrate specificity profiles in diverse protease families

    PubMed Central

    Poreba, Marcin; Szalek, Aleksandra; Rut, Wioletta; Kasperkiewicz, Paulina; Rutkowska-Wlodarczyk, Izabela; Snipas, Scott J.; Itoh, Yoshifumi; Turk, Dusan; Turk, Boris; Overall, Christopher M.; Kaczmarek, Leszek; Salvesen, Guy S.; Drag, Marcin

    2017-01-01

    Internally quenched fluorescent (IQF) peptide substrates originating from FRET (Förster Resonance Energy Transfer) are powerful tool for examining the activity and specificity of proteases, and a variety of donor/acceptor pairs are extensively used to design individual substrates and combinatorial libraries. We developed a highly sensitive and adaptable donor/acceptor pair that can be used to investigate the substrate specificity of cysteine proteases, serine proteases and metalloproteinases. This novel pair comprises 7-amino-4-carbamoylmethylcoumarin (ACC) as the fluorophore and 2,4-dinitrophenyl-lysine (Lys(DNP)) as the quencher. Using caspase-3, caspase-7, caspase-8, neutrophil elastase, legumain, and two matrix metalloproteinases (MMP2 and MMP9), we demonstrated that substrates containing ACC/Lys(DNP) exhibit 7 to 10 times higher sensitivity than conventional 7-methoxy-coumarin-4-yl acetic acid (MCA)/Lys(DNP) substrates; thus, substantially lower amounts of substrate and enzyme can be used for each assay. We therefore propose that the ACC/Lys(DNP) pair can be considered a novel and sensitive scaffold for designing substrates for any group of endopeptidases. We further demonstrate that IQF substrates containing unnatural amino acids can be used to investigate protease activities/specificities for peptides containing post-translationally modified amino acids. Finally, we used IQF substrates to re-investigate the P1-Asp characteristic of caspases, thus demonstrating that some human caspases can also hydrolyze substrates after glutamic acid. PMID:28230157

  11. Development and characterization of site specific target sensitive liposomes for the delivery of thrombolytic agents.

    PubMed

    Vaidya, Bhuvaneshwar; Nayak, Manasa K; Dash, Debabrata; Agrawal, G P; Vyas, Suresh P

    2011-01-17

    In recent times, search for potent and highly selective thrombolytic agents with minimal side effects has become a major area of research. The aim of the present study was to develop and characterize target sensitive (TS) liposomes encapsulating streptokinase, a thrombolytic agent. The developed TS liposomes were composed of dioleylphophatidyl ethanolamine (DOPE) and dipalmityl-c(RGDfK) (10:1mol/mol). Dipalmityl-c(RGDfK) was synthesized using typical carbodiimide chemistry using palmitic acid and c(RGDfK), while lysine was used as a spacer. Liposomes were of 100-120nm size. In vitro drug release study showed that nearly 40% drug of the entrapped drug was released in 12h in the PBS (pH 7.4), however on incubation with activated platelet about 90% of drug was released within 45min. The results suggested target sensitivity of the liposomes. Further, targeting potential was confirmed using fluorescent microscopy and flow cytometry. Clot lysis study revealed that TS liposomes could not only reduce the clot lysis time but also increase the extent of clot lysis as compared to non-liposomal streptokinase solution. In conclusion, the present liposomal formulation will target the thrombolytic agent to the activated platelets in the thrombus and hence will improve the therapeutic efficacy of the drug.

  12. Temperature-Sensitive Mutations That Cause Stage-Specific Defects in Zebrafish Fin Regeneration

    PubMed Central

    Johnson, S. L.; Weston, J. A.

    1995-01-01

    When amputated, the fins of adult zebrafish rapidly regenerate the missing tissue. Fin regeneration proceeds through several stages, including wound healing, establishment of the wound epithelium, recruitment of the blastema from mesenchymal cells underlying the wound epithelium, and differentiation and outgrowth of the regenerate. We screened for temperature-sensitive mutations that affect the regeneration of the fin. Seven mutations were identified, including five that fail to regenerate their fins, one that causes slow growth during regeneration, and one that causes dysmorphic bumps or tumors to develop in the regenerating fin. reg5 mutants fail to regenerate their caudal fins, whereas reg6 mutants develop dysmorphic bumps in their regenerates at the restrictive temperature. Temperature-shift experiments indicate that reg5 and reg6 affect different stages of regeneration. The critical period for reg5 occurs during the early stages of regeneration before or during establishment of the blastema, resulting in defects in subsequent growth of the blastema and failure to differentiate bone-forming cells. The critical period for reg6 occurs after the onset of bone differentiation and during early stages of regenerative outgrowth. Both reg5 and reg6 also show temperature-sensitive defects in embryonic development or in ontogenetic outgrowth of the juvenile fin. PMID:8601496

  13. Specific capture of the hydrolysate on magnetic beads for sensitive detecting plant vacuolar processing enzyme activity.

    PubMed

    Zhou, Jun; Cheng, Meng; Zeng, Lizhang; Liu, Weipeng; Zhang, Tao; Xing, Da

    2016-05-15

    Conventional plant protease detection always suffers from high background interference caused by the complex coloring metabolites in plant cells. In this study, a bio-modified magnetic beads-based strategy was developed for sensitive and quantitative detection of plant vacuolar processing enzyme (VPE) activity. Cleavage of the peptide substrate (ESENCRK-FITC) after asparagine residue by VPE resulted in the 2-cyano-6-amino-benzothiazole (CABT)-functionalized magnetic beads capture of the severed substrate CRK-FITC via a condensation reaction between CABT and cysteine (Cys). The catalytic activity was subsequently obtained by the confocal microscopy imaging and flow cytometry quantitative analysis. The sensor system integrated advantages of (i) the high efficient enrichment and separation capabilities of magnetic beads and (ii) the catalyst-free properties of the CABT-Cys condensation reaction. It exhibited a linear relationship between the fluorescence signal and the concentration of severed substrate in the range of 10-600 pM. The practical results showed that, compared with normal growth conditions, VPE activity was increased by 2.7-fold (307.2 ± 25.3 μM min(-1)g(-1)) upon cadmium toxicity stress. This platform effectively overcame the coloring metabolites-caused background interference, showing fine applicability for the detection of VPE activity in real samples. The strategy offers great sensitivity and may be further extended to other protease activity detection.

  14. Auditory Profiles of Classical, Jazz, and Rock Musicians: Genre-Specific Sensitivity to Musical Sound Features.

    PubMed

    Tervaniemi, Mari; Janhunen, Lauri; Kruck, Stefanie; Putkinen, Vesa; Huotilainen, Minna

    2015-01-01

    When compared with individuals without explicit training in music, adult musicians have facilitated neural functions in several modalities. They also display structural changes in various brain areas, these changes corresponding to the intensity and duration of their musical training. Previous studies have focused on investigating musicians with training in Western classical music. However, musicians involved in different musical genres may display highly differentiated auditory profiles according to the demands set by their genre, i.e., varying importance of different musical sound features. This hypothesis was tested in a novel melody paradigm including deviants in tuning, timbre, rhythm, melody transpositions, and melody contour. Using this paradigm while the participants were watching a silent video and instructed to ignore the sounds, we compared classical, jazz, and rock musicians' and non-musicians' accuracy of neural encoding of the melody. In all groups of participants, all deviants elicited an MMN response, which is a cortical index of deviance discrimination. The strength of the MMN and the subsequent attentional P3a responses reflected the importance of various sound features in each music genre: these automatic brain responses were selectively enhanced to deviants in tuning (classical musicians), timing (classical and jazz musicians), transposition (jazz musicians), and melody contour (jazz and rock musicians). Taken together, these results indicate that musicians with different training history have highly specialized cortical reactivity to sounds which violate the neural template for melody content.

  15. Auditory Profiles of Classical, Jazz, and Rock Musicians: Genre-Specific Sensitivity to Musical Sound Features

    PubMed Central

    Tervaniemi, Mari; Janhunen, Lauri; Kruck, Stefanie; Putkinen, Vesa; Huotilainen, Minna

    2016-01-01

    When compared with individuals without explicit training in music, adult musicians have facilitated neural functions in several modalities. They also display structural changes in various brain areas, these changes corresponding to the intensity and duration of their musical training. Previous studies have focused on investigating musicians with training in Western classical music. However, musicians involved in different musical genres may display highly differentiated auditory profiles according to the demands set by their genre, i.e., varying importance of different musical sound features. This hypothesis was tested in a novel melody paradigm including deviants in tuning, timbre, rhythm, melody transpositions, and melody contour. Using this paradigm while the participants were watching a silent video and instructed to ignore the sounds, we compared classical, jazz, and rock musicians' and non-musicians' accuracy of neural encoding of the melody. In all groups of participants, all deviants elicited an MMN response, which is a cortical index of deviance discrimination. The strength of the MMN and the subsequent attentional P3a responses reflected the importance of various sound features in each music genre: these automatic brain responses were selectively enhanced to deviants in tuning (classical musicians), timing (classical and jazz musicians), transposition (jazz musicians), and melody contour (jazz and rock musicians). Taken together, these results indicate that musicians with different training history have highly specialized cortical reactivity to sounds which violate the neural template for melody content. PMID:26779055

  16. Sensitivity and accuracy of high-throughput metabarcoding methods used to describe aquatic communities for early detection of invasve fish species

    EPA Science Inventory

    For early detection biomonitoring of aquatic invasive species, sensitivity to rare individuals and accurate, high-resolution taxonomic classification are critical to minimize Type I and II detection errors. Given the great expense and effort associated with morphological identifi...

  17. Sensitivity and Specificity of Proposed DSM-5 Criteria for Autism Spectrum Disorder in Toddlers

    ERIC Educational Resources Information Center

    Barton, Marianne L.; Robins, Diana L.; Jashar, Dasal; Brennan, Laura; Fein, Deborah

    2013-01-01

    Autism spectrum disorder (ASD) diagnosis is based on behavioral presentation; changes in conceptual models or defining behaviors may significantly impact diagnosis and uptake of ASD-specific interventions. The literature examining impact of DSM-5 criteria is equivocal. Toddlers may be especially vulnerable to the stringent requirements of…

  18. Sensitivity and Specificity of Long Wave Infrared Imaging for Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Coben, Robert; Myers, Thomas E.

    2009-01-01

    Objective: This study was the first to investigate the efficacy of long wave infrared (LWIR) imaging as a diagnostic tool for ADHD. Method: with ADHD and a high level of specificity (94%) in discriminating those with ADHD from those with other diagnoses. The overall classification rate was 73.16%. This was indicative of a high level of…

  19. Nanogold-functionalized g-C3N4 nanohybrids for sensitive impedimetric immunoassay of prostate-specific antigen using enzymatic biocatalytic precipitation.

    PubMed

    Ding, Li-Li; Ge, Jing-Ping; Zhou, Wen-Quan; Gao, Jian-Ping; Zhang, Zheng-Yu; Xiong, Ya

    2016-11-15

    This work reports on a new impedimetric immunosensing strategy for sensitive detection of prostate-specific antigen (PSA) in biological fluids. The assay was carried out on monoclonal anti-PSA capture antibody-modified glassy carbon electrode with a sandwich-type detection format. Gold nanoparticles-decorated g-C3N4 nanosheets (AuNP/g-C3N4), synthesized by the wet-chemistry method, were utilized for the labeling of polyclonal anti-PSA detection antibody and horseradish peroxidase (HRP). Upon target PSA introduction, the sandwiched immunocomplex could be formed between capture antibody and detection antibody. Followed by the AuNP/g-C3N4, the labeled HRP could catalyze 4-choloro-1-naphthol into benzo-4-chlorohexadienone. The as-generated insoluble product was coated on the electrode surface, thus increasing the Faradaic impedance of Fe(CN)6(4-/3)(-) indicator between the solution and the base electrode. Under the optimal conditions, the impedance increased with the increasing target PSA in the sample, and exhibited a wide linear range from 10pgmL(-1) and 30ngmL(-1) with a detection limit of 5.2pgmL(-1). A repeatability and intermediate precision of <14% was accomplished. The specificity and method accuracy in comparison with commercial PSA ELISA kit for analysis of human serum specimens were relatively satisfactory.

  20. Anisakis/Ascaris IgE ratio improves specificity for the diagnosis of Anisakis simplex sensitization in travellers and immigrants.

    PubMed

    Carballeda-Sangiao, N; Rodríguez-Mahillo, A I; Puente, S; Gutiérrez, M T; Moneo, I; González-Muñoz, M

    2014-10-01

    Anisakis simplex is a fish parasite responsible for human infection and is able to induce IgE-mediated reactions with several clinical manifestations. Laboratory diagnosis of Anisakis allergy is based on the detection of specific IgE using parasite whole antigen. Unfortunately, these diagnostic tools detect cross-reactivities with other nematodes and micro-organisms leading to low specificity of the diagnostic tests. The aim of this retrospective study was to assess the diagnostic value of specific IgE to Anisakis for diagnosis of A. simplex-sensitization in native Spanish residents (IMM, n=766) and subjects coming from tropical and sub-tropical geographic areas (TRO, n=233). Since Ascaris is the human parasite most closely related to Anisakis, specific IgE to Ascaris was also determined to assess Anisakis cross-reaction with other nematodes and the diagnostic value of Anisakis/Ascaris IgE ratio for Anisakis allergy was examined. IMM and TRO groups showed similar specific IgE to Anisakis levels, while TRO had higher levels of specific IgE to Ascaris than IMM group (p=0.001). ROC curve analysis determined that an Anisakis specific IgE threshold of 0.71 kU/L yielded 93% and 82% specificities in IMM and TRO groups, respectively. A cut-off value ≥4.4 for Anisakis/Ascaris IgE ratio increased specificity to 95% for samples having IgE to Ascaris ≥0.35. In conclusion, the ratio of specific IgE to Anisakis and Ascaris improved remarkably the specificity and this parameter easily obtained from the commercially available system could be useful in the diagnosis of hypersensitivity to A. simplex.

  1. Microshell Arrays Enhanced Sensitivity in Detection of Specific Antibody for Reduced Graphene Oxide Optical Sensor

    PubMed Central

    Jiang, Wen-Shuai; Xin, Wei; Chen, Shao-Nan; Li, Cun-Bo; Gao, Xiao-Guang; Pan, Lei-Ting; Liu, Zhi-Bo; Tian, Jian-Guo

    2017-01-01

    Protein-protein interactions play an important role in the investigation of biomolecules. In this paper, we reported on the use of a reduced graphene oxide microshell (RGOM)-based optical biosensor for the determination of goat anti-rabbit IgG. The biosensor was prepared through a self-assembly of monolayers of monodisperse polystyrene microspheres, combined with a high-temperature reduction, in order to decorate the RGOM with rabbit IgG. The periodic microshells allowed a simpler functionalization and modification of RGOM with bioreceptor units, than reduced graphene oxide (RGO). With additional antibody-antigen binding, the RGOM-based biosensor achieved better real-time and label-free detection. The RGOM-based biosensor presented a more satisfactory response to goat anti-rabbit IgG than the RGO-based biosensor. This method is promising for immobilizing biomolecules on graphene surfaces and for the fabrication of biosensors with enhanced sensitivity. PMID:28125011

  2. Sensitivity and specificity of rapid diagnostic tests for detection of group B streptococcal antigen in bacteremic neonates.

    PubMed Central

    Greenberg, D N; Ascher, D P; Yoder, B A; Hensley, D M; Heiman, H S; Keith, J F

    1995-01-01

    Latex particle agglutination (LPA) testing for antigen to group B streptococcus (GBS) has been useful in the diagnosis of GBS sepsis in newborns. However, recent reports have demonstrated that the sensitivity of LPA assays may be as low as 27 to 54%. The purposes of the present study were to directly compare the abilities of four urine antigen assays to detect GBS antigen with clinical urine samples from neonates with GBS bacteremia and to evaluate the effect of the urine concentration on the sensitivities and specificities of these assays. Urine samples were collected serially from neonates with blood cultures positive for GBS or on admission from healthy full-term infants. One milliliter of urine was removed, and the remainder was concentrated to a volume of 1 ml. Unconcentrated samples were serially diluted with normal saline and were assayed to determine the highest dilution which would produce a positive test result. The Wellcogen, Bactigen, and Directigen LPA tests and ICON immunoassay were directly compared by using concentrated and unconcentrated urine specimens and urine specimens with known titers. A total of 94 urine specimens, including 61 concentrated and 75 unconcentrated specimens, from bacteremic infants were available for sensitivity testing, and 220 urine specimens from uninfected infants were available for specificity testing. There were significant differences in sensitivity among the four assays when they were performed on concentrated urine specimens, as follows: Directigen, 98%; Bactigen, 92%; ICON, 89%; Wellcogen, 68%. When the assays were performed on unconcentrated urine specimens, the Directigen (84%) and Bactigen (76%) assays were each significantly more sensitive than the ICON (59%) or Wellcogen (43%) assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7699040

  3. Applied genomics: data mining reveals species-specific malaria diagnostic targets more sensitive than 18S rRNA.

    PubMed

    Demas, Allison; Oberstaller, Jenna; DeBarry, Jeremy; Lucchi, Naomi W; Srinivasamoorthy, Ganesh; Sumari, Deborah; Kabanywanyi, Abdunoor M; Villegas, Leopoldo; Escalante, Ananias A; Kachur, S Patrick; Barnwell, John W; Peterson, David S; Udhayakumar, Venkatachalam; Kissinger, Jessica C

    2011-07-01

    Accurate and rapid diagnosis of malaria infections is crucial for implementing species-appropriate treatment and saving lives. Molecular diagnostic tools are the most accurate and sensitive method of detecting Plasmodium, differentiating between Plasmodium species, and detecting subclinical infections. Despite available whole-genome sequence data for Plasmodium falciparum and P. vivax, the majority of PCR-based methods still rely on the 18S rRNA gene targets. Historically, this gene has served as the best target for diagnostic assays. However, it is limited in its ability to detect mixed infections in multiplex assay platforms without the use of nested PCR. New diagnostic targets are needed. Ideal targets will be species specific, highly sensitive, and amenable to both single-step and multiplex PCRs. We have mined the genomes of P. falciparum and P. vivax to identify species-specific, repetitive sequences that serve as new PCR targets for the detection of malaria. We show that these targets (Pvr47 and Pfr364) exist in 14 to 41 copies and are more sensitive than 18S rRNA when utilized in a single-step PCR. Parasites are routinely detected at levels of 1 to 10 parasites/μl. The reaction can be multiplexed to detect both species in a single reaction. We have examined 7 P. falciparum strains and 91 P. falciparum clinical isolates from Tanzania and 10 P. vivax strains and 96 P. vivax clinical isolates from Venezuela, and we have verified a sensitivity and specificity of ∼100% for both targets compared with a nested 18S rRNA approach. We show that bioinformatics approaches can be successfully applied to identify novel diagnostic targets and improve molecular methods for pathogen detection. These novel targets provide a powerful alternative molecular diagnostic method for the detection of P. falciparum and P. vivax in conventional or multiplex PCR platforms.

  4. Sensitivity analysis of a validated subject-specific finite element model of the human craniofacial skeleton.

    PubMed

    Szwedowski, T D; Fialkov, J; Whyne, C M

    2011-01-01

    Developing a more complete understanding of the mechanical response of the craniofacial skeleton (CFS) to physiological loads is fundamental to improving treatment for traumatic injuries, reconstruction due to neoplasia, and deformities. Characterization of the biomechanics of the CFS is challenging due to its highly complex structure and heterogeneity, motivating the utilization of experimentally validated computational models. As such, the objective of this study was to develop, experimentally validate, and parametrically analyse a patient-specific finite element (FE) model of the CFS to elucidate a better understanding of the factors that are of intrinsic importance to the skeletal structural behaviour of the human CFS. An FE model of a cadaveric craniofacial skeleton was created from subject-specific computed tomography data. The model was validated based on bone strain measurements taken under simulated physiological-like loading through the masseter and temporalis muscles (which are responsible for the majority of craniofacial physiologic loading due to mastication). The baseline subject-specific model using locally defined cortical bone thicknesses produced the strongest correlation to the experimental data (r2 = 0.73). Large effects on strain patterns arising from small parametric changes in cortical thickness suggest that the very thin bony structures present in the CFS are crucial to characterizing the local load distribution in the CFS accurately.

  5. Immunoregulatory adherent cells in human tuberculosis: radiation-sensitive antigen-specific suppression by monocytes

    SciTech Connect

    Kleinhenz, M.E.; Ellner, J.J.

    1985-07-01

    In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKM1-reactive monocytes. Adherent cell suppression was studied in the (/sup 3/H)thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fc portion of IgG (T gamma cells) as antigen-responsive cells. PPD-induced (/sup 3/H)thymidine incorporation by these non gamma T cells was uniformly reduced (mean, 42% +/- 10% (SD)) when autologous AMC were added to non gamma T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-rosetting T cells or treatment with indomethacin. However, AMC treated with OKM1 and complement or gamma irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKM1-reactive, non-erythrocyte-rosetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition.

  6. Cerebrospinal fluid eosinophilia is a sensitive and specific test for the diagnosis of Parelaphostrongylus tenuis in camelids in the northeastern United States.

    PubMed

    Pinn, Toby L; Bender, Hannah S; Stokol, Tracy; Erb, Hollis N; Schlafer, Donald H; Perkins, Gillian A

    2013-01-01

    Aberrant migration of Parelaphostrongylus tenuis in camelids results in neurologic deficits, recumbency, and sometimes death. An antemortem diagnosis of P. tenuis in camelids is typically based upon the presence of characteristic asymmetric neurologic deficits, known exposure to white-tailed deer, cerebrospinal fluid (CSF) eosinophilia, and response to treatment. The diagnostic accuracy of CSF eosinophil percentage for the diagnosis of P. tenuis in camelids has not been critically examined. The objective of the current study was to determine the sensitivity (Se) and specificity (Sp) of CSF eosinophil percentage, CSF eosinophil concentration, total nucleated cell concentration, and protein concentration for the antemortem diagnosis of P. tenuis. Medical records of camelids admitted to Cornell University with clinical signs of neurologic disease, CSF analysis, and necropsy were examined from January 2000 through December 2009. Se and Sp were determined by receiver operating characteristic curves in camelids diagnosed with P. tenuis (n = 13) or other conditions (n = 24) based on postmortem examination. More than 17% of eosinophils in CSF had a Se of 85% and Sp of 92% for P. tenuis diagnosis (area under the curve [AUC]: 0.87; SE AUC: 0.07; P < 0.0001; 95% confidence interval [CI] AUC: 0.72-0.96), and >1.4 eosinophils/µl of CSF had a Se of 85% and Sp of 96% (AUC: 0.9; SE AUC: 0.06; P < 0.0001; 95% CI AUC: 0.76-0.97). Cerebrospinal fluid eosinophil percentage and concentration are sensitive and specific methods for diagnosing P. tenuis antemortem in camelids residing in regions endemic to white-tailed deer.

  7. Combination of miR-125b and miR-27a enhances sensitivity and specificity of AFP-based diagnosis of hepatocellular carcinoma.

    PubMed

    Zuo, Duo; Chen, Liwei; Liu, Xiaoqian; Wang, Xia; Xi, Qing; Luo, Yi; Zhang, Ning; Guo, Hua

    2016-05-01

    Non-invasive biomarkers of early-stage hepatocellular carcinoma (HCC) could offer immense benefits. Currently available tumor markers for HCC are of not much clinical relevance. In this study, we investigated the potential for using a panel of serum microRNAs (miRNAs) as novel tumor markers in conjunction with serum alpha-fetoprotein (AFP) for diagnosis of HCC. Serum expression of four miRNAs was assessed in 150 subjects (90 cases of HCC and 60 cases without cancer) by quantitative real-time polymerase chain reaction (qRT-PCR). Logistic regression analysis was performed to assess the potential use of miRNAs for detection of HCC. Receiver operating characteristic curves were used to evaluate diagnostic accuracy. A panel of serum miRNAs (miR-125b, miR-223, miR-27a, and miR-26a) used in conjunction with AFP helped differentiate HCC patients from those in the non-cancer group after adjusting for age and gender, with the area under the curve of 0.870. In addition, the use of miR-125b/miR-27a panel differentiated HBV-related early-stage HCC with a high sensitivity (80.0 %) and specificity (87.2 %) in AFP-negative (-) subjects. A combination of serum miR-125b, miR-223, miR-27a, and miR-26a as a second-line tests could help detect HCC in AFP (-) subjects. The panel of miR-125b/miR-27a/AFP had a higher sensitivity and specificity for diagnosis of early-stage HCC as compared to that of a single marker.

  8. Urinary microRNA-based signature improves accuracy of detection of clinically relevant prostate cancer within the prostate-specific antigen grey zone

    PubMed Central

    SALIDO-GUADARRAMA, ALBERTO IVAN; MORALES-MONTOR, JORGE GUSTAVO; RANGEL-ESCAREÑO, CLAUDIA; LANGLEY, ELIZABETH; PERALTA-ZARAGOZA, OSCAR; COLIN, JOSE LUIS CRUZ; RODRIGUEZ-DORANTES, MAURICIO

    2016-01-01

    At present, prostate-specific antigen (PSA) is used as a clinical biomarker for prostate cancer (PCa) diagnosis; however, a large number of patients with benign prostate hyperplasia (BPH) with PSA levels in the ʻgray areaʼ (4–10 ng/ml) are currently subjected to unnecessary biopsy due to overdiagnosis. Certain microRNAs (miRs) have been proven to be useful biomarkers, several of which are detectable in bodily fluids. The present study identified and validated a urinary miR-based signature to enhance the specificity of PCa diagnosis and to reduce the number of patients with benign conditions undergoing biopsy. Seventy-three urine samples from Mexican patients with diagnosis of PCa with a Gleason score ≥7 and 70 patients diagnosed with BPH were collected after digital rectal examination (DRE) of the prostate. miR expression profiles were determined using TaqMan Low Density Array experiments, and normalized Ct values for the miRs were compared between PCa and BPH groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether miR detection in urine is suitable for distinguishing patients with PCa from those with BPH. The identified miR-100/200b signature was significantly correlated with PCa. Using a multivariable logistic regression approach, a base model including the clinical variables age, prostate-specific antigen (PSA), the percentage of free PSA and DRE was generated, and a second base model additionally contained the miR-100/200b signature. ROC analysis demonstrated that the combined model significantly outperformed the capacity of PSA (P<0.001) and the base model (P=0.01) to discriminate between PCa and BPH patients. In terms of evaluation of the sub-group of patients in the gray zone of PSA levels, the performance of the combined model for predicting PCa cases was significantly superior to PSA level determination (P<0.001) and the base model (P=0.009). In addition, decision curve analysis demonstrated that the use of

  9. Lysophosphatidylcholine hydrolases of human erythrocytes, lymphocytes, and brain: Sensitive targets of conserved specificity for organophosphorus delayed neurotoxicants

    SciTech Connect

    Vose, Sarah C.; Holland, Nina T.; Eskenazi, Brenda; Casida, John E.

