Sensitivity Analysis of Multidisciplinary Rotorcraft Simulations

NASA Technical Reports Server (NTRS)

Wang, Li; Diskin, Boris; Biedron, Robert T.; Nielsen, Eric J.; Bauchau, Olivier A.

2017-01-01

A multidisciplinary sensitivity analysis of rotorcraft simulations involving tightly coupled high-fidelity computational fluid dynamics and comprehensive analysis solvers is presented and evaluated. An unstructured sensitivity-enabled Navier-Stokes solver, FUN3D, and a nonlinear flexible multibody dynamics solver, DYMORE, are coupled to predict the aerodynamic loads and structural responses of helicopter rotor blades. A discretely-consistent adjoint-based sensitivity analysis available in FUN3D provides sensitivities arising from unsteady turbulent flows and unstructured dynamic overset meshes, while a complex-variable approach is used to compute DYMORE structural sensitivities with respect to aerodynamic loads. The multidisciplinary sensitivity analysis is conducted through integrating the sensitivity components from each discipline of the coupled system. Numerical results verify accuracy of the FUN3D/DYMORE system by conducting simulations for a benchmark rotorcraft test model and comparing solutions with established analyses and experimental data. Complex-variable implementation of sensitivity analysis of DYMORE and the coupled FUN3D/DYMORE system is verified by comparing with real-valued analysis and sensitivities. Correctness of adjoint formulations for FUN3D/DYMORE interfaces is verified by comparing adjoint-based and complex-variable sensitivities. Finally, sensitivities of the lift and drag functions obtained by complex-variable FUN3D/DYMORE simulations are compared with sensitivities computed by the multidisciplinary sensitivity analysis, which couples adjoint-based flow and grid sensitivities of FUN3D and FUN3D/DYMORE interfaces with complex-variable sensitivities of DYMORE structural responses.

Cluster subgroups based on overall pressure pain sensitivity and psychosocial factors in chronic musculoskeletal pain: Differences in clinical outcomes.

PubMed

Almeida, Suzana C; George, Steven Z; Leite, Raquel D V; Oliveira, Anamaria S; Chaves, Thais C

2018-05-17

We aimed to empirically derive psychosocial and pain sensitivity subgroups using cluster analysis within a sample of individuals with chronic musculoskeletal pain (CMP) and to investigate derived subgroups for differences in pain and disability outcomes. Eighty female participants with CMP answered psychosocial and disability scales and were assessed for pressure pain sensitivity. A cluster analysis was used to derive subgroups, and analysis of variance (ANOVA) was used to investigate differences between subgroups. Psychosocial factors (kinesiophobia, pain catastrophizing, anxiety, and depression) and overall pressure pain threshold (PPT) were entered into the cluster analysis. Three subgroups were empirically derived: cluster 1 (high pain sensitivity and high psychosocial distress; n = 12) characterized by low overall PPT and high psychosocial scores; cluster 2 (high pain sensitivity and intermediate psychosocial distress; n = 39) characterized by low overall PPT and intermediate psychosocial scores; and cluster 3 (low pain sensitivity and low psychosocial distress; n = 29) characterized by high overall PPT and low psychosocial scores compared to the other subgroups. Cluster 1 showed higher values for mean pain intensity (F (2,77)  = 10.58, p < 0.001) compared with cluster 3, and cluster 1 showed higher values for disability (F (2,77)  = 3.81, p = 0.03) compared with both clusters 2 and 3. Only cluster 1 was distinct from cluster 3 according to both pain and disability outcomes. Pain catastrophizing, depression, and anxiety were the psychosocial variables that best differentiated the subgroups. Overall, these results call attention to the importance of considering pain sensitivity and psychosocial variables to obtain a more comprehensive characterization of CMP patients' subtypes.

Two-step sensitivity testing of parametrized and regionalized life cycle assessments: methodology and case study.

PubMed

Mutel, Christopher L; de Baan, Laura; Hellweg, Stefanie

2013-06-04

Comprehensive sensitivity analysis is a significant tool to interpret and improve life cycle assessment (LCA) models, but is rarely performed. Sensitivity analysis will increase in importance as inventory databases become regionalized, increasing the number of system parameters, and parametrized, adding complexity through variables and nonlinear formulas. We propose and implement a new two-step approach to sensitivity analysis. First, we identify parameters with high global sensitivities for further examination and analysis with a screening step, the method of elementary effects. Second, the more computationally intensive contribution to variance test is used to quantify the relative importance of these parameters. The two-step sensitivity test is illustrated on a regionalized, nonlinear case study of the biodiversity impacts from land use of cocoa production, including a worldwide cocoa products trade model. Our simplified trade model can be used for transformable commodities where one is assessing market shares that vary over time. In the case study, the highly uncertain characterization factors for the Ivory Coast and Ghana contributed more than 50% of variance for almost all countries and years examined. The two-step sensitivity test allows for the interpretation, understanding, and improvement of large, complex, and nonlinear LCA systems.

The application of sensitivity analysis to models of large scale physiological systems

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1974-01-01

A survey of the literature of sensitivity analysis as it applies to biological systems is reported as well as a brief development of sensitivity theory. A simple population model and a more complex thermoregulatory model illustrate the investigatory techniques and interpretation of parameter sensitivity analysis. The role of sensitivity analysis in validating and verifying models, and in identifying relative parameter influence in estimating errors in model behavior due to uncertainty in input data is presented. This analysis is valuable to the simulationist and the experimentalist in allocating resources for data collection. A method for reducing highly complex, nonlinear models to simple linear algebraic models that could be useful for making rapid, first order calculations of system behavior is presented.

Performance of the high-sensitivity troponin assay in diagnosing acute myocardial infarction: systematic review and meta-analysis

PubMed Central

Al-Saleh, Ayman; Alazzoni, Ashraf; Al Shalash, Saleh; Ye, Chenglin; Mbuagbaw, Lawrence; Thabane, Lehana; Jolly, Sanjit S.

2014-01-01

Background High-sensitivity cardiac troponin assays have been adopted by many clinical centres worldwide; however, clinicians are uncertain how to interpret the results. We sought to assess the utility of these assays in diagnosing acute myocardial infarction (MI). Methods We carried out a systematic review and meta-analysis of studies comparing high-sensitivity with conventional assays of cardiac troponin levels among adults with suspected acute MI in the emergency department. We searched MEDLINE, EMBASE and Cochrane databases up to April 2013 and used bivariable random-effects modelling to obtain summary parameters for diagnostic accuracy. Results We identified 9 studies that assessed the use of high-sensitivity troponin T assays (n = 9186 patients). The summary sensitivity of these tests in diagnosing acute MI at presentation to the emergency department was estimated to be 0.94 (95% confidence interval [CI] 0.89–0.97); for conventional tests, it was 0.72 (95% CI 0.63–0.79). The summary specificity was 0.73 (95% CI 0.64–0.81) for the high-sensitivity assay compared with 0.95 (95% CI 0.93–0.97) for the conventional assay. The differences in estimates of the summary sensitivity and specificity between the high-sensitivity and conventional assays were statistically significant (p < 0.01). The area under the curve was similar for both tests carried out 3–6 hours after presentation. Three studies assessed the use of high-sensitivity troponin I assays and showed similar results. Interpretation Used at presentation to the emergency department, the high-sensitivity cardiac troponin assay has improved sensitivity, but reduced specificity, compared with the conventional troponin assay. With repeated measurements over 6 hours, the area under the curve is similar for both tests, indicating that the major advantage of the high-sensitivity test is early diagnosis. PMID:25295240

Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism

PubMed Central

Vandell, Alexander G; Walker, Joseph; Brown, Karen S; Zhang, George; Lin, Min; Grosso, Michael A; Mercuri, Michele F

2017-01-01

Objective The aim of this study was to investigate whether genetic variants can identify patients with venous thromboembolism (VTE) at an increased risk of bleeding with warfarin. Methods Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin. In this subanalysis of Hokusai VTE, patients genotyped for variants in CYP2C9 and VKORC1 genes were divided into three warfarin sensitivity types (normal, sensitive and highly sensitive) based on their genotypes. An exploratory analysis was also conducted comparing normal responders to pooled sensitive responders (ie, sensitive and highly sensitive responders). Results The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE. Among 1978 patients randomised to warfarin, 63.0% (1247) were normal responders, 34.1% (675) were sensitive responders and 2.8% (56) were highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders had heparin therapy discontinued earlier (p<0.001), had a decreased final weekly warfarin dose (p<0.001), spent more time overanticoagulated (p<0.001) and had an increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252). Conclusion In this study, CYP2C9 and VKORC1 genotypes identified patients with VTE at increased bleeding risk with warfarin. Trial registration number NCT00986154. PMID:28689179

A geostatistics-informed hierarchical sensitivity analysis method for complex groundwater flow and transport modeling: GEOSTATISTICAL SENSITIVITY ANALYSIS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Heng; Chen, Xingyuan; Ye, Ming

Sensitivity analysis is an important tool for quantifying uncertainty in the outputs of mathematical models, especially for complex systems with a high dimension of spatially correlated parameters. Variance-based global sensitivity analysis has gained popularity because it can quantify the relative contribution of uncertainty from different sources. However, its computational cost increases dramatically with the complexity of the considered model and the dimension of model parameters. In this study we developed a hierarchical sensitivity analysis method that (1) constructs an uncertainty hierarchy by analyzing the input uncertainty sources, and (2) accounts for the spatial correlation among parameters at each level ofmore » the hierarchy using geostatistical tools. The contribution of uncertainty source at each hierarchy level is measured by sensitivity indices calculated using the variance decomposition method. Using this methodology, we identified the most important uncertainty source for a dynamic groundwater flow and solute transport in model at the Department of Energy (DOE) Hanford site. The results indicate that boundary conditions and permeability field contribute the most uncertainty to the simulated head field and tracer plume, respectively. The relative contribution from each source varied spatially and temporally as driven by the dynamic interaction between groundwater and river water at the site. By using a geostatistical approach to reduce the number of realizations needed for the sensitivity analysis, the computational cost of implementing the developed method was reduced to a practically manageable level. The developed sensitivity analysis method is generally applicable to a wide range of hydrologic and environmental problems that deal with high-dimensional spatially-distributed parameters.« less

A highly sensitive method for analysis of 7-dehydrocholesterol for the study of Smith-Lemli-Opitz syndrome[S

PubMed Central

Liu, Wei; Xu, Libin; Lamberson, Connor; Haas, Dorothea; Korade, Zeljka; Porter, Ned A.

2014-01-01

We describe a highly sensitive method for the detection of 7-dehydrocholesterol (7-DHC), the biosynthetic precursor of cholesterol, based on its reactivity with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) in a Diels-Alder cycloaddition reaction. Samples of biological tissues and fluids with added deuterium-labeled internal standards were derivatized with PTAD and analyzed by LC-MS. This protocol permits fast processing of samples, short chromatography times, and high sensitivity. We applied this method to the analysis of cells, blood, and tissues from several sources, including human plasma. Another innovative aspect of this study is that it provides a reliable and highly reproducible measurement of 7-DHC in 7-dehydrocholesterol reductase (Dhcr7)-HET mouse (a model for Smith-Lemli-Opitz syndrome) samples, showing regional differences in the brain tissue. We found that the levels of 7-DHC are consistently higher in Dhcr7-HET mice than in controls, with the spinal cord and peripheral nerve showing the biggest differences. In addition to 7-DHC, sensitive analysis of desmosterol in tissues and blood was also accomplished with this PTAD method by assaying adducts formed from the PTAD “ene” reaction. The method reported here may provide a highly sensitive and high throughput way to identify at-risk populations having errors in cholesterol biosynthesis. PMID:24259532

How the definition of acceptable antigens and epitope analysis can facilitate transplantation of highly sensitized patients with excellent long-term graft survival.

PubMed

Heidt, Sebastiaan; Haasnoot, Geert W; Claas, Frans H J

2018-05-24

Highly sensitized patients awaiting a renal transplant have a low chance of receiving an organ offer. Defining acceptable antigens and using this information for allocation purposes can vastly enhance transplantation of this subgroup of patients, which is the essence of the Eurotransplant Acceptable Mismatch program. Acceptable antigens can be determined by extensive laboratory testing, as well as on basis of human leukocyte antigen (HLA) epitope analyses. Within the Acceptable Mismatch program, there is no effect of HLA mismatches on long-term graft survival. Furthermore, patients transplanted through the Acceptable Mismatch program have similar long-term graft survival to nonsensitized patients transplanted through regular allocation. Although HLA epitope analysis is already being used for defining acceptable HLA antigens for highly sensitized patients in the Acceptable Mismatch program, increasing knowledge on HLA antibody - epitope interactions will pave the way toward the definition of acceptable epitopes for highly sensitized patients in the future. Allocation based on acceptable antigens can facilitate transplantation of highly sensitized patients with excellent long-term graft survival.

Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism.

PubMed

Vandell, Alexander G; Walker, Joseph; Brown, Karen S; Zhang, George; Lin, Min; Grosso, Michael A; Mercuri, Michele F

2017-11-01

The aim of this study was to investigate whether genetic variants can identify patients with venous thromboembolism (VTE) at an increased risk of bleeding with warfarin. Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin. In this subanalysis of Hokusai VTE, patients genotyped for variants in CYP2C9 and VKORC1 genes were divided into three warfarin sensitivity types (normal, sensitive and highly sensitive) based on their genotypes. An exploratory analysis was also conducted comparing normal responders to pooled sensitive responders (ie, sensitive and highly sensitive responders). The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE. Among 1978 patients randomised to warfarin, 63.0% (1247) were normal responders, 34.1% (675) were sensitive responders and 2.8% (56) were highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders had heparin therapy discontinued earlier (p<0.001), had a decreased final weekly warfarin dose (p<0.001), spent more time overanticoagulated (p<0.001) and had an increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252). In this study, CYP2C9 and VKORC1 genotypes identified patients with VTE at increased bleeding risk with warfarin. NCT00986154. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients.

PubMed

Redfield, Robert R; Scalea, Joseph R; Zens, Tiffany J; Mandelbrot, Didier A; Leverson, Glen; Kaufman, Dixon B; Djamali, Arjang

2016-10-01

We sought to determine whether the mode of sensitization in highly sensitized patients contributed to kidney allograft survival. An analysis of the United Network for Organ Sharing dataset involving all kidney transplants between 1997 and 2014 was undertaken. Highly sensitized adult kidney transplant recipients [panel reactive antibody (PRA) ≥98%] were compared with adult, primary non-sensitized and re-transplant recipients. Kaplan-Meier survival analyses were used to determine allograft survival rates. Cox proportional hazards regression analyses were conducted to determine the association of graft loss with key predictors. Fifty-three percent of highly sensitized patients transplanted were re-transplants. Pregnancy and transfusion were the only sensitizing event in 20 and 5%, respectively. The 10-year actuarial graft survival for highly sensitized recipients was 43.9% compared with 52.4% for non-sensitized patients, P < 0.001. The combination of being highly sensitized by either pregnancy or blood transfusion increased the risk of graft loss by 23% [hazard ratio (HR) 1.230, confidence interval (CI) 1.150-1.315, P < 0.001], and the combination of being highly sensitized from a prior transplant increased the risk of graft loss by 58.1% (HR 1.581, CI 1.473-1.698, P < 0.001). The mode of sensitization predicts graft survival in highly sensitized kidney transplant recipients (PRA ≥98%). Patients who are highly sensitized from re-transplants have inferior graft survival compared with patients who are highly sensitized from other modes of sensitization. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Diagnostic performance of contrast-enhanced spectral mammography: Systematic review and meta-analysis.

PubMed

Tagliafico, Alberto Stefano; Bignotti, Bianca; Rossi, Federica; Signori, Alessio; Sormani, Maria Pia; Valdora, Francesca; Calabrese, Massimo; Houssami, Nehmat

2016-08-01

To estimate sensitivity and specificity of CESM for breast cancer diagnosis. Systematic review and meta-analysis of the accuracy of CESM in finding breast cancer in highly selected women. We estimated summary receiver operating characteristic curves, sensitivity and specificity according to quality criteria with QUADAS-2. Six hundred four studies were retrieved, 8 of these reporting on 920 patients with 994 lesions, were eligible for inclusion. Estimated sensitivity from all studies was: 0.98 (95% CI: 0.96-1.00). Specificity was estimated from six studies reporting raw data: 0.58 (95% CI: 0.38-0.77). The majority of studies were scored as at high risk of bias due to the very selected populations. CESM has a high sensitivity but very low specificity. The source studies were based on highly selected case series and prone to selection bias. High-quality studies are required to assess the accuracy of CESM in unselected cases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multidisciplinary design optimization using multiobjective formulation techniques

NASA Technical Reports Server (NTRS)

Chattopadhyay, Aditi; Pagaldipti, Narayanan S.

1995-01-01

This report addresses the development of a multidisciplinary optimization procedure using an efficient semi-analytical sensitivity analysis technique and multilevel decomposition for the design of aerospace vehicles. A semi-analytical sensitivity analysis procedure is developed for calculating computational grid sensitivities and aerodynamic design sensitivities. Accuracy and efficiency of the sensitivity analysis procedure is established through comparison of the results with those obtained using a finite difference technique. The developed sensitivity analysis technique are then used within a multidisciplinary optimization procedure for designing aerospace vehicles. The optimization problem, with the integration of aerodynamics and structures, is decomposed into two levels. Optimization is performed for improved aerodynamic performance at the first level and improved structural performance at the second level. Aerodynamic analysis is performed by solving the three-dimensional parabolized Navier Stokes equations. A nonlinear programming technique and an approximate analysis procedure are used for optimization. The proceduredeveloped is applied to design the wing of a high speed aircraft. Results obtained show significant improvements in the aircraft aerodynamic and structural performance when compared to a reference or baseline configuration. The use of the semi-analytical sensitivity technique provides significant computational savings.

Sensitivity Analysis for Multidisciplinary Systems (SAMS)

DTIC Science & Technology

2016-12-01

support both mode-based structural representations and time-dependent, nonlinear finite element structural dynamics. This interim report describes...Adaptation, & Sensitivity Toolkit • Elasticity, heat transfer, & compressible flow • Adjoint solver for sensitivity analysis • High-order finite elements ...PROGRAM ELEMENT NUMBER 62201F 6. AUTHOR(S) Richard D. Snyder 5d. PROJECT NUMBER 2401 5e. TASK NUMBER N/A 5f. WORK UNIT NUMBER Q1FS 7

Do We Know Who Will Drop out?: A Review of the Predictors of Dropping out of High School--Precision, Sensitivity, and Specificity

ERIC Educational Resources Information Center

Bowers, Alex J.; Sprott, Ryan; Taff, Sherry A.

2013-01-01

The purpose of this study is to review the literature on the most accurate indicators of students at risk of dropping out of high school. We used Relative Operating Characteristic (ROC) analysis to compare the sensitivity and specificity of 110 dropout flags across 36 studies. Our results indicate that 1) ROC analysis provides a means to compare…

A Comparative Study of Very High Burning Rate Materials - HIVELITE compositions 300511 and 300435

DTIC Science & Technology

1982-08-01

explosives and more or as sensitive as RDX and HMX . Thermal Sensitivity Differential Thermal Analysis/Thermogravimetric Analysis (DTA/TGA) Simultaneous...impact than Comp B end RDX but is less sensitive than lead azide. HIVELITE 30051i on the other hand, is less sensitive than Comp B and RDX on the ERL...represents the alpha to beta phase transition of KNO 3 . This endotherm is followed by four exotherms with peaks at 538 K (265*C), 567 K (2940C), 598 K

Case-Deletion Diagnostics for Maximum Likelihood Multipoint Quantitative Trait Locus Linkage Analysis

PubMed Central

Mendoza, Maria C.B.; Burns, Trudy L.; Jones, Michael P.

2009-01-01

Objectives Case-deletion diagnostic methods are tools that allow identification of influential observations that may affect parameter estimates and model fitting conclusions. The goal of this paper was to develop two case-deletion diagnostics, the exact case deletion (ECD) and the empirical influence function (EIF), for detecting outliers that can affect results of sib-pair maximum likelihood quantitative trait locus (QTL) linkage analysis. Methods Subroutines to compute the ECD and EIF were incorporated into the maximum likelihood QTL variance estimation components of the linkage analysis program MAPMAKER/SIBS. Performance of the diagnostics was compared in simulation studies that evaluated the proportion of outliers correctly identified (sensitivity), and the proportion of non-outliers correctly identified (specificity). Results Simulations involving nuclear family data sets with one outlier showed EIF sensitivities approximated ECD sensitivities well for outlier-affected parameters. Sensitivities were high, indicating the outlier was identified a high proportion of the time. Simulations also showed the enormous computational time advantage of the EIF. Diagnostics applied to body mass index in nuclear families detected observations influential on the lod score and model parameter estimates. Conclusions The EIF is a practical diagnostic tool that has the advantages of high sensitivity and quick computation. PMID:19172086

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.

Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with high-grade glioma, a systematic review and meta-analysis.

PubMed

van Dijken, Bart R J; van Laar, Peter Jan; Holtman, Gea A; van der Hoorn, Anouk

2017-10-01

Treatment response assessment in high-grade gliomas uses contrast enhanced T1-weighted MRI, but is unreliable. Novel advanced MRI techniques have been studied, but the accuracy is not well known. Therefore, we performed a systematic meta-analysis to assess the diagnostic accuracy of anatomical and advanced MRI for treatment response in high-grade gliomas. Databases were searched systematically. Study selection and data extraction were done by two authors independently. Meta-analysis was performed using a bivariate random effects model when ≥5 studies were included. Anatomical MRI (five studies, 166 patients) showed a pooled sensitivity and specificity of 68% (95%CI 51-81) and 77% (45-93), respectively. Pooled apparent diffusion coefficients (seven studies, 204 patients) demonstrated a sensitivity of 71% (60-80) and specificity of 87% (77-93). DSC-perfusion (18 studies, 708 patients) sensitivity was 87% (82-91) with a specificity of 86% (77-91). DCE-perfusion (five studies, 207 patients) sensitivity was 92% (73-98) and specificity was 85% (76-92). The sensitivity of spectroscopy (nine studies, 203 patients) was 91% (79-97) and specificity was 95% (65-99). Advanced techniques showed higher diagnostic accuracy than anatomical MRI, the highest for spectroscopy, supporting the use in treatment response assessment in high-grade gliomas. • Treatment response assessment in high-grade gliomas with anatomical MRI is unreliable • Novel advanced MRI techniques have been studied, but diagnostic accuracy is unknown • Meta-analysis demonstrates that advanced MRI showed higher diagnostic accuracy than anatomical MRI • Highest diagnostic accuracy for spectroscopy and perfusion MRI • Supports the incorporation of advanced MRI in high-grade glioma treatment response assessment.

Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems With Switching [Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems

DOE PAGES

Zhang, Hong; Abhyankar, Shrirang; Constantinescu, Emil; ...

2017-01-24

Sensitivity analysis is an important tool for describing power system dynamic behavior in response to parameter variations. It is a central component in preventive and corrective control applications. The existing approaches for sensitivity calculations, namely, finite-difference and forward sensitivity analysis, require a computational effort that increases linearly with the number of sensitivity parameters. In this paper, we investigate, implement, and test a discrete adjoint sensitivity approach whose computational effort is effectively independent of the number of sensitivity parameters. The proposed approach is highly efficient for calculating sensitivities of larger systems and is consistent, within machine precision, with the function whosemore » sensitivity we are seeking. This is an essential feature for use in optimization applications. Moreover, our approach includes a consistent treatment of systems with switching, such as dc exciters, by deriving and implementing the adjoint jump conditions that arise from state-dependent and time-dependent switchings. The accuracy and the computational efficiency of the proposed approach are demonstrated in comparison with the forward sensitivity analysis approach. In conclusion, this paper focuses primarily on the power system dynamics, but the approach is general and can be applied to hybrid dynamical systems in a broader range of fields.« less

Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems With Switching [Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hong; Abhyankar, Shrirang; Constantinescu, Emil

Sensitivity analysis is an important tool for describing power system dynamic behavior in response to parameter variations. It is a central component in preventive and corrective control applications. The existing approaches for sensitivity calculations, namely, finite-difference and forward sensitivity analysis, require a computational effort that increases linearly with the number of sensitivity parameters. In this paper, we investigate, implement, and test a discrete adjoint sensitivity approach whose computational effort is effectively independent of the number of sensitivity parameters. The proposed approach is highly efficient for calculating sensitivities of larger systems and is consistent, within machine precision, with the function whosemore » sensitivity we are seeking. This is an essential feature for use in optimization applications. Moreover, our approach includes a consistent treatment of systems with switching, such as dc exciters, by deriving and implementing the adjoint jump conditions that arise from state-dependent and time-dependent switchings. The accuracy and the computational efficiency of the proposed approach are demonstrated in comparison with the forward sensitivity analysis approach. In conclusion, this paper focuses primarily on the power system dynamics, but the approach is general and can be applied to hybrid dynamical systems in a broader range of fields.« less

Analysis of the causes of discrepancies in troponin I concentrations as measured by ARCHITECT High-Sensitive Troponin I ST and STACIA CLEIA cTnI.

PubMed

Kondo, Takashi; Kobayashi, Daisuke; Mochizuki, Maki; Asanuma, Kouichi; Takahashi, Satoshi

2017-01-01

Background Recently developed reagents for the highly sensitive measurement of cardiac troponin I are useful for early diagnosis of acute coronary syndrome. However, differences in measured values between these new reagents and previously used reagents have not been well studied. In this study, we aimed to compare the values between ARCHITECT High-Sensitive Troponin I ST (newly developed reagents), ARCHITECT Troponin I ST and STACIA CLEIA cardiac troponin I (two previously developed reagent kits). Methods Gel filtration high-performance liquid chromatography was used to analyse the causes of differences in measured values. Results The measured values differed between ARCHITECT High-Sensitive Troponin I ST and STACIA CLEIA cardiac troponin I reagents (r = 0.82). Cross-reactivity tests using plasma with added skeletal-muscle troponin I resulted in higher reactivity (2.17-3.03%) for the STACIA CLEIA cardiac troponin I reagents compared with that for the ARCHITECT High-Sensitive Troponin I ST reagents (less than 0.014%). In addition, analysis of three representative samples using gel filtration high-performance liquid chromatography revealed reagent-specific differences in the reactivity against each cardiac troponin I complex; this could explain the differences in values observed for some of the samples. Conclusion The newly developed ARCHITECT High-Sensitive Troponin I ST reagents were not affected by the presence of skeletal-muscle troponin I in the blood and may be useful for routine examinations.

High Sensitivity Combined with Extended Structural Coverage of Labile Compounds via Nanoelectrospray Ionization at Subambient Pressures

DOE PAGES

Cox, Jonathan T.; Kronewitter, Scott R.; Shukla, Anil K.; ...

2014-09-15

Subambient pressure ionization with nanoelectrospray (SPIN) has proven to be effective in producing ions with high efficiency and transmitting them to low pressures for high sensitivity mass spectrometry (MS) analysis. Here we present evidence that not only does the SPIN source improve MS sensitivity but also allows for gentler ionization conditions. The gentleness of a conventional heated capillary electrospray ionization (ESI) source and the SPIN source was compared by the liquid chromatography mass spectrometry (LC-MS) analysis of colominic acid. Colominic acid is a mixture of sialic acid polymers of different lengths containing labile glycosidic linkages between monomer units necessitating amore » gentle ion source. By coupling the SPIN source with high resolution mass spectrometry and using advanced data processing tools, we demonstrate much extended coverage of sialic acid polymer chains as compared to using the conventional ESI source. Additionally we show that SPIN-LC-MS is effective in elucidating polymer features with high efficiency and high sensitivity previously unattainable by the conventional ESI-LC-MS methods.« less

Pseudotargeted MS Method for the Sensitive Analysis of Protein Phosphorylation in Protein Complexes.

PubMed

Lyu, Jiawen; Wang, Yan; Mao, Jiawei; Yao, Yating; Wang, Shujuan; Zheng, Yong; Ye, Mingliang

2018-05-15

In this study, we presented an enrichment-free approach for the sensitive analysis of protein phosphorylation in minute amounts of samples, such as purified protein complexes. This method takes advantage of the high sensitivity of parallel reaction monitoring (PRM). Specifically, low confident phosphopeptides identified from the data-dependent acquisition (DDA) data set were used to build a pseudotargeted list for PRM analysis to allow the identification of additional phosphopeptides with high confidence. The development of this targeted approach is very easy as the same sample and the same LC-system were used for the discovery and the targeted analysis phases. No sample fractionation or enrichment was required for the discovery phase which allowed this method to analyze minute amount of sample. We applied this pseudotargeted MS method to quantitatively examine phosphopeptides in affinity purified endogenous Shc1 protein complexes at four temporal stages of EGF signaling and identified 82 phospho-sites. To our knowledge, this is the highest number of phospho-sites identified from the protein complexes. This pseudotargeted MS method is highly sensitive in the identification of low abundance phosphopeptides and could be a powerful tool to study phosphorylation-regulated assembly of protein complex.

Rapid, sensitive and direct analysis of exopolysaccharides from biofilm on aluminum surfaces exposed to sea water using MALDI-TOF MS.

PubMed

Hasan, Nazim; Gopal, Judy; Wu, Hui-Fen

2011-11-01

Biofilm studies have extensive significance since their results can provide insights into the behavior of bacteria on material surfaces when exposed to natural water. This is the first attempt of using matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) for detecting the polysaccharides formed in a complex biofilm consisting of a mixed consortium of marine microbes. MALDI-MS has been applied to directly analyze exopolysaccharides (EPS) in the biofilm formed on aluminum surfaces exposed to seawater. The optimal conditions for MALDI-MS applied to EPS analysis of biofilm have been described. In addition, microbiologically influenced corrosion of aluminum exposed to sea water by a marine fungus was also observed and the fungus identity established using MALDI-MS analysis of EPS. Rapid, sensitive and direct MALDI-MS analysis on biofilm would dramatically speed up and provide new insights into biofilm studies due to its excellent advantages such as simplicity, high sensitivity, high selectivity and high speed. This study introduces a novel, fast, sensitive and selective platform for biofilm study from natural water without the need of tedious culturing steps or complicated sample pretreatment procedures. Copyright © 2011 John Wiley & Sons, Ltd.

Enhanced electrochemical nanoring electrode for analysis of cytosol in single cells.

PubMed

Zhuang, Lihong; Zuo, Huanzhen; Wu, Zengqiang; Wang, Yu; Fang, Danjun; Jiang, Dechen

2014-12-02

A microelectrode array has been applied for single cell analysis with relatively high throughput; however, the cells were typically cultured on the microelectrodes under cell-size microwell traps leading to the difficulty in the functionalization of an electrode surface for higher detection sensitivity. Here, nanoring electrodes embedded under the microwell traps were fabricated to achieve the isolation of the electrode surface and the cell support, and thus, the electrode surface can be modified to obtain enhanced electrochemical sensitivity for single cell analysis. Moreover, the nanometer-sized electrode permitted a faster diffusion of analyte to the surface for additional improvement in the sensitivity, which was evidenced by the electrochemical characterization and the simulation. To demonstrate the concept of the functionalized nanoring electrode for single cell analysis, the electrode surface was deposited with prussian blue to detect intracellular hydrogen peroxide at a single cell. Hundreds of picoamperes were observed on our functionalized nanoring electrode exhibiting the enhanced electrochemical sensitivity. The success in the achievement of a functionalized nanoring electrode will benefit the development of high throughput single cell electrochemical analysis.

Diagnostic staging laparoscopy in gastric cancer treatment: A cost-effectiveness analysis.

PubMed

Li, Kevin; Cannon, John G D; Jiang, Sam Y; Sambare, Tanmaya D; Owens, Douglas K; Bendavid, Eran; Poultsides, George A

2018-05-01

Accurate preoperative staging helps avert morbidity, mortality, and cost associated with non-therapeutic laparotomy in gastric cancer (GC) patients. Diagnostic staging laparoscopy (DSL) can detect metastases with high sensitivity, but its cost-effectiveness has not been previously studied. We developed a decision analysis model to assess the cost-effectiveness of preoperative DSL in GC workup. Analysis was based on a hypothetical cohort of GC patients in the U.S. for whom initial imaging shows no metastases. The cost-effectiveness of DSL was measured as cost per quality-adjusted life-year (QALY) gained. Drivers of cost-effectiveness were assessed in sensitivity analysis. Preoperative DSL required an investment of $107 012 per QALY. In sensitivity analysis, DSL became cost-effective at a threshold of $100 000/QALY when the probability of occult metastases exceeded 31.5% or when test sensitivity for metastases exceeded 86.3%. The likelihood of cost-effectiveness increased from 46% to 93% when both parameters were set at maximum reported values. The cost-effectiveness of DSL for GC patients is highly dependent on patient and test characteristics, and is more likely when DSL is used selectively where procedure yield is high, such as for locally advanced disease or in detecting peritoneal and superficial versus deep liver lesions. © 2017 Wiley Periodicals, Inc.

Development of Multiobjective Optimization Techniques for Sonic Boom Minimization

NASA Technical Reports Server (NTRS)

Chattopadhyay, Aditi; Rajadas, John Narayan; Pagaldipti, Naryanan S.

1996-01-01

A discrete, semi-analytical sensitivity analysis procedure has been developed for calculating aerodynamic design sensitivities. The sensitivities of the flow variables and the grid coordinates are numerically calculated using direct differentiation of the respective discretized governing equations. The sensitivity analysis techniques are adapted within a parabolized Navier Stokes equations solver. Aerodynamic design sensitivities for high speed wing-body configurations are calculated using the semi-analytical sensitivity analysis procedures. Representative results obtained compare well with those obtained using the finite difference approach and establish the computational efficiency and accuracy of the semi-analytical procedures. Multidisciplinary design optimization procedures have been developed for aerospace applications namely, gas turbine blades and high speed wing-body configurations. In complex applications, the coupled optimization problems are decomposed into sublevels using multilevel decomposition techniques. In cases with multiple objective functions, formal multiobjective formulation such as the Kreisselmeier-Steinhauser function approach and the modified global criteria approach have been used. Nonlinear programming techniques for continuous design variables and a hybrid optimization technique, based on a simulated annealing algorithm, for discrete design variables have been used for solving the optimization problems. The optimization procedure for gas turbine blades improves the aerodynamic and heat transfer characteristics of the blades. The two-dimensional, blade-to-blade aerodynamic analysis is performed using a panel code. The blade heat transfer analysis is performed using an in-house developed finite element procedure. The optimization procedure yields blade shapes with significantly improved velocity and temperature distributions. The multidisciplinary design optimization procedures for high speed wing-body configurations simultaneously improve the aerodynamic, the sonic boom and the structural characteristics of the aircraft. The flow solution is obtained using a comprehensive parabolized Navier Stokes solver. Sonic boom analysis is performed using an extrapolation procedure. The aircraft wing load carrying member is modeled as either an isotropic or a composite box beam. The isotropic box beam is analyzed using thin wall theory. The composite box beam is analyzed using a finite element procedure. The developed optimization procedures yield significant improvements in all the performance criteria and provide interesting design trade-offs. The semi-analytical sensitivity analysis techniques offer significant computational savings and allow the use of comprehensive analysis procedures within design optimization studies.

Application of a sensitivity analysis technique to high-order digital flight control systems

NASA Technical Reports Server (NTRS)

Paduano, James D.; Downing, David R.

1987-01-01

A sensitivity analysis technique for multiloop flight control systems is studied. This technique uses the scaled singular values of the return difference matrix as a measure of the relative stability of a control system. It then uses the gradients of these singular values with respect to system and controller parameters to judge sensitivity. The sensitivity analysis technique is first reviewed; then it is extended to include digital systems, through the derivation of singular-value gradient equations. Gradients with respect to parameters which do not appear explicitly as control-system matrix elements are also derived, so that high-order systems can be studied. A complete review of the integrated technique is given by way of a simple example: the inverted pendulum problem. The technique is then demonstrated on the X-29 control laws. Results show linear models of real systems can be analyzed by this sensitivity technique, if it is applied with care. A computer program called SVA was written to accomplish the singular-value sensitivity analysis techniques. Thus computational methods and considerations form an integral part of many of the discussions. A user's guide to the program is included. The SVA is a fully public domain program, running on the NASA/Dryden Elxsi computer.

Analyses of a heterogeneous lattice hydrodynamic model with low and high-sensitivity vehicles

NASA Astrophysics Data System (ADS)

Kaur, Ramanpreet; Sharma, Sapna

2018-06-01

Basic lattice model is extended to study the heterogeneous traffic by considering the optimal current difference effect on a unidirectional single lane highway. Heterogeneous traffic consisting of low- and high-sensitivity vehicles is modeled and their impact on stability of mixed traffic flow has been examined through linear stability analysis. The stability of flow is investigated in five distinct regions of the neutral stability diagram corresponding to the amount of higher sensitivity vehicles present on road. In order to investigate the propagating behavior of density waves non linear analysis is performed and near the critical point, the kink antikink soliton is obtained by driving mKdV equation. The effect of fraction parameter corresponding to high sensitivity vehicles is investigated and the results indicates that the stability rise up due to the fraction parameter. The theoretical findings are verified via direct numerical simulation.

A Multi-Objective Decision-Making Model for Resources Allocation in Humanitarian Relief

DTIC Science & Technology

2007-03-01

Applied Mathematics and Computation 163, 2005, pp756 19. Malczewski, J., GIS and Multicriteria Decision Analysis , John Wiley and Sons, New York... used when interpreting the results of the analysis . (Raimo et al. 2002) (7) Sensitivity analysis Sensitivity analysis in a DA process answers...Budget Scenario Analysis The MILP is solved ( using LINDO 6.1) for high, medium and low budget scenarios in both damage degree levels. Tables 17 and

Improving the sensitivity and accuracy of gamma activation analysis for the rapid determination of gold in mineral ores.

PubMed

Tickner, James; Ganly, Brianna; Lovric, Bojan; O'Dwyer, Joel

2017-04-01

Mining companies rely on chemical analysis methods to determine concentrations of gold in mineral ore samples. As gold is often mined commercially at concentrations around 1 part-per-million, it is necessary for any analysis method to provide good sensitivity as well as high absolute accuracy. We describe work to improve both the sensitivity and accuracy of the gamma activation analysis (GAA) method for gold. We present analysis results for several suites of ore samples and discuss the design of a GAA facility designed to replace conventional chemical assay in industrial applications. Copyright © 2017. Published by Elsevier Ltd.

Multiple shooting shadowing for sensitivity analysis of chaotic dynamical systems

NASA Astrophysics Data System (ADS)

Blonigan, Patrick J.; Wang, Qiqi

2018-02-01

Sensitivity analysis methods are important tools for research and design with simulations. Many important simulations exhibit chaotic dynamics, including scale-resolving turbulent fluid flow simulations. Unfortunately, conventional sensitivity analysis methods are unable to compute useful gradient information for long-time-averaged quantities in chaotic dynamical systems. Sensitivity analysis with least squares shadowing (LSS) can compute useful gradient information for a number of chaotic systems, including simulations of chaotic vortex shedding and homogeneous isotropic turbulence. However, this gradient information comes at a very high computational cost. This paper presents multiple shooting shadowing (MSS), a more computationally efficient shadowing approach than the original LSS approach. Through an analysis of the convergence rate of MSS, it is shown that MSS can have lower memory usage and run time than LSS.

Blinded study determination of high sensitivity and specificity microchip electrophoresis–SSCP/HA to detect mutations in the p53 gene

PubMed Central

Hestekin, Christa N.; Lin, Jennifer S.; Senderowicz, Lionel; Jakupciak, John P.; O’Connell, Catherine; Rademaker, Alfred; Barron, Annelise E.

2012-01-01

Knowledge of the genetic changes that lead to disease has grown and continues to grow at a rapid pace. However, there is a need for clinical devices that can be used routinely to translate this knowledge into the treatment of patients. Use in a clinical setting requires high sensitivity and specificity (>97%) in order to prevent misdiagnoses. Single strand conformational polymorphism (SSCP) and heteroduplex analysis (HA) are two DNA-based, complementary methods for mutation detection that are inexpensive and relatively easy to implement. However, both methods are most commonly detected by slab gel electrophoresis, which can be labor-intensive, time-consuming, and often the methods are unable to produce high sensitivity and specificity without the use of multiple analysis conditions. Here we demonstrate the first blinded study using microchip electrophoresis-SSCP/HA. We demonstrate the ability of microchip electrophoresis-SSCP/HA to detect with 98% sensitivity and specificity >100 samples from the p53 gene exons 5–9 in a blinded study in an analysis time of less than 10 minutes. PMID:22002021

Ethical Sensitivity in Nursing Ethical Leadership: A Content Analysis of Iranian Nurses Experiences

PubMed Central

Esmaelzadeh, Fatemeh; Abbaszadeh, Abbas; Borhani, Fariba; Peyrovi, Hamid

2017-01-01

Background: Considering that many nursing actions affect other people’s health and life, sensitivity to ethics in nursing practice is highly important to ethical leaders as a role model. Objective: The study aims to explore ethical sensitivity in ethical nursing leaders in Iran. Method: This was a qualitative study based on the conventional content analysis in 2015. Data were collected using deep and semi-structured interviews with 20 Iranian nurses. The participants were chosen using purposive sampling. Data were analyzed using conventional content analysis. In order to increase the accuracy and integrity of the data, Lincoln and Guba's criteria were considered. Results: Fourteen sub-categories and five main categories emerged. Main categories consisted of sensitivity to care, sensitivity to errors, sensitivity to communication, sensitivity in decision making and sensitivity to ethical practice. Conclusion: Ethical sensitivity appears to be a valuable attribute for ethical nurse leaders, having an important effect on various aspects of professional practice and help the development of ethics in nursing practice. PMID:28584564

New Uses for Sensitivity Analysis: How Different Movement Tasks Effect Limb Model Parameter Sensitivity

NASA Technical Reports Server (NTRS)

Winters, J. M.; Stark, L.

1984-01-01

Original results for a newly developed eight-order nonlinear limb antagonistic muscle model of elbow flexion and extension are presented. A wider variety of sensitivity analysis techniques are used and a systematic protocol is established that shows how the different methods can be used efficiently to complement one another for maximum insight into model sensitivity. It is explicitly shown how the sensitivity of output behaviors to model parameters is a function of the controller input sequence, i.e., of the movement task. When the task is changed (for instance, from an input sequence that results in the usual fast movement task to a slower movement that may also involve external loading, etc.) the set of parameters with high sensitivity will in general also change. Such task-specific use of sensitivity analysis techniques identifies the set of parameters most important for a given task, and even suggests task-specific model reduction possibilities.

Sensitivity analysis of Jacobian determinant used in treatment planning for lung cancer

NASA Astrophysics Data System (ADS)

Shao, Wei; Gerard, Sarah E.; Pan, Yue; Patton, Taylor J.; Reinhardt, Joseph M.; Durumeric, Oguz C.; Bayouth, John E.; Christensen, Gary E.

2018-03-01

Four-dimensional computed tomography (4DCT) is regularly used to visualize tumor motion in radiation therapy for lung cancer. These 4DCT images can be analyzed to estimate local ventilation by finding a dense correspondence map between the end inhalation and the end exhalation CT image volumes using deformable image registration. Lung regions with ventilation values above a threshold are labeled as regions of high pulmonary function and are avoided when possible in the radiation plan. This paper investigates a sensitivity analysis of the relative Jacobian error to small registration errors. We present a linear approximation of the relative Jacobian error. Next, we give a formula for the sensitivity of the relative Jacobian error with respect to the Jacobian of perturbation displacement field. Preliminary sensitivity analysis results are presented using 4DCT scans from 10 individuals. For each subject, we generated 6400 random smooth biologically plausible perturbation vector fields using a cubic B-spline model. We showed that the correlation between the Jacobian determinant and the Frobenius norm of the sensitivity matrix is close to -1, which implies that the relative Jacobian error in high-functional regions is less sensitive to noise. We also showed that small displacement errors on the average of 0.53 mm may lead to a 10% relative change in Jacobian determinant. We finally showed that the average relative Jacobian error and the sensitivity of the system for all subjects are positively correlated (close to +1), i.e. regions with high sensitivity has more error in Jacobian determinant on average.

First- and Second-Order Sensitivity Analysis of a P-Version Finite Element Equation Via Automatic Differentiation

NASA Technical Reports Server (NTRS)

Hou, Gene

1998-01-01

Sensitivity analysis is a technique for determining derivatives of system responses with respect to design parameters. Among many methods available for sensitivity analysis, automatic differentiation has been proven through many applications in fluid dynamics and structural mechanics to be an accurate and easy method for obtaining derivatives. Nevertheless, the method can be computational expensive and can require a high memory space. This project will apply an automatic differentiation tool, ADIFOR, to a p-version finite element code to obtain first- and second- order then-nal derivatives, respectively. The focus of the study is on the implementation process and the performance of the ADIFOR-enhanced codes for sensitivity analysis in terms of memory requirement, computational efficiency, and accuracy.

Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq)-A Method for High-Throughput Analysis of Differentially Methylated CCGG Sites in Plants with Large Genomes.

PubMed

Chwialkowska, Karolina; Korotko, Urszula; Kosinska, Joanna; Szarejko, Iwona; Kwasniewski, Miroslaw

2017-01-01

Epigenetic mechanisms, including histone modifications and DNA methylation, mutually regulate chromatin structure, maintain genome integrity, and affect gene expression and transposon mobility. Variations in DNA methylation within plant populations, as well as methylation in response to internal and external factors, are of increasing interest, especially in the crop research field. Methylation Sensitive Amplification Polymorphism (MSAP) is one of the most commonly used methods for assessing DNA methylation changes in plants. This method involves gel-based visualization of PCR fragments from selectively amplified DNA that are cleaved using methylation-sensitive restriction enzymes. In this study, we developed and validated a new method based on the conventional MSAP approach called Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq). We improved the MSAP-based approach by replacing the conventional separation of amplicons on polyacrylamide gels with direct, high-throughput sequencing using Next Generation Sequencing (NGS) and automated data analysis. MSAP-Seq allows for global sequence-based identification of changes in DNA methylation. This technique was validated in Hordeum vulgare . However, MSAP-Seq can be straightforwardly implemented in different plant species, including crops with large, complex and highly repetitive genomes. The incorporation of high-throughput sequencing into MSAP-Seq enables parallel and direct analysis of DNA methylation in hundreds of thousands of sites across the genome. MSAP-Seq provides direct genomic localization of changes and enables quantitative evaluation. We have shown that the MSAP-Seq method specifically targets gene-containing regions and that a single analysis can cover three-quarters of all genes in large genomes. Moreover, MSAP-Seq's simplicity, cost effectiveness, and high-multiplexing capability make this method highly affordable. Therefore, MSAP-Seq can be used for DNA methylation analysis in crop plants with large and complex genomes.

Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq)—A Method for High-Throughput Analysis of Differentially Methylated CCGG Sites in Plants with Large Genomes

PubMed Central

Chwialkowska, Karolina; Korotko, Urszula; Kosinska, Joanna; Szarejko, Iwona; Kwasniewski, Miroslaw

2017-01-01

Epigenetic mechanisms, including histone modifications and DNA methylation, mutually regulate chromatin structure, maintain genome integrity, and affect gene expression and transposon mobility. Variations in DNA methylation within plant populations, as well as methylation in response to internal and external factors, are of increasing interest, especially in the crop research field. Methylation Sensitive Amplification Polymorphism (MSAP) is one of the most commonly used methods for assessing DNA methylation changes in plants. This method involves gel-based visualization of PCR fragments from selectively amplified DNA that are cleaved using methylation-sensitive restriction enzymes. In this study, we developed and validated a new method based on the conventional MSAP approach called Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq). We improved the MSAP-based approach by replacing the conventional separation of amplicons on polyacrylamide gels with direct, high-throughput sequencing using Next Generation Sequencing (NGS) and automated data analysis. MSAP-Seq allows for global sequence-based identification of changes in DNA methylation. This technique was validated in Hordeum vulgare. However, MSAP-Seq can be straightforwardly implemented in different plant species, including crops with large, complex and highly repetitive genomes. The incorporation of high-throughput sequencing into MSAP-Seq enables parallel and direct analysis of DNA methylation in hundreds of thousands of sites across the genome. MSAP-Seq provides direct genomic localization of changes and enables quantitative evaluation. We have shown that the MSAP-Seq method specifically targets gene-containing regions and that a single analysis can cover three-quarters of all genes in large genomes. Moreover, MSAP-Seq's simplicity, cost effectiveness, and high-multiplexing capability make this method highly affordable. Therefore, MSAP-Seq can be used for DNA methylation analysis in crop plants with large and complex genomes. PMID:29250096

A two-step sensitivity analysis for hydrological signatures in Jinhua River Basin, East China

NASA Astrophysics Data System (ADS)

Pan, S.; Fu, G.; Chiang, Y. M.; Xu, Y. P.

2016-12-01

Owing to model complexity and large number of parameters, calibration and sensitivity analysis are difficult processes for distributed hydrological models. In this study, a two-step sensitivity analysis approach is proposed for analyzing the hydrological signatures in Jinhua River Basin, East China, using the Distributed Hydrology-Soil-Vegetation Model (DHSVM). A rough sensitivity analysis is firstly conducted to obtain preliminary influential parameters via Analysis of Variance. The number of parameters was greatly reduced from eighteen-three to sixteen. Afterwards, the sixteen parameters are further analyzed based on a variance-based global sensitivity analysis, i.e., Sobol's sensitivity analysis method, to achieve robust sensitivity rankings and parameter contributions. Parallel-Computing is applied to reduce computational burden in variance-based sensitivity analysis. The results reveal that only a few number of model parameters are significantly sensitive, including rain LAI multiplier, lateral conductivity, porosity, field capacity, wilting point of clay loam, understory monthly LAI, understory minimum resistance and root zone depths of croplands. Finally several hydrological signatures are used for investigating the performance of DHSVM. Results show that high value of efficiency criteria didn't indicate excellent performance of hydrological signatures. For most samples from Sobol's sensitivity analysis, water yield was simulated very well. However, lowest and maximum annual daily runoffs were underestimated. Most of seven-day minimum runoffs were overestimated. Nevertheless, good performances of the three signatures above still exist in a number of samples. Analysis of peak flow shows that small and medium floods are simulated perfectly while slight underestimations happen to large floods. The work in this study helps to further multi-objective calibration of DHSVM model and indicates where to improve the reliability and credibility of model simulation.

LASER BIOLOGY AND MEDICINE: Application of tunable diode lasers for a highly sensitive analysis of gaseous biomarkers in exhaled air

NASA Astrophysics Data System (ADS)

Stepanov, E. V.; Milyaev, Varerii A.

2002-11-01

The application of tunable diode lasers for a highly sensitive analysis of gaseous biomarkers in exhaled air in biomedical diagnostics is discussed. The principle of operation and the design of a laser analyser for studying the composition of exhaled air are described. The results of detection of gaseous biomarkers in exhaled air, including clinical studies, which demonstrate the diagnostic possibilities of the method, are presented.

Birth weight, current anthropometric markers, and high sensitivity C-reactive protein in Brazilian school children.

PubMed

Boscaini, Camile; Pellanda, Lucia Campos

2015-01-01

Studies have shown associations of birth weight with increased concentrations of high sensitivity C-reactive protein. This study assessed the relationship between birth weight, anthropometric and metabolic parameters during childhood, and high sensitivity C-reactive protein. A total of 612 Brazilian school children aged 5-13 years were included in the study. High sensitivity C-reactive protein was measured by particle-enhanced immunonephelometry. Nutritional status was assessed by body mass index, waist circumference, and skinfolds. Total cholesterol and fractions, triglycerides, and glucose were measured by enzymatic methods. Insulin sensitivity was determined by the homeostasis model assessment method. Statistical analysis included chi-square test, General Linear Model, and General Linear Model for Gamma Distribution. Body mass index, waist circumference, and skinfolds were directly associated with birth weight (P < 0.001, P = 0.001, and P = 0.015, resp.). Large for gestational age children showed higher high sensitivity C-reactive protein levels (P < 0.001) than small for gestational age. High birth weight is associated with higher levels of high sensitivity C-reactive protein, body mass index, waist circumference, and skinfolds. Large for gestational age altered high sensitivity C-reactive protein and promoted additional risk factor for atherosclerosis in these school children, independent of current nutritional status.