    2007-10-01

    Brain neuropathy target esterase (NTE), associated with organophosphorus (OP)-induced delayed neuropathy, has the same OP inhibitor sensitivity and specificity profiles assayed in the classical way (paraoxon-resistant, mipafox-sensitive hydrolysis of phenyl valerate) or with lysophosphatidylcholine (LysoPC) as the substrate. Extending our earlier observation with mice, we now examine human erythrocyte, lymphocyte, and brain LysoPC hydrolases as possible sensitive targets for OP delayed neurotoxicants and insecticides. Inhibitor profiling of human erythrocytes and lymphocytes gave the surprising result of essentially the same pattern as with brain. Human erythrocyte LysoPC hydrolases are highly sensitive to OP delayed neurotoxicants, with in vitro IC{sub 50} values of 0.13-85 nM for longer alkyl analogs, and poorly sensitive to the current OP insecticides. In agricultural workers, erythrocyte LysoPC hydrolyzing activities are similar for newborn children and their mothers and do not vary with paraoxonase status but have high intersample variation that limits their use as a biomarker. Mouse erythrocyte LysoPC hydrolase activity is also of low sensitivity in vitro and in vivo to the OP insecticides whereas the delayed neurotoxicant ethyl n-octylphosphonyl fluoride inhibits activity in vivo at 1-3 mg/kg. Overall, inhibition of blood LysoPC hydrolases is as good as inhibition of brain NTE as a predictor of OP inducers of delayed neuropathy. NTE and lysophospholipases (LysoPLAs) both hydrolyze LysoPC, yet they are in distinct enzyme families with no sequence homology and very different catalytic sites. The relative contributions of NTE and LysoPLAs to LysoPC hydrolysis and clearance from erythrocytes, lymphocytes, and brain remain to be defined.

  10. Assessment of Actin FS and Actin FSL sensitivity to specific clotting factor deficiencies.

    PubMed

    Lawrie, A S; Kitchen, S; Purdy, G; Mackie, I J; Preston, F E; Machin, S J

    1998-06-01

    We present a two centre study designed to assess the sensitivity of Actin FS and Actin FSL to deficiencies of factor VIII, IX, XI or XII. The study was undertaken at two centres to avoid bias due to the investigations being undertaken on one analyser. Samples from patients with a factor VIII (n = 36, F VIII = < 1.0-50 iu/dl), factor IX (n = 22, F IX = 2-48 iu/dl), factor XI (n = 23, F XI = 5-50 u/dl) or a factor XII (n = 18, F XII = 1-50 u/dl) deficient state were studied. Activated partial thromboplastin times (APTT) were determined using two batches of Actin FS and of Actin FSL; comparison of APTT results between centres was facilitated by the conversion of clotting times to ratios (test divided by geometric mean normal clotting time). APTT ratios were considered to be elevated if greater than two standard deviations above the mean normal. The factor deficient status of each sample was verified by assaying all samples for factors VIII, IX, XI and XII. Clotting factor assays were performed on a Sysmex CA-1000 fitted with research software, which permitted the auto-dilution and testing of three serial dilution of both a reference preparation and each patient's sample. Assay results were calculated using parallel-line Bioassay principles. This procedure allowed for variation in clotting times due to the effect of temporal drift of any of the reagents within the assay system. Actin FS and Actin FSL demonstrate acceptable sensitivity to factor VIII deficiency, however, both reagents failed to detect a large proportion of factor XI (17.4% and 30.4% of samples, respectively) and factor XII (66.7% and 72.2%, respectively) deficiencies. The detection rate with Actin FSL for factor IX deficiency was also poor (36.4% not detected). As factor IX and XI deficiencies are both associated with haemorrhagic disorders, the inability of these reagents to detect such abnormalities gave cause for concern.

  11. Cell-type specific expression of ATP-sensitive potassium channels in the rat hippocampus

    PubMed Central

    Zawar, C; Plant, T D; Schirra, C; Konnerth, A; Neumcke, B

    1999-01-01

    The distribution of ATP-sensitive K+ channels (KATP channels) was investigated in four cell types in hippocampal slices prepared from 10- to 13-day-old rats: CA1 pyramidal cells, interneurones of stratum radiatum in CA1, complex glial cells of the same area and granule cells of the dentate gyrus. The neuronal cell types were identified visually and characterized by the shapes and patterns of their action potentials and by neurobiotin labelling.The patch-clamp technique was used to study the sensitivity of whole-cell currents to diazoxide (0·3 mm), a KATP channel opener, and to tolbutamide (0·5 mm) or glibenclamide (20 μm), two KATP channel inhibitors. The fraction of cells in which whole-cell currents were activated by diazoxide and inhibited by tolbutamide was 26% of pyramidal cells, 89% of interneurones, 100% of glial cells and 89% of granule cells. The reversal potential of the diazoxide-induced current was at the K+ equilibrium potential and a similar current activated spontaneously when cells were dialysed with an ATP-free pipette solution.Using the single-cell RT-PCR method, the presence of mRNA encoding KATP channel subunits (Kir6.1, Kir6.2, SUR1 and SUR2) was examined in CA1 pyramidal cells and interneurones. Subunit mRNA combinations that can result in functional KATP channels (Kir6.1 together with SUR1, Kir6.2 together with SUR1 or SUR2) were detected in only 17% of the pyramidal cells. On the other hand, KATP channelsmay be formed in 75%of the interneurones, mainly by the combination of Kir6.2 with SUR1 (58% of all interneurones).The results of these combined analyses indicate that functional KATP channels are present in principal neurones, interneurones and glial cells of the rat hippocampus, but at highly different densities in the four cell types studied. PMID:9852317

  12. Sensitive and selective detection of prostate-specific antigen using a photonic crystal nanolaser.

    PubMed

    Hachuda, Shoji; Watanabe, Takumi; Takahashi, Daichi; Baba, Toshihiko

    2016-06-13

    The detection of low-concentration biomarkers is expected to facilitate the early diagnosis of severe diseases, including malignant tumors. Using photonic crystal nanolaser sensors, we detected prostate-specific antigen (PSA) from a concentration of 1 fM, which is difficult to detect by conventional enzyme-linked immunosorbent assay. The signal intensity and stability were improved by using a surfactant (i.e., ethanolamine). Even when a contaminant such as bovine serum albumin was mixed into the PSA sample, thereby increasing the concentration of the contaminant ten billion times, it was still possible to maintain a high level of detection.

  13. Sensitivity and specificity of cerebrospinal fluid flow cytometry for the diagnosis of leukemic meningitis in acute lymphoblastic leukemia/lymphoma.

    PubMed

    Mitri, Zahi; Siddiqui, Momin T; El Rassi, Fuad; Holden, Jeannine T; Heffner, Leonard T; Langston, Amelia; Waller, Edmund K; Winton, Elliott; McLemore, Morgan; Bernal-Mizrachi, Leon; Jaye, David; Arellano, Martha; Khoury, Hanna Jean

    2014-07-01

    The presence of leukemic blasts detected by light microscopy in cerebrospinal fluid (CSF) establishes the diagnosis of leukemic meningitis in acute lymphoblastic leukemia/lymphoma (ALL). Flow cytometry immunophenotyping (FCI) is a very sensitive method that detects a minute number of aberrant cells, and is increasingly performed on CSF samples. We sought to determine the sensitivity and specificity of CSF FCI for the diagnosis of leukemic meningitis in ALL. Between November 2007 and August 2011, 800 CSF samples from 80 patients with ALL were available from diagnostic lumbar punctures (LPs; n = 80), follow-up LPs (n = 687) and at the time of relapse (n = 33). FCI was performed on 267 samples, and only identified aberrant cells in cytologically confirmed cases of leukemic meningitis. A blinded review of all cases with detectable CSF nucleated cells confirmed these findings. We conclude that CSF FCI has a 100% sensitivity and specificity for the detection of lymphoblasts. However, additional studies are needed to define the role this procedure plays in the diagnosis of leukemic meningitis.

  14. Human genome-specific real-time PCR method for sensitive detection and reproducible quantitation of human cells in mice.

    PubMed

    Song, Pengyue; Xie, Zhenhua; Guo, Ling; Wang, Chengmei; Xie, Weidong; Wu, Yaojiong

    2012-12-01

    Xenotransplantation of human cells into immunodeficiency mice has been frequently used to study stem cells in tissue repair and regeneration and cancer cell metastasis. However, a sensitive and reproducible method to quantify cell engraftment lacks. Here, we developed a Real-Time PCR-based method which facilitated consistent detection and quantification of small amounts of human cells distributed in mouse organs after infusion. The principle of the method was to directly detect a humans-specific sequence in the human-murine genomic DNA mixture. In a mouse myocardial infarction model, the Real-Time PCR-based method consistently determined the amounts of human mesenchymal stem cells (hMSCs) engrafted into the heart and other organs 7 days after infusion of as little as 2.5 × 10(5) cells, indicating a high sensitivity, and the amounts of hMSCs detected in mice highly correlated to the numbers of hMSCs transplanted. Importantly, different from previous PCR-based methods, our method produced highly consistent and reproducible results. The reliability of the method was further proven by parallel analyses of DiI-labeled hMSCs in tissue sections and in single cell suspensions of mice. Our data show that the present human genomic DNA-specific primers-based Real-Time PCR method is sensitive and highly reproducible in determining the amount of xenotransplanted human cells in murine tissues.

  15. The influence of heat exchange between a sensitive element and its surroundings on the specific detectivity of pyroelectric detectors

    NASA Astrophysics Data System (ADS)

    Neumann, N.; Möhling, S.

    1993-10-01

    The specific detectivity of pyroelectric sensors at low frequencies is mainly influenced by the thermal conditions within the sensor. The temperature noise caused by heat exchange between the sensitive element and its surroundings is transformed into an increase of the dielectric loss due to electrothermal coupling. The complex normalized current responsivity is used to calculate the influence of thermal conditions. While the absolute value ¦ TR¦ gives the frequency response of the sensitivity, the additional dielectric loss tan δ T is deduced from the imaginary part. The loss due to electrothermal coupling tan δ T exceeds the dielectric intrinsic loss tan δ i for most sensor structures within the frequency range up to 100 Hz. Thus, the maximum attainable specific detectivity of a pyroelectric sensor at normal operation frequencies is dependent on its construction rather than on the material parameter dielectric intrinsic loss tan δ i which is frequently referred to. The effect of electrothermal coupling can be employed in sensors with reduced sensitivity at low frequencies as used for FTIR-devices.

  16. Pyrilamine-sensitive proton-coupled organic cation (H(+)/OC) antiporter for brain-specific drug delivery.

    PubMed

    Wang, Xinyi; Qi, Bowen; Su, Huifang; Li, Jianbo; Sun, Xun; He, Qin; Fu, Yao; Zhang, Zhirong

    2017-03-27

    Blood-brain barrier (BBB) represents the greatest challenge that hampers therapeutic molecules entering the brain. Here, we described a novel brain-specific delivery strategy targeting to pyrilamine-sensitive H(+)/OC antiporter to facilitate therapeutic molecules cross the BBB and penetrate into the brain. In this study, four cyclic tertiary amines were selected as the brain-targeting moieties to modify naproxen (NP), a non-steroidal anti-inflammatory drug. The obtained NP conjugates displayed cell uptake efficiencies over 144-fold higher than that of unmodified NP in endothelial cells. The cell uptake process of the conjugates was primarily driven by pyrilamine-sensitive H(+)/OC antiporter in a pH-dependent, Na(+)-independent, and membrane potential-independent pathway, which could be further inhibited by pyrilamine, propranolol, and imipramine. Moreover, the NP conjugates showed significantly higher AUC0-t and Cmax in the brain compared with unmodified NP, and significantly higher accumulation than NP in the in situ brain perfusion study. Also, the conjugates showed superior neuroprotective effect in vitro and in vivo. Thus, the chemical modification of therapeutics with a cyclic tertiary amine moiety represents a promising and efficient strategy for brain-specific drug delivery via pyrilamine-sensitive H(+)/OC antiporter.

  17. Molecular Models Underlying the Sensitive and Specific Determination of Copy Number Changes in the Human Genome and Transcriptome

    NASA Astrophysics Data System (ADS)

    Laderman, Stephen

    2004-03-01

    DNA microarrays enable the measurement of relative abundances of messenger RNA (mRNA) molecules across biological conditions on a gene-by-gene basis for tens of thousands of genes at a time, encompassing essentially all the mRNA molecules present in the sample's cells. These highly multiplexed molecular measurements are greatly accelerating basic and applied research in disease progression and developmental biology. In the study of cancer and certain genetic disorders, similar snapshots of copy numbers of genomic DNA are also of great interest. For example, tumor suppressor genes that protect against improper cell growth are lost from the genome and oncogenes that accelerate cell proliferation are multiplied within the genome as cancer cells evolve. Microarray measurements of mRNA and DNA are themselves an aggregate of molecular level phenomena. Quantitative models of in vitro behavior at the molecular scale are essential for creating effective measurement systems that have sufficient sensitivity and specificity to realize the highest utility. Such models are actively used in critical areas such as designing the means of incorporating fluorophores into the sample molecules, building high quality DNA sequences onto the microarrays, and developing assay parameters that balance high sensitivity with an ability to distinguish genes from each other. Trends in the applications of the technology ensure continued development towards even more precise, reproducible, sensitive and specific measurement systems, encouraging the further development and application of relevant molecular models.

  18. Oligonucleotide-stabilized fluorescent silver nanoclusters for the specific and sensitive detection of biotin.

    PubMed

    Xiong, Xiaoli; Tang, Yan; Zhao, Jingjin; Zhao, Shulin

    2016-02-21

    A novel biotin fluorescent probe based on oligonucleotide-stabilized silver nanoclusters (DNA-AgNCs) was synthesized by employing a biotinylated cytosine-rich sequence as a synthesized template. The fluorescence properties of the DNA-AgNCs are related to the modified position of the DNA. When biotin is linked to the middle thymine base of the DNA sequence, the DNA-AgNCs emit the strongest fluorescence. Moreover, the stability of the DNA-AgNCs was affected by avidin through biotin-avidin binding, quenching the fluorescence of the DNA-AgNCs. In contrast, if free biotin is further introduced into this system, the quenching is apparently weakened by competition, leading to the restoration of fluorescence. This phenomenon can be utilized for the detection of biotin. Under the optimal conditions, the fluorescence recovery is linearly proportional to the concentration of biotin in the range of 10 nM-1.0 μM with a detection limit of 6.0 nM. This DNA-AgNCs probe with excellent fluorescent properties is sensitive and selective for the detection of biotin and has been applied for the determination of biotin in wheat flour.

  19. Parametric sensitivity analysis applied to a specific one-dimensional internal bone remodelling problem.

    PubMed

    Ramtani, S

    2007-08-01

    The relative importance of the various parameters in inducing bone mass loss and osteoclastic perforations is still controversial. Therefore, there is a significant motivation to better understand the parameters behind such dynamic response, and great interest to carry out a parametric sensitivity study as it can provide useful information. As an application, the widely-accepted bone remodelling equation [M.G. Mullender, R. Huiskes, H. Weinans, A physiological approach to the simulation of bone remodeling as self organizational control process, J. Biomech. 27 (1994) 1389.] is investigated using the "n units" model [M. Zidi, S. Ramtani, Bone remodeling theory applied to the study of n unit-elements model, J Biomech. 32 (1999) 743.]. This analysis pointed out that the power in the modulus density relationship p and the power to which density is raised in normalizing the energy stimulus q, known as strongly implicated in the stability condition of the remodelling process, were also stated as insensitive parameters in the bone loss area.

  20. A nanoparticle label/immunochromatographic electrochemical biosensor for rapid and sensitive detection of prostate-specific antigen

    SciTech Connect

    Lin, Ying-Ying; Wang, Jun; Liu, Guodong; Wu, Hong; Wai, Chien M.; Lin, Yuehe

    2008-06-15

    We present a nanoparticle (NP) label/immunochromatographic electrochemical biosensor (IEB) for rapid and sensitive detection of prostate-specific antigen (PSA) in human serum. This IEB integrates the immunochromatographic strip with the electrochemical detector for transducing quantitative signals. The NP label, made of CdSe@ZnS, serves as a signal-amplifier vehicle. A sandwich immunoreaction was performed on the immunochromatographic strip. The captured NP labels in the test zone were determined by highly sensitive stripping voltammetric measurement of the dissolved metallic component (cadmium) with a disposable-screen-printed electrode, which is embedded underneath the membrane of the test zone. Experimental parameters (e.g., immunoreaction time, the amount of anti-PSA-NP conjugations applied) and electrochemical detection conditions (e.g., preconcentration potential and time) were optimized using this biosensor for PSA detection. The analytical performance of this biosensor was evaluated with serum PSA samples according to the “figure-of-merits” (e.g., dynamic range, reproducibility, and detection limit). The results were validated with enzyme-linked immunosorbent assay (ELISA) and show high consistency. It is found that this biosensor is very sensitive with the detection limit of 0.02 ng/mL PSA and is quite reproducible. This method is rapid, clinically accurate, and less expensive than other diagnosis tools for PSA; therefore, this IEB coupled with a portable electrochemical analyzer shows great promise for simple, sensitive, quantitative point-of-care testing of disease-related protein biomarkers.

  1. A human T cell clone that mediates the monocyte procoagulant response to specific sensitizing antigen.

    PubMed

    Schwartz, B S; Reitnauer, P J; Hank, J A; Sondel, P M

    1985-09-01

    A panel of human purified protein derivative of the tubercle bacillus (PPD)-reactive T cell clones was derived by cloning out of soft agar followed by cultivation on inactivated feeder cells in the presence of interleukin-2. 1 of 4 clones tested was able to mediate an increase in monocyte procoagulant activity (PCA) in response to PPD. All four clones had identical surface marker phenotypes (T4+, T8-) and proliferated in response to antigen. The reactive T cell clone possessed no PCA of its own, but upon being presented with PPD was able to instruct monocytes to increase their expression of PCA. Antigen presentation could be performed only by autologous monocytes; allogeneic monocytes from donors unrelated to the donor of the reactive clone could not present antigen to cells of the clone in a way that would initiate the procoagulant response. Cells of the reactive clone did not mediate increased monocyte PCA in response to Candida, even though peripheral blood mononuclear cells from the donor demonstrated increased PCA to both Candida and PPD. Thus, the PCA response to specific antigen can be mediated by a single clone of cells that shows specificity in the recognition of both antigen and antigen presenting cell.

  2. Sensitivity of Force Specifications to the Errors in Measuring the Interface Force

    NASA Technical Reports Server (NTRS)

    Worth, Daniel

    1999-01-01

    Force-Limited Random Vibration Testing has been applied in the last several years at NASA/GSFC for various programs at the instrument and system level. Different techniques have been developed over the last few decades to estimate the dynamic forces that the test article under consideration will encounter in the operational environment. Some of these techniques are described in the handbook, NASA-HDBK-7004, and the monograph, NASA-RP-1403. A key element in the ability to perform force-limited testing is multi-component force gauges. This paper will show how some measurement and calibration errors in force gauges are compensated for w en tie force specification is calculated. The resulting notches in the acceleration spectrum, when a random vibration test is performed, are the same as the notches produced during an uncompensated test that has no measurement errors. The paper will also present the results of tests that were used to validate this compensation. Knowing that the force specification can compensate for some measurement errors allows tests to continue after force gauge failures or allows dummy gauges to be used in places that are inaccessible.

  3. Sensitive and species-specific detection of Erwinia amylovora by polymerase chain reaction analysis.

    PubMed Central

    Bereswill, S; Pahl, A; Bellemann, P; Zeller, W; Geider, K

    1992-01-01

    Detection and identification of the fire blight pathogen, Erwinia amylovora, can be accurately done by polymerase chain reaction (PCR) analysis in less than 6 h. Two oligomers derived from a 29-kb plasmid which is common to all strains of E. amylovora were used to amplify a 0.9-kb fragment of the plasmid. By separation of the PCR products on agarose gel, this fragment wa specifically detected when E. amylovora DNA was present in the amplification assay. It was not found when DNA from other plant-pathogenic bacteria was used for the assay. A visible band specific to the 0.9-kb fragment was produced with DNA from fewer than 100 E. amylovora cells. A signal of similar strength was also obtained from E. amylovora cell lysates in the presence of the mild detergent Tween 20. Signals were weaker when bacteria were added to the PCR mixture without the detergent. As with results obtained from hybridization experiments using pEA29 DNA< the PCR signal was obtained with E. amylovora isolates from various geographic regions. This technique could also be used for detection of the fire blight pathogen in extracts of tissue obtained from infected plant material. Images PMID:1482178

  4. Modeling Analysis of Signal Sensitivity and Specificity by Vibrio fischeri LuxR Variants

    PubMed Central

    Colton, Deanna M.; Stabb, Eric V.; Hagen, Stephen J.

    2015-01-01

    The LuxR protein of the bacterium Vibrio fischeri belongs to a family of transcriptional activators that underlie pheromone-mediated signaling by responding to acyl-homoserine lactones (-HSLs) or related molecules. V. fischeri produces two acyl-HSLs, N-3-oxo-hexanoyl-HSL (3OC6-HSL) and N-octanoyl-HSL (C8-HSL), each of which interact with LuxR to facilitate its binding to a “lux box” DNA sequence, thereby enabling LuxR to activate transcription of the lux operon responsible for bioluminescence. We have investigated the HSL sensitivity of four different variants of V. fischeri LuxR: two derived from wild-type strains ES114 and MJ1, and two derivatives of LuxRMJ1 generated by directed evolution. For each LuxR variant, we measured the bioluminescence induced by combinations of C8-HSL and 3OC6-HSL. We fit these data to a model in which the two HSLs compete with each other to form multimeric LuxR complexes that directly interact with lux to activate bioluminescence. The model reproduces the observed effects of HSL combinations on the bioluminescence responses directed by LuxR variants, including competition and non-monotonic responses to C8-HSL and 3OC6-HSL. The analysis yields robust estimates for the underlying dissociation constants and cooperativities (Hill coefficients) of the LuxR-HSL complexes and their affinities for the lux box. It also reveals significant differences in the affinities of LuxRMJ1 and LuxRES114 for 3OC6-HSL. Further, LuxRMJ1 and LuxRES114 differed sharply from LuxRs retrieved by directed evolution in the cooperativity of LuxR-HSL complex formation and the affinity of these complexes for lux. These results show how computational modeling of in vivo experimental data can provide insight into the mechanistic consequences of directed evolution. PMID:25962099

  5. Impact of dataset diversity on accuracy and sensitivity of parallel factor analysis model of dissolved organic matter fluorescence excitation-emission matrix

    PubMed Central

    Yu, Huarong; Liang, Heng; Qu, Fangshu; Han, Zheng-shuang; Shao, Senlin; Chang, Haiqing; Li, Guibai

    2015-01-01

    Parallel factor (PARAFAC) analysis enables a quantitative analysis of excitation-emission matrix (EEM). The impact of a spectral variability stemmed from a diverse dataset on the representativeness of the PARAFAC model needs to be examined. In this study, samples from a river, effluent of a wastewater treatment plant, and algae secretion were collected and subjected to PARAFAC analysis. PARAFAC models of global dataset and individual datasets were compared. It was found that the peak shift derived from source diversity undermined the accuracy of the global model. The results imply that building a universal PARAFAC model that can be widely available for fitting new EEMs would be quite difficult, but fitting EEMs to existing PARAFAC model that belong to a similar environment would be more realistic. The accuracy of online monitoring strategy that monitors the fluorescence intensities at the peaks of PARAFAC components was examined by correlating the EEM data with the maximum fluorescence (Fmax) modeled by PARAFAC. For the individual datasets, remarkable correlations were obtained around the peak positions. However, an analysis of cocktail datasets implies that the involvement of foreign components that are spectrally similar to local components would undermine the online monitoring strategy. PMID:25958786

  6. An inexpensive, fast and sensitive quantitative lateral flow magneto-immunoassay for total prostate specific antigen.

    PubMed

    Barnett, Jacqueline M; Wraith, Patrick; Kiely, Janice; Persad, Raj; Hurley, Katrina; Hawkins, Peter; Luxton, Richard

    2014-09-01

    We describe the detection characteristics of a device the Resonant Coil Magnetometer (RCM) to quantify paramagnetic particles (PMPs) in immunochromatographic (lateral flow) assays. Lateral flow assays were developed using PMPs for the measurement of total prostate specific antigen (PSA) in serum samples. A detection limit of 0.8 ng/mL was achieved for total PSA using the RCM and is at clinically significant concentrations. Comparison of data obtained in a pilot study from the analysis of serum samples with commercially available immunoassays shows good agreement. The development of a quantitative magneto-immunoassay in lateral flow format for total PSA suggests the potential of the RCM to operate with many immunoassay formats. The RCM has the potential to be modified to quantify multiple analytes in this format. This research shows promise for the development of an inexpensive device capable of quantifying multiple analytes at the point-of-care using a magneto-immunoassay in lateral flow format.

  7. An Inexpensive, Fast and Sensitive Quantitative Lateral Flow Magneto-Immunoassay for Total Prostate Specific Antigen

    PubMed Central

    Barnett, Jacqueline M.; Wraith, Patrick; Kiely, Janice; Persad, Raj; Hurley, Katrina; Hawkins, Peter; Luxton, Richard

    2014-01-01

    We describe the detection characteristics of a device the Resonant Coil Magnetometer (RCM) to quantify paramagnetic particles (PMPs) in immunochromatographic (lateral flow) assays. Lateral flow assays were developed using PMPs for the measurement of total prostate specific antigen (PSA) in serum samples. A detection limit of 0.8 ng/mL was achieved for total PSA using the RCM and is at clinically significant concentrations. Comparison of data obtained in a pilot study from the analysis of serum samples with commercially available immunoassays shows good agreement. The development of a quantitative magneto-immunoassay in lateral flow format for total PSA suggests the potential of the RCM to operate with many immunoassay formats. The RCM has the potential to be modified to quantify multiple analytes in this format. This research shows promise for the development of an inexpensive device capable of quantifying multiple analytes at the point-of-care using a magneto-immunoassay in lateral flow format. PMID:25587419

  8. The specificity of some agonists and antagonists for nicotine-sensitive receptors in ganglia

    PubMed Central

    Barlow, R.B.; Bowman, Frances; Ison, R.R.; McQueen, D.S.

    1974-01-01

    1 The guinea-pig isolated ileum has been used to estimate the ability of substituted phenylalkylonium salts (related to nicotine) to stimulate or block receptors in ganglia. The effects of hexamethonium were used to indicate which were the most specific ganglion stimulants; these were tested on the blood-pressure of pithed rats and for neuromuscular blocking activity on the rat diaphragm preparation. 2 m-Hydroxyphenylpropyltrimethylammonium and 3,4-dihydroxyphenethyltrimethylammonium (coryneine, `quaternary dopamine') were the most active and specific ganglion stimulants but their usefulness in vivo may be limited by their neuromuscular blocking activity. The analogous tertiary compounds are being investigated. 3 The affinities of substances which were blocking agents at ganglionic receptors were measured on the isolated ileum with m-hydroxyphenylpropyltrimethylammonium as agonist. The affinities of selected compounds for postganglionic receptors were measured in experiments on the ileum in the presence of hexamethonium and with carbachol as agonist. Some of the compounds were tested for neuromuscular blocking activity on the rat diaphragm. 4 Phenylbutyldiethylamine had ganglion-blocking activity greater than pempidine and little postganglionic blocking or neuromuscular blocking activity. Its triethylammonium analogue had higher ganglion-blocking activity but had appreciable neuromuscular blocking activity. 5 The aromatic ring system is not essential either for activity or affinity and the effects of substituents are not related to their effects on electron distribution. Stimulant activity is enhanced only by hydroxyl or amino groups in suitable positions; it is not improved by the presence of rigid features (double or triple bonds or a cyclopropane ring) in the side chain. Affinity is slightly increased by chloro or bromo groups in suitable positions but the unsubstituted compounds are among those with the highest affinity. Substituents have similar effects on

  9. Neuron-specific (pro)renin receptor knockout prevents the development of salt-sensitive hypertension.

    PubMed

    Li, Wencheng; Peng, Hua; Mehaffey, Eamonn P; Kimball, Christie D; Grobe, Justin L; van Gool, Jeanette M G; Sullivan, Michelle N; Earley, Scott; Danser, A H Jan; Ichihara, Atsuhiro; Feng, Yumei

    2014-02-01

    The (pro)renin receptor (PRR), which binds both renin and prorenin, is a newly discovered component of the renin-angiotensin system that is highly expressed in the central nervous system. The significance of brain PRRs in mediating local angiotensin II formation and regulating blood pressure remains unclear. The current study was performed to test the hypothesis that PRR-mediated, nonproteolytic activation of prorenin is the main source of angiotensin II in the brain. Thus, PRR knockout in the brain is expected to prevent angiotensin II formation and development of deoxycorticosterone acetate-salt-induced hypertension. A neuron-specific PRR (ATP6AP2) knockout mouse model was generated using the Cre-LoxP system. Physiological parameters were recorded by telemetry. PRR expression, detected by immunostaining and reverse transcription-polymerase chain reaction, was significantly decreased in the brains of knockout mice compared with wild-type mice. Intracerebroventricular infusion of mouse prorenin increased blood pressure and angiotensin II formation in wild-type mice. This hypertensive response was abolished in PRR-knockout mice in association with a reduction in angiotensin II levels. Deoxycorticosterone acetate-salt increased PRR expression and angiotensin II formation in the brains of wild-type mice, an effect that was attenuated in PRR-knockout mice. PRR knockout in neurons prevented the development of deoxycorticosterone acetate-salt-induced hypertension as well as activation of cardiac and vasomotor sympathetic tone. In conclusion, nonproteolytic activation of prorenin through binding to the PRR mediates angiotensin II formation in the brain. Neuron-specific PRR knockout prevents the development of deoxycorticosterone acetate-salt-induced hypertension, possibly through diminished angiotensin II formation.

  10. Inter-rater agreement, sensitivity, and specificity of the prone hip extension test and active straight leg raise test

    PubMed Central

    2014-01-01

    Background Two clinical tests used to assess for neuromuscular control deficits in low back pain (LBP) patients are the prone hip extension (PHE) test and active straight leg raise (ASLR) test. For these tests, it has been suggested examiners classify patients as “positive” or “negative” based on the presence or absence (respectively) of specific “abnormal” lumbopelvic motion patterns. The inter-rater agreement of such a classification scheme has been reported for the PHE test, but not for the ASLR test. In addition, the sensitivity and specificity of such classification schemes have not been reported for either test. The primary objectives of the current study were to investigate: 1) the inter-rater agreement of the examiner-reported classification schemes for these two tests, and 2) the sensitivity and specificity of the classification schemes. Methods Thirty participants with LBP and 40 asymptomatic controls took part in this cross-sectional observational study. Participants performed 3–4 repetitions of each test whilst two examiners classified them as “positive” or “negative” based on the presence or absence (respectively) of specific “abnormal” lumbopelvic motion patterns. The inter-rater agreement (Kappa statistic), sensitivity (LBP patients), and specificity (controls) were calculated for each test. Results Both tests demonstrated substantial inter-rater agreement (PHE test: Kappa = 0.76, 95% CI = 0.57-0.95, p < 0.001; ASLR test: Kappa = 0.76, 95% CI = 0.57-0.96, p < 0.001). For the PHE test, the sensitivity was 0.18-0.27 and the specificity was 0.63-0.78; the odds ratio (OR) of “positive” classifications in the LBP group was 1.25 (95% CI = 0.58-2.72; Examiner 1) and 1.27 (95% CI = 0.52-3.12; Examiner 2). For the ASLR test, the sensitivity was 0.20-0.25 and the specificity was 0.84-0.86; the OR of “positive” classifications in the LBP group was 1.72 (95% CI = 0.75-3.95; Examiner 1) and 1

  11. Sensitivity and specificity of photography and direct ophthalmoscopy in screening for sight threatening eye disease: the Liverpool Diabetic Eye Study.

    PubMed Central

    Harding, S. P.; Broadbent, D. M.; Neoh, C.; White, M. C.; Vora, J.

    1995-01-01

    OBJECTIVE--To evaluate different methods for community based screening for sight threatening diabetic eye disease. DESIGN--Prospective study. SETTING--Mobile screening unit visiting inner city community clinics; hospital assessment clinic (tertiary centre). SUBJECTS--395 diabetic patients registered with four general practices in an inner city location. INTERVENTIONS--Community based photography with mydriasis and direct ophthalmoscopy through dilated pupils by an experienced ophthalmologist, both compared with reference standard of slit lamp biomicroscopy by a consultant specialist in medical retinal disease. MAIN OUTCOME MEASURES--Sensitivity and specificity of screening method and prevalence of sight threatening diabetic eye disease (moderate preproliferative retinopathy, circinate maculopathy, exudate within 1 disc diameter of fixation, other diabetes related eye disease). RESULTS--358 subjects underwent photography, 326 attended hospital clinic for ophthalmoscopy, and six were ungradable on photographs and biomicroscopy, leaving 320 for analysis. Of these 295 (91%) attended clinic within four months of photography. Sensitivity of detection of eye disease by photography was 89% (95% confidence interval 80% to 98%), significantly better than for direct ophthalmoscopy (65% (51% to 79%)). Analysis of patients with false negative results indicated possible improvement of photographic sensitivity to 93% by addition of stereoscopic macular pair photographs. Specificity of detection of sight threatening eye disease was 86% (82% to 90%) for photography and 97% (95% to 99%) for direct ophthalmoscopy. CONCLUSIONS--Since high sensitivity is essential for an effective screening programme, a photographic method should be considered as preferred option in national, community based screening programmes. Even in the hands of an experienced ophthalmologist, direct ophthalmoscopy is limited by weaknesses inherent to the instrument. PMID:7580708

  12. Effect of hapten structures on specific and sensitive enzyme-linked immunosorbent assays for N-methylcarbamate insecticide metolcarb.

    PubMed

    Zhang, Qi; Wu, Yunru; Wang, Limin; Hu, Baishi; Li, Peiwu; Liu, Fengquan

    2008-09-05

    Five different haptens of the N-methylcarbamate insecticide metolcarb were designed and synthesized. All of the haptens were conjugated with ovalbumin (OVA) for the coating antigen, and one hapten containing all of the structure of metolcarb was conjugated with bovine serum albumin (BSA) for the immunogen. Two polyclonal antisera were raised against the BSA conjugate, and ten antibody/coating conjugate combinations were selected for studies of assay sensitivity and specificity for metolcarb. A class-specific combination was found, with the I50 of the assay ranged from 0.64 to 20.98 microg mL(-1) for seven tested N-methylcarbamate insecticides except for pirimicarb. Considering titer, I50 and cross-reactivity of all combinations of antibody/coating conjugate, a competitive indirect enzyme-linked immunosorbent assay (ELISA) in a homologous system, whose limit of detection (LoD) reached 1.4 ng mL(-1), was presented. The results of competitive ELISAs indicated that coating hapten structure can significantly affect not only assay sensitivity but also its specificity.

  13. A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment.

    PubMed

    Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

    2015-08-04

    Digital PCR has developed rapidly since it was first reported in the 1990 s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.

  14. Specific and sensitive detection of Plasmodium falciparum lactate dehydrogenase by DNA-scaffolded silver nanoclusters combined with an aptamer.

    PubMed

    Wang, Wei-Xian; Cheung, Yee-Wai; Dirkzwager, Roderick M; Wong, Wai-Chung; Tanner, Julian A; Li, Hong-Wei; Wu, Yuqing

    2017-02-27

    Innovative nanomaterials offer significant potential for diagnosis of severe diseases of the developing world such as malaria. Small sized silver nanoclusters have shown promise for diagnostics due to their intense fluorescence emission and photo-stabilities. Here, double-stranded DNA-scaffolded silver nanoclusters (AgNCs-dsDNA) were prepared to detect the established malaria biomarker, Plasmodium falciparum lactate dehydrogenase (PfLDH). Significant luminescence enhancement over a wide concentration range of PfLDH was demonstrated. In addition, a low limit of detection at 0.20 nM (7.4 pg μL(-1)) was achieved for PfLDH in buffer solution, sensitive enough for practical use correlating with the clinical level of PfLDH in plasma from malaria-infected patients. Unique specificity was observed towards Plasmodium falciparum over Plasmodium vivax and human lactate dehydrogenase, as well as other non-specific proteins, by combining the use of AgNCs-dsDNA with a DNA aptamer against PfLDH. Moreover, the intrinsic mechanism was revealed in detail for the two-step luminescence response. The combination of DNA-scaffolded silver nanoclusters coupled to a selective single-stranded DNA aptamer allows for a highly specific and sensitive detection of PfLDH with significant promise for malaria diagnosis in future.

  15. A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment

    PubMed Central

    Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

    2015-01-01

    Digital PCR has developed rapidly since it was first reported in the 1990s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products. PMID:26239916

  16. Detection of Echinococcus multilocularis by MC-PCR: evaluation of diagnostic sensitivity and specificity without gold standard

    PubMed Central

    Wahlström, Helene; Comin, Arianna; Isaksson, Mats; Deplazes, Peter

    2016-01-01

    Introduction A semi-automated magnetic capture probe-based DNA extraction and real-time PCR method (MC-PCR), allowing for a more efficient large-scale surveillance of Echinococcus multilocularis occurrence, has been developed. The test sensitivity has previously been evaluated using the sedimentation and counting technique (SCT) as a gold standard. However, as the sensitivity of the SCT is not 1, test characteristics of the MC-PCR was also evaluated using latent class analysis, a methodology not requiring a gold standard. Materials and methods Test results, MC-PCR and SCT, from a previous evaluation of the MC-PCR using 177 foxes shot in the spring (n=108) and autumn 2012 (n=69) in high prevalence areas in Switzerland were used. Latent class analysis was used to estimate the test characteristics of the MC-PCR. Although it is not the primary aim of this study, estimates of the test characteristics of the SCT were also obtained. Results and discussion This study showed that the sensitivity of the MC-PCR was 0.88 [95% posterior credible interval (PCI) 0.80–0.93], which was not significantly different than the SCT, 0.83 (95% PCI 0.76–0.88), which is currently considered as the gold standard. The specificity of both tests was high, 0.98 (95% PCI 0.94–0.99) for the MC-PCR and 0.99 (95% PCI 0.99–1) for the SCT. In a previous study, using fox scats from a low prevalence area, the specificity of the MC-PCR was higher, 0.999% (95% PCI 0.997–1). One reason for the lower estimate of the specificity in this study could be that the MC-PCR detects DNA from infected but non-infectious rodents eaten by foxes. When using MC-PCR in low prevalence areas or areas free from the parasite, a positive result in the MC-PCR should be regarded as a true positive. Conclusion The sensitivity of the MC-PCR (0.88) was comparable to the sensitivity of SCT (0.83). PMID:26968153

  17. microRNA160 dictates stage-specific auxin and cytokinin sensitivities and directs soybean nodule development.

    PubMed

    Nizampatnam, Narasimha Rao; Schreier, Spencer John; Damodaran, Suresh; Adhikari, Sajag; Subramanian, Senthil

    2015-10-01

    Legume nodules result from coordinated interactions between the plant and nitrogen-fixing rhizobia. The phytohormone cytokinin promotes nodule formation, and recent findings suggest that the phytohormone auxin inhibits nodule formation. Here we show that microRNA160 (miR160) is a key signaling element that determines the auxin/cytokinin balance during nodule development in soybean (Glycine max). miR160 appears to promote auxin activity by suppressing the levels of the ARF10/16/17 family of repressor ARF transcription factors. Using quantitative PCR assays and a fluorescence miRNA sensor, we show that miR160 levels are relatively low early during nodule formation and high in mature nodules. We had previously shown that ectopic expression of miR160 in soybean roots led to a severe reduction in nodule formation, coupled with enhanced sensitivity to auxin and reduced sensitivity to cytokinin. Here we show that exogenous cytokinin restores nodule formation in miR160 over-expressing roots. Therefore, low miR160 levels early during nodule development favor cytokinin activity required for nodule formation. Suppression of miR160 levels using a short tandem target mimic (STTM160) resulted in reduced sensitivity to auxin and enhanced sensitivity to cytokinin. In contrast to miR160 over-expressing roots, STTM160 roots had increased nodule formation, but nodule maturation was significantly delayed. Exogenous auxin partially restored proper nodule formation and maturation in STTM160 roots, suggesting that high miR160 activity later during nodule development favors auxin activity and promotes nodule maturation. Therefore, miR160 dictates developmental stage-specific sensitivities to auxin and cytokinin to direct proper nodule formation and maturation in soybean.

  18. Strain-specific differences in the grazing sensitivities of closely related ultramicrobacteria affiliated with the Polynucleobacter cluster.

    PubMed

    Boenigk, Jens; Stadler, Peter; Wiedlroither, Anneliese; Hahn, Martin W

    2004-10-01

    Ultramicrobacteria (cell volume < 0.1 microm(3)) are the numerically dominant organisms in the plankton of marine and freshwater habitats. Flagellates and other protists are assumed to be the most important predators of these ultramicrobacteria as well as of larger planktonic bacteria. However, due to controversial observations conducted previously, it is not clear as to whether fractions of the ultramicrobacteria are resistant to flagellate predation. Furthermore, it is not known if closely related bacteria vary significantly in their sensitivity to flagellate predation. We investigated the sensitivity of ultramicrobacteria affiliated with the cosmopolitan Polynucleobacter cluster to grazing by Spumella-like nanoflagellates. Laboratory grazing experiments with four closely related (> or =99.6% 16S rRNA gene sequence similarity) bacteria and three closely related (100% 18S rRNA gene sequence similarity) flagellates were performed. In comparison to larger bacteria, predation on the ultramicrobacterial Polynucleobacter strains was weak, and the growth of the predating flagellates was slow. Specific clearance rates ranged between 0.14 x 10(5) and 2.8 x 10(5) units of predator size h(-1). Feeding rates strongly depended on the flagellate and bacterial strain (P < 0.001). Grazing mortality rates of the three flagellate strains investigated varied for the same prey strain by up to almost fourfold. We conclude that (i) ultramicrobacteria affiliated with the Polynucleobacter cluster are not protected from grazing, (ii) strain-specific variations in grazing sensitivity even between closely related bacteria are high, and (iii) strain-specific differences in predator-prey interaction could be an important factor in the evolution and maintenance of microbial microdiversity.

  19. UV and arsenate toxicity: a specific and sensitive yeast bioluminescence assay.

    PubMed

    Bakhrat, Anya; Eltzov, Evgeni; Finkelstein, Yishay; Marks, Robert S; Raveh, Dina

    2011-06-01

    We describe a Saccharomyces cerevisiae bioluminescence assay for UV and arsenate in which bacterial luciferase genes are regulated by the promoter of the yeast gene, UFO1. UFO1 encodes the F-box subunit of the Skp1–Cdc53–F-box protein ubiquitin ligase complex and is induced by DNA damage and by arsenate. We engineered the UFO1 promoter into an existing yeast bioreporter that employs human genes for detection of steroid hormone-disrupting compounds in water bodies. Our analysis indicates that use of an endogenous yeast promoter in different mutant backgrounds allows discrimination between different environmental signals. The UFO1-engineered yeast give a robust bioluminescence response to UVB and can be used for evaluating UV protective sunscreens. They are also effective in detecting extremely low concentrations of arsenate, particularly in pdr5Δ mutants that lack a mechanism to extrude toxic chemicals; however, they do not respond to cadmium or mercury. Combined use of endogenous yeast promoter elements and mutants of stress response pathways may facilitate development of high-specificity yeast bioreporters able to discriminate between closely related chemicals present together in the environment.

  20. New specific and sensitive biomonitoring methods for chemicals of emerging health relevance.

    PubMed

    Leng, Gabriele; Gries, Wolfgang

    2016-09-20

    In this publication the challenges to cope for the aim to obtain innovative biomonitoring methods in our laboratory are visualized for di(2-propylheptyl)phthalate, 2-mercaptobenzothiazole, 3,5-di-tert-butyl-4-hydroxytoluene, 4-nonylphenol, 4-tert-octylphenol, 3-(4-methylbenzylidene)camphor, 4,4'-methylene diphenyl diisocyanate, and Hexabromocyclododecane. For these substances new specific markers were explored based on animal or human kinetic data with urine being the preferred matrix compared to blood. The determination of these markers was complex in all cases, because the sample preparation as well as the detection by high performance liquid chromatography, capillary gas chromatography coupled to tandem mass spectrometers or high resolution mass spectrometry should enable the lowest possible detection limit by use of minimal biological sample volumes. To get a first hint of a possible background level, the analytical methods were applied to urine samples of about 40 persons for each chemical. For Di(2-propylheptyl)phthalate and 2-Mercaptobenzothiazole first results are presented from population biomonitoring.

  1. Autologous serum skin test vs autologous plasma skin test in patients with chronic urticaria: evaluation of reproducibility, sensitivity and specificity and relationship with disease activity, quality of life and anti-thyroid antibodies.

    PubMed

    Kocatürk, Emek; Kavala, Mukaddes; Kural, Esra; Sarıgul, Sukran; Zındancı, Ilkin

    2011-01-01

    Recent concerns have arisen about the specificity and interpretation of the autologous serum skin test (ASST), suggesting that ASST might produce false-positive results, and proposing the use of autologous plasma (APST) instead for intradermal testing in autoreactive urticaria. We investigated autoreactivity to autologous plasma and compared the results for reproducibility, sensitivity, specificity and accuracy and evaluated their association with quality of life and anti-TPO antibodies. 70 adults with chronic spontaneous urticaria (CU) and 62 controls underwent testing with ASST and APST and the tests were repeated two days after the first visit. Blood tests measured anti-TPO levels. Disease activity was assessed by urticaria activity score (UAS-7) and quality of life impairment was assessed by DLQI and CU-Q(2)oL. There were no statistically significant differences between ASST (+) and ASST (-) and also APST (+) and APST (-) patients with regard to disease duration, anti-TPO antibodies, urticaria activity scores, DLQI scores and CU-Q(2)oL scores. The results of first ASST and APST were well correlated with the results of second ASST and APST. The specificity of the two tests was similar, while ASST had a higher sensitivity and accuracy. Our results showed that there is no need to use autologous plasma instead of autologous serum for intradermal testing in CU.

  2. Development of a method for the determination of total bisphenol a at trace levels in human blood and urine and elucidation of factors influencing method accuracy and sensitivity.

    PubMed

    Markham, Dan; Waechter, John; Budinsky, Robert; Gries, Wolfgang; Beyer, Dieter; Snyder, Stephanie; Dimond, Stephen; Rajesh, V N; Rao, Narayana; Connolly, Paul; Neeley, Mark; Hentges, Steven

    2014-05-01

    This publication describes a method for the determination of total bisphenol A (BPA and conjugated BPA) following enzyme hydrolysis and is intended as a companion to our previously developed analytical method for the determination of free BPA (the aglycone) in human blood and urine using high-performance liquid chromatography-tandem mass spectrometry ( 1). That free BPA method provided a means to account for and/or eliminate background contamination and demonstrated accuracy and reproducibility in both matrices fortified with BPA or a surrogate analyte ((13)C BPA) at a low method quantitation limit (MQL) of 0.1-0.2 ng/mL. In contrast to the free BPA method results and based on stringent accuracy, precision and confirmation criteria set for the MQLs of the method developed for total BPA, the MQL achieved in blood was 1.020-2.550 and 0.510-1.020 ng/mL in urine. These data showed higher MQLs than the desired MQLs of 0.5 ng/mL (blood) and 0.2 ng/mL (urine) with increased variability between analyses which demonstrates the importance of generating method validation data with each analysis. In contrast, the MQL achieved for (13)C BPA-G (monoglucuronide as a surrogate analyte in blood was 0.2-0.5 and 0.2 ng/mL in urine illustrating that the method is capable of meeting lower MQL requirements if the contribution from exogenous BPA can be well controlled. This method for the determination total BPA in human blood and urine is intended to be used in conjunction with the free BPA method ( 1) to obtain accurate and complete BPA biomonitoring data to support human exposure assessments.

  3. Sensitivity of WRF-chem predictions to dust source function specification in West Asia

    NASA Astrophysics Data System (ADS)

    Nabavi, Seyed Omid; Haimberger, Leopold; Samimi, Cyrus

    2017-02-01

    Dust storms tend to form in sparsely populated areas covered by only few observations. Dust source maps, known as source functions, are used in dust models to allocate a certain potential of dust release to each place. Recent research showed that the well known Ginoux source function (GSF), currently used in Weather Research and Forecasting Model coupled with Chemistry (WRF-chem), exhibits large errors over some regions in West Asia, particularly near the IRAQ/Syrian border. This study aims to improve the specification of this critical part of dust forecasts. A new source function based on multi-year analysis of satellite observations, called West Asia source function (WASF), is therefore proposed to raise the quality of WRF-chem predictions in the region. WASF has been implemented in three dust schemes of WRF-chem. Remotely sensed and ground-based observations have been used to verify the horizontal and vertical extent and location of simulated dust clouds. Results indicate that WRF-chem performance is significantly improved in many areas after the implementation of WASF. The modified runs (long term simulations over the summers 2008-2012, using nudging) have yielded an average increase of Spearman correlation between observed and forecast aerosol optical thickness by 12-16 percent points compared to control runs with standard source functions. They even outperform MACC and DREAM dust simulations over many dust source regions. However, the quality of the forecasts decreased with distance from sources, probably due to deficiencies in the transport and deposition characteristics of the forecast model in these areas.

  4. Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release

    PubMed Central

    Chu, David S.H.; Johnson, Russell N.; Pun, Suzie H.

    2011-01-01

    Degradable cationic polymers are desirable for in vivo nucleic acid delivery because they offer significantly decreased toxicity over non-degradable counterparts. Peptide linkers provide chemical stability and high specificity for particular endopeptidases but have not been extensively studied for nucleic acid delivery applications. In this work, enzymatically degradable peptide-HPMA copolymers were synthesized by RAFT polymerization of HPMA with methacrylated peptide macromonomers, resulting in polymers with low polydispersity and near quantitative incorporation of peptides. Three peptide-HPMA copolymers were evaluated: (i) pHCathK10, containing peptides composed of the linker phe-lys-phe-leu (FKFL), a substrate of the endosomal/lysosomal endopeptidase cathepsin B, connected to oligo-(l)-lysine for nucleic acid binding, (ii) pHCath(d)K10, containing the FKFL linker with oligo-(d)-lysine, and (iii) pH(d)Cath(d)K10, containing all (d) amino acids. Cathepsin B degraded copolymers pHCathK10 and pHCath(d)K10 within one hour while no degradation of pH(d)Cath(d)K10 was observed. Polyplexes formed with pHCathK10 copolymers show DNA release by 4 hrs of treatment with cathepsin B; comparatively, polyplexes formed with pHCath(d)K10 and pH(d)Cath(d)K10 show no DNA release within 8 hrs. Transfection efficiency in HeLa and NIH/3T3 cells were comparable between the copolymers but pHCathK10 was less toxic. This work demonstrates the successful application of peptide linkers for degradable cationic polymers and DNA release. PMID:22036879

  5. Globular hepatic amyloid is highly sensitive and specific for LECT2 amyloidosis.

    PubMed

    Chandan, Vishal S; Shah, Sejal S; Lam-Himlin, Dora M; Petris, Giovanni De; Mereuta, Oana M; Dogan, Ahmet; Torbenson, Michael S; Wu, Tsung-Teh

    2015-04-01

    Globular hepatic amyloid (GHA) is rare, and its clinical significance remains unclear. Recently, leukocyte chemotactic factor-associated amyloidosis (ALECT2) has been reported to involve the liver, showing a globular pattern. We reviewed 70 consecutive cases of hepatic amyloidosis to determine the prevalence and morphology of hepatic amyloid subtypes, especially ALECT2 and its association with GHA. Each case was reviewed for amyloid subtype (immunohistochemistry and/or mass spectrometry), its pattern (linear or globular), and distribution (vascular, perisinusoidal, or stromal). In addition, 24 cases of confirmed hepatic ALECT2 on mass spectrometry from our consultation files were also reviewed. LECT2 immunostaining was performed in 49 cases. Of the 70 cases, immunoglobulin light chain (AL) type was most common with 41 cases (59%), followed by transthyretin (ATTR) 15 cases (22%), 3 cases each of fibrinogen A (AFib) (4%), serum amyloid A (AA) (4%), and ALECT2 (4%), 2 cases of apolipoproteins (AApoA1) (3%), and 3 cases (4%) were unclassified. Three of our 70 cases (4%), with ALECT2, and all 24 cases (100%) of mass spectrometry-confirmed hepatic ALECT2 showed only GHA deposits in the hepatic sinusoids and portal tracts. Three (4%) other cases of AL type showed a focal globular pattern admixed with prominent linear amyloid. None of the other amyloid subtypes showed GHA. LECT2 immunostain was positive in all 27 cases (100%) of ALECT2 and negative in the other 22 non-ALECT2 cases (100%) (14 AL, 5 ATTR, 1 AA, 1 AFib, 1 AApoA1). Pure GHA is uncommon (4%) but is highly specific for ALECT2, and LECT2 immunostain is helpful in confirming this amyloid type.

  6. Purification, crystallization and preliminary crystallographic analysis of Est25: a ketoprofen-specific hormone-sensitive lipase

    SciTech Connect

    Kim, SeungBum; Joo, Sangbum; Yoon, Hyun C.; Ryu, Yeonwoo; Kim, Kyeong Kyu; Kim, T. Doohun

    2007-07-01

    Est25, a ketoprofen-specific hormone-sensitive lipase from a metagenomic library, was crystallized and diffraction data were collected to 1.49 Å resolution. Ketoprofen, a nonsteroidal anti-inflammatory drug, inhibits the synthesis of prostaglandin. A novel hydrolase (Est25) with high ketoprofen specificity has previously been identified using a metagenomic library from environmental samples. Recombinant Est25 protein with a histidine tag at the N-terminus was expressed in Escherichia coli and purified in a homogenous form. Est25 was crystallized from 2.4 M sodium malonate pH 7.0 and X-ray diffraction data were collected to 1.49 Å using synchrotron radiation. The crystals belong to the monoclinic space group C2, with unit-cell parameters a = 197.8, b = 95.2, c = 99.4 Å, β = 97.1°.