Highly sensitive refractive index fiber inline Mach-Zehnder interferometer fabricated by femtosecond laser micromachining and chemical etching

NASA Astrophysics Data System (ADS)

Sun, Xiao-Yan; Chu, Dong-Kai; Dong, Xin-Ran; Zhou, Chu; Li, Hai-Tao; Luo-Zhi; Hu, You-Wang; Zhou, Jian-Ying; Cong-Wang; Duan, Ji-An

2016-03-01

A High sensitive refractive index (RI) sensor based on Mach-Zehnder interferometer (MZI) in a conventional single-mode optical fiber is proposed, which is fabricated by femtosecond laser transversal-scanning inscription method and chemical etching. A rectangular cavity structure is formed in part of fiber core and cladding interface. The MZI sensor shows excellent refractive index sensitivity and linearity, which exhibits an extremely high RI sensitivity of -17197 nm/RIU (refractive index unit) with the linearity of 0.9996 within the refractive index range of 1.3371-1.3407. The experimental results are consistent with theoretical analysis.

Detection of somatic mutations by high-resolution DNA melting (HRM) analysis in multiple cancers.

PubMed

Gonzalez-Bosquet, Jesus; Calcei, Jacob; Wei, Jun S; Garcia-Closas, Montserrat; Sherman, Mark E; Hewitt, Stephen; Vockley, Joseph; Lissowska, Jolanta; Yang, Hannah P; Khan, Javed; Chanock, Stephen

2011-01-17

Identification of somatic mutations in cancer is a major goal for understanding and monitoring the events related to cancer initiation and progression. High resolution melting (HRM) curve analysis represents a fast, post-PCR high-throughput method for scanning somatic sequence alterations in target genes. The aim of this study was to assess the sensitivity and specificity of HRM analysis for tumor mutation screening in a range of tumor samples, which included 216 frozen pediatric small rounded blue-cell tumors as well as 180 paraffin-embedded tumors from breast, endometrial and ovarian cancers (60 of each). HRM analysis was performed in exons of the following candidate genes known to harbor established commonly observed mutations: PIK3CA, ERBB2, KRAS, TP53, EGFR, BRAF, GATA3, and FGFR3. Bi-directional sequencing analysis was used to determine the accuracy of the HRM analysis. For the 39 mutations observed in frozen samples, the sensitivity and specificity of HRM analysis were 97% and 87%, respectively. There were 67 mutation/variants in the paraffin-embedded samples, and the sensitivity and specificity for the HRM analysis were 88% and 80%, respectively. Paraffin-embedded samples require higher quantity of purified DNA for high performance. In summary, HRM analysis is a promising moderate-throughput screening test for mutations among known candidate genomic regions. Although the overall accuracy appears to be better in frozen specimens, somatic alterations were detected in DNA extracted from paraffin-embedded samples.

Detection of Somatic Mutations by High-Resolution DNA Melting (HRM) Analysis in Multiple Cancers

PubMed Central

Gonzalez-Bosquet, Jesus; Calcei, Jacob; Wei, Jun S.; Garcia-Closas, Montserrat; Sherman, Mark E.; Hewitt, Stephen; Vockley, Joseph; Lissowska, Jolanta; Yang, Hannah P.; Khan, Javed; Chanock, Stephen

2011-01-01

Identification of somatic mutations in cancer is a major goal for understanding and monitoring the events related to cancer initiation and progression. High resolution melting (HRM) curve analysis represents a fast, post-PCR high-throughput method for scanning somatic sequence alterations in target genes. The aim of this study was to assess the sensitivity and specificity of HRM analysis for tumor mutation screening in a range of tumor samples, which included 216 frozen pediatric small rounded blue-cell tumors as well as 180 paraffin-embedded tumors from breast, endometrial and ovarian cancers (60 of each). HRM analysis was performed in exons of the following candidate genes known to harbor established commonly observed mutations: PIK3CA, ERBB2, KRAS, TP53, EGFR, BRAF, GATA3, and FGFR3. Bi-directional sequencing analysis was used to determine the accuracy of the HRM analysis. For the 39 mutations observed in frozen samples, the sensitivity and specificity of HRM analysis were 97% and 87%, respectively. There were 67 mutation/variants in the paraffin-embedded samples, and the sensitivity and specificity for the HRM analysis were 88% and 80%, respectively. Paraffin-embedded samples require higher quantity of purified DNA for high performance. In summary, HRM analysis is a promising moderate-throughput screening test for mutations among known candidate genomic regions. Although the overall accuracy appears to be better in frozen specimens, somatic alterations were detected in DNA extracted from paraffin-embedded samples. PMID:21264207

The cross-cut statistic and its sensitivity to bias in observational studies with ordered doses of treatment.

PubMed

Rosenbaum, Paul R

2016-03-01

A common practice with ordered doses of treatment and ordered responses, perhaps recorded in a contingency table with ordered rows and columns, is to cut or remove a cross from the table, leaving the outer corners--that is, the high-versus-low dose, high-versus-low response corners--and from these corners to compute a risk or odds ratio. This little remarked but common practice seems to be motivated by the oldest and most familiar method of sensitivity analysis in observational studies, proposed by Cornfield et al. (1959), which says that to explain a population risk ratio purely as bias from an unobserved binary covariate, the prevalence ratio of the covariate must exceed the risk ratio. Quite often, the largest risk ratio, hence the one least sensitive to bias by this standard, is derived from the corners of the ordered table with the central cross removed. Obviously, the corners use only a portion of the data, so a focus on the corners has consequences for the standard error as well as for bias, but sampling variability was not a consideration in this early and familiar form of sensitivity analysis, where point estimates replaced population parameters. Here, this cross-cut analysis is examined with the aid of design sensitivity and the power of a sensitivity analysis. © 2015, The International Biometric Society.

Importance of optimizing chromatographic conditions and mass spectrometric parameters for supercritical fluid chromatography/mass spectrometry.

PubMed

Fujito, Yuka; Hayakawa, Yoshihiro; Izumi, Yoshihiro; Bamba, Takeshi

2017-07-28

Supercritical fluid chromatography/mass spectrometry (SFC/MS) has great potential in high-throughput and the simultaneous analysis of a wide variety of compounds, and it has been widely used in recent years. The use of MS for detection provides the advantages of high sensitivity and high selectivity. However, the sensitivity of MS detection depends on the chromatographic conditions and MS parameters. Thus, optimization of MS parameters corresponding to the SFC condition is mandatory for maximizing performance when connecting SFC to MS. The aim of this study was to reveal a way to decide the optimum composition of the mobile phase and the flow rate of the make-up solvent for MS detection in a wide range of compounds. Additionally, we also showed the basic concept for determination of the optimum values of the MS parameters focusing on the MS detection sensitivity in SFC/MS analysis. To verify the versatility of these findings, a total of 441 pesticides with a wide polarity range (logP ow from -4.21 to 7.70) and pKa (acidic, neutral and basic). In this study, a new SFC-MS interface was used, which can transfer the entire volume of eluate into the MS by directly coupling the SFC with the MS. This enabled us to compare the sensitivity or optimum MS parameters for MS detection between LC/MS and SFC/MS for the same sample volume introduced into the MS. As a result, it was found that the optimum values of some MS parameters were completely different from those of LC/MS, and that SFC/MS-specific optimization of the analytical conditions is required. Lastly, we evaluated the sensitivity of SFC/MS using fully optimized analytical conditions. As a result, we confirmed that SFC/MS showed much higher sensitivity than LC/MS when the analytical conditions were fully optimized for SFC/MS; and the high sensitivity also increase the number of the compounds that can be detected with good repeatability in real sample analysis. This result indicates that SFC/MS has potential for practical use in the multiresidue analysis of a wide range of compounds that requires high sensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the Sensitivity of Surface Downward Longwave Radiation to Changes in Water Vapor at Two High Elevation Sites

NASA Technical Reports Server (NTRS)

Chen, Yonghua; Naud, Catherine M.; Rangwala, Imtiaz; Landry, Christopher C.; Miller, James R.

2014-01-01

Among the potential reasons for enhanced warming rates in many high elevation regions is the nonlinear relationship between surface downward longwave radiation (DLR) and specific humidity (q). In this study we use ground-based observations at two neighboring high elevation sites in Southwestern Colorado that have different local topography and are 1.3 kilometers apart horizontally and 348 meters vertically. We examine the spatial consistency of the sensitivities (partial derivatives) of DLR with respect to changes in q, and the sensitivities are obtained from the Jacobian matrix of a neural network analysis. Although the relationship between DLR and q is the same at both sites, the sensitivities are higher when q is smaller, which occurs more frequently at the higher elevation site. There is a distinct hourly distribution in the sensitivities at both sites especially for high sensitivity cases, although the range is greater at the lower elevation site. The hourly distribution of the sensitivities relates to that of q. Under clear skies during daytime, q is similar between the two sites, however under cloudy skies or at night, it is not. This means that the DLR-q sensitivities are similar at the two sites during daytime but not at night, and care must be exercised when using data from one site to infer the impact of water vapor feedbacks at another site, particularly at night. Our analysis suggests that care should be exercised when using the lapse rate adjustment to infill high frequency data in a complex topographical region, particularly when one of the stations is subject to cold air pooling as found here.

Supersonic molecular beam-hyperthermal surface ionisation coupled with time-of-flight mass spectrometry applied to trace level detection of polynuclear aromatic hydrocarbons in drinking water for reduced sample preparation and analysis time.

PubMed

Davis, S C; Makarov, A A; Hughes, J D

1999-01-01

Analysis of sub-ppb levels of polynuclear aromatic hydrocarbons (PAHs) in drinking water by high performance liquid chromatography (HPLC) fluorescence detection typically requires large water samples and lengthy extraction procedures. The detection itself, although selective, does not give compound identity confirmation. Benchtop gas chromatography/mass spectrometry (GC/MS) systems operating in the more sensitive selected ion monitoring (SIM) acquisition mode discard spectral information and, when operating in scanning mode, are less sensitive and scan too slowly. The selectivity of hyperthermal surface ionisation (HSI), the high column flow rate capacity of the supersonic molecular beam (SMB) GC/MS interface, and the high acquisition rate of time-of-flight (TOF) mass analysis, are combined here to facilitate a rapid, specific and sensitive technique for the analysis of trace levels of PAHs in water. This work reports the advantages gained by using the GC/HSI-TOF system over the HPLC fluorescence method, and discusses in some detail the nature of the instrumentation used.

Wide-Field Imaging of Single-Nanoparticle Extinction with Sub-nm2 Sensitivity

NASA Astrophysics Data System (ADS)

Payne, Lukas M.; Langbein, Wolfgang; Borri, Paola

2018-03-01

We report on a highly sensitive wide-field imaging technique for quantitative measurement of the optical extinction cross section σext of single nanoparticles. The technique is simple and high speed, and it enables the simultaneous acquisition of hundreds of nanoparticles for statistical analysis. Using rapid referencing, fast acquisition, and a deconvolution analysis, a shot-noise-limited sensitivity down to 0.4 nm2 is achieved. Measurements on a set of individual gold nanoparticles of 5 nm diameter using this method yield σext=(10.0 ±3.1 ) nm2, which is consistent with theoretical expectations and well above the background fluctuations of 0.9 nm2 .

Integrating heterogeneous drug sensitivity data from cancer pharmacogenomic studies.

PubMed

Pozdeyev, Nikita; Yoo, Minjae; Mackie, Ryan; Schweppe, Rebecca E; Tan, Aik Choon; Haugen, Bryan R

2016-08-09

The consistency of in vitro drug sensitivity data is of key importance for cancer pharmacogenomics. Previous attempts to correlate drug sensitivities from the large pharmacogenomics databases, such as the Cancer Cell Line Encyclopedia (CCLE) and the Genomics of Drug Sensitivity in Cancer (GDSC), have produced discordant results. We developed a new drug sensitivity metric, the area under the dose response curve adjusted for the range of tested drug concentrations, which allows integration of heterogeneous drug sensitivity data from the CCLE, the GDSC, and the Cancer Therapeutics Response Portal (CTRP). We show that there is moderate to good agreement of drug sensitivity data for many targeted therapies, particularly kinase inhibitors. The results of this largest cancer cell line drug sensitivity data analysis to date are accessible through the online portal, which serves as a platform for high power pharmacogenomics analysis.

Recent advances on multidimensional liquid chromatography-mass spectrometry for proteomics: from qualitative to quantitative analysis--a review.

PubMed

Wu, Qi; Yuan, Huiming; Zhang, Lihua; Zhang, Yukui

2012-06-20

With the acceleration of proteome research, increasing attention has been paid to multidimensional liquid chromatography-mass spectrometry (MDLC-MS) due to its high peak capacity and separation efficiency. Recently, many efforts have been put to improve MDLC-based strategies including "top-down" and "bottom-up" to enable highly sensitive qualitative and quantitative analysis of proteins, as well as accelerate the whole analytical procedure. Integrated platforms with combination of sample pretreatment, multidimensional separations and identification were also developed to achieve high throughput and sensitive detection of proteomes, facilitating highly accurate and reproducible quantification. This review summarized the recent advances of such techniques and their applications in qualitative and quantitative analysis of proteomes. Copyright © 2012 Elsevier B.V. All rights reserved.

Blinded study determination of high sensitivity and specificity microchip electrophoresis-SSCP/HA to detect mutations in the p53 gene.

PubMed

Hestekin, Christa N; Lin, Jennifer S; Senderowicz, Lionel; Jakupciak, John P; O'Connell, Catherine; Rademaker, Alfred; Barron, Annelise E

2011-11-01

Knowledge of the genetic changes that lead to disease has grown and continues to grow at a rapid pace. However, there is a need for clinical devices that can be used routinely to translate this knowledge into the treatment of patients. Use in a clinical setting requires high sensitivity and specificity (>97%) in order to prevent misdiagnoses. Single-strand conformational polymorphism (SSCP) and heteroduplex analysis (HA) are two DNA-based, complementary methods for mutation detection that are inexpensive and relatively easy to implement. However, both methods are most commonly detected by slab gel electrophoresis, which can be labor-intensive, time-consuming, and often the methods are unable to produce high sensitivity and specificity without the use of multiple analysis conditions. Here, we demonstrate the first blinded study using microchip electrophoresis (ME)-SSCP/HA. We demonstrate the ability of ME-SSCP/HA to detect with 98% sensitivity and specificity >100 samples from the p53 gene exons 5-9 in a blinded study in an analysis time of <10 min. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computational simulation and aerodynamic sensitivity analysis of film-cooled turbines

NASA Astrophysics Data System (ADS)

Massa, Luca

A computational tool is developed for the time accurate sensitivity analysis of the stage performance of hot gas, unsteady turbine components. An existing turbomachinery internal flow solver is adapted to the high temperature environment typical of the hot section of jet engines. A real gas model and film cooling capabilities are successfully incorporated in the software. The modifications to the existing algorithm are described; both the theoretical model and the numerical implementation are validated. The accuracy of the code in evaluating turbine stage performance is tested using a turbine geometry typical of the last stage of aeronautical jet engines. The results of the performance analysis show that the predictions differ from the experimental data by less than 3%. A reliable grid generator, applicable to the domain discretization of the internal flow field of axial flow turbine is developed. A sensitivity analysis capability is added to the flow solver, by rendering it able to accurately evaluate the derivatives of the time varying output functions. The complex Taylor's series expansion (CTSE) technique is reviewed. Two of them are used to demonstrate the accuracy and time dependency of the differentiation process. The results are compared with finite differences (FD) approximations. The CTSE is more accurate than the FD, but less efficient. A "black box" differentiation of the source code, resulting from the automated application of the CTSE, generates high fidelity sensitivity algorithms, but with low computational efficiency and high memory requirements. New formulations of the CTSE are proposed and applied. Selective differentiation of the method for solving the non-linear implicit residual equation leads to sensitivity algorithms with the same accuracy but improved run time. The time dependent sensitivity derivatives are computed in run times comparable to the ones required by the FD approach.

Head-To-Head Comparison Between High- and Standard-b-Value DWI for Detecting Prostate Cancer: A Systematic Review and Meta-Analysis.

PubMed

Woo, Sungmin; Suh, Chong Hyun; Kim, Sang Youn; Cho, Jeong Yeon; Kim, Seung Hyup

2018-01-01

The purpose of this study was to perform a head-to-head comparison between high-b-value (> 1000 s/mm 2 ) and standard-b-value (800-1000 s/mm 2 ) DWI regarding diagnostic performance in the detection of prostate cancer. The MEDLINE and EMBASE databases were searched up to April 1, 2017. The analysis included diagnostic accuracy studies in which high- and standard-b-value DWI were used for prostate cancer detection with histopathologic examination as the reference standard. Methodologic quality was assessed with the revised Quality Assessment of Diagnostic Accuracy Studies tool. Sensitivity and specificity of all studies were calculated and were pooled and plotted in a hierarchic summary ROC plot. Meta-regression and multiple-subgroup analyses were performed to compare the diagnostic performances of high- and standard-b-value DWI. Eleven studies (789 patients) were included. High-b-value DWI had greater pooled sensitivity (0.80 [95% CI, 0.70-0.87]) (p = 0.03) and specificity (0.92 [95% CI, 0.87-0.95]) (p = 0.01) than standard-b-value DWI (sensitivity, 0.78 [95% CI, 0.66-0.86]); specificity, 0.87 [95% CI, 0.77-0.93] (p < 0.01). Multiple-subgroup analyses showed that specificity was consistently higher for high- than for standard-b-value DWI (p ≤ 0.05). Sensitivity was significantly higher for high- than for standard-b-value DWI only in the following subgroups: peripheral zone only, transition zone only, multiparametric protocol (DWI and T2-weighted imaging), visual assessment of DW images, and per-lesion analysis (p ≤ 0.04). In a head-to-head comparison, high-b-value DWI had significantly better sensitivity and specificity for detection of prostate cancer than did standard-b-value DWI. Multiple-subgroup analyses showed that specificity was consistently superior for high-b-value DWI.

Imaging modalities for characterising focal pancreatic lesions.

PubMed

Best, Lawrence Mj; Rawji, Vishal; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-17

Increasing numbers of incidental pancreatic lesions are being detected each year. Accurate characterisation of pancreatic lesions into benign, precancerous, and cancer masses is crucial in deciding whether to use treatment or surveillance. Distinguishing benign lesions from precancerous and cancerous lesions can prevent patients from undergoing unnecessary major surgery. Despite the importance of accurately classifying pancreatic lesions, there is no clear algorithm for management of focal pancreatic lesions. To determine and compare the diagnostic accuracy of various imaging modalities in detecting cancerous and precancerous lesions in people with focal pancreatic lesions. We searched the CENTRAL, MEDLINE, Embase, and Science Citation Index until 19 July 2016. We searched the references of included studies to identify further studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We planned to include studies reporting cross-sectional information on the index test (CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle aspiration)) and reference standard (confirmation of the nature of the lesion was obtained by histopathological examination of the entire lesion by surgical excision, or histopathological examination for confirmation of precancer or cancer by biopsy and clinical follow-up of at least six months in people with negative index tests) in people with pancreatic lesions irrespective of language or publication status or whether the data were collected prospectively or retrospectively. Two review authors independently searched the references to identify relevant studies and extracted the data. We planned to use the bivariate analysis to calculate the summary sensitivity and specificity with their 95% confidence intervals and the hierarchical summary receiver operating characteristic (HSROC) to compare the tests and assess heterogeneity, but used simpler models (such as univariate random-effects model and univariate fixed-effect model) for combining studies when appropriate because of the sparse data. We were unable to compare the diagnostic performance of the tests using formal statistical methods because of sparse data. We included 54 studies involving a total of 3,196 participants evaluating the diagnostic accuracy of various index tests. In these 54 studies, eight different target conditions were identified with different final diagnoses constituting benign, precancerous, and cancerous lesions. None of the studies was of high methodological quality. None of the comparisons in which single studies were included was of sufficiently high methodological quality to warrant highlighting of the results. For differentiation of cancerous lesions from benign or precancerous lesions, we identified only one study per index test. The second analysis, of studies differentiating cancerous versus benign lesions, provided three tests in which meta-analysis could be performed. The sensitivities and specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95% confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00); EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to 0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39 to 0.84). The third analysis, of studies differentiating precancerous or cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence intervals reflecting the heterogeneity between the studies). The fourth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (dysplasia) provided three tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing invasive carcinoma were: CT: sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97); EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to 0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI 0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high-grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate-grade dysplasia) provided six tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing cancer (high-grade dysplasia or invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity 0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92), specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to 0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen 200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19 to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI 0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95% CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in which meta-analysis was performed. The seventh analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests in which meta-analysis was performed. The sensitivity and specificity for diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity 0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92), specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or benign lesions provided no test in which meta-analysis was performed.There were no major alterations in the subgroup analysis of cystic pancreatic focal lesions (42 studies; 2086 participants). None of the included studies evaluated EUS elastography or sequential testing. We were unable to arrive at any firm conclusions because of the differences in the way that study authors classified focal pancreatic lesions into cancerous, precancerous, and benign lesions; the inclusion of few studies with wide confidence intervals for each comparison; poor methodological quality in the studies; and heterogeneity in the estimates within comparisons.

Label-free and high-sensitive detection for genetic point mutation based on hyperspectral interferometry

NASA Astrophysics Data System (ADS)

Fu, Rongxin; Li, Qi; Zhang, Junqi; Wang, Ruliang; Lin, Xue; Xue, Ning; Su, Ya; Jiang, Kai; Huang, Guoliang

2016-10-01

Label free point mutation detection is particularly momentous in the area of biomedical research and clinical diagnosis since gene mutations naturally occur and bring about highly fatal diseases. In this paper, a label free and high sensitive approach is proposed for point mutation detection based on hyperspectral interferometry. A hybridization strategy is designed to discriminate a single-base substitution with sequence-specific DNA ligase. Double-strand structures will take place only if added oligonucleotides are perfectly paired to the probe sequence. The proposed approach takes full use of the inherent conformation of double-strand DNA molecules on the substrate and a spectrum analysis method is established to point out the sub-nanoscale thickness variation, which benefits to high sensitive mutation detection. The limit of detection reach 4pg/mm2 according to the experimental result. A lung cancer gene point mutation was demonstrated, proving the high selectivity and multiplex analysis capability of the proposed biosensor.

Improving the analysis of slug tests

USGS Publications Warehouse

McElwee, C.D.

2002-01-01

This paper examines several techniques that have the potential to improve the quality of slug test analysis. These techniques are applicable in the range from low hydraulic conductivities with overdamped responses to high hydraulic conductivities with nonlinear oscillatory responses. Four techniques for improving slug test analysis will be discussed: use of an extended capability nonlinear model, sensitivity analysis, correction for acceleration and velocity effects, and use of multiple slug tests. The four-parameter nonlinear slug test model used in this work is shown to allow accurate analysis of slug tests with widely differing character. The parameter ?? represents a correction to the water column length caused primarily by radius variations in the wellbore and is most useful in matching the oscillation frequency and amplitude. The water column velocity at slug initiation (V0) is an additional model parameter, which would ideally be zero but may not be due to the initiation mechanism. The remaining two model parameters are A (parameter for nonlinear effects) and K (hydraulic conductivity). Sensitivity analysis shows that in general ?? and V0 have the lowest sensitivity and K usually has the highest. However, for very high K values the sensitivity to A may surpass the sensitivity to K. Oscillatory slug tests involve higher accelerations and velocities of the water column; thus, the pressure transducer responses are affected by these factors and the model response must be corrected to allow maximum accuracy for the analysis. The performance of multiple slug tests will allow some statistical measure of the experimental accuracy and of the reliability of the resulting aquifer parameters. ?? 2002 Elsevier Science B.V. All rights reserved.

Accelerated Sensitivity Analysis in High-Dimensional Stochastic Reaction Networks

PubMed Central

Arampatzis, Georgios; Katsoulakis, Markos A.; Pantazis, Yannis

2015-01-01

Existing sensitivity analysis approaches are not able to handle efficiently stochastic reaction networks with a large number of parameters and species, which are typical in the modeling and simulation of complex biochemical phenomena. In this paper, a two-step strategy for parametric sensitivity analysis for such systems is proposed, exploiting advantages and synergies between two recently proposed sensitivity analysis methodologies for stochastic dynamics. The first method performs sensitivity analysis of the stochastic dynamics by means of the Fisher Information Matrix on the underlying distribution of the trajectories; the second method is a reduced-variance, finite-difference, gradient-type sensitivity approach relying on stochastic coupling techniques for variance reduction. Here we demonstrate that these two methods can be combined and deployed together by means of a new sensitivity bound which incorporates the variance of the quantity of interest as well as the Fisher Information Matrix estimated from the first method. The first step of the proposed strategy labels sensitivities using the bound and screens out the insensitive parameters in a controlled manner. In the second step of the proposed strategy, a finite-difference method is applied only for the sensitivity estimation of the (potentially) sensitive parameters that have not been screened out in the first step. Results on an epidermal growth factor network with fifty parameters and on a protein homeostasis with eighty parameters demonstrate that the proposed strategy is able to quickly discover and discard the insensitive parameters and in the remaining potentially sensitive parameters it accurately estimates the sensitivities. The new sensitivity strategy can be several times faster than current state-of-the-art approaches that test all parameters, especially in “sloppy” systems. In particular, the computational acceleration is quantified by the ratio between the total number of parameters over the number of the sensitive parameters. PMID:26161544

Enabling Predictive Simulation and UQ of Complex Multiphysics PDE Systems by the Development of Goal-Oriented Variational Sensitivity Analysis and a-Posteriori Error Estimation Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Estep, Donald

2015-11-30

This project addressed the challenge of predictive computational analysis of strongly coupled, highly nonlinear multiphysics systems characterized by multiple physical phenomena that span a large range of length- and time-scales. Specifically, the project was focused on computational estimation of numerical error and sensitivity analysis of computational solutions with respect to variations in parameters and data. In addition, the project investigated the use of accurate computational estimates to guide efficient adaptive discretization. The project developed, analyzed and evaluated new variational adjoint-based techniques for integration, model, and data error estimation/control and sensitivity analysis, in evolutionary multiphysics multiscale simulations.

Sensitivity Enhancement of FBG-Based Strain Sensor.

PubMed

Li, Ruiya; Chen, Yiyang; Tan, Yuegang; Zhou, Zude; Li, Tianliang; Mao, Jian

2018-05-17

A novel fiber Bragg grating (FBG)-based strain sensor with a high-sensitivity is presented in this paper. The proposed FBG-based strain sensor enhances sensitivity by pasting the FBG on a substrate with a lever structure. This typical mechanical configuration mechanically amplifies the strain of the FBG to enhance overall sensitivity. As this mechanical configuration has a high stiffness, the proposed sensor can achieve a high resonant frequency and a wide dynamic working range. The sensing principle is presented, and the corresponding theoretical model is derived and validated. Experimental results demonstrate that the developed FBG-based strain sensor achieves an enhanced strain sensitivity of 6.2 pm/με, which is consistent with the theoretical analysis result. The strain sensitivity of the developed sensor is 5.2 times of the strain sensitivity of a bare fiber Bragg grating strain sensor. The dynamic characteristics of this sensor are investigated through the finite element method (FEM) and experimental tests. The developed sensor exhibits an excellent strain-sensitivity-enhancing property in a wide frequency range. The proposed high-sensitivity FBG-based strain sensor can be used for small-amplitude micro-strain measurement in harsh industrial environments.

Sensitivity Enhancement of FBG-Based Strain Sensor

PubMed Central

Chen, Yiyang; Tan, Yuegang; Zhou, Zude; Mao, Jian

2018-01-01

A novel fiber Bragg grating (FBG)-based strain sensor with a high-sensitivity is presented in this paper. The proposed FBG-based strain sensor enhances sensitivity by pasting the FBG on a substrate with a lever structure. This typical mechanical configuration mechanically amplifies the strain of the FBG to enhance overall sensitivity. As this mechanical configuration has a high stiffness, the proposed sensor can achieve a high resonant frequency and a wide dynamic working range. The sensing principle is presented, and the corresponding theoretical model is derived and validated. Experimental results demonstrate that the developed FBG-based strain sensor achieves an enhanced strain sensitivity of 6.2 pm/με, which is consistent with the theoretical analysis result. The strain sensitivity of the developed sensor is 5.2 times of the strain sensitivity of a bare fiber Bragg grating strain sensor. The dynamic characteristics of this sensor are investigated through the finite element method (FEM) and experimental tests. The developed sensor exhibits an excellent strain-sensitivity-enhancing property in a wide frequency range. The proposed high-sensitivity FBG-based strain sensor can be used for small-amplitude micro-strain measurement in harsh industrial environments. PMID:29772826

Systematic review: Comparison of Xpert MTB/RIF, LAMP and SAT methods for the diagnosis of pulmonary tuberculosis.

PubMed

Yan, Liping; Xiao, Heping; Zhang, Qing

2016-01-01

Technological advances in nucleic acid amplification have led to breakthroughs in the early detection of PTB compared to traditional sputum smear tests. The sensitivity and specificity of loop-mediated isothermal amplification (LAMP), simultaneous amplification testing (SAT), and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis were evaluated. A critical review of previous studies of LAMP, SAT, and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis that used laboratory culturing as the reference method was carried out together with a meta-analysis. In 25 previous studies, the pooled sensitivity and specificity of the diagnosis of tuberculosis were 93% and 94% for LAMP, 96% and 88% for SAT, and 89% and 98% for Xpert MTB/RIF. The I(2) values for the pooled data were >80%, indicating significant heterogeneity. In the smear-positive subgroup analysis of LAMP, the sensitivity increased from 93% to 98% (I(2) = 2.6%), and specificity was 68% (I(2) = 38.4%). In the HIV-infected subgroup analysis of Xpert MTB/RIF, the pooled sensitivity and specificity were 79% (I(2) = 72.9%) and 99% (I(2) = 64.4%). In the HIV-negative subgroup analysis for Xpert MTB/RIF, the pooled sensitivity and specificity were 72% (I(2) = 49.6%) and 99% (I(2) = 64.5%). LAMP, SAT and Xpert MTB/RIF had comparably high levels of sensitivity and specificity for the diagnosis of tuberculosis. The diagnostic sensitivity and specificity of three methods were similar, with LAMP being highly sensitive for the diagnosis of smear-positive PTB. The cost effectiveness of LAMP and SAT make them particularly suitable tests for diagnosing PTB in developing countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamic sensitivity analysis of long running landslide models through basis set expansion and meta-modelling

NASA Astrophysics Data System (ADS)

Rohmer, Jeremy

2016-04-01

Predicting the temporal evolution of landslides is typically supported by numerical modelling. Dynamic sensitivity analysis aims at assessing the influence of the landslide properties on the time-dependent predictions (e.g., time series of landslide displacements). Yet two major difficulties arise: 1. Global sensitivity analysis require running the landslide model a high number of times (> 1000), which may become impracticable when the landslide model has a high computation time cost (> several hours); 2. Landslide model outputs are not scalar, but function of time, i.e. they are n-dimensional vectors with n usually ranging from 100 to 1000. In this article, I explore the use of a basis set expansion, such as principal component analysis, to reduce the output dimensionality to a few components, each of them being interpreted as a dominant mode of variation in the overall structure of the temporal evolution. The computationally intensive calculation of the Sobol' indices for each of these components are then achieved through meta-modelling, i.e. by replacing the landslide model by a "costless-to-evaluate" approximation (e.g., a projection pursuit regression model). The methodology combining "basis set expansion - meta-model - Sobol' indices" is then applied to the La Frasse landslide to investigate the dynamic sensitivity analysis of the surface horizontal displacements to the slip surface properties during the pore pressure changes. I show how to extract information on the sensitivity of each main modes of temporal behaviour using a limited number (a few tens) of long running simulations. In particular, I identify the parameters, which trigger the occurrence of a turning point marking a shift between a regime of low values of landslide displacements and one of high values.

Competitive amplification of differentially melting amplicons (CADMA) enables sensitive and direct detection of all mutation types by high-resolution melting analysis.

PubMed

Kristensen, Lasse S; Andersen, Gitte B; Hager, Henrik; Hansen, Lise Lotte

2012-01-01

Sensitive and specific mutation detection is of particular importance in cancer diagnostics, prognostics, and individualized patient treatment. However, the majority of molecular methodologies that have been developed with the aim of increasing the sensitivity of mutation testing have drawbacks in terms of specificity, convenience, or costs. Here, we have established a new method, Competitive Amplification of Differentially Melting Amplicons (CADMA), which allows very sensitive and specific detection of all mutation types. The principle of the method is to amplify wild-type and mutated sequences simultaneously using a three-primer system. A mutation-specific primer is designed to introduce melting temperature decreasing mutations in the resulting mutated amplicon, while a second overlapping primer is designed to amplify both wild-type and mutated sequences. When combined with a third common primer very sensitive mutation detection becomes possible, when using high-resolution melting (HRM) as detection platform. The introduction of melting temperature decreasing mutations in the mutated amplicon also allows for further mutation enrichment by fast coamplification at lower denaturation temperature PCR (COLD-PCR). For proof-of-concept, we have designed CADMA assays for clinically relevant BRAF, EGFR, KRAS, and PIK3CA mutations, which are sensitive to, between 0.025% and 0.25%, mutated alleles in a wild-type background. In conclusion, CADMA enables highly sensitive and specific mutation detection by HRM analysis. © 2011 Wiley Periodicals, Inc.

Extending Raman's reach: enabling applications via greater sensitivity and speed

NASA Astrophysics Data System (ADS)

Creasey, David; Sullivan, Mike; Paul, Chris; Rathmell, Cicely

2018-02-01

Over the last decade, miniature fiber optic spectrometers have greatly expanded the ability of Raman spectroscopy to tackle practical applications in the field, from mobile pharmaceutical ID to hazardous material assessment in remote locations. There remains a gap, however, between the typical diode array spectrometer and their more sensitive benchtop analogs. High sensitivity, cooled Raman spectrometers have the potential to narrow that gap by providing greater sensitivity, better SNR, and faster measurement times. In this paper, we'll look at the key factors in the design of high sensitivity miniature Raman spectrometers and their associated accessories, as well as the key metric for direct comparison of these systems - limit of detection. With the availability of our high sensitivity Raman systems operating at wavelengths from the UV to NIR, many applications are now becoming practical in the field, from trace level detection to analysis of complex biological samples.

Upper limb strength estimation of physically impaired persons using a musculoskeletal model: A sensitivity analysis.

PubMed

Carmichael, Marc G; Liu, Dikai

2015-01-01

Sensitivity of upper limb strength calculated from a musculoskeletal model was analyzed, with focus on how the sensitivity is affected when the model is adapted to represent a person with physical impairment. Sensitivity was calculated with respect to four muscle-tendon parameters: muscle peak isometric force, muscle optimal length, muscle pennation, and tendon slack length. Results obtained from a musculoskeletal model of average strength showed highest sensitivity to tendon slack length, followed by muscle optimal length and peak isometric force, which is consistent with existing studies. Muscle pennation angle was relatively insensitive. The analysis was repeated after adapting the musculoskeletal model to represent persons with varying severities of physical impairment. Results showed that utilizing the weakened model significantly increased the sensitivity of the calculated strength at the hand, with parameters previously insensitive becoming highly sensitive. This increased sensitivity presents a significant challenge in applications utilizing musculoskeletal models to represent impaired individuals.

Use of an Antecedent Analysis and a Force Sensitive Platform to Compare Stereotyped Movements and Motor Tics

ERIC Educational Resources Information Center

Crosland, Kimberly A.; Zarcone, Jennifer R.; Schroeder, Stephen; Zarcane, Troy; Fowler, Stephen

2005-01-01

Stereotyped movements displayed by 6 participants and tics displayed by 6 children were evaluated using an antecedent behavioral analysis and a force sensitive platform. We found that tics occurred more often in an alone condition when compared to high preference toy and play conditions, whereas stereotyped movements were more variable across…

Factors dominating 3-dimensional ozone distribution during high tropospheric ozone period.

PubMed

Chen, Xiaoyang; Liu, Yiming; Lai, Anqi; Han, Shuangshuang; Fan, Qi; Wang, Xuemei; Ling, Zhenhao; Huang, Fuxiang; Fan, Shaojia

2018-01-01

Data from an in situ monitoring network and five ozone sondes are analysed during August of 2012, and a high tropospheric ozone episode is observed around the 8th of AUG. The Community Multi-scale Air Quality (CMAQ) model and its process analysis tool were used to study factors and mechanisms for high ozone mixing ratio at different levels of ozone vertical profiles. A sensitive scenario without chemical initial and boundary conditions (ICBCs) from MOZART4-GEOS5 was applied to study the impact of stratosphere-troposphere exchange (STE) on vertical ozone. The simulation results indicated that the first high ozone peak near the tropopause was dominated by STE. Results from process analysis showed that: in the urban area, the second peak at approximately 2 km above ground height was mainly caused by local photochemical production. The third peak (near surface) was mainly caused by the upwind transportation from the suburban/rural areas; in the suburban/rural areas, local photochemical production of ozone dominated the high ozone mixing ratio from the surface to approximately 3 km height. Furthermore, the capability of indicators to distinguish O 3 -precursor sensitivity along the vertical O 3 profiles was investigated. Two sensitive scenarios, which had cut 30% anthropogenic NO X or VOC emissions, showed that O 3 -precursor indicators, specifically the ratios of O 3 /NOy, H 2 O 2 /HNO 3 or H 2 O 2 /NO Z , could partly distinguish the O 3 -precursor sensitivity between VOCs-sensitive and NOx-sensitive along the vertical profiles. In urban area, the O 3 -precursor relationship transferred from VOCs-sensitive within the boundary layer to NOx-sensitive at approximately 1-3 km above ground height, further confirming the dominant roles of transportation and photochemical production in high O 3 peaks at the near-ground layer and 2 km above ground height, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fast and sensitive trace analysis of malachite green using a surface-enhanced Raman microfluidic sensor.

PubMed

Lee, Sangyeop; Choi, Junghyun; Chen, Lingxin; Park, Byungchoon; Kyong, Jin Burm; Seong, Gi Hun; Choo, Jaebum; Lee, Yeonjung; Shin, Kyung-Hoon; Lee, Eun Kyu; Joo, Sang-Woo; Lee, Kyeong-Hee

2007-05-08

A rapid and highly sensitive trace analysis technique for determining malachite green (MG) in a polydimethylsiloxane (PDMS) microfluidic sensor was investigated using surface-enhanced Raman spectroscopy (SERS). A zigzag-shaped PDMS microfluidic channel was fabricated for efficient mixing between MG analytes and aggregated silver colloids. Under the optimal condition of flow velocity, MG molecules were effectively adsorbed onto silver nanoparticles while flowing along the upper and lower zigzag-shaped PDMS channel. A quantitative analysis of MG was performed based on the measured peak height at 1615 cm(-1) in its SERS spectrum. The limit of detection, using the SERS microfluidic sensor, was found to be below the 1-2 ppb level and this low detection limit is comparable to the result of the LC-Mass detection method. In the present study, we introduce a new conceptual detection technology, using a SERS microfluidic sensor, for the highly sensitive trace analysis of MG in water.

Maternal sensitivity: a concept analysis.

PubMed

Shin, Hyunjeong; Park, Young-Joo; Ryu, Hosihn; Seomun, Gyeong-Ae

2008-11-01

The aim of this paper is to report a concept analysis of maternal sensitivity. Maternal sensitivity is a broad concept encompassing a variety of interrelated affective and behavioural caregiving attributes. It is used interchangeably with the terms maternal responsiveness or maternal competency, with no consistency of use. There is a need to clarify the concept of maternal sensitivity for research and practice. A search was performed on the CINAHL and Ovid MEDLINE databases using 'maternal sensitivity', 'maternal responsiveness' and 'sensitive mothering' as key words. The searches yielded 54 records for the years 1981-2007. Rodgers' method of evolutionary concept analysis was used to analyse the material. Four critical attributes of maternal sensitivity were identified: (a) dynamic process involving maternal abilities; (b) reciprocal give-and-take with the infant; (c) contingency on the infant's behaviour and (d) quality of maternal behaviours. Maternal identity and infant's needs and cues are antecedents for these attributes. The consequences are infant's comfort, mother-infant attachment and infant development. In addition, three positive affecting factors (social support, maternal-foetal attachment and high self-esteem) and three negative affecting factors (maternal depression, maternal stress and maternal anxiety) were identified. A clear understanding of the concept of maternal sensitivity could be useful for developing ways to enhance maternal sensitivity and to maximize the developmental potential of infants. Knowledge of the attributes of maternal sensitivity identified in this concept analysis may be helpful for constructing measuring items or dimensions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ying

My graduate research has focused on separation science and bioanalytical analysis, which emphasized in method development. It includes three major areas: enantiomeric separations using high performance liquid chromatography (HPLC), Super/subcritical fluid chromatography (SFC), and capillary electrophoresis (CE); drug-protein binding behavior studies using CE; and carbohydrate analysis using liquid chromatograph-electrospray ionization mass spectrometry (LC-ESI-MS). Enantiomeric separations continue to be extremely important in the pharmaceutical industry. An in-depth evaluation of the enantiomeric separation capabilities of macrocyclic glycopeptides CSPs with SFC mobile phases was investigated using a set of over 100 chiral compounds. It was found that the macrocyclic based CSPs were ablemore » to separate enantiomers of various compounds with different polarities and functionalities. Seventy percent of all separations were achieved in less than 4 min due to the high flow rate (4.0 ml/min) that can be used in SFC. Drug-protein binding is an important process in determining the activity and fate of a drug once it enters the body. Two drug/protein systems have been studied using frontal analysis CE method. More sensitive fluorescence detection was introduced in this assay, which overcame the problem of low sensitivity that is common when using UV detection for drug-protein studies. In addition, the first usage of an argon ion laser with 257 nm beam coupled with CCD camera as a frontal analysis detection method enabled the simultaneous observation of drug fluorescence as well as the protein fluorescence. LC-ESI-MS was used for the separation and characterization of underivatized oligosaccharide mixtures. With the limits of detection as low as 50 picograms, all individual components of oligosaccharide mixtures (up to 11 glucose-units long) were baseline resolved on a Cyclobond I 2000 column and detected using ESI-MS. This system is characterized by high chromatographic resolution, high column stability, and high sensitivity. In addition, this method showed potential usefulness for the sensitive and quick analysis of hydrolysis products of polysaccharides, and for trace level analysis of individual oligosaccharides or oligosaccharide isomers from biological systems.« less

Sensitivity Analysis of Biome-Bgc Model for Dry Tropical Forests of Vindhyan Highlands, India

NASA Astrophysics Data System (ADS)

Kumar, M.; Raghubanshi, A. S.

2011-08-01

A process-based model BIOME-BGC was run for sensitivity analysis to see the effect of ecophysiological parameters on net primary production (NPP) of dry tropical forest of India. The sensitivity test reveals that the forest NPP was highly sensitive to the following ecophysiological parameters: Canopy light extinction coefficient (k), Canopy average specific leaf area (SLA), New stem C : New leaf C (SC:LC), Maximum stomatal conductance (gs,max), C:N of fine roots (C:Nfr), All-sided to projected leaf area ratio and Canopy water interception coefficient (Wint). Therefore, these parameters need more precision and attention during estimation and observation in the field studies.

Importance analysis for Hudson River PCB transport and fate model parameters using robust sensitivity studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, S.; Toll, J.; Cothern, K.

1995-12-31

The authors have performed robust sensitivity studies of the physico-chemical Hudson River PCB model PCHEPM to identify the parameters and process uncertainties contributing the most to uncertainty in predictions of water column and sediment PCB concentrations, over the time period 1977--1991 in one segment of the lower Hudson River. The term ``robust sensitivity studies`` refers to the use of several sensitivity analysis techniques to obtain a more accurate depiction of the relative importance of different sources of uncertainty. Local sensitivity analysis provided data on the sensitivity of PCB concentration estimates to small perturbations in nominal parameter values. Range sensitivity analysismore » provided information about the magnitude of prediction uncertainty associated with each input uncertainty. Rank correlation analysis indicated which parameters had the most dominant influence on model predictions. Factorial analysis identified important interactions among model parameters. Finally, term analysis looked at the aggregate influence of combinations of parameters representing physico-chemical processes. The authors scored the results of the local and range sensitivity and rank correlation analyses. The authors considered parameters that scored high on two of the three analyses to be important contributors to PCB concentration prediction uncertainty, and treated them probabilistically in simulations. They also treated probabilistically parameters identified in the factorial analysis as interacting with important parameters. The authors used the term analysis to better understand how uncertain parameters were influencing the PCB concentration predictions. The importance analysis allowed us to reduce the number of parameters to be modeled probabilistically from 16 to 5. This reduced the computational complexity of Monte Carlo simulations, and more importantly, provided a more lucid depiction of prediction uncertainty and its causes.« less

Ecological Sensitivity Evaluation of Tourist Region Based on Remote Sensing Image - Taking Chaohu Lake Area as a Case Study

NASA Astrophysics Data System (ADS)

Lin, Y.; Li, W. J.; Yu, J.; Wu, C. Z.

2018-04-01

Remote sensing technology is of significant advantages for monitoring and analysing ecological environment. By using of automatic extraction algorithm, various environmental resources information of tourist region can be obtained from remote sensing imagery. Combining with GIS spatial analysis and landscape pattern analysis, relevant environmental information can be quantitatively analysed and interpreted. In this study, taking the Chaohu Lake Basin as an example, Landsat-8 multi-spectral satellite image of October 2015 was applied. Integrated the automatic ELM (Extreme Learning Machine) classification results with the data of digital elevation model and slope information, human disturbance degree, land use degree, primary productivity, landscape evenness , vegetation coverage, DEM, slope and normalized water body index were used as the evaluation factors to construct the eco-sensitivity evaluation index based on AHP and overlay analysis. According to the value of eco-sensitivity evaluation index, by using of GIS technique of equal interval reclassification, the Chaohu Lake area was divided into four grades: very sensitive area, sensitive area, sub-sensitive areas and insensitive areas. The results of the eco-sensitivity analysis shows: the area of the very sensitive area was 4577.4378 km2, accounting for about 37.12 %, the sensitive area was 5130.0522 km2, accounting for about 37.12 %; the area of sub-sensitive area was 3729.9312 km2, accounting for 26.99 %; the area of insensitive area was 382.4399 km2, accounting for about 2.77 %. At the same time, it has been found that there were spatial differences in ecological sensitivity of the Chaohu Lake basin. The most sensitive areas were mainly located in the areas with high elevation and large terrain gradient. Insensitive areas were mainly distributed in slope of the slow platform area; the sensitive areas and the sub-sensitive areas were mainly agricultural land and woodland. Through the eco-sensitivity analysis of the study area, the automatic recognition and analysis techniques for remote sensing imagery are integrated into the ecological analysis and ecological regional planning, which can provide a reliable scientific basis for rational planning and regional sustainable development of the Chaohu Lake tourist area.

[Spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic syndrome complicated by urinary tract infection: an analysis of 97 cases].

PubMed

Song, Shao-Na; Zhang, Bi-Li; Wang, Wen-Hong; Zhang, Xuan

2012-09-01

To investigate the spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic syndrome (NS) complicated by urinary tract infection (UTI). A retrospective analysis was performed on the spectrum and drug sensitivity of pathogenic bacteria in 97 children with NS complicated by UTI, who hospitalized from January to December, 2011. The incidence of UTI in children with NS was 36.5%. It was significantly more common in children with recurrent NS than in those with primary NS (44.0% vs 31.9%; P<0.05). These cases mainly presented with asymptomatic bacteriuria. Enterococcus was the most common pathogenic bacteria (50.5%), including Enterococcus faecium (29.4%) and Enterococcus faecalis (21.1%), followed by Gram-negative bacteria, such as Escherichia coli (15.6%) and Klebsiella pneumoniae (14.7%). Enterococcus was highly sensitive to nitrofurantoin, vacomycin and linezolid, but was highly resistant to tetracycline and moxifloxacin. More multi-resistant strains were detected in Enterococcus faecium than in Enterococcus faecalis (72% vs 17%; P<0.05). Escherichia coli and Klebsiella pneumoniae were highly sensitive to amikacin, imipenem and piperacillin/tazobactam. Of the Gram-negative bacteria, 25% produced extended spectrum β-lactamases (ESBLs). ESBLs-producing bacteria had 100% sensitivity to imipenem, amikacin and piperacillin/tazobactam but were highly resistant to ampicillin, cefazolin and ceftriaxone. Children with recurrent NS are more susceptible to UTI than those with primary NS. Enterococcus is becoming major pathogenic bacteria for UTI in children with NS and has relatively high drug resistance, and most strains of Enterococcus faecium are multi-resistant.

A new u-statistic with superior design sensitivity in matched observational studies.

PubMed

Rosenbaum, Paul R

2011-09-01

In an observational or nonrandomized study of treatment effects, a sensitivity analysis indicates the magnitude of bias from unmeasured covariates that would need to be present to alter the conclusions of a naïve analysis that presumes adjustments for observed covariates suffice to remove all bias. The power of sensitivity analysis is the probability that it will reject a false hypothesis about treatment effects allowing for a departure from random assignment of a specified magnitude; in particular, if this specified magnitude is "no departure" then this is the same as the power of a randomization test in a randomized experiment. A new family of u-statistics is proposed that includes Wilcoxon's signed rank statistic but also includes other statistics with substantially higher power when a sensitivity analysis is performed in an observational study. Wilcoxon's statistic has high power to detect small effects in large randomized experiments-that is, it often has good Pitman efficiency-but small effects are invariably sensitive to small unobserved biases. Members of this family of u-statistics that emphasize medium to large effects can have substantially higher power in a sensitivity analysis. For example, in one situation with 250 pair differences that are Normal with expectation 1/2 and variance 1, the power of a sensitivity analysis that uses Wilcoxon's statistic is 0.08 while the power of another member of the family of u-statistics is 0.66. The topic is examined by performing a sensitivity analysis in three observational studies, using an asymptotic measure called the design sensitivity, and by simulating power in finite samples. The three examples are drawn from epidemiology, clinical medicine, and genetic toxicology. © 2010, The International Biometric Society.

Human salivary glucose analysis by high-performance ion-exchange chromatography and pulsed amperometric detection.

PubMed

Gough, H; Luke, G A; Beeley, J A; Geddes, D A

1996-02-01

The aim of this project was to develop an analytical procedure with the required level of sensitivity for the determination of glucose concentrations in small volumes of unstimulated fasting whole saliva. The technique involves high-performance ion-exchange chromatography at high pH and pulsed amperometric detection. It has a high level of reproducibility, a sensitivity as low as 0.1 mumol/l and requires only 50 microliters samples (sensitivity = 0.002 pmol). Inhibition of glucose metabolism, by procedures such as collection into 0.1% (w/v) sodium fluoride, was shown to be essential if accurate results are to be obtained. Collection on to ice followed by storage at -20 degrees C was shown to be unsuitable and resulted in glucose loss by degradation. There were inter- and intraindividual variations in the glucose concentration in unstimulated mixed saliva (range; 0.02-0.4 mmol/l). The procedure can be used for the analysis of other salivary carbohydrates and for monitoring the clearance of dietary carbohydrates from the mouth.

Sensitivity Challenge of Steep Transistors

NASA Astrophysics Data System (ADS)

Ilatikhameneh, Hesameddin; Ameen, Tarek A.; Chen, ChinYi; Klimeck, Gerhard; Rahman, Rajib

2018-04-01

Steep transistors are crucial in lowering power consumption of the integrated circuits. However, the difficulties in achieving steepness beyond the Boltzmann limit experimentally have hindered the fundamental challenges in application of these devices in integrated circuits. From a sensitivity perspective, an ideal switch should have a high sensitivity to the gate voltage and lower sensitivity to the device design parameters like oxide and body thicknesses. In this work, conventional tunnel-FET (TFET) and negative capacitance FET are shown to suffer from high sensitivity to device design parameters using full-band atomistic quantum transport simulations and analytical analysis. Although Dielectric Engineered (DE-) TFETs based on 2D materials show smaller sensitivity compared with the conventional TFETs, they have leakage issue. To mitigate this challenge, a novel DE-TFET design has been proposed and studied.

A fluorescent graphitic carbon nitride nanosheet biosensor for highly sensitive, label-free detection of alkaline phosphatase.