  7. Region-specific sensitivity of anemophilous pollen deposition to temperature and precipitation.

    PubMed

    Donders, Timme H; Hagemans, Kimberley; Dekker, Stefan C; de Weger, Letty A; de Klerk, Pim; Wagner-Cremer, Friederike

    2014-01-01

    Understanding relations between climate and pollen production is important for several societal and ecological challenges, importantly pollen forecasting for pollinosis treatment, forensic studies, global change biology, and high-resolution palaeoecological studies of past vegetation and climate fluctuations. For these purposes, we investigate the role of climate variables on annual-scale variations in pollen influx, test the regional consistency of observed patterns, and evaluate the potential to reconstruct high-frequency signals from sediment archives. A 43-year pollen-trap record from the Netherlands is used to investigate relations between annual pollen influx, climate variables (monthly and seasonal temperature and precipitation values), and the North Atlantic Oscillation climate index. Spearman rank correlation analysis shows that specifically in Alnus, Betula, Corylus, Fraxinus, Quercus and Plantago both temperature in the year prior to (T-1), as well as in the growing season (T), are highly significant factors (TApril rs between 0.30 [P<0.05[ and 0.58 [P<0.0001]; TJuli-1 rs between 0.32 [P<0.05[ and 0.56 [P<0.0001]) in the annual pollen influx of wind-pollinated plants. Total annual pollen prediction models based on multiple climate variables yield R2 between 0.38 and 0.62 (P<0.0001). The effect of precipitation is minimal. A second trapping station in the SE Netherlands, shows consistent trends and annual variability, suggesting the climate factors are regionally relevant. Summer temperature is thought to influence the formation of reproductive structures, while temperature during the flowering season influences pollen release. This study provides a first predictive model for seasonal pollen forecasting, and also aides forensic studies. Furthermore, variations in pollen accumulation rates from a sub-fossil peat deposit are comparable with the pollen trap data. This suggests that high frequency variability pollen records from natural archives reflect

  8. Region-Specific Sensitivity of Anemophilous Pollen Deposition to Temperature and Precipitation

    PubMed Central

    Donders, Timme H.; Hagemans, Kimberley; Dekker, Stefan C.; de Weger, Letty A.; de Klerk, Pim; Wagner-Cremer, Friederike

    2014-01-01

    Understanding relations between climate and pollen production is important for several societal and ecological challenges, importantly pollen forecasting for pollinosis treatment, forensic studies, global change biology, and high-resolution palaeoecological studies of past vegetation and climate fluctuations. For these purposes, we investigate the role of climate variables on annual-scale variations in pollen influx, test the regional consistency of observed patterns, and evaluate the potential to reconstruct high-frequency signals from sediment archives. A 43-year pollen-trap record from the Netherlands is used to investigate relations between annual pollen influx, climate variables (monthly and seasonal temperature and precipitation values), and the North Atlantic Oscillation climate index. Spearman rank correlation analysis shows that specifically in Alnus, Betula, Corylus, Fraxinus, Quercus and Plantago both temperature in the year prior to (T-1), as well as in the growing season (T), are highly significant factors (TApril rs between 0.30 [P<0.05[ and 0.58 [P<0.0001]; TJuli-1 rs between 0.32 [P<0.05[ and 0.56 [P<0.0001]) in the annual pollen influx of wind-pollinated plants. Total annual pollen prediction models based on multiple climate variables yield R2 between 0.38 and 0.62 (P<0.0001). The effect of precipitation is minimal. A second trapping station in the SE Netherlands, shows consistent trends and annual variability, suggesting the climate factors are regionally relevant. Summer temperature is thought to influence the formation of reproductive structures, while temperature during the flowering season influences pollen release. This study provides a first predictive model for seasonal pollen forecasting, and also aides forensic studies. Furthermore, variations in pollen accumulation rates from a sub-fossil peat deposit are comparable with the pollen trap data. This suggests that high frequency variability pollen records from natural archives reflect

  9. Development and validation of a specific and sensitive GC-FID method for the determination of impurities in 5-chlorovaleroyl chloride.

    PubMed

    Tang, Liya; Kim, Alexandre; Miller, Scott A; Lloyd, David K

    2010-11-02

    5-Chlorovaleroyl chloride (5-CVC) is commonly used as an alkylating agent in the synthesis of pharmaceutical intermediates, active ingredients, as well as other specialty chemicals. It is critical to monitor the impurities present in 5-CVC as they may have a direct impact on the impurity profile and quality of the final product. This paper describes the development and validation of a GC-FID method for the analysis of low level impurities of 5-CVC. This is the first method reported in the literature for the impurity determination of 5-CVC. The results of GC method development, with and without sample derivatization, are presented. The final method uses methanol for derivatization and separates methyl esters of 5-CVC and the key impurities, 4-pentenoyl chloride, 4-chlorovaleroyl chloride, 5-chlorohexanoyl chloride, and 4-methyl-5-chlorovaleroyl chloride. 3-Methoxypyridine was used in the sample solvent to enable the detection of 5-chlorovaleric acid (5-CVA) which is the major degradant of 5-CVC. The method was validated for specificity, linearity, accuracy, precision, sensitivity, and robustness. This simple and robust GC approach may be applicable to impurity analysis of other acid chlorides or acid halides.

  10. A sensitive and specific liquid chromatography mass spectrometry method for simultaneous determination of berberine, palmatine, coptisine, epiberberine and jatrorrhizine from Coptidis Rhizoma in rat plasma

    NASA Astrophysics Data System (ADS)

    Yu, Sen; Pang, Xiaoyan; Deng, Yuanxiong; Liu, Li; Liang, Yan; Liu, Xiaodong; Xie, Lin; Wang, Guangji; Wang, Xinting

    2007-11-01

    A sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method has been developed and validated for the identification and quantification of five protoberberine alkaloids, which are berberine, palmatine, coptisine, epiberberine and jatrorrhizine, in rat plasma using tetrahydroberberine as an internal standard. Following solid-phase extraction, the analytes were separated by linear gradient elution on a Shim-pack ODS (4.6 [mu]m, 150 mm × 2.0 mm i.d.) column and analyzed in selected ion monitoring (SIM) mode with a positive electrospray ionization (ESI) interface using the respective [M]+ and [M + H]+ ions, [M]+ = 336 for berberine; 320 for coptisine; 336 for epiberberine; 338 for jatrorrhizine; 352 for palmatine and [M + H]+ = 340 for the internal standard. The method was validated over the concentration range of 0.31-20 ng mL-1 for all the five protoberberine alkaloids. Within-batch and between-batch precisions (R.S.D.%) were all within 15% and accuracy (%Er) ranged from -5 to 5%. The lower limits of quantification were 0.31 ng mL-1 for all analytes. The extraction recoveries were on average 80.8% for berberine, 67E0% for coptisine, 66.2% for epiberberine, 71.8% for jatrorrhizine and 73E2% for palmatine. The validated method was used to study the pharmacokinetic profile of the five protoberberine alkaloids in rat plasma after oral administration of Coptidis Rhizoma extract.

  11. High-sensitivity liquid chromatography-tandem mass spectrometry for the simultaneous determination of five drugs and their cytochrome P450-specific probe metabolites in human plasma.

    PubMed

    Oh, Kyung-Suk; Park, Su-Jin; Shinde, Dhananjay D; Shin, Jae-Gook; Kim, Dong-Hyun

    2012-05-01

    A sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method with electrospray ionization was developed for the simultaneous quantitation of five probe drugs and their metabolites in human plasma for assessing the in vivo activities of cytochrome P450 (CYP). CYP isoform specific substrates and their metabolites of CYP1A2 (caffeine), CYP2C9 (losartan), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan) and CYP3A (midazolam) were all simultaneously analyzed using LC-MS/MS after administration of a mixture of five drugs (i.e., a "cocktail approach") to healthy volunteers. The assay uses propranolol as an internal standard; dual liquid extraction; a Xbridge MS C(18) (100 mm × 2.1mm, 3.5 μm) column; a gradient mobile phase of 0.1% formic acid/acetonitrile (7/3→3/7); mass spectrometric detection in positive ion mode. The method was validated from 5 to 500 ng/mL for caffeine and paraxanthine, 0.1-40 ng/mL for losartan and EXP3174, 0.05-20 ng/mL for omeprazole and 5-hydroxyomeprazole, 0.008-0.8 ng/mL for dextromethorphan and dextrorphan, 0.01-1.0 ng/mL for midazolam, and 0.04-4 ng/mL for 1'-hydroxymidazolam. The intra- and inter-day precision over the concentration ranges for all analytes were lower than 12.5% and 13.8% (relative standard deviation, %RSD), and accuracy was between 86.5% and 108.4% and between 87.0% and 107.0%, respectively. This highly sensitive and quantitative method allowed a pharmacokinetic study in subjects receiving doses 10-100 times lower than typical therapeutic doses.

  12. Predictive Accuracy of Exercise Stress Testing the Healthy Adult.

    ERIC Educational Resources Information Center

    Lamont, Linda S.

    1981-01-01

    Exercise stress testing provides information on the aerobic capacity, heart rate, and blood pressure responses to graded exercises of a healthy adult. The reliability of exercise tests as a diagnostic procedure is discussed in relation to sensitivity and specificity and predictive accuracy. (JN)

  13. An evaluation, comparison, and accurate benchmarking of several publicly available MS/MS search algorithms: Sensitivity and Specificity analysis.

    SciTech Connect

    Kapp, Eugene; Schutz, Frederick; Connolly, Lisa M.; Chakel, John A.; Meza, Jose E.; Miller, Christine A.; Fenyo, David; Eng, Jimmy K.; Adkins, Joshua N.; Omenn, Gilbert; Simpson, Richard

    2005-08-01

    MS/MS and associated database search algorithms are essential proteomic tools for identifying peptides. Due to their widespread use, it is now time to perform a systematic analysis of the various algorithms currently in use. Using blood specimens used in the HUPO Plasma Proteome Project, we have evaluated five search algorithms with respect to their sensitivity and specificity, and have also accurately benchmarked them based on specified false-positive (FP) rates. Spectrum Mill and SEQUEST performed well in terms of sensitivity, but were inferior to MASCOT, X-Tandem, and Sonar in terms of specificity. Overall, MASCOT, a probabilistic search algorithm, correctly identified most peptides based on a specified FP rate. The rescoring algorithm, Peptide Prophet, enhanced the overall performance of the SEQUEST algorithm, as well as provided predictable FP error rates. Ideally, score thresholds should be calculated for each peptide spectrum or minimally, derived from a reversed-sequence search as demonstrated in this study based on a validated data set. The availability of open-source search algorithms, such as X-Tandem, makes it feasible to further improve the validation process (manual or automatic) on the basis of ''consensus scoring'', i.e., the use of multiple (at least two) search algorithms to reduce the number of FPs. complement.

  14. Specific nonpeptide inhibitors of puromycin-sensitive aminopeptidase with a 2,4(1H,3H)-quinazolinedione skeleton.

    PubMed

    Kakuta, Hiroki; Tanatani, Aya; Nagasawa, Kazuo; Hashimoto, Yuichi

    2003-11-01

    Potent, specific, chemically stable and non-peptide/small-molecular inhibitors of puromycin-sensitive aminopeptidase, such as 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione (PAQ-22, 5), were prepared by the structural development of a potent PSA inhibitor, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22, 4). The design was carried out partly by applying electrostatic potential field information obtained from PIQ-22 (4) and its derivatives based on thalidomide (2). This information revealed that a positive electrostatic potential field around the benzylic methylene in the tetrahydroisoquinoline ring is necessary for potent activity. Lineweaver-Burk plot analysis showed that PAQ-22 (5) and its derivatives inhibit puromycin-sensitive aminopeptidase (PSA) in a non-competitive manner. These potent and specific PSA inhibitors showed dose-dependent cell invasion-inhibitory activity in a Matrigel assay using mouse melanoma B16F10/L5 cells, in spite of their low cell toxicity.

  15. Specificity and detection limit of a dermal temperature histamine sensitization test for absence of residual pertussis toxin in vaccines.

    PubMed

    Jensen, Sten E; Illigen, Kristin E Engelhart; Badsberg, Jens Henrik; Hasløv, Kaare R

    2012-01-01

    Currently, an assay based on fatal sensitization of mice to histamine challenge is widely used for testing absence of residual pertussis toxin in acellular pertussis containing vaccines. For replacement of this lethal end-point assay, an alternative method based on body temperature measurement in mice has been presented, and in this study the specificity and detection limit of a dermal temperature-based assay were assessed. Test preparations containing pertussis toxin were prepared in aluminum-adjuvanted pertussis toxoid vaccine and injected intraperitoneally in histamine sensitive mice. Later the mice were challenged with histamine and the pertussis toxin-induced decrease in dermal temperature recorded. By comparison of mice treated with pertussis toxoid vaccine spiked with pertussis toxin with mice treated with pertussis toxoid vaccine alone, the assay gave a response that specifically could detect presence of pertussis toxin. The acellular pertussis containing vaccine did not interfere with the pertussis toxin-induced temperature response recorded. In tests for presence of pertussis toxin in the pertussis vaccine preparation, the detection limit of the assay was estimated to approximately 5 ng pertussis toxin per human dose of pertussis toxoid. The dermal temperature-based assay was found to be a valid method to be applied in routine quality control of vaccines.

  16. Sensitivity and Specificity Improvement in Abdominal Obesity Diagnosis Using Cluster Analysis during Waist Circumference Cut-Off Point Selection

    PubMed Central

    Bermúdez, Valmore; Añez, Roberto; Toledo, Alexandra; Bello, Luis; Apruzzese, Vanessa; González, Robys; Chacín, Maricarmen; Cabrera, Mayela; Cano, Clímaco; Velasco, Manuel; López-Miranda, José

    2015-01-01

    Introduction. The purpose of this study was to analyze the influence of metabolic phenotypes during the construction of ROC curves for waist circumference (WC) cutpoint selection. Materials and Methods. A total of 1,902 subjects of both genders were selected from the Maracaibo City Metabolic Syndrome Prevalence Study database. Two-Step Cluster Analysis (TSCA) was applied to select metabolically healthy and sick men and women. ROC curves were constructed to determine WC cutoff points by gender. Results. Through TSCA, metabolic phenotype predictive variables were selected: HOMA2-IR and HOMA2-βcell for women and HOMA2-IR, HOMA2-βcell, and TAG for men. Subjects were classified as healthy normal weight, metabolically obese normal weight, healthy and metabolically disturbed overweight, and healthy and metabolically disturbed obese. Final WC cutpoints were 91.50 cm for women (93.4% sensitivity, 93.7% specificity) and 98.15 cm for men (96% sensitivity, 99.5% specificity). Conclusions. TSCA in the selection of the groups used in ROC curves construction proved to be an important tool, aiding in the detection of MOWN and MHO which cannot be identified with WC alone. The resulting WC cutpoints were <91.00 cm for women and <98.00 cm for men. Furthermore, anthropometry is insufficient to determine healthiness, and, biochemical analysis is needed to properly filter subjects during classification. PMID:25945356

  17. Sensitivity and specificity of polymerase chain reaction in Giemsa-stained slides for diagnosis of visceral leishmaniasis in children.

    PubMed

    Brustoloni, Yvone Maia; Lima, Rosimar Batista; da Cunha, Rivaldo Venâncio; Dorval, Maria Elizabeth; Oshiro, Elisa Teruya; de Oliveira, Ana Lúcia Lyrio; Pirmez, Claude

    2007-06-01

    The aim of this study was to evaluate the sensitivity and specificity of polymerase chain reaction (PCR) in the detection of Leishmania DNA in archived Giemsa-stained bone marrow slides for diagnosis of visceral leishmaniasis (VL), and to compare PCR with conventional diagnostic techniques, like direct microscopy and parasite culture. Specimens of archived Giemsa-stained bone marrow slides from 91 patients with VL and from 79 controls with other diseases or conditions were studied. PCR showed the highest sensitivity (92.3%) and had good specificity (97.5%). Direct examination detected 79.1% and culture 59% of positive samples. In addition, PCR was able to detect VL in 16 of 19 patients (84.2%) with negative microscopy. PCR in Giemsa-stained bone marrow slides is a suitable tool for confirming diagnosis in patients with VL and may be useful in the diagnosis of difficult cases. Slide smears are easily stored, do not require special storage conditions such as low temperatures, and can be easily mailed to centers where PCR is available, making it an excellent option for diagnosis in the field.

  18. Development of Species-Specific Ah Receptor-Responsive Third Generation CALUX Cell Lines with Increased Sensitivity and Responsiveness

    PubMed Central

    Brennan, Jennifer C.; He, Guochun; Tsutsumi, Tomoaki; Zhao, Jing; Wirth, Ed; Fulton, Michael H.; Denison, Michael S.

    2016-01-01

    The Ah receptor (AhR)-responsive CALUX (chemically-activated luciferase expression) cell bioassay is commonly used for rapid screening of samples for the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), dioxin-like compounds, and AhR agonists/antagonists. By increasing the number of AhR DNA recognition sites (dioxin responsive elements), we previously generated a novel third generation (G3) recombinant AhR-responsive mouse CALUX cell line (H1L7.5c3) with significantly enhanced sensitivity and response to DLCs compared to existing AhR-CALUX cell bioassays. However, the elevated background luciferase activity of these cells and the absence of comparable G3 cell lines derived from other species have limited their utility for screening purposes. Here, we describe the development and characterization of species-specific G3 recombinant AhR-responsive CALUX cell lines (rat, human, and guinea pig) that exhibit significantly improved sensitivity and dramatically increased TCDD induction response. The low background luciferase activity, low minimal detection limit (0.1 pM TCDD) and enhanced induction response of the rat G3 cell line (H4L7.5c2) over the H1L7.5c3 mouse G3 cells, identifies them as a more optimal cell line for screening purposes. The utility of the new G3 CALUX cell lines were demonstrated by screening sediment extracts and a small chemical compound library for the presence of AhR agonists. The increased sensitivity and response of these new G3 CALUX cell lines will facilitate species-specific analysis of DLCs and AhR agonists in samples with low levels of contamination and/or in small sample volumes. PMID:26366531

  19. Human and rodent carboxylesterases: immunorelatedness, overlapping substrate specificity, differential sensitivity to serine enzyme inhibitors, and tumor-related expression.

    PubMed

    Xie, Mingxing; Yang, Dongfang; Liu, Lan; Xue, Bob; Yan, Bingfang

    2002-05-01

    Carboxylesterases hydrolyze numerous endogenous and foreign compounds with diverse structures. Humans and rodents express multiple forms of carboxylesterases, which share a high degree of sequence identity (approximately 70%). Alignment analyses locate in carboxylesterases several functional subsites such the catalytic triad as seen in acetylcholinesterase. The aim of this study was to determine among human and rodent carboxylesterases the immunorelatedness, overlapping substrate specificity, differential sensitivity to serine enzyme inhibitors, tissue distribution, and tumor-related expression. Six antibodies against whole carboxylesterases or synthetic peptides were tested for their reactivity toward 11 human or rodent recombinant carboxylesterases. The antibodies against whole proteins generally exhibited a broader cross-reactivity than the anti-peptide antibodies. All carboxylesterases hydrolyzed para-nitrophenylacetate and para-nitrophenylbutyrate. However, the relative activity varied markedly from enzyme to enzyme (>20-fold), and some carboxylesterases showed a clear substrate preference. Carboxylesterases with the same functional subsites had a similar profile on substrate specificity and sensitivity toward phenylmethylsulfonyl fluoride (PMSF) and paraoxon, suggesting that these subsites play determinant roles in the recognition of substrates and inhibitors. Among three human carboxylesterases, HCE-1 hydrolyzed both substrates to a similar extent, whereas HCE-2 and HCE-3 showed an opposite substrate preference. All three enzymes were inhibited by PMSF and paraoxon, but they showed a marked difference in relative sensitivities. Based on immunoblotting analyses, HCE-1 was present in all tissues examined, whereas HCE-2 and HCE-3 were expressed in a tissue-restricted pattern. Colon carcinomas expressed slightly higher levels of HCE-1 and HCE-2 than the adjacent normal tissues, whereas the opposite was true with HCE-3.

  20. Sensitive and specific enzyme-linked immunosorbent assay for detecting serum antibodies against Mycobacterium avium subsp. paratuberculosis in fallow deer.

    PubMed

    Prieto, José M; Balseiro, Ana; Casais, Rosa; Abendaño, Naiara; Fitzgerald, Liam E; Garrido, Joseba M; Juste, Ramon A; Alonso-Hearn, Marta

    2014-08-01

    The enzyme-linked immunosorbent assay (ELISA) is the diagnostic test most commonly used in efforts to control paratuberculosis in domestic ruminants. However, commercial ELISAs have not been validated for detecting antibodies against Mycobacterium avium subsp. paratuberculosis in wild animals. In this study, we compared the sensitivities and specificities of five ELISAs using individual serum samples collected from 41 fallow deer with or without histopathological lesions consistent with paratuberculosis. Two target antigenic preparations were selected, an ethanol-treated protoplasmic preparation obtained from a fallow deer M. avium subsp. paratuberculosis isolate (ELISAs A and B) and a paratuberculosis protoplasmic antigen (PPA3) (ELISAs C and D). Fallow deer antibodies bound to the immobilized antigens were detected by using a horseradish peroxidase (HRP)-conjugated anti-fallow deer IgG antibody (ELISAs A and C) or HRP-conjugated protein G (ELISAs B and D). A commercially available assay, ELISA-E, which was designed to detect M. avium subsp. paratuberculosis antibodies in cattle, sheep, and goats, was also tested. Although ELISAs A, C, and E had the same sensitivity (72%), ELISAs A and C were more specific (100%) for detecting fallow deer with lesions consistent with paratuberculosis at necropsy than was the ELISA-E (87.5%). In addition, the ELISA-A was particularly sensitive for detecting fallow deer in the latent stages of infection (62.5%). The antibody responses detected with the ELISA-A correlated with both the severity of enteric lesions and the presence of acid-fast bacteria in gut tissue samples. In summary, our study shows that the ELISA-A can be a cost-effective diagnostic tool for preventing the spread of paratuberculosis among fallow deer populations.

  1. Accuracy of perturbative master equations.

    PubMed

    Fleming, C H; Cummings, N I

    2011-03-01

    We consider open quantum systems with dynamics described by master equations that have perturbative expansions in the system-environment interaction. We show that, contrary to intuition, full-time solutions of order-2n accuracy require an order-(2n+2) master equation. We give two examples of such inaccuracies in the solutions to an order-2n master equation: order-2n inaccuracies in the steady state of the system and order-2n positivity violations. We show how these arise in a specific example for which exact solutions are available. This result has a wide-ranging impact on the validity of coupling (or friction) sensitive results derived from second-order convolutionless, Nakajima-Zwanzig, Redfield, and Born-Markov master equations.

  2. Sensitivity and specificity of the Streptococcus pneumoniae urinary antigen test for unconcentrated urine from adult patients with pneumonia: a meta-analysis.

    PubMed

    Horita, Nobuyuki; Miyazawa, Naoki; Kojima, Ryota; Kimura, Naoko; Inoue, Miyo; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

    2013-11-01

    Studies on the sensitivity and specificity of the Binax Now Streptococcus pneumonia urinary antigen test (index test) show considerable variance of results. Those written in English provided sufficient original data to evaluate the sensitivity and specificity of the index test using unconcentrated urine to identify S. pneumoniae infection in adults with pneumonia. Reference tests were conducted with at least one culture and/or smear. We estimated sensitivity and two specificities. One was the specificity evaluated using only patients with pneumonia of identified other aetiologies ('specificity (other)'). The other was the specificity evaluated based on both patients with pneumonia of unknown aetiology and those with pneumonia of other aetiologies ('specificity (unknown and other)') using a fixed model for meta-analysis. We found 10 articles involving 2315 patients. The analysis of 10 studies involving 399 patients yielded a pooled sensitivity of 0.75 (95% confidence interval: 0.71-0.79) without heterogeneity or publication bias. The analysis of six studies involving 258 patients yielded a pooled specificity (other) of 0.95 (95% confidence interval: 0.92-0.98) without no heterogeneity or publication bias. We attempted to conduct a meta-analysis with the 10 studies involving 1916 patients to estimate specificity (unknown and other), but it remained unclear due to moderate heterogeneity and possible publication bias. In our meta-analysis, sensitivity of the index test was moderate and specificity (other) was high; however, the specificity (unknown and other) remained unclear.

  3. Validation of the FAMACHA© eye colour chart using sensitivity/specificity analysis on two South African sheep farms.

    PubMed

    Reynecke, D P; van Wyk, J A; Gummow, B; Dorny, P; Boomker, J

    2011-05-11

    of the error on Farm 1 was very consistent on average over the entire trial period. The results of this study indicate that (i) persons introduced to the system should not only be trained, but also be evaluated for accuracy of application; (ii) the sensitivity of the FAMACHA(©) diagnostic system should ideally be evaluated at shorter intervals to avoid production losses due to failure to detect anaemic animals which may be at risk of death; (iii) that calibration of the FAMACHA(©) scoring is essential per individual evaluator, and (iv) that animals should be examined at weekly intervals during periods of the highest worm challenge.

  4. Dendritic structure DNA for specific metal ion biosensor based on catalytic hairpin assembly and a sensitive synergistic amplification strategy.

    PubMed

    Zhao, Jianmin; Jing, Pei; Xue, Shuyan; Xu, Wenju

    2017-01-15

    In this work, a sensitive electrochemical biosensing to Pb(2+) was proposed based on the high specificity of DNAzymes to Pb(2+). The response signal was efficiently amplified by the catalytic hairpin assembly induced by strand replacement reaction and the formation of dendritic structure DNA (DSDNA) by layer-by-layer assembly. Firstly, in the presence of Pb(2+), the substrate strand (S1) of the Pb(2+)-specific DNAzymes was specifically cleaved by Pb(2+). Secondly, one of the two fragments (rS1) introduced into the electrode surface was hybridized with a hairpin DNA (H1) and further replaced by another hairpin DNA (H2) by the hybridization reaction of H1 with H2. The released rS1 then induced the next hybridization with H1. After repeated cycles, the catalytic recycling assembly of H2 with H1 was completed. Thirdly, two bioconjugates of Pt@Pd nanocages (Pt@PdNCs) labeled with DNA S3/S4 and electroactive toluidine blue (Tb) (Tb-S3-Pt@PdNCs and Tb-S4-Pt@PdNCs) were captured onto the resultant electrode surface through the hybridization of S3 and H2, S3 and S4, resulting in the formation of DSDNA triggered by layer-by-layer assembly. This formed DSDNA greatly facilitated the immobilization of manganese(III) meso-tetrakis (4-N-methylpyridiniumyl)-porphyrin (MnTMPyP) as mimicking enzyme. Under the synergistic catalysis of Pt@PdNCs and MnTMPyP to H2O2 reduction, the effective signal amplification of the developed Pb(2+) biosensor was achieved. As a result, the sensitive detection of the proposed electrochemical strategy for Pb(2+) was greatly improved in the range of 0.1pM-200nM with a detection limit of 0.033pM.

  5. Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease, an Endemic Osteoarthritis, in China.

    PubMed

    Yu, Fang Fang; Ping, Zhi Guang; Yao, Chong; Wang, Zhi Wen; Wang, Fu Qi; Guo, Xiong

    2017-02-01

    This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity.

  6. Enhancing the prediction accuracy of bovine lameness models through transformations of limb movement variables.

    PubMed

    Liu, J; Neerchal, N K; Tasch, U; Dyer, R M; Rajkondawar, P G

    2009-06-01

    The issue of modeling bovine lameness was explored by testing the hypothesis that B-spline transformation of limb movement variables (LMV) employed in predictive models improved model accuracy. The objectives were to determine the effect of number of B-spline knots and the degree of the underlying polynomial approximation (degree of freedom) on model accuracy. Knot number used in B-spline transformation improved model accuracy by improving model specificity and to a lesser extent model sensitivity. Degree of polynomial approximation had no effect on model predictive accuracy from the data set of 261 cows. Model stability, defined as changes in predictive accuracy associated with the superimposition of perturbations (0.5 and 1.0%) in LMV on the measured data, was explored. Model specificity and to a lesser degree, sensitivity, increased with increased knot number across data set perturbations. Specificity and sensitivity increased by 43 and 11%, respectively, when knot number increased from 0 to 7 for a perturbation level of 0.5%. When the perturbation level was 1%, the corresponding increases in specificity and sensitivity were 32 and 4%, respectively. Nevertheless, different levels of LMV perturbation varied the optimal knot number associated with highest model accuracy. The optimal knot number for 0.5% perturbation was 8, whereas for 1% perturbation the optimal knot number was 7. The B-spline transformation improved specificity and sensitivity of predictive models for lameness, provided the appropriate number of knots was selected.

  7. Accuracy and reliability of GPS devices for measurement of sports-specific movement patterns related to cricket, tennis, and field-based team sports.

    PubMed

    Vickery, William M; Dascombe, Ben J; Baker, John D; Higham, Dean G; Spratford, Wayne A; Duffield, Rob

    2014-06-01

    The aim of this study was to determine the accuracy and reliability of 5, 10, and 15 Hz global positioning system (GPS) devices. Two male subjects (mean ± SD; age, 25.5 ± 0.7 years; height, 1.75 ± 0.01 m; body mass, 74 ± 5.7 kg) completed 10 repetitions of drills replicating movements typical of tennis, cricket, and field-based (football) sports. All movements were completed wearing two 5 and 10 Hz MinimaxX and 2 GPS-Sports 15 Hz GPS devices in a specially designed harness. Criterion movement data for distance and speed were provided from a 22-camera VICON system sampling at 100 Hz. Accuracy was determined using 1-way analysis of variance with Tukey's post hoc tests. Interunit reliability was determined using intraclass correlation (ICC), and typical error was estimated as coefficient of variation (CV). Overall, for the majority of distance and speed measures, as measured using the 5, 10, and 15 Hz GPS devices, were not significantly different (p > 0.05) to the VICON data. Additionally, no improvements in the accuracy or reliability of GPS devices were observed with an increase in the sampling rate. However, the CV for the 5 and 15 Hz devices for distance and speed measures ranged between 3 and 33%, with increasing variability evident in higher speed zones. The majority of ICC measures possessed a low level of interunit reliability (r = -0.35 to 0.39). Based on these results, practitioners of these devices should be aware that measurements of distance and speed may be consistently underestimated, regardless of the movements performed.

  8. Specific repression of mutant K-RAS by 10-23 DNAzyme: Sensitizing cancer cell to anti-cancer therapies

    SciTech Connect

    Yu, S.-H.; Wang, T.-H.; Au, L.-C.

    2009-01-09

    Point mutations of the Ras family are frequently found in human cancers at a prevalence rate of 30%. The most common mutation K-Ras(G12V), required for tumor proliferation, survival, and metastasis due to its constitutively active GTPase activity, has provided an ideal target for cancer therapy. 10-23 DNAzyme, an oligodeoxyribonucleotide-based ribonuclease consisting of a 15-nucleotide catalytical domain flanked by two target-specific complementary arms, has been shown to effectively cleave the target mRNA at purine-pyrimidine dinucleotide. Taking advantage of this specific property, 10-23 DNAzyme was designed to cleave mRNA of K-Ras(G12V)(GGU {yields} GUU) at the GU dinucleotide while left the wild-type (WT) K-Ras mRNA intact. The K-Ras(G12V)-specific 10-23 DNAzyme was able to reduce K-Ras(G12V) at both mRNA and protein levels in SW480 cell carrying homozygous K-Ras(G12V). No effect was observed on the WT K-Ras in HEK cells. Although K-Ras(G12V)-specific DNAzymes alone did not inhibit proliferation of SW480 or HEK cells, pre-treatment of this DNAzyme sensitized the K-Ras(G12V) mutant cells to anti-cancer agents such as doxorubicin and radiation. These results offer a potential of using allele-specific 10-23 DNAzyme in combination with other cancer therapies to achieve better effectiveness on cancer treatment.

  9. Rapid and Sensitive Multiplex Detection of Burkholderia pseudomallei-Specific Antibodies in Melioidosis Patients Based on a Protein Microarray Approach

    PubMed Central

    Kohler, Christian; Dunachie, Susanna J.; Müller, Elke; Kohler, Anne; Jenjaroen, Kemajittra; Teparrukkul, Prapit; Baier, Vico; Ehricht, Ralf; Steinmetz, Ivo

    2016-01-01

    Background The environmental bacterium Burkholderia pseudomallei causes the infectious disease melioidosis with a high case-fatality rate in tropical and subtropical regions. Direct pathogen detection can be difficult, and therefore an indirect serological test which might aid early diagnosis is desirable. However, current tests for antibodies against B. pseudomallei, including the reference indirect haemagglutination assay (IHA), lack sensitivity, specificity and standardization. Consequently, serological tests currently do not play a role in the diagnosis of melioidosis in endemic areas. Recently, a number of promising diagnostic antigens have been identified, but a standardized, easy-to-perform clinical laboratory test for sensitive multiplex detection of antibodies against B. pseudomallei is still lacking. Methods and Principal Findings In this study, we developed and validated a protein microarray which can be used in a standard 96-well format. Our array contains 20 recombinant and purified B. pseudomallei proteins, previously identified as serodiagnostic candidates in melioidosis. In total, we analyzed 196 sera and plasmas from melioidosis patients from northeast Thailand and 210 negative controls from melioidosis-endemic and non-endemic regions. Our protein array clearly discriminated between sera from melioidosis patients and controls with a specificity of 97%. Importantly, the array showed a higher sensitivity than did the IHA in melioidosis patients upon admission (cut-off IHA titer ≥1:160: IHA 57.3%, protein array: 86.7%; p = 0.0001). Testing of sera from single patients at 0, 12 and 52 weeks post-admission revealed that protein antigens induce either a short- or long-term antibody response. Conclusions Our protein array provides a standardized, rapid, easy-to-perform test for the detection of B. pseudomallei-specific antibody patterns. Thus, this system has the potential to improve the serodiagnosis of melioidosis in clinical settings. Moreover, our

  10. High-accuracy imputation for HLA class I and II genes based on high-resolution SNP data of population-specific references.

    PubMed

    Khor, S-S; Yang, W; Kawashima, M; Kamitsuji, S; Zheng, X; Nishida, N; Sawai, H; Toyoda, H; Miyagawa, T; Honda, M; Kamatani, N; Tokunaga, K

    2015-12-01

    Statistical imputation of classical human leukocyte antigen (HLA) alleles is becoming an indispensable tool for fine-mappings of disease association signals from case-control genome-wide association studies. However, most currently available HLA imputation tools are based on European reference populations and are not suitable for direct application to non-European populations. Among the HLA imputation tools, The HIBAG R package is a flexible HLA imputation tool that is equipped with a wide range of population-based classifiers; moreover, HIBAG R enables individual researchers to build custom classifiers. Here, two data sets, each comprising data from healthy Japanese individuals of difference sample sizes, were used to build custom classifiers. HLA imputation accuracy in five HLA classes (HLA-A, HLA-B, HLA-DRB1, HLA-DQB1 and HLA-DPB1) increased from the 82.5-98.8% obtained with the original HIBAG references to 95.2-99.5% with our custom classifiers. A call threshold (CT) of 0.4 is recommended for our Japanese classifiers; in contrast, HIBAG references recommend a CT of 0.5. Finally, our classifiers could be used to identify the risk haplotypes for Japanese narcolepsy with cataplexy, HLA-DRB1*15:01 and HLA-DQB1*06:02, with 100% and 99.7% accuracy, respectively; therefore, these classifiers can be used to supplement the current lack of HLA genotyping data in widely available genome-wide association study data sets.

  11. A selective historical review of congener-specific human tissue measurements as sensitive and specific biomarkers of exposure to dioxins and related compounds.

    PubMed

    Schecter, A

    1998-04-01

    Estimating internal exposure or dose of dioxins and related chemicals such as dibenzofurans and dioxinlike polychlorinated biphenyls is relatively straightforward in laboratory animals because a known dose is given and the amount absorbed can be measured. In wildlife, direct tissue measurement and measurement of environmental samples have both recently been used to estimate exposure. Until recently, human studies used only indirect indicators such as skin lesions to qualitatively estimate exposure to these chlorinated organic compounds. Environmental measurements have also sometimes been used to estimate human exposure. Dioxins in human tissue were not measured until the 1970s, when 2,3,7,8-tetrachlorodibenzo-p-dioxin was measured in mothers' milk; congener-specific measurement of dioxins and dibenzofurans in tissues (blood, milk, and adipose tissue) of the general population and exposed workers was first performed in the United States in the 1980s. Measurement in a sensitive and specific fashion of the 17 toxic dioxin and dibenzofuran congeners currently found in human tissue from industrial countries began in the 1980s. The use of known chemical standards, capillary columns, high resolution gas chromatography and mass spectrometry (GC-MS) has now become relatively common. GC-MS analysis of blood is currently accepted as the gold standard for estimating human exposure to dioxins. However, analyses are still costly and time consuming, and worldwide there are few qualified laboratories. There is currently a lack of knowledge concerning kinetics at higher and lower exposure levels for most of the toxic dioxin congeners and of levels in target tissues of concern.

  12. A selective historical review of congener-specific human tissue measurements as sensitive and specific biomarkers of exposure to dioxins and related compounds.

    PubMed Central

    Schecter, A

    1998-01-01

    Estimating internal exposure or dose of dioxins and related chemicals such as dibenzofurans and dioxinlike polychlorinated biphenyls is relatively straightforward in laboratory animals because a known dose is given and the amount absorbed can be measured. In wildlife, direct tissue measurement and measurement of environmental samples have both recently been used to estimate exposure. Until recently, human studies used only indirect indicators such as skin lesions to qualitatively estimate exposure to these chlorinated organic compounds. Environmental measurements have also sometimes been used to estimate human exposure. Dioxins in human tissue were not measured until the 1970s, when 2,3,7,8-tetrachlorodibenzo-p-dioxin was measured in mothers' milk; congener-specific measurement of dioxins and dibenzofurans in tissues (blood, milk, and adipose tissue) of the general population and exposed workers was first performed in the United States in the 1980s. Measurement in a sensitive and specific fashion of the 17 toxic dioxin and dibenzofuran congeners currently found in human tissue from industrial countries began in the 1980s. The use of known chemical standards, capillary columns, high resolution gas chromatography and mass spectrometry (GC-MS) has now become relatively common. GC-MS analysis of blood is currently accepted as the gold standard for estimating human exposure to dioxins. However, analyses are still costly and time consuming, and worldwide there are few qualified laboratories. There is currently a lack of knowledge concerning kinetics at higher and lower exposure levels for most of the toxic dioxin congeners and of levels in target tissues of concern. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9599725

  13. Production of dumbbell probe through hairpin cleavage-ligation and increasing RCA sensitivity and specificity by circle to circle amplification

    PubMed Central

    Wei, Hua; Tang, Suming; Hu, Tianyu; Zhao, Guojie; Guan, Yifu

    2016-01-01

    Dumbbell probe (DP) attracts increasing interests in rolling circle amplification (RCA). A universal DP production method through cleavage-ligation of hairpin was proposed and optimized. The production is characterized by restriction endonuclease (RE)-induced cleavage ends ligation. It has the advantage of phosphorylation-free, splint-free and purification-free. To optimize designing, we found that the position of RE cleavage sequence in the stem and the primer position in the loop affected the formation and amplification of DP obviously. Both sticky and blunt ends cleaved by RE produce DP efficiently. Moreover, we introduced this DP into circle to circle (C2C) RCA based on the same cleavage-ligation principle, and acquired high sensitivity. By combining a two-ligation design and the C2C strategy, specificity for detecting let-7 family members was increased extremely. Furthermore, coreaction of different steps facilitated convenient formation and amplification process of DP. PMID:27385060

  14. High Sensitivity and High Detection Specificity of Gold-Nanoparticle-Grafted Nanostructured Silicon Mass Spectrometry for Glucose Analysis.

    PubMed

    Tsao, Chia-Wen; Yang, Zhi-Jie

    2015-10-14

    Desorption/ionization on silicon (DIOS) is a high-performance matrix-free mass spectrometry (MS) analysis method that involves using silicon nanostructures as a matrix for MS desorption/ionization. In this study, gold nanoparticles grafted onto a nanostructured silicon (AuNPs-nSi) surface were demonstrated as a DIOS-MS analysis approach with high sensitivity and high detection specificity for glucose detection. A glucose sample deposited on the AuNPs-nSi surface was directly catalyzed to negatively charged gluconic acid molecules on a single AuNPs-nSi chip for MS analysis. The AuNPs-nSi surface was fabricated using two electroless deposition steps and one electroless etching step. The effects of the electroless fabrication parameters on the glucose detection efficiency were evaluated. Practical application of AuNPs-nSi MS glucose analysis in urine samples was also demonstrated in this study.

  15. A sensitive and specific assay for superoxide anion released by neutrophils or macrophages based on bioluminescence of polynoidin.

    PubMed

    Colepicolo, P; Camarero, V C; Nicolas, M T; Bassot, J M; Karnovsky, M L; Hastings, J W

    1990-02-01

    Using the luminescent protein polynoidin, present in the bioluminescent system isolated from the marine annelid Harmothoe lunulata, we have developed a new method to measure, specifically, superoxide anion (O2-) released by macrophages or neutrophils. A small quantity of an aqueous crude extract of polynoidin is used to detect O2- released by stimulated cells. Light emission is linearly dependent on the number of cells over a wide range (10(3) to 10(7) cells), and the assay is thus more sensitive than either luminol or ferricytochrome c reduction. Luminescence is enhanced 20% by mannitol, 80% by catalase, and is totally quenched by superoxide dismutase. For the same number of cells, neutrophils showed a threefold higher release of O2- and a twofold faster first-order light decay than stimulated macrophages, in accordance with data obtained by other methods.

  16. A better confidence interval for the sensitivity at a fixed level of specificity for diagnostic tests with continuous endpoints.

    PubMed

    Shan, Guogen

    2017-02-01

    For a diagnostic test with continuous measurement, it is often important to construct confidence intervals for the sensitivity at a fixed level of specificity. Bootstrap-based confidence intervals were shown to have good performance as compared to others, and the one by Zhou and Qin (2005) was recommended as the best existing confidence interval, named the BTII interval. We propose two new confidence intervals based on the profile variance method and conduct extensive simulation studies to compare the proposed intervals and the BTII intervals under a wide range of conditions. An example from a medical study on severe head trauma is used to illustrate application of the new intervals. The new proposed intervals generally have better performance than the BTII interval.

  17. Suitability of digoxin as a P-glycoprotein probe: implications of other transporters on sensitivity and specificity.

    PubMed

    Nader, Ahmed M; Foster, David R

    2014-01-01

    The study of transporter-mediated drug-drug interactions (DDI) requires use of appropriate probes to reflect transporter function. Digoxin is often used as a probe in DDI studies involving P-glycoprotein (P-gp) and is recommended by FDA for this purpose, despite several lingering questions regarding suitability of digoxin as P-gp probe. This review aims to critically evaluate use of digoxin as a probe for P-gp-mediated clinical DDI studies, with focus on sensitivity and specificity of digoxin for P-gp. Although previous reviews have evaluated digoxin transport by P-gp, the purpose of the current review is to critically evaluate such literature in light of newly evolving literature suggesting digoxin transport by non-P-gp transporters.

  18. Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS.

    PubMed

    Momen-Heravi, Fatemeh; Bala, Shashi; Kodys, Karen; Szabo, Gyongyi

    2015-05-14

    Hepatocyte damage and inflammation in monocytes/macrophages are central to the pathogenesis of alcoholic hepatitis (AH). MicroRNAs (miRNAs) regulate all of these processes. MiRNA-122 is abundantly expressed in hepatocytes while monocytes/macrophages have low levels. The role of exosomes in AH and possible cross talk between hepatocyte-derived exosomes and immune cells is not explored yet. Here, we show that the number of exosomes significantly increases in the sera of healthy individuals after alcohol binge drinking and in mice after binge or chronic alcohol consumption. Exosomes isolated from sera after alcohol consumption or from in vitro ethanol-treated hepatocytes contained miRNA-122. Exosomes derived from ethanol-treated Huh7.5 cells were taken up by the recipients THP1 monocytes and horizontally transferred a mature form of liver-specific miRNA-122. In vivo, liver mononuclear cells and Kupffer cells from alcohol-fed mice had increased miRNA-122 levels. In monocytes, miRNA-122 transferred via exosomes inhibited the HO-1 pathway and sensitized to LPS stimulation and increased levels of pro-inflammatory cytokines. Finally, inflammatory effects of exosomes from ethanol-treated hepatocytes were prevented by using RNA interference via exosome-mediated delivery of a miRNA-122 inhibitor. These results demonstrate that first, exosomes mediate communication between hepatocytes and monocytes/macrophages and second, hepatocyte-derived miRNA-122 can reprogram monocytes inducing sensitization to LPS.

  19. Tympanometry in Infants: A Study of the Sensitivity and Specificity of 226-Hz and 1,000-Hz Probe Tones

    PubMed Central

    Carmo, Michele Picanço; Costa, Nayara Thais de Oliveira; Momensohn-Santos, Teresa Maria

    2013-01-01

    Introduction For infants under 6 months, the literature recommends 1,000-Hz tympanometry, which has a greater sensitivity for the correct identification of middle ear disorders in this population. Objective To systematically analyze national and international publications found in electronic databases that used tympanometry with 226-Hz and 1,000-Hz probe tones. Data Synthesis Initially, we identified 36 articles in the SciELO database, 11 in the Latin American and Caribbean Literature on the Health Sciences (LILACS) database, 199 in MEDLINE, 0 in the Cochrane database, 16 in ISI Web of Knowledge, and 185 in the Scopus database. We excluded 433 articles because they did not fit the selection criteria, leaving 14 publications that were analyzed in their entirety. Conclusions The 1,000-Hz tone test has greater sensitivity and specificity for the correct identification of tympanometric curve changes. However, it is necessary to clarify the doubts that still exist regarding the use of this test frequency. Improved methods for rating curves, standardization of normality criteria, and the types of curves found in infants should be addressed. PMID:25992044

  20. Design of Peptide Substrate for Sensitively and Specifically Detecting Two Aβ-Degrading Enzymes: Neprilysin and Angiotensin-Converting Enzyme.

    PubMed

    Chen, Po-Ting; Chen, Chao-Long; Lin, Lilian Tsai-Wei; Lo, Chun-Hsien; Hu, Chaur-Jong; Chen, Rita P-Y; Wang, Steven S-S

    2016-01-01

    Upregulation of neprilysin (NEP) to reduce Aβ accumulation in the brain is a promising strategy for the prevention of Alzheimer's disease (AD). This report describes the design and synthesis of a quenched fluorogenic peptide substrate qf-Aβ(12-16)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus. This peptide emitted strong fluorescence upon cleavage. Our results showed that qf-Aβ(12-16)AAC is more sensitive to NEP than the previously reported peptide substrates, so that concentrations of NEP as low as 0.03 nM could be detected at peptide concentration of 2 μM. Moreover, qf-Aβ(12-16)AAC had superior enzymatic specificity for both NEP and angiotensin-converting enzyme (ACE), but was inert with other Aβ-degrading enzymes. This peptide, used in conjunction with a previously reported peptide substrate qf-Aβ(1-7)C [which is sensitive to NEP and insulin-degrading enzyme (IDE)], could be used for high-throughput screening of compounds that only upregulate NEP. The experimental results of cell-based activity assays using both qf-Aβ(1-7)C and qf-Aβ(12-16)AAC as the substrates confirm that somatostatin treatment most likely upregulates IDE, but not NEP, in neuroblastoma cells.

  1. Design of Peptide Substrate for Sensitively and Specifically Detecting Two Aβ-Degrading Enzymes: Neprilysin and Angiotensin-Converting Enzyme

    PubMed Central

    Chen, Po-Ting; Chen, Chao-Long; Lin, Lilian Tsai-Wei; Lo, Chun-Hsien; Hu, Chaur-Jong; Chen, Rita P.-Y.; Wang, Steven S.-S.

    2016-01-01

    Upregulation of neprilysin (NEP) to reduce Aβ accumulation in the brain is a promising strategy for the prevention of Alzheimer’s disease (AD). This report describes the design and synthesis of a quenched fluorogenic peptide substrate qf-Aβ(12–16)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus. This peptide emitted strong fluorescence upon cleavage. Our results showed that qf-Aβ(12–16)AAC is more sensitive to NEP than the previously reported peptide substrates, so that concentrations of NEP as low as 0.03 nM could be detected at peptide concentration of 2 μM. Moreover, qf-Aβ(12–16)AAC had superior enzymatic specificity for both NEP and angiotensin-converting enzyme (ACE), but was inert with other Aβ-degrading enzymes. This peptide, used in conjunction with a previously reported peptide substrate qf-Aβ(1–7)C [which is sensitive to NEP and insulin-degrading enzyme (IDE)], could be used for high-throughput screening of compounds that only upregulate NEP. The experimental results of cell-based activity assays using both qf-Aβ(1–7)C and qf-Aβ(12–16)AAC as the substrates confirm that somatostatin treatment most likely upregulates IDE, but not NEP, in neuroblastoma cells. PMID:27096746

  2. L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition.

    PubMed

    Antonescu, Cristina R; Busam, Klaus J; Francone, Todd D; Wong, Grace C; Guo, Tianhua; Agaram, Narasimhan P; Besmer, Peter; Jungbluth, Achim; Gimbel, Mark; Chen, Chin-Tung; Veach, Darren; Clarkson, Bayard D; Paty, Philip B; Weiser, Martin R

    2007-07-15

    Activating mutations in either BRAF or NRAS are seen in a significant number of malignant melanomas, but their incidence appears to be dependent to ultraviolet light exposure. Thus, BRAF mutations have the highest incidence in non-chronic sun damaged (CSD), and are uncommon in acral, mucosal and CSD melanomas. More recently, activating KIT mutations have been described in rare cases of metastatic melanoma, without further reference to their clinical phenotypes. This finding is intriguing since KIT expression is downregulated in most melanomas progressing to more aggressive lesions. In this study, we investigated a group of anal melanomas for the presence of BRAF, NRAS, KIT and PDGFRA mutations. A heterozygous KIT exon 11 L576P substitution was identified in 3 of 20 cases tested. The 3 KIT mutation-carrying tumors were strongly immunopositive for KIT protein. No KIT mutations were identified in tumors with less than 4+ KIT immunostaining. NRAS mutation was identified in one tumor. No BRAF or PDGFRA mutations were identified in either KIT positive or negative anal melanomas. In vitro drug testing of stable transformant Ba/F3 KIT(L576P) mutant cells showed sensitivity for dasatinib (previously known as BMS-354825), a dual SRC/ABL kinase inhibitor, and imatinib. However, compared to an imatinib-sensitive KIT mutant, dasatinib was potent at lower doses than imatinib in the KIT(L576P) mutant. These results suggest that a subset of anal melanomas show activating KIT mutations, which are susceptible for therapy with specific kinase inhibitors.

  3. Low molecular-weight chitosan as a pH-sensitive stealth coating for tumor-specific drug delivery

    PubMed Central

    Amoozgar, Zohreh; Park, Joonyoung; Lin, Qingnuo; Yeo, Yoon

    2012-01-01

    When a nanoparticle is developed for systemic application, its surface is typically protected by polyethylene glycol (PEG) to help their prolonged circulation and evasion of immune clearance. On the other hand, PEG can interfere with interactions between nanocarriers and target cells and negatively influence the therapeutic outcomes. To overcome this challenge, we propose low molecular-weight chitosan (LMWC) as an alternative surface coating, which can protect the nanomedicine in neutral pH but allow cellular interactions in weakly acidic pH of tumors. LMWCs with a molecular weight of 2–4 kDa, 4–6.5 kDa, and 11–22 kDa were produced by hydrogen peroxide digestion and covalently conjugated with poly(lactic-co-glycolic acid) (PLGA). Nanoparticles created with PLGA-LMWC conjugates showed pH-sensitive cell interactions, which enabled specific drug delivery to cells in a weakly acidic environment. The hydrophilic LMWC layer reduced opsonization and phagocytic uptake. These properties qualify LMWCs as a promising biomaterial for pH-sensitive stealth coating. PMID:22489704

  4. Sensitivity and specificity of a nested polymerase chain reaction for detection of lentivirus infection in lions (Panthera leo).

    PubMed

    Adams, Hayley; van Vuuren, Moritz; Kania, Stephen; Bosman, Anna-Mari; Keet, Dewald; New, John; Kennedy, Melissa

    2010-12-01

    Feline immunodeficiency virus (FIV) is a lentivirus in the Retroviridae family that causes lifelong infection in domestic cats. The lentivirus of African lions (Panthera leo), referred to as FIVple, is endemic in certain lion populations in eastern and southern Africa. Lentivirus infection leads to immunologic dysfunction and immunosuppressive disease in domestic cats; however, little is known about the pathogenic effects of infection in lions, nor about the epidemiologic impact on free-ranging and captive populations. Whole blood and serum samples were collected opportunistically from free-ranging lions in Kruger National Park, Republic of South Africa (RSA). Whole blood and serum samples were also collected from captive wild lions in the RSA. A nested polymerase chain reaction (PCR) assay for detection of FIV was performed on all whole blood samples. In addition, serum samples were tested for cross-reactive antibodies to domestic feline lentivirus antigens and puma lentivirus synthetic envelope peptide antigen. The PCR assay successfully amplified the lion lentivirus from African lions. The relative sensitivity and relative specificity were 79% and 100%, respectively, and the positive and negative predictive values were 100% and 67%, respectively. This research represents the first study to compare genetic material with antibody-based methods of lentivirus detection on lions in RSA. Using PCR as an additional diagnostic test for FIV in lions will increase screening sensitivity and will allow viral characterization among circulating isolates and monitoring of changes in the viral epidemiology within geographic regions and populations over time.