PubMed

Xiang, Mei-Hao; Liu, Jin-Wen; Li, Na; Tang, Hao; Yu, Ru-Qin; Jiang, Jian-Hui

2016-02-28

Graphitic C3N4 (g-C3N4) nanosheets provide an attractive option for bioprobes and bioimaging applications. Utilizing highly fluorescent and water-dispersible ultrathin g-C3N4 nanosheets, a highly sensitive, selective and label-free biosensor has been developed for ALP detection for the first time. The developed approach utilizes a natural substrate of ALP in biological systems and thus affords very high catalytic efficiency. This novel biosensor is demonstrated to enable quantitative analysis of ALP in a wide range from 0.1 to 1000 U L(-1) with a low detection limit of 0.08 U L(-1), which is among the most sensitive assays for ALP. It is expected that the developed method may provide a low-cost, convenient, rapid and highly sensitive platform for ALP-based clinical diagnostics and biomedical applications.

Intracellular flow cytometry may be combined with good quality and high sensitivity RT-qPCR analysis.

PubMed

Sandstedt, Mikael; Jonsson, Marianne; Asp, Julia; Dellgren, Göran; Lindahl, Anders; Jeppsson, Anders; Sandstedt, Joakim

2015-12-01

Flow cytometry (FCM) has become a well-established method for analysis of both intracellular and cell-surface proteins, while quantitative RT-PCR (RT-qPCR) is used to determine gene expression with high sensitivity and specificity. Combining these two methods would be of great value. The effects of intracellular staining on RNA integrity and RT-qPCR sensitivity and quality have not, however, been fully examined. We, therefore, intended to assess these effects further. Cells from the human lung cancer cell line A549 were fixed, permeabilized and sorted by FCM. Sorted cells were analyzed using RT-qPCR. RNA integrity was determined by RNA quality indicator analysis. A549 cells were then mixed with cells of the mouse cardiomyocyte cell line HL-1. A549 cells were identified by the cell surface marker ABCG2, while HL-1 cells were identified by intracellular cTnT. Cells were sorted and analyzed by RT-qPCR. Finally, cell cultures from human atrial biopsies were used to evaluate the effects of fixation and permeabilization on RT-qPCR analysis of nonimmortalized cells stored prior to analysis by FCM. A large amount of RNA could be extracted even when cells had been fixed and permeabilized. Permeabilization resulted in increased RNA degradation and a moderate decrease in RT-qPCR sensitivity. Gene expression levels were also affected to a moderate extent. Sorted populations from the mixed A549 and HL-1 cell samples showed gene expression patterns that corresponded to FCM data. When samples were stored before FCM sorting, the RT-qPCR analysis could still be performed with high sensitivity and quality. In summary, our results show that intracellular FCM may be performed with only minor impairment of the RT-qPCR sensitivity and quality when analyzing sorted cells; however, these effects should be considered when comparing RT-qPCR data of not fixed samples with those of fixed and permeabilized samples. © 2015 International Society for Advancement of Cytometry.

Highly sensitive image-derived indices of water-stressed plants using hyperspectral imaging in SWIR and histogram analysis

PubMed Central

Kim, David M.; Zhang, Hairong; Zhou, Haiying; Du, Tommy; Wu, Qian; Mockler, Todd C.; Berezin, Mikhail Y.

2015-01-01

The optical signature of leaves is an important monitoring and predictive parameter for a variety of biotic and abiotic stresses, including drought. Such signatures derived from spectroscopic measurements provide vegetation indices – a quantitative method for assessing plant health. However, the commonly used metrics suffer from low sensitivity. Relatively small changes in water content in moderately stressed plants demand high-contrast imaging to distinguish affected plants. We present a new approach in deriving sensitive indices using hyperspectral imaging in a short-wave infrared range from 800 nm to 1600 nm. Our method, based on high spectral resolution (1.56 nm) instrumentation and image processing algorithms (quantitative histogram analysis), enables us to distinguish a moderate water stress equivalent of 20% relative water content (RWC). The identified image-derived indices 15XX nm/14XX nm (i.e. 1529 nm/1416 nm) were superior to common vegetation indices, such as WBI, MSI, and NDWI, with significantly better sensitivity, enabling early diagnostics of plant health. PMID:26531782

A Small Range Six-Axis Accelerometer Designed with High Sensitivity DCB Elastic Element

PubMed Central

Sun, Zhibo; Liu, Jinhao; Yu, Chunzhan; Zheng, Yili

2016-01-01

This paper describes a small range six-axis accelerometer (the measurement range of the sensor is ±g) with high sensitivity DCB (Double Cantilever Beam) elastic element. This sensor is developed based on a parallel mechanism because of the reliability. The accuracy of sensors is affected by its sensitivity characteristics. To improve the sensitivity, a DCB structure is applied as the elastic element. Through dynamic analysis, the dynamic model of the accelerometer is established using the Lagrange equation, and the mass matrix and stiffness matrix are obtained by a partial derivative calculation and a conservative congruence transformation, respectively. By simplifying the structure of the accelerometer, a model of the free vibration is achieved, and the parameters of the sensor are designed based on the model. Through stiffness analysis of the DCB structure, the deflection curve of the beam is calculated. Compared with the result obtained using a finite element analysis simulation in ANSYS Workbench, the coincidence rate of the maximum deflection is 89.0% along the x-axis, 88.3% along the y-axis and 87.5% along the z-axis. Through strain analysis of the DCB elastic element, the sensitivity of the beam is obtained. According to the experimental result, the accuracy of the theoretical analysis is found to be 90.4% along the x-axis, 74.9% along the y-axis and 78.9% along the z-axis. The measurement errors of linear accelerations ax, ay and az in the experiments are 2.6%, 0.6% and 1.31%, respectively. The experiments prove that accelerometer with DCB elastic element performs great sensitive and precision characteristics. PMID:27657089

Analysis strategies for high-resolution UHF-fMRI data.

PubMed

Polimeni, Jonathan R; Renvall, Ville; Zaretskaya, Natalia; Fischl, Bruce

2018-03-01

Functional MRI (fMRI) benefits from both increased sensitivity and specificity with increasing magnetic field strength, making it a key application for Ultra-High Field (UHF) MRI scanners. Most UHF-fMRI studies utilize the dramatic increases in sensitivity and specificity to acquire high-resolution data reaching sub-millimeter scales, which enable new classes of experiments to probe the functional organization of the human brain. This review article surveys advanced data analysis strategies developed for high-resolution fMRI at UHF. These include strategies designed to mitigate distortion and artifacts associated with higher fields in ways that attempt to preserve spatial resolution of the fMRI data, as well as recently introduced analysis techniques that are enabled by these extremely high-resolution data. Particular focus is placed on anatomically-informed analyses, including cortical surface-based analysis, which are powerful techniques that can guide each step of the analysis from preprocessing to statistical analysis to interpretation and visualization. New intracortical analysis techniques for laminar and columnar fMRI are also reviewed and discussed. Prospects for single-subject individualized analyses are also presented and discussed. Altogether, there are both specific challenges and opportunities presented by UHF-fMRI, and the use of proper analysis strategies can help these valuable data reach their full potential. Copyright © 2017 Elsevier Inc. All rights reserved.

High sensitivity refractive index sensor based on adiabatic tapered optical fiber deposited with nanofilm by ALD.

PubMed

Zhu, Shan; Pang, Fufei; Huang, Sujuan; Zou, Fang; Dong, Yanhua; Wang, Tingyun

2015-06-01

Atomic layer deposition (ALD) technology is introduced to fabricate a high sensitivity refractive index sensor based on an adiabatic tapered optical fiber. Different thickness of Al₂O₃ nanofilm is coated around fiber taper precisely and uniformly under different deposition cycles. Attributed to the high refractive index of the Al₂O₃ nanofilm, an asymmetry Fabry-Perot like interferometer is constructed along the fiber taper. Based on the ray-optic analysis, total internal reflection happens on the nanofilm-surrounding interface. With the ambient refractive index changing, the phase delay induced by the Goos-Hänchen shift is changed. Correspondingly, the transmission resonant spectrum shifts, which can be utilized for realizing high sensitivity sensor. The high sensitivity sensor with 6008 nm/RIU is demonstrated by depositing 3000 layers Al₂O₃ nanofilm as the ambient refractive index is close to 1.33. This high sensitivity refractive index sensor is expected to have wide applications in biochemical sensors.

Optimizing the interpretation of CT for appendicitis: modeling health utilities for clinical practice.

PubMed

Blackmore, C Craig; Terasawa, Teruhiko

2006-02-01

Error in radiology can be reduced by standardizing the interpretation of imaging studies to the optimum sensitivity and specificity. In this report, the authors demonstrate how the optimal interpretation of appendiceal computed tomography (CT) can be determined and how it varies in different clinical scenarios. Utility analysis and receiver operating characteristic (ROC) curve modeling were used to determine the trade-off between false-positive and false-negative test results to determine the optimal operating point on the ROC curve for the interpretation of appendicitis CT. Modeling was based on a previous meta-analysis for the accuracy of CT and on literature estimates of the utilities of various health states. The posttest probability of appendicitis was derived using Bayes's theorem. At a low prevalence of disease (screening), appendicitis CT should be interpreted at high specificity (97.7%), even at the expense of lower sensitivity (75%). Conversely, at a high probability of disease, high sensitivity (97.4%) is preferred (specificity 77.8%). When the clinical diagnosis of appendicitis is equivocal, CT interpretation should emphasize both sensitivity and specificity (sensitivity 92.3%, specificity 91.5%). Radiologists can potentially decrease medical error and improve patient health by varying the interpretation of appendiceal CT on the basis of the clinical probability of appendicitis. This report is an example of how utility analysis can be used to guide radiologists in the interpretation of imaging studies and provide guidance on appropriate targets for the standardization of interpretation.

Diagnostic Accuracy of Memory Measures in Alzheimer’s Dementia and Mild Cognitive Impairment: a Systematic Review and Meta-Analysis

PubMed Central

Weissberger, Gali H.; Strong, Jessica V.; Stefanidis, Kayla B.; Summers, Mathew J.; Bondi, Mark W.; Stricker, Nikki H.

2018-01-01

With an increasing focus on biomarkers in dementia research, illustrating the role of neuropsychological assessment in detecting mild cognitive impairment (MCI) and Alzheimer’s dementia (AD) is important. This systematic review and meta-analysis, conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) standards, summarizes the sensitivity and specificity of memory measures in individuals with MCI and AD. Both meta-analytic and qualitative examination of AD versus healthy control (HC) studies (n = 47) revealed generally high sensitivity and specificity (≥ 80% for AD comparisons) for measures of immediate (sensitivity = 87%, specificity = 88%) and delayed memory (sensitivity = 89%, specificity = 89%), especially those involving word-list recall. Examination of MCI versus HC studies (n = 38) revealed generally lower diagnostic accuracy for both immediate (sensitivity = 72%, specificity = 81%) and delayed memory (sensitivity = 75%, specificity = 81%). Measures that differentiated AD from other conditions (n = 10 studies) yielded mixed results, with generally high sensitivity in the context of low or variable specificity. Results confirm that memory measures have high diagnostic accuracy for identification of AD, are promising but require further refinement for identification of MCI, and provide support for ongoing investigation of neuropsychological assessment as a cognitive biomarker of preclinical AD. Emphasizing diagnostic test accuracy statistics over null hypothesis testing in future studies will promote the ongoing use of neuropsychological tests as Alzheimer’s disease research and clinical criteria increasingly rely upon cerebrospinal fluid (CSF) and neuroimaging biomarkers. PMID:28940127

Multidisciplinary Analysis and Optimal Design: As Easy as it Sounds?

NASA Technical Reports Server (NTRS)

Moore, Greg; Chainyk, Mike; Schiermeier, John

2004-01-01

The viewgraph presentation examines optimal design for precision, large aperture structures. Discussion focuses on aspects of design optimization, code architecture and current capabilities, and planned activities and collaborative area suggestions. The discussion of design optimization examines design sensitivity analysis; practical considerations; and new analytical environments including finite element-based capability for high-fidelity multidisciplinary analysis, design sensitivity, and optimization. The discussion of code architecture and current capabilities includes basic thermal and structural elements, nonlinear heat transfer solutions and process, and optical modes generation.

Cavity-enhanced resonant photoacoustic spectroscopy with optical feedback cw diode lasers: A novel technique for ultratrace gas analysis and high-resolution spectroscopy.

PubMed

Hippler, Michael; Mohr, Christian; Keen, Katherine A; McNaghten, Edward D

2010-07-28

Cavity-enhanced resonant photoacoustic spectroscopy with optical feedback cw diode lasers (OF-CERPAS) is introduced as a novel technique for ultratrace gas analysis and high-resolution spectroscopy. In the scheme, a single-mode cw diode laser (3 mW, 635 nm) is coupled into a high-finesse linear cavity and stabilized to the cavity by optical feedback. Inside the cavity, a build-up of laser power to at least 2.5 W occurs. Absorbing gas phase species inside the cavity are detected with high sensitivity by the photoacoustic effect using a microphone embedded in the cavity. To increase sensitivity further, coupling into the cavity is modulated at a frequency corresponding to a longitudinal resonance of an organ pipe acoustic resonator (f=1.35 kHz and Q approximately 10). The technique has been characterized by measuring very weak water overtone transitions near 635 nm. Normalized noise-equivalent absorption coefficients are determined as alpha approximately 4.4x10(-9) cm(-1) s(1/2) (1 s integration time) and 2.6x10(-11) cm(-1) s(1/2) W (1 s integration time and 1 W laser power). These sensitivities compare favorably with existing state-of-the-art techniques. As an advantage, OF-CERPAS is a "zero-background" method which increases selectivity and sensitivity, and its sensitivity scales with laser power.

Improving multi-objective reservoir operation optimization with sensitivity-informed dimension reduction

NASA Astrophysics Data System (ADS)

Chu, J.; Zhang, C.; Fu, G.; Li, Y.; Zhou, H.

2015-08-01

This study investigates the effectiveness of a sensitivity-informed method for multi-objective operation of reservoir systems, which uses global sensitivity analysis as a screening tool to reduce computational demands. Sobol's method is used to screen insensitive decision variables and guide the formulation of the optimization problems with a significantly reduced number of decision variables. This sensitivity-informed method dramatically reduces the computational demands required for attaining high-quality approximations of optimal trade-off relationships between conflicting design objectives. The search results obtained from the reduced complexity multi-objective reservoir operation problems are then used to pre-condition the full search of the original optimization problem. In two case studies, the Dahuofang reservoir and the inter-basin multi-reservoir system in Liaoning province, China, sensitivity analysis results show that reservoir performance is strongly controlled by a small proportion of decision variables. Sensitivity-informed dimension reduction and pre-conditioning are evaluated in their ability to improve the efficiency and effectiveness of multi-objective evolutionary optimization. Overall, this study illustrates the efficiency and effectiveness of the sensitivity-informed method and the use of global sensitivity analysis to inform dimension reduction of optimization problems when solving complex multi-objective reservoir operation problems.

Improving multi-objective reservoir operation optimization with sensitivity-informed problem decomposition

NASA Astrophysics Data System (ADS)

Chu, J. G.; Zhang, C.; Fu, G. T.; Li, Y.; Zhou, H. C.

2015-04-01

This study investigates the effectiveness of a sensitivity-informed method for multi-objective operation of reservoir systems, which uses global sensitivity analysis as a screening tool to reduce the computational demands. Sobol's method is used to screen insensitive decision variables and guide the formulation of the optimization problems with a significantly reduced number of decision variables. This sensitivity-informed problem decomposition dramatically reduces the computational demands required for attaining high quality approximations of optimal tradeoff relationships between conflicting design objectives. The search results obtained from the reduced complexity multi-objective reservoir operation problems are then used to pre-condition the full search of the original optimization problem. In two case studies, the Dahuofang reservoir and the inter-basin multi-reservoir system in Liaoning province, China, sensitivity analysis results show that reservoir performance is strongly controlled by a small proportion of decision variables. Sensitivity-informed problem decomposition and pre-conditioning are evaluated in their ability to improve the efficiency and effectiveness of multi-objective evolutionary optimization. Overall, this study illustrates the efficiency and effectiveness of the sensitivity-informed method and the use of global sensitivity analysis to inform problem decomposition when solving the complex multi-objective reservoir operation problems.

Results of an integrated structure-control law design sensitivity analysis

NASA Technical Reports Server (NTRS)

Gilbert, Michael G.

1988-01-01

Next generation air and space vehicle designs are driven by increased performance requirements, demanding a high level of design integration between traditionally separate design disciplines. Interdisciplinary analysis capabilities have been developed, for aeroservoelastic aircraft and large flexible spacecraft control for instance, but the requisite integrated design methods are only beginning to be developed. One integrated design method which has received attention is based on hierarchal problem decompositions, optimization, and design sensitivity analyses. This paper highlights a design sensitivity analysis method for Linear Quadratic Cost, Gaussian (LQG) optimal control laws, which predicts change in the optimal control law due to changes in fixed problem parameters using analytical sensitivity equations. Numerical results of a design sensitivity analysis for a realistic aeroservoelastic aircraft example are presented. In this example, the sensitivity of the optimally controlled aircraft's response to various problem formulation and physical aircraft parameters is determined. These results are used to predict the aircraft's new optimally controlled response if the parameter was to have some other nominal value during the control law design process. The sensitivity results are validated by recomputing the optimal control law for discrete variations in parameters, computing the new actual aircraft response, and comparing with the predicted response. These results show an improvement in sensitivity accuracy for integrated design purposes over methods which do not include changess in the optimal control law. Use of the analytical LQG sensitivity expressions is also shown to be more efficient that finite difference methods for the computation of the equivalent sensitivity information.

[The history of hepatitis B virus-related determination tests and inspection and the measurements of problems in Japan].

PubMed

Shibata, Hiroshi

2013-09-01

Since Hepatitis B virus was detected as the cause of hepatitis, many high-sensitive measurement methods have been developed. In the development history, there are many problems in accuracy, sensitivity and health insurance regulations among different types of kits with different measurement principles. Advanced medical treatments cause problems of gene mutation or reactivation of HBV, leading to the necessity for high sensitive and sophisticated determination. The history of clinical analysis for the detection of HBV was reviewed from the viewpoint of our experiences.

Geotechnical properties of ash deposits near Hilo, Hawaii

USGS Publications Warehouse

Wieczorek, G.F.; Jibson, R.W.; Wilson, R.C.; Buchanan-Banks, J. M.

1982-01-01

Two holes were hand augered and sampled in ash deposits near Hilo, Hawaii. Color, water content and sensitivity of the ash were measured in the field. The ash alternated between reddish brown and dark reddish brown in color and had water contents as high as 392%. A downhole vane shear device measured sensitivities as high as 6.9. A series of laboratory tests including grain size distribution, Atterberg limits, X-ray diffraction analysis, total carbon determination, vane shear, direct shear and triaxial tests were performed to determine the composition and geotechnical properties of the ash. The ash is very fine grained, highly plastic and composed mostly of gibbsite and amorphous material presumably allophane. The ash has a high angle of internal friction ranging from 40-43? and is classified as medium to very sensitive. A series of different ash layers was distinguished on the basis of plasticity and other geotechnical properties. Sensitivity may be due to a metastable fabric, cementation, leaching, high organic content, and thixotropy. The sensitivity of the volcanic ash deposits near Hilo is consistent with documented slope instability during earthquakes in Hawaii. The high angles of internal friction and cementation permit very steep slopes under static conditions. However, because of high sensitivity of the ash, these slopes are particularly susceptible to seismically-induced landsliding.

Finding the bottom and using it

PubMed Central

Sandoval, Ruben M.; Wang, Exing; Molitoris, Bruce A.

2014-01-01

Maximizing 2-photon parameters used in acquiring images for quantitative intravital microscopy, especially when high sensitivity is required, remains an open area of investigation. Here we present data on correctly setting the black level of the photomultiplier tube amplifier by adjusting the offset to allow for accurate quantitation of low intensity processes. When the black level is set too high some low intensity pixel values become zero and a nonlinear degradation in sensitivity occurs rendering otherwise quantifiable low intensity values virtually undetectable. Initial studies using a series of increasing offsets for a sequence of concentrations of fluorescent albumin in vitro revealed a loss of sensitivity for higher offsets at lower albumin concentrations. A similar decrease in sensitivity, and therefore the ability to correctly determine the glomerular permeability coefficient of albumin, occurred in vivo at higher offset. Finding the offset that yields accurate and linear data are essential for quantitative analysis when high sensitivity is required. PMID:25313346

Disgusted by Sexual Abuse: Exploring the Association Between Disgust Sensitivity and Posttraumatic Stress Symptoms Among Mothers of Sexually Abused Children.

PubMed

van Delft, Ivanka; Finkenauer, Catrin; Tybur, Joshua M; Lamers-Winkelman, Francien

2016-06-01

Nonoffending mothers of sexually abused children often exhibit high levels of posttraumatic stress (PTS) symptoms. Emerging evidence suggests that trait-like individual differences in sensitivity to disgust play a role in the development of PTS symptoms. One such individual difference, disgust sensitivity, has not been examined as far as we are aware among victims of secondary traumatic stress. The current study examined associations between disgust sensitivity and PTS symptoms among mothers of sexually abused children (N = 72). Mothers completed the Impact of Event Scale-Revised and the Three Domain Disgust Scale (Tybur, Lieberman, & Griskevicius, 2009). More than one third of mothers scored above a suggested cutoff (mean score = 1.5) for high levels of PTS symptoms. Hierarchical linear regression analysis results indicated that sexual disgust sensitivity (β = .39, p = .002) was associated with PTS symptoms (R(2) = .18). An interaction analysis showed that sexual disgust sensitivity was associated with maternal PTS symptoms only when the perpetrator was not biologically related to the child (β = -.32, p = .047; R(2) = .28). Our findings suggested that sexual disgust sensitivity may be a risk factor for developing PTS symptoms among mothers of sexually abused children. Copyright © 2016 International Society for Traumatic Stress Studies.

Diagnostic Performance of DNA Hypermethylation Markers in Peripheral Blood for the Detection of Colorectal Cancer: A Meta-Analysis and Systematic Review

PubMed Central

Li, Bingsheng; Gan, Aihua; Chen, Xiaolong; Wang, Xinying; He, Weifeng; Zhang, Xiaohui; Huang, Renxiang; Zhou, Shuzhu; Song, Xiaoxiao; Xu, Angao

2016-01-01

DNA hypermethylation in blood is becoming an attractive candidate marker for colorectal cancer (CRC) detection. To assess the diagnostic accuracy of blood hypermethylation markers for CRC in different clinical settings, we conducted a meta-analysis of published reports. Of 485 publications obtained in the initial literature search, 39 studies were included in the meta-analysis. Hypermethylation markers in peripheral blood showed a high degree of accuracy for the detection of CRC. The summary sensitivity was 0.62 [95% confidence interval (CI), 0.56–0.67] and specificity was 0.91 (95% CI, 0.89–0.93). Subgroup analysis showed significantly greater sensitivity for the methylated Septin 9 gene (SEPT9) subgroup (0.75; 95% CI, 0.67–0.81) than for the non-methylated SEPT9 subgroup (0.58; 95% CI, 0.52–0.64). Sensitivity and specificity were not affected significantly by target gene number, CRC staging, study region, or methylation analysis method. These findings show that hypermethylation markers in blood are highly sensitive and specific for CRC detection, with methylated SEPT9 being particularly robust. The diagnostic performance of hypermethylation markers, which have varied across different studies, can be improved by marker optimization. Future research should examine variation in diagnostic accuracy according to non-neoplastic factors. PMID:27158984

Sensitivity Analysis for Coupled Aero-structural Systems

NASA Technical Reports Server (NTRS)

Giunta, Anthony A.

1999-01-01

A novel method has been developed for calculating gradients of aerodynamic force and moment coefficients for an aeroelastic aircraft model. This method uses the Global Sensitivity Equations (GSE) to account for the aero-structural coupling, and a reduced-order modal analysis approach to condense the coupling bandwidth between the aerodynamic and structural models. Parallel computing is applied to reduce the computational expense of the numerous high fidelity aerodynamic analyses needed for the coupled aero-structural system. Good agreement is obtained between aerodynamic force and moment gradients computed with the GSE/modal analysis approach and the same quantities computed using brute-force, computationally expensive, finite difference approximations. A comparison between the computational expense of the GSE/modal analysis method and a pure finite difference approach is presented. These results show that the GSE/modal analysis approach is the more computationally efficient technique if sensitivity analysis is to be performed for two or more aircraft design parameters.

Population and High-Risk Group Screening for Glaucoma: The Los Angeles Latino Eye Study

PubMed Central

Francis, Brian A.; Vigen, Cheryl; Lai, Mei-Ying; Winarko, Jonathan; Nguyen, Betsy; Azen, Stanley

2011-01-01

Purpose. To evaluate the ability of various screening tests, both individually and in combination, to detect glaucoma in the general Latino population and high-risk subgroups. Methods. The Los Angeles Latino Eye Study is a population-based study of eye disease in Latinos 40 years of age and older. Participants (n = 6082) underwent Humphrey visual field testing (HVF), frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP) and central corneal thickness (CCT), and independent assessment of optic nerve vertical cup disc (C/D) ratio. Screening parameters were evaluated for three definitions of glaucoma based on optic disc, visual field, and a combination of both. Analyses were also conducted for high-risk subgroups (family history of glaucoma, diabetes mellitus, and age ≥65 years). Sensitivity, specificity, and receiver operating characteristic curves were calculated for those continuous parameters independently associated with glaucoma. Classification and regression tree (CART) analysis was used to develop a multivariate algorithm for glaucoma screening. Results. Preset cutoffs for screening parameters yielded a generally poor balance of sensitivity and specificity (sensitivity/specificity for IOP ≥21 mm Hg and C/D ≥0.8 was 0.24/0.97 and 0.60/0.98, respectively). Assessment of high-risk subgroups did not improve the sensitivity/specificity of individual screening parameters. A CART analysis using multiple screening parameters—C/D, HVF, and IOP—substantially improved the balance of sensitivity and specificity (sensitivity/specificity 0.92/0.92). Conclusions. No single screening parameter is useful for glaucoma screening. However, a combination of vertical C/D ratio, HVF, and IOP provides the best balance of sensitivity/specificity and is likely to provide the highest yield in glaucoma screening programs. PMID:21245400

Integrated analysis of rice transcriptomic and metabolomic responses to elevated night temperatures identifies sensitivity- and tolerance-related profiles.

PubMed

Glaubitz, Ulrike; Li, Xia; Schaedel, Sandra; Erban, Alexander; Sulpice, Ronan; Kopka, Joachim; Hincha, Dirk K; Zuther, Ellen

2017-01-01

Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein-protein interactions, jasmonate response and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall-related genes, of ABA signaling and secondary metabolism. Additionally, metabolite profiles revealed a highly activated TCA cycle under HNT and concomitantly increased levels in pathways branching off that could be corroborated by enzyme activity measurements. Integrated data analysis using clustering based on one-dimensional self-organizing maps identified two profiles highly correlated with HNT sensitivity. The sensitivity profile included genes of the functional bins abiotic stress, hormone metabolism, cell wall, signaling, redox state, transcription factors, secondary metabolites and defence genes. In the tolerance profile, similar bins were affected with slight differences in hormone metabolism and transcription factor responses. Metabolites of the two profiles revealed involvement of GABA signaling, thus providing a link to the TCA cycle status in sensitive cultivars and of myo-inositol as precursor for inositol phosphates linking jasmonate signaling to the HNT response specifically in tolerant cultivars. © 2016 John Wiley & Sons Ltd.

High frequency QRS ECG predicts ischemic defects during myocardial perfusion imaging

NASA Technical Reports Server (NTRS)

2004-01-01

Changes in high frequency QRS components of the electrocardiogram (HF QRS ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting ischemia during adenosine tetrofosmin myocardial perfusion imaging (MPI). 12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium-99 tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphological score that incorporated the number, type and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square (RMS) voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P less than 0.00l). Analysis of 12-lead HF QRS ECG is highly sensitive and specific for detecting ischemic perfusion defects during adenosine MPI stress tests and significantly more sensitive than analysis of conventional ST segments.

High frequency QRS ECG predicts ischemic defects during myocardial perfusion imaging

NASA Technical Reports Server (NTRS)

Rahman, Atiar

2006-01-01

Background: Changes in high frequency QRS components of the electrocardiogram (HF QRS ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting ischemia during adenosine tetrofosmin myocardial perfusion imaging (MPI). Methods and Results: 12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium-99 tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphological score that incorporated the number, type and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square (RMS) voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P<0.001). Conclusions: Analysis of 12-lead HF QRS ECG is highly sensitive and specific for detecting ischemic perfusion defects during adenosine MPI stress tests and significantly more sensitive than analysis of conventional ST segments.

Systemic analysis of different colorectal cancer cell lines and TCGA datasets identified IGF-1R/EGFR-PPAR-CASPASE axis as important indicator for radiotherapy sensitivity.

PubMed

Chen, Lin; Zhu, Zhe; Gao, Wei; Jiang, Qixin; Yu, Jiangming; Fu, Chuangang

2017-09-05

Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the development of many types of cancers. But, little is known about its roles in radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF-1R expression value was associated with the better radiotherapy sensitivity of CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated expression value of epidermal growth factor receptor (EGFR) was observed in CRC cell lines (HT29, RKO) with high radio-sensitivity compared with those with low sensitivity (SW480, LOVO). The irradiation induced apoptosis rates of wild type and EGFR agonist (EGF) or IGF-1R inhibitor (NVP-ADW742) treated HT29 and SW480 cells were quantified by flow cytometry. As a result, the apoptosis rate of EGF and NVP-ADW742 treated HT29 cells was significantly higher than that of those wild type ones, which indicated that high EGFR and low IGF-1R expression level in CRC was associated with the high sensitivity to radiotherapy. We next conducted systemic bioinformatics analysis of genome-wide expression profiles of CRC samples from the Cancer Genome Atlas (TCGA). Differential expression analysis between IGF-1R and EGFR abnormal CRC samples, i.e. CRC samples with higher IGF-1R and lower EGFR expression levels based on their median expression values, and the rest of CRC samples identified potential genes contribute to radiotherapy sensitivity. Functional enrichment of analysis of those differential expression genes (DEGs) in the Database for Annotation, Visualization and Integrated Discovery (DAVID) indicated PPAR signaling pathway as an important pathway for the radio-resistance of CRC. Our study identified the potential biomarkers for the rational selection of radiotherapy for CRC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

[Meta-analysis of diagnostic capability of frequency-doubling technology (FDT) for primary glaucoma].

PubMed

Liu, Ting; He, Xiang-ge

2006-05-01

To evaluate the overall diagnostic capabilities of frequency-doubling technology (FDT) in patients of primary glaucoma, with standard automated perimetry (SAP) and/or optic disc appearance as the gold standard. A comprehensive electric search in MEDLINE, EMBASE, Cochrane Library, BIOSIS, Previews, HMIC, IPA, OVID, CNKI, CBMdisc, VIP information, CMCC, CCPD, SSreader and 21dmedia and a manual search in related textbooks, journals, congress articles and their references were performed to identify relevant English and Chinese language articles. Criteria for adaptability were established according to validity criteria for diagnostic research published by the Cochrane Methods Group on Screening and Diagnostic Tests. Quality of the included articles was assessed and relevant materials were extracted for studying. Statistical analysis was performed with Meta Test version 0.6 software. Heterogeneity of the included articles was tested, which was used to select appropriate effect model to calculate pooled weighted sensitivity and specificity. Summary Receiver Operating Characteristic (SROC) curve was established and the area under the curve (AUC) was calculated. Finally, sensitivity analysis was performed. Fifteen English articles (21 studies) of 206 retrieved articles were included in the present study, with a total of 3172 patients. The reported sensitivity of FDT ranged from 0.51 to 1.00, and specificity from 0.58 to 1.00. The pooled weighted sensitivity and specificity for FDT with 95% confidence intervals (95% CI) after correction for standard error were 0.86 (0.80 - 0.90), 0.87 (0.81 - 0.91), respectively. The AUC of SROC was 93.01%. Sensitivity analysis demonstrated no disproportionate influences of individual study. The included articles are of good quality and FDT can be a highly efficient diagnostic test for primary glaucoma based on Meta-analysis. However, a high quality perspective study is still required for further analysis.

Testing of stack-unit/aquifer sensitivity analysis using contaminant plume distribution in the subsurface of Savannah River Site, South Carolina, USA

USGS Publications Warehouse

Rine, J.M.; Shafer, J.M.; Covington, E.; Berg, R.C.

2006-01-01

Published information on the correlation and field-testing of the technique of stack-unit/aquifer sensitivity mapping with documented subsurface contaminant plumes is rare. The inherent characteristic of stack-unit mapping, which makes it a superior technique to other analyses that amalgamate data, is the ability to deconstruct the sensitivity analysis on a unit-by-unit basis. An aquifer sensitivity map, delineating the relative sensitivity of the Crouch Branch aquifer of the Administrative/Manufacturing Area (A/M) at the Savannah River Site (SRS) in South Carolina, USA, incorporates six hydrostratigraphic units, surface soil units, and relevant hydrologic data. When this sensitivity map is compared with the distribution of the contaminant tetrachloroethylene (PCE), PCE is present within the Crouch Branch aquifer within an area classified as highly sensitive, even though the PCE was primarily released on the ground surface within areas classified with low aquifer sensitivity. This phenomenon is explained through analysis of the aquifer sensitivity map, the groundwater potentiometric surface maps, and the plume distributions within the area on a unit-by- unit basis. The results of this correlation show how the paths of the PCE plume are influenced by both the geology and the groundwater flow. ?? Springer-Verlag 2006.

Sensitive Multi-Species Emissions Monitoring: Infrared Laser-Based Detection of Trace-Level Contaminants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steill, Jeffrey D.; Huang, Haifeng; Hoops, Alexandra A.

This report summarizes our development of spectroscopic chemical analysis techniques and spectral modeling for trace-gas measurements of highly-regulated low-concentration species present in flue gas emissions from utility coal boilers such as HCl under conditions of high humidity. Detailed spectral modeling of the spectroscopy of HCl and other important combustion and atmospheric species such as H 2 O, CO 2 , N 2 O, NO 2 , SO 2 , and CH 4 demonstrates that IR-laser spectroscopy is a sensitive multi-component analysis strategy. Experimental measurements from techniques based on IR laser spectroscopy are presented that demonstrate sub-ppm sensitivity levels to thesemore » species. Photoacoustic infrared spectroscopy is used to detect and quantify HCl at ppm levels with extremely high signal-to-noise even under conditions of high relative humidity. Additionally, cavity ring-down IR spectroscopy is used to achieve an extremely high sensitivity to combustion trace gases in this spectral region; ppm level CH 4 is one demonstrated example. The importance of spectral resolution in the sensitivity of a trace-gas measurement is examined by spectral modeling in the mid- and near-IR, and efforts to improve measurement resolution through novel instrument development are described. While previous project reports focused on benefits and complexities of the dual-etalon cavity ring-down infrared spectrometer, here details on steps taken to implement this unique and potentially revolutionary instrument are described. This report also illustrates and critiques the general strategy of IR- laser photodetection of trace gases leading to the conclusion that mid-IR laser spectroscopy techniques provide a promising basis for further instrument development and implementation that will enable cost-effective sensitive detection of multiple key contaminant species simultaneously.« less

Sensitive sub-Doppler nonlinear spectroscopy for hyperfine-structure analysis using simple atomizers

NASA Astrophysics Data System (ADS)

Mickadeit, Fritz K.; Kemp, Helen; Schafer, Julia; Tong, William M.

1998-05-01

Laser wave-mixing spectroscopy is presented as a sub-Doppler method that offers not only high spectral resolution, but also excellent detection sensitivity. It offers spectral resolution suitable for hyperfine structure analysis and isotope ratio measurements. In a non-planar backward- scattering four-wave mixing optical configuration, two of the three input beams counter propagate and the Doppler broadening is minimized, and hence, spectral resolution is enhanced. Since the signal is a coherent beam, optical collection is efficient and signal detection is convenient. This simple multi-photon nonlinear laser method offers un usually sensitive detection limits that are suitable for trace-concentration isotope analysis using a few different types of simple analytical atomizers. Reliable measurement of hyperfine structures allows effective determination of isotope ratios for chemical analysis.

Highly sensitive analysis of polycyclic aromatic hydrocarbons in environmental water with porous cellulose/zeolitic imidazolate framework-8 composite microspheres as a novel adsorbent coupled with high-performance liquid chromatography.

PubMed

Liang, Xiaotong; Liu, Shengquan; Zhu, Rong; Xiao, Lixia; Yao, Shouzhuo

2016-07-01

In this work, novel cellulose/zeolitic imidazolate frameworks-8 composite microspheres have been successfully fabricated and utilized as sorbent for environmental polycyclic aromatic hydrocarbons efficient extraction and sensitive analysis. The composite microspheres were synthesized through the in situ hydrothermal growth of zeolitic imidazolate frameworks-8 on cellulose matrix, and exhibited favorable hierarchical structure with chemical composition as assumed through scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction patterns, and Brunauer-Emmett-Teller surface areas characterization. A robust and highly efficient method was then successfully developed with as-prepared composite microspheres as novel solid-phase extraction sorbent with optimum extraction conditions, such as sorbent amount, sample volume, extraction time, desorption conditions, volume of organic modifier, and ionic strength. The method exhibited high sensitivity with low limit of detection down to 0.1-1.0 ng/L and satisfactory linearity with correlation coefficients ranging from 0.9988 to 0.9999, as well as good recoveries of 66.7-121.2% with relative standard deviations less than 10% for environmental polycyclic aromatic hydrocarbons analysis. Thus, our method was convenient and efficient for polycyclic aromatic hydrocarbons extraction and detection, potential for future environmental water samples analysis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systematic analysis of Ca2+ homeostasis in Saccharomyces cerevisiae based on chemical-genetic interaction profiles

PubMed Central

Ghanegolmohammadi, Farzan; Yoshida, Mitsunori; Ohnuki, Shinsuke; Sukegawa, Yuko; Okada, Hiroki; Obara, Keisuke; Kihara, Akio; Suzuki, Kuninori; Kojima, Tetsuya; Yachie, Nozomu; Hirata, Dai; Ohya, Yoshikazu

2017-01-01

We investigated the global landscape of Ca2+ homeostasis in budding yeast based on high-dimensional chemical-genetic interaction profiles. The morphological responses of 62 Ca2+-sensitive (cls) mutants were quantitatively analyzed with the image processing program CalMorph after exposure to a high concentration of Ca2+. After a generalized linear model was applied, an analysis of covariance model was used to detect significant Ca2+–cls interactions. We found that high-dimensional, morphological Ca2+–cls interactions were mixed with positive (86%) and negative (14%) chemical-genetic interactions, whereas one-dimensional fitness Ca2+–cls interactions were all negative in principle. Clustering analysis with the interaction profiles revealed nine distinct gene groups, six of which were functionally associated. In addition, characterization of Ca2+–cls interactions revealed that morphology-based negative interactions are unique signatures of sensitized cellular processes and pathways. Principal component analysis was used to discriminate between suppression and enhancement of the Ca2+-sensitive phenotypes triggered by inactivation of calcineurin, a Ca2+-dependent phosphatase. Finally, similarity of the interaction profiles was used to reveal a connected network among the Ca2+ homeostasis units acting in different cellular compartments. Our analyses of high-dimensional chemical-genetic interaction profiles provide novel insights into the intracellular network of yeast Ca2+ homeostasis. PMID:28566553

Highly sensitive index of sympathetic activity based on time-frequency spectral analysis of electrodermal activity.

PubMed

Posada-Quintero, Hugo F; Florian, John P; Orjuela-Cañón, Álvaro D; Chon, Ki H

2016-09-01

Time-domain indices of electrodermal activity (EDA) have been used as a marker of sympathetic tone. However, they often show high variation between subjects and low consistency, which has precluded their general use as a marker of sympathetic tone. To examine whether power spectral density analysis of EDA can provide more consistent results, we recently performed a variety of sympathetic tone-evoking experiments (43). We found significant increase in the spectral power in the frequency range of 0.045 to 0.25 Hz when sympathetic tone-evoking stimuli were induced. The sympathetic tone assessed by the power spectral density of EDA was found to have lower variation and more sensitivity for certain, but not all, stimuli compared with the time-domain analysis of EDA. We surmise that this lack of sensitivity in certain sympathetic tone-inducing conditions with time-invariant spectral analysis of EDA may lie in its inability to characterize time-varying dynamics of the sympathetic tone. To overcome the disadvantages of time-domain and time-invariant power spectral indices of EDA, we developed a highly sensitive index of sympathetic tone, based on time-frequency analysis of EDA signals. Its efficacy was tested using experiments designed to elicit sympathetic dynamics. Twelve subjects underwent four tests known to elicit sympathetic tone arousal: cold pressor, tilt table, stand test, and the Stroop task. We hypothesize that a more sensitive measure of sympathetic control can be developed using time-varying spectral analysis. Variable frequency complex demodulation, a recently developed technique for time-frequency analysis, was used to obtain spectral amplitudes associated with EDA. We found that the time-varying spectral frequency band 0.08-0.24 Hz was most responsive to stimulation. Spectral power for frequencies higher than 0.24 Hz were determined to be not related to the sympathetic dynamics because they comprised less than 5% of the total power. The mean value of time-varying spectral amplitudes in the frequency band 0.08-0.24 Hz were used as the index of sympathetic tone, termed TVSymp. TVSymp was found to be overall the most sensitive to the stimuli, as evidenced by a low coefficient of variation (0.54), and higher consistency (intra-class correlation, 0.96) and sensitivity (Youden's index > 0.75), area under the receiver operating characteristic (ROC) curve (>0.8, accuracy > 0.88) compared with time-domain and time-invariant spectral indices, including heart rate variability. Copyright © 2016 the American Physiological Society.

FLOCK cluster analysis of mast cell event clustering by high-sensitivity flow cytometry predicts systemic mastocytosis.

PubMed

Dorfman, David M; LaPlante, Charlotte D; Pozdnyakova, Olga; Li, Betty

2015-11-01

In our high-sensitivity flow cytometric approach for systemic mastocytosis (SM), we identified mast cell event clustering as a new diagnostic criterion for the disease. To objectively characterize mast cell gated event distributions, we performed cluster analysis using FLOCK, a computational approach to identify cell subsets in multidimensional flow cytometry data in an unbiased, automated fashion. FLOCK identified discrete mast cell populations in most cases of SM (56/75 [75%]) but only a minority of non-SM cases (17/124 [14%]). FLOCK-identified mast cell populations accounted for 2.46% of total cells on average in SM cases and 0.09% of total cells on average in non-SM cases (P < .0001) and were predictive of SM, with a sensitivity of 75%, a specificity of 86%, a positive predictive value of 76%, and a negative predictive value of 85%. FLOCK analysis provides useful diagnostic information for evaluating patients with suspected SM, and may be useful for the analysis of other hematopoietic neoplasms. Copyright© by the American Society for Clinical Pathology.

Surrogate-based Analysis and Optimization

NASA Technical Reports Server (NTRS)

Queipo, Nestor V.; Haftka, Raphael T.; Shyy, Wei; Goel, Tushar; Vaidyanathan, Raj; Tucker, P. Kevin

2005-01-01

A major challenge to the successful full-scale development of modem aerospace systems is to address competing objectives such as improved performance, reduced costs, and enhanced safety. Accurate, high-fidelity models are typically time consuming and computationally expensive. Furthermore, informed decisions should be made with an understanding of the impact (global sensitivity) of the design variables on the different objectives. In this context, the so-called surrogate-based approach for analysis and optimization can play a very valuable role. The surrogates are constructed using data drawn from high-fidelity models, and provide fast approximations of the objectives and constraints at new design points, thereby making sensitivity and optimization studies feasible. This paper provides a comprehensive discussion of the fundamental issues that arise in surrogate-based analysis and optimization (SBAO), highlighting concepts, methods, techniques, as well as practical implications. The issues addressed include the selection of the loss function and regularization criteria for constructing the surrogates, design of experiments, surrogate selection and construction, sensitivity analysis, convergence, and optimization. The multi-objective optimal design of a liquid rocket injector is presented to highlight the state of the art and to help guide future efforts.

Analysis of glycosaminoglycan-derived disaccharides by capillary electrophoresis using laser-induced fluorescence detection

PubMed Central

Chang, Yuqing; Yang, Bo; Zhao, Xue; Linhardt, Robert J.

2012-01-01

A quantitative and highly sensitive method for the analysis of glycosaminoglycan (GAG)-derived disaccharides is presented that relies on capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection. This method enables complete separation of seventeen GAG-derived disaccharides in a single run. Unsaturated disaccharides were derivatized with 2-aminoacridone (AMAC) to improve sensitivity. The limit of detection was at the attomole level and about 100-fold more sensitive than traditional CE-ultraviolet detection. A CE separation timetable was developed to achieve complete resolution and shorten analysis time. The RSD of migration time and peak areas at both low and high concentrations of unsaturated disaccharides are all less than 2.7% and 3.2%, respectively, demonstrating that this is a reproducible method. This analysis was successfully applied to cultured Chinese hamster ovary cell samples for determination of GAG disaccharides. The current method simplifies GAG extraction steps, and reduces inaccuracy in calculating ratios of heparin/heparan sulfate to chondroitin sulfate/dermatan sulfate, resulting from the separate analyses of a single sample. PMID:22609076

An approach to measure parameter sensitivity in watershed ...

EPA Pesticide Factsheets

Hydrologic responses vary spatially and temporally according to watershed characteristics. In this study, the hydrologic models that we developed earlier for the Little Miami River (LMR) and Las Vegas Wash (LVW) watersheds were used for detail sensitivity analyses. To compare the relative sensitivities of the hydrologic parameters of these two models, we used Normalized Root Mean Square Error (NRMSE). By combining the NRMSE index with the flow duration curve analysis, we derived an approach to measure parameter sensitivities under different flow regimes. Results show that the parameters related to groundwater are highly sensitive in the LMR watershed, whereas the LVW watershed is primarily sensitive to near surface and impervious parameters. The high and medium flows are more impacted by most of the parameters. Low flow regime was highly sensitive to groundwater related parameters. Moreover, our approach is found to be useful in facilitating model development and calibration. This journal article describes hydrological modeling of climate change and land use changes on stream hydrology, and elucidates the importance of hydrological model construction in generating valid modeling results.

Highly sensitive and quantitative detection of rare pathogens through agarose droplet microfluidic emulsion PCR at the single-cell level.

PubMed

Zhu, Zhi; Zhang, Wenhua; Leng, Xuefei; Zhang, Mingxia; Guan, Zhichao; Lu, Jiangquan; Yang, Chaoyong James

2012-10-21

Genetic alternations can serve as highly specific biomarkers to distinguish fatal bacteria or cancer cells from their normal counterparts. However, these mutations normally exist in very rare amount in the presence of a large excess of non-mutated analogs. Taking the notorious pathogen E. coli O157:H7 as the target analyte, we have developed an agarose droplet-based microfluidic ePCR method for highly sensitive, specific and quantitative detection of rare pathogens in the high background of normal bacteria. Massively parallel singleplex and multiplex PCR at the single-cell level in agarose droplets have been successfully established. Moreover, we challenged the system with rare pathogen detection and realized the sensitive and quantitative analysis of a single E. coli O157:H7 cell in the high background of 100,000 excess normal K12 cells. For the first time, we demonstrated rare pathogen detection through agarose droplet microfluidic ePCR. Such a multiplex single-cell agarose droplet amplification method enables ultra-high throughput and multi-parameter genetic analysis of large population of cells at the single-cell level to uncover the stochastic variations in biological systems.

Normal range of serum highly-sensitive troponin-T in patients with chronic kidney disease stage 3-5.

PubMed

Chotivanawan, Thunnop; Krittayaphong, Rungroj

2012-02-01

Serum troponin-T concentrations are commonly increased in chronic kidney disease (CKD) without acute coronary syndrome. Highly-sensitive troponin-T the new tool that helpful for diagnosis of acute coronary syndrome, provides few data about normal value in patients with chronic kidney disease. The authors studied 89 patients with CKD stage 3-5: 40 had CKD stage 3, 26 had CKD stage 4 and 23 had CKD stage 5. Serum samples were collected for the analysis of highly-sensitive troponin-T levels. The values of highly-sensitive troponin-T of the total group and each CKD stage were presented. The level of highly-sensitive troponin-T in patients with CKD stage 3-5 was 0.044 +/- 0.076 ng/ml. For CKD stages 3, 4 and 5 levels were 0.015 +/- 0.016, 0.043 +/- 0.056, 0.098 +/- 0.121 ng/ml, respectively. 95th percentile of the total group was 0.139 ng/ml. 95th percentile for stage 3, 4 and 5 were 0.052, 0.136, 0.297 ng/ml, respectively. 95th percentile for highly-sensitive troponin-T of patients with CKD stage 3-5 was 0.139 ng/ml. This number may be considered as the cut-off value for diagnosis of acute myocardial infarction.

Heart rate and blood pressure variabilities in salt-sensitive hypertension.

PubMed

Piccirillo, G; Bucca, C; Durante, M; Santagada, E; Munizzi, M R; Cacciafesta, M; Marigliano, V

1996-12-01

In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P < .05) and of heart rate at rest (59.2 +/- 2.4 normalized units [NU], P < .001) than salt-resistant subjects (6.6 +/- 0.3 mm Hg2, 55.0 +/- 3.2 NU) and normotensive control subjects (5.1 +/- 0.5 mm Hg2, 41.6 +/- 2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P < .001) and the ratio of low- to high-power frequency (P < .001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0 +/- 0.7 to 17.5 +/- 0.7 ms/mm Hg, P < .001) and salt-resistant subjects (from 6.9 +/- 0.7 to 13.9 +/- 0.9, P < .05) but not in salt-sensitive subjects (7.4 +/- 0.3 to 7.9 +/- 0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity.

Molecular imprinting ratiometric fluorescence sensor for highly selective and sensitive detection of phycocyanin.

PubMed

Wang, Xiaoyan; Yu, Jialuo; Kang, Qi; Shen, Dazhong; Li, Jinhua; Chen, Lingxin

2016-03-15

A facile strategy was developed to prepare molecular imprinting ratiometric fluorescence sensor for highly selective and sensitive detection of phycocyanin (PC) based on fluorescence resonance energy transfer (FRET), via a sol-gel polymerization process using nitrobenzoxadiazole (NBD) as fluorescent signal source. The ratio of two fluorescence peak emission intensities of NBD and PC was utilized to determine the concentration of PC, which could effectively reduce the background interference and fluctuation of diverse conditions. As a result, this sensor obtained high sensitivity with a low detection limit of 0.14 nM within 6 min, and excellent recognition specificity for PC over its analogues with a high imprinting factor of 9.1. Furthermore, the sensor attained high recoveries in the range of 93.8-110.2% at three spiking levels of PC, with precisions below 4.7% in seawater and lake water samples. The developed sensor strategy demonstrated simplicity, reliability, rapidity, high selectivity and high sensitivity, proving to be a feasible way to develop high efficient fluorescence sensors and thus potentially applicable for ultratrace analysis of complicated matrices. Copyright © 2015 Elsevier B.V. All rights reserved.

A 3-Year Study of Predictive Factors for Positive and Negative Appendicectomies.

PubMed

Chang, Dwayne T S; Maluda, Melissa; Lee, Lisa; Premaratne, Chandrasiri; Khamhing, Srisongham

2018-03-06

Early and accurate identification or exclusion of acute appendicitis is the key to avoid the morbidity of delayed treatment for true appendicitis or unnecessary appendicectomy, respectively. We aim (i) to identify potential predictive factors for positive and negative appendicectomies; and (ii) to analyse the use of ultrasound scans (US) and computed tomography (CT) scans for acute appendicitis. All appendicectomies that took place at our hospital from the 1st of January 2013 to the 31st of December 2015 were retrospectively recorded. Test results of potential predictive factors of acute appendicitis were recorded. Statistical analysis was performed using Fisher exact test, logistic regression analysis, sensitivity, specificity, and positive and negative predictive values calculation. 208 patients were included in this study. 184 patients had histologically proven acute appendicitis. The other 24 patients had either nonappendicitis pathology or normal appendix. Logistic regression analysis showed statistically significant associations between appendicitis and white cell count, neutrophil count, C-reactive protein, and bilirubin. Neutrophil count was the test with the highest sensitivity and negative predictive values, whereas bilirubin was the test with the highest specificity and positive predictive values (PPV). US and CT scans had high sensitivity and PPV for diagnosing appendicitis. No single test was sufficient to diagnose or exclude acute appendicitis by itself. Combining tests with high sensitivity (abnormal neutrophil count, and US and CT scans) and high specificity (raised bilirubin) may predict acute appendicitis more accurately.

Chromatographic-ICPMS methods for trace element and isotope analysis of water and biogenic calcite

NASA Astrophysics Data System (ADS)

Klinkhammer, G. P.; Haley, B. A.; McManus, J.; Palmer, M. R.

2003-04-01

ICP-MS is a powerful technique because of its sensitivity and speed of analysis. This is especially true for refractory elements that are notoriously difficult using TIMS and less energetic techniques. However, as ICP-MS instruments become more sensitive to elements of interest they also become more sensitive to interference. This becomes a pressing issue when analyzing samples with high total dissolved solids. This paper describes two trace element methods that overcome these problems by using chromatographic techniques to precondition samples prior to analysis by ICP-MS: separation of rare earth elements (REEs) from seawater using HPLC-ICPMS, and flow-through dissolution of foraminiferal calcite. Using HPLC in combination with ICP-MS it is possible to isolate the REEs from matrix, other transition elements, and each other. This method has been developed for small volume samples (5ml) making it possible to analyze sediment pore waters. As another example, subjecting foram shells to flow-through reagent addition followed by time-resolved analysis in the ICP-MS allows for systematic cleaning and dissolution of foram shells. This method provides information about the relationship between dissolution tendency and elemental composition. Flow-through is also amenable to automation thus yielding the high sample throughput required for paleoceanography, and produces a highly resolved elemental matrix that can be statistically analyzed.

Comparative Sensitivity Analysis of Muscle Activation Dynamics

PubMed Central

Günther, Michael; Götz, Thomas

2015-01-01

We mathematically compared two models of mammalian striated muscle activation dynamics proposed by Hatze and Zajac. Both models are representative for a broad variety of biomechanical models formulated as ordinary differential equations (ODEs). These models incorporate parameters that directly represent known physiological properties. Other parameters have been introduced to reproduce empirical observations. We used sensitivity analysis to investigate the influence of model parameters on the ODE solutions. In addition, we expanded an existing approach to treating initial conditions as parameters and to calculating second-order sensitivities. Furthermore, we used a global sensitivity analysis approach to include finite ranges of parameter values. Hence, a theoretician striving for model reduction could use the method for identifying particularly low sensitivities to detect superfluous parameters. An experimenter could use it for identifying particularly high sensitivities to improve parameter estimation. Hatze's nonlinear model incorporates some parameters to which activation dynamics is clearly more sensitive than to any parameter in Zajac's linear model. Other than Zajac's model, Hatze's model can, however, reproduce measured shifts in optimal muscle length with varied muscle activity. Accordingly we extracted a specific parameter set for Hatze's model that combines best with a particular muscle force-length relation. PMID:26417379

Photoacoustic Spectroscopy Analysis of Traditional Chinese Medicine

NASA Astrophysics Data System (ADS)

Chen, Lu; Zhao, Bin-xing; Xiao, Hong-tao; Tong, Rong-sheng; Gao, Chun-ming

2013-09-01

Chinese medicine is a historic cultural legacy of China. It has made a significant contribution to medicine and healthcare for generations. The development of Chinese herbal medicine analysis is emphasized by the Chinese pharmaceutical industry. This study has carried out the experimental analysis of ten kinds of Chinese herbal powder including Fritillaria powder, etc., based on the photoacoustic spectroscopy (PAS) method. First, a photoacoustic spectroscopy system was designed and constructed, especially a highly sensitive solid photoacoustic cell was established. Second, the experimental setup was verified through the characteristic emission spectrum of the light source, obtained by using carbon as a sample in the photoacoustic cell. Finally, as the photoacoustic spectroscopy analysis of Fritillaria, etc., was completed, the specificity of the Chinese herb medicine analysis was verified. This study shows that the PAS can provide a valid, highly sensitive analytical method for the specificity of Chinese herb medicine without preparing and damaging samples.

Bacteriophage-based assays for the rapid detection of rifampicin resistance in Mycobacterium tuberculosis: a meta-analysis.

PubMed

Pai, Madhukar; Kalantri, Shriprakash; Pascopella, Lisa; Riley, Lee W; Reingold, Arthur L

2005-10-01

To summarize, using meta-analysis, the accuracy of bacteriophage-based assays for the detection of rifampicin resistance in Mycobacterium tuberculosis. By searching multiple databases and sources we identified a total of 21 studies eligible for meta-analysis. Of these, 14 studies used phage amplification assays (including eight studies on the commercial FASTPlaque-TB kits), and seven used luciferase reporter phage (LRP) assays. Sensitivity, specificity, and agreement between phage assay and reference standard (e.g. agar proportion method or BACTEC 460) results were the main outcomes of interest. When performed on culture isolates (N=19 studies), phage assays appear to have relatively high sensitivity and specificity. Eleven of 19 (58%) studies reported sensitivity and specificity estimates > or =95%, and 13 of 19 (68%) studies reported > or =95% agreement with reference standard results. Specificity estimates were slightly lower and more variable than sensitivity; 5 of 19 (26%) studies reported specificity <90%. Only two studies performed phage assays directly on sputum specimens; although one study reported sensitivity and specificity of 100 and 99%, respectively, another reported sensitivity of 86% and specificity of 73%. Current evidence is largely restricted to the use of phage assays for the detection of rifampicin resistance in culture isolates. When used on culture isolates, these assays appear to have high sensitivity, but variable and slightly lower specificity. In contrast, evidence is lacking on the accuracy of these assays when they are directly applied to sputum specimens. If phage-based assays can be directly used on clinical specimens and if they are shown to have high accuracy, they have the potential to improve the diagnosis of MDR-TB. However, before phage assays can be successfully used in routine practice, several concerns have to be addressed, including unexplained false positives in some studies, potential for contamination and indeterminate results.

Functionalized Gold Nanoparticles for the Detection of C-Reactive Protein

PubMed Central

António, Maria

2018-01-01

C-reactive protein (CRP) is a very important biomarker of infection and inflammation for a number of diseases. Routine CRP measurements with high sensitivity and reliability are highly relevant to the assessment of states of inflammation and the efficacy of treatment intervention, and require the development of very sensitive, selective, fast, robust and reproducible assays. Gold nanoparticles (Au NPs) are distinguished for their unique electrical and optical properties and the ability to conjugate with biomolecules. Au NP-based probes have attracted considerable attention in the last decade in the analysis of biological samples due to their simplicity, high sensitivity and selectivity. Thus, this article aims to be a critical and constructive analysis of the literature of the last three years regarding the advances made in the development of bioanalytical assays based on gold nanoparticles for the in vitro detection and quantification of C-reactive protein from biological samples. Current methods for Au NP synthesis and the strategies for surface modification aiming at selectivity towards CRP are highlighted. PMID:29597295

Diagnostic Accuracy of Memory Measures in Alzheimer's Dementia and Mild Cognitive Impairment: a Systematic Review and Meta-Analysis.

PubMed

Weissberger, Gali H; Strong, Jessica V; Stefanidis, Kayla B; Summers, Mathew J; Bondi, Mark W; Stricker, Nikki H

2017-12-01

With an increasing focus on biomarkers in dementia research, illustrating the role of neuropsychological assessment in detecting mild cognitive impairment (MCI) and Alzheimer's dementia (AD) is important. This systematic review and meta-analysis, conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) standards, summarizes the sensitivity and specificity of memory measures in individuals with MCI and AD. Both meta-analytic and qualitative examination of AD versus healthy control (HC) studies (n = 47) revealed generally high sensitivity and specificity (≥ 80% for AD comparisons) for measures of immediate (sensitivity = 87%, specificity = 88%) and delayed memory (sensitivity = 89%, specificity = 89%), especially those involving word-list recall. Examination of MCI versus HC studies (n = 38) revealed generally lower diagnostic accuracy for both immediate (sensitivity = 72%, specificity = 81%) and delayed memory (sensitivity = 75%, specificity = 81%). Measures that differentiated AD from other conditions (n = 10 studies) yielded mixed results, with generally high sensitivity in the context of low or variable specificity. Results confirm that memory measures have high diagnostic accuracy for identification of AD, are promising but require further refinement for identification of MCI, and provide support for ongoing investigation of neuropsychological assessment as a cognitive biomarker of preclinical AD. Emphasizing diagnostic test accuracy statistics over null hypothesis testing in future studies will promote the ongoing use of neuropsychological tests as Alzheimer's disease research and clinical criteria increasingly rely upon cerebrospinal fluid (CSF) and neuroimaging biomarkers.

Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density

PubMed Central

Edwards, D. L.; Saleh, A. A.; Greenspan, S. L.

2015-01-01

Summary We performed a systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for DXA-determined osteoporosis or low bone density. Commonly evaluated risk instruments showed high sensitivity approaching or exceeding 90 % at particular thresholds within various populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. Introduction The purpose of the study is to systematically review the performance of clinical risk assessment instruments for screening for dual-energy X-ray absorptiometry (DXA)-determined osteoporosis or low bone density. Methods Systematic review and meta-analysis were performed. Multiple literature sources were searched, and data extracted and analyzed from included references. Results One hundred eight references met inclusion criteria. Studies assessed many instruments in 34 countries, most commonly the Osteoporosis Self-Assessment Tool (OST), the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument, the Osteoporosis Self-Assessment Tool for Asians (OSTA), the Osteoporosis Risk Assessment Instrument (ORAI), and body weight criteria. Meta-analyses of studies evaluating OST using a cutoff threshold of <1 to identify US postmenopausal women with osteoporosis at the femoral neck provided summary sensitivity and specificity estimates of 89 % (95%CI 82–96 %) and 41 % (95%CI 23–59 %), respectively. Meta-analyses of studies evaluating OST using a cutoff threshold of 3 to identify US men with osteoporosis at the femoral neck, total hip, or lumbar spine provided summary sensitivity and specificity estimates of 88 % (95%CI 79–97 %) and 55 % (95%CI 42–68 %), respectively. Frequently evaluated instruments each had thresholds and populations for which sensitivity for osteoporosis or low bone mass detection approached or exceeded 90 % but always with a trade-off of relatively low specificity. Conclusions Commonly evaluated clinical risk assessment instruments each showed high sensitivity approaching or exceeding 90 % for identifying individuals with DXA-determined osteoporosis or low BMD at certain thresholds in different populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. PMID:25644147

Post-Launch Analysis of Swift's Gamma-Ray Burst Detection Sensitivity

NASA Technical Reports Server (NTRS)

Band, David L.

2005-01-01

The dependence of Swift#s detection sensitivity on a burst#s temporal and spectral properties shapes the detected burst population. Using s implified models of the detector hardware and the burst trigger syste m I find that Swift is more sensitive to long, soft bursts than CGRO# s BATSE, a reference mission because of its large burst database. Thu s Swift has increased sensitivity in the parameter space region into which time dilation and spectral redshifting shift high redshift burs ts.

Disclosure of sensitive behaviors across self-administered survey modes: a meta-analysis.

PubMed

Gnambs, Timo; Kaspar, Kai

2015-12-01

In surveys, individuals tend to misreport behaviors that are in contrast to prevalent social norms or regulations. Several design features of the survey procedure have been suggested to counteract this problem; particularly, computerized surveys are supposed to elicit more truthful responding. This assumption was tested in a meta-analysis of survey experiments reporting 460 effect sizes (total N =125,672). Self-reported prevalence rates of several sensitive behaviors for which motivated misreporting has been frequently observed were compared across self-administered paper-and-pencil versus computerized surveys. The results revealed that computerized surveys led to significantly more reporting of socially undesirable behaviors than comparable surveys administered on paper. This effect was strongest for highly sensitive behaviors and surveys administered individually to respondents. Moderator analyses did not identify interviewer effects or benefits of audio-enhanced computer surveys. The meta-analysis highlighted the advantages of computerized survey modes for the assessment of sensitive topics.

[Quantitative surface analysis of Pt-Co, Cu-Au and Cu-Ag alloy films by XPS and AES].

PubMed

Li, Lian-Zhong; Zhuo, Shang-Jun; Shen, Ru-Xiang; Qian, Rong; Gao, Jie

2013-11-01

In order to improve the quantitative analysis accuracy of AES, We associated XPS with AES and studied the method to reduce the error of AES quantitative analysis, selected Pt-Co, Cu-Au and Cu-Ag binary alloy thin-films as the samples, used XPS to correct AES quantitative analysis results by changing the auger sensitivity factors to make their quantitative analysis results more similar. Then we verified the accuracy of the quantitative analysis of AES when using the revised sensitivity factors by other samples with different composition ratio, and the results showed that the corrected relative sensitivity factors can reduce the error in quantitative analysis of AES to less than 10%. Peak defining is difficult in the form of the integral spectrum of AES analysis since choosing the starting point and ending point when determining the characteristic auger peak intensity area with great uncertainty, and to make analysis easier, we also processed data in the form of the differential spectrum, made quantitative analysis on the basis of peak to peak height instead of peak area, corrected the relative sensitivity factors, and verified the accuracy of quantitative analysis by the other samples with different composition ratio. The result showed that the analytical error in quantitative analysis of AES reduced to less than 9%. It showed that the accuracy of AES quantitative analysis can be highly improved by the way of associating XPS with AES to correct the auger sensitivity factors since the matrix effects are taken into account. Good consistency was presented, proving the feasibility of this method.

HCIT Contrast Performance Sensitivity Studies: Simulation Versus Experiment

NASA Technical Reports Server (NTRS)

Sidick, Erkin; Shaklan, Stuart; Krist, John; Cady, Eric J.; Kern, Brian; Balasubramanian, Kunjithapatham

2013-01-01

Using NASA's High Contrast Imaging Testbed (HCIT) at the Jet Propulsion Laboratory, we have experimentally investigated the sensitivity of dark hole contrast in a Lyot coronagraph for the following factors: 1) Lateral and longitudinal translation of an occulting mask; 2) An opaque spot on the occulting mask; 3) Sizes of the controlled dark hole area. Also, we compared the measured results with simulations obtained using both MACOS (Modeling and Analysis for Controlled Optical Systems) and PROPER optical analysis programs with full three-dimensional near-field diffraction analysis to model HCIT's optical train and coronagraph.

Technical advances in flow cytometry-based diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria

PubMed Central

Correia, Rodolfo Patussi; Bento, Laiz Cameirão; Bortolucci, Ana Carolina Apelle; Alexandre, Anderson Marega; Vaz, Andressa da Costa; Schimidell, Daniela; Pedro, Eduardo de Carvalho; Perin, Fabricio Simões; Nozawa, Sonia Tsukasa; Mendes, Cláudio Ernesto Albers; Barroso, Rodrigo de Souza; Bacal, Nydia Strachman

2016-01-01

ABSTRACT Objective: To discuss the implementation of technical advances in laboratory diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria for validation of high-sensitivity flow cytometry protocols. Methods: A retrospective study based on analysis of laboratory data from 745 patient samples submitted to flow cytometry for diagnosis and/or monitoring of paroxysmal nocturnal hemoglobinuria. Results: Implementation of technical advances reduced test costs and improved flow cytometry resolution for paroxysmal nocturnal hemoglobinuria clone detection. Conclusion: High-sensitivity flow cytometry allowed more sensitive determination of paroxysmal nocturnal hemoglobinuria clone type and size, particularly in samples with small clones. PMID:27759825

Evaluation and construction of diagnostic criteria for inclusion body myositis

PubMed Central

Mammen, Andrew L.; Amato, Anthony A.; Weiss, Michael D.; Needham, Merrilee

2014-01-01

Objective: To use patient data to evaluate and construct diagnostic criteria for inclusion body myositis (IBM), a progressive disease of skeletal muscle. Methods: The literature was reviewed to identify all previously proposed IBM diagnostic criteria. These criteria were applied through medical records review to 200 patients diagnosed as having IBM and 171 patients diagnosed as having a muscle disease other than IBM by neuromuscular specialists at 2 institutions, and to a validating set of 66 additional patients with IBM from 2 other institutions. Machine learning techniques were used for unbiased construction of diagnostic criteria. Results: Twenty-four previously proposed IBM diagnostic categories were identified. Twelve categories all performed with high (≥97%) specificity but varied substantially in their sensitivities (11%–84%). The best performing category was European Neuromuscular Centre 2013 probable (sensitivity of 84%). Specialized pathologic features and newly introduced strength criteria (comparative knee extension/hip flexion strength) performed poorly. Unbiased data-directed analysis of 20 features in 371 patients resulted in construction of higher-performing data-derived diagnostic criteria (90% sensitivity and 96% specificity). Conclusions: Published expert consensus–derived IBM diagnostic categories have uniformly high specificity but wide-ranging sensitivities. High-performing IBM diagnostic category criteria can be developed directly from principled unbiased analysis of patient data. Classification of evidence: This study provides Class II evidence that published expert consensus–derived IBM diagnostic categories accurately distinguish IBM from other muscle disease with high specificity but wide-ranging sensitivities. PMID:24975859

Thermal effects on nonlinear vibration of a carbon nanotube-based mass sensor using finite element analysis

NASA Astrophysics Data System (ADS)

Kang, Dong-Keun; Kim, Chang-Wan; Yang, Hyun-Ik

2017-01-01

In the present study we carried out a dynamic analysis of a CNT-based mass sensor by using a finite element method (FEM)-based nonlinear analysis model of the CNT resonator to elucidate the combined effects of thermal effects and nonlinear oscillation behavior upon the overall mass detection sensitivity. Mass sensors using carbon nanotube (CNT) resonators provide very high sensing performance. Because CNT-based resonators can have high aspect ratios, they can easily exhibit nonlinear oscillation behavior due to large displacements. Also, CNT-based devices may experience high temperatures during their manufacture and operation. These geometrical nonlinearities and temperature changes affect the sensing performance of CNT-based mass sensors. However, it is very hard to find previous literature addressing the detection sensitivity of CNT-based mass sensors including considerations of both these nonlinear behaviors and thermal effects. We modeled the nonlinear equation of motion by using the von Karman nonlinear strain-displacement relation, taking into account the additional axial force associated with the thermal effect. The FEM was employed to solve the nonlinear equation of motion because it can effortlessly handle the more complex geometries and boundary conditions. A doubly clamped CNT resonator actuated by distributed electrostatic force was the configuration subjected to the numerical experiments. Thermal effects upon the fundamental resonance behavior and the shift of resonance frequency due to attached mass, i.e., the mass detection sensitivity, were examined in environments of both high and low (or room) temperature. The fundamental resonance frequency increased with decreasing temperature in the high temperature environment, and increased with increasing temperature in the low temperature environment. The magnitude of the shift in resonance frequency caused by an attached mass represents the sensing performance of a mass sensor, i.e., its mass detection sensitivity, and it can be seen that this shift is affected by the temperature change and the amount of electrostatic force. The thermal effects on the mass detection sensitivity are intensified in the linear oscillation regime and increase with increasing CNT length; this intensification can either improve or worsen the detection sensitivity.

High mass resolution time of flight mass spectrometer for measuring products in heterogeneous catalysis in highly sensitive microreactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersen, T.; Jensen, R.; Christensen, M. K.

2012-07-15

We demonstrate a combined microreactor and time of flight system for testing and characterization of heterogeneous catalysts with high resolution mass spectrometry and high sensitivity. Catalyst testing is performed in silicon-based microreactors which have high sensitivity and fast thermal response. Gas analysis is performed with a time of flight mass spectrometer with a modified nude Bayard-Alpert ionization gauge as gas ionization source. The mass resolution of the time of flight mass spectrometer using the ion gauge as ionization source is estimated to m/{Delta}m > 2500. The system design is superior to conventional batch and flow reactors with accompanying product detectionmore » by quadrupole mass spectrometry or gas chromatography not only due to the high sensitivity, fast temperature response, high mass resolution, and fast acquisition time of mass spectra but it also allows wide mass range (0-5000 amu in the current configuration). As a demonstration of the system performance we present data from ammonia oxidation on a Pt thin film showing resolved spectra of OH and NH{sub 3}.« less

High mass resolution time of flight mass spectrometer for measuring products in heterogeneous catalysis in highly sensitive microreactors

NASA Astrophysics Data System (ADS)

Andersen, T.; Jensen, R.; Christensen, M. K.; Pedersen, T.; Hansen, O.; Chorkendorff, I.

2012-07-01

We demonstrate a combined microreactor and time of flight system for testing and characterization of heterogeneous catalysts with high resolution mass spectrometry and high sensitivity. Catalyst testing is performed in silicon-based microreactors which have high sensitivity and fast thermal response. Gas analysis is performed with a time of flight mass spectrometer with a modified nude Bayard-Alpert ionization gauge as gas ionization source. The mass resolution of the time of flight mass spectrometer using the ion gauge as ionization source is estimated to m/Δm > 2500. The system design is superior to conventional batch and flow reactors with accompanying product detection by quadrupole mass spectrometry or gas chromatography not only due to the high sensitivity, fast temperature response, high mass resolution, and fast acquisition time of mass spectra but it also allows wide mass range (0-5000 amu in the current configuration). As a demonstration of the system performance we present data from ammonia oxidation on a Pt thin film showing resolved spectra of OH and NH3.

High mass resolution time of flight mass spectrometer for measuring products in heterogeneous catalysis in highly sensitive microreactors.

PubMed

Andersen, T; Jensen, R; Christensen, M K; Pedersen, T; Hansen, O; Chorkendorff, I

2012-07-01

We demonstrate a combined microreactor and time of flight system for testing and characterization of heterogeneous catalysts with high resolution mass spectrometry and high sensitivity. Catalyst testing is performed in silicon-based microreactors which have high sensitivity and fast thermal response. Gas analysis is performed with a time of flight mass spectrometer with a modified nude Bayard-Alpert ionization gauge as gas ionization source. The mass resolution of the time of flight mass spectrometer using the ion gauge as ionization source is estimated to m/Δm > 2500. The system design is superior to conventional batch and flow reactors with accompanying product detection by quadrupole mass spectrometry or gas chromatography not only due to the high sensitivity, fast temperature response, high mass resolution, and fast acquisition time of mass spectra but it also allows wide mass range (0-5000 amu in the current configuration). As a demonstration of the system performance we present data from ammonia oxidation on a Pt thin film showing resolved spectra of OH and NH(3).

Noise spectroscopy as an equilibrium analysis tool for highly sensitive electrical biosensing

NASA Astrophysics Data System (ADS)

Guo, Qiushi; Kong, Tao; Su, Ruigong; Zhang, Qi; Cheng, Guosheng

2012-08-01

We demonstrate an approach for highly sensitive bio-detection based on silicon nanowire field-effect transistors by employing low frequency noise spectroscopy analysis. The inverse of noise amplitude of the device exhibits an enhanced gate coupling effect in strong inversion regime when measured in buffer solution than that in air. The approach was further validated by the detection of cardiac troponin I of 0.23 ng/ml in fetal bovine serum, in which 2 orders of change in noise amplitude was characterized. The selectivity of the proposed approach was also assessed by the addition of 10 μg/ml bovine serum albumin solution.

Parallel human genome analysis: microarray-based expression monitoring of 1000 genes.

PubMed Central

Schena, M; Shalon, D; Heller, R; Chai, A; Brown, P O; Davis, R W

1996-01-01

Microarrays containing 1046 human cDNAs of unknown sequence were printed on glass with high-speed robotics. These 1.0-cm2 DNA "chips" were used to quantitatively monitor differential expression of the cognate human genes using a highly sensitive two-color hybridization assay. Array elements that displayed differential expression patterns under given experimental conditions were characterized by sequencing. The identification of known and novel heat shock and phorbol ester-regulated genes in human T cells demonstrates the sensitivity of the assay. Parallel gene analysis with microarrays provides a rapid and efficient method for large-scale human gene discovery. Images Fig. 1 Fig. 2 Fig. 3 PMID:8855227

High Sensitivity Analysis of Nanoliter Volumes of Volatile and Nonvolatile Compounds using Matrix Assisted Ionization (MAI) Mass Spectrometry

NASA Astrophysics Data System (ADS)

Hoang, Khoa; Pophristic, Milan; Horan, Andrew J.; Johnston, Murray V.; McEwen, Charles N.

2016-10-01

First results are reported using a simple, fast, and reproducible matrix-assisted ionization (MAI) sample introduction method that provides substantial improvements relative to previously published MAI methods. The sensitivity of the new MAI methods, which requires no laser, high voltage, or nebulizing gas, is comparable to those reported for MALDI-TOF and n-ESI. High resolution full acquisition mass spectra having low chemical background are acquired from low nanoliters of solution using only a few femtomoles of analyte. The limit-of-detection for angiotensin II is less than 50 amol on an Orbitrap Exactive mass spectrometer. Analysis of peptides, including a bovine serum albumin digest, and drugs, including drugs in urine without a purification step, are reported using a 1 μL zero dead volume syringe in which only the analyte solution wetting the walls of the syringe needle is used in the analysis.

Multisite-multivariable sensitivity analysis of distributed watershed models: enhancing the perceptions from computationally frugal methods

USDA-ARS?s Scientific Manuscript database

This paper assesses the impact of different likelihood functions in identifying sensitive parameters of the highly parameterized, spatially distributed Soil and Water Assessment Tool (SWAT) watershed model for multiple variables at multiple sites. The global one-factor-at-a-time (OAT) method of Morr...

Intelligence and Interpersonal Sensitivity: A Meta-Analysis

ERIC Educational Resources Information Center

Murphy, Nora A.; Hall, Judith A.

2011-01-01

A meta-analytic review investigated the association between general intelligence and interpersonal sensitivity. The review involved 38 independent samples with 2988 total participants. There was a highly significant small-to-medium effect for intelligence measures to be correlated with decoding accuracy (r=0.19, p less than 0.001). Significant…

Behavioral Dimensions in One-Year-Olds and Dimensional Stability in Infancy.

ERIC Educational Resources Information Center

Hagekull, Berit; And Others

1980-01-01

The dimensional structure of infants' behavioral repertoire was shown to be highly stable over 3 to 15 months of age. Factor analysis of parent questionnaire data produced seven factors named Intensity/Activity, Regularity, Approach-Withdrawal, Sensory Sensitivity, Attentiveness, Manageability and Sensitivity to New Food. An eighth factor,…

Pain sensitivity profiles in patients with advanced knee osteoarthritis

PubMed Central

Frey-Law, Laura A.; Bohr, Nicole L.; Sluka, Kathleen A.; Herr, Keela; Clark, Charles R.; Noiseux, Nicolas O.; Callaghan, John J; Zimmerman, M Bridget; Rakel, Barbara A.

2016-01-01

The development of patient profiles to subgroup individuals on a variety of variables has gained attention as a potential means to better inform clinical decision-making. Patterns of pain sensitivity response specific to quantitative sensory testing (QST) modality have been demonstrated in healthy subjects. It has not been determined if these patterns persist in a knee osteoarthritis population. In a sample of 218 participants, 19 QST measures along with pain, psychological factors, self-reported function, and quality of life were assessed prior to total knee arthroplasty. Component analysis was used to identify commonalities across the 19 QST assessments to produce standardized pain sensitivity factors. Cluster analysis then grouped individuals that exhibited similar patterns of standardized pain sensitivity component scores. The QST resulted in four pain sensitivity components: heat, punctate, temporal summation, and pressure. Cluster analysis resulted in five pain sensitivity profiles: a “low pressure pain” group, an “average pain” group, and three “high pain” sensitivity groups who were sensitive to different modalities (punctate, heat, and temporal summation). Pain and function differed between pain sensitivity profiles, along with sex distribution; however no differences in OA grade, medication use, or psychological traits were found. Residualizing QST data by age and sex resulted in similar components and pain sensitivity profiles. Further, these profiles are surprisingly similar to those reported in healthy populations suggesting that individual differences in pain sensitivity are a robust finding even in an older population with significant disease. PMID:27152688

Automated metal-free multiple-column nanoLC for improved phosphopeptide analysis sensitivity and throughput

PubMed Central

Zhao, Rui; Ding, Shi-Jian; Shen, Yufeng; Camp, David G.; Livesay, Eric A.; Udseth, Harold; Smith, Richard D.

2009-01-01

We report on the development and characterization of automated metal-free multiple-column nanoLC instrumentation for sensitive and high-throughput analysis of phosphopeptides with mass spectrometry analysis. The system implements a multiple-column capillary LC fluidic design developed for high-throughput analysis of peptides (Anal. Chem. 2001, 73, 3011–3021), incorporating modifications to achieve broad and sensitive analysis of phosphopeptides. The integrated nanoLC columns (50 µm i.d. × 30 cm containing 5 µm C18 particles) and the on-line solid phase extraction columns (150 µm i.d. × 4 cm containing 5 µm C18 particles) were connected to automatic switching valves with non-metal chromatographic accessories, and other modifications to avoid the exposure of the analyte to any metal surfaces during handling, separation, and electrospray ionization. The nanoLC developed provided a separation peak capacity of ∼250 for phosphopeptides (and ∼400 for normal peptides). A detection limit of 0.4 fmol was obtained when a linear ion trap tandem mass spectrometer (Finnegan LTQ) was coupled to a 50-µm i.d. column of the nanoLC. The separation power and sensitivity provided by the nanoLC-LTQ enabled identification of ∼4600 phosphopeptide candidates from ∼60 µg COS-7 cell tryptic digest followed by IMAC enrichment and ∼520 tyrosine phosphopeptides from ∼2 mg of human T cells digests followed by phosphotyrosine peptide immunoprecipitation. PMID:19217835

Analysis of hepatitis B surface antigen (HBsAg) using high-sensitivity HBsAg assays in hepatitis B virus carriers in whom HBsAg seroclearance was confirmed by conventional assays.

PubMed

Ozeki, Itaru; Nakajima, Tomoaki; Suii, Hirokazu; Tatsumi, Ryoji; Yamaguchi, Masakatsu; Kimura, Mutsuumi; Arakawa, Tomohiro; Kuwata, Yasuaki; Ohmura, Takumi; Hige, Shuhei; Karino, Yoshiyasu; Toyota, Joji

2018-02-01

We investigated the utility of high-sensitivity hepatitis B surface antigen (HBsAg) assays compared with conventional HBsAg assays. Using serum samples from 114 hepatitis B virus (HBV) carriers in whom HBsAg seroclearance was confirmed by conventional HBsAg assays (cut-off value, 0.05 IU/mL), the amount of HBsAg was re-examined by high-sensitivity HBsAg assays (cut-off value, 0.005 IU/mL). Cases negative for HBsAg in both assays were defined as consistent cases, and cases positive for HBsAg in the high-sensitivity HBsAg assay only were defined as discrepant cases. There were 55 (48.2%) discrepant cases, and the range of HBsAg titers determined by high-sensitivity HBsAg assays was 0.005-0.056 IU/mL. Multivariate analysis showed that the presence of nucleos(t)ide analog therapy, liver cirrhosis, and negative anti-HBs contributed to the discrepancies between the two assays. Cumulative anti-HBs positivity rates among discrepant cases were 12.7%, 17.2%, 38.8%, and 43.9% at baseline, 1 year, 3 years, and 5 years, respectively, whereas the corresponding rates among consistent cases were 50.8%, 56.0%, 61.7%, and 68.0%, respectively. Hepatitis B virus DNA negativity rates were 56.4% and 81.4% at baseline, 51.3% and 83.3% at 1 year, and 36.8% and 95.7% at 3 years, among discrepant and consistent cases, respectively. Hepatitis B surface antigen reversion was observed only in discrepant cases. Re-examination by high-sensitivity HBsAg assays revealed that HBsAg was positive in approximately 50% of cases. Cumulative anti-HBs seroconversion rates and HBV-DNA seroclearance rates were lower in these cases, suggesting a population at risk for HBsAg reversion. © 2017 The Japan Society of Hepatology.

Diagnostic value of stool DNA testing for multiple markers of colorectal cancer and advanced adenoma: a meta-analysis.

PubMed

Yang, Hua; Xia, Bing-Qing; Jiang, Bo; Wang, Guozhen; Yang, Yi-Peng; Chen, Hao; Li, Bing-Sheng; Xu, An-Gao; Huang, Yun-Bo; Wang, Xin-Ying

2013-08-01

The diagnostic value of stool DNA (sDNA) testing for colorectal neoplasms remains controversial. To compensate for the lack of large-scale unbiased population studies, a meta-analysis was performed to evaluate the diagnostic value of sDNA testing for multiple markers of colorectal cancer (CRC) and advanced adenoma. The PubMed, Science Direct, Biosis Review, Cochrane Library and Embase databases were systematically searched in January 2012 without time restriction. Meta-analysis was performed using a random-effects model using sensitivity, specificity, diagnostic OR (DOR), summary ROC curves, area under the curve (AUC), and 95% CIs as effect measures. Heterogeneity was measured using the χ(2) test and Q statistic; subgroup analysis was also conducted. A total of 20 studies comprising 5876 individuals were eligible. There was no heterogeneity for CRC, but adenoma and advanced adenoma harboured considerable heterogeneity influenced by risk classification and various detection markers. Stratification analysis according to risk classification showed that multiple markers had a high DOR for the high-risk subgroups of both CRC (sensitivity 0.759 [95% CI 0.711 to 0.804]; specificity 0.883 [95% CI 0.846 to 0.913]; AUC 0.906) and advanced adenoma (sensitivity 0.683 [95% CI 0.584 to 0.771]; specificity 0.918 [95% CI 0.866 to 0.954]; AUC 0.946) but not for the average-risk subgroups of either. In the methylation subgroup, sDNA testing had significantly higher DOR for CRC (sensitivity 0.753 [95% CI 0.685 to 0.812]; specificity 0.913 [95% CI 0.860 to 0.950]; AUC 0.918) and advanced adenoma (sensitivity 0.623 [95% CI 0.527 to 0.712]; specificity 0.926 [95% CI 0.882 to 0.958]; AUC 0.910) compared with the mutation subgroup. There was no significant heterogeneity among studies for subgroup analysis. sDNA testing for multiple markers had strong diagnostic significance for CRC and advanced adenoma in high-risk subjects. Methylation makers had more diagnostic value than mutation markers.

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 overall classification accuracy above a median value of 0.63, but for most sensitivity was around or even lower than a median value of 0.5. Conclusions When taking into account sensitivity, specificity and overall classification accuracy Random Forests and Linear Discriminant analysis rank first among all the classifiers tested in prediction of dementia using several neuropsychological tests. These methods may be used to improve accuracy, sensitivity and specificity of Dementia predictions from neuropsychological testing. PMID:21849043

A hydrogeologic framework for characterizing summer streamflow sensitivity to climate warming in the Pacific Northwest, USA

NASA Astrophysics Data System (ADS)

Safeeq, M.; Grant, G. E.; Lewis, S. L.; Kramer, M. G.; Staab, B.

2014-09-01

Summer streamflows in the Pacific Northwest are largely derived from melting snow and groundwater discharge. As the climate warms, diminishing snowpack and earlier snowmelt will cause reductions in summer streamflow. Most regional-scale assessments of climate change impacts on streamflow use downscaled temperature and precipitation projections from general circulation models (GCMs) coupled with large-scale hydrologic models. Here we develop and apply an analytical hydrogeologic framework for characterizing summer streamflow sensitivity to a change in the timing and magnitude of recharge in a spatially explicit fashion. In particular, we incorporate the role of deep groundwater, which large-scale hydrologic models generally fail to capture, into streamflow sensitivity assessments. We validate our analytical streamflow sensitivities against two empirical measures of sensitivity derived using historical observations of temperature, precipitation, and streamflow from 217 watersheds. In general, empirically and analytically derived streamflow sensitivity values correspond. Although the selected watersheds cover a range of hydrologic regimes (e.g., rain-dominated, mixture of rain and snow, and snow-dominated), sensitivity validation was primarily driven by the snow-dominated watersheds, which are subjected to a wider range of change in recharge timing and magnitude as a result of increased temperature. Overall, two patterns emerge from this analysis: first, areas with high streamflow sensitivity also have higher summer streamflows as compared to low-sensitivity areas. Second, the level of sensitivity and spatial extent of highly sensitive areas diminishes over time as the summer progresses. Results of this analysis point to a robust, practical, and scalable approach that can help assess risk at the landscape scale, complement the downscaling approach, be applied to any climate scenario of interest, and provide a framework to assist land and water managers in adapting to an uncertain and potentially challenging future.

Surface Desorption Dielectric-Barrier Discharge Ionization Mass Spectrometry.

PubMed

Zhang, Hong; Jiang, Jie; Li, Na; Li, Ming; Wang, Yingying; He, Jing; You, Hong

2017-07-18

A variant of dielectric-barrier discharge named surface desorption dielectric-barrier discharge ionization (SDDBDI) mass spectrometry was developed for high-efficiency ion transmission and high spatial resolution imaging. In SDDBDI, a tungsten nanotip and the inlet of the mass spectrometer are used as electrodes, and a piece of coverslip is used as a sample plate as well as an insulating dielectric barrier, which simplifies the configuration of instrument and thus the operation. Different from volume dielectric-barrier discharge (VDBD), the microdischarges are generated on the surface at SDDBDI, and therefore the plasma density is extremely high. Analyte ions are guided directly into the MS inlet without any deflection. This configuration significantly improves the ion transmission efficiency and thus the sensitivity. The dependence of sensitivity and spatial resolution of the SDDBDI on the operation parameters were systematically investigated. The application of SDDBDI was successfully demonstrated by analysis of multiple species including amino acids, pharmaceuticals, putative cancer biomarkers, and mixtures of both fatty acids and hormones. Limits of detection (S/N = 3) were determined to be 0.84 and 0.18 pmol, respectively, for the analysis of l-alanine and metronidazole. A spatial resolution of 22 μm was obtained for the analysis of an imprinted cyclophosphamide pattern, and imaging of a "T" character was successfully demonstrated under ambient conditions. These results indicate that SDDBDI has high-efficiency ion transmission, high sensitivity, and high spatial resolution, which render it a potential tool for mass spectrometry imaging.

Highly sensitive measurement of whole blood chromium by inductively coupled plasma mass spectrometry.

PubMed

Cieslak, Wendy; Pap, Kathleen; Bunch, Dustin R; Reineks, Edmunds; Jackson, Raymond; Steinle, Roxanne; Wang, Sihe

2013-02-01

Chromium (Cr), a trace metal element, is implicated in diabetes and cardiovascular disease. A hypochromic state has been associated with poor blood glucose control and unfavorable lipid metabolism. Sensitive and accurate measurement of blood chromium is very important to assess the chromium nutritional status. However, interferents in biological matrices and contamination make the sensitive analysis challenging. The primary goal of this study was to develop a highly sensitive method for quantification of total Cr in whole blood by inductively coupled plasma mass spectrometry (ICP-MS) and to validate the reference interval in a local healthy population. This method was developed on an ICP-MS with a collision/reaction cell. Interference was minimized using both kinetic energy discrimination between the quadrupole and hexapole and a selective collision gas (helium). Reference interval was validated in whole blood samples (n=51) collected in trace element free EDTA tubes from healthy adults (12 males, 39 females), aged 19-64 years (38.8±12.6), after a minimum of 8 h fasting. Blood samples were aliquoted into cryogenic vials and stored at -70 °C until analysis. The assay linearity was 3.42 to 1446.59 nmol/L with an accuracy of 87.7 to 99.8%. The high sensitivity was achieved by minimization of interference through selective kinetic energy discrimination and selective collision using helium. The reference interval for total Cr using a non-parametric method was verified to be 3.92 to 7.48 nmol/L. This validated ICP-MS methodology is highly sensitive and selective for measuring total Cr in whole blood. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Published by Elsevier Inc. All rights reserved.

Sensitivity analysis of hydrodynamic stability operators

NASA Technical Reports Server (NTRS)

Schmid, Peter J.; Henningson, Dan S.; Khorrami, Mehdi R.; Malik, Mujeeb R.

1992-01-01

The eigenvalue sensitivity for hydrodynamic stability operators is investigated. Classical matrix perturbation techniques as well as the concept of epsilon-pseudoeigenvalues are applied to show that parts of the spectrum are highly sensitive to small perturbations. Applications are drawn from incompressible plane Couette, trailing line vortex flow and compressible Blasius boundary layer flow. Parametric studies indicate a monotonically increasing effect of the Reynolds number on the sensitivity. The phenomenon of eigenvalue sensitivity is due to the non-normality of the operators and their discrete matrix analogs and may be associated with large transient growth of the corresponding initial value problem.

Cost Analysis of a High Support Housing Initiative for Persons with Severe Mental Illness and Long-Term Psychiatric Hospitalization.

PubMed

Rudoler, David; de Oliveira, Claire; Jacob, Binu; Hopkins, Melonie; Kurdyak, Paul

2018-01-01

The objective of this article was to conduct a cost analysis comparing the costs of a supportive housing intervention to inpatient care for clients with severe mental illness who were designated alternative-level care while inpatient at the Centre for Addiction and Mental Health in Toronto. The intervention, called the High Support Housing Initiative, was implemented in 2013 through a collaboration between 15 agencies in the Toronto area. The perspective of this cost analysis was that of the Ontario Ministry of Health and Long-Term Care. We compared the cost of inpatient mental health care to high-support housing. Cost data were derived from a variety of sources, including health administrative data, expenditures reported by housing providers, and document analysis. The High Support Housing Initiative was cost saving relative to inpatient care. The average cost savings per diem were between $140 and $160. This amounts to an annual cost savings of approximately $51,000 to $58,000. When tested through sensitivity analysis, the intervention remained cost saving in most scenarios; however, the result was highly sensitive to health system costs for clients of the High Support Housing Initiative program. This study suggests the High Support Housing Initiative is potentially cost saving relative to inpatient hospitalization at the Centre for Addiction and Mental Health.

Sobol‧ sensitivity analysis of NAPL-contaminated aquifer remediation process based on multiple surrogates

NASA Astrophysics Data System (ADS)

Luo, Jiannan; Lu, Wenxi

2014-06-01

Sobol‧ sensitivity analyses based on different surrogates were performed on a trichloroethylene (TCE)-contaminated aquifer to assess the sensitivity of the design variables of remediation duration, surfactant concentration and injection rates at four wells to remediation efficiency First, the surrogate models of a multi-phase flow simulation model were constructed by applying radial basis function artificial neural network (RBFANN) and Kriging methods, and the two models were then compared. Based on the developed surrogate models, the Sobol‧ method was used to calculate the sensitivity indices of the design variables which affect the remediation efficiency. The coefficient of determination (R2) and the mean square error (MSE) of these two surrogate models demonstrated that both models had acceptable approximation accuracy, furthermore, the approximation accuracy of the Kriging model was slightly better than that of the RBFANN model. Sobol‧ sensitivity analysis results demonstrated that the remediation duration was the most important variable influencing remediation efficiency, followed by rates of injection at wells 1 and 3, while rates of injection at wells 2 and 4 and the surfactant concentration had negligible influence on remediation efficiency. In addition, high-order sensitivity indices were all smaller than 0.01, which indicates that interaction effects of these six factors were practically insignificant. The proposed Sobol‧ sensitivity analysis based on surrogate is an effective tool for calculating sensitivity indices, because it shows the relative contribution of the design variables (individuals and interactions) to the output performance variability with a limited number of runs of a computationally expensive simulation model. The sensitivity analysis results lay a foundation for the optimal groundwater remediation process optimization.

High-performance liquid chromatography with fluorescence detection for the rapid analysis of pheophytins and pyropheophytins in virgin olive oil.

PubMed

Li, Xueqi; Woodman, Michael; Wang, Selina C

2015-08-01

Pheophytins and pyropheophytin are degradation products of chlorophyll pigments, and their ratios can be used as a sensitive indicator of stress during the manufacturing and storage of olive oil. They increase over time depending on the storage condition and if the oil is exposed to heat treatments during the refining process. The traditional analysis method includes solvent- and time-consuming steps of solid-phase extraction followed by analysis by high-performance liquid chromatography with ultraviolet detection. We developed an improved dilute/fluorescence method where multi-step sample preparation was replaced by a simple isopropanol dilution before the high-performance liquid chromatography injection. A quaternary solvent gradient method was used to include a fourth strong solvent wash on a quaternary gradient pump, which avoided the need to premix any solvents and greatly reduced the oil residues on the column from previous analysis. This new method not only reduces analysis cost and time but shows reliability, repeatability, and improved sensitivity, especially important for low-level samples. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Value of high-sensitivity C-reactive protein assays in predicting atrial fibrillation recurrence: a systematic review and meta-analysis.

PubMed

Yo, Chia-Hung; Lee, Si-Huei; Chang, Shy-Shin; Lee, Matthew Chien-Hung; Lee, Chien-Chang

2014-02-20

We performed a systematic review and meta-analysis of studies on high-sensitivity C-reactive protein (hs-CRP) assays to see whether these tests are predictive of atrial fibrillation (AF) recurrence after cardioversion. Systematic review and meta-analysis. PubMed, EMBASE and Cochrane databases as well as a hand search of the reference lists in the retrieved articles from inception to December 2013. This review selected observational studies in which the measurements of serum CRP were used to predict AF recurrence. An hs-CRP assay was defined as any CRP test capable of measuring serum CRP to below 0.6 mg/dL. We summarised test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. Meta-regression analysis was performed to explore the source of heterogeneity. We included nine qualifying studies comprising a total of 347 patients with AF recurrence and 335 controls. A CRP level higher than the optimal cut-off point was an independent predictor of AF recurrence after cardioversion (summary adjusted OR: 3.33; 95% CI 2.10 to 5.28). The estimated pooled sensitivity and specificity for hs-CRP was 71.0% (95% CI 63% to 78%) and 72.0% (61% to 81%), respectively. Most studies used a CRP cut-off point of 1.9 mg/L to predict long-term AF recurrence (77% sensitivity, 65% specificity), and 3 mg/L to predict short-term AF recurrence (73% sensitivity, 71% specificity). hs-CRP assays are moderately accurate in predicting AF recurrence after successful cardioversion.

Immuno-magnetic beads-based extraction-capillary zone electrophoresis-deep UV laser-induced fluorescence analysis of erythropoietin.

PubMed

Wang, Heye; Dou, Peng; Lü, Chenchen; Liu, Zhen

2012-07-13

Erythropoietin (EPO) is an important glycoprotein hormone. Recombinant human EPO (rhEPO) is an important therapeutic drug and can be also used as doping reagent in sports. The analysis of EPO glycoforms in pharmaceutical and sports areas greatly challenges analytical scientists from several aspects, among which sensitive detection and effective and facile sample preparation are two essential issues. Herein, we investigated new possibilities for these two aspects. Deep UV laser-induced fluorescence detection (deep UV-LIF) was established to detect the intrinsic fluorescence of EPO while an immuno-magnetic beads-based extraction (IMBE) was developed to specifically extract EPO glycoforms. Combined with capillary zone electrophoresis (CZE), CZE-deep UV-LIF allows high resolution glycoform profiling with improved sensitivity. The detection sensitivity was improved by one order of magnitude as compared with UV absorbance detection. An additional advantage is that the original glycoform distribution can be completely preserved because no fluorescent labeling is needed. By combining IMBE with CZE-deep UV-LIF, the overall detection sensitivity was 1.5 × 10⁻⁸ mol/L, which was enhanced by two orders of magnitude relative to conventional CZE with UV absorbance detection. It is applicable to the analysis of pharmaceutical preparations of EPO, but the sensitivity is insufficient for the anti-doping analysis of EPO in blood and urine. IMBE can be straightforward and effective approach for sample preparation. However, antibodies with high specificity were the key for application to urine samples because some urinary proteins can severely interfere the immuno-extraction. Copyright © 2012 Elsevier B.V. All rights reserved.

PREVALENCE OF METABOLIC SYNDROME IN YOUNG MEXICANS: A SENSITIVITY ANALYSIS ON ITS COMPONENTS.

PubMed

Murguía-Romero, Miguel; Jiménez-Flores, J Rafael; Sigrist-Flores, Santiago C; Tapia-Pancardo, Diana C; Jiménez-Ramos, Arnulfo; Méndez-Cruz, A René; Villalobos-Molina, Rafael

2015-07-28

obesity is a worldwide epidemic, and the high prevalence of diabetes type II (DM2) and cardiovascular disease (CVD) is in great part a consequence of that epidemic. Metabolic syndrome is a useful tool to estimate the risk of a young population to evolve to DM2 and CVD. to estimate the MetS prevalence in young Mexicans, and to evaluate each parameter as an independent indicator through a sensitivity analysis. the prevalence of MetS was estimated in 6 063 young of the México City metropolitan area. A sensitivity analysis was conducted to estimate the performance of each one of the components of MetS, as an indicator of the presence of MetS itself. Five statistical of the sensitivity analysis were calculated for each MetS component and the other parameters included: sensitivity, specificity, positive predictive value or precision, negative predictive value, and accuracy. the prevalence of MetS in Mexican young population was estimated to be 13.4%. Waist circumference presented the highest sensitivity (96.8% women; 90.0% men), blood pressure presented the highest specificity for women (97.7%) and glucose for men (91.0%). When all the five statistical are considered triglycerides is the component with the highest values, showing a value of 75% or more in four of them. Differences by sex are detected for averages of all components of MetS in young without alterations. Mexican young are highly prone to acquire MetS: 71% have at least one and up to five MetS parameters altered, and 13.4% of them have MetS. From all the five components of MetS, waist circumference presented the highest sensitivity as a predictor of MetS, and triglycerides is the best parameter if a single factor is to be taken as sole predictor of MetS in Mexican young population, triglycerides is also the parameter with the highest accuracy. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Nuclear morphology for the detection of alterations in bronchial cells from lung cancer: an attempt to improve sensitivity and specificity.

PubMed

Fafin-Lefevre, Mélanie; Morlais, Fabrice; Guittet, Lydia; Clin, Bénédicte; Launoy, Guy; Galateau-Sallé, Françoise; Plancoulaine, Benoît; Herlin, Paulette; Letourneux, Marc

2011-08-01

To identify which morphologic or densitometric parameters are modified in cell nuclei from bronchopulmonary cancer based on 18 parameters involving shape, intensity, chromatin, texture, and DNA content and develop a bronchopulmonary cancer screening method relying on analysis of sputum sample cell nuclei. A total of 25 sputum samples from controls and 22 bronchial aspiration samples from patients presenting with bronchopulmonary cancer who were professionally exposed to cancer were used. After Feulgen staining, 18 morphologic and DNA content parameters were measured on cell nuclei, via image cytom- etry. A method was developed for analyzing distribution quantiles, compared with simply interpreting mean values, to characterize morphologic modifications in cell nuclei. Distribution analysis of parameters enabled us to distinguish 13 of 18 parameters that demonstrated significant differences between controls and cancer cases. These parameters, used alone, enabled us to distinguish two population types, with both sensitivity and specificity > 70%. Three parameters offered 100% sensitivity and specificity. When mean values offered high sensitivity and specificity, comparable or higher sensitivity and specificity values were observed for at least one of the corresponding quantiles. Analysis of modification in morphologic parameters via distribution analysis proved promising for screening bronchopulmonary cancer from sputum.

A fully battery-powered inexpensive spectrophotometric system for high-sensitivity point-of-care analysis on a microfluidic chip

PubMed Central

Dou, Maowei; Lopez, Juan; Rios, Misael; Garcia, Oscar; Xiao, Chuan; Eastman, Michael

2016-01-01

A cost-effective battery-powered spectrophotometric system (BASS) was developed for quantitative point-of-care (POC) analysis on a microfluidic chip. By using methylene blue as a model analyte, we first compared the performance of the BASS with a commercial spectrophotometric system, and further applied the BASS for loop-mediated isothermal amplification (LAMP) detection and subsequent quantitative nucleic acid analysis which exhibited a comparable limit of detection to that of Nanodrop. Compared to the commercial spectrophotometric system, our spectrophotometric system is lower-cost, consumes less reagents, and has a higher detection sensitivity. Most importantly, it does not rely on external power supplies. All these features make our spectrophotometric system highly suitable for a variety of POC analyses, such as field detection. PMID:27143408

Stochastic sensitivity measure for mistuned high-performance turbines

NASA Technical Reports Server (NTRS)

Murthy, Durbha V.; Pierre, Christophe

1992-01-01

A stochastic measure of sensitivity is developed in order to predict the effects of small random blade mistuning on the dynamic aeroelastic response of turbomachinery blade assemblies. This sensitivity measure is based solely on the nominal system design (i.e., on tuned system information), which makes it extremely easy and inexpensive to calculate. The measure has the potential to become a valuable design tool that will enable designers to evaluate mistuning effects at a preliminary design stage and thus assess the need for a full mistuned rotor analysis. The predictive capability of the sensitivity measure is illustrated by examining the effects of mistuning on the aeroelastic modes of the first stage of the oxidizer turbopump in the Space Shuttle Main Engine. Results from a full analysis mistuned systems confirm that the simple stochastic sensitivity measure predicts consistently the drastic changes due to misturning and the localization of aeroelastic vibration to a few blades.