  5. Regional specification of threshold sensitivity and response time in CBA/CaJ mouse spiral ganglion neurons.

    PubMed

    Liu, Qing; Davis, Robin L

    2007-10-01

    Previous studies of spiral ganglion neuron electrophysiology have shown that specific parameters differ according to cochlear location, with apical neurons being distinctly different from basal neurons. To align these features more precisely along the tonotopic axis of the cochlea, we developed a novel spiral ganglion culture system in which positional information is retained. Patch-clamp recordings made from neurons of known gangliotopic location revealed two basic firing pattern distributions. Membrane characteristics related to spike timing, such as accommodation, latency and onset tau, were distinctly heterogeneous, yet when averaged, they were distributed in a graded manner along the length of the cochlea. Action potential threshold levels also displayed a wide range, the averages of which were distributed nonmonotonically such that neurons with the greatest sensitivity were localized to the mid-regions of the ganglion. These studies shed new light on the complexity and sophistication of the intrinsic firing features of spiral ganglion neurons. Because timing-related elements are organized in an overall tonotopic manner, it is hypothesized that they contribute to aspects of frequency-dependent acoustic processing. On the other hand, the different distribution of threshold levels, with the greatest sensitivity in the middle region of the tonotopic map, suggests that this neuronal parameter is regulated differently and thus may contribute a distinct realm of auditory sensory processing.

  6. Helicobacter pylori FliD protein is a highly sensitive and specific marker for serologic diagnosis of H. pylori infection.

    PubMed

    Khalifeh Gholi, Mohammad; Kalali, Behnam; Formichella, Luca; Göttner, Gereon; Shamsipour, Fereshteh; Zarnani, Amir Hassan; Hosseini, Mostafa; Busch, Dirk H; Shirazi, Mohammad Hasan; Gerhard, Markus

    2013-12-01

    Screening for H. pylori in large populations continues to be a challenging task, since available tests have limited sensitivity and specificity, which, in population-based approaches, leads to significant numbers of false positive and false negative results. Various H. pylori proteins associated with virulence are highly immunogenic and therefore candidates to detect the infection. There are currently no defined markers that are recognized in all H. pylori infected patients and that do not show cross-reactivity with other bacterial proteins. We identified the H. pylori "hook-associated protein 2 homologue", FliD (UniProtKB/Swiss-Prot: P96786.4) as a novel marker of infection for serological analysis. The H. pylori FliD protein is an essential element in the assembly of the functional flagella. However, this virulence factor has not yet been tested as a diagnostic marker in serology. For this purpose FliD was recombinantly expressed in E. coli, purified by affinity chromatography and gel filtration and used to coat ELISA plates or immobilized on nitrocellulose stripes. To evaluate its antigenicity we screened a defined panel of patient sera. The recombinant H. pylori FliD protein reacted with a high percentage of human sera. Among 318 samples reported positive by histology, 310 (97.4%) were tested positive by FliD Line assay, and 165 out of 170 samples were tested positive by ELISA (97%). We could also reconfirm 297 out of 300 (99%) negative sera by Line assay and 73 from 76 (96%) by ELISA. Taken together, application of FliD in serological diagnosis of H. pylori infection presents a high specificity of up to 99% and a sensitivity of up to 97%. This makes especially the FliD ELISA a simple, cost effective and highly efficient tool to detect H. pylori infection in developing countries where prevalence is high and other screening methods are either not available or are unaffordable.

  7. Calcium and phosphor intake in preterm infants: sensitivity and specifity of 6-hour urine samples to detect deficiency.

    PubMed

    Mihatsch, W; Trotter, A; Pohlandt, F

    2012-03-01

    Aim of the present study was to test whether six-hour (6 h) urine specimens predict the 24-hour (24 h) mineral homeostasis in individual infants born preterm. Urinary Calcium (Ca) and Phosphate (P) concentrations were studied in 60 stable infants; gestational age 34 (25-42) weeks. In 58 infants four 6 h urine specimens and in 2 infants all spot urine specimens obtained within 24 h were analyzed. In 39 infants born preterm coefficients of variation were 0.42 (SD 0.26) and 0.41 (SD 0.26) for Ca and P measurements in the four 6 h urine specimens obtained within 24 h, respectively, The mineral homeostasis of the infants was defined as Ca or P surplus homeostasis if the 24 h urinary concentrations were ≥1 mmol/l. The sensitivity, specificity, and PPV of a 6 h urinary specimen to predict Ca deficiency homeostasis (24 h urinary Ca <1 mmol/l) were 0.93 (0.77-0.98; 95%CI), 0.72 (0.43-0.90) and 0.90 (0.74-0.96). The sensitivity, specificity and PPV for urinary P were 0.8 (0.38-0.96), 0.97 (0.85-0.995), and 0.8 (0.38-0.96). In conclusion, in infants born preterm on regular 3 or 4 h feedings, 6 h urine sampling is sufficiently precise for prediction of Ca and P mineral deficiency homeostasis (PPV 0.92 and 0.83). However, measurements at regular intervals (twice weekly) are recommended not to miss any infant in mineral deficiency homeostasis.

  8. Immunohistochemistry is highly sensitive and specific for detecting the BRAF V600E mutation in papillary thyroid carcinoma.

    PubMed

    Sun, Jian; Zhang, Jing; Lu, Junliang; Gao, Jie; Lu, Tao; Ren, Xinyu; Duan, Huanli; Liang, Zhiyong

    2015-01-01

    The V600E mutation in the B-type Raf kinase (BRAF) gene is a common genetic change in cases of papillary thyroid carcinoma (PTC) that appears to play a key role in the development and progression of this disease. We sought to assess the sensitivity and specificity of immunohistochemical detection of this mutation with a V600E mutated BRAF antibody in a Chinese PTC cohort. In this study, we used fully automated immunohistochemistry (IHC) assay with a BRAF V600E (VE1) mouse monoclonal primary antibody to screen for the BRAF V600E mutation in 556 cases of PTC. Moreover, to verify the IHC staining results, real-time PCR was applied to detect this mutation in the same patient cohort. Among the 556 cases in the examined primary PTC cohort, 414 (74.5%) cases and 419 (75.4%) cases were positive for the BRAF V600E mutation by IHC staining and by real-time PCR, respectively. The real-time PCR results indicated that the sensitivity and specificity of IHC staining for the BRAF V600E mutation were 98.8% and 100%, respectively. The BRAF V600E mutation was common among Chinese patients with primary PTC, and was strongly correlated with older patient age and the conventional subtype of PTC but was not associated with parameters of clinicopathological aggressiveness. The fully automated IHC is a reliable technique that can serve as an alternative to molecular biological approaches for the routine detection of the BRAF V600E mutation in PTC patients.

  9. Sex-Specific Differences in Agonistic Behaviour, Sound Production and Auditory Sensitivity in the Callichthyid Armoured Catfish Megalechis thoracata

    PubMed Central

    Hadjiaghai, Oliwia; Ladich, Friedrich

    2015-01-01

    Background Data on sex-specific differences in sound production, acoustic behaviour and hearing abilities in fishes are rare. Representatives of numerous catfish families are known to produce sounds in agonistic contexts (intraspecific aggression and interspecific disturbance situations) using their pectoral fins. The present study investigates differences in agonistic behaviour, sound production and hearing abilities in males and females of a callichthyid catfish. Methodology/Principal Findings Eight males and nine females of the armoured catfish Megalechis thoracata were investigated. Agonistic behaviour displayed during male-male and female-female dyadic contests and sounds emitted were recorded, sound characteristics analysed and hearing thresholds measured using the auditory evoked potential (AEP) recording technique. Male pectoral spines were on average 1.7-fold longer than those of same-sized females. Visual and acoustic threat displays differed between sexes. Males produced low-frequency harmonic barks at longer distances and thumps at close distances, whereas females emitted broad-band pulsed crackles when close to each other. Female aggressive sounds were significantly shorter than those of males (167 ms versus 219 to 240 ms) and of higher dominant frequency (562 Hz versus 132 to 403 Hz). Sound duration and sound level were positively correlated with body and pectoral spine length, but dominant frequency was inversely correlated only to spine length. Both sexes showed a similar U-shaped hearing curve with lowest thresholds between 0.2 and 1 kHz and a drop in sensitivity above 1 kHz. The main energies of sounds were located at the most sensitive frequencies. Conclusions/Significance Current data demonstrate that both male and female M. thoracata produce aggressive sounds, but the behavioural contexts and sound characteristics differ between sexes. Sexes do not differ in hearing, but it remains to be clarified if this is a general pattern among fish. This

  10. A breast-specific, negligible-dose scatter correction technique for dedicated cone-beam breast CT: a physics-based approach to improve Hounsfield Unit accuracy

    NASA Astrophysics Data System (ADS)

    Yang, Kai; Burkett, George, Jr.; Boone, John M.

    2014-11-01

    The purpose of this research was to develop a method to correct the cupping artifact caused from x-ray scattering and to achieve consistent Hounsfield Unit (HU) values of breast tissues for a dedicated breast CT (bCT) system. The use of a beam passing array (BPA) composed of parallel-holes has been previously proposed for scatter correction in various imaging applications. In this study, we first verified the efficacy and accuracy using BPA to measure the scatter signal on a cone-beam bCT system. A systematic scatter correction approach was then developed by modeling the scatter-to-primary ratio (SPR) in projection images acquired with and without BPA. To quantitatively evaluate the improved accuracy of HU values, different breast tissue-equivalent phantoms were scanned and radially averaged HU profiles through reconstructed planes were evaluated. The dependency of the correction method on object size and number of projections was studied. A simplified application of the proposed method on five clinical patient scans was performed to demonstrate efficacy. For the typical 10-18 cm breast diameters seen in the bCT application, the proposed method can effectively correct for the cupping artifact and reduce the variation of HU values of breast equivalent material from 150 to 40 HU. The measured HU values of 100% glandular tissue, 50/50 glandular/adipose tissue, and 100% adipose tissue were approximately 46, -35, and -94, respectively. It was found that only six BPA projections were necessary to accurately implement this method, and the additional dose requirement is less than 1% of the exam dose. The proposed method can effectively correct for the cupping artifact caused from x-ray scattering and retain consistent HU values of breast tissues.

  11. Sensitivity to Spatiotemporal Percepts Predicts the Perception of Emotion

    PubMed Central

    Castro, Vanessa L.; Boone, R. Thomas

    2015-01-01

    The present studies examined how sensitivity to spatiotemporal percepts such as rhythm, angularity, configuration, and force predicts accuracy in perceiving emotion. In Study 1, participants (N = 99) completed a nonverbal test battery consisting of three nonverbal emotion perception tests and two perceptual sensitivity tasks assessing rhythm sensitivity and angularity sensitivity. Study 2 (N = 101) extended the findings of Study 1 with the addition of a fourth nonverbal test, a third configural sensitivity task, and a fourth force sensitivity task. Regression analyses across both studies revealed partial support for the association between perceptual sensitivity to spatiotemporal percepts and greater emotion perception accuracy. Results indicate that accuracy in perceiving emotions may be predicted by sensitivity to specific percepts embedded within channel- and emotion-specific displays. The significance of such research lies in the understanding of how individuals acquire emotion perception skill and the processes by which distinct features of percepts are related to the perception of emotion. PMID:26339111

  12. Activity and substrate specificity of pyrimidine phosphorylases and their role in fluoropyrimidine sensitivity in colon cancer cell lines.

    PubMed

    Temmink, Olaf H; de Bruin, Michiel; Turksma, Annelies W; Cricca, Silvia; Laan, Adrie C; Peters, Godefridus J

    2007-01-01

    Thymidine phosphorylase (TP) and uridine phosphorylase (UP) are often upregulated in solid tumors and catalyze the phosphorolysis of natural (deoxy)nucleosides and a wide variety of fluorinated pyrimidine nucleosides. Because the relative contribution of each of the two enzymes to these reactions is still largely unknown, we investigated the substrate specificity of TP and UP in colon cancer cells for the (fluoro)pyrimidine nucleosides thymidine (TdR), uridine (Urd), 5'-deoxy-5-fluorouridine (5'DFUR), and 5FU. Specific inhibitors of TP (TPI) and UP (BAU) were used to determine the contribution of each enzyme in relation to their cytotoxic effect. The high TP expressing Colo320TP1 cells were most sensitive to 5'DFUR and 5FU, with IC50 values of 1.4 and 0.2 microM, respectively, while SW948 and SW1398 were insensitive to 5'DFUR (IC50>150 microM for 5'DFUR). TPI and BAU only moderately affected sensitivity of Colo320, SW948, and SW1398, whereas TPI significantly increased IC(50) for 5'DFUR (50-fold) and 5FU (11-fold) in Colo320TP1 and BAU that in C26A (9-fold for 5'DFUR; p<0.01). In the epithelial skin cell line HaCaT both inhibitors were able to decrease sensitivity to 5'DFUR and 5FU separately. HaCaT might be a model for 5'DFUR toxicity. In the colon cancer cells 5'DFUR degradation varied from 0.4 to 50 nmol 5FU/h/10(6)cells, that of TdR from 0.3 to 103 nmol thymine/h/10(6)cells, that of Urd from 0.8 to 79 nmol uracil/h/10(6)cells, while conversion of 5FU to FUrd was from 0.3 to 46 nmol/h/10(6)cells. SW948 and SW1398 were about equally sensitive to 5'DFUR and 5FU, but SW1398 had higher phosphorylase activity (>65-fold) compared to SW948. In SW948 and HaCaT TPI and BAU inhibited TdR and Urd phosphorolysis (>80%), respectively. Both TP and UP contributed to the phosphorolysis of 5'DFUR and 5FU. In the presence of both inhibitors, still phosphorolysis of 5FU (>40%) was detected in the tumor and HaCaT cell lines, and remarkably, that of all four substrates in SW1398

  13. Testing of the Bio-Seeq (Smiths Detection Handheld PCR Instrument): Sensitivity, Specificity, and Effect of Interferents on Yersinia Pestis Assay Performance

    DTIC Science & Technology

    2005-04-01

    HANDHELD PCR INSTRUMENT): SENSITIVITY, SPECIFICITY, AND EFFECT OF INTERFERENTS ON YERSINIA PESTIS ASSAY PERFORMANCE Kevin P. O’Connell Patricia E...Bio-Seeq® (Smiths Detection Handheld PCR Instrument): Sensitivity, Specificity, and Effect of Interferents on Yersinia pestis Assay 5b. GRANT NUMBER...DIR, ECBC, ATTN: AMSRD-ECB- RT -BM, APG, MD 21010-5424 NUMBER ECBC-TR-437 9. SPONSORING I MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSORIMONITOR’S

  14. Sensitive and specific modified Hodge test for KPC and metallo-beta- lactamase detection in Pseudomonas aeruginosa by use of a novel indicator strain, Klebsiella pneumoniae ATCC 700603.

    PubMed

    Pasteran, Fernando; Veliz, Omar; Rapoport, Melina; Guerriero, Leonor; Corso, Alejandra

    2011-12-01

    We evaluated the ability of the modified Hodge test to discriminate between KPC- and metallo-beta-lactamase (MBL)-producing Pseudomonas aeruginosa isolates and carbapenemase nonproducers. With Escherichia coli ATCC 25922 as the indicator strain, the MHT resulted in low sensitivity, specificity, and repeatability. Replacing the indicator strain with Klebsiella pneumoniae ATCC 700603 led to an improved performance (100%, 97%, 0%, and 100% sensitivity, specificity, indeterminate results and repeatability, respectively).

  15. Enterocyte-specific A20 deficiency sensitizes to tumor necrosis factor–induced toxicity and experimental colitis

    PubMed Central

    Vereecke, Lars; Sze, Mozes; Guire, Conor Mc; Rogiers, Brecht; Chu, Yuanyuan; Schmidt-Supprian, Marc; Pasparakis, Manolis

    2010-01-01

    A20 is a nuclear factor κB (NF-κB) target gene that encodes a ubiquitin-editing enzyme that is essential for the termination of NF-κB activation after tumor necrosis factor (TNF) or microbial product stimulation and for the prevention of TNF-induced apoptosis. Mice lacking A20 succumb to inflammation in several organs, including the intestine, and A20 mutations have been associated with Crohn’s disease. However, ablation of NF-κB activity, specifically in intestinal epithelial cells (IECs), promotes intestinal inflammation. As A20 deficiency sensitizes cells to TNF-induced apoptosis yet also promotes NF-κB activity, it is not clear if A20 deficiency in IECs would exacerbate or ameliorate intestinal inflammation. We generated mice lacking A20 specifically in IECs. These mice did not show spontaneous intestinal inflammation but exhibited increased susceptibility to experimental colitis, and their IECs were hypersensitive to TNF-induced apoptosis. The resulting TNF-driven breakdown of the intestinal barrier permitted commensal bacterial infiltration and led to systemic inflammation. These studies define A20 as a major antiapoptotic protein in the intestinal epithelium and further indicate that defects in A20 might contribute to inflammatory bowel disease in humans. PMID:20530205

  16. Silicon nanowire-based molecular beacons for high-sensitivity and sequence-specific DNA multiplexed analysis.

    PubMed

    Su, Shao; Wei, Xinpan; Zhong, Yiling; Guo, Yuanyuan; Su, Yuanyuan; Huang, Qing; Lee, Shuit-Tong; Fan, Chunhai; He, Yao

    2012-03-27

    Nanomaterial-based molecular beacons (nanoMBs) have been extensively explored due to unique merits of nanostructures, including gold nanoparticle (AuNP)-, carbon nanotube (CNT)-, and graphene-based nanoMBs. Those nanoMBs are well-studied; however, they possess relatively poor salt stability or low specificity, limiting their wide applications. Here, we present a novel kind of multicolor silicon-based nanoMBs by using AuNP-decorated silicon nanowires as high-performance quenchers. Significantly, the nanoMBs feature robust stability in high-concentration (0.1 M) salt solution and wide-ranging temperature (10-80 °C), high quenching efficiency (>90%) for various fluorophores (e.g., FAM, Cy5, and ROX), and large surfaces for simultaneous assembly of different DNA strands. We further show that silicon-based nanoMBs are highly effective for sensitive and specific multidetection of DNA targets. The unprecedented advantages of silicon-based multicolor nanoMBs would bring new opportunities for challenging bioapplications, such as allele discrimination, early cancer diagnosis, and molecular engineering, etc.

  17. Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification.

    PubMed

    Liu, Ling; Liu, Xu; Ren, Xudong; Tian, Yue; Chen, Zhenyu; Xu, Xiangjie; Du, Yanhua; Jiang, Cizhong; Fang, Yujiang; Liu, Zhongliang; Fan, Beibei; Zhang, Quanbin; Jin, Guohua; Yang, Xiao; Zhang, Xiaoqing

    2016-02-24

    The transforming growth factor beta (TGFβ) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFβ signals. Here, we show that Smad3 is an insensitive TGFβ transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFβ signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFβ signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFβ/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity and differential transcriptional activity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFβ signaling and have distinct roles in regulating early developmental events.

  18. Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification

    PubMed Central

    Liu, Ling; Liu, Xu; Ren, Xudong; Tian, Yue; Chen, Zhenyu; Xu, Xiangjie; Du, Yanhua; Jiang, Cizhong; Fang, Yujiang; Liu, Zhongliang; Fan, Beibei; Zhang, Quanbin; Jin, Guohua; Yang, Xiao; Zhang, Xiaoqing

    2016-01-01

    The transforming growth factor beta (TGFβ) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFβ signals. Here, we show that Smad3 is an insensitive TGFβ transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFβ signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFβ signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFβ/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity and differential transcriptional activity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFβ signaling and have distinct roles in regulating early developmental events. PMID:26905010

  19. A sensitive and specific PCR assay for the detection of Baylisascaris schroederi eggs in giant panda feces.

    PubMed

    Wang, Ning; Li, De-Sheng; Zhou, Xuan; Xie, Yue; Liang, Yi-Nan; Wang, Cheng-Dong; Yu, Hua; Chen, Shi-Jie; Yan, Yu-Bo; Gu, Xiao-Bin; Wang, Shu-Xian; Peng, Xue-Rong; Yang, Guang-You

    2013-10-01

    Baylisascaris schroederi is one of the most common intestinal nematodes in giant pandas. It can cause severe baylisascariasis which is highly infectious in its natural hosts. A rapid and reliable diagnosis of parasite infections is crucial to protect giant pandas, as well as for environmental monitoring and disease surveillance. Here, we established a specific PCR assay for B. schroederi detection which was targeting a 331-bp long fragment of the mitochondrial cytochrome c oxidase subunit II (COII) gene. Fifty fresh fecal samples collected from captive giant pandas were tested by the established PCR assay and the traditional flotation technique. DNA extracted from a single B. schroederi egg could be successfully amplified, while no cross-reactivity was found with DNA from Ancylostoma caninum eggs. The detection rate of the PCR assay was 68%, which was higher than that of the traditional egg flotation (46%). Our findings demonstrated that the PCR assay is sensitive and specific for the detection and identification of B. schroederi eggs. Therefore, it could become a useful tool for the investigation of B. schroederi infections in giant pandas.

  20. Comprehensive profiles of human milk oligosaccharides yield highly sensitive and specific markers for determining secretor status in lactating mothers.

    PubMed

    Totten, Sarah M; Zivkovic, Angela M; Wu, Shuai; Ngyuen, UyenThao; Freeman, Samara L; Ruhaak, L Renee; Darboe, Momodou K; German, J Bruce; Prentice, Andrew M; Lebrilla, Carlito B

    2012-12-07

    Human milk oligosaccharides (HMOs), as an abundant and bioactive component of breast milk, work in many ways to promote the health of breast fed infants. The expression of HMOs has been shown to vary in accordance with Lewis blood type and secretor status, as women of different blood types differ in the expression of α1,2 fucosyltransferase (FUT2) and α1,3/4 fucosyltransferase (FUT3). In this study, HMOs were extracted from the milk of 60 women from The Gambia, Africa with various Lewis and secretor blood types. The HMOs were profiled using high resolution HPLC-Chip/TOF mass spectrometry. Notably, the amounts of fucosylation varied significantly between Le(a+b-) nonsecretors, Le(a-b+) and Le(a-b-) secretors, and Le(a-b-) nonsecretors. With higher frequency of expression of the recessive Lewis negative and nonsecretor phenotypes in West African populations, the HMO profiles of several milks from women of these phenotypes were examined, demonstrating decreased amounts of total oligosaccharide abundance and lower relative amounts of fucosylation. Also in this study, four specific fucosylated structures (2'FL, LNFP I, LDFT, and LNDFH I) were determined to be specific and sensitive glycan markers for rapidly determining secretor status without the need for serological testing.

  1. Development of a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of phenylethanolamine A in tissue and feed samples and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS).

    PubMed

    Cao, Biyun; He, Guangzhao; Yang, Hong; Chang, Huafang; Li, Shuqun; Deng, Anping

    2013-10-15

    Phenylethanolamine A (PA) is a new emerged β-adrenergic agonist illegally used as feed additives for growth promotion. In this study, a highly sensitive and specific indirect competitive enzyme-linked immunosorbent assay (ELISA) for the detection of PA in tissue and feed samples was developed and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS). By reduction of nitryl group to amino group, the PA derivative was synthesized and coupled to carrier proteins with diazobenzidine method. The antisera obtained from four immunized rabbits were characterized in terms of sensitivity and specificity. All antisera displayed high sensitivity with IC50 values lower than 0.48 ng mL(-1). The most sensitive ELISA was established with IC50 and limit of detection (LOD) values of 0.049 ng mL(-1) and 0.003 ng mL(-1), respectively. The cross-reactivity (CR) values of the antisera with three frequently used β-adrenergic agonists (clenbuterol, salbutamol and ractopamine) were lesser than 0.39%; there was no CR of the antisera with other six compounds including two structurally related substances (isoproterenol, phenylephrine). To investigate the accuracy and precision of the assay, swine kidney, liver, meat and feed samples were fortified with PA at different content and analyzed by ELISA. Acceptable recovery rates of 92.2-113.7% and intra-assay coefficients of variation of 3.8-10.9% (n=3) were achieved. Seven spiked samples were simultaneously analyzed by ELISA and LC-MS/MS. There was a high correlation coefficient of 0.9956 (n=7) between the two methods. The proposed ELISA proven to be a feasible quantitative/screening method for PA analysis in tissue and feed samples with the properties of high sensitivity and specificity, high sample throughput and low expensive.

  2. Staphylococcal superantigen-specific IgE antibodies: degree of sensitization and association with severity of asthma

    PubMed Central

    Elabras, José; Mello, Fernanda Carvalho de Queiroz; Lupi, Omar; Bica, Blanca Elena Rios Gomes; Papi, José Angelo de Souza; França, Alfeu Tavares

    2016-01-01

    ABSTRACT Objective: To determine the presence of staphylococcal superantigen-specific IgE antibodies and degree of IgE-mediated sensitization, as well as whether or not those are associated with the severity of asthma in adult patients. Methods: This was a cross-sectional study involving outpatients with asthma under treatment at a tertiary care university hospital in the city of Rio de Janeiro, Brazil. Consecutive patients were divided into two groups according to the severity of asthma based on the Global Initiative for Asthma criteria: mild asthma (MA), comprising patients with mild intermittent or persistent asthma; and moderate or severe asthma (MSA). We determined the serum levels of staphylococcal toxin-specific IgE antibodies, comparing the results and performing a statistical analysis. Results: The study included 142 patients: 72 in the MA group (median age = 46 years; 59 females) and 70 in the MSA group (median age = 56 years; 60 females). In the sample as a whole, 62 patients (43.7%) presented positive results for staphylococcal toxin-specific IgE antibodies: staphylococcal enterotoxin A (SEA), in 29 (20.4%); SEB, in 35 (24.6%); SEC, in 33 (23.2%); and toxic shock syndrome toxin (TSST), in 45 (31.7%). The mean serum levels of IgE antibodies to SEA, SEB, SEC, and TSST were 0.96 U/L, 1.09 U/L, 1.21 U/L, and 1.18 U/L, respectively. There were no statistically significant differences between the two groups in terms of the qualitative or quantitative results. Conclusions: Serum IgE antibodies to SEA, SEB, SEC, and TSST were detected in 43.7% of the patients in our sample. However, neither the qualitative nor quantitative results showed a statistically significant association with the clinical severity of asthma. PMID:27812635

  3. Specific detection of Flt3 point mutations by highly sensitive real-time polymerase chain reaction in acute myeloid leukemia.