Discrete sensitivity derivatives of the Navier-Stokes equations with a parallel Krylov solver

NASA Technical Reports Server (NTRS)

Ajmani, Kumud; Taylor, Arthur C., III

1994-01-01

This paper solves an 'incremental' form of the sensitivity equations derived by differentiating the discretized thin-layer Navier Stokes equations with respect to certain design variables of interest. The equations are solved with a parallel, preconditioned Generalized Minimal RESidual (GMRES) solver on a distributed-memory architecture. The 'serial' sensitivity analysis code is parallelized by using the Single Program Multiple Data (SPMD) programming model, domain decomposition techniques, and message-passing tools. Sensitivity derivatives are computed for low and high Reynolds number flows over a NACA 1406 airfoil on a 32-processor Intel Hypercube, and found to be identical to those computed on a single-processor Cray Y-MP. It is estimated that the parallel sensitivity analysis code has to be run on 40-50 processors of the Intel Hypercube in order to match the single-processor processing time of a Cray Y-MP.

Antiresonant reflecting guidance mechanism in hollow-core fiber for gas pressure sensing.

PubMed

Hou, Maoxiang; Zhu, Feng; Wang, Ying; Wang, Yiping; Liao, Changrui; Liu, Shen; Lu, Peixiang

2016-11-28

A gas pressure sensor based on an antiresonant reflecting guidance mechanism in a hollow-core fiber (HCF) with an open microchannel is experimentally demonstrated for gas pressure sensing. The microchannel was created on the ring cladding of the HCF by femtosecond laser drilling to provide an air-core pressure equivalent to the external environment. The HCF cladding functions as an antiresonant reflecting waveguide, which induces sharp periodic lossy dips in the transmission spectrum. The proposed sensor exhibits a high pressure sensitivity of 3.592 nm/MPa and a low temperature cross-sensitivity of 7.5 kPa/°C. Theoretical analysis indicates that the observed high gas pressure sensitivity originates from the pressure induced refractive index change of the air in the hollow-core. The good operation durability and fabrication simplicity make the device an attractive candidate for reliable and highly sensitive gas pressure measurement in harsh environments.

Elucidation of high sensitivity of δ-HMX: New insight from first principles simulations

NASA Astrophysics Data System (ADS)

Kuklja, Maija M.; Tsyshevsky, Roman V.; Sharia, Onise

2017-01-01

Understanding of a significant difference in sensitivities of β and δ phases of cyclotetramethylene-tetranitramine (HMX) has been long one of the challenges in the field of high energy density materials. Despite many experimental and theoretical efforts to explain the high sensitivity of the δ phase, convincing reasons behind the HMX behavior remained unclear. We established that the presence of a polar surface in δ-HMX has fundamental implications for stability and overall chemical behavior of the material. A comparative quantum-chemical analysis of decomposition mechanisms in polar δ-HMX and nonpolar β-HMX discovered a considerable difference in dominating dissociation reactions, activation barriers, and reaction rates. The polarization-induced charge transfer offered a logical explanation for different sensitivity of β-HMX and δ-HMX polymorphs to detonation initiation. Our conclusions also removed long-standing contradictions and explained a large range of experimental data on thermal decomposition of HMX.

Specialized Binary Analysis for Vetting Android APPS Using GUI Logic

DTIC Science & Technology

2016-04-01

the use of high- level reasoning based on the GUI design logic of an app to enable a security analyst to diagnose and triage the potentially sensitive...execution paths of an app. Levels of Inconsistency We have identified three- levels of logical inconsistencies: Event- level inconsistency A sensitive...operation (e.g., taking a picture) is not trigged by user action on a GUI component. Layout- level inconsistency A sensitive operation is triggered by

Integrated Droplet-Based Microextraction with ESI-MS for Removal of Matrix Interference in Single-Cell Analysis.

PubMed

Zhang, Xiao-Chao; Wei, Zhen-Wei; Gong, Xiao-Yun; Si, Xing-Yu; Zhao, Yao-Yao; Yang, Cheng-Dui; Zhang, Si-Chun; Zhang, Xin-Rong

2016-04-29

Integrating droplet-based microfluidics with mass spectrometry is essential to high-throughput and multiple analysis of single cells. Nevertheless, matrix effects such as the interference of culture medium and intracellular components influence the sensitivity and the accuracy of results in single-cell analysis. To resolve this problem, we developed a method that integrated droplet-based microextraction with single-cell mass spectrometry. Specific extraction solvent was used to selectively obtain intracellular components of interest and remove interference of other components. Using this method, UDP-Glc-NAc, GSH, GSSG, AMP, ADP and ATP were successfully detected in single MCF-7 cells. We also applied the method to study the change of unicellular metabolites in the biological process of dysfunctional oxidative phosphorylation. The method could not only realize matrix-free, selective and sensitive detection of metabolites in single cells, but also have the capability for reliable and high-throughput single-cell analysis.

Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy

PubMed Central

Zur, RM; Roy, LM; Ito, S; Beyene, J; Carew, C; Ungar, WJ

2016-01-01

Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3–87.0%) and 98.9% (96.3–100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1–99.4%) and 100.0% (99.9–100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4–95.5%) and 92.6% (86.5–96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6–97.5%) and 99.2% (98.4–99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines. PMID:27217052

Comparative transcriptome profiling of a thermal resistant vs. sensitive silkworm strain in response to high temperature under stressful humidity condition

PubMed Central

Xiao, Jinshu; Wang, La; Liu, Taihang; Wu, Yunfei; Dong, Feifan; Jiang, Yaming; Pan, Minhui; Zhang, Youhong; Lu, Cheng

2017-01-01

Thermotolerance is important particularly for poikilotherms such as insects. Understanding the mechanisms by which insects respond to high temperatures can provide insights into their adaptation to the environment. Therefore, in this study, we performed a transcriptome analysis of two silkworm strains with significantly different resistance to heat as well as humidity; the thermo-resistant strain 7532 and the thermos-sensitive strain Knobbed. We identified in total 4,944 differentially expressed genes (DEGs) using RNA-Seq. Among these, 4,390 were annotated and 554 were novel. Gene Ontology (GO) analysis of 747 DEGs identified between RT_48h (Resistant strain with high-temperature Treatment for 48 hours) and ST_48h (Sensitive strain with high-temperature Treatment for 48 hours) showed significant enrichment of 12 GO terms including metabolic process, extracellular region and serine-type peptidase activity. Moreover, we discovered 12 DEGs that may contribute to the heat-humidity stress response in the silkworm. Our data clearly showed that 48h post-exposure may be a critical time point for silkworm to respond to high temperature and humidity. These results provide insights into the genes and biological processes involved in high temperature and humidity tolerance in the silkworm, and advance our understanding of thermal tolerance in insects. PMID:28542312

Comparative transcriptome profiling of a thermal resistant vs. sensitive silkworm strain in response to high temperature under stressful humidity condition.

PubMed

Xiao, Wenfu; Chen, Peng; Xiao, Jinshu; Wang, La; Liu, Taihang; Wu, Yunfei; Dong, Feifan; Jiang, Yaming; Pan, Minhui; Zhang, Youhong; Lu, Cheng

2017-01-01

Thermotolerance is important particularly for poikilotherms such as insects. Understanding the mechanisms by which insects respond to high temperatures can provide insights into their adaptation to the environment. Therefore, in this study, we performed a transcriptome analysis of two silkworm strains with significantly different resistance to heat as well as humidity; the thermo-resistant strain 7532 and the thermos-sensitive strain Knobbed. We identified in total 4,944 differentially expressed genes (DEGs) using RNA-Seq. Among these, 4,390 were annotated and 554 were novel. Gene Ontology (GO) analysis of 747 DEGs identified between RT_48h (Resistant strain with high-temperature Treatment for 48 hours) and ST_48h (Sensitive strain with high-temperature Treatment for 48 hours) showed significant enrichment of 12 GO terms including metabolic process, extracellular region and serine-type peptidase activity. Moreover, we discovered 12 DEGs that may contribute to the heat-humidity stress response in the silkworm. Our data clearly showed that 48h post-exposure may be a critical time point for silkworm to respond to high temperature and humidity. These results provide insights into the genes and biological processes involved in high temperature and humidity tolerance in the silkworm, and advance our understanding of thermal tolerance in insects.

[Tourism function zoning of Jinyintan Grassland Scenic Area in Qinghai Province based on ecological sensitivity analysis].

PubMed

Zhong, Lin-sheng; Tang, Cheng-cai; Guo, Hua

2010-07-01

Based on the statistical data of natural ecology and social economy in Jinyintan Grassland Scenic Area in Qinghai Province in 2008, an evaluation index system for the ecological sensitivity of this area was established from the aspects of protected area rank, vegetation type, slope, and land use type. The ecological sensitivity of the sub-areas with higher tourism value and ecological function in the area was evaluated, and the tourism function zoning of these sub-areas was made by the technology of GIS and according to the analysis of eco-environmental characteristics and ecological sensitivity of each sensitive sub-area. It was suggested that the Jinyintan Grassland Scenic Area could be divided into three ecological sensitivity sub-areas (high, moderate, and low), three tourism functional sub-areas (restricted development ecotourism, moderate development ecotourism, and mass tourism), and six tourism functional sub-areas (wetland protection, primitive ecological sightseeing, agriculture and pasture tourism, grassland tourism, town tourism, and rural tourism).

Nano-LC/MALDI-MS using a column-integrated spotting probe for analysis of complex biomolecule samples.

PubMed

Hioki, Yusaku; Tanimura, Ritsuko; Iwamoto, Shinichi; Tanaka, Koichi

2014-03-04

Nanoflow liquid chromatography (nano-LC) is an essential technique for highly sensitive analysis of complex biological samples, and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is advantageous for rapid identification of proteins and in-depth analysis of post-translational modifications (PTMs). A combination of nano-LC and MALDI-MS (nano-LC/MALDI-MS) is useful for highly sensitive and detailed analysis in life sciences. However, the existing system does not fully utilize the advantages of each technique, especially in the interface of eluate transfer from nano-LC to a MALDI plate. To effectively combine nano-LC with MALDI-MS, we integrated a nano-LC column and a deposition probe for the first time (column probe) and incorporated it into a nano-LC/MALDI-MS system. Spotting nanoliter eluate droplets directly from the column onto the MALDI plate prevents postcolumn diffusion and preserves the chromatographic resolution. A DHB prespotted plate was prepared to suit the fabricated column probe to concentrate the droplets of nano-LC eluate. The performance of the advanced nano-LC/MALDI-MS system was substantiated by analyzing protein digests. When the system was coupled with multidimensional liquid chromatography (MDLC), trace amounts of glycopeptides that spiked into complex samples were successfully detected. Thus, a nano-LC/MALDI-MS direct-spotting system that eliminates postcolumn diffusion was constructed, and the efficacy of the system was demonstrated through highly sensitive analysis of the protein digests or spiked glycopeptides.

Identification of biomarkers in human head and neck tumor cell lines that predict for in vitro sensitivity to gefitinib.

PubMed

Hickinson, D Mark; Marshall, Gayle B; Beran, Garry J; Varella-Garcia, Marileila; Mills, Elizabeth A; South, Marie C; Cassidy, Andrew M; Acheson, Kerry L; McWalter, Gael; McCormack, Rose M; Bunn, Paul A; French, Tim; Graham, Alex; Holloway, Brian R; Hirsch, Fred R; Speake, Georgina

2009-06-01

Potential biomarkers were identified for in vitro sensitivity to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in head and neck cancer. Gefitinib sensitivity was determined in cell lines, followed by transcript profiling coupled with a novel pathway analysis approach. Eleven cell lines were highly sensitive to gefitinib (inhibitor concentration required to give 50% growth inhibition [GI(50)] < 1 microM), three had intermediate sensitivity (GI(50) 1-7 microM), and six were resistant (GI(50) > 7 microM); an exploratory principal component analysis revealed a separation between the genomic profiles of sensitive and resistant cell lines. Subsequently, a hypothesis-driven analysis of Affymetrix data (Affymetrix, Inc., Santa Clara, CA, USA) revealed higher mRNA levels for E-cadherin (CDH1); transforming growth factor, alpha (TGF-alpha); amphiregulin (AREG); FLJ22662; EGFR; p21-activated kinase 6 (PAK6); glutathione S-transferase Pi (GSTP1); and ATP-binding cassette, subfamily C, member 5 (ABCC5) in sensitive versus resistant cell lines. A hypothesis-free analysis identified 46 gene transcripts that were strongly differentiated, seven of which had a known association with EGFR and head and neck cancer (human EGF receptor 3 [HER3], TGF-alpha, CDH1, EGFR, keratin 16 [KRT16], fibroblast growth factor 2 [FGF2], and cortactin [CTTN]). Polymerase chain reaction (PCR) and enzyme-linked immunoabsorbant assay analysis confirmed Affymetrix data, and EGFR gene mutation, amplification, and genomic gain correlated strongly with gefitinib sensitivity. We identified biomarkers that predict for in vitro responsiveness to gefitinib, seven of which have known association with EGFR and head and neck cancer. These in vitro predictive biomarkers may have potential utility in the clinic and warrant further investigation.

CAFNA{reg{underscore}sign}, coded aperture fast neutron analysis for contraband detection: Preliminary results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, L.; Lanza, R.C.

1999-12-01

The authors have developed a near field coded aperture imaging system for use with fast neutron techniques as a tool for the detection of contraband and hidden explosives through nuclear elemental analysis. The technique relies on the prompt gamma rays produced by fast neutron interactions with the object being examined. The position of the nuclear elements is determined by the location of the gamma emitters. For existing fast neutron techniques, in Pulsed Fast Neutron Analysis (PFNA), neutrons are used with very low efficiency; in Fast Neutron Analysis (FNS), the sensitivity for detection of the signature gamma rays is very low.more » For the Coded Aperture Fast Neutron Analysis (CAFNA{reg{underscore}sign}) the authors have developed, the efficiency for both using the probing fast neutrons and detecting the prompt gamma rays is high. For a probed volume of n{sup 3} volume elements (voxels) in a cube of n resolution elements on a side, they can compare the sensitivity with other neutron probing techniques. As compared to PFNA, the improvement for neutron utilization is n{sup 2}, where the total number of voxels in the object being examined is n{sup 3}. Compared to FNA, the improvement for gamma-ray imaging is proportional to the total open area of the coded aperture plane; a typical value is n{sup 2}/2, where n{sup 2} is the number of total detector resolution elements or the number of pixels in an object layer. It should be noted that the actual signal to noise ratio of a system depends also on the nature and distribution of background events and this comparison may reduce somewhat the effective sensitivity of CAFNA. They have performed analysis, Monte Carlo simulations, and preliminary experiments using low and high energy gamma-ray sources. The results show that a high sensitivity 3-D contraband imaging and detection system can be realized by using CAFNA.« less

Genome-wide association analysis of diverse soybean genotypes reveals novel markers for nitrogen traits

USDA-ARS?s Scientific Manuscript database

Nitrogen is a primary plant nutrient that plays a major role in achieving maximum economic yield. Insufficient availability most often limits soybean crop growth. Symbiotic N2 fixation in soybean is highly sensitive to limited water availability, and breeding for reduced N2 fixation sensitivity to ...

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

USDA-ARS?s Scientific Manuscript database

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...

Applications of Quantum Cascade Laser Scanners for Remote Detection of Chemical and Biological Threats and Weapons of Mass Destruction

DTIC Science & Technology

2014-07-09

Rivera. Highly Sensitive Filter Paper Substrate for SERS Trace Explosives Detection , International Journal of Spectroscopy, (09 2012): 0. doi: 10.1155...Highly Sensitive Filter Paper Substrate for SERS Field Detection of Trace Threat Chemicals”, PITTCON-2013: Forensic Analysis in the Lab and Crime Scene...the surface. In addition, built-in algorithms were used for nearly real-time sample detection . Trace and bulk concentrations of the other substances

Microfluidic-Based Enrichment and Retrieval of Circulating Tumor Cells for RT-PCR Analysis.

PubMed

Gogoi, Priya; Sepehri, Saedeh; Chow, Will; Handique, Kalyan; Wang, Yixin

2017-01-01

Molecular analysis of circulating tumor cells (CTCs) is hindered by low sensitivity and high level of background leukocytes of currently available CTC enrichment technologies. We have developed a novel device to enrich and retrieve CTCs from blood samples by using a microfluidic chip. The Celsee PREP100 device captures CTCs with high sensitivity and allows the captured CTCs to be retrieved for molecular analysis. It uses the microfluidic chip which has approximately 56,320 capture chambers. Based on differences in cell size and deformability, each chamber ensures that small blood escape while larger CTCs of varying sizes are trapped and isolated in the chambers. In this report, we used the Celsee PREP100 to capture cancer cells spiked into normal donor blood samples. We were able to show that the device can capture as low as 10 cells with high reproducibility. The captured CTCs were retrieved from the microfluidic chip. The cell recovery rate of this back-flow procedure is 100% and the level of remaining background leukocytes is very low (about 300-400 cells). RNA from the retrieved cells are extracted and converted to cDNA, and gene expression analysis of selected cancer markers can be carried out by using RT-PCR assays. The sensitive and easy-to-use Celsee PREP100 system represents a promising technology for capturing and molecular characterization of CTCs.

Using solute and heat tracers for aquifer characterization in a strongly heterogeneous alluvial aquifer

NASA Astrophysics Data System (ADS)

Sarris, Theo S.; Close, Murray; Abraham, Phillip

2018-03-01

A test using Rhodamine WT and heat as tracers, conducted over a 78 day period in a strongly heterogeneous alluvial aquifer, was used to evaluate the utility of the combined observation dataset for aquifer characterization. A highly parameterized model was inverted, with concentration and temperature time-series as calibration targets. Groundwater heads recorded during the experiment were boundary dependent and were ignored during the inversion process. The inverted model produced a high resolution depiction of the hydraulic conductivity and porosity fields. Statistical properties of these fields are in very good agreement with estimates from previous studies at the site. Spatially distributed sensitivity analysis suggests that both solute and heat transport were most sensitive to the hydraulic conductivity and porosity fields and less sensitive to dispersivity and thermal distribution factor, with sensitivity to porosity greatly reducing outside the monitored area. The issues of model over-parameterization and non-uniqueness are addressed through identifiability analysis. Longitudinal dispersivity and thermal distribution factor are highly identifiable, however spatially distributed parameters are only identifiable near the injection point. Temperature related density effects became observable for both heat and solute, as the temperature anomaly increased above 12 degrees centigrade, and affected down gradient propagation. Finally we demonstrate that high frequency and spatially dense temperature data cannot inform a dual porosity model in the absence of frequent solute concentration measurements.

Highly sensitive catalytic spectrophotometric determination of ruthenium

NASA Astrophysics Data System (ADS)

Naik, Radhey M.; Srivastava, Abhishek; Prasad, Surendra

2008-01-01

A new and highly sensitive catalytic kinetic method (CKM) for the determination of ruthenium(III) has been established based on its catalytic effect on the oxidation of L-phenylalanine ( L-Pheala) by KMnO 4 in highly alkaline medium. The reaction has been followed spectrophotometrically by measuring the decrease in the absorbance at 526 nm. The proposed CKM is based on the fixed time procedure under optimum reaction conditions. It relies on the linear relationship where the change in the absorbance (Δ At) versus added Ru(III) amounts in the range of 0.101-2.526 ng ml -1 is plotted. Under the optimum conditions, the sensitivity of the proposed method, i.e. the limit of detection corresponding to 5 min is 0.08 ng ml -1, and decreases with increased time of analysis. The method is featured with good accuracy and reproducibility for ruthenium(III) determination. The ruthenium(III) has also been determined in presence of several interfering and non-interfering cations, anions and polyaminocarboxylates. No foreign ions interfered in the determination ruthenium(III) up to 20-fold higher concentration of foreign ions. In addition to standard solutions analysis, this method was successfully applied for the quantitative determination of ruthenium(III) in drinking water samples. The method is highly sensitive, selective and very stable. A review of recently published catalytic spectrophotometric methods for the determination of ruthenium(III) has also been presented for comparison.

Time-Resolved Fluorescent Immunochromatography of Aflatoxin B1 in Soybean Sauce: A Rapid and Sensitive Quantitative Analysis.

PubMed

Wang, Du; Zhang, Zhaowei; Li, Peiwu; Zhang, Qi; Zhang, Wen

2016-07-14

Rapid and quantitative sensing of aflatoxin B1 with high sensitivity and specificity has drawn increased attention of studies investigating soybean sauce. A sensitive and rapid quantitative immunochromatographic sensing method was developed for the detection of aflatoxin B1 based on time-resolved fluorescence. It combines the advantages of time-resolved fluorescent sensing and immunochromatography. The dynamic range of a competitive and portable immunoassay was 0.3-10.0 µg·kg(-1), with a limit of detection (LOD) of 0.1 µg·kg(-1) and recoveries of 87.2%-114.3%, within 10 min. The results showed good correlation (R² > 0.99) between time-resolved fluorescent immunochromatographic strip test and high performance liquid chromatography (HPLC). Soybean sauce samples analyzed using time-resolved fluorescent immunochromatographic strip test revealed that 64.2% of samples contained aflatoxin B1 at levels ranging from 0.31 to 12.5 µg·kg(-1). The strip test is a rapid, sensitive, quantitative, and cost-effective on-site screening technique in food safety analysis.

Novel approach based on one-tube nested PCR and a lateral flow strip for highly sensitive diagnosis of tuberculous meningitis.

PubMed

Sun, Yajuan; Chen, Jiajun; Li, Jia; Xu, Yawei; Jin, Hui; Xu, Na; Yin, Rui; Hu, Guohua

2017-01-01

Rapid and sensitive detection of Mycobacterium tuberculosis (M. Tb) in cerebrospinal fluid is crucial in the diagnosis of tuberculous meningitis (TBM), but conventional diagnostic technologies have limited sensitivity and specificity or are time-consuming. In this work, a novel, highly sensitive molecular diagnostic method, one-tube nested PCR-lateral flow strip test (OTNPCR-LFST), was developed for detecting M. tuberculosis. This one-tube nested PCR maintains the sensitivity of conventional two-step nested PCR and reduces both the chance of cross-contamination and the time required for analysis. The PCR product was detected by a lateral flow strip assay, which provided a basis for migration of the test to a point-of-care (POC) microfluidic format. The developed assay had an improved sensitivity compared with traditional PCR, and the limit of detection was up to 1 fg DNA isolated from M. tuberculosis. The assay was also specific for M. tuberculosis, and no cross-reactions were found in other non-target bacteria. The application of this technique to clinical samples was successfully evaluated, and OTNPCR-LFST showed 89% overall sensitivity and 100% specificity for TBM patients. This one-tube nested PCR-lateral flow strip assay is useful for detecting M. tuberculosis in TBM due to its rapidity, high sensitivity and simple manipulation.

Algorithm sensitivity analysis and parameter tuning for tissue image segmentation pipelines

PubMed Central

Kurç, Tahsin M.; Taveira, Luís F. R.; Melo, Alba C. M. A.; Gao, Yi; Kong, Jun; Saltz, Joel H.

2017-01-01

Abstract Motivation: Sensitivity analysis and parameter tuning are important processes in large-scale image analysis. They are very costly because the image analysis workflows are required to be executed several times to systematically correlate output variations with parameter changes or to tune parameters. An integrated solution with minimum user interaction that uses effective methodologies and high performance computing is required to scale these studies to large imaging datasets and expensive analysis workflows. Results: The experiments with two segmentation workflows show that the proposed approach can (i) quickly identify and prune parameters that are non-influential; (ii) search a small fraction (about 100 points) of the parameter search space with billions to trillions of points and improve the quality of segmentation results (Dice and Jaccard metrics) by as much as 1.42× compared to the results from the default parameters; (iii) attain good scalability on a high performance cluster with several effective optimizations. Conclusions: Our work demonstrates the feasibility of performing sensitivity analyses, parameter studies and auto-tuning with large datasets. The proposed framework can enable the quantification of error estimations and output variations in image segmentation pipelines. Availability and Implementation: Source code: https://github.com/SBU-BMI/region-templates/. Contact: teodoro@unb.br Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28062445

Algorithm sensitivity analysis and parameter tuning for tissue image segmentation pipelines.

PubMed

Teodoro, George; Kurç, Tahsin M; Taveira, Luís F R; Melo, Alba C M A; Gao, Yi; Kong, Jun; Saltz, Joel H

2017-04-01

Sensitivity analysis and parameter tuning are important processes in large-scale image analysis. They are very costly because the image analysis workflows are required to be executed several times to systematically correlate output variations with parameter changes or to tune parameters. An integrated solution with minimum user interaction that uses effective methodologies and high performance computing is required to scale these studies to large imaging datasets and expensive analysis workflows. The experiments with two segmentation workflows show that the proposed approach can (i) quickly identify and prune parameters that are non-influential; (ii) search a small fraction (about 100 points) of the parameter search space with billions to trillions of points and improve the quality of segmentation results (Dice and Jaccard metrics) by as much as 1.42× compared to the results from the default parameters; (iii) attain good scalability on a high performance cluster with several effective optimizations. Our work demonstrates the feasibility of performing sensitivity analyses, parameter studies and auto-tuning with large datasets. The proposed framework can enable the quantification of error estimations and output variations in image segmentation pipelines. Source code: https://github.com/SBU-BMI/region-templates/ . teodoro@unb.br. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Real-time polymerase chain reaction for diagnosing infectious mononucleosis in pediatric patients: A systematic review and meta-analysis.

PubMed

Jiang, Sha-Yi; Yang, Jing-Wei; Shao, Jing-Bo; Liao, Xue-Lian; Lu, Zheng-Hua; Jiang, Hui

2016-05-01

In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis. © 2015 Wiley Periodicals, Inc.

Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett's esophagus

NASA Astrophysics Data System (ADS)

Muldoon, Timothy J.; Thekkek, Nadhi; Roblyer, Darren; Maru, Dipen; Harpaz, Noam; Potack, Jonathan; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

2010-03-01

Early detection of neoplasia in patients with Barrett's esophagus is essential to improve outcomes. The aim of this ex vivo study was to evaluate the ability of high-resolution microendoscopic imaging and quantitative image analysis to identify neoplastic lesions in patients with Barrett's esophagus. Nine patients with pathologically confirmed Barrett's esophagus underwent endoscopic examination with biopsies or endoscopic mucosal resection. Resected fresh tissue was imaged with fiber bundle microendoscopy; images were analyzed by visual interpretation or by quantitative image analysis to predict whether the imaged sites were non-neoplastic or neoplastic. The best performing pair of quantitative features were chosen based on their ability to correctly classify the data into the two groups. Predictions were compared to the gold standard of histopathology. Subjective analysis of the images by expert clinicians achieved average sensitivity and specificity of 87% and 61%, respectively. The best performing quantitative classification algorithm relied on two image textural features and achieved a sensitivity and specificity of 87% and 85%, respectively. This ex vivo pilot trial demonstrates that quantitative analysis of images obtained with a simple microendoscope system can distinguish neoplasia in Barrett's esophagus with good sensitivity and specificity when compared to histopathology and to subjective image interpretation.

Aptamer-based microspheres for highly sensitive protein detection using fluorescently-labeled DNA nanostructures.

PubMed

Han, Daehoon; Hong, Jinkee; Kim, Hyun Cheol; Sung, Jong Hwan; Lee, Jong Bum

2013-11-01

Many highly sensitive protein detection techniques have been developed and have played an important role in the analysis of proteins. Herein, we report a novel technique that can detect proteins sensitively and effectively using aptamer-based DNA nanostructures. Thrombin was used as a target protein and aptamer was used to capture fluorescent dye-labeled DNA nanobarcodes or thrombin on a microsphere. The captured DNA nanobarcodes were replaced by a thrombin and aptamer interaction. The detection ability of this approach was confirmed by flow cytometry with different concentrations of thrombin. Our detection method has great potential for rapid and simple protein detection with a variety of aptamers.

Sensitivity Analysis of Fatigue Crack Growth Model for API Steels in Gaseous Hydrogen.

PubMed

Amaro, Robert L; Rustagi, Neha; Drexler, Elizabeth S; Slifka, Andrew J

2014-01-01

A model to predict fatigue crack growth of API pipeline steels in high pressure gaseous hydrogen has been developed and is presented elsewhere. The model currently has several parameters that must be calibrated for each pipeline steel of interest. This work provides a sensitivity analysis of the model parameters in order to provide (a) insight to the underlying mathematical and mechanistic aspects of the model, and (b) guidance for model calibration of other API steels.

Analysis and amelioration about the cross-sensitivity of a high resolution MOEMS accelerometer based on diffraction grating

NASA Astrophysics Data System (ADS)

Lu, Qianbo; Bai, Jian; Wang, Kaiwei; Lou, Shuqi; Jiao, Xufen; Han, Dandan

2016-10-01

Cross-sensitivity is a crucial parameter since it detrimentally affect the performance of an accelerometer, especially for a high resolution accelerometer. In this paper, a suite of analytical and finite-elements-method (FEM) models for characterizing the mechanism and features of the cross-sensitivity of a single-axis MOEMS accelerometer composed of a diffraction grating and a micromachined mechanical sensing chip are presented, which have not been systematically investigated yet. The mechanism and phenomena of the cross-sensitivity of this type MOEMS accelerometer based on diffraction grating differ quite a lot from the traditional ones owing to the identical sensing principle. By analyzing the models, some ameliorations and the modified design are put forward to suppress the cross-sensitivity. The modified design, achieved by double sides etching on a specific double-substrate-layer silicon-on-insulator (SOI) wafer, is validated to have a far smaller cross-sensitivity compared with the design previously reported in the literature. Moreover, this design can suppress the cross-sensitivity dramatically without compromising the acceleration sensitivity and resolution.

Investigating and understanding fouling in a planar setup using ultrasonic methods.

PubMed

Wallhäusser, E; Hussein, M A; Becker, T

2012-09-01

Fouling is an unwanted deposit on heat transfer surfaces and occurs regularly in foodstuff heat exchangers. Fouling causes high costs because cleaning of heat exchangers has to be carried out and cleaning success cannot easily be monitored. Thus, used cleaning cycles in foodstuff industry are usually too long leading to high costs. In this paper, a setup is described with which it is possible, first, to produce dairy protein fouling similar to the one found in industrial heat exchangers and, second, to detect the presence and absence of such fouling using an ultrasonic based measuring method. The developed setup resembles a planar heat exchanger in which fouling can be made and cleaned reproducible. Fouling presence, absence, and cleaning progress can be monitored by using an ultrasonic detection unit. The setup is described theoretically based on electrical and mechanical lumped circuits to derive the wave equation and the transfer function to perform a sensitivity analysis. Sensitivity analysis was done to determine influencing quantities and showed that fouling is measurable. Also, first experimental results are compared with results from sensitivity analysis.

Analysis of single quantum-dot mobility inside 1D nanochannel devices

NASA Astrophysics Data System (ADS)

Hoang, H. T.; Segers-Nolten, I. M.; Tas, N. R.; van Honschoten, J. W.; Subramaniam, V.; Elwenspoek, M. C.

2011-07-01

We visualized individual quantum dots using a combination of a confining nanochannel and an ultra-sensitive microscope system, equipped with a high numerical aperture lens and a highly sensitive camera. The diffusion coefficients of the confined quantum dots were determined from the experimentally recorded trajectories according to the classical diffusion theory for Brownian motion in two dimensions. The calculated diffusion coefficients were three times smaller than those in bulk solution. These observations confirm and extend the results of Eichmann et al (2008 Langmuir 24 714-21) to smaller particle diameters and more narrow confinement. A detailed analysis shows that the observed reduction in mobility cannot be explained by conventional hydrodynamic theory.

Analysis of the sensitivity of soils to the leaching of agricultural pesticides in Ohio

USGS Publications Warehouse

Schalk, C.W.

1998-01-01

Pesticides have not been found frequently in the ground waters of Ohio even though large amounts of agricultural pesticides are applied to fields in Ohio every year. State regulators, including representatives from Ohio Environmental Protection Agency and Departments of Agriculture, Health, and Natural Resources, are striving to limit the presence of pesticides in ground water at a minimum. A proposed pesticide management plan for the State aims at protecting Ohio's ground water by assessing pesticide-leaching potential using geographic information system (GIS) technology and invoking a monitoring plan that targets aquifers deemed most likely to be vulnerable to pesticide leaching. The U.S. Geological Survey, in cooperation with Ohio Department of Agriculture, assessed the sensitivity of mapped soil units in Ohio to pesticide leaching. A soils data base (STATSGO) compiled by U.S. Department of Agriculture was used iteratively to estimate soil units as being of high to low sensitivity on the basis of soil permeability, clay content, and organic-matter content. Although this analysis did not target aquifers directly, the results can be used as a first estimate of areas most likely to be subject to pesticide contamination from normal agricultural practices. High-sensitivity soil units were found in lakefront areas and former lakefront beach ridges, buried valleys in several river basins, and parts of central and south- central Ohio. Medium-high-sensitivity soil units were found in other river basins, along Lake Erie in north-central Ohio, and in many of the upland areas of the Muskingum River Basin. Low-sensitivity map units dominated the northwestern quadrant of Ohio.

An UPLC-ESI-MS/MS Assay Using 6-Aminoquinolyl-N-Hydroxysuccinimidyl Carbamate Derivatization for Targeted Amino Acid Analysis: Application to Screening of Arabidopsis thaliana Mutants.

PubMed

Salazar, Carolina; Armenta, Jenny M; Shulaev, Vladimir

2012-07-06

In spite of the large arsenal of methodologies developed for amino acid assessment in complex matrices, their implementation in metabolomics studies involving wide-ranging mutant screening is hampered by their lack of high-throughput, sensitivity, reproducibility, and/or wide dynamic range. In response to the challenge of developing amino acid analysis methods that satisfy the criteria required for metabolomic studies, improved reverse-phase high-performance liquid chromatography-mass spectrometry (RPHPLC-MS) methods have been recently reported for large-scale screening of metabolic phenotypes. However, these methods focus on the direct analysis of underivatized amino acids and, therefore, problems associated with insufficient retention and resolution are observed due to the hydrophilic nature of amino acids. It is well known that derivatization methods render amino acids more amenable for reverse phase chromatographic analysis by introducing highly-hydrophobic tags in their carboxylic acid or amino functional group. Therefore, an analytical platform that combines the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) pre-column derivatization method with ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) is presented in this article. For numerous reasons typical amino acid derivatization methods would be inadequate for large scale metabolic projects. However, AQC derivatization is a simple, rapid and reproducible way of obtaining stable amino acid adducts amenable for UPLC-ESI-MS/MS and the applicability of the method for high-throughput metabolomic analysis in Arabidopsis thaliana is demonstrated in this study. Overall, the major advantages offered by this amino acid analysis method include high-throughput, enhanced sensitivity and selectivity; characteristics that showcase its utility for the rapid screening of the preselected plant metabolites without compromising the quality of the metabolic data. The presented method enabled thirty-eight metabolites (proteinogenic amino acids and related compounds) to be analyzed within 10 min with detection limits down to 1.02 × 10-11 M (i.e., atomole level on column), which represents an improved sensitivity of 1 to 5 orders of magnitude compared to existing methods. Our UPLC-ESI-MS/MS method is one of the seven analytical platforms used by the Arabidopsis Metabolomics Consortium. The amino acid dataset obtained by analysis of Arabidopsis T-DNA mutant stocks with our platform is captured and open to the public in the web portal PlantMetabolomics.org. The analytical platform herein described could find important applications in other studies where the rapid, high-throughput and sensitive assessment of low abundance amino acids in complex biosamples is necessary.

An UPLC-ESI-MS/MS Assay Using 6-Aminoquinolyl-N-Hydroxysuccinimidyl Carbamate Derivatization for Targeted Amino Acid Analysis: Application to Screening of Arabidopsis thaliana Mutants

PubMed Central

Salazar, Carolina; Armenta, Jenny M.; Shulaev, Vladimir

2012-01-01

In spite of the large arsenal of methodologies developed for amino acid assessment in complex matrices, their implementation in metabolomics studies involving wide-ranging mutant screening is hampered by their lack of high-throughput, sensitivity, reproducibility, and/or wide dynamic range. In response to the challenge of developing amino acid analysis methods that satisfy the criteria required for metabolomic studies, improved reverse-phase high-performance liquid chromatography-mass spectrometry (RPHPLC-MS) methods have been recently reported for large-scale screening of metabolic phenotypes. However, these methods focus on the direct analysis of underivatized amino acids and, therefore, problems associated with insufficient retention and resolution are observed due to the hydrophilic nature of amino acids. It is well known that derivatization methods render amino acids more amenable for reverse phase chromatographic analysis by introducing highly-hydrophobic tags in their carboxylic acid or amino functional group. Therefore, an analytical platform that combines the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) pre-column derivatization method with ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) is presented in this article. For numerous reasons typical amino acid derivatization methods would be inadequate for large scale metabolic projects. However, AQC derivatization is a simple, rapid and reproducible way of obtaining stable amino acid adducts amenable for UPLC-ESI-MS/MS and the applicability of the method for high-throughput metabolomic analysis in Arabidopsis thaliana is demonstrated in this study. Overall, the major advantages offered by this amino acid analysis method include high-throughput, enhanced sensitivity and selectivity; characteristics that showcase its utility for the rapid screening of the preselected plant metabolites without compromising the quality of the metabolic data. The presented method enabled thirty-eight metabolites (proteinogenic amino acids and related compounds) to be analyzed within 10 min with detection limits down to 1.02 × 10−11 M (i.e., atomole level on column), which represents an improved sensitivity of 1 to 5 orders of magnitude compared to existing methods. Our UPLC-ESI-MS/MS method is one of the seven analytical platforms used by the Arabidopsis Metabolomics Consortium. The amino acid dataset obtained by analysis of Arabidopsis T-DNA mutant stocks with our platform is captured and open to the public in the web portal PlantMetabolomics.org. The analytical platform herein described could find important applications in other studies where the rapid, high-throughput and sensitive assessment of low abundance amino acids in complex biosamples is necessary. PMID:24957640

Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability.

PubMed

Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide

2009-06-01

It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

Skeletal mechanism generation for surrogate fuels using directed relation graph with error propagation and sensitivity analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niemeyer, Kyle E.; Sung, Chih-Jen; Raju, Mandhapati P.

2010-09-15

A novel implementation for the skeletal reduction of large detailed reaction mechanisms using the directed relation graph with error propagation and sensitivity analysis (DRGEPSA) is developed and presented with examples for three hydrocarbon components, n-heptane, iso-octane, and n-decane, relevant to surrogate fuel development. DRGEPSA integrates two previously developed methods, directed relation graph-aided sensitivity analysis (DRGASA) and directed relation graph with error propagation (DRGEP), by first applying DRGEP to efficiently remove many unimportant species prior to sensitivity analysis to further remove unimportant species, producing an optimally small skeletal mechanism for a given error limit. It is illustrated that the combination ofmore » the DRGEP and DRGASA methods allows the DRGEPSA approach to overcome the weaknesses of each, specifically that DRGEP cannot identify all unimportant species and that DRGASA shields unimportant species from removal. Skeletal mechanisms for n-heptane and iso-octane generated using the DRGEP, DRGASA, and DRGEPSA methods are presented and compared to illustrate the improvement of DRGEPSA. From a detailed reaction mechanism for n-alkanes covering n-octane to n-hexadecane with 2115 species and 8157 reactions, two skeletal mechanisms for n-decane generated using DRGEPSA, one covering a comprehensive range of temperature, pressure, and equivalence ratio conditions for autoignition and the other limited to high temperatures, are presented and validated. The comprehensive skeletal mechanism consists of 202 species and 846 reactions and the high-temperature skeletal mechanism consists of 51 species and 256 reactions. Both mechanisms are further demonstrated to well reproduce the results of the detailed mechanism in perfectly-stirred reactor and laminar flame simulations over a wide range of conditions. The comprehensive and high-temperature n-decane skeletal mechanisms are included as supplementary material with this article. (author)« less

ASKI: A modular toolbox for scattering-integral-based seismic full waveform inversion and sensitivity analysis utilizing external forward codes

NASA Astrophysics Data System (ADS)

Schumacher, Florian; Friederich, Wolfgang

Due to increasing computational resources, the development of new numerically demanding methods and software for imaging Earth's interior remains of high interest in Earth sciences. Here, we give a description from a user's and programmer's perspective of the highly modular, flexible and extendable software package ASKI-Analysis of Sensitivity and Kernel Inversion-recently developed for iterative scattering-integral-based seismic full waveform inversion. In ASKI, the three fundamental steps of solving the seismic forward problem, computing waveform sensitivity kernels and deriving a model update are solved by independent software programs that interact via file output/input only. Furthermore, the spatial discretizations of the model space used for solving the seismic forward problem and for deriving model updates, respectively, are kept completely independent. For this reason, ASKI does not contain a specific forward solver but instead provides a general interface to established community wave propagation codes. Moreover, the third fundamental step of deriving a model update can be repeated at relatively low costs applying different kinds of model regularization or re-selecting/weighting the inverted dataset without need to re-solve the forward problem or re-compute the kernels. Additionally, ASKI offers the user sensitivity and resolution analysis tools based on the full sensitivity matrix and allows to compose customized workflows in a consistent computational environment. ASKI is written in modern Fortran and Python, it is well documented and freely available under terms of the GNU General Public License (http://www.rub.de/aski).

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. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Phase sensitive spectral domain interferometry for label free biomolecular interaction analysis and biosensing applications

NASA Astrophysics Data System (ADS)

Chirvi, Sajal

Biomolecular interaction analysis (BIA) plays vital role in wide variety of fields, which include biomedical research, pharmaceutical industry, medical diagnostics, and biotechnology industry. Study and quantification of interactions between natural biomolecules (proteins, enzymes, DNA) and artificially synthesized molecules (drugs) is routinely done using various labeled and label-free BIA techniques. Labeled BIA (Chemiluminescence, Fluorescence, Radioactive) techniques suffer from steric hindrance of labels on interaction site, difficulty of attaching labels to molecules, higher cost and time of assay development. Label free techniques with real time detection capabilities have demonstrated advantages over traditional labeled techniques. The gold standard for label free BIA is surface Plasmon resonance (SPR) that detects and quantifies the changes in refractive index of the ligand-analyte complex molecule with high sensitivity. Although SPR is a highly sensitive BIA technique, it requires custom-made sensor chips and is not well suited for highly multiplexed BIA required in high throughput applications. Moreover implementation of SPR on various biosensing platforms is limited. In this research work spectral domain phase sensitive interferometry (SD-PSI) has been developed for label-free BIA and biosensing applications to address limitations of SPR and other label free techniques. One distinct advantage of SD-PSI compared to other label-free techniques is that it does not require use of custom fabricated biosensor substrates. Laboratory grade, off-the-shelf glass or plastic substrates of suitable thickness with proper surface functionalization are used as biosensor chips. SD-PSI is tested on four separate BIA and biosensing platforms, which include multi-well plate, flow cell, fiber probe with integrated optics and fiber tip biosensor. Sensitivity of 33 ng/ml for anti-IgG is achieved using multi-well platform. Principle of coherence multiplexing for multi-channel label-free biosensing applications is introduced. Simultaneous interrogation of multiple biosensors is achievable with a single spectral domain phase sensitive interferometer by coding the individual sensograms in coherence-multiplexed channels. Experimental results demonstrating multiplexed quantitative biomolecular interaction analysis of antibodies binding to antigen coated functionalized biosensor chip surfaces on different platforms are presented.

Analysis of different anthropometric indicators in the detection of high blood pressure in school adolescents: a cross-sectional study with 8295 adolescents.

PubMed

Christofaro, Diego G D; Farah, Breno Q; Vanderlei, Luiz Carlos M; Delfino, Leandro D; Tebar, William R; Barros, Mauro Virgílio G de; Ritti-Dias, Raphael M

High blood pressure is strongly associated with obesity in different populations. However, it is unclear whether different anthropometric indicators of obesity can satisfactorily predict high blood pressure in the school setting. This study evaluated the sensitivity and specificity of body mass index, waist circumference, and waist to height ratio in the detection of high blood pressure in adolescents. The sample consisted of 8295 adolescents aged 10-17 years. Weight was measured using a digital scale, height with a stadiometer, and waist circumference using a tape measure. Blood pressure was measured by an automatic blood pressure measuring device. ROC curves were used for the analysis of sensitivity and specificity of the three anthropometric indices in identifying high blood pressure. Binary Logistic Regression was used to assess the association of body mass index, waist circumference, and waist to height ratio with high blood pressure. Low values of sensitivity were observed for body mass index (0.35), waist circumference (0.37), and waist to height ratio (0.31) and high values of specificity for body mass index (0.86), waist circumference (0.82), and waist to height ratio (0.83) in the detection of high blood pressure. An association was observed between adolescents classified with high body mass index (OR=3.57 [95% CI=3.10-4.10]), waist cirumference (OR=3.24 [95% CI=2.83-3.72]), and waist to height ratio (OR=2.94 [95% CI=2.54-3.40]) with high blood pressure. Body mass index, waist circumference, and waist to height ratio presented low sensitivity to identify adolescents with high blood pressure. However, adolescents classified with high body mass index, waist circumference, and waist to height ratio demonstrated a high association of presenting high blood pressure. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Effects of age, sex, and genotype on high-sensitivity metabolomic profiles in the fruit fly, Drosophila melanogaster

PubMed Central

Hoffman, Jessica M; Soltow, Quinlyn A; Li, Shuzhao; Sidik, Alfire; Jones, Dean P; Promislow, Daniel E L

2014-01-01

Researchers have used whole-genome sequencing and gene expression profiling to identify genes associated with age, in the hope of understanding the underlying mechanisms of senescence. But there is a substantial gap from variation in gene sequences and expression levels to variation in age or life expectancy. In an attempt to bridge this gap, here we describe the effects of age, sex, genotype, and their interactions on high-sensitivity metabolomic profiles in the fruit fly, Drosophila melanogaster. Among the 6800 features analyzed, we found that over one-quarter of all metabolites were significantly associated with age, sex, genotype, or their interactions, and multivariate analysis shows that individual metabolomic profiles are highly predictive of these traits. Using a metabolomic equivalent of gene set enrichment analysis, we identified numerous metabolic pathways that were enriched among metabolites associated with age, sex, and genotype, including pathways involving sugar and glycerophospholipid metabolism, neurotransmitters, amino acids, and the carnitine shuttle. Our results suggest that high-sensitivity metabolomic studies have excellent potential not only to reveal mechanisms that lead to senescence, but also to help us understand differences in patterns of aging among genotypes and between males and females. PMID:24636523

Flexible nanopillar-based electrochemical sensors for genetic detection of foodborne pathogens

NASA Astrophysics Data System (ADS)

Park, Yoo Min; Lim, Sun Young; Jeong, Soon Woo; Song, Younseong; Bae, Nam Ho; Hong, Seok Bok; Choi, Bong Gill; Lee, Seok Jae; Lee, Kyoung G.

2018-06-01

Flexible and highly ordered nanopillar arrayed electrodes have brought great interest for many electrochemical applications, especially to the biosensors, because of its unique mechanical and topological properties. Herein, we report an advanced method to fabricate highly ordered nanopillar electrodes produced by soft-/photo-lithography and metal evaporation. The highly ordered nanopillar array exhibited the superior electrochemical and mechanical properties in regard with the wide space to response with electrolytes, enabling the sensitive analysis. As-prepared gold and silver electrodes on nanopillar arrays exhibit great and stable electrochemical performance to detect the amplified gene from foodborne pathogen of Escherichia coli O157:H7. Additionally, lightweight, flexible, and USB-connectable nanopillar-based electrochemical sensor platform improves the connectivity, portability, and sensitivity. Moreover, we successfully confirm the performance of genetic analysis using real food, specially designed intercalator, and amplified gene from foodborne pathogens with high reproducibility (6% standard deviation) and sensitivity (10 × 1.01 CFU) within 25 s based on the square wave voltammetry principle. This study confirmed excellent mechanical and chemical characteristics of nanopillar electrodes have a great and considerable electrochemical activity to apply as genetic biosensor platform in the fields of point-of-care testing (POCT).

Sensitivity and uncertainty analysis for Abreu & Johnson numerical vapor intrusion model.

PubMed

Ma, Jie; Yan, Guangxu; Li, Haiyan; Guo, Shaohui

2016-03-05

This study conducted one-at-a-time (OAT) sensitivity and uncertainty analysis for a numerical vapor intrusion model for nine input parameters, including soil porosity, soil moisture, soil air permeability, aerobic biodegradation rate, building depressurization, crack width, floor thickness, building volume, and indoor air exchange rate. Simulations were performed for three soil types (clay, silt, and sand), two source depths (3 and 8m), and two source concentrations (1 and 400 g/m(3)). Model sensitivity and uncertainty for shallow and high-concentration vapor sources (3m and 400 g/m(3)) are much smaller than for deep and low-concentration sources (8m and 1g/m(3)). For high-concentration sources, soil air permeability, indoor air exchange rate, and building depressurization (for high permeable soil like sand) are key contributors to model output uncertainty. For low-concentration sources, soil porosity, soil moisture, aerobic biodegradation rate and soil gas permeability are key contributors to model output uncertainty. Another important finding is that impacts of aerobic biodegradation on vapor intrusion potential of petroleum hydrocarbons are negligible when vapor source concentration is high, because of insufficient oxygen supply that limits aerobic biodegradation activities. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced photovoltaic performance of a quantum dot-sensitized solar cell using a Nb-doped TiO2 electrode.

PubMed

Jiang, Lei; You, Ting; Deng, Wei-Qiao

2013-10-18

In this work Nb-doped anatase TiO2 nanocrystals are used as the photoanode of quantum-dot-sensitized solar cells. A solar cell with CdS/CdSe quantum dots co-sensitized 2.5 mol% Nb-doped anatase TiO2 nanocrystals can achieve a photovoltaic conversion efficiency of 3.3%, which is almost twice as high as the 1.7% obtained by a cell based on undoped TiO2 nanocrystals. The incident photon-to-current conversion efficiency can reach as high as 91%, which is a record for all quantum-dot-sensitized solar cells. Detailed analysis shows that such an enhancement is due to improved lifetime and diffusion length of electrons in the solar cell.

Using Real-time Event Tracking Sensitivity Analysis to Overcome Sensor Measurement Uncertainties of Geo-Information Management in Drilling Disasters

NASA Astrophysics Data System (ADS)

Tavakoli, S.; Poslad, S.; Fruhwirth, R.; Winter, M.

2012-04-01

This paper introduces an application of a novel EventTracker platform for instantaneous Sensitivity Analysis (SA) of large scale real-time geo-information. Earth disaster management systems demand high quality information to aid a quick and timely response to their evolving environments. The idea behind the proposed EventTracker platform is the assumption that modern information management systems are able to capture data in real-time and have the technological flexibility to adjust their services to work with specific sources of data/information. However, to assure this adaptation in real time, the online data should be collected, interpreted, and translated into corrective actions in a concise and timely manner. This can hardly be handled by existing sensitivity analysis methods because they rely on historical data and lazy processing algorithms. In event-driven systems, the effect of system inputs on its state is of value, as events could cause this state to change. This 'event triggering' situation underpins the logic of the proposed approach. Event tracking sensitivity analysis method describes the system variables and states as a collection of events. The higher the occurrence of an input variable during the trigger of event, the greater its potential impact will be on the final analysis of the system state. Experiments were designed to compare the proposed event tracking sensitivity analysis with existing Entropy-based sensitivity analysis methods. The results have shown a 10% improvement in a computational efficiency with no compromise for accuracy. It has also shown that the computational time to perform the sensitivity analysis is 0.5% of the time required compared to using the Entropy-based method. The proposed method has been applied to real world data in the context of preventing emerging crises at drilling rigs. One of the major purposes of such rigs is to drill boreholes to explore oil or gas reservoirs with the final scope of recovering the content of such reservoirs; both in onshore regions as well as in offshore regions. Drilling a well is always guided by technical, economic and security constraints to prevent crew, equipment and environment from injury, damage and pollution. Although risk assessment and local practice provides a high degree of security, uncertainty is given by the behaviour of the formation which may cause crucial situations at the rig. To overcome such uncertainties real-time sensor measurements form a base to predict and thus prevent such crises, the proposed method supports the identification of the data necessary for that.