    PubMed

    Scholl, Sebastian; Krause, Claudia; Loncarevic, Ivan F; Müller, Rouven; Kunert, Christa; Wedding, Ulrich; Sayer, Herbert G; Clement, Joachim H; Höffken, Klaus

    2005-06-01

    Among activating class III receptor tyrosine kinase (Flt3) mutations, internal tandem duplications of Flt3 (Flt3-ITD) are detected in about 25% of patients with acute myeloid leukemia (AML). In contrast, mutations within the tyrosine kinase domain of Flt3 (Flt3-TKD mutations) are less frequent (approximately 7%), and there are only limited data on the frequency of recently demonstrated activating Flt3 point mutation at codon 592 (Flt3-V592A mutation). We evaluated a new approach for rapid screening of Flt3-TKD and Flt3-V592A mutations using the fluorescence resonance energy transfer (FRET) principle in a group of 122 patients. Based on individual Flt3-TKD mutations, we designed patient-specific primers to perform a highly sensitive polymerase chain reaction (PCR) assay for rapid detection of minimal residual disease (MRD). We also used a model system with MonoMac-6 cells carrying the Flt3-V592A mutation to establish a mutation-specific real-time PCR approach also for this molecular aberration. We identified 9 cases (8%) of Flt3-TKD mutations (5 cases of mutation D835Y, 3 cases of mutation D835H, and 1 case of mutation Del836), and no cases of Flt3-V592A mutation. Screening for Flt3-TKD mutations with fluorescent probes is equivalent to conventional screening using standard PCR followed by EcoRV restriction. We present a real-time PCR protocol that can be used for MRD analyses based on individual Flt3-TKD mutations. Examples of MRD analyses are presented for all 3 subtypes of Flt3-TKD mutation identified in this study. In summary, we demonstrate new methodological approaches for rapid screening of Flt3 point mutations and for detection of MRD based on patient-specific Flt3-TKD mutations.

  4. The wrist hyperflexion and abduction of the thumb (WHAT) test: a more specific and sensitive test to diagnose de Quervain tenosynovitis than the Eichhoff's Test.

    PubMed

    Goubau, J F; Goubau, L; Van Tongel, A; Van Hoonacker, P; Kerckhove, D; Berghs, B

    2014-03-01

    De Quervain's disease has different clinical features. Different tests have been described in the past, the most popular test being the Eichhoff's test, often wrongly named as the Finkelstein's test. Over the years, a misinterpretation has occurred between these two tests, the latter being confused with the first. To compare the Eichhoff's test with a new test, the wrist hyperflexion and abduction of the thumb test, we set up a prospective study over a period of three years for a cohort of 100 patients (88 women, 12 men) presenting spontaneous pain over the radial side of the styloid of the radius (de Quervain tendinopathy). The purpose of the study was to compare the accuracy of the Eichhoff's test and wrist hyperflexion and abduction of the thumb test to diagnose correctly de Quervain's disease by comparing clinical findings using those tests with the results on ultrasound. The wrist hyperflexion and abduction of the thumb test revealed greater sensitivity (0.99) and an improved specificity (0.29) together with a slightly better positive predictive value (0.95) and an improved negative predictive value (0.67). Moreover, the study showed us that the wrist hyperflexion and abduction of the thumb test is very valuable in diagnosing dynamic instability after successful decompression of the first extensor compartment. Our results support that the wrist hyperflexion and abduction of the thumb test is a more precise tool for the diagnosis of de Quervain's disease than the Eichhoff's test and thus could be adopted to guide clinical diagnosis in the early stages of de Quervain's tendinopathy.

  5. Tackling reproducibility in microcantilever biosensors: a statistical approach for sensitive and specific end-point detection of immunoreactions.

    PubMed

    Kosaka, Priscila M; Tamayo, Javier; Ruz, José J; Puertas, Sara; Polo, Ester; Grazu, Valeria; de la Fuente, Jesús M; Calleja, Montserrat

    2013-02-21

    In the last decade, microcantilever biosensors have shown enormous potential for highly sensitive label-free detection of nucleic acid and proteins. Despite the enormous advances, the promise of applications of this technology in the biomedical field has been frustrated because of its low reproducibility. Here we tackle the reproducibility issue in microcantilever biosensors and provide the guidelines to minimize the deviations in the biosensor response between different assays. We use as a model system the label-free end-point detection of horseradish peroxidase. We choose the end-point detection mode because of its suitability for implementation in the clinical field that requires simplicity and point-of-care capability. Our study comprises the analysis of 1012 cantilevers with different antibody surface densities, two blocking strategies based on polyethylene-glycol (PEG) and bovine serum albumin (BSA) and stringent controls. The study reveals that the performance of the assay critically depends on both antibody surface density and blocking strategies. We find that the optimal conditions involve antibody surface densities near but below saturation and blocking with PEG. We find that the surface stress induced by the antibody-antigen binding is significantly correlated with the surface stress generated during the antibody attachment and blocking steps. The statistical correlation is harnessed to identify immobilization failure or success, and thus enhancing the specificity and sensitivity of the assay. This procedure enables achieving rates of true positives and true negatives of 90% and 91% respectively. The detection limit is of 10 ng mL(-1) (250 pM) that is similar to the detection limit obtained in our enzyme-linked immunosorbent assay (ELISA) and at least two orders of magnitude smaller than that achieved with well-established label-free biosensors such as a quartz crystal microbalance (QCM) and surface plasmon resonance (SPR) sensor.

  6. External quality assessment of tumour marker analysis: state of the art and consequences for estimating diagnostic sensitivity and specificity.

    PubMed

    Reinauer, Hans; Wood, William Graham

    2005-05-30

    This review shows the current analytical quality for the following analytes used as tumour markers in the external quality assessment (EQA)-programmes of Instand e.V., a national EQA-organiser in Germany: Corticotropin (ACTH), growth hormone (GH, hGH), prolactin (PRL), chorionic gonadotropin (CG, hCG), calcitonin (CT, hCT), thyroglobulin (Tg), carcinoembryonic antigen (CEA), CA-Antigens 125, 72-4, 15-3 and 19-9, alpha foetoprotein (AFP) and prostate-specific antigen (PSA). The results from the participants show a large variation in the precision of the methods used as well as in the comparability of results between methods for the same analyte. In general, the hormones used as tumour markers show better performance than the "CA-markers", which are often inadequately standardised and defined. In the case of one CA-marker (CA 72-4/TAG 72-4), the differences between the lowest kit median concentration and highest kit median concentration for one sample pair were 440% and 580%. The corresponding figures for ACTH were 123% and 156% and for CEA 180% and 184%. The classical tumour markers such as carcinoembryonic antigen (CEA) and alpha foetoprotein (AFP) performed markedly better than the CA-markers and PSA with regards to both inter- and intra-method comparability. The inter-laboratory precision for a given kit and marker was acceptable in many cases. The results show that only results from the same kit/method for each tumour marker can be used for cumulative or time-dependent comparison of results - for example pre-operative and post-operative follow up. In the case of prostate specific antigen (PSA), the kits used for free and total PSA must come from the same producer, if the generally accepted ratios are to have any diagnostic value. The need for kit- and laboratory-specific reference ranges and cut-off values for setting diagnostic specificity and sensitivity is highlighted from the EQA-results. The situation for inter-method comparability for the CA-Markers has

  7. Validation Test Report for NFLUX PRE: Validation of Specific Humidity, Surface Air Temperature, and Wind Speed Precision and Accuracy for Assimilation into Global and Regional Models

    DTIC Science & Technology

    2013-12-17

    NRL/MR/7320--14-9523 Validation Test Report for NFLUX PRE: Validation of Specific Humidity, Surface Air Temperature, and Wind Speed...REPORT DATE 17 DEC 2013 2. REPORT TYPE 3. DATES COVERED 00-00-2013 to 00-00-2013 4. TITLE AND SUBTITLE Validation Test Report for NFLUX PRE...products overlay the existing global product estimate. The location of the observations is tested to see if it falls within one of the regional areas

  8. Accuracy of cause of death data routinely recorded in a population-based cancer registry: impact on cause-specific survival and validation using the Geneva cancer registry

    PubMed Central

    2013-01-01

    Background Information on the underlying cause of death of cancer patients is of interest because it can be used to estimate net survival. The population-based Geneva Cancer Registry is unique because registrars are able to review the official cause of death. This study aims to describe the difference between the official and revised cause-of-death variables and the impact on cancer survival estimates. Methods The recording process for each cause of death variable is summarised. We describe the differences between the two cause-of-death variables for the 5,065 deceased patients out of the 10,534 women diagnosed with breast cancer between 1970 and 2009. The Kappa statistic and logistic regression are applied to evaluate the degree of concordance. The impact of discordance on cause-specific survival is examined using the Kaplan Meier method. Results The overall agreement between the two variables was high. However, several subgroups presented a lower concordance, suggesting differences in calendar time and less attention given to older patients and more advanced diseases. Similarly, the impact of discordance on cause-specific survival was small on overall survival but larger for several subgroups. Conclusion Estimation of cancer-specific survival could therefore be prone to bias when using the official cause of death. Breast cancer is not the more lethal cancer and our results can certainly not be generalised to more lethal tumours. PMID:24373194

  9. Sensitive and Specific Biomimetic Lipid Coated Microfluidics to Isolate Viable Circulating Tumor Cells and Microemboli for Cancer Detection

    PubMed Central

    Chen, Jia-Yang; Tsai, Wen-Sy; Shao, Hung-Jen; Wu, Jen-Chia; Lai, Jr-Ming; Lu, Si-Hong; Hung, Tsung-Fu; Yang, Chih-Tsung; Wu, Liang-Chun; Chen, Jinn-Shiun; Lee, Wen-Hwa; Chang, Ying-Chih

    2016-01-01

    Here we presented a simple and effective membrane mimetic microfluidic device with antibody conjugated supported lipid bilayer (SLB) “smart coating” to capture viable circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) directly from whole blood of all stage clinical cancer patients. The non-covalently bound SLB was able to promote dynamic clustering of lipid-tethered antibodies to CTC antigens and minimized non-specific blood cells retention through its non-fouling nature. A gentle flow further flushed away loosely-bound blood cells to achieve high purity of CTCs, and a stream of air foam injected disintegrate the SLB assemblies to release intact and viable CTCs from the chip. Human blood spiked cancer cell line test showed the ~95% overall efficiency to recover both CTCs and CTMs. Live/dead assay showed that at least 86% of recovered cells maintain viability. By using 2 mL of peripheral blood, the CTCs and CTMs counts of 63 healthy and colorectal cancer donors were positively correlated with the cancer progression. In summary, a simple and effective strategy utilizing biomimetic principle was developed to retrieve viable CTCs for enumeration, molecular analysis, as well as ex vivo culture over weeks. Due to the high sensitivity and specificity, it is the first time to show the high detection rates and quantity of CTCs in non-metastatic cancer patients. This work offers the values in both early cancer detection and prognosis of CTC and provides an accurate non-invasive strategy for routine clinical investigation on CTCs. PMID:26938471

  10. Species-Specific Flight Styles of Flies are Reflected in the Response Dynamics of a Homolog Motion-Sensitive Neuron

    PubMed Central

    Geurten, Bart R. H.; Kern, Roland; Egelhaaf, Martin

    2012-01-01

    Hoverflies and blowflies have distinctly different flight styles. Yet, both species have been shown to structure their flight behavior in a way that facilitates extraction of 3D information from the image flow on the retina (optic flow). Neuronal candidates to analyze the optic flow are the tangential cells in the third optical ganglion – the lobula complex. These neurons are directionally selective and integrate the optic flow over large parts of the visual field. Homolog tangential cells in hoverflies and blowflies have a similar morphology. Because blowflies and hoverflies have similar neuronal layout but distinctly different flight behaviors, they are an ideal substrate to pinpoint potential neuronal adaptations to the different flight styles. In this article we describe the relationship between locomotion behavior and motion vision on three different levels: (1) We compare the different flight styles based on the categorization of flight behavior into prototypical movements. (2) We measure the species-specific dynamics of the optic flow under naturalistic flight conditions. We found the translational optic flow of both species to be very different. (3) We describe possible adaptations of a homolog motion-sensitive neuron. We stimulate this cell in blowflies (Calliphora) and hoverflies (Eristalis) with naturalistic optic flow generated by both species during free flight. The characterized hoverfly tangential cell responds faster to transient changes in the optic flow than its blowfly homolog. It is discussed whether and how the different dynamical response properties aid optic flow analysis. PMID:22485089

  11. pH-sensitive nanocargo based on smart polymer functionalized graphene oxide for site-specific drug delivery.

    PubMed

    Kavitha, Thangavelu; Abdi, Syed Izhar Haider; Park, Soo-Young

    2013-04-14

    Graphene oxide (GO) was functionalized covalently with pH-sensitive poly(2-(diethylamino) ethyl methacrylate) (PDEA) by surface-initiated in situ atom transfer radical polymerization. The structure of the PDEA-grafted GO (GO-PDEA) were examined by Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis and atomic force microscopy. The grafted PDEA endowed the GO sheets with good solubility and stability in physiological solutions. Simple physisorption by π-π stacking and hydrophobic interactions on GO-PDEA can be used to load camptothecin (CPT), a widely used water-insoluble cancer drug. The loaded CPT was released only at the lower (acidic) pH normally found in a tumor environment but not in basic and neutral pH. GO-PDEA did not show practical toxicity to N2a cancer cells but the GO-PDEA-CPT complex exhibited high potency in killing N2a cancer cells in vitro. These results suggest that the GO-PDEA nanocargo carrier might be a promising material for site-specific anticancer drug delivery and controlled release.

  12. A silicon-based electrochemical sensor for highly sensitive, specific, label-free and real-time DNA detection.

    PubMed

    Guo, Yuanyuan; Su, Shao; Wei, Xinpan; Zhong, Yiling; Su, Yuanyuan; Huang, Qing; Fan, Chunhai; He, Yao

    2013-11-08

    We herein present a new kind of silicon-based electrochemical sensor using a gold nanoparticles-decorated silicon wafer (AuNPs@Si) as a high-performance electrode, which is facilely prepared via in situ AuNPs growth on a silicon wafer. Particularly significantly, the resultant electrochemical sensor is efficacious for label-free DNA detection with high sensitivity due to the unique merits of the prepared silicon-based electrode. Typically, DNA at remarkably low concentrations (1-10 fM) could be readily detected without requiring additional signal-amplification procedures, which is better than or comparable to the lowest DNA concentration ever detected via well-studied signal-amplification-assisted electrochemical sensors. Moreover, the silicon-based sensor features high specificity, allowing unambiguous discrimination of single-based mismatches. We further show that real-time DNA assembly is readily monitored via recording the intensity changes of current signals due to the robust thermal stability of the silicon-based electrode. The unprecedented advantages of the silicon-based electrochemical sensor would offer new opportunities for myriad sensing applications.

  13. A sensitive test for the detection of specific DSB repair defects in primary cells from breast cancer specimens.

    PubMed

    Keimling, Marlen; Kaur, Jatinder; Bagadi, Sarangadhara Appala Raju; Kreienberg, Rolf; Wiesmüller, Lisa; Ralhan, Ranju

    2008-08-01

    Increasing evidence indicates that breast cancer pathogenesis is linked with DNA double-strand break (DSB) repair dysfunction. This conclusion is based on advances in the study of functions of breast cancer susceptibility genes such as BRCA1 and BRCA2, on the identification of breast cancer-associated changes regarding the genetics, expression, and localization of multiple DSB repair factors, and on observations indicating enhanced radiation-induced chromosomal damage in cells from predisposed individuals and sporadic breast cancer patients. In this pilot study, we describe a sensitive method for the analysis of DSB repair functions in mammary carcinomas. Using this method we firstly document alterations in pathway-specific DSB repair activities in primary cells originating from familial as well as sporadic breast cancer. In particular, we identified increases in the mutagenic nonhomologous end joining and single-strand annealing mechanisms in sporadic breast cancers with wild-type BRCA1 and BRCA2, and, thus, similar phenotypes to tumors with mutant alleles of BRCA1 and BRCA2. This suggests that detection of error-prone DSB repair activities may be useful to extend the limits of genotypic characterization of high-risk susceptibility genes. This method may, therefore, serve as a marker for breast cancer risk assessment and, even more importantly, for the prediction of responsiveness to targeted therapies such as to inhibitors of poly(ADP-ribose)polymerase (PARP1).

  14. Quantitative wound healing studies using a portable, low cost, handheld near-infrared optical scanner: preliminary sensitivity and specificity analysis

    NASA Astrophysics Data System (ADS)

    Lei, Jiali; Rodriguez, Suset; Jayachandran, Maanasa; Solis, Elizabeth; Gonzalez, Stephanie; Perez-Clavijo, Francesco; Wigley, Stephen; Godavarty, Anuradha

    2016-03-01

    Lower extremity ulcers are devastating complications that are still un-recognized. To date, clinicians employ visual inspection of the wound site during its standard 4-week of healing process via monitoring of surface granulation. A novel ultra-portable near-infrared optical scanner (NIROS) has been developed at the Optical Imaging Laboratory that can perform non-contact 2D area imaging of the wound site. From preliminary studies it was observed that the nonhealing wounds had a greater absorption contrast with respect to the normal site, unlike in the healing wounds. Currently, non-contact near-infrared (NIR) imaging studies were carried out on 22 lower extremity wounds at two podiatric clinics, and the sensitivity and specificity of the scanner evaluated. A quantitative optical biometric was developed that differentiates healing from non-healing wounds, based on the threshold values obtained during ROC analysis. In addition, optical images of the wound obtained from weekly imaging studies are also assessed to determine the ability of the device to predict wound healing consistently on a periodic basis. This can potentially impact early intervention in the treatment of lower extremity ulcers when an objective and quantitative wound healing approach is developed. Lastly, the incorporation of MATLAB graphical user interface (GUI) to automate the process of image acquisition, image processing and image analysis realizes the potential of NIROS to perform non-contact and real-time imaging on lower extremity wounds.

  15. Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin

    PubMed Central

    Chen, Qing; Long, Miaomiao; Qiu, Lipeng; Zhu, Mengqin; Li, Zhen; Qiao, Mingxi; Hu, Haiyang; Zhao, Xiuli; Chen, Dawei

    2016-01-01

    To improve the targeting efficacy of hyaluronic acid (HA)-based micelles, pH-sensitive mixed micelles based on HA-g-poly(L-histidine) (PHis) and d-α-tocopheryl polyethylene glycol 2000 copolymers were prepared and decorated with human epidermal growth factor receptor 2 (Her2) peptide, a tumor cell-specific peptide ligand, on their surface. The doxorubicin-loaded micelles (HA-PHis/peptide–d-α-tocopheryl polyethylene glycol 2000 mixed micelles [PHTM]) were characterized to have a unimodal size distribution and pH-dependent drug release pattern. In vitro tumor targeting studies demonstrated that PHTM exhibited the pronounced cytotoxicity and efficient internalization in MDA-MB-231 cells overexpressing CD44 and Her2 receptors. In vivo investigation into micelles in MDA-MB-231 tumor-bearing mice confirmed that PTHM could reach the tumor site more effectively and exert excellent tumor killing activity. In general, Her2 peptide decoration can enhance the selective cytotoxicity and antitumor activity of HA-based micelles. PMID:27799766

  16. Prenatal Particulate Air Pollution and Neurodevelopment in Urban Children: Examining Sensitive Windows and Sex-specific Associations

    PubMed Central

    Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Coull, Brent A.; Bellinger, David C.; Kloog, Itai; Schwartz, Joel; Wright, Robert O.; Wright, Rosalind J.

    2015-01-01

    Background Brain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex. Objectives We implemented innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter≤2.5μm (PM2.5) and children’s neurodevelopment. Methods We assessed 267 full-term urban children’s prenatal daily PM2.5 exposure using a validated satellite-based spatio-temporally resolved prediction model. Outcomes included IQ (WISC-IV), attention (omission errors [OEs], commission errors [CEs], hit reaction time [HRT], and HRT standard error [HRT-SE] on the Conners’ CPT-II), and memory (general memory [GM] index and its components - verbal [VEM] and visual [VIM] memory, and attention-concentration [AC] indices on the WRAML-2) assessed at age 6.5±0.98 years. To identify the role of exposure timing, we used distributed lag models to examine associations between weekly prenatal PM2.5 exposure and neurodevelopment. Sex-specific associations were also examined. Results Mothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12 years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31–38 weeks with lower IQ, at 20–26 weeks gestation with increased OEs, at 32–36 weeks with slower HRT, and at 22–40 weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18–26 weeks with reduced VIM, at 12–20 weeks with reduced GM). Conclusions Increased PM2.5 exposure in specific prenatal windows was associated with poorer function across memory and attention domains with variable associations based on sex. Refined determination of time window- and sex-specific associations may enhance insight into underlying mechanisms and identification of vulnerable subgroups. PMID

  17. Accuracy of diagnostic testing in primary ciliary dyskinesia

    PubMed Central

    Jackson, Claire L.; Behan, Laura; Goggin, Patricia M.; Adam, Elizabeth C.; Coles, Janice L.; Evans, Hazel J.; Harris, Amanda; Lackie, Peter; Packham, Samantha; Page, Anton; Thompson, James; Walker, Woolf T.; Kuehni, Claudia

    2016-01-01

    Diagnosis of primary ciliary dyskinesia (PCD) lacks a “gold standard” test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach. Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests. HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30 nL·min−1 cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific. In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (≤30 nL·min−1) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ∼10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority. PMID:26647444

  18. Inter-observer agreement, diagnostic sensitivity and specificity of animal-based indicators of young lamb welfare.

    PubMed

    Phythian, C J; Toft, N; Cripps, P J; Michalopoulou, E; Winter, A C; Jones, P H; Grove-White, D; Duncan, J S

    2013-07-01

    A scientific literature review and consensus of expert opinion used the welfare definitions provided by the Farm Animal Welfare Council (FAWC) Five Freedoms as the framework for selecting a set of animal-based indicators that were sensitive to the current on-farm welfare issues of young lambs (aged ≤ 6 weeks). Ten animal-based indicators assessed by observation - demeanour, response to stimulation, shivering, standing ability, posture, abdominal fill, body condition, lameness, eye condition and salivation were tested as part of the objective of developing valid, reliable and feasible animal-based measures of lamb welfare The indicators were independently tested on 966 young lambs from 17 sheep flocks across Northwest England and Wales during December 2008 to April 2009 by four trained observers. Inter-observer reliability was assessed using Fleiss's kappa (κ), and the pair-wise agreement with an experienced, observer designated as the 'test standard observer' (TSO) was examined using Cohen's κ. Latent class analysis (LCA) estimated the sensitivity (Se) and specificity (Sp) of each observer without assuming a gold standard and predicted the Se and Sp of randomly selected observers who may apply the indicators in the future. Overall, good levels of inter-observer reliability, and high levels of Sp were identified for demeanour (κ = 0.54, Se ≥ 0.70, Sp ≥ 0.98), stimulation (κ = 0.57, Se = 0.30 to 0.77, Sp ≥ 0.98), shivering (κ = 0.55, Se = 0.37 to 0.85, Sp ≥ 0.99), standing ability (0.54, Se ≥ 0.80, Sp ≥ 0.99), posture (κ = 0.45, Se ≥ 0.56, Sp = 0.99), abdominal fill (κ = 0.44, Se = 0.39 to 0.98, Sp = 0.99), body condition (κ = 0.72, Se ⩾ 0.38 to 0.90, Sp = 0.99), lameness (κ = 0.68, Se > 0.73, Sp = 1.00), and eye condition (κ = 0.72, Se ≥ 0.86, Sp = 0.99). LCA predicted that randomly selected observers had Se > 0.77 (acceptable), and Sp ≥ 0.98 (high) for assessments of demeanour, lameness, abdominal fill posture, body condition and eye

  19. Sensitivity of the urban airshed model to ozone precursor vehicular emissions. Volume 1. Sensitivity analysis for a specific geographical location. Final report

    SciTech Connect

    Wu, B.; Miller, J.S.; Demetsky, M.J.

    1996-05-01

    Volume I outlines how ground-level ozone is formed as well as its relationship to vehicle emissions. This volume also describes the Environmental Protection Agency (EPA) sponsored Urban Airshed Model (UAM) system and how the author employed this model to investigate the sensitivity of ozone to changes in vehicle emissions. A detailed interpretation of the findings is provided as well as recommendations for future studies.

  20. Elf5 is an epithelium-specific, fibroblast growth factor-sensitive transcription factor in the embryonic lung.

    PubMed

    Metzger, David E; Xu, Yan; Shannon, John M

    2007-05-01

    Fibroblast growth factor (FGF) signaling has been shown to be essential for many aspects of normal lung development. To determine epithelial targets of FGF signaling, we cultured embryonic day (E) 11.5 mouse lungs for 24 hr in the presence or absence of the FGF receptor antagonist SU5402, which inhibited branching morphogenesis. Affymetrix gene chip analysis of treated and control epithelia identified several genes regulated by FGF signaling, including Elf5, a member of the Epithelial-specific Ets family of transcription factors. SU5402 reduced Elf5 expression in mesenchyme-free cultures of E12.5 epithelium, demonstrating that the inhibition was direct. In situ hybridization revealed that Elf5 had a dynamic pattern of expression during lung development. We found that expression of Elf5 was induced by FGF7 and FGF10, ligands that primarily bind FGFR2b. To further define the pathways by which FGFs activate Elf5 expression, we cultured E11.5 lung tips in the presence of compounds to inhibit FGF receptors (SU5402), PI3-Kinase/Akt-mediated signaling (LY294002), and MAP Kinase/Erk-mediated signaling (U0126). We found that SU5402 and LY294002 significantly reduced Elf5 expression, whereas U0126 had no effect. LY294002 also reduced Elf5 expression in cultures of purified epithelium. Finally, pAkt was coexpressed with Elf5 in the proximal epithelial airways of E17.5 lungs. These results demonstrate that Elf5 is an FGF-sensitive transcription factor in the lung with a dynamic pattern of expression and that FGF regulation of Elf5 by means of FGFR2b occurs through the PI3-Kinase/Akt pathway.

  1. Semi-Metric Topology of the Human Connectome: Sensitivity and Specificity to Autism and Major Depressive Disorder

    PubMed Central

    Simas, Tiago; Chattopadhyay, Shayanti; Hagan, Cindy; Kundu, Prantik; Patel, Ameera; Holt, Rosemary; Floris, Dorothea; Graham, Julia; Ooi, Cinly; Tait, Roger; Spencer, Michael; Baron-Cohen, Simon; Sahakian, Barbara; Bullmore, Ed; Goodyer, Ian; Suckling, John

    2015-01-01

    Introduction The human functional connectome is a graphical representation, consisting of nodes connected by edges, of the inter-relationships of blood oxygenation-level dependent (BOLD) time-series measured by MRI from regions encompassing the cerebral cortices and, often, the cerebellum. Semi-metric analysis of the weighted, undirected connectome distinguishes an edge as either direct (metric), such that there is no alternative path that is accumulatively stronger, or indirect (semi-metric), where one or more alternative paths exist that have greater strength than the direct edge. The sensitivity and specificity of this method of analysis is illustrated by two case-control analyses with independent, matched groups of adolescents with autism spectrum conditions (ASC) and major depressive disorder (MDD). Results Significance differences in the global percentage of semi-metric edges was observed in both groups, with increases in ASC and decreases in MDD relative to controls. Furthermore, MDD was associated with regional differences in left frontal and temporal lobes, the right limbic system and cerebellum. In contrast, ASC had a broadly increased percentage of semi-metric edges with a more generalised distribution of effects and some areas of reduction. In summary, MDD was characterised by localised, large reductions in the percentage of semi-metric edges, whilst ASC is characterised by more generalised, subtle increases. These differences were corroborated in greater detail by inspection of the semi-metric backbone for each group; that is, the sub-graph of semi-metric edges present in >90% of participants, and by nodal degree differences in the semi-metric connectome. Conclusion These encouraging results, in what we believe is the first application of semi-metric analysis to neuroimaging data, raise confidence in the methodology as potentially capable of detection and characterisation of a range of neurodevelopmental and psychiatric disorders. PMID:26308854

  2. Activated phosphonated trifunctional chelates for highly sensitive lanthanide-based FRET immunoassays applied to total prostate specific antigen detection.