The Accuracy of Integrated [18F] Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Detection of Pelvic and Para-aortic Nodal Metastasis in Patients with High Risk Endometrial Cancer

PubMed Central

Gholkar, Nikhil Shirish; Saha, Subhas Chandra; Prasad, GRV; Bhattacharya, Anish; Srinivasan, Radhika; Suri, Vanita

2014-01-01

Lymph nodal (LN) metastasis is the most important prognostic factor in high-risk endometrial cancer. However, the benefit of routine lymphadenectomy in endometrial cancer is controversial. This study was conducted to assess the accuracy of [18F] fluorodeoxyglucose-positron emission tomography/computed tomography ([18F] FDG-PET/CT) in detection of pelvic and para-aortic nodal metastases in high-risk endometrial cancer. 20 patients with high-risk endometrial carcinoma underwent [18F] FDG-PET/CT followed by total abdominal hysterectomy, bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy. The findings on histopathology were compared with [18F] FDG-PET/CT findings to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F] FDG-PET/CT. The pelvic nodal findings were analyzed on a patient and nodal chain based criteria. The para-aortic nodal findings were reported separately. Histopathology documented nodal involvement in two patients (10%). For detection of pelvic nodes, on a patient based analysis, [18F] FDG-PET/CT had a sensitivity of 100%, specificity of 61.11%, PPV of 22.22%, NPV of 100% and accuracy of 65% and on a nodal chain based analysis, [18F] FDG-PET/CT had a sensitivity of 100%, specificity of 80%, PPV of 20%, NPV of 100%, and accuracy of 80.95%. For detection of para-aortic nodes, [18F] FDG-PET/CT had sensitivity of 100%, specificity of 66.67%, PPV of 20%, NPV of 100%, and accuracy of 69.23%. Although [18F] FDG-PET/CT has high sensitivity for detection of LN metastasis in endometrial carcinoma, it had moderate accuracy and high false positivity. However, the high NPV is important in selecting patients in whom lymphadenectomy may be omitted. PMID:25538488

Geostationary Coastal and Air Pollution Events (GEO-CAPE) Sensitivity Analysis Experiment

NASA Technical Reports Server (NTRS)

Lee, Meemong; Bowman, Kevin

2014-01-01

Geostationary Coastal and Air pollution Events (GEO-CAPE) is a NASA decadal survey mission to be designed to provide surface reflectance at high spectral, spatial, and temporal resolutions from a geostationary orbit necessary for studying regional-scale air quality issues and their impact on global atmospheric composition processes. GEO-CAPE's Atmospheric Science Questions explore the influence of both gases and particles on air quality, atmospheric composition, and climate. The objective of the GEO-CAPE Observing System Simulation Experiment (OSSE) is to analyze the sensitivity of ozone to the global and regional NOx emissions and improve the science impact of GEO-CAPE with respect to the global air quality. The GEO-CAPE OSSE team at Jet propulsion Laboratory has developed a comprehensive OSSE framework that can perform adjoint-sensitivity analysis for a wide range of observation scenarios and measurement qualities. This report discusses the OSSE framework and presents the sensitivity analysis results obtained from the GEO-CAPE OSSE framework for seven observation scenarios and three instrument systems.

Quantitative mass spectrometry methods for pharmaceutical analysis

PubMed Central

Loos, Glenn; Van Schepdael, Ann

2016-01-01

Quantitative pharmaceutical analysis is nowadays frequently executed using mass spectrometry. Electrospray ionization coupled to a (hybrid) triple quadrupole mass spectrometer is generally used in combination with solid-phase extraction and liquid chromatography. Furthermore, isotopically labelled standards are often used to correct for ion suppression. The challenges in producing sensitive but reliable quantitative data depend on the instrumentation, sample preparation and hyphenated techniques. In this contribution, different approaches to enhance the ionization efficiencies using modified source geometries and improved ion guidance are provided. Furthermore, possibilities to minimize, assess and correct for matrix interferences caused by co-eluting substances are described. With the focus on pharmaceuticals in the environment and bioanalysis, different separation techniques, trends in liquid chromatography and sample preparation methods to minimize matrix effects and increase sensitivity are discussed. Although highly sensitive methods are generally aimed for to provide automated multi-residue analysis, (less sensitive) miniaturized set-ups have a great potential due to their ability for in-field usage. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644982

Adjoint Sensitivity Analysis for Scale-Resolving Turbulent Flow Solvers

NASA Astrophysics Data System (ADS)

Blonigan, Patrick; Garai, Anirban; Diosady, Laslo; Murman, Scott

2017-11-01

Adjoint-based sensitivity analysis methods are powerful design tools for engineers who use computational fluid dynamics. In recent years, these engineers have started to use scale-resolving simulations like large-eddy simulations (LES) and direct numerical simulations (DNS), which resolve more scales in complex flows with unsteady separation and jets than the widely-used Reynolds-averaged Navier-Stokes (RANS) methods. However, the conventional adjoint method computes large, unusable sensitivities for scale-resolving simulations, which unlike RANS simulations exhibit the chaotic dynamics inherent in turbulent flows. Sensitivity analysis based on least-squares shadowing (LSS) avoids the issues encountered by conventional adjoint methods, but has a high computational cost even for relatively small simulations. The following talk discusses a more computationally efficient formulation of LSS, ``non-intrusive'' LSS, and its application to turbulent flows simulated with a discontinuous-Galkerin spectral-element-method LES/DNS solver. Results are presented for the minimal flow unit, a turbulent channel flow with a limited streamwise and spanwise domain.

Manufacturing error sensitivity analysis and optimal design method of cable-network antenna structures

NASA Astrophysics Data System (ADS)

Zong, Yali; Hu, Naigang; Duan, Baoyan; Yang, Guigeng; Cao, Hongjun; Xu, Wanye

2016-03-01

Inevitable manufacturing errors and inconsistency between assumed and actual boundary conditions can affect the shape precision and cable tensions of a cable-network antenna, and even result in failure of the structure in service. In this paper, an analytical sensitivity analysis method of the shape precision and cable tensions with respect to the parameters carrying uncertainty was studied. Based on the sensitivity analysis, an optimal design procedure was proposed to alleviate the effects of the parameters that carry uncertainty. The validity of the calculated sensitivities is examined by those computed by a finite difference method. Comparison with a traditional design method shows that the presented design procedure can remarkably reduce the influence of the uncertainties on the antenna performance. Moreover, the results suggest that especially slender front net cables, thick tension ties, relatively slender boundary cables and high tension level can improve the ability of cable-network antenna structures to resist the effects of the uncertainties on the antenna performance.

Diagnostic Performance of CT for Diagnosis of Fat-Poor Angiomyolipoma in Patients With Renal Masses: A Systematic Review and Meta-Analysis.

PubMed

Woo, Sungmin; Suh, Chong Hyun; Cho, Jeong Yeon; Kim, Sang Youn; Kim, Seung Hyup

2017-11-01

The purpose of this article is to systematically review and perform a meta-analysis of the diagnostic performance of CT for diagnosis of fat-poor angiomyolipoma (AML) in patients with renal masses. MEDLINE and EMBASE were systematically searched up to February 2, 2017. We included diagnostic accuracy studies that used CT for diagnosis of fat-poor AML in patients with renal masses, using pathologic examination as the reference standard. Two independent reviewers assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity of included studies were calculated and were pooled and plotted in a hierarchic summary ROC plot. Sensitivity analyses using several clinically relevant covariates were performed to explore heterogeneity. Fifteen studies (2258 patients) were included. Pooled sensitivity and specificity were 0.67 (95% CI, 0.48-0.81) and 0.97 (95% CI, 0.89-0.99), respectively. Substantial and considerable heterogeneity was present with regard to sensitivity and specificity (I 2 = 91.21% and 78.53%, respectively). At sensitivity analyses, the specificity estimates were comparable and consistently high across all subgroups (0.93-1.00), but sensitivity estimates showed significant variation (0.14-0.82). Studies using pixel distribution analysis (n = 3) showed substantially lower sensitivity estimates (0.14; 95% CI, 0.04-0.40) compared with the remaining 12 studies (0.81; 95% CI, 0.76-0.85). CT shows moderate sensitivity and excellent specificity for diagnosis of fat-poor AML in patients with renal masses. When methods other than pixel distribution analysis are used, better sensitivity can be achieved.

Exploring the impact of forcing error characteristics on physically based snow simulations within a global sensitivity analysis framework

NASA Astrophysics Data System (ADS)

Raleigh, M. S.; Lundquist, J. D.; Clark, M. P.

2015-07-01

Physically based models provide insights into key hydrologic processes but are associated with uncertainties due to deficiencies in forcing data, model parameters, and model structure. Forcing uncertainty is enhanced in snow-affected catchments, where weather stations are scarce and prone to measurement errors, and meteorological variables exhibit high variability. Hence, there is limited understanding of how forcing error characteristics affect simulations of cold region hydrology and which error characteristics are most important. Here we employ global sensitivity analysis to explore how (1) different error types (i.e., bias, random errors), (2) different error probability distributions, and (3) different error magnitudes influence physically based simulations of four snow variables (snow water equivalent, ablation rates, snow disappearance, and sublimation). We use the Sobol' global sensitivity analysis, which is typically used for model parameters but adapted here for testing model sensitivity to coexisting errors in all forcings. We quantify the Utah Energy Balance model's sensitivity to forcing errors with 1 840 000 Monte Carlo simulations across four sites and five different scenarios. Model outputs were (1) consistently more sensitive to forcing biases than random errors, (2) generally less sensitive to forcing error distributions, and (3) critically sensitive to different forcings depending on the relative magnitude of errors. For typical error magnitudes found in areas with drifting snow, precipitation bias was the most important factor for snow water equivalent, ablation rates, and snow disappearance timing, but other forcings had a more dominant impact when precipitation uncertainty was due solely to gauge undercatch. Additionally, the relative importance of forcing errors depended on the model output of interest. Sensitivity analysis can reveal which forcing error characteristics matter most for hydrologic modeling.

Tumor necrosis factor α level in cerebrospinal fluid for bacterial and aseptic meningitis: a diagnostic meta-analysis.

PubMed

Lv, S; Zhao, J; Zhang, J; Kwon, S; Han, M; Bian, R; Fu, H; Zhang, Y; Pan, H

2014-08-01

In our previous study, tumor necrosis factor α (TNF-α) was identified as an effective target for sepsis patients (Int J Clin Pract, 68, 2014, 520). TNF-α in cerebrospinal fluid (CSF) was also investigated for its utility in the differential diagnosis of bacterial and aseptic meningitis. However, there has been neither definite nor convincing evidence so far. Here the overall diagnostic accuracy of TNF-α in differentiation between bacterial and aseptic meningitis was evaluated through the meta-analysis of diagnostic tests. The sensitivity, specificity and other measures of accuracy were pooled using random effect models. Summary receiver operating characteristic curves were used to assess overall test performance. Publication bias was evaluated using funnel plots, and sensitivity analysis was also introduced. A total of 21 studies involving bacterial meningitis (678) and aseptic meningitis (694) involved a total of 1372 patients. The pooled sensitivity and specificity for the TNF-α test were 0.83 [95% confidence interval (CI) 0.80-0.86, I(2)  = 65.1] and 0.92 (95% CI 0.89-0.94, I(2)  = 61.8), respectively. The positive likelihood ratio was 12.05 (95% CI 7.41-19.60, I(2)  = 36.5), the negative likelihood ratio was 0.17 (95% CI 0.13-0.24, I(2)  = 59.4), and TNF-α was significantly associated with bacterial meningitis, with a diagnostic odds ratio of 49.84 (95% CI 28.53-87.06, I(2)  = 47.9). The overall accuracy of the TNF-α test was very high with the area under the curve 0.9317. Publication bias was absent, and sensitivity analysis suggested that our results were highly stable. Our meta-analysis suggested that TNF-α could be recommended as a useful marker for diagnosis of bacterial meningitis and differential diagnosis between bacterial and aseptic meningitis with high sensitivity and specificity. Thus, hospitals should be encouraged to conduct TNF-α tests in CSF after lumbar puncture. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

Automatic detection of DNA double strand breaks after irradiation using an γH2AX assay.

PubMed

Hohmann, Tim; Kessler, Jacqueline; Grabiec, Urszula; Bache, Matthias; Vordermark, Dyrk; Dehghani, Faramarz

2018-05-01

Radiation therapy belongs to the most common approaches for cancer therapy leading amongst others to DNA damage like double strand breaks (DSB). DSB can be used as a marker for the effect of radiation on cells. For visualization and assessing the extent of DNA damage the γH2AX foci assay is frequently used. The analysis of the γH2AX foci assay remains complicated as the number of γH2AX foci has to be counted. The quantification is mostly done manually, being time consuming and leading to person-dependent variations. Therefore, we present a method to automatically analyze the number of foci inside nuclei, facilitating and quickening the analysis of DSBs with high reliability in fluorescent images. First nuclei were detected in fluorescent images. Afterwards, the nuclei were analyzed independently from each other with a local thresholding algorithm. This approach allowed accounting for different levels of noise and detection of the foci inside the respective nucleus, using Hough transformation searching for circles. The presented algorithm was able to correctly classify most foci in cases of "high" and "average" image quality (sensitivity>0.8) with a low rate of false positive detections (positive predictive value (PPV)>0.98). In cases of "low" image quality the approach had a decreased sensitivity (0.7-0.9), depending on the manual control counter. The PPV remained high (PPV>0.91). Compared to other automatic approaches the presented algorithm had a higher sensitivity and PPV. The used automatic foci detection algorithm was capable of detecting foci with high sensitivity and PPV. Thus it can be used for automatic analysis of images of varying quality.

High-Speed Real-Time Resting-State fMRI Using Multi-Slab Echo-Volumar Imaging

PubMed Central

Posse, Stefan; Ackley, Elena; Mutihac, Radu; Zhang, Tongsheng; Hummatov, Ruslan; Akhtari, Massoud; Chohan, Muhammad; Fisch, Bruce; Yonas, Howard

2013-01-01

We recently demonstrated that ultra-high-speed real-time fMRI using multi-slab echo-volumar imaging (MEVI) significantly increases sensitivity for mapping task-related activation and resting-state networks (RSNs) compared to echo-planar imaging (Posse et al., 2012). In the present study we characterize the sensitivity of MEVI for mapping RSN connectivity dynamics, comparing independent component analysis (ICA) and a novel seed-based connectivity analysis (SBCA) that combines sliding-window correlation analysis with meta-statistics. This SBCA approach is shown to minimize the effects of confounds, such as movement, and CSF and white matter signal changes, and enables real-time monitoring of RSN dynamics at time scales of tens of seconds. We demonstrate highly sensitive mapping of eloquent cortex in the vicinity of brain tumors and arterio-venous malformations, and detection of abnormal resting-state connectivity in epilepsy. In patients with motor impairment, resting-state fMRI provided focal localization of sensorimotor cortex compared with more diffuse activation in task-based fMRI. The fast acquisition speed of MEVI enabled segregation of cardiac-related signal pulsation using ICA, which revealed distinct regional differences in pulsation amplitude and waveform, elevated signal pulsation in patients with arterio-venous malformations and a trend toward reduced pulsatility in gray matter of patients compared with healthy controls. Mapping cardiac pulsation in cortical gray matter may carry important functional information that distinguishes healthy from diseased tissue vasculature. This novel fMRI methodology is particularly promising for mapping eloquent cortex in patients with neurological disease, having variable degree of cooperation in task-based fMRI. In conclusion, ultra-high-real-time speed fMRI enhances the sensitivity of mapping the dynamics of resting-state connectivity and cerebro-vascular pulsatility for clinical and neuroscience research applications. PMID:23986677

Gene expression analysis using a highly sensitive DNA microarray for colorectal cancer screening.

PubMed

Koga, Yoshikatsu; Yamazaki, Nobuyoshi; Takizawa, Satoko; Kawauchi, Junpei; Nomura, Osamu; Yamamoto, Seiichiro; Saito, Norio; Kakugawa, Yasuo; Otake, Yosuke; Matsumoto, Minori; Matsumura, Yasuhiro

2014-01-01

Half of all patients with small, right-sided, non-metastatic colorectal cancer (CRC) have negative results for the fecal occult blood test (FOBT). In the present study, the usefulness of CRC screening with a highly sensitive DNA microarray was evaluated in comparison with that by FOBT using fecal samples. A total of 53 patients with CRC and 61 healthy controls were divided into "training" and "validation sets". For the gene profiling, total RNA extracted from 0.5 g of feces was hybridized to a highly sensitive DNA chip. The expressions of 43 genes were significantly higher in the patients with CRC than in healthy controls (p<0.05). In the training set, the sensitivity and specificity of the DNA chip assay using six genes were 85.4% and 85.2%, respectively. On the other hand, in the validation set, the sensitivity and specificity of the DNA chip assay were 85.2% and 85.7%, respectively. The sensitivities of the DNA chip assay were higher than those of FOBT in cases of the small, right-sided, early-CRC, tumor invading up to the muscularis propria (i.e. surface tumor) subgroups. In particular, the sensitivities of the DNA chip assay in the surface tumor and early-CRC subgroups were significantly higher than those of FOBT (p=0.023 and 0.019, respectively.). Gene profiling assay using a highly sensitive DNA chip was more effective than FOBT at detecting patients with small, right-sided, surface tumor, and early-stage CRC.

Interpersonal sensitivity and functioning impairment in youth at ultra-high risk for psychosis.

PubMed

Masillo, A; Valmaggia, L R; Saba, R; Brandizzi, M; Lindau, J F; Solfanelli, A; Curto, M; Narilli, F; Telesforo, L; Kotzalidis, G D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

2016-01-01

A personality trait that often elicits poor and uneasy interpersonal relationships is interpersonal sensitivity. The aim of the present study was to explore the relationship between interpersonal sensitivity and psychosocial functioning in individuals at ultra-high risk for psychosis as compared to help-seeking individuals who screened negative for an ultra-high risk of psychosis. A total sample of 147 adolescents and young adult who were help seeking for emerging mental health problems participated in the study. The sample was divided into two groups: 39 individuals who met criteria for an ultra-high-risk mental state (UHR), and 108 (NS). The whole sample completed the Interpersonal Sensitivity Measure (IPSM) and the Global Functioning: Social and Role Scale (GF:SS; GF:RS). Mediation analysis was used to explore whether attenuated negative symptoms mediated the relationship between interpersonal sensitivity and social functioning. Individuals with UHR state showed higher IPSM scores and lower GF:SS and GF:RS scores than NS participants. A statistically negative significant correlation between two IPSM subscales (Interpersonal Awareness and Timidity) and GF:SS was found in both groups. Our results also suggest that the relationship between the aforementioned aspects of interpersonal sensitivity and social functioning was not mediated by negative prodromal symptoms. This study suggests that some aspects of interpersonal sensitivity were associated with low level of social functioning. Assessing and treating interpersonal sensitivity may be a promising therapeutic target to improve social functioning in young help-seeking individuals.

Development of techniques for the analysis of isoflavones in soy foods and nutraceuticals.

PubMed

Dentith, Susan; Lockwood, Brian

2008-05-01

For over 20 years, soy isoflavones have been investigated for their ability to prevent a wide range of cancers and cardiovascular problems, and numerous other disease states. This research is underpinned by the ability of researchers to analyse isoflavones in various forms in a range of raw materials and biological fluids. This review summarizes the techniques recently used in their analysis. The speed of high performance liquid chromatography analysis has been improved, allowing analysis of more samples, and increasing the sensitivity of detection techniques allows quantification of isoflavones down to nanomoles per litre levels in biological fluids. The combination of high-performance liquid chromatography with immunoassay has allowed identification and estimation of low-level soy isoflavones. The use of soy isoflavone supplements has shown an increase in their circulating levels in plasma and urine, aiding investigation of their biological effects. The significance of the metabolite equol has spurned research into new areas, and recently the specific enantiomers have been studied. High-performance liquid chromatography, capillary electrophoresis and gas chromatography are widely used with a range of detection systems. Increasingly, immunoassay is being used because of its high sensitivity and low cost.

High-throughput determination of vancomycin in human plasma by a cost-effective system of two-dimensional liquid chromatography.

PubMed

Sheng, Yanghao; Zhou, Boting

2017-05-26

Therapeutic drug monitoring (TDM) is one of the most important services of clinical laboratories. Two main techniques are commonly used: the immunoassay and chromatography method. We have developed a cost-effective system of two-dimensional liquid chromatography with ultraviolet detection (2D-LC-UV) for high-throughput determination of vancomycin in human plasma that combines the automation and low start-up costs of the immunoassay with the high selectivity and sensitivity of the liquid chromatography coupled with mass spectrometric detection without incurring their disadvantages, achieving high cost-effectiveness. This 2D-LC system offers a large volume injection to provide sufficient sensitivity and uses simulated gradient peak compression technology to control peak broadening and to improve peak shape. A middle column was added to reduce the analysis cycle time and make it suitable for high-throughput routine clinical assays. The analysis cycle time was 4min and the peak width was 0.8min. Compared with other chromatographic methods that have been developed, the analysis cycle time and peak width for vancomycin was reduced significantly. The lower limit of quantification was 0.20μg/mL for vancomycin, which is the same as certain LC-MS/MS methods that have been recently developed and validated. The method is rapid, automated, and low-cost and has high selectivity and sensitivity for the quantification of vancomycin in human plasma, thus making it well-suited for use in hospital clinical laboratories. Copyright © 2017 Elsevier B.V. All rights reserved.

Value of high-sensitivity C-reactive protein assays in predicting atrial fibrillation recurrence: a systematic review and meta-analysis

PubMed Central

Yo, Chia-Hung; Lee, Si-Huei; Chang, Shy-Shin; Lee, Matthew Chien-Hung; Lee, Chien-Chang

2014-01-01

Objectives We performed a systematic review and meta-analysis of studies on high-sensitivity C-reactive protein (hs-CRP) assays to see whether these tests are predictive of atrial fibrillation (AF) recurrence after cardioversion. Design Systematic review and meta-analysis. Data sources PubMed, EMBASE and Cochrane databases as well as a hand search of the reference lists in the retrieved articles from inception to December 2013. Study eligibility criteria This review selected observational studies in which the measurements of serum CRP were used to predict AF recurrence. An hs-CRP assay was defined as any CRP test capable of measuring serum CRP to below 0.6 mg/dL. Primary and secondary outcome measures We summarised test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. Meta-regression analysis was performed to explore the source of heterogeneity. Results We included nine qualifying studies comprising a total of 347 patients with AF recurrence and 335 controls. A CRP level higher than the optimal cut-off point was an independent predictor of AF recurrence after cardioversion (summary adjusted OR: 3.33; 95% CI 2.10 to 5.28). The estimated pooled sensitivity and specificity for hs-CRP was 71.0% (95% CI 63% to 78%) and 72.0% (61% to 81%), respectively. Most studies used a CRP cut-off point of 1.9 mg/L to predict long-term AF recurrence (77% sensitivity, 65% specificity), and 3 mg/L to predict short-term AF recurrence (73% sensitivity, 71% specificity). Conclusions hs-CRP assays are moderately accurate in predicting AF recurrence after successful cardioversion. PMID:24556243

A Versatile PDMS/Paper Hybrid Microfluidic Platform for Sensitive Infectious Disease Diagnosis

PubMed Central

2015-01-01

Bacterial meningitis is a serious health concern worldwide. Given that meningitis can be fatal and many meningitis cases occurred in high-poverty areas, a simple, low-cost, highly sensitive method is in great need for immediate and early diagnosis of meningitis. Herein, we report a versatile and cost-effective polydimethylsiloxane (PDMS)/paper hybrid microfluidic device integrated with loop-mediated isothermal amplification (LAMP) for the rapid, sensitive, and instrument-free detection of the main meningitis-causing bacteria, Neisseria meningitidis (N. meningitidis). The introduction of paper into the microfluidic device for LAMP reactions enables stable test results over a much longer period of time than a paper-free microfluidic system. This hybrid system also offers versatile functions, by providing not only on-site qualitative diagnostic analysis (i.e., a yes or no answer), but also confirmatory testing and quantitative analysis in laboratory settings. The limit of detection of N. meningitidis is about 3 copies per LAMP zone within 45 min, close to single-bacterium detection sensitivity. In addition, we have achieved simple pathogenic microorganism detection without a laborious sample preparation process and without the use of centrifuges. This low-cost hybrid microfluidic system provides a simple and highly sensitive approach for fast instrument-free diagnosis of N. meningitidis in resource-limited settings. This versatile PDMS/paper microfluidic platform has great potential for the point of care (POC) diagnosis of a wide range of infectious diseases, especially for developing nations. PMID:25019330

Compliance and stress sensitivity of spur gear teeth

NASA Technical Reports Server (NTRS)

Cornell, R. W.

1983-01-01

The magnitude and variation of tooth pair compliance with load position affects the dynamics and loading significantly, and the tooth root stressing per load varies significantly with load position. Therefore, the recently developed time history, interactive, closed form solution for the dynamic tooth loads for both low and high contact ratio spur gears was expanded to include improved and simplified methods for calculating the compliance and stress sensitivity for three involute tooth forms as a function of load position. The compliance analysis has an improved fillet/foundation. The stress sensitivity analysis is a modified version of the Heywood method but with an improvement in the magnitude and location of the peak stress in the fillet. These improved compliance and stress sensitivity analyses are presented along with their evaluation using test, finite element, and analytic transformation results, which showed good agreement.

Projected Changes in Hydrological Extremes in a Cold Region Watershed: Sensitivity of Results to Statistical Methods of Analysis

NASA Astrophysics Data System (ADS)

Dibike, Y. B.; Eum, H. I.; Prowse, T. D.

2017-12-01

Flows originating from alpine dominated cold region watersheds typically experience extended winter low flows followed by spring snowmelt and summer rainfall driven high flows. In a warmer climate, there will be temperature- induced shift in precipitation from snow towards rain as well as changes in snowmelt timing affecting the frequency of extreme high and low flow events which could significantly alter ecosystem services. This study examines the potential changes in the frequency and severity of hydrologic extremes in the Athabasca River watershed in Alberta, Canada based on the Variable Infiltration Capacity (VIC) hydrologic model and selected and statistically downscaled climate change scenario data from the latest Coupled Model Intercomparison Project (CMIP5). The sensitivity of these projected changes is also examined by applying different extreme flow analysis methods. The hydrological model projections show an overall increase in mean annual streamflow in the watershed and a corresponding shift in the freshet timing to earlier period. Most of the streams are projected to experience increases during the winter and spring seasons and decreases during the summer and early fall seasons, with an overall projected increases in extreme high flows, especially for low frequency events. While the middle and lower parts of the watershed are characterised by projected increases in extreme high flows, the high elevation alpine region is mainly characterised by corresponding decreases in extreme low flow events. However, the magnitude of projected changes in extreme flow varies over a wide range, especially for low frequent events, depending on the climate scenario and period of analysis, and sometimes in a nonlinear way. Nonetheless, the sensitivity of the projected changes to the statistical method of analysis is found to be relatively small compared to the inter-model variability.

Three Minute Method for Amino Acid Analysis by UHPLC and high resolution quadrupole orbitrap mass spectrometry

PubMed Central

Nemkov, Travis; D'Alessandro, Angelo; Hansen, Kirk C.

2015-01-01

Amino acid analysis is a powerful bioanalytical technique for many biomedical research endeavors, including cancer, emergency medicine, nutrition and neuroscience research. In the present study, we present a three minute analytical method for underivatized amino acid analysis that employs ultra-high performance liquid chromatography and high resolution quadrupole orbitrap mass spectrometry. This method has demonstrated linearity (mM to nM range), reproducibility (intra-day<5%, inter-day<20%), sensitivity (low fmol) and selectivity. Here, we illustrate the rapidity and accuracy of the method through comparison with conventional liquid chromatography-mass spectrometry methods. We further demonstrate the robustness and sensitivity of this method on a diverse range of biological matrices. Using this method we were able to selectively discriminate murine pancreatic cancer cells with and without knocked down expression of Hypoxia Inducible Factor 1α; plasma, lymph and bronchioalveolar lavage fluid samples from control versus hemorrhaged rats; and muscle tissue samples harvested from rats subjected to both low fat and high fat diets. Furthermore, we were able to exploit the sensitivity of the method to detect and quantify the release of glutamate from sparsely isolated murine taste buds. Spiked in light or heavy standards (13C6-arginine, 13C6-lysine, 13C515N2-glutamine) or xenometabolites were used to determine coefficient of variations, confirm linearity of relative quantitation in four different matrices, and overcome matrix effects for absolute quantitation. The presented method enables high-throughput analysis of low abundance samples requiring only one percent of the material extracted from 100,000 cells, 10 μl of biological fluid, or 2 mg of muscle tissue. PMID:26058356

Sensitivities to Early Exchange in Synchronous Computer-Supported Collaborative Learning (CSCL) Groups

ERIC Educational Resources Information Center

Kapur, Manu; Voiklis, John; Kinzer, Charles K.

2008-01-01

This study reports the impact of high sensitivity to early exchange in 11th-grade, CSCL triads solving well- and ill-structured problems in Newtonian Kinematics. A mixed-method analysis of the evolution of participation inequity (PI) in group discussions suggested that participation levels tended to get locked-in relatively early on in the…

Meta-Analysis of the Relations of Anxiety Sensitivity to the Depressive and Anxiety Disorders

ERIC Educational Resources Information Center

Naragon-Gainey, Kristin

2010-01-01

There is a substantial literature relating the personality trait "anxiety sensitivity" (AS; tendency to fear anxiety-related sensations) and its lower order dimensions to the mood and anxiety (i.e., internalizing) disorders. However, particularly given the disorders' high comorbidity rates, it remains unclear whether AS is broadly related to these…

Sensitive and comprehensive analysis of O-glycosylation in biotherapeutics: a case study of novel erythropoiesis stimulating protein.

PubMed

Kim, Unyong; Oh, Myung Jin; Seo, Youngsuk; Jeon, Yinae; Eom, Joon-Ho; An, Hyun Joo

2017-09-01

Glycosylation of recombinant human erythropoietins (rhEPOs) is significantly associated with drug's quality and potency. Thus, comprehensive characterization of glycosylation is vital to assess the biotherapeutic quality and establish the equivalency of biosimilar rhEPOs. However, current glycan analysis mainly focuses on the N-glycans due to the absence of analytical tools to liberate O-glycans with high sensitivity. We developed selective and sensitive method to profile native O-glycans on rhEPOs. O-glycosylation on rhEPO including O-acetylation on a sialic acid was comprehensively characterized. Details such as O-glycan structure and O-acetyl-modification site were obtained from tandem MS. This method may be applied to QC and batch analysis of not only rhEPOs but also other biotherapeutics bearing multiple O-glycosylations.

Comparison of loop-mediated isothermal amplification assay and smear microscopy with culture for the diagnostic accuracy of tuberculosis.

PubMed

Gelaw, Baye; Shiferaw, Yitayal; Alemayehu, Marta; Bashaw, Abate Assefa

2017-01-17

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading causes of death from infectious diseases worldwide. Sputum smear microscopy remains the most widely available pulmonary TB diagnostic tool particularly in resource limited settings. A highly sensitive diagnostic with minimal infrastructure, cost and training is required. Hence, we assessed the diagnostic performance of Loop-mediated isothermal amplification (LAMP) assay in detecting M.tuberculosis infection in sputum sample compared to LED fluorescent smear microscopy and culture. A cross-sectional study was conducted at the University of Gondar Hospital from June 01, 2015 to August 30, 2015. Pulmonary TB diagnosis using sputum LED fluorescence smear microscopy, TB-LAMP assay and culture were done. A descriptive analysis was used to determine demographic characteristics of the study participants. Analysis of sensitivity and specificity for smear microscopy and TB-LAMP compared with culture as a reference test was performed. Cohen's kappa was calculated as a measure of agreement between the tests. A total of 78 pulmonary presumptive TB patients sputum sample were analyzed. The overall sensitivity and specificity of LAMP were 75 and 98%, respectively. Among smear negative sputum samples, 33.3% sensitivity and 100% specificity of LAMP were observed. Smear microscopy showed 78.6% sensitivity and 98% specificity. LAMP and smear in series had sensitivity of 67.8% and specificity of 100%. LAMP and smear in parallel had sensitivity of 85.7% and specificity of 96%. The agreement between LAMP and fluorescent smear microscopy tests was very good (κ = 0.83, P-value ≤0.0001). TB-LAMP showed similar specificity but a slightly lower sensitivity with LED fluorescence microscopy. The specificity of LAMP and smear microscopy in series was high. The sensitivity of LAMP was insufficient for smear negative sputum samples.

Sensitivity Analysis of Mechanical Parameters of Different Rock Layers to the Stability of Coal Roadway in Soft Rock Strata

PubMed Central

Zhao, Zeng-hui; Wang, Wei-ming; Gao, Xin; Yan, Ji-xing

2013-01-01

According to the geological characteristics of Xinjiang Ili mine in western area of China, a physical model of interstratified strata composed of soft rock and hard coal seam was established. Selecting the tunnel position, deformation modulus, and strength parameters of each layer as influencing factors, the sensitivity coefficient of roadway deformation to each parameter was firstly analyzed based on a Mohr-Columb strain softening model and nonlinear elastic-plastic finite element analysis. Then the effect laws of influencing factors which showed high sensitivity were further discussed. Finally, a regression model for the relationship between roadway displacements and multifactors was obtained by equivalent linear regression under multiple factors. The results show that the roadway deformation is highly sensitive to the depth of coal seam under the floor which should be considered in the layout of coal roadway; deformation modulus and strength of coal seam and floor have a great influence on the global stability of tunnel; on the contrary, roadway deformation is not sensitive to the mechanical parameters of soft roof; roadway deformation under random combinations of multi-factors can be deduced by the regression model. These conclusions provide theoretical significance to the arrangement and stability maintenance of coal roadway. PMID:24459447

Highly sensitive detection using microring resonator and nanopores

NASA Astrophysics Data System (ADS)

Bougot-Robin, K.; Hoste, J. W.; Le Thomas, N.; Bienstman, P.; Edel, J. B.

2016-04-01

One of the most significant challenges facing physical and biological scientists is the accurate detection and identification of single molecules in free-solution environments. The ability to perform such sensitive and selective measurements opens new avenues for a large number of applications in biological, medical and chemical analysis, where small sample volumes and low analyte concentrations are the norm. Access to information at the single or few molecules scale is rendered possible by a fine combination of recent advances in technologies. We propose a novel detection method that combines highly sensitive label-free resonant sensing obtained with high-Q microcavities and position control in nanoscale pores (nanopores). In addition to be label-free and highly sensitive, our technique is immobilization free and does not rely on surface biochemistry to bind probes on a chip. This is a significant advantage, both in term of biology uncertainties and fewer biological preparation steps. Through combination of high-Q photonic structures with translocation through nanopore at the end of a pipette, or through a solid-state membrane, we believe significant advances can be achieved in the field of biosensing. Silicon microrings are highly advantageous in term of sensitivity, multiplexing, and microfabrication and are chosen for this study. In term of nanopores, we both consider nanopore at the end of a nanopipette, with the pore being approach from the pipette with nanoprecise mechanical control. Alternatively, solid state nanopores can be fabricated through a membrane, supporting the ring. Both configuration are discussed in this paper, in term of implementation and sensitivity.

High resolution melting analysis for epidermal growth factor receptor mutations in formalin-fixed paraffin-embedded tissue and plasma free DNA from non-small cell lung cancer patients.

PubMed

Jing, Chang-Wen; Wang, Zhuo; Cao, Hai-Xia; Ma, Rong; Wu, Jian-Zhong

2014-01-01

The aim of the research was to explore a cost effective, fast, easy to perform, and sensitive method for epidermal growth factor receptor (EGFR) mutation testing. High resolution melting analysis (HRM) was introduced to evaluate the efficacy of the analysis for dectecting EGFR mutations in exons 18 to 21 using formalin-fixed paraffin-embedded (FFPE) tissues and plasma free DNA from 120 patients. The total EGFR mutation rate was 37.5% (45/120) detected by direct sequencing. There were 48 mutations in 120 FFPE tissues assessed by HRM. For plasma free DNA, the EGFR mutation rate was 25.8% (31/120). The sensitivity of HRM assays in FFPE samples was 100% by HRM. There was a low false-positive mutation rate but a high false-negative rate in plasma free DNA detected by HRM. Our results show that HRM analysis has the advantage of small tumor sample need. HRM applied with plasma free DNA showed a high false-negative rate but a low false-positive rate. Further research into appropriate methods and analysis needs to be performed before HRM for plasma free DNA could be accepted as an option in diagnostic or screening settings.

13C labeling analysis of sugars by high resolution-mass spectrometry for metabolic flux analysis.

PubMed

Acket, Sébastien; Degournay, Anthony; Merlier, Franck; Thomasset, Brigitte

2017-06-15

Metabolic flux analysis is particularly complex in plant cells because of highly compartmented metabolism. Analysis of free sugars is interesting because it provides data to define fluxes around hexose, pentose, and triose phosphate pools in different compartment. In this work, we present a method to analyze the isotopomer distribution of free sugars labeled with carbon 13 using a liquid chromatography-high resolution mass spectrometry, without derivatized procedure, adapted for Metabolic flux analysis. Our results showed a good sensitivity, reproducibility and better accuracy to determine isotopic enrichments of free sugars compared to our previous methods [5, 6]. Copyright © 2017 Elsevier Inc. All rights reserved.

Gold nanoparticle-sensitized quartz crystal microbalance sensor for rapid and highly selective determination of Cu(II) ions.

PubMed

Jin, Yulong; Huang, Yanyan; Liu, Guoquan; Zhao, Rui

2013-09-21

A novel quartz crystal microbalance (QCM) sensor for rapid, highly selective and sensitive detection of copper ions was developed. As a signal amplifier, gold nanoparticles (Au NPs) were self-assembled onto the surface of the sensor. A simple dip-and-dry method enabled the whole detection procedure to be accomplished within 20 min. High selectivity of the sensor towards copper ions is demonstrated by both individual and coexisting assays with interference ions. This gold nanoparticle mediated amplification allowed a detection limit down to 3.1 μM. Together with good repeatability and regeneration, the QCM sensor was also applied to the analysis of copper contamination in drinking water. This work provides a flexible method for fabricating QCM sensors for the analysis of important small molecules in environmental and biological samples.

A novel quantitative analysis method of three-dimensional fluorescence spectra for vegetable oils contents in edible blend oil

NASA Astrophysics Data System (ADS)

Xu, Jing; Wang, Yu-Tian; Liu, Xiao-Fei

2015-04-01

Edible blend oil is a mixture of vegetable oils. Eligible blend oil can meet the daily need of two essential fatty acids for human to achieve the balanced nutrition. Each vegetable oil has its different composition, so vegetable oils contents in edible blend oil determine nutritional components in blend oil. A high-precision quantitative analysis method to detect the vegetable oils contents in blend oil is necessary to ensure balanced nutrition for human being. Three-dimensional fluorescence technique is high selectivity, high sensitivity, and high-efficiency. Efficiency extraction and full use of information in tree-dimensional fluorescence spectra will improve the accuracy of the measurement. A novel quantitative analysis is proposed based on Quasi-Monte-Carlo integral to improve the measurement sensitivity and reduce the random error. Partial least squares method is used to solve nonlinear equations to avoid the effect of multicollinearity. The recovery rates of blend oil mixed by peanut oil, soybean oil and sunflower are calculated to verify the accuracy of the method, which are increased, compared the linear method used commonly for component concentration measurement.

Preventive behaviors by the level of perceived infection sensitivity during the Korea outbreak of Middle East Respiratory Syndrome in 2015.

PubMed

Lee, Soon Young; Yang, Hee Jeong; Kim, Gawon; Cheong, Hae-Kwan; Choi, Bo Youl

2016-01-01

This study was performed to investigate the relationship between community residents' infection sensitivity and their levels of preventive behaviors during the 2015 Middle East Respiratory Syndrome (MERS) outbreak in Korea. Seven thousands two hundreds eighty one participants from nine areas in Gyeonggi-do including Pyeongtaek, the origin of the outbreak in 2015 agreed to participate in the survey and the data from 6,739 participants were included in the final analysis. The data on the perceived infection sensitivity were subjected to cluster analysis. The levels of stress, reliability/practice of preventive behaviors, hand washing practice and policy credibility during the outbreak period were analyzed for each cluster. Cluster analysis of infection sensitivity due to the MERS outbreak resulted in classification of participants into four groups: the non-sensitive group (14.5%), social concern group (17.4%), neutral group (29.1%), and overall sensitive group (39.0%). A logistic regression analysis found that the overall sensitive group with high sensitivity had higher stress levels (17.80; 95% confidence interval [CI], 13.77 to 23.00), higher reliability on preventive behaviors (5.81; 95% CI, 4.84 to 6.98), higher practice of preventive behaviors (4.53; 95% CI, 3.83 to 5.37) and higher practice of hand washing (2.71; 95% CI, 2.13 to 3.43) during the outbreak period, compared to the non-sensitive group. Infection sensitivity of community residents during the MERS outbreak correlated with gender, age, occupation, and health behaviors. When there is an outbreak in the community, there is need to maintain a certain level of sensitivity while reducing excessive stress, as well as promote the practice of preventive behaviors among local residents. In particular, target groups need to be notified and policies need to be established with a consideration of the socio-demographic characteristics of the community.

Sensitive Quantification of Cannabinoids in Milk by Alkaline Saponification-Solid Phase Extraction Combined with Isotope Dilution UPLC-MS/MS.

PubMed

Wei, Binnian; McGuffey, James E; Blount, Benjamin C; Wang, Lanqing

2016-01-01

Maternal exposure to marijuana during the lactation period-either active or passive-has prompted concerns about transmission of cannabinoids to breastfed infants and possible subsequent adverse health consequences. Assessing these health risks requires a sensitive analytical approach that is able to quantitatively measure trace-level cannabinoids in breast milk. Here, we describe a saponification-solid phase extraction approach combined with ultra-high-pressure liquid chromatography-tandem mass spectrometry for simultaneously quantifying Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) in breast milk. We demonstrate for the first time that constraints on sensitivity can be overcome by utilizing alkaline saponification of the milk samples. After extensively optimizing the saponification procedure, the validated method exhibited limits of detections of 13, 4, and 66 pg/mL for THC, CBN, and CBD, respectively. Notably, the sensitivity achieved was significantly improved, for instance, the limits of detection for THC is at least 100-fold more sensitive compared to that previously reported in the literature. This is essential for monitoring cannabinoids in breast milk resulting from passive or nonrecent active maternal exposure. Furthermore, we simultaneously acquired multiple reaction monitoring transitions for 12 C- and 13 C-analyte isotopes. This combined analysis largely facilitated data acquisition by reducing the repetitive analysis rate for samples exceeding the linear limits of 12 C-analytes. In addition to high sensitivity and broad quantitation range, this method delivers excellent accuracy (relative error within ±10%), precision (relative standard deviation <10%), and efficient analysis. In future studies, we expect this method to play a critical role in assessing infant exposure to cannabinoids through breastfeeding.

Design and numerical analysis of highly sensitive Au-MoS2-graphene based hybrid surface plasmon resonance biosensor

NASA Astrophysics Data System (ADS)

Rahman, M. Saifur; Anower, Md. Shamim; Hasan, Md. Rabiul; Hossain, Md. Biplob; Haque, Md. Ismail

2017-08-01

We demonstrate a highly sensitive Au-MoS2-Graphene based hybrid surface plasmon resonance (SPR) biosensor for the detection of DNA hybridization. The performance parameters of the proposed sensor are investigated in terms of sensitivity, detection accuracy and quality factor at operating wavelength of 633 nm. We observed in the numerical study that sensitivity can be greatly increased by adding MoS2 layer in the middle of a Graphene-on-Au layer. It is shown that by using single layer of MoS2 in between gold and graphene layer, the proposed biosensor exhibits simultaneously high sensitivity of 87.8 deg/RIU, high detection accuracy of 1.28 and quality factor of 17.56 with gold layer thickness of 50 nm. This increased performance is due to the absorption ability and optical characteristics of graphene biomolecules and high fluorescence quenching ability of MoS2. On the basis of changing in SPR angle and minimum reflectance, the proposed sensor can sense nucleotides bonding happened between double-stranded DNA (dsDNA) helix structures. Therefore, this sensor can successfully detect the hybridization of target DNAs to the probe DNAs pre-immobilized on the Au-MoS2-Graphene hybrid with capability of distinguishing single-base mismatch.

An optimized rapid bisulfite conversion method with high recovery of cell-free DNA.

PubMed

Yi, Shaohua; Long, Fei; Cheng, Juanbo; Huang, Daixin

2017-12-19

Methylation analysis of cell-free DNA is a encouraging tool for tumor diagnosis, monitoring and prognosis. Sensitivity of methylation analysis is a very important matter due to the tiny amounts of cell-free DNA available in plasma. Most current methods of DNA methylation analysis are based on the difference of bisulfite-mediated deamination of cytosine between cytosine and 5-methylcytosine. However, the recovery of bisulfite-converted DNA based on current methods is very poor for the methylation analysis of cell-free DNA. We optimized a rapid method for the crucial steps of bisulfite conversion with high recovery of cell-free DNA. A rapid deamination step and alkaline desulfonation was combined with the purification of DNA on a silica column. The conversion efficiency and recovery of bisulfite-treated DNA was investigated by the droplet digital PCR. The optimization of the reaction results in complete cytosine conversion in 30 min at 70 °C and about 65% of recovery of bisulfite-treated cell-free DNA, which is higher than current methods. The method allows high recovery from low levels of bisulfite-treated cell-free DNA, enhancing the analysis sensitivity of methylation detection from cell-free DNA.

Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosal associated lymphoid tissues from elk by real time quaking-induced conversion

USGS Publications Warehouse

Haley, Nicholas J.; Siepker, Chris; Hoon-Hanks , Laura L.; Mitchell, Gordon; Walter, W. David; Manca, Matteo; Monello, Ryan J.; Powers, Jenny G.; Wild, Margaret A.; Hoover, Edward A.; Caughey, Byron; Richt, Jürgen a.; Fenwick, B.W.

2016-01-01

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.

Small-volume cavity cell using hollow optical fiber for Raman scattering-based gas detection

NASA Astrophysics Data System (ADS)

Okita, Y.; Katagiri, T.; Matsuura, Y.

2011-03-01

The highly sensitive Raman cell based on the hollow optical fiber that is suitable for the real-time breath analysis is reported. Hollow optical fiber with inner coating of silver is used as a gas cell and a Stokes light collector. A very small cell whose volume is only 0.4 ml or less enables fast response and real-time measurement of trace gases. To increase the sensitivity the cell is arranged in a cavity which includes of a long-pass filter and a high reflective mirror. The sensitivity of the cavity cell is more than two times higher than that of the cell without cavity.

Ion-Sensitive Field-Effect Transistor for Biological Sensing

PubMed Central

Lee, Chang-Soo; Kim, Sang Kyu; Kim, Moonil

2009-01-01

In recent years there has been great progress in applying FET-type biosensors for highly sensitive biological detection. Among them, the ISFET (ion-sensitive field-effect transistor) is one of the most intriguing approaches in electrical biosensing technology. Here, we review some of the main advances in this field over the past few years, explore its application prospects, and discuss the main issues, approaches, and challenges, with the aim of stimulating a broader interest in developing ISFET-based biosensors and extending their applications for reliable and sensitive analysis of various biomolecules such as DNA, proteins, enzymes, and cells. PMID:22423205

Novel approach based on one-tube nested PCR and a lateral flow strip for highly sensitive diagnosis of tuberculous meningitis

PubMed Central

Sun, Yajuan; Chen, Jiajun; Li, Jia; Xu, Yawei; Jin, Hui; Xu, Na; Yin, Rui

2017-01-01

Rapid and sensitive detection of Mycobacterium tuberculosis (M. Tb) in cerebrospinal fluid is crucial in the diagnosis of tuberculous meningitis (TBM), but conventional diagnostic technologies have limited sensitivity and specificity or are time-consuming. In this work, a novel, highly sensitive molecular diagnostic method, one-tube nested PCR-lateral flow strip test (OTNPCR-LFST), was developed for detecting M. tuberculosis. This one-tube nested PCR maintains the sensitivity of conventional two-step nested PCR and reduces both the chance of cross-contamination and the time required for analysis. The PCR product was detected by a lateral flow strip assay, which provided a basis for migration of the test to a point-of-care (POC) microfluidic format. The developed assay had an improved sensitivity compared with traditional PCR, and the limit of detection was up to 1 fg DNA isolated from M. tuberculosis. The assay was also specific for M. tuberculosis, and no cross-reactions were found in other non-target bacteria. The application of this technique to clinical samples was successfully evaluated, and OTNPCR-LFST showed 89% overall sensitivity and 100% specificity for TBM patients. This one-tube nested PCR-lateral flow strip assay is useful for detecting M. tuberculosis in TBM due to its rapidity, high sensitivity and simple manipulation. PMID:29084241

Line-Focused Optical Excitation of Parallel Acoustic Focused Sample Streams for High Volumetric and Analytical Rate Flow Cytometry.

PubMed

Kalb, Daniel M; Fencl, Frank A; Woods, Travis A; Swanson, August; Maestas, Gian C; Juárez, Jaime J; Edwards, Bruce S; Shreve, Andrew P; Graves, Steven W

2017-09-19

Flow cytometry provides highly sensitive multiparameter analysis of cells and particles but has been largely limited to the use of a single focused sample stream. This limits the analytical rate to ∼50K particles/s and the volumetric rate to ∼250 μL/min. Despite the analytical prowess of flow cytometry, there are applications where these rates are insufficient, such as rare cell analysis in high cellular backgrounds (e.g., circulating tumor cells and fetal cells in maternal blood), detection of cells/particles in large dilute samples (e.g., water quality, urine analysis), or high-throughput screening applications. Here we report a highly parallel acoustic flow cytometer that uses an acoustic standing wave to focus particles into 16 parallel analysis points across a 2.3 mm wide optical flow cell. A line-focused laser and wide-field collection optics are used to excite and collect the fluorescence emission of these parallel streams onto a high-speed camera for analysis. With this instrument format and fluorescent microsphere standards, we obtain analysis rates of 100K/s and flow rates of 10 mL/min, while maintaining optical performance comparable to that of a commercial flow cytometer. The results with our initial prototype instrument demonstrate that the integration of key parallelizable components, including the line-focused laser, particle focusing using multinode acoustic standing waves, and a spatially arrayed detector, can increase analytical and volumetric throughputs by orders of magnitude in a compact, simple, and cost-effective platform. Such instruments will be of great value to applications in need of high-throughput yet sensitive flow cytometry analysis.