    PubMed

    Nchimi-Nono, Katia; Wegner, K David; Lindén, Stina; Lecointre, Alexandre; Ehret-Sabatier, Laurence; Shakir, Shakir; Hildebrandt, Niko; Charbonnière, Loïc J

    2013-10-14

    The first example of an activated phosphonated trifunctional chelate (TFC) is presented, which combines a non-macrocyclic coordination site for lanthanide coordination based on two aminobis-methylphosphonate coordinating arms, a central bispyrazolylpyridyl antenna and an N-hydroxysuccinimide ester in para position of the central pyridine as an activated function for the labeling of biomaterial. The synthesis of the TFC is presented together with photo-physical studies of the related Tb and Eu complexes. Excited state lifetime measurements in H2O and D2O confirmed an excellent shielding of the cation from water molecules with a hydration number of zero. The Tb complex provides a high photoluminescence (PL) quantum yield of 24% in aqueous solutions (0.01 M Tris-HCl, pH 7.4) and a very long luminescence lifetime of 2.6 ms. The activated ligand was conjugated to different biological compounds such as streptavidin, and a monoclonal antibody against total prostate specific antigen (TPSA). In combination with AlexaFluor647 (AF647) and crosslinked allophycocyanin (XL665) antibody (ABs) conjugates, homogeneous time-resolved Fluorescence Resonance Energy Transfer (FRET) immunoassays of TPSA were performed in serum samples. The Tb donor-dye acceptor FRET pairs provided large Förster distances of 5.3 nm (AF647) and 7.1 nm (XL665). A detailed time-resolved FRET analysis of Tb donor and dye acceptor PL decays revealed average donor-acceptor distances of 4.2 nm (AF647) and 6.3 nm (XL665) within the sandwich immunocomplex and FRET efficiencies of 0.79 and 0.68, respectively. Very low detection limits of 1.4 ng mL(-1) (43 pM) and 2.4 ng mL(-1) (74 pM) TPSA were determined using a KRYPTOR fluorescence immunoanalyzer. These results demonstrate the applicability of our novel Tb-bioconjugates for highly sensitive clinical diagnostics.

  3. Sensitivity and specificity of culture and PCR of smegma samples of bulls experimentally infected with Tritrichomonas foetus.

    PubMed

    Cobo, E R; Favetto, P H; Lane, V M; Friend, A; VanHooser, K; Mitchell, J; BonDurant, R H

    2007-10-01

    The sensitivity (Se) and specificity (Sp) of different testing schemes were estimated for detecting Tritrichomonas foetus (T. foetus) in smegma samples from experimentally infected bulls. Culture and polymerase chain reaction (PCR) on smegma samples were evaluated alone and in parallel testing. Mature dairy bulls (n=79) were intrapreputially inoculated with T. foetus (n=19); Campylobacter (C.) fetus venerealis (n=13); both T. foetus and C. fetus venerealis (n=11); Tetratrichomonas spp. (n=9); C. fetus fetus (n=8); or were not inoculated (n=19). For each bull, smegma samples were collected for 6 week post-inoculation and tested for T. foetus by In Pouch TF culture and PCR. Most T. foetus-inoculated bulls became infected, according to culture (86.7%), PCR (90.0%), and both tests together (93.3%). In T. foetus-inoculated bulls, both tests combined in parallel on a single sample had a Se (78.3%) and Sp (98.5%) similar to two cultures (Se 76.0%, Sp 98.5%) or two PCR (Se 78.0%, Sp 96.7%) sampled on consecutive weeks. The PCR on three consecutive weekly samples (Se 85.0%, Sp 95.4%) and both tests applied in parallel on three consecutive weekly samples (Se 87.5%, Sp 95.6%) were similar to the current gold-standard of six weekly cultures (Se 86.7% and Sp 97.5%). Both tests used in parallel six times had the highest Se (93.3%), with similar Sp (92.5%). Tetratrichomonas spp. were only sporadically detected by culture or PCR. In conclusion, we have proposed alternative strategies for T. foetus diagnostics (for the AI industry), including a combination of tests and repeat testing strategies that may reduce time and cost for bull surveillance.

  4. Comparing the Predictive Value of Task Performance and Task-Specific Sensitivity During Physical Function Testing Among People With Knee Osteoarthritis.

    PubMed

    Wideman, Timothy H; Edwards, Robert R; Finan, Patrick H; Haythornthwaite, Jennifer A; Smith, Michael T

    2016-05-01

    Study Design Cross-sectional cohort. Background Knee osteoarthritis (OA) is a leading cause of pain and mobility restriction. Past research has advocated the use of brief, functional tasks to evaluate these restrictions, such as the six-minute-walk test and the timed up-and-go test. Typically, only task performance (ie, walking distance, completion time) is used to inform clinical practice. Recent research, however, suggests that individual variance in how people feel while completing these tasks (ie, task sensitivity) might also have important clinical value. Objective To compare the predictive value of task performance and task-specific sensitivity in determining OA-related physical function (measured by the Western Ontario and McMaster Universities Osteoarthritis Index) and pain-related interference (measured by the Multidimensional Pain Inventory). Methods One hundred eight participants with chronic knee OA completed the six-minute-walk test and the timed up-and-go test, and reported levels of discomfort and affective response (mood) associated with each test. Results In separate regression models, both task performance and task-specific sensitivity predicted OA-related physical function and pain-related interference. A final regression model including all significant predictors showed that task-specific sensitivity (specifically, post-six-minute-walk discomfort) emerged as a unique predictor of both outcomes. Conclusion These findings highlight the value of a novel clinical assessment strategy for patients with knee OA. While clinicians commonly focus on how patients perform on standardized functional tasks, these results highlight the value of also considering levels of posttask sensitivity. Measures of task-specific sensitivity relate to Maitland's concept of pain irritability, which may be a useful framework for future research on sensitizing factors and pain-related disability. J Orthop Sports Phys Ther 2016;46(5):346-356. Epub 21 Mar 2016. doi:10

  5. On the accuracy of the general, state-specific polarizable-continuum model for the description of correlated ground- and excited states in solution.

    PubMed

    Mewes, Jan-Michael; Herbert, John M; Dreuw, Andreas

    2017-01-04

    Equilibrium and non-equilibrium formulations of the state-specific polarizable-continuum model (SS-PCM) are evaluated in combination with correlated ground- and excited-state densities provided by the algebraic-diagrammatic construction method (ADC) for the polarization propagator via the computationally efficient intermediate-state representation (ISR) formalism. Since the influence of the SS-PCM onto quantum-chemical method is naturally limited to the presence of the apparent surface charges in the one-electron Hamiltonian and hence fully contained in the polarized MOs, the herein presented solvent model can be combined with all implemented orders and variants of ADC. Employing ADC/SS-PCM, the symmetric, ionized dimers of neon, ethene and nitromethane are investigated. Their broken-symmetry wavefunctions exhibit a low-lying charge-transfer state that is symmetry-equivalent to the ground state. This curious though ultimately artificial feature is convenient as it allows for a direct comparison of ADC/SS-PCM for the CT state to the Møller-Plesset/PCM description of the ground state. The agreement down to 0.02 eV for a wide range of dielectric constants validates the ADC/SS-PCM approach. Eventually, the relaxed potential-energy surfaces of the ground and lowest excited states of 4-(N,N)-dimethylaminobenzonitrile in cyclohexane and acetonitrile are computed, and it is demonstrated that the ADC(2)/SS-PCM approach affords excellent agreement with experimental fluorescence data. Only at the ADC(3) level of theory, however, the experimentally observed solvent-dependent dual fluorescence can be explained.

  6. Estimating the sensitivity and specificity of Kato-Katz stool examination technique for detection of hookworms, Ascaris lumbricoides and Trichuris trichiura infections in humans in the absence of a 'gold standard'.

    PubMed

    Tarafder, M R; Carabin, H; Joseph, L; Balolong, E; Olveda, R; McGarvey, S T

    2010-03-15

    The accuracy of the Kato-Katz technique in identifying individuals with soil-transmitted helminth (STH) infections is limited by day-to-day variation in helminth egg excretion, confusion with other parasites and the laboratory technicians' experience. We aimed to estimate the sensitivity and specificity of the Kato-Katz technique to detect infection with Ascaris lumbricoides, hookworm and Trichuris trichiura using a Bayesian approach in the absence of a 'gold standard'. Data were obtained from a longitudinal study conducted between January 2004 and December 2005 in Samar Province, the Philippines. Each participant provided between one and three stool samples over consecutive days. Stool samples were examined using the Kato-Katz technique and reported as positive or negative for STHs. In the presence of measurement error, the true status of each individual is considered as latent data. Using a Bayesian method, we calculated marginal posterior densities of sensitivity and specificity parameters from the product of the likelihood function of observed and latent data. A uniform prior distribution was used (beta distribution: alpha=1, beta=1). A total of 5624 individuals provided at least one stool sample. One, two and three stool samples were provided by 1582, 1893 and 2149 individuals, respectively. All STHs showed variation in test results from day to day. Sensitivity estimates of the Kato-Katz technique for one stool sample were 96.9% (95% Bayesian Credible Interval [BCI]: 96.1%, 97.6%), 65.2% (60.0%, 69.8%) and 91.4% (90.5%, 92.3%), for A. lumbricoides, hookworm and T. trichiura, respectively. Specificity estimates for one stool sample were 96.1% (95.5%, 96.7%), 93.8% (92.4%, 95.4%) and 94.4% (93.2%, 95.5%), for A. lumbricoides, hookworm and T. trichiura, respectively. Our results show that the Kato-Katz technique can perform with reasonable accuracy with one day's stool collection for A. lumbricoides and T. trichiura. Low sensitivity of the Kato-Katz for detection

  7. High-accuracy measurements of N2O concentration and site-specific nitrogen isotopes in small or high concentration samples

    NASA Astrophysics Data System (ADS)

    Palmer, M. R.; Arata, C.; Huang, K.

    2014-12-01

    Nitrous oxide (N2O) gas is among the major contributors to global warming and ozone depletion in stratosphere. Quantitative estimate of N­2O production in various pathways and N­2O fluxes across different reservoirs is the key to understanding the role of N­2O in the global change. To achieve this goal, accurate and concurrent measurement of both N2O concentration ([N2O]) and its site-specific isotopic composition (SP-δ15N), namely δ15Nα and δ15Nβ, is desired. Recent developments in Cavity Ring-Down Spectroscopy (CRDS) have enabled high precision measurements of [N2O] and SP-δ15N of a continuous gas flow. However, many N­­2O samples are discrete with limited volume (< 500 ml), and/or high [N2O] (> 2 ppm), and are not suitable for direct measurements by CRDS. Here we present results of a Small Sample Isotope Module 2 (SSIM2) which is coupled to and automatically coordinated with a Picarro isotopic N2O CRDS analyzer to handle and measure high concentration and/or small volume samples. The SSIM2 requires 20 ml of sample per analysis, and transfers the sample to the CRDS for high precision measurement. When the sample injection is < 20 ml, a zero gas is optionally filled to make up the volume. We used the SSIM2 to dilute high [N2O] samples and < 20 ml samples, and tested the effect of dilution on the measured SP-δ15N. In addition, we employed and tested a newly developed double injection method for samples adequate for two 20 ml injections. After the SSIM2 and the CRDS cavity was primed with the first injection, the second injection, which has negligible dilution of the sample, can be accurately measured for both [N2O] and SP-δ15N. Results of these experiments indicate that the precision of SSIM2-CRDS is similar to that of the continuous measurements using the CRDS alone, and that dilution has minimal effect on SP-δ15N, as along as the [N2O] is > 300 ppb after dilution. Overall, the precision of SP-δ15N measured using the SSIM2 is < 0.5 ‰.

  8. Sensitivity and specificity of histology for diagnoses of four common pathogens and detection of nontarget pathogens in adult Chinook salmon (Oncorhynchus tshawytscha) in fresh water.

    PubMed

    Kent, Michael L; Benda, Susan; St-Hilaire, Sophie; Schreck, Carl B

    2013-05-01

    Histology is often underutilized in aquatic animal disease screening and diagnostics. The agreement between histological classifications of infection and results using diagnostic testing from the American Fisheries Society's Blue Book was conducted with 4 common salmon pathogens: Aeromonas salmonicida, Renibacterium salmoninarum, Ceratomyxa shasta, and Nanophyetus salmincola. Adult Chinook salmon (Oncorhynchus tshawytscha) in Oregon were evaluated, and agreement between tests was calculated. Live and dead (both pre- and postspawning) salmon were collected from the Willamette River, Oregon, its tributaries, the Willamette Hatchery, and after holding in cool, pathogen-free water during maturation at Oregon State University. Sensitivity and specificity of histology compared to Blue Book methods for all fish, live fish only, and dead (pre- and postspawned combined) fish only were, respectively, as follows: A. salmonicida (n = 105): specificity 87.5%, 87.5%, 87.5% and sensitivity 38.6%, 14.8%, 60.0%; R. salmoninarum (n = 111): specificity 91.9%, 85.7%, 97.7% and sensitivity 16.0%, 7.1%, 27.2%; C. shasta (n = 136): specificity 56.0%, 63.3%, 28.6% and sensitivity 83.3%, 86.2%, 71.4%; N. salmincola (n = 228): specificity 68.2%, 66.7%, not possible to calculate for dead fish and sensitivity 83.5%, 80.5%, 87.3%. The specificity was good for bacterial pathogens. This was not the case for C. shasta, likely due to detection of presporogenic forms only by histology. Sensitivity of histology for bacterial pathogens was low with the exception of dead fish with A. salmonicida. Kappa analysis for agreement between Blue Book and histology methods was poor to moderate. However, histological observations revealed the presence of other pathogens that would not be detected by other methods.

  9. Sensitivity and specificity of real-time PCR and bacteriological culture for francisellosis in farm-raised Nile tilapia (Oreochromis niloticus L.).

    PubMed

    Assis, G B N; de Oliveira, T F; Gardner, I A; Figueiredo, H C P; Leal, C A G

    2016-09-27

    Despite the worldwide occurrence of Francisella noatunensis subsp. orientalis (Fno) infection in farmed tilapia, sensitivity and specificity estimates of commonly used diagnostic tests have not been reported. This study aimed to estimate the sensitivity and specificity of bacteriological culture and qPCR to detect Fno infection. We tested 559 fish, sampled from four farms with different epidemiological scenarios: (i) healthy fish in a hatchery free of Fno; (ii) targeted sampling of diseased fish with suggestive external clinical signs of francisellosis during an outbreak; (iii) convenience sampling of diseased and clinically healthy fish during an outbreak; and (iv) sampling of healthy fish in a cage farm without a history of outbreaks, but with francisellosis reported in other farms in the same reservoir. The qPCR had higher median sensitivity (range, 48.8-99.5%) than culture (range, 1.6-74.4%). Culture had a substantially lower median sensitivity (1.6%) than qPCR (48.8%) to detect Fno in carrier tilapia (farm 4). Median specificity estimates for both tests were >99.2%. The qPCR is the superior test for use in surveillance and monitoring programmes for francisellosis in farmed Nile tilapia, but both tests have high sensitivity and specificity which make them fit for use in the diagnosis of Fno outbreaks.

  10. Silicon photonic crystal microarrays for high throughput label-free detection of lung cancer cell line lysates with sensitivity and specificity

    NASA Astrophysics Data System (ADS)

    Chakravarty, Swapnajit; Lai, Wei-Cheng; Zou, Yi; Gemmill, Robert M.; Chen, Ray T.

    2013-03-01

    Detection of biomolecules on microarrays based on label-free on-chip optical biosensors is very attractive since this format avoids complex chemistries caused by steric hindrance of labels. Application areas include the detection of cancers and allergens, and food-borne pathogens to name a few. We have demonstrated photonic crystal microcavity biosensors with high sensitivity down to 1pM concentrations (67pg/ml). High sensitivities were achieved by slow light engineering which reduced the radiation loss and increased the stored energy in the photonic crystal microcavity resonance mode. Resonances with high quality factor Q~26,760 in liquid ambient, coupled with larger optical mode volumes allowed enhanced interaction with the analyte biomolecules which resulted in sensitivities down to 10 cells per micro-liter to lung cancer cell lysates. The specificity of detection was ensured by multiplexed detections from multiple photonic crystal microcavities arrayed on the arms of a multimode interference power splitter. Specific binding interactions and control experiments were performed simultaneously at the same instant of time with the same 60 microliter sample volume. Specificity is further ensured by sandwich assay methods in the multiplexed experiment. Sandwich assay based amplification increased the sensitivity further resulting in the detection of lung cancer cell lysates down to concentrations of 2 cells per micro-liter. The miniaturization enabled by photonic crystal biosensors coupled with waveguide interconnected layout thus offers the potential of high throughput proteomics with high sensitivity and specificity.

  11. Evaluating clinical accuracy of continuous glucose monitoring devices: other methods.

    PubMed

    Wentholt, Iris M E; Hart, August A; Hoekstra, Joost B L; DeVries, J Hans

    2008-08-01

    With more and more continuous glucose monitoring devices entering the market, the importance of adequate accuracy assessment grows. This review discusses pros and cons of Regression Analysis and Correlation Coefficient, Relative Difference measures, Bland Altman plot, ISO criteria, combined curve fitting, and epidemiological analyses, the latter including sensitivity, specificity and positive predictive value for hypoglycaemia. Finally, recommendations for much needed head-to-head studies are given. This paper is a revised and adapted version of How to assess and compare the accuracy of continuous glucose monitors?, Diabetes Technology and Therapeutics 2007, in press, published with permission of the editor.

  12. The combination of health anxiety and somatic symptoms: Specificity to anxiety sensitivity cognitive concerns among patients in primary care.

    PubMed

    Fergus, Thomas A; Kelley, Lance P; Griggs, Jackson O

    2016-05-30

    Prior research has found that health anxiety is related to poor patient outcomes in primary care settings. Health anxiety is characterized by at least two presentations: with either severe or no/mild somatic symptoms. Preliminary data indicate that anxiety sensitivity may be important for understanding the presentation of health anxiety with severe somatic symptoms. We further examined whether the combination of health anxiety and somatic symptoms was related to anxiety sensitivity. Participants were adults presenting for treatment at a community health center (N=538). As predicted, the interactive effect between health anxiety and somatic symptoms was associated with anxiety sensitivity cognitive concerns. Health anxiety shared a stronger association with anxiety sensitivity cognitive concerns when coupled with severe, relative to mild, somatic symptoms. Contrary to predictions, the interactive effect was not associated with the other dimensions of anxiety sensitivity. We discuss the potential relevancy of anxiety sensitivity cognitive concerns to the combined presentation of health anxiety and severe somatic symptoms, as well as how this dimension of anxiety sensitivity could be treated in primary care settings.

  13. Meta-analyses of the sensitivity and specificity of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis in the UK and Ireland.

    PubMed

    Nuñez-Garcia, Javier; Downs, Sara H; Parry, Jessica E; Abernethy, Darrell A; Broughan, Jennifer M; Cameron, Angus R; Cook, Alasdair J; de la Rua-Domenech, Ricardo; Goodchild, Anthony V; Gunn, Jane; More, Simon J; Rhodes, Shelley; Rolfe, Simon; Sharp, Michael; Upton, Paul A; Vordermeier, H Martin; Watson, Eamon; Welsh, Michael; Whelan, Adam O; Woolliams, John A; Clifton-Hadley, Richard S; Greiner, Matthias

    2017-03-06

    Bovine Tuberculosis (bTB) in cattle is a global health problem and eradication of the disease requires accurate estimates of diagnostic test performance to optimize their efficiency. The objective of this study was, through statistical meta-analyses, to obtain estimates of sensitivity (Se) and specificity (Sp), for 14 different ante-mortem and post-mortem diagnostic tests for bTB in cattle. Using data from a systematic review of the scientific literature (published 1934-2009) diagnostic Se and Sp were estimated using Bayesian logistic regression models adjusting for confounding factors. Random effect terms were used to account for unexplained heterogeneity. Parameters in the models were implemented using Markov Chain Monte Carlo (MCMC), and posterior distributions for the diagnostic parameters with adjustment for covariates (confounding factors) were obtained using the inverse logit function. Estimates for Se and/or Sp of the tuberculin skin tests and the IFN-γ blood test were compared with estimates published 2010-2015. Median Se for the single intradermal comparative cervical tuberculin skin (SICCT) test (standard interpretation) was 0.50 and Bayesian credible intervals (CrI) were wide (95% CrI 0.26, 0.78). Median Sp for the SICCT test was 1.00 (95% CrI 0.99, 1.00). Estimates for the IFN-γ blood test Bovine Purified Protein Derivative (PPD)-Avian PPD and Early Secreted Antigen target 6 and Culture Filtrate Protein 10 (ESAT-6/CFP10) ESAT6/CFP10 were 0.67 (95% CrI 0.49, 0.82) and 0.78 (95% CrI 0.60, 0.90) respectively for Se, and 0.98 (95% CrI 0.96, 0.99) and 0.99 (95% CrI 0.99, 1.00) for Sp. The study provides an overview of the accuracy of a range of contemporary diagnostic tests for bTB in cattle. Better understanding of diagnostic test performance is essential for the design of effective control strategies and their evaluation.

  14. Specific and Sensitive Isothermal Electrochemical Biosensor for Plant Pathogen DNA Detection with Colloidal Gold Nanoparticles as Probes.

    PubMed

    Lau, Han Yih; Wu, Haoqi; Wee, Eugene J H; Trau, Matt; Wang, Yuling; Botella, Jose R

    2017-01-17

    Developing quick and sensitive molecular diagnostics for plant pathogen detection is challenging. Herein, a nanoparticle based electrochemical biosensor was developed for rapid and sensitive detection of plant pathogen DNA on disposable screen-printed carbon electrodes. This 60 min assay relied on the rapid isothermal amplification of target pathogen DNA sequences by recombinase polymerase amplification (RPA) followed by gold nanoparticle-based electrochemical assessment with differential pulse voltammetry (DPV). Our method was 10,000 times more sensitive than conventional polymerase chain reaction (PCR)/gel electrophoresis and could readily identify P. syringae infected plant samples even before the disease symptoms were visible. On the basis of the speed, sensitivity, simplicity and portability of the approach, we believe the method has potential as a rapid disease management solution for applications in agriculture diagnostics.

  15. Specific and Sensitive Isothermal Electrochemical Biosensor for Plant Pathogen DNA Detection with Colloidal Gold Nanoparticles as Probes

    NASA Astrophysics Data System (ADS)

    Lau, Han Yih; Wu, Haoqi; Wee, Eugene J. H.; Trau, Matt; Wang, Yuling; Botella, Jose R.

    2017-01-01

    Developing quick and sensitive molecular diagnostics for plant pathogen detection is challenging. Herein, a nanoparticle based electrochemical biosensor was developed for rapid and sensitive detection of plant pathogen DNA on disposable screen-printed carbon electrodes. This 60 min assay relied on the rapid isothermal amplification of target pathogen DNA sequences by recombinase polymerase amplification (RPA) followed by gold nanoparticle-based electrochemical assessment with differential pulse voltammetry (DPV). Our method was 10,000 times more sensitive than conventional polymerase chain reaction (PCR)/gel electrophoresis and could readily identify P. syringae infected plant samples even before the disease symptoms were visible. On the basis of the speed, sensitivity, simplicity and portability of the approach, we believe the method has potential as a rapid disease management solution for applications in agriculture diagnostics.

  16. Specific and Sensitive Isothermal Electrochemical Biosensor for Plant Pathogen DNA Detection with Colloidal Gold Nanoparticles as Probes

    PubMed Central

    Lau, Han Yih; Wu, Haoqi; Wee, Eugene J. H.; Trau, Matt; Wang, Yuling; Botella, Jose R.

    2017-01-01

    Developing quick and sensitive molecular diagnostics for plant pathogen detection is challenging. Herein, a nanoparticle based electrochemical biosensor was developed for rapid and sensitive detection of plant pathogen DNA on disposable screen-printed carbon electrodes. This 60 min assay relied on the rapid isothermal amplification of target pathogen DNA sequences by recombinase polymerase amplification (RPA) followed by gold nanoparticle-based electrochemical assessment with differential pulse voltammetry (DPV). Our method was 10,000 times more sensitive than conventional polymerase chain reaction (PCR)/gel electrophoresis and could readily identify P. syringae infected plant samples even before the disease symptoms were visible. On the basis of the speed, sensitivity, simplicity and portability of the approach, we believe the method has potential as a rapid disease management solution for applications in agriculture diagnostics. PMID:28094255

  17. A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma[S

    PubMed Central

    Jiang, Xuntian; Sidhu, Rohini; Porter, Forbes D.; Yanjanin, Nicole M.; Speak, Anneliese O.; te Vruchte, Danielle Taylor; Platt, Frances M.; Fujiwara, Hideji; Scherrer, David E.; Zhang, Jessie; Dietzen, Dennis J.; Schaffer, Jean E.; Ory, Daniel S.

    2011-01-01

    Niemann-Pick type C1 (NPC1) disease is a rare, progressively fatal neurodegenerative disease for which there are no FDA-approved therapies. A major barrier to developing new therapies for this disorder has been the lack of a sensitive and noninvasive diagnostic test. Recently, we demonstrated that two cholesterol oxidation products, specifically cholestane-3β,5α,6β-triol (3β,5α,6β-triol) and 7-ketocholesterol (7-KC), were markedly increased in the plasma of human NPC1 subjects, suggesting a role for these oxysterols in diagnosis of NPC1 disease and evaluation of therapeutics in clinical trials. In the present study, we describe the development of a sensitive and specific LC-MS/MS method for quantifying 3β,5α,6β-triol and 7-KC human plasma after derivatization with N,N-dimethylglycine. We show that dimethylglycine derivatization successfully enhanced the ionization and fragmentation of 3β,5α,6β-triol and 7-KC for mass spectrometric detection of the oxysterol species in human plasma. The oxysterol dimethylglycinates were resolved with high sensitivity and selectivity, and enabled accurate quantification of 3β,5α,6β-triol and 7-KC concentrations in human plasma. The LC-MS/MS assay was able to discriminate with high sensitivity and specificity between control and NPC1 subjects, and offers for the first time a noninvasive, rapid, and highly sensitive method for diagnosis of NPC1 disease. PMID:21518695

  18. Sensitive and specific detection of classical scrapie prions in the brain of goats by real-time quaking-induced conversion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The real-time quaking-induced conversion (RT-QuIC) is a rapid, specific, and sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect sub-infectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully us...

  19. Reliability, Validity, and Sensitivity to Change of Turkish Activities-Specific Balance Confidence Scale in Patients with Unilateral Peripheral Vestibular Disease

    ERIC Educational Resources Information Center

    Kara