Integrated multidisciplinary design optimization using discrete sensitivity analysis for geometrically complex aeroelastic configurations

NASA Astrophysics Data System (ADS)

Newman, James Charles, III

1997-10-01

The first two steps in the development of an integrated multidisciplinary design optimization procedure capable of analyzing the nonlinear fluid flow about geometrically complex aeroelastic configurations have been accomplished in the present work. For the first step, a three-dimensional unstructured grid approach to aerodynamic shape sensitivity analysis and design optimization has been developed. The advantage of unstructured grids, when compared with a structured-grid approach, is their inherent ability to discretize irregularly shaped domains with greater efficiency and less effort. Hence, this approach is ideally suited for geometrically complex configurations of practical interest. In this work the time-dependent, nonlinear Euler equations are solved using an upwind, cell-centered, finite-volume scheme. The discrete, linearized systems which result from this scheme are solved iteratively by a preconditioned conjugate-gradient-like algorithm known as GMRES for the two-dimensional cases and a Gauss-Seidel algorithm for the three-dimensional; at steady-state, similar procedures are used to solve the accompanying linear aerodynamic sensitivity equations in incremental iterative form. As shown, this particular form of the sensitivity equation makes large-scale gradient-based aerodynamic optimization possible by taking advantage of memory efficient methods to construct exact Jacobian matrix-vector products. Various surface parameterization techniques have been employed in the current study to control the shape of the design surface. Once this surface has been deformed, the interior volume of the unstructured grid is adapted by considering the mesh as a system of interconnected tension springs. Grid sensitivities are obtained by differentiating the surface parameterization and the grid adaptation algorithms with ADIFOR, an advanced automatic-differentiation software tool. To demonstrate the ability of this procedure to analyze and design complex configurations of practical interest, the sensitivity analysis and shape optimization has been performed for several two- and three-dimensional cases. In twodimensions, an initially symmetric NACA-0012 airfoil and a high-lift multielement airfoil were examined. For the three-dimensional configurations, an initially rectangular wing with uniform NACA-0012 cross-sections was optimized; in addition, a complete Boeing 747-200 aircraft was studied. Furthermore, the current study also examines the effect of inconsistency in the order of spatial accuracy between the nonlinear fluid and linear shape sensitivity equations. The second step was to develop a computationally efficient, high-fidelity, integrated static aeroelastic analysis procedure. To accomplish this, a structural analysis code was coupled with the aforementioned unstructured grid aerodynamic analysis solver. The use of an unstructured grid scheme for the aerodynamic analysis enhances the interaction compatibility with the wing structure. The structural analysis utilizes finite elements to model the wing so that accurate structural deflections may be obtained. In the current work, parameters have been introduced to control the interaction of the computational fluid dynamics and structural analyses; these control parameters permit extremely efficient static aeroelastic computations. To demonstrate and evaluate this procedure, static aeroelastic analysis results for a flexible wing in low subsonic, high subsonic (subcritical), transonic (supercritical), and supersonic flow conditions are presented.

Diagnostic Validity of High-Density Barium Sulfate in Gastric Cancer Screening: Follow-up of Screenees by Record Linkage with the Osaka Cancer Registry

PubMed Central

Yamamoto, Kenyu; Yamazaki, Hideo; Kuroda, Chikazumi; Kubo, Tsugio; Oshima, Akira; Katsuda, Toshizo; Kuwano, Tadao; Takeda, Yoshihiro

2010-01-01

Background The use of high-density barium sulfate was recommended by the Japan Society of Gastroenterological Cancer Screening (JSGCS) in 2004. We evaluated the diagnostic validity of gastric cancer screening that used high-density barium sulfate. Methods The study subjects were 171 833 residents of Osaka, Japan who underwent gastric cancer screening tests at the Osaka Cancer Prevention and Detection Center during the period from 1 January 2000 through 31 December 2001. Screening was conducted using either high-density barium sulfate (n = 48 336) or moderate-density barium sulfate (n = 123 497). The subjects were followed up and their medical records were linked to those of the Osaka Cancer Registry through 31 December 2002. The results of follow-up during 1 year were defined as the gold standard, and test performance values were calculated. Results The sensitivity and specificity of the screening test using moderate-density barium sulfate were 92.3% and 91.0%, respectively, while the sensitivity and specificity of the high-density barium test were 91.8% and 91.4%, respectively. The results of area under receiver-operating-characteristic (ROC) curve analysis revealed no significant difference between the 2 screening tests. Conclusions Screening tests using high- and moderate-density barium sulfate had similar validity, as determined by sensitivity, specificity, and ROC curve analysis. PMID:20551581

Redesign of a Variable-Gain Output Feedback Longitudinal Controller Flown on the High-Alpha Research Vehicle (HARV)

NASA Technical Reports Server (NTRS)

Ostroff, Aaron J.

1998-01-01

This paper describes a redesigned longitudinal controller that flew on the High-Alpha Research Vehicle (HARV) during calendar years (CY) 1995 and 1996. Linear models are developed for both the modified controller and a baseline controller that was flown in CY 1994. The modified controller was developed with three gain sets for flight evaluation, and several linear analysis results are shown comparing the gain sets. A Neal-Smith flying qualities analysis shows that performance for the low- and medium-gain sets is near the level 1 boundary, depending upon the bandwidth assumed, whereas the high-gain set indicates a sensitivity problem. A newly developed high-alpha Bode envelope criterion indicates that the control system gains may be slightly high, even for the low-gain set. A large motion-base simulator in the United Kingdom was used to evaluate the various controllers. Desired performance, which appeared to be satisfactory for flight, was generally met with both the low- and medium-gain sets. Both the high-gain set and the baseline controller were very sensitive, and it was easy to generate pilot-induced oscillation (PIO) in some of the target-tracking maneuvers. Flight target-tracking results varied from level 1 to level 3 and from no sensitivity to PIO. These results were related to pilot technique and whether actuator rate saturation was encountered.

Quantum-Dot-Based Electrochemical Immunoassay for High-Throughput Screening of the Prostate-Specific Antigen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jun; Liu, Guodong; Wu, Hong

2008-01-01

In this paper, we demonstrate an electrochemical high-throughput sensing platform for simple, sensitive detection of PSA based on QD labels. This sensing platform uses a microplate for immunoreactions and disposable screen-printed electrodes (SPE) for electrochemical stripping analysis of metal ions released from QD labels. With the 96-well microplate, capturing antibodies are conveniently immobilized to the well surface, and the process of immunoreaction is easily controlled. The formed sandwich complexes on the well surface are also easily isolated from reaction solutions. In particular, a microplate-based electrochemical assay can make it feasible to conduct a parallel analysis of several samples or multiplemore » protein markers. This assay offers a number of advantages including (1) simplicity, cost-effectiveness, (2) high sensitivity, (3) capability to sense multiple samples or targets in parallel, and (4) a potentially portable device with an SPE array implanted in the microplate. This PSA assay is sensitive because it uses two amplification processes: (1) QDs as a label for enhancing electrical signal since secondary antibodies are linked to QDs that contain a large number of metal atoms and (2) there is inherent signal amplification for electrochemical stripping analysis—preconcentration of metal ion onto the electrode surface for amplifying electrical signals. Therefore, the high sensitivity of this method, stemming from dual signal amplification via QD labels and pre-concentration, allows low concentration levels to be detected while using small sample volumes. Thus, this QD-based electrochemical detection approach offers a simple, rapid, cost-effective, and high throughput assay of PSA.« less

Development of a generalized perturbation theory method for sensitivity analysis using continuous-energy Monte Carlo methods

DOE PAGES

Perfetti, Christopher M.; Rearden, Bradley T.

2016-03-01

The sensitivity and uncertainty analysis tools of the ORNL SCALE nuclear modeling and simulation code system that have been developed over the last decade have proven indispensable for numerous application and design studies for nuclear criticality safety and reactor physics. SCALE contains tools for analyzing the uncertainty in the eigenvalue of critical systems, but cannot quantify uncertainty in important neutronic parameters such as multigroup cross sections, fuel fission rates, activation rates, and neutron fluence rates with realistic three-dimensional Monte Carlo simulations. A more complete understanding of the sources of uncertainty in these design-limiting parameters could lead to improvements in processmore » optimization, reactor safety, and help inform regulators when setting operational safety margins. A novel approach for calculating eigenvalue sensitivity coefficients, known as the CLUTCH method, was recently explored as academic research and has been found to accurately and rapidly calculate sensitivity coefficients in criticality safety applications. The work presented here describes a new method, known as the GEAR-MC method, which extends the CLUTCH theory for calculating eigenvalue sensitivity coefficients to enable sensitivity coefficient calculations and uncertainty analysis for a generalized set of neutronic responses using high-fidelity continuous-energy Monte Carlo calculations. Here, several criticality safety systems were examined to demonstrate proof of principle for the GEAR-MC method, and GEAR-MC was seen to produce response sensitivity coefficients that agreed well with reference direct perturbation sensitivity coefficients.« less

A theoretical-experimental methodology for assessing the sensitivity of biomedical spectral imaging platforms, assays, and analysis methods.

PubMed

Leavesley, Silas J; Sweat, Brenner; Abbott, Caitlyn; Favreau, Peter; Rich, Thomas C

2018-01-01

Spectral imaging technologies have been used for many years by the remote sensing community. More recently, these approaches have been applied to biomedical problems, where they have shown great promise. However, biomedical spectral imaging has been complicated by the high variance of biological data and the reduced ability to construct test scenarios with fixed ground truths. Hence, it has been difficult to objectively assess and compare biomedical spectral imaging assays and technologies. Here, we present a standardized methodology that allows assessment of the performance of biomedical spectral imaging equipment, assays, and analysis algorithms. This methodology incorporates real experimental data and a theoretical sensitivity analysis, preserving the variability present in biomedical image data. We demonstrate that this approach can be applied in several ways: to compare the effectiveness of spectral analysis algorithms, to compare the response of different imaging platforms, and to assess the level of target signature required to achieve a desired performance. Results indicate that it is possible to compare even very different hardware platforms using this methodology. Future applications could include a range of optimization tasks, such as maximizing detection sensitivity or acquisition speed, providing high utility for investigators ranging from design engineers to biomedical scientists. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The use of droplet digital PCR in liquid biopsies: A highly sensitive technique for MYD88 p.(L265P) detection in cerebrospinal fluid.

PubMed

Hiemcke-Jiwa, Laura S; Minnema, Monique C; Radersma-van Loon, Joyce H; Jiwa, N Mehdi; de Boer, Mirthe; Leguit, Roos J; de Weger, Roel A; Huibers, Manon M H

2018-04-01

The gold standard for diagnosis of central nervous system lymphomas still regards a stereotactic brain biopsy, with the risk of major complications for the patient. As tumor cells can be detected in cerebrospinal fluid (CSF), CSF analysis can be used as an alternative. In this respect, mutation analysis in CSF can be of added value to other diagnostic parameters such a cytomorphology and clonality analysis. A well-known example of targeted mutation analysis entails MYD88 p.(L265P) detection, which is present in the majority of Bing Neel syndrome and primary central nervous system lymphoma (PCNSL) patients. Unfortunately, tumor yield in CSF can be very low. Therefore, use of the highly sensitive droplet digital PCR (ddPCR) might be a suitable analysis strategy for targeted mutation detection. We analyzed 26 formalin fixed paraffin embedded (FFPE) samples (8 positive and 18 negative for MYD88 p.(L265P) mutation) by ddPCR, of which the results were compared with next generation sequencing (NGS). Subsequently, 32 CSF samples were analyzed by ddPCR. ddPCR and NGS results on FFPE material showed 100% concordance. Among the 32 CSF samples, 9 belonged to patients with lymphoplasmacytic lymphoma (LPL) and clinical suspicion of Bing Neel syndrome, and 3 belonged to patients with PCNSL. Nine of these samples tested positive for MYD88 p.(L265P) (8 LPL and 1 PCNSL). This study shows that sensitive MYD88 mutation analysis by ddPCR in CSF is highly reliable and can be applied even when DNA input is low. Therefore, ddPCR is of added value to current diagnostic parameters, especially when the available amount of DNA is limited. Copyright © 2017 John Wiley & Sons, Ltd.

Single quantum dot analysis enables multiplexed point mutation detection by gap ligase chain reaction.

PubMed

Song, Yunke; Zhang, Yi; Wang, Tza-Huei

2013-04-08

Gene point mutations present important biomarkers for genetic diseases. However, existing point mutation detection methods suffer from low sensitivity, specificity, and a tedious assay processes. In this report, an assay technology is proposed which combines the outstanding specificity of gap ligase chain reaction (Gap-LCR), the high sensitivity of single-molecule coincidence detection, and the superior optical properties of quantum dots (QDs) for multiplexed detection of point mutations in genomic DNA. Mutant-specific ligation products are generated by Gap-LCR and subsequently captured by QDs to form DNA-QD nanocomplexes that are detected by single-molecule spectroscopy (SMS) through multi-color fluorescence burst coincidence analysis, allowing for multiplexed mutation detection in a separation-free format. The proposed assay is capable of detecting zeptomoles of KRAS codon 12 mutation variants with near 100% specificity. Its high sensitivity allows direct detection of KRAS mutation in crude genomic DNA without PCR pre-amplification. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High-throughput and sensitive analysis of 3-monochloropropane-1,2-diol fatty acid esters in edible oils by supercritical fluid chromatography/tandem mass spectrometry.

PubMed

Hori, Katsuhito; Matsubara, Atsuki; Uchikata, Takato; Tsumura, Kazunobu; Fukusaki, Eiichiro; Bamba, Takeshi

2012-08-10

We have established a high-throughput and sensitive analytical method based on supercritical fluid chromatography (SFC) coupled with triple quadrupole mass spectrometry (QqQ MS) for 3-monochloropropane-1,2-diol (3-MCPD) fatty acid esters in edible oils. All analytes were successfully separated within 9 min without sample purification. The system was precise and sensitive, with a limit of detection less than 0.063 mg/kg. The recovery rate of 3-MCPD fatty acid esters spiked into oil samples was in the range of 62.68-115.23%. Furthermore, several edible oils were tested for analyzing 3-MCPD fatty acid ester profiles. This is the first report on the analysis of 3-MCPD fatty acid esters by SFC/QqQ MS. The developed method will be a powerful tool for investigating 3-MCPD fatty acid esters in edible oils. Copyright © 2012 Elsevier B.V. All rights reserved.

Photochemical modeling and analysis of meteorological parameters during ozone episodes in Kaohsiung, Taiwan

NASA Astrophysics Data System (ADS)

Chen, K. S.; Ho, Y. T.; Lai, C. H.; Chou, Youn-Min

The events of high ozone concentrations and meteorological conditions covering the Kaohsiung metropolitan area were investigated based on data analysis and model simulation. A photochemical grid model was employed to analyze two ozone episodes in autumn (2000) and winter (2001) seasons, each covering three consecutive days (or 72 h) in the Kaohsiung City. The potential influence of the initial and boundary conditions on model performance was assessed. Model performance can be improved by separately considering the daytime and nighttime ozone concentrations on the lateral boundary conditions of the model domain. The sensitivity analyses of ozone concentrations to the emission reductions in volatile organic compounds (VOC) and nitrogen oxides (NO x) show a VOC-sensitive regime for emission reductions to lower than 30-40% VOC and 30-50% NO x and a NO x-sensitive regime for larger percentage reductions. Meteorological parameters show that warm temperature, sufficient sunlight, low wind, and high surface pressure are distinct parameters that tend to trigger ozone episodes in polluted urban areas, like Kaohsiung.

A flexible, interpretable framework for assessing sensitivity to unmeasured confounding.

PubMed

Dorie, Vincent; Harada, Masataka; Carnegie, Nicole Bohme; Hill, Jennifer

2016-09-10

When estimating causal effects, unmeasured confounding and model misspecification are both potential sources of bias. We propose a method to simultaneously address both issues in the form of a semi-parametric sensitivity analysis. In particular, our approach incorporates Bayesian Additive Regression Trees into a two-parameter sensitivity analysis strategy that assesses sensitivity of posterior distributions of treatment effects to choices of sensitivity parameters. This results in an easily interpretable framework for testing for the impact of an unmeasured confounder that also limits the number of modeling assumptions. We evaluate our approach in a large-scale simulation setting and with high blood pressure data taken from the Third National Health and Nutrition Examination Survey. The model is implemented as open-source software, integrated into the treatSens package for the R statistical programming language. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Fines classification based on sensitivity to pore-fluid chemistry

USGS Publications Warehouse

Jang, Junbong; Santamarina, J. Carlos

2016-01-01

The 75-μm particle size is used to discriminate between fine and coarse grains. Further analysis of fine grains is typically based on the plasticity chart. Whereas pore-fluid-chemistry-dependent soil response is a salient and distinguishing characteristic of fine grains, pore-fluid chemistry is not addressed in current classification systems. Liquid limits obtained with electrically contrasting pore fluids (deionized water, 2-M NaCl brine, and kerosene) are combined to define the soil “electrical sensitivity.” Liquid limit and electrical sensitivity can be effectively used to classify fine grains according to their fluid-soil response into no-, low-, intermediate-, or high-plasticity fine grains of low, intermediate, or high electrical sensitivity. The proposed methodology benefits from the accumulated experience with liquid limit in the field and addresses the needs of a broader range of geotechnical engineering problems.

Streamflow sensitivity to water storage changes across Europe

NASA Astrophysics Data System (ADS)

Berghuijs, Wouter R.; Hartmann, Andreas; Woods, Ross A.

2016-03-01

Terrestrial water storage is the primary source of river flow. We introduce storage sensitivity of streamflow (ɛS), which for a given flow rate indicates the relative change in streamflow per change in catchment water storage. ɛS can be directly derived from streamflow observations. Analysis of 725 catchments in Europe reveals that ɛS is high in, e.g., parts of Spain, England, Germany, and Denmark, whereas flow regimes in parts of the Alps are more resilient (that is, less sensitive) to storage changes. A regional comparison of ɛS with observations indicates that ɛS is significantly correlated with variability of low (R2 = 0.41), median (R2 = 0.27), and high flow conditions (R2 = 0.35). Streamflow sensitivity provides new guidance for a changing hydrosphere where groundwater abstraction and climatic changes are altering water storage and flow regimes.

Optimizing human activity patterns using global sensitivity analysis.

PubMed

Fairchild, Geoffrey; Hickmann, Kyle S; Mniszewski, Susan M; Del Valle, Sara Y; Hyman, James M

2014-12-01

Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule's regularity for a population. We show how to tune an activity's regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. We use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.

Optimizing human activity patterns using global sensitivity analysis

PubMed Central

Hickmann, Kyle S.; Mniszewski, Susan M.; Del Valle, Sara Y.; Hyman, James M.

2014-01-01

Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule’s regularity for a population. We show how to tune an activity’s regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. We use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations. PMID:25580080

Optimizing human activity patterns using global sensitivity analysis

DOE PAGES

Fairchild, Geoffrey; Hickmann, Kyle S.; Mniszewski, Susan M.; ...

2013-12-10

Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule’s regularity for a population. We show how to tune an activity’s regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimizationmore » problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. Here we use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Finally, though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.« less

Validation of a next-generation sequencing assay for clinical molecular oncology.

PubMed

Cottrell, Catherine E; Al-Kateb, Hussam; Bredemeyer, Andrew J; Duncavage, Eric J; Spencer, David H; Abel, Haley J; Lockwood, Christina M; Hagemann, Ian S; O'Guin, Stephanie M; Burcea, Lauren C; Sawyer, Christopher S; Oschwald, Dayna M; Stratman, Jennifer L; Sher, Dorie A; Johnson, Mark R; Brown, Justin T; Cliften, Paul F; George, Bijoy; McIntosh, Leslie D; Shrivastava, Savita; Nguyen, Tudung T; Payton, Jacqueline E; Watson, Mark A; Crosby, Seth D; Head, Richard D; Mitra, Robi D; Nagarajan, Rakesh; Kulkarni, Shashikant; Seibert, Karen; Virgin, Herbert W; Milbrandt, Jeffrey; Pfeifer, John D

2014-01-01

Currently, oncology testing includes molecular studies and cytogenetic analysis to detect genetic aberrations of clinical significance. Next-generation sequencing (NGS) allows rapid analysis of multiple genes for clinically actionable somatic variants. The WUCaMP assay uses targeted capture for NGS analysis of 25 cancer-associated genes to detect mutations at actionable loci. We present clinical validation of the assay and a detailed framework for design and validation of similar clinical assays. Deep sequencing of 78 tumor specimens (≥ 1000× average unique coverage across the capture region) achieved high sensitivity for detecting somatic variants at low allele fraction (AF). Validation revealed sensitivities and specificities of 100% for detection of single-nucleotide variants (SNVs) within coding regions, compared with SNP array sequence data (95% CI = 83.4-100.0 for sensitivity and 94.2-100.0 for specificity) or whole-genome sequencing (95% CI = 89.1-100.0 for sensitivity and 99.9-100.0 for specificity) of HapMap samples. Sensitivity for detecting variants at an observed 10% AF was 100% (95% CI = 93.2-100.0) in HapMap mixes. Analysis of 15 masked specimens harboring clinically reported variants yielded concordant calls for 13/13 variants at AF of ≥ 15%. The WUCaMP assay is a robust and sensitive method to detect somatic variants of clinical significance in molecular oncology laboratories, with reduced time and cost of genetic analysis allowing for strategic patient management. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

High-frequency phase shift measurement greatly enhances the sensitivity of QCM immunosensors.

PubMed

March, Carmen; García, José V; Sánchez, Ángel; Arnau, Antonio; Jiménez, Yolanda; García, Pablo; Manclús, Juan J; Montoya, Ángel

2015-03-15

In spite of being widely used for in liquid biosensing applications, sensitivity improvement of conventional (5-20MHz) quartz crystal microbalance (QCM) sensors remains an unsolved challenging task. With the help of a new electronic characterization approach based on phase change measurements at a constant fixed frequency, a highly sensitive and versatile high fundamental frequency (HFF) QCM immunosensor has successfully been developed and tested for its use in pesticide (carbaryl and thiabendazole) analysis. The analytical performance of several immunosensors was compared in competitive immunoassays taking carbaryl insecticide as the model analyte. The highest sensitivity was exhibited by the 100MHz HFF-QCM carbaryl immunosensor. When results were compared with those reported for 9MHz QCM, analytical parameters clearly showed an improvement of one order of magnitude for sensitivity (estimated as the I50 value) and two orders of magnitude for the limit of detection (LOD): 30μgl(-1) vs 0.66μgL(-1)I50 value and 11μgL(-1) vs 0.14μgL(-1) LOD, for 9 and 100MHz, respectively. For the fungicide thiabendazole, I50 value was roughly the same as that previously reported for SPR under the same biochemical conditions, whereas LOD improved by a factor of 2. The analytical performance achieved by high frequency QCM immunosensors surpassed those of conventional QCM and SPR, closely approaching the most sensitive ELISAs. The developed 100MHz QCM immunosensor strongly improves sensitivity in biosensing, and therefore can be considered as a very promising new analytical tool for in liquid applications where highly sensitive detection is required. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of microarray data normalization procedures using spike-in experiments

PubMed Central

Rydén, Patrik; Andersson, Henrik; Landfors, Mattias; Näslund, Linda; Hartmanová, Blanka; Noppa, Laila; Sjöstedt, Anders

2006-01-01

Background Recently, a large number of methods for the analysis of microarray data have been proposed but there are few comparisons of their relative performances. By using so-called spike-in experiments, it is possible to characterize the analyzed data and thereby enable comparisons of different analysis methods. Results A spike-in experiment using eight in-house produced arrays was used to evaluate established and novel methods for filtration, background adjustment, scanning, channel adjustment, and censoring. The S-plus package EDMA, a stand-alone tool providing characterization of analyzed cDNA-microarray data obtained from spike-in experiments, was developed and used to evaluate 252 normalization methods. For all analyses, the sensitivities at low false positive rates were observed together with estimates of the overall bias and the standard deviation. In general, there was a trade-off between the ability of the analyses to identify differentially expressed genes (i.e. the analyses' sensitivities) and their ability to provide unbiased estimators of the desired ratios. Virtually all analysis underestimated the magnitude of the regulations; often less than 50% of the true regulations were observed. Moreover, the bias depended on the underlying mRNA-concentration; low concentration resulted in high bias. Many of the analyses had relatively low sensitivities, but analyses that used either the constrained model (i.e. a procedure that combines data from several scans) or partial filtration (a novel method for treating data from so-called not-found spots) had with few exceptions high sensitivities. These methods gave considerable higher sensitivities than some commonly used analysis methods. Conclusion The use of spike-in experiments is a powerful approach for evaluating microarray preprocessing procedures. Analyzed data are characterized by properties of the observed log-ratios and the analysis' ability to detect differentially expressed genes. If bias is not a major problem; we recommend the use of either the CM-procedure or partial filtration. PMID:16774679

Analysis of DNA methylation in Arabidopsis thaliana based on methylation-sensitive AFLP markers.

PubMed

Cervera, M T; Ruiz-García, L; Martínez-Zapater, J M

2002-12-01

AFLP analysis using restriction enzyme isoschizomers that differ in their sensitivity to methylation of their recognition sites has been used to analyse the methylation state of anonymous CCGG sequences in Arabidopsis thaliana. The technique was modified to improve the quality of fingerprints and to visualise larger numbers of scorable fragments. Sequencing of amplified fragments indicated that detection was generally associated with non-methylation of the cytosine to which the isoschizomer is sensitive. Comparison of EcoRI/ HpaII and EcoRI/ MspI patterns in different ecotypes revealed that 35-43% of CCGG sites were differentially digested by the isoschizomers. Interestingly, the pattern of digestion among different plants belonging to the same ecotype is highly conserved, with the rate of intra-ecotype methylation-sensitive polymorphisms being less than 1%. However, pairwise comparisons of methylation patterns between samples belonging to different ecotypes revealed differences in up to 34% of the methylation-sensitive polymorphisms. The lack of correlation between inter-ecotype similarity matrices based on methylation-insensitive or methylation-sensitive polymorphisms suggests that whatever the mechanisms regulating methylation may be, they are not related to nucleotide sequence variation.

Increasing Electrochemiluminescence Intensity of a Wireless Electrode Array Chip by Thousands of Times Using a Diode for Sensitive Visual Detection by a Digital Camera.

PubMed

Qi, Liming; Xia, Yong; Qi, Wenjing; Gao, Wenyue; Wu, Fengxia; Xu, Guobao

2016-01-19

Both a wireless electrochemiluminescence (ECL) electrode microarray chip and the dramatic increase in ECL by embedding a diode in an electromagnetic receiver coil have been first reported. The newly designed device consists of a chip and a transmitter. The chip has an electromagnetic receiver coil, a mini-diode, and a gold electrode array. The mini-diode can rectify alternating current into direct current and thus enhance ECL intensities by 18 thousand times, enabling a sensitive visual detection using common cameras or smart phones as low cost detectors. The detection limit of hydrogen peroxide using a digital camera is comparable to that using photomultiplier tube (PMT)-based detectors. Coupled with a PMT-based detector, the device can detect luminol with higher sensitivity with linear ranges from 10 nM to 1 mM. Because of the advantages including high sensitivity, high throughput, low cost, high portability, and simplicity, it is promising in point of care testing, drug screening, and high throughput analysis.

High Sensitivity, Wearable, Piezoresistive Pressure Sensors Based on Irregular Microhump Structures and Its Applications in Body Motion Sensing.

PubMed

Wang, Zongrong; Wang, Shan; Zeng, Jifang; Ren, Xiaochen; Chee, Adrian J Y; Yiu, Billy Y S; Chung, Wai Choi; Yang, Yong; Yu, Alfred C H; Roberts, Robert C; Tsang, Anderson C O; Chow, Kwok Wing; Chan, Paddy K L

2016-07-01

A pressure sensor based on irregular microhump patterns has been proposed and developed. The devices show high sensitivity and broad operating pressure regime while comparing with regular micropattern devices. Finite element analysis (FEA) is utilized to confirm the sensing mechanism and predict the performance of the pressure sensor based on the microhump structures. Silicon carbide sandpaper is employed as the mold to develop polydimethylsiloxane (PDMS) microhump patterns with various sizes. The active layer of the piezoresistive pressure sensor is developed by spin coating PSS on top of the patterned PDMS. The devices show an averaged sensitivity as high as 851 kPa(-1) , broad operating pressure range (20 kPa), low operating power (100 nW), and fast response speed (6.7 kHz). Owing to their flexible properties, the devices are applied to human body motion sensing and radial artery pulse. These flexible high sensitivity devices show great potential in the next generation of smart sensors for robotics, real-time health monitoring, and biomedical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improving guideline sensitivity and specificity for the identification of proactive gastrostomy placement in patients with head and neck cancer.

PubMed

Brown, Teresa E; Crombie, Jane; Spurgin, Ann-Louise; Tripcony, Lee; Keller, Jacqui; Hughes, Brett G M; Dickie, Graeme; Kenny, Lizbeth Moira; Hodge, Robert A

2016-04-01

Swallowing and nutrition guidelines for patients with head and neck cancer are available for identification of proactive gastrostomy placement in patients with high nutritional risk. The purpose of this study was to investigate improvements to the validity of these guidelines. A multivariate analysis was fitted to the original dataset (n = 501) to examine the variables that may predict gastrostomy placement (eg, tumor site, treatment, sex, and age). Using these factors, the high risk category was modified and retrospectively validated in the same cohort to provide new measures of sensitivity and specificity. The following were positive predictors of gastrostomy placement: T3 (p = .01), T4 (p < .001), and chemoradiotherapy (p < .001). Laryngeal (p = .02) and skin cancer (p < .001) were negative predictors. Modification of the high risk definition improved sensitivity to 58% and maintained specificity at 92%. Minor modifications to the high risk definition in the guidelines have improved the guideline sensitivity for future use. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1163-E1171, 2016. © 2015 Wiley Periodicals, Inc.

GRIDSS: sensitive and specific genomic rearrangement detection using positional de Bruijn graph assembly

PubMed Central

Do, Hongdo; Molania, Ramyar

2017-01-01

The identification of genomic rearrangements with high sensitivity and specificity using massively parallel sequencing remains a major challenge, particularly in precision medicine and cancer research. Here, we describe a new method for detecting rearrangements, GRIDSS (Genome Rearrangement IDentification Software Suite). GRIDSS is a multithreaded structural variant (SV) caller that performs efficient genome-wide break-end assembly prior to variant calling using a novel positional de Bruijn graph-based assembler. By combining assembly, split read, and read pair evidence using a probabilistic scoring, GRIDSS achieves high sensitivity and specificity on simulated, cell line, and patient tumor data, recently winning SV subchallenge #5 of the ICGC-TCGA DREAM8.5 Somatic Mutation Calling Challenge. On human cell line data, GRIDSS halves the false discovery rate compared to other recent methods while matching or exceeding their sensitivity. GRIDSS identifies nontemplate sequence insertions, microhomologies, and large imperfect homologies, estimates a quality score for each breakpoint, stratifies calls into high or low confidence, and supports multisample analysis. PMID:29097403

Mesoporous structured MIPs@CDs fluorescence sensor for highly sensitive detection of TNT.

PubMed

Xu, Shoufang; Lu, Hongzhi

2016-11-15

A facile strategy was developed to prepare mesoporous structured molecularly imprinted polymers capped carbon dots (M-MIPs@CDs) fluorescence sensor for highly sensitive and selective determination of TNT. The strategy using amino-CDs directly as "functional monomer" for imprinting simplify the imprinting process and provide well recognition sites accessibility. The as-prepared M-MIPs@CDs sensor, using periodic mesoporous silica as imprinting matrix, and amino-CDs directly as "functional monomer", exhibited excellent selectivity and sensitivity toward TNT with detection limit of 17nM. The recycling process was sustainable for 10 times without obvious efficiency decrease. The feasibility of the developed method in real samples was successfully evaluated through the analysis of TNT in soil and water samples with satisfactory recoveries of 88.6-95.7%. The method proposed in this work was proved to be a convenient and practical way to prepare high sensitive and selective fluorescence MIPs@CDs sensors. Copyright © 2016 Elsevier B.V. All rights reserved.

System and method for high precision isotope ratio destructive analysis

DOEpatents

Bushaw, Bruce A; Anheier, Norman C; Phillips, Jon R

2013-07-02

A system and process are disclosed that provide high accuracy and high precision destructive analysis measurements for isotope ratio determination of relative isotope abundance distributions in liquids, solids, and particulate samples. The invention utilizes a collinear probe beam to interrogate a laser ablated plume. This invention provides enhanced single-shot detection sensitivity approaching the femtogram range, and isotope ratios that can be determined at approximately 1% or better precision and accuracy (relative standard deviation).

Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance.

PubMed

Li, Shi-Rong; Wang, Zhen-Ming; Wang, Yu-Hui; Wang, Xi-Bo; Zhao, Jian-Qiang; Xue, Hai-Bin; Jiang, Fu-Guo

2015-01-01

Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chi- square test was used to test the differences of PAX1 methylation or HPV infection between groups. The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

High-throughput microfluidic single-cell digital polymerase chain reaction.

PubMed

White, A K; Heyries, K A; Doolin, C; Vaninsberghe, M; Hansen, C L

2013-08-06

Here we present an integrated microfluidic device for the high-throughput digital polymerase chain reaction (dPCR) analysis of single cells. This device allows for the parallel processing of single cells and executes all steps of analysis, including cell capture, washing, lysis, reverse transcription, and dPCR analysis. The cDNA from each single cell is distributed into a dedicated dPCR array consisting of 1020 chambers, each having a volume of 25 pL, using surface-tension-based sample partitioning. The high density of this dPCR format (118,900 chambers/cm(2)) allows the analysis of 200 single cells per run, for a total of 204,000 PCR reactions using a device footprint of 10 cm(2). Experiments using RNA dilutions show this device achieves shot-noise-limited performance in quantifying single molecules, with a dynamic range of 10(4). We performed over 1200 single-cell measurements, demonstrating the use of this platform in the absolute quantification of both high- and low-abundance mRNA transcripts, as well as micro-RNAs that are not easily measured using alternative hybridization methods. We further apply the specificity and sensitivity of single-cell dPCR to performing measurements of RNA editing events in single cells. High-throughput dPCR provides a new tool in the arsenal of single-cell analysis methods, with a unique combination of speed, precision, sensitivity, and specificity. We anticipate this approach will enable new studies where high-performance single-cell measurements are essential, including the analysis of transcriptional noise, allelic imbalance, and RNA processing.

Motif-based analysis of large nucleotide data sets using MEME-ChIP

PubMed Central

Ma, Wenxiu; Noble, William S; Bailey, Timothy L

2014-01-01

MEME-ChIP is a web-based tool for analyzing motifs in large DNA or RNA data sets. It can analyze peak regions identified by ChIP-seq, cross-linking sites identified by cLIP-seq and related assays, as well as sets of genomic regions selected using other criteria. MEME-ChIP performs de novo motif discovery, motif enrichment analysis, motif location analysis and motif clustering, providing a comprehensive picture of the DNA or RNA motifs that are enriched in the input sequences. MEME-ChIP performs two complementary types of de novo motif discovery: weight matrix–based discovery for high accuracy; and word-based discovery for high sensitivity. Motif enrichment analysis using DNA or RNA motifs from human, mouse, worm, fly and other model organisms provides even greater sensitivity. MEME-ChIP’s interactive HTML output groups and aligns significant motifs to ease interpretation. this protocol takes less than 3 h, and it provides motif discovery approaches that are distinct and complementary to other online methods. PMID:24853928

A comparative study of biomass integrated gasification combined cycle power systems: Performance analysis.

PubMed

Zang, Guiyan; Tejasvi, Sharma; Ratner, Albert; Lora, Electo Silva

2018-05-01

The Biomass Integrated Gasification Combined Cycle (BIGCC) power system is believed to potentially be a highly efficient way to utilize biomass to generate power. However, there is no comparative study of BIGCC systems that examines all the latest improvements for gasification agents, gas turbine combustion methods, and CO 2 Capture and Storage options. This study examines the impact of recent advancements on BIGCC performance through exergy analysis using Aspen Plus. Results show that the exergy efficiency of these systems is ranged from 22.3% to 37.1%. Furthermore, exergy analysis indicates that the gas turbine with external combustion has relatively high exergy efficiency, and Selexol CO 2 removal method has low exergy destruction. Moreover, the sensitivity analysis shows that the system exergy efficiency is more sensitive to the initial temperature and pressure ratio of the gas turbine, whereas has a relatively weak dependence on the initial temperature and initial pressure of the steam turbine. Copyright © 2018 Elsevier Ltd. All rights reserved.

Proteomic differential display analysis for TS-1-resistant and -sensitive pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry.

PubMed

Yoshida, Kanako; Kuramitsu, Yasuhiro; Murakami, Kohei; Ryozawa, Shomei; Taba, Kumiko; Kaino, Seiji; Zhang, Xiulian; Sakaida, Isao; Nakamura, Kazuyuki

2011-06-01

TS-1 is an oral anticancer agent containing two biochemical modulators for 5-fluorouracil (5-FU) and tegafur (FT), a metabolically activated prodrug of 5-FU. TS-1 has been recognized as an effective anticancer drug using standard therapies for patients with advanced pancreatic cancer along with gemcitabine. However, a high level of inherent and acquired tumor resistance to TS-1 induces difficulty in the treatment. To identify proteins linked to the TS-1-resistance of pancreatic cancer, we profiled protein expression levels in samples of TS-1-resistant and -sensitive pancreatic cancer cell lines by using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The cytotoxicity of a 5-FU/5-chloro-2,4-dihydroxypyridine (CDHP) combination towards pancreatic cancer cell lines was evaluated by MTS assay. Panc-1, BxPC-3, MiaPaCa-2 and PK59 showed high sensitivity to the 5-FU/CDHP combination (TS-1-sensitive), whereas PK45p and KLM-1 were much less sensitive (TS-1-resistant). Proteomic analysis showed that eleven spots, including T-complex protein 1 subunit beta, ribonuclease inhibitor, elongation factor 1-delta, peroxiredoxin-2 and superoxide dismutase (Cu-Zn), appeared to be down-regulated, and 29 spots, including hypoxia up-regulated protein 1, lamin-A/C, endoplasmin, fascin and annexin A1, appeared to be up-regulated in TS-1-resistant cells compared with -sensitive cells. These results suggest that the identified proteins showing different expression between TS-1-sensitive and -resistant pancreatic cancer cells possibly relate to TS-1-sensitivity. These findings could be useful to overcome the TS-1-resistance of pancreatic cancer cells.

Sensitivity analysis and nonlinearity assessment of steam cracking furnace process

NASA Astrophysics Data System (ADS)

Rosli, M. N.; Sudibyo, Aziz, N.

2017-11-01

In this paper, sensitivity analysis and nonlinearity assessment of cracking furnace process are presented. For the sensitivity analysis, the fractional factorial design method is employed as a method to analyze the effect of input parameters, which consist of four manipulated variables and two disturbance variables, to the output variables and to identify the interaction between each parameter. The result of the factorial design method is used as a screening method to reduce the number of parameters, and subsequently, reducing the complexity of the model. It shows that out of six input parameters, four parameters are significant. After the screening is completed, step test is performed on the significant input parameters to assess the degree of nonlinearity of the system. The result shows that the system is highly nonlinear with respect to changes in an air-to-fuel ratio (AFR) and feed composition.

The performance of magnetic resonance imaging in the detection of triangular fibrocartilage complex injury: a meta-analysis.

PubMed

Wang, Z X; Chen, S L; Wang, Q Q; Liu, B; Zhu, J; Shen, J

2015-06-01

The aim of this study was to evaluate the accuracy of magnetic resonance imaging in the detection of triangular fibrocartilage complex injury through a meta-analysis. A comprehensive literature search was conducted before 1 April 2014. All studies comparing magnetic resonance imaging results with arthroscopy or open surgery findings were reviewed, and 25 studies that satisfied the eligibility criteria were included. Data were pooled to yield pooled sensitivity and specificity, which were respectively 0.83 and 0.82. In detection of central and peripheral tears, magnetic resonance imaging had respectively a pooled sensitivity of 0.90 and 0.88 and a pooled specificity of 0.97 and 0.97. Six high-quality studies using Ringler's recommended magnetic resonance imaging parameters were selected for analysis to determine whether optimal imaging protocols yielded better results. The pooled sensitivity and specificity of these six studies were 0.92 and 0.82, respectively. The overall accuracy of magnetic resonance imaging was acceptable. For peripheral tears, the pooled data showed a relatively high accuracy. Magnetic resonance imaging with appropriate parameters are an ideal method for diagnosing different types of triangular fibrocartilage complex tears. © The Author(s) 2015.

Sensitivity Analysis in Engineering

NASA Technical Reports Server (NTRS)

Adelman, Howard M. (Compiler); Haftka, Raphael T. (Compiler)

1987-01-01

The symposium proceedings presented focused primarily on sensitivity analysis of structural response. However, the first session, entitled, General and Multidisciplinary Sensitivity, focused on areas such as physics, chemistry, controls, and aerodynamics. The other four sessions were concerned with the sensitivity of structural systems modeled by finite elements. Session 2 dealt with Static Sensitivity Analysis and Applications; Session 3 with Eigenproblem Sensitivity Methods; Session 4 with Transient Sensitivity Analysis; and Session 5 with Shape Sensitivity Analysis.

Modelling ecological and human exposure to POPs in Venice lagoon - Part II: Quantitative uncertainty and sensitivity analysis in coupled exposure models.

PubMed

Radomyski, Artur; Giubilato, Elisa; Ciffroy, Philippe; Critto, Andrea; Brochot, Céline; Marcomini, Antonio

2016-11-01

The study is focused on applying uncertainty and sensitivity analysis to support the application and evaluation of large exposure models where a significant number of parameters and complex exposure scenarios might be involved. The recently developed MERLIN-Expo exposure modelling tool was applied to probabilistically assess the ecological and human exposure to PCB 126 and 2,3,7,8-TCDD in the Venice lagoon (Italy). The 'Phytoplankton', 'Aquatic Invertebrate', 'Fish', 'Human intake' and PBPK models available in MERLIN-Expo library were integrated to create a specific food web to dynamically simulate bioaccumulation in various aquatic species and in the human body over individual lifetimes from 1932 until 1998. MERLIN-Expo is a high tier exposure modelling tool allowing propagation of uncertainty on the model predictions through Monte Carlo simulation. Uncertainty in model output can be further apportioned between parameters by applying built-in sensitivity analysis tools. In this study, uncertainty has been extensively addressed in the distribution functions to describe the data input and the effect on model results by applying sensitivity analysis techniques (screening Morris method, regression analysis, and variance-based method EFAST). In the exposure scenario developed for the Lagoon of Venice, the concentrations of 2,3,7,8-TCDD and PCB 126 in human blood turned out to be mainly influenced by a combination of parameters (half-lives of the chemicals, body weight variability, lipid fraction, food assimilation efficiency), physiological processes (uptake/elimination rates), environmental exposure concentrations (sediment, water, food) and eating behaviours (amount of food eaten). In conclusion, this case study demonstrated feasibility of MERLIN-Expo to be successfully employed in integrated, high tier exposure assessment. Copyright © 2016 Elsevier B.V. All rights reserved.

A New Framework for Effective and Efficient Global Sensitivity Analysis of Earth and Environmental Systems Models

NASA Astrophysics Data System (ADS)

Razavi, Saman; Gupta, Hoshin

2015-04-01

Earth and Environmental Systems (EES) models are essential components of research, development, and decision-making in science and engineering disciplines. With continuous advances in understanding and computing power, such models are becoming more complex with increasingly more factors to be specified (model parameters, forcings, boundary conditions, etc.). To facilitate better understanding of the role and importance of different factors in producing the model responses, the procedure known as 'Sensitivity Analysis' (SA) can be very helpful. Despite the availability of a large body of literature on the development and application of various SA approaches, two issues continue to pose major challenges: (1) Ambiguous Definition of Sensitivity - Different SA methods are based in different philosophies and theoretical definitions of sensitivity, and can result in different, even conflicting, assessments of the underlying sensitivities for a given problem, (2) Computational Cost - The cost of carrying out SA can be large, even excessive, for high-dimensional problems and/or computationally intensive models. In this presentation, we propose a new approach to sensitivity analysis that addresses the dual aspects of 'effectiveness' and 'efficiency'. By effective, we mean achieving an assessment that is both meaningful and clearly reflective of the objective of the analysis (the first challenge above), while by efficiency we mean achieving statistically robust results with minimal computational cost (the second challenge above). Based on this approach, we develop a 'global' sensitivity analysis framework that efficiently generates a newly-defined set of sensitivity indices that characterize a range of important properties of metric 'response surfaces' encountered when performing SA on EES models. Further, we show how this framework embraces, and is consistent with, a spectrum of different concepts regarding 'sensitivity', and that commonly-used SA approaches (e.g., Sobol, Morris, etc.) are actually limiting cases of our approach under specific conditions. Multiple case studies are used to demonstrate the value of the new framework. The results show that the new framework provides a fundamental understanding of the underlying sensitivities for any given problem, while requiring orders of magnitude fewer model runs.

Simple and sensitive analysis of long-chain free fatty acids in milk by fluorogenic derivatization and high-performance liquid chromatography.

PubMed

Lu, Chi-Yu; Wu, Hsin-Lung; Chen, Su-Hwei; Kou, Hwang-Shang; Wu, Shou-Mei

2002-01-02

A highly sensitive high-performance liquid chromatography (HPLC) method is described for the simultaneous determination of some important saturated and unsaturated fatty acids in milk, including lauric (dodecanoic), myristic (tetradecanoic), palmitic (hexadecanoic), stearic (octadecanoic), palmitoleic (hexadecenoic), oleic (octadecenoic), and linoleic acids (octadecadienoic acids). The fatty acids were fluorogenically derivatized with 2-(2-naphthoxy)ethyl 2-(piperidino)ethanesulfonate (NOEPES) as their naphthoxyethyl derivatives. The resulting derivatives were separated by isocratic HPLC and monitored with a fluorometric detector (lambdaex = 235 nm, lambdaem = 350 nm). The fatty acids in milk were extracted with toluene, and the extract with the fatty acids was directly derivatized with NOEPES without solvent replacement. Determination of long-chain free fatty acids in milk is feasible by a standard addition method. A small amount of milk product, 10 microL, is sufficient for the analysis.

National and International Security Applications of Cryogenic Detectors—Mostly Nuclear Safeguards

NASA Astrophysics Data System (ADS)

Rabin, Michael W.

2009-12-01

As with science, so with security—in both arenas, the extraordinary sensitivity of cryogenic sensors enables high-confidence detection and high-precision measurement even of the faintest signals. Science applications are more mature, but several national and international security applications have been identified where cryogenic detectors have high potential payoff. International safeguards and nuclear forensics are areas needing new technology and methods to boost speed, sensitivity, precision and accuracy. Successfully applied, improved nuclear materials analysis will help constrain nuclear materials diversion pathways and contribute to treaty verification. Cryogenic microcalorimeter detectors for X-ray, gamma-ray, neutron, and alpha-particle spectrometry are under development with these aims in mind. In each case the unsurpassed energy resolution of microcalorimeters reveals previously invisible spectral features of nuclear materials. Preliminary results of quantitative analysis indicate substantial improvements are still possible, but significant work will be required to fully understand the ultimate performance limits.

The diagnostic value of narrow-band imaging for early and invasive lung cancer: a meta-analysis.

PubMed

Zhu, Juanjuan; Li, Wei; Zhou, Jihong; Chen, Yuqing; Zhao, Chenling; Zhang, Ting; Peng, Wenjia; Wang, Xiaojing

2017-07-01

This study aimed to compare the ability of narrow-band imaging to detect early and invasive lung cancer with that of conventional pathological analysis and white-light bronchoscopy. We searched the PubMed, EMBASE, Sinomed, and China National Knowledge Infrastructure databases for relevant studies. Meta-disc software was used to perform data analysis, meta-regression analysis, sensitivity analysis, and heterogeneity testing, and STATA software was used to determine if publication bias was present, as well as to calculate the relative risks for the sensitivity and specificity of narrow-band imaging vs those of white-light bronchoscopy for the detection of early and invasive lung cancer. A random-effects model was used to assess the diagnostic efficacy of the above modalities in cases in which a high degree of between-study heterogeneity was noted with respect to their diagnostic efficacies. The database search identified six studies including 578 patients. The pooled sensitivity and specificity of narrow-band imaging were 86% (95% confidence interval: 83-88%) and 81% (95% confidence interval: 77-84%), respectively, and the pooled sensitivity and specificity of white-light bronchoscopy were 70% (95% confidence interval: 66-74%) and 66% (95% confidence interval: 62-70%), respectively. The pooled relative risks for the sensitivity and specificity of narrow-band imaging vs the sensitivity and specificity of white-light bronchoscopy for the detection of early and invasive lung cancer were 1.33 (95% confidence interval: 1.07-1.67) and 1.09 (95% confidence interval: 0.84-1.42), respectively, and sensitivity analysis showed that narrow-band imaging exhibited good diagnostic efficacy with respect to detecting early and invasive lung cancer and that the results of the study were stable. Narrow-band imaging was superior to white light bronchoscopy with respect to detecting early and invasive lung cancer; however, the specificities of the two modalities did not differ significantly.

Fracture experience among participants from the FROCAT study: what thresholding is appropriate using the FRAX tool?

PubMed

Azagra, R; Zwart, M; Aguyé, A; Martín-Sánchez, J C; Casado, E; Díaz-Herrera, M A; Moriña, D; Cooper, C; Díez-Pérez, A; Dennison, E M

2016-01-01

To perform an external validation of FRAX algorithm thresholds for reporting level of risk of fracture in Spanish women (low < 5%; intermediate ≥ 5% and < 7.5%; high ≥ 7.5%) taken from a prospective cohort "FRIDEX". A retrospective study of 1090 women aged ≥ 40 and ≤ 90 years old obtained from the general population (FROCAT cohort). FRAX was calculated with data registered in 2002. All fractures were validated in 2012. Sensitivity analysis was performed. When analyzing the cohort (884) excluding current or past anti osteoporotic medication (AOM), using our nominated thresholds, among the 621 (70.2%) women at low risk of fracture, 5.2% [CI95%: 3.4-7.6] sustained a fragility fracture; among the 99 at intermediate risk, 12.1% [6.4-20.2]; and among the 164 defined as high risk, 15.9% [10.6-24.2]. Sensitivity analysis against model risk stratification FRIDEX of FRAX Spain shows no significant difference. By including 206 women with AOM, the sensitivity analysis shows no difference in the group of intermediate and high risk and minimal differences in the low risk group. Our findings support and validate the use of FRIDEX thresholds of FRAX when discussing the risk of fracture and the initiation of therapy with patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Seizure semiology identifies patients with bilateral temporal lobe epilepsy.

PubMed

Loesch, Anna Mira; Feddersen, Berend; Tezer, F Irsel; Hartl, Elisabeth; Rémi, Jan; Vollmar, Christian; Noachtar, Soheyl

2015-01-01

Laterality in temporal lobe epilepsy is usually defined by EEG and imaging results. We investigated whether the analysis of seizure semiology including lateralizing seizure phenomena identifies bilateral independent temporal lobe seizure onset. We investigated the seizure semiology in 17 patients in whom invasive EEG-video-monitoring documented bilateral temporal seizure onset. The results were compared to 20 left and 20 right consecutive temporal lobe epilepsy (TLE) patients who were seizure free after anterior temporal lobe resection. The seizure semiology was analyzed using the semiological seizure classification with particular emphasis on the sequence of seizure phenomena over time and lateralizing seizure phenomena. Statistical analysis included chi-square test or Fisher's exact test. Bitemporal lobe epilepsy patients had more frequently different seizure semiology (100% vs. 40%; p<0.001) and significantly more often lateralizing seizure phenomena pointing to bilateral seizure onset compared to patients with unilateral TLE (67% vs. 11%; p<0.001). The sensitivity of identical vs. different seizure semiology for the identification of bilateral TLE was high (100%) with a specificity of 60%. Lateralizing seizure phenomena had a low sensitivity (59%) but a high specificity (89%). The combination of lateralizing seizure phenomena and different seizure semiology showed a high specificity (94%) but a low sensitivity (59%). The analysis of seizure semiology including lateralizing seizure phenomena adds important clinical information to identify patients with bilateral TLE. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular Tools for Diagnosis of Visceral Leishmaniasis: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

PubMed Central

de Ruiter, C. M.; van der Veer, C.; Leeflang, M. M. G.; Deborggraeve, S.; Lucas, C.

2014-01-01

Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. PMID:24829226

Performance of the ASAS classification criteria for axial and peripheral spondyloarthritis: a systematic literature review and meta-analysis.

PubMed

Sepriano, Alexandre; Rubio, Roxana; Ramiro, Sofia; Landewé, Robert; van der Heijde, Désirée

2017-05-01

To summarise the evidence on the performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) (also imaging and clinical arm separately), peripheral (p)SpA and the entire set, when tested against the rheumatologist's diagnosis ('reference standard'). A systematic literature review was performed to identify eligible studies. Raw data on SpA diagnosis and classification were extracted or, if necessary, obtained from the authors of the selected publications. A meta-analysis was performed to obtain pooled estimates for sensitivity, specificity, positive and negative likelihood ratios, by fitting random effects models. Nine papers fulfilled the inclusion criteria (N=5739 patients). The entire set of the ASAS SpA criteria yielded a high pooled sensitivity (73%) and specificity (88%). Similarly, good results were found for the axSpA criteria (sensitivity: 82%; specificity: 88%). Splitting the axSpA criteria in 'imaging arm only' and 'clinical arm only' resulted in much lower sensitivity (30% and 23% respectively), but very high specificity was retained (97% and 94% respectively). The pSpA criteria were less often tested than the axSpA criteria and showed a similarly high pooled specificity (87%) but lower sensitivity (63%). Accumulated evidence from studies with more than 5500 patients confirms the good performance of the various ASAS SpA criteria as tested against the rheumatologist's diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Large-area, uniform and low-cost dual-mode plasmonic naked-eye colorimetry and SERS sensor with handheld Raman spectrometer

NASA Astrophysics Data System (ADS)

Xu, Zhida; Jiang, Jing; Wang, Xinhao; Han, Kevin; Ameen, Abid; Khan, Ibrahim; Chang, Te-Wei; Liu, Gang Logan

2016-03-01

We demonstrated a highly-sensitive, wafer-scale, highly-uniform plasmonic nano-mushroom substrate based on plastic for naked-eye plasmonic colorimetry and surface-enhanced Raman spectroscopy (SERS). We gave it the name FlexBrite. The dual-mode functionality of FlexBrite allows for label-free qualitative analysis by SERS with an enhancement factor (EF) of 108 and label-free quantitative analysis by naked-eye colorimetry with a sensitivity of 611 nm RIU-1. The SERS EF of FlexBrite in the wet state was found to be 4.81 × 108, 7 times stronger than in the dry state, making FlexBrite suitable for aqueous environments such as microfluid systems. The label-free detection of biotin-streptavidin interaction by both SERS and colorimetry was demonstrated with FlexBrite. The detection of trace amounts of the narcotic drug methamphetamine in drinking water by SERS was implemented with a handheld Raman spectrometer and FlexBrite. This plastic-based dual-mode nano-mushroom substrate has the potential to be used as a sensing platform for easy and fast analysis in chemical and biological assays.We demonstrated a highly-sensitive, wafer-scale, highly-uniform plasmonic nano-mushroom substrate based on plastic for naked-eye plasmonic colorimetry and surface-enhanced Raman spectroscopy (SERS). We gave it the name FlexBrite. The dual-mode functionality of FlexBrite allows for label-free qualitative analysis by SERS with an enhancement factor (EF) of 108 and label-free quantitative analysis by naked-eye colorimetry with a sensitivity of 611 nm RIU-1. The SERS EF of FlexBrite in the wet state was found to be 4.81 × 108, 7 times stronger than in the dry state, making FlexBrite suitable for aqueous environments such as microfluid systems. The label-free detection of biotin-streptavidin interaction by both SERS and colorimetry was demonstrated with FlexBrite. The detection of trace amounts of the narcotic drug methamphetamine in drinking water by SERS was implemented with a handheld Raman spectrometer and FlexBrite. This plastic-based dual-mode nano-mushroom substrate has the potential to be used as a sensing platform for easy and fast analysis in chemical and biological assays. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08357e

Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection

PubMed Central

Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

2015-01-01

Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close “neighborhood” of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa. PMID:26327290

Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection.

PubMed

Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

2015-01-01

Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close "neighborhood" of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa.

Development and evaluation of a microdevice for amino acid biomarker detection and analysis on Mars

PubMed Central

Skelley, Alison M.; Scherer, James R.; Aubrey, Andrew D.; Grover, William H.; Ivester, Robin H. C.; Ehrenfreund, Pascale; Grunthaner, Frank J.; Bada, Jeffrey L.; Mathies, Richard A.

2005-01-01

The Mars Organic Analyzer (MOA), a microfabricated capillary electrophoresis (CE) instrument for sensitive amino acid biomarker analysis, has been developed and evaluated. The microdevice consists of a four-wafer sandwich combining glass CE separation channels, microfabricated pneumatic membrane valves and pumps, and a nanoliter fluidic network. The portable MOA instrument integrates high voltage CE power supplies, pneumatic controls, and fluorescence detection optics necessary for field operation. The amino acid concentration sensitivities range from micromolar to 0.1 nM, corresponding to part-per-trillion sensitivity. The MOA was first used in the lab to analyze soil extracts from the Atacama Desert, Chile, detecting amino acids ranging from 10–600 parts per billion. Field tests of the MOA in the Panoche Valley, CA, successfully detected amino acids at 70 parts per trillion to 100 parts per billion in jarosite, a sulfate-rich mineral associated with liquid water that was recently detected on Mars. These results demonstrate the feasibility of using the MOA to perform sensitive in situ amino acid biomarker analysis on soil samples representative of a Mars-like environment. PMID:15657130

Development and evaluation of a microdevice for amino acid biomarker detection and analysis on Mars.

PubMed

Skelley, Alison M; Scherer, James R; Aubrey, Andrew D; Grover, William H; Ivester, Robin H C; Ehrenfreund, Pascale; Grunthaner, Frank J; Bada, Jeffrey L; Mathies, Richard A

2005-01-25

The Mars Organic Analyzer (MOA), a microfabricated capillary electrophoresis (CE) instrument for sensitive amino acid biomarker analysis, has been developed and evaluated. The microdevice consists of a four-wafer sandwich combining glass CE separation channels, microfabricated pneumatic membrane valves and pumps, and a nanoliter fluidic network. The portable MOA instrument integrates high voltage CE power supplies, pneumatic controls, and fluorescence detection optics necessary for field operation. The amino acid concentration sensitivities range from micromolar to 0.1 nM, corresponding to part-per-trillion sensitivity. The MOA was first used in the lab to analyze soil extracts from the Atacama Desert, Chile, detecting amino acids ranging from 10-600 parts per billion. Field tests of the MOA in the Panoche Valley, CA, successfully detected amino acids at 70 parts per trillion to 100 parts per billion in jarosite, a sulfate-rich mineral associated with liquid water that was recently detected on Mars. These results demonstrate the feasibility of using the MOA to perform sensitive in situ amino acid biomarker analysis on soil samples representative of a Mars-like environment.

Mixed kernel function support vector regression for global sensitivity analysis

NASA Astrophysics Data System (ADS)

Cheng, Kai; Lu, Zhenzhou; Wei, Yuhao; Shi, Yan; Zhou, Yicheng

2017-11-01

Global sensitivity analysis (GSA) plays an important role in exploring the respective effects of input variables on an assigned output response. Amongst the wide sensitivity analyses in literature, the Sobol indices have attracted much attention since they can provide accurate information for most models. In this paper, a mixed kernel function (MKF) based support vector regression (SVR) model is employed to evaluate the Sobol indices at low computational cost. By the proposed derivation, the estimation of the Sobol indices can be obtained by post-processing the coefficients of the SVR meta-model. The MKF is constituted by the orthogonal polynomials kernel function and Gaussian radial basis kernel function, thus the MKF possesses both the global characteristic advantage of the polynomials kernel function and the local characteristic advantage of the Gaussian radial basis kernel function. The proposed approach is suitable for high-dimensional and non-linear problems. Performance of the proposed approach is validated by various analytical functions and compared with the popular polynomial chaos expansion (PCE). Results demonstrate that the proposed approach is an efficient method for global sensitivity analysis.

Ultra-high resolution, polarization sensitive transversal optical coherence tomography for structural analysis and strain mapping

NASA Astrophysics Data System (ADS)

Wiesauer, Karin; Pircher, Michael; Goetzinger, Erich; Hitzenberger, Christoph K.; Engelke, Rainer; Ahrens, Gisela; Pfeiffer, Karl; Ostrzinski, Ute; Gruetzner, Gabi; Oster, Reinhold; Stifter, David

2006-02-01

Optical coherence tomography (OCT) is a contactless and non-invasive technique nearly exclusively applied for bio-medical imaging of tissues. Besides the internal structure, additionally strains within the sample can be mapped when OCT is performed in a polarization sensitive (PS) way. In this work, we demonstrate the benefits of PS-OCT imaging for non-biological applications. We have developed the OCT technique beyond the state-of-the-art: based on transversal ultra-high resolution (UHR-)OCT, where an axial resolution below 2 μm within materials is obtained using a femtosecond laser as light source, we have modified the setup for polarization sensitive measurements (transversal UHR-PS-OCT). We perform structural analysis and strain mapping for different types of samples: for a highly strained elastomer specimen we demonstrate the necessity of UHR-imaging. Furthermore, we investigate epoxy waveguide structures, photoresist moulds for the fabrication of micro-electromechanical parts (MEMS), and the glass-fibre composite outer shell of helicopter rotor blades where cracks are present. For these examples, transversal scanning UHR-PS-OCT is shown to provide important information about the structural properties and the strain distribution within the samples.

Environmental management zoning for coal mining in mainland China based on ecological and resources conditions.

PubMed

Geng, Haiqing; Chen, Fan; Wang, Zhiyuan; Liu, Jie; Xu, Weihua

2017-05-01

The purpose of this research is to establish an environmental management zoning for coal mining industry which is served as a basis for making environmental management policies. Based on the specific impacts of coal mining and regional characteristics of environment and resources, the ecological impact, water resources impact, and arable land impact are chose as the zoning indexes to construct the index system. The ecological sensitivity is graded into three levels of low, medium, and high according to analytical hierarchy processes and gray fixed weight clustering analysis, and the water resources sensitivity is divided into five levels of lower, low, medium, high, and higher according to the weighted sum of sub-indexes, while only the arable land sensitive zone was extracted on the basis of the ratio of arable land to the county or city. By combining the ecological sensitivity zoning and the water resources sensitive zoning and then overlapping the arable-sensitive areas, the mainland China is classified into six types of environmental management zones for coal mining except to the forbidden exploitation areas.

Partially reduced graphene oxide based FRET on fiber-optic interferometer for biochemical detection

NASA Astrophysics Data System (ADS)

Yao, B. C.; Wu, Y.; Yu, C. B.; He, J. R.; Rao, Y. J.; Gong, Y.; Fu, F.; Chen, Y. F.; Li, Y. R.

2016-03-01

Fluorescent resonance energy transfer (FRET) with naturally exceptional selectivity is a powerful technique and widely used in chemical and biomedical analysis. However, it is still challenging for conventional FRET to perform as a high sensitivity compact sensor. Here we propose a novel ‘FRET on Fiber’ concept, in which a partially reduced graphene oxide (prGO) film is deposited on a fiber-optic modal interferometer, acting as both the fluorescent quencher for the FRET and the sensitive cladding for optical phase measurement due to refractive index changes in biochemical detection. The target analytes induced fluorescence recovery with good selectivity and optical phase shift with high sensitivity are measured simultaneously. The functionalized prGO film coated on the fiber-optic interferometer shows high sensitivities for the detections of metal ion, dopamine and single-stranded DNA (ssDNA), with detection limits of 1.2 nM, 1.3 μM and 1 pM, respectively. Such a prGO based ‘FRET on fiber’ configuration, bridging the FRET and the fiber-optic sensing technology, may serve as a platform for the realization of series of integrated ‘FRET on Fiber’ sensors for on-line environmental, chemical, and biomedical detection, with excellent compactness, high sensitivity, good selectivity and fast response

Chemically Designed Metallic/Insulating Hybrid Nanostructures with Silver Nanocrystals for Highly Sensitive Wearable Pressure Sensors.

PubMed

Kim, Haneun; Lee, Seung-Wook; Joh, Hyungmok; Seong, Mingi; Lee, Woo Seok; Kang, Min Su; Pyo, Jun Beom; Oh, Soong Ju

2018-01-10

With the increase in interest in wearable tactile pressure sensors for e-skin, researches to make nanostructures to achieve high sensitivity have been actively conducted. However, limitations such as complex fabrication processes using expensive equipment still exist. Herein, simple lithography-free techniques to develop pyramid-like metal/insulator hybrid nanostructures utilizing nanocrystals (NCs) are demonstrated. Ligand-exchanged and unexchanged silver NC thin films are used as metallic and insulating components, respectively. The interfaces of each NC layer are chemically engineered to create discontinuous insulating layers, i.e., spacers for improved sensitivity, and eventually to realize fully solution-processed pressure sensors. Device performance analysis with structural, chemical, and electronic characterization and conductive atomic force microscopy study reveals that hybrid nanostructure based pressure sensor shows an enhanced sensitivity of higher than 500 kPa -1 , reliability, and low power consumption with a wide range of pressure sensing. Nano-/micro-hierarchical structures are also designed by combining hybrid nanostructures with conventional microstructures, exhibiting further enhanced sensing range and achieving a record sensitivity of 2.72 × 10 4 kPa -1 . Finally, all-solution-processed pressure sensor arrays with high pixel density, capable of detecting delicate signals with high spatial selectivity much better than the human tactile threshold, are introduced.

Partially reduced graphene oxide based FRET on fiber-optic interferometer for biochemical detection

PubMed Central

Yao, B. C.; Wu, Y.; Yu, C. B.; He, J. R.; Rao, Y. J.; Gong, Y.; Fu, F.; Chen, Y. F.; Li, Y. R.

2016-01-01

Fluorescent resonance energy transfer (FRET) with naturally exceptional selectivity is a powerful technique and widely used in chemical and biomedical analysis. However, it is still challenging for conventional FRET to perform as a high sensitivity compact sensor. Here we propose a novel ‘FRET on Fiber’ concept, in which a partially reduced graphene oxide (prGO) film is deposited on a fiber-optic modal interferometer, acting as both the fluorescent quencher for the FRET and the sensitive cladding for optical phase measurement due to refractive index changes in biochemical detection. The target analytes induced fluorescence recovery with good selectivity and optical phase shift with high sensitivity are measured simultaneously. The functionalized prGO film coated on the fiber-optic interferometer shows high sensitivities for the detections of metal ion, dopamine and single-stranded DNA (ssDNA), with detection limits of 1.2 nM, 1.3 μM and 1 pM, respectively. Such a prGO based ‘FRET on fiber’ configuration, bridging the FRET and the fiber-optic sensing technology, may serve as a platform for the realization of series of integrated ‘FRET on Fiber’ sensors for on-line environmental, chemical, and biomedical detection, with excellent compactness, high sensitivity, good selectivity and fast response PMID:27010752

Palladium Gate All Around - Hetero Dielectric -Tunnel FET based highly sensitive Hydrogen Gas Sensor

NASA Astrophysics Data System (ADS)

Madan, Jaya; Chaujar, Rishu

2016-12-01

The paper presents a novel highly sensitive Hetero-Dielectric-Gate All Around Tunneling FET (HD-GAA-TFET) based Hydrogen Gas Sensor, incorporating the advantages of band to band tunneling (BTBT) mechanism. Here, the Palladium supported silicon dioxide is used as a sensing media and sensing relies on the interaction of hydrogen with Palladium-SiO2-Si. The high surface to volume ratio in the case of cylindrical GAA structure enhances the fortuities for surface reactions between H2 gas and Pd, and thus improves the sensitivity and stability of the sensor. Behaviour of the sensor in presence of hydrogen and at elevated temperatures is discussed. The conduction path of the sensor which is dependent on sensors radius has also been varied for the optimized sensitivity and static performance analysis of the sensor where the proposed design exhibits a superior performance in terms of threshold voltage, subthreshold swing, and band to band tunneling rate. Stability of the sensor with respect to temperature affectability has also been studied, and it is found that the device is reasonably stable and highly sensitive over the bearable temperature range. The successful utilization of HD-GAA-TFET in gas sensors may open a new door for the development of novel nanostructure gas sensing devices.

LSENS: A General Chemical Kinetics and Sensitivity Analysis Code for homogeneous gas-phase reactions. Part 3: Illustrative test problems

NASA Technical Reports Server (NTRS)

Bittker, David A.; Radhakrishnan, Krishnan

1994-01-01

LSENS, the Lewis General Chemical Kinetics and Sensitivity Analysis Code, has been developed for solving complex, homogeneous, gas-phase chemical kinetics problems and contains sensitivity analysis for a variety of problems, including nonisothermal situations. This report is part 3 of a series of three reference publications that describe LSENS, provide a detailed guide to its usage, and present many example problems. Part 3 explains the kinetics and kinetics-plus-sensitivity analysis problems supplied with LSENS and presents sample results. These problems illustrate the various capabilities of, and reaction models that can be solved by, the code and may provide a convenient starting point for the user to construct the problem data file required to execute LSENS. LSENS is a flexible, convenient, accurate, and efficient solver for chemical reaction problems such as static system; steady, one-dimensional, inviscid flow; reaction behind incident shock wave, including boundary layer correction; and perfectly stirred (highly backmixed) reactor. In addition, the chemical equilibrium state can be computed for the following assigned states: temperature and pressure, enthalpy and pressure, temperature and volume, and internal energy and volume. For static problems the code computes the sensitivity coefficients of the dependent variables and their temporal derivatives with respect to the initial values of the dependent variables and/or the three rate coefficient parameters of the chemical reactions.

Towards a Better Understanding of Water Stores and Fluxes: Model Observation Synthesis in a Snowmelt Dominated Research Watershed

NASA Astrophysics Data System (ADS)

Ryken, A.; Gochis, D.; Carroll, R. W. H.; Bearup, L. A.; Williams, K. H.; Maxwell, R. M.

2017-12-01

The hydrology of high-elevation, mountainous regions is poorly represented in Earth Systems Models (ESMs). In addition to regulating downstream water delivery, these ecosystems play an important role in the storage and land-atmosphere exchange of carbon and water. Water balances are sensitive to the amount of water stored in the snowpack (SWE) and the amount of water leaving the system in the form of evapotranspiration—two pieces of the hydrologic cycle that are difficult to observe and model in heterogeneous mountainous regions due to spatially variant weather patterns. In an effort to resolve this hydrologic gap in ESMs, this study seeks to better understand the interactions between groundwater, carbon flux, and the lower atmosphere in these high-altitude environments through integration of field observations and model simulations. We compare model simulations to field observations to elucidate process performance combined with a sensitivity analysis to better understand parameter uncertainty. Observations from a meteorological station in the East River Basin are used to force an integrated single-column hydrologic model, ParFlow-CLM. This met station is co-located with an eddy covariance tower, which, along with snow surveys, is used to better constrain the water, carbon, and energy fluxes in the coupled land-atmosphere model to increase our understanding of high-altitude headwaters. Preliminary results suggest the model compares well to the eddy covariance tower and field observations, shown through both correct magnitude and timing of peak SWE along with similar magnitudes and diurnal patterns of heat and water fluxes. Initial sensitivity analysis results show that an increase in temperature leads to a decrease in peak SWE as well as an increase in latent heat revealing a sensitivity of the model to air temperature. Further sensitivity analysis will help us understand more parameter uncertainty. Through obtaining more accurate and higher resolution meteorological data and applying it to a coupled hydrologic model, this study can lead to better representation of mountainous environments in all ESMs.

Retrospective validation of the laparoscopic ICG SLN mapping in patients with grade 3 endometrial cancer.

PubMed

Papadia, Andrea; Gasparri, Maria Luisa; Radan, Anda P; Stämpfli, Chantal A L; Rau, Tilman T; Mueller, Michael D

2018-04-24

To evaluate the sensitivity, negative predictive value (NPV) and false-negative (FN) rate of the near infrared (NIR) indocyanine green (ICG) sentinel lymph node (SLN) mapping in patients with poorly differentiated endometrial cancer who have undergone a full pelvic and para-aortic lymphadenectomy after SLN mapping. We performed a retrospective analysis of patients with endometrial cancer undergoing a laparoscopic NIR-ICG SLN mapping followed by a systematic pelvic and para-aortic lymphadenectomy. Inclusion criteria were a grade 3 endometrial cancer or a high-risk histology (papillary serous, clear cell carcinoma, carcinosarcoma, and neuroendocrine carcinoma) and a completion pelvic and para-aortic lymphadenectomy to the renal vessels after SLN mapping. Overall and bilateral detection rates, sensitivity, NPV, and FN rates were calculated. From December 2012 until January 2017, 42 patients fulfilled inclusion criteria. Overall and bilateral detection rates were 100 and 90.5%, respectively. Overall, 23.8% of the patients had lymph node metastases. In one patient, despite negative bilateral pelvic SLNs, a metastatic non-SLN-isolated para-aortic metastasis was detected. This NSLN was clinically suspicious and sent to frozen section analysis during the surgery. FN rate, sensitivity, and NPV were 10, 90, and 97.1%, respectively. For the SLN mapping algorithm, FN rate, sensitivity, and NPV were 0, 100, and 100%, respectively. Laparoscopic NIR-ICG SLN mapping in high-risk endometrial cancer patients has acceptable sensitivity, FN rate, and NPV.

Sensitivity and accuracy of hybrid fluorescence-mediated tomography in deep tissue regions.

PubMed

Rosenhain, Stefanie; Al Rawashdeh, Wa'el; Kiessling, Fabian; Gremse, Felix

2017-09-01

Fluorescence-mediated tomography (FMT) enables noninvasive assessment of the three-dimensional distribution of near-infrared fluorescence in mice. The combination with micro-computed tomography (µCT) provides anatomical data, enabling improved fluorescence reconstruction and image analysis. The aim of our study was to assess sensitivity and accuracy of µCT-FMT under realistic in vivo conditions in deeply-seated regions. Accordingly, we acquired fluorescence reflectance images (FRI) and µCT-FMT scans of mice which were prepared with rectal insertions with different amounts of fluorescent dye. Default and high-sensitivity scans were acquired and background signal was analyzed for three FMT channels (670 nm, 745 nm, and 790 nm). Analysis was performed for the original and an improved FMT reconstruction using the µCT data. While FRI and the original FMT reconstruction could detect 100 pmol, the improved FMT reconstruction could detect 10 pmol and significantly improved signal localization. By using a finer sampling grid and increasing the exposure time, the sensitivity could be further improved to detect 0.5 pmol. Background signal was highest in the 670 nm channel and most prominent in the gastro-intestinal tract and in organs with high relative amounts of blood. In conclusion, we show that µCT-FMT allows sensitive and accurate assessment of fluorescence in deep tissue regions. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ultrahigh-Sensitivity Piezoresistive Pressure Sensors for Detection of Tiny Pressure.

PubMed

Li, Hongwei; Wu, Kunjie; Xu, Zeyang; Wang, Zhongwu; Meng, Yancheng; Li, Liqiang

2018-06-20

High-sensitivity pressure sensors are crucial for the ultrasensitive touch technology and E-skin, especially at the tiny-pressure range below 100 Pa. However, it is highly challenging to substantially promote sensitivity beyond the current level at several to 200 kPa -1 and to improve the detection limit lower than 0.1 Pa, which is significant for the development of pressure sensors toward ultrasensitive and highly precise detection. Here, we develop an efficient strategy to greatly improve the sensitivity near to 2000 kPa -1 using short-channel coplanar device structure and sharp microstructure, which is systematically proposed for the first time and rationalized by the mathematic calculation and analysis. Significantly, benefiting from the ultrahigh sensitivity, the detection limit is improved to be as small as 0.075 Pa. The sensitivity and detection limit are both superior to the current levels and far surpass the function of human skin. Furthermore, the sensor shows fast response time (50 μs), excellent reproducibility and stability, and low power consumption. Remarkably, the sensor shows excellent detection capacity in the tiny-pressure range, including light-emitting diode switching with a pressure of 7 Pa, ringtone (2-20 Pa) recognition, and ultrasensitive (0.1 Pa) electronic glove. This work represents a performance and strategic progress in the field of pressure sensing.

Absorption of CO2 on Carbon-based Sensors: First-Principle Analysis

NASA Astrophysics Data System (ADS)

Tit, Nacir; Elezzi, Mohammed; Abdullah, Hasan; Bahlouli, Hocine; Yamani, Zain

We present first-principle investigation of the adsorption properties of CO and CO2 molecules on both graphene and carbon nano-tubes (CNTs) in presence of metal catalysis, mainly iron (Fe). The relaxations were carried out using the self-consistent-charge density-functional tight-binding (SCC-DFTB) code in neglect of heat effects. The results show the following: (1) Defected graphene is found to have high sensitivity and high selectivity towards chemisorption of CO molecules and weak physisorption with CO2 molecules. (2) In case of CNTs, the iron ``Fe'' catalyst plays an essential role in capturing CO2 molecules. The Fe ad-atoms on the surface of CNT introduce huge density of states at Fermi level, but the capture of CO2 molecules would reduce that density and consequently reduce conductivity and increase sensitivity. Concerning the selectivity, we have studied the sensitivity versus various gas molecules (such as: O2, N2, H2, H2O, and CO). Furthermore, to assess the effect of catalysis on sensitivity, we have studied the sensitivity of other metal catalysts (such as: Ni, Co, Ti, and Sc). We found that CNT-Fe is highly sensitive and selective towards detection of CO and CO2 molecules. CNT being conductive or semiconducting does not matter much on the adsorption properties.

Effect of aberrations in human eye on contrast sensitivity function

NASA Astrophysics Data System (ADS)

Quan, Wei; Wang, Feng-lin; Wang, Zhao-qi

2011-06-01

The quantitative analysis of the effect of aberrations in human eye on vision has important clinical value in the correction of aberrations. The wave-front aberrations of human eyes were measured with the Hartmann-Shack wave-front sensor and modulation transfer function (MTF) was computed from the wave-front aberrations. Contrast sensitivity function (CSF) was obtained from MTF and the retinal aerial image modulation (AIM). It is shown that the 2nd, 3rd, 4th, 5th, 6th Zernike aberrations deteriorate contrast sensitivity function. When the 2nd, 3rd, 4th, 5th, 6th Zernike aberrations are corrected high contrast sensitivity function can be obtained.

SiPM electro-optical detection system noise suppression method

NASA Astrophysics Data System (ADS)

Bi, Xiangli; Yang, Suhui; Hu, Tao; Song, Yiheng

2014-11-01

In this paper, the single photon detection principle of Silicon Photomultipliers (SiPM) device is introduced. The main noise factors that infect the sensitivity of the electro-optical detection system are analyzed, including background light noise, detector dark noise, preamplifier noise and signal light noise etc. The Optical, electrical and thermodynamic methods are used to suppress the SiPM electro-optical detection system noise, which improved the response sensitivity of the detector. Using SiPM optoelectronic detector with a even high sensitivity, together with small field large aperture optical system, high cutoff narrow bandwidth filters, low-noise operational amplifier circuit, the modular design of functional circuit, semiconductor refrigeration technology, greatly improved the sensitivity of optical detection system, reduced system noise and achieved long-range detection of weak laser radiation signal. Theoretical analysis and experimental results show that the proposed methods are reasonable and efficient.

Highly Sensitive Hot-Wire Anemometry Based on Macro-Sized Double-Walled Carbon Nanotube Strands.

PubMed

Wang, Dingqu; Xiong, Wei; Zhou, Zhaoying; Zhu, Rong; Yang, Xing; Li, Weihua; Jiang, Yueyuan; Zhang, Yajun

2017-08-01

This paper presents a highly sensitive flow-rate sensor with carbon nanotubes (CNTs) as sensing elements. The sensor uses micro-size centimeters long double-walled CNT (DWCNT) strands as hot-wires to sense fluid velocity. In the theoretical analysis, the sensitivity of the sensor is demonstrated to be positively related to the ratio of its surface. We assemble the flow sensor by suspending the DWCNT strand directly on two tungsten prongs and dripping a small amount of silver glue onto each contact between the DWCNT and the prongs. The DWCNT exhibits a positive TCR of 1980 ppm/K. The self-heating effect on the DWCNT was observed while constant current was applied between the two prongs. This sensor can evidently respond to flow rate, and requires only several milliwatts to operate. We have, thus far, demonstrated that the CNT-based flow sensor has better sensitivity than the Pt-coated DWCNT sensor.

Laser ablation surface-enhanced Raman microspectroscopy.

PubMed

Londero, Pablo S; Lombardi, John R; Leona, Marco

2013-06-04

Improved identification of trace organic compounds in complex matrixes is critical for a variety of fields such as material science, heritage science, and forensics. Surface-enhanced Raman scattering (SERS) is a vibrational spectroscopy technique that can attain single-molecule sensitivity and has been shown to complement mass spectrometry, but lacks widespread application without a robust method that utilizes the effect. We demonstrate a new, highly sensitive, and widely applicable approach to SERS analysis based on laser ablation in the presence of a tailored plasmonic substrate. We analyze several challenging compounds, including non-water-soluble pigments and dyed leather from an ancient Egyptian chariot, achieving sensitivity as high as 120 amol for a 1:1 signal-to-noise ratio and 5 μm spatial resolution. This represents orders of magnitude improvement in spatial resolution and sensitivity compared to those of other SERS approaches intended for widespread application, greatly increasing the applicability of SERS.

Theoretical foundations for finite-time transient stability and sensitivity analysis of power systems

NASA Astrophysics Data System (ADS)

Dasgupta, Sambarta

Transient stability and sensitivity analysis of power systems are problems of enormous academic and practical interest. These classical problems have received renewed interest, because of the advancement in sensor technology in the form of phasor measurement units (PMUs). The advancement in sensor technology has provided unique opportunity for the development of real-time stability monitoring and sensitivity analysis tools. Transient stability problem in power system is inherently a problem of stability analysis of the non-equilibrium dynamics, because for a short time period following a fault or disturbance the system trajectory moves away from the equilibrium point. The real-time stability decision has to be made over this short time period. However, the existing stability definitions and hence analysis tools for transient stability are asymptotic in nature. In this thesis, we discover theoretical foundations for the short-term transient stability analysis of power systems, based on the theory of normally hyperbolic invariant manifolds and finite time Lyapunov exponents, adopted from geometric theory of dynamical systems. The theory of normally hyperbolic surfaces allows us to characterize the rate of expansion and contraction of co-dimension one material surfaces in the phase space. The expansion and contraction rates of these material surfaces can be computed in finite time. We prove that the expansion and contraction rates can be used as finite time transient stability certificates. Furthermore, material surfaces with maximum expansion and contraction rate are identified with the stability boundaries. These stability boundaries are used for computation of stability margin. We have used the theoretical framework for the development of model-based and model-free real-time stability monitoring methods. Both the model-based and model-free approaches rely on the availability of high resolution time series data from the PMUs for stability prediction. The problem of sensitivity analysis of power system, subjected to changes or uncertainty in load parameters and network topology, is also studied using the theory of normally hyperbolic manifolds. The sensitivity analysis is used for the identification and rank ordering of the critical interactions and parameters in the power network. The sensitivity analysis is carried out both in finite time and in asymptotic. One of the distinguishing features of the asymptotic sensitivity analysis is that the asymptotic dynamics of the system is assumed to be a periodic orbit. For asymptotic sensitivity analysis we employ combination of tools from ergodic theory and geometric theory of dynamical systems.

Vitamin D deficiency in childhood obesity is associated with high levels of circulating inflammatory mediators, and low insulin sensitivity.

PubMed

Reyman, M; Verrijn Stuart, A A; van Summeren, M; Rakhshandehroo, M; Nuboer, R; de Boer, F K; van den Ham, H J; Kalkhoven, E; Prakken, B; Schipper, H S

2014-01-01

Childhood obesity is accompanied by low-grade systemic inflammation, which contributes to the development of insulin resistance and cardiovascular complications later in life. As vitamin D exhibits profound immunomodulatory functions and vitamin D deficiency is highly prevalent in childhood obesity, we hypothesized that vitamin D deficiency in childhood obesity coincides with enhanced systemic inflammation and reduced insulin sensitivity. In a cross-sectional study of 64 obese and 32 healthy children aged 6-16 years, comprehensive profiling of 32 circulating inflammatory mediators was performed, together with assessment of 25-hydroxyvitamin D (25(OH)D) levels and measures for insulin sensitivity. Severe vitamin D insufficiency, which is further referred to as vitamin D deficiency, was defined as a 25(OH)D level ≤37.5 nmol l(-1), and was highly prevalent in obese (56%) versus healthy control children (16%). Throughout the study, 25(OH)D-deficient children were compared with the other children, including 25(OH)D insufficient (37.5-50 nmol l(-1)) and 25(OH)D sufficient children (≥50 nmol l(-1)). First, 25(OH)D-deficient obese children showed a lower insulin sensitivity than other obese children, as measured by a lower quantitative insulin sensitivity check index. Second, the association between 25(OH)D deficiency and insulin resistance in childhood obesity was confirmed with multiple regression analysis. Third, 25(OH)D-deficient obese children showed higher levels of the inflammatory mediators cathepsin S, chemerin and soluble vascular adhesion molecule (sVCAM), compared with the other obese children. Finally, hierarchical cluster analysis revealed an over-representation of 25(OH)D deficiency in obese children expressing inflammatory mediator clusters with high levels of cathepsin S, sVCAM and chemerin. 25(OH)D deficiency in childhood obesity was associated with enhanced systemic inflammation and reduced insulin sensitivity. The high cathepsin S and sVCAM levels may reflect activation of a pro-inflammatory, pro-diabetic and atherogenic pathway, which could be inhibited by vitamin D supplementation.

Landscape sensitivity in a dynamic environment

NASA Astrophysics Data System (ADS)

Lin, Jiun-Chuan; Jen, Chia-Horn

2010-05-01

Landscape sensitivity at different scales and topics is presented in this study. Methodological approach composed most of this paper. According to the environmental records in the south eastern Asia, the environment change is highly related with five factors, such as scale of influence area, background of environment characters, magnitude and frequency of events, thresholds of occurring hazards and influence by time factor. This paper tries to demonstrate above five points from historical and present data. It is found that landscape sensitivity is highly related to the degree of vulnerability of the land and the processes which put on the ground including human activities. The scale of sensitivity and evaluation of sensitivities is demonstrated in this paper by the data around east Asia. The methods of classification are mainly from the analysis of environmental data and the records of hazards. From the trend of rainfall records, rainfall intensity and change of temperature, the magnitude and frequency of earthquake, dust storm, days of draught, number of hazards, there are many coincidence on these factors with landscape sensitivities. In conclusion, the landscape sensitivities could be classified as four groups: physical stable, physical unstable, unstable, extremely unstable. This paper explain the difference.

Sensitivity analysis of radionuclides atmospheric dispersion following the Fukushima accident

NASA Astrophysics Data System (ADS)

Girard, Sylvain; Korsakissok, Irène; Mallet, Vivien

2014-05-01

Atmospheric dispersion models are used in response to accidental releases with two purposes: - minimising the population exposure during the accident; - complementing field measurements for the assessment of short and long term environmental and sanitary impacts. The predictions of these models are subject to considerable uncertainties of various origins. Notably, input data, such as meteorological fields or estimations of emitted quantities as function of time, are highly uncertain. The case studied here is the atmospheric release of radionuclides following the Fukushima Daiichi disaster. The model used in this study is Polyphemus/Polair3D, from which derives IRSN's operational long distance atmospheric dispersion model ldX. A sensitivity analysis was conducted in order to estimate the relative importance of a set of identified uncertainty sources. The complexity of this task was increased by four characteristics shared by most environmental models: - high dimensional inputs; - correlated inputs or inputs with complex structures; - high dimensional output; - multiplicity of purposes that require sophisticated and non-systematic post-processing of the output. The sensitivities of a set of outputs were estimated with the Morris screening method. The input ranking was highly dependent on the considered output. Yet, a few variables, such as horizontal diffusion coefficient or clouds thickness, were found to have a weak influence on most of them and could be discarded from further studies. The sensitivity analysis procedure was also applied to indicators of the model performance computed on a set of gamma dose rates observations. This original approach is of particular interest since observations could be used later to calibrate the input variables probability distributions. Indeed, only the variables that are influential on performance scores are likely to allow for calibration. An indicator based on emission peaks time matching was elaborated in order to complement classical statistical scores which were dominated by deposit dose rates and almost insensitive to lower atmosphere dose rates. The substantial sensitivity of these performance indicators is auspicious for future calibration attempts and indicates that the simple perturbations used here may be sufficient to represent an essential part of the overall uncertainty.

A global sensitivity analysis approach for morphogenesis models.

PubMed

Boas, Sonja E M; Navarro Jimenez, Maria I; Merks, Roeland M H; Blom, Joke G

2015-11-21

Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such 'black-box' models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all 'black-box' models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

Performance of FDG-PET/CT in solitary pulmonary nodule based on pre-test likelihood of malignancy: results from the ITALIAN retrospective multicenter trial.

PubMed

Evangelista, Laura; Cuocolo, Alberto; Pace, Leonardo; Mansi, Luigi; Del Vecchio, Silvana; Miletto, Paolo; Sanfilippo, Silvia; Pellegrino, Sara; Guerra, Luca; Pepe, Giovanna; Peluso, Giuseppina; Salvatore, Marco; Galicchio, Rosj; Zuffante, Michele; Annunziata, Salvatore; Farsad, Mohsen; Chiaravalloti, Agostino; Spadafora, Marco

2018-05-07

The aim of this study was to determine the performance of 18 F-FDG-PET/CT in patients with solitary pulmonary nodule (SPN), stratifying the risk according to the likelihood of pulmonary malignancy. FDG-PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. FDG uptake in SPN was assessed by a 4-point scoring system and semiquantitative analysis using the ratio between SUVmax in SPN and SUVmean in mediastinal blood pool (BP) and between SUVmax in SPN and SUVmean in liver (L). Histopathology and/or follow-up data were used as standard of reference. SPN was malignant in 180 (36%) patients, benign in 175 (35%), and indeterminate in 147 (29%). The 355 patients with a definitive SPN nature (malignant or benign) were considered for the analysis. Considering FDG uptake ≥ 2, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were 85.6%, 85.7%, 86%, 85.2%, and 85.6% respectively. Sensitivity and PPV were higher (P < 0.05) in intermediate and high-risk patients, while specificity and NPV were higher (P < 0.05) in low-risk patients. On receiver operating characteristic curve analysis, the cut-offs for better discrimination between benign and malignant SPN were 1.56 (sensitivity 81% and specificity 87%) and 1.12 (sensitivity 81% and specificity 86%) for SUVmax/SUVmeanBP and SUVmax/SUVmeanL respectively. In intermediate and high-risk patients, including the SUVmax/SUVmeanBP, the specificity shifted from 85% and 50% to 100%. Visual FDG-PET/CT has an acceptable performance in patients with SPN, but accuracy improves when SUVratios are considered, particularly in patients with intermediate and high risk of malignancy.

Critical comparison of mass analyzers for forensic hair analysis by ambient ionization mass spectrometry.

PubMed

Duvivier, Wilco F; van Beek, Teris A; Nielen, Michel W F

2016-11-15

Recently, several direct and/or ambient mass spectrometry (MS) approaches have been suggested for drugs of abuse imaging in hair. The use of mass spectrometers with insufficient selectivity could result in false-positive measurements due to isobaric interferences. Different mass analyzers have been evaluated regarding their selectivity and sensitivity for the detection of Δ9-tetrahydrocannabinol (THC) from intact hair samples using direct analysis in real time (DART) ionization. Four different mass analyzers, namely (1) an orbitrap, (2) a quadrupole orbitrap, (3) a triple quadrupole, and (4) a quadrupole time-of-flight (QTOF), were evaluated. Selectivity and sensitivity were assessed by analyzing secondary THC standard dilutions on stainless steel mesh screens and blank hair samples, and by the analysis of authentic cannabis user hair samples. Additionally, separation of isobaric ions by use of travelling wave ion mobility (TWIM) was investigated. The use of a triple quadrupole instrument resulted in the highest sensitivity; however, transitions used for multiple reaction monitoring were only found to be specific when using high mass resolution product ion measurements. A mass resolution of at least 30,000 FWHM at m/z 315 was necessary to avoid overlap of THC with isobaric ions originating from the hair matrix. Even though selectivity was enhanced by use of TWIM, the QTOF instrument in resolution mode could not indisputably differentiate THC from endogenous isobaric ions in drug user hair samples. Only the high resolution of the (quadrupole) orbitrap instruments and the QTOF instrument in high-resolution mode distinguished THC in hair samples from endogenous isobaric interferences. As expected, enhanced selectivity compromises sensitivity and THC was only detectable in hair from heavy users. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhao, Jianhua; Zeng, Haishan; Kalia, Sunil; Lui, Harvey

2017-02-01

Background: Raman spectroscopy is a non-invasive optical technique which can measure molecular vibrational modes within tissue. A large-scale clinical study (n = 518) has demonstrated that real-time Raman spectroscopy could distinguish malignant from benign skin lesions with good diagnostic accuracy; this was validated by a follow-up independent study (n = 127). Objective: Most of the previous diagnostic algorithms have typically been based on analyzing the full band of the Raman spectra, either in the fingerprint or high wavenumber regions. Our objective in this presentation is to explore wavenumber selection based analysis in Raman spectroscopy for skin cancer diagnosis. Methods: A wavenumber selection algorithm was implemented using variably-sized wavenumber windows, which were determined by the correlation coefficient between wavenumbers. Wavenumber windows were chosen based on accumulated frequency from leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were then generated from the selected wavenumber windows using multivariate statistical analyses, including principal component and general discriminant analysis (PC-GDA) and partial least squares (PLS). A total cohort of 645 confirmed lesions from 573 patients encompassing skin cancers, precancers and benign skin lesions were included. Lesion measurements were divided into training cohort (n = 518) and testing cohort (n = 127) according to the measurement time. Result: The area under the receiver operating characteristic curve (ROC) improved from 0.861-0.891 to 0.891-0.911 and the diagnostic specificity for sensitivity levels of 0.99-0.90 increased respectively from 0.17-0.65 to 0.20-0.75 by selecting specific wavenumber windows for analysis. Conclusion: Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels.

Optical Coherence Tomography Minimum Intensity as an Objective Measure for the Detection of Hydroxychloroquine Toxicity.

PubMed

Allahdina, Ali M; Stetson, Paul F; Vitale, Susan; Wong, Wai T; Chew, Emily Y; Ferris, Fredrick L; Sieving, Paul A; Cukras, Catherine

2018-04-01

As optical coherence tomography (OCT) minimum intensity (MI) analysis provides a quantitative assessment of changes in the outer nuclear layer (ONL), we evaluated the ability of OCT-MI analysis to detect hydroxychloroquine toxicity. Fifty-seven predominantly female participants (91.2% female; mean age, 55.7 ± 10.4 years; mean time on hydroxychloroquine, 15.0 ± 7.5 years) were enrolled in a case-control study and categorized into affected (i.e., with toxicity, n = 19) and unaffected (n = 38) groups using objective multifocal electroretinographic (mfERG) criteria. Spectral-domain OCT scans of the macula were analyzed and OCT-MI values quantitated for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. A two-sample U-test and a cross-validation approach were used to assess the sensitivity and specificity of toxicity detection according to OCT-MI criteria. The medians of the OCT-MI values in all nine of the ETDRS subfields were significantly elevated in the affected group relative to the unaffected group (P < 0.005 for all comparisons), with the largest difference found for the inner inferior subfield (P < 0.0001). The receiver operating characteristic analysis of median MI values of the inner inferior subfields showed high sensitivity and high specificity in the detection of toxicity with area under the curve = 0.99. Retinal changes secondary to hydroxychloroquine toxicity result in increased OCT reflectivity in the ONL that can be detected and quantitated using OCT-MI analysis. Analysis of OCT-MI values demonstrates high sensitivity and specificity for detecting the presence of hydroxychloroquine toxicity in this cohort and may contribute additionally to current screening practices.

Optical Coherence Tomography Minimum Intensity as an Objective Measure for the Detection of Hydroxychloroquine Toxicity

PubMed Central

Allahdina, Ali M.; Stetson, Paul F.; Vitale, Susan; Wong, Wai T.; Chew, Emily Y.; Ferris, Fredrick L.; Sieving, Paul A.

2018-01-01

Purpose As optical coherence tomography (OCT) minimum intensity (MI) analysis provides a quantitative assessment of changes in the outer nuclear layer (ONL), we evaluated the ability of OCT-MI analysis to detect hydroxychloroquine toxicity. Methods Fifty-seven predominantly female participants (91.2% female; mean age, 55.7 ± 10.4 years; mean time on hydroxychloroquine, 15.0 ± 7.5 years) were enrolled in a case-control study and categorized into affected (i.e., with toxicity, n = 19) and unaffected (n = 38) groups using objective multifocal electroretinographic (mfERG) criteria. Spectral-domain OCT scans of the macula were analyzed and OCT-MI values quantitated for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. A two-sample U-test and a cross-validation approach were used to assess the sensitivity and specificity of toxicity detection according to OCT-MI criteria. Results The medians of the OCT-MI values in all nine of the ETDRS subfields were significantly elevated in the affected group relative to the unaffected group (P < 0.005 for all comparisons), with the largest difference found for the inner inferior subfield (P < 0.0001). The receiver operating characteristic analysis of median MI values of the inner inferior subfields showed high sensitivity and high specificity in the detection of toxicity with area under the curve = 0.99. Conclusions Retinal changes secondary to hydroxychloroquine toxicity result in increased OCT reflectivity in the ONL that can be detected and quantitated using OCT-MI analysis. Analysis of OCT-MI values demonstrates high sensitivity and specificity for detecting the presence of hydroxychloroquine toxicity in this cohort and may contribute additionally to current screening practices. PMID:29677357

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

PubMed Central

dos Santos, Marcelo R.; Sayegh, Ana L.C.; Armani, Rafael; Costa-Hong, Valéria; de Souza, Francis R.; Toschi-Dias, Edgar; Bortolotto, Luiz A.; Yonamine, Mauricio; Negrão, Carlos E.; Alves, Maria-Janieire N.N.

2018-01-01

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population. PMID:29791601

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users.

PubMed

Santos, Marcelo R Dos; Sayegh, Ana L C; Armani, Rafael; Costa-Hong, Valéria; Souza, Francis R de; Toschi-Dias, Edgar; Bortolotto, Luiz A; Yonamine, Mauricio; Negrão, Carlos E; Alves, Maria-Janieire N N

2018-05-21

Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

Neurobehavioral deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

PubMed

Bellanger, Martine; Demeneix, Barbara; Grandjean, Philippe; Zoeller, R Thomas; Trasande, Leonardo

2015-04-01

Epidemiological studies and animal models demonstrate that endocrine-disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. The objective was to estimate neurodevelopmental disability and associated costs that can be reasonably attributed to EDC exposure in the European Union. An expert panel applied a weight-of-evidence characterization adapted from the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and approximate burden of disease. Cost estimation as of 2010 utilized lifetime economic productivity estimates, lifetime cost estimates for autism spectrum disorder, and annual costs for attention-deficit hyperactivity disorder. Setting, Patients and Participants, and Intervention: Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. The panel identified a 70-100% probability that polybrominated diphenyl ether and organophosphate exposures contribute to IQ loss in the European population. Polybrominated diphenyl ether exposures were associated with 873,000 (sensitivity analysis, 148,000 to 2.02 million) lost IQ points and 3290 (sensitivity analysis, 3290 to 8080) cases of intellectual disability, at costs of €9.59 billion (sensitivity analysis, €1.58 billion to €22.4 billion). Organophosphate exposures were associated with 13.0 million (sensitivity analysis, 4.24 million to 17.1 million) lost IQ points and 59 300 (sensitivity analysis, 16,500 to 84,400) cases of intellectual disability, at costs of €146 billion (sensitivity analysis, €46.8 billion to €194 billion). Autism spectrum disorder causation by multiple EDCs was assigned a 20-39% probability, with 316 (sensitivity analysis, 126-631) attributable cases at a cost of €199 million (sensitivity analysis, €79.7 million to €399 million). Attention-deficit hyperactivity disorder causation by multiple EDCs was assigned a 20-69% probability, with 19 300 to 31 200 attributable cases at a cost of €1.21 billion to €2.86 billion. EDC exposures in Europe contribute substantially to neurobehavioral deficits and disease, with a high probability of >€150 billion costs/year. These results emphasize the advantages of controlling EDC exposure.

Goal-oriented sensitivity analysis for lattice kinetic Monte Carlo simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arampatzis, Georgios, E-mail: garab@math.uoc.gr; Department of Mathematics and Statistics, University of Massachusetts, Amherst, Massachusetts 01003; Katsoulakis, Markos A., E-mail: markos@math.umass.edu

2014-03-28

In this paper we propose a new class of coupling methods for the sensitivity analysis of high dimensional stochastic systems and in particular for lattice Kinetic Monte Carlo (KMC). Sensitivity analysis for stochastic systems is typically based on approximating continuous derivatives with respect to model parameters by the mean value of samples from a finite difference scheme. Instead of using independent samples the proposed algorithm reduces the variance of the estimator by developing a strongly correlated-“coupled”- stochastic process for both the perturbed and unperturbed stochastic processes, defined in a common state space. The novelty of our construction is that themore » new coupled process depends on the targeted observables, e.g., coverage, Hamiltonian, spatial correlations, surface roughness, etc., hence we refer to the proposed method as goal-oriented sensitivity analysis. In particular, the rates of the coupled Continuous Time Markov Chain are obtained as solutions to a goal-oriented optimization problem, depending on the observable of interest, by considering the minimization functional of the corresponding variance. We show that this functional can be used as a diagnostic tool for the design and evaluation of different classes of couplings. Furthermore, the resulting KMC sensitivity algorithm has an easy implementation that is based on the Bortz–Kalos–Lebowitz algorithm's philosophy, where events are divided in classes depending on level sets of the observable of interest. Finally, we demonstrate in several examples including adsorption, desorption, and diffusion Kinetic Monte Carlo that for the same confidence interval and observable, the proposed goal-oriented algorithm can be two orders of magnitude faster than existing coupling algorithms for spatial KMC such as the Common Random Number approach. We also provide a complete implementation of the proposed sensitivity analysis algorithms, including various spatial KMC examples, in a supplementary MATLAB source code.« less

Sensitivity analysis of periodic errors in heterodyne interferometry

NASA Astrophysics Data System (ADS)

Ganguly, Vasishta; Kim, Nam Ho; Kim, Hyo Soo; Schmitz, Tony

2011-03-01

Periodic errors in heterodyne displacement measuring interferometry occur due to frequency mixing in the interferometer. These nonlinearities are typically characterized as first- and second-order periodic errors which cause a cyclical (non-cumulative) variation in the reported displacement about the true value. This study implements an existing analytical periodic error model in order to identify sensitivities of the first- and second-order periodic errors to the input parameters, including rotational misalignments of the polarizing beam splitter and mixing polarizer, non-orthogonality of the two laser frequencies, ellipticity in the polarizations of the two laser beams, and different transmission coefficients in the polarizing beam splitter. A local sensitivity analysis is first conducted to examine the sensitivities of the periodic errors with respect to each input parameter about the nominal input values. Next, a variance-based approach is used to study the global sensitivities of the periodic errors by calculating the Sobol' sensitivity indices using Monte Carlo simulation. The effect of variation in the input uncertainty on the computed sensitivity indices is examined. It is seen that the first-order periodic error is highly sensitive to non-orthogonality of the two linearly polarized laser frequencies, while the second-order error is most sensitive to the rotational misalignment between the laser beams and the polarizing beam splitter. A particle swarm optimization technique is finally used to predict the possible setup imperfections based on experimentally generated values for periodic errors.

High-Throughput Effect-Directed Analysis Using Downscaled in Vitro Reporter Gene Assays To Identify Endocrine Disruptors in Surface Water

PubMed Central

2018-01-01

Effect-directed analysis (EDA) is a commonly used approach for effect-based identification of endocrine disruptive chemicals in complex (environmental) mixtures. However, for routine toxicity assessment of, for example, water samples, current EDA approaches are considered time-consuming and laborious. We achieved faster EDA and identification by downscaling of sensitive cell-based hormone reporter gene assays and increasing fractionation resolution to allow testing of smaller fractions with reduced complexity. The high-resolution EDA approach is demonstrated by analysis of four environmental passive sampler extracts. Downscaling of the assays to a 384-well format allowed analysis of 64 fractions in triplicate (or 192 fractions without technical replicates) without affecting sensitivity compared to the standard 96-well format. Through a parallel exposure method, agonistic and antagonistic androgen and estrogen receptor activity could be measured in a single experiment following a single fractionation. From 16 selected candidate compounds, identified through nontargeted analysis, 13 could be confirmed chemically and 10 were found to be biologically active, of which the most potent nonsteroidal estrogens were identified as oxybenzone and piperine. The increased fractionation resolution and the higher throughput that downscaling provides allow for future application in routine high-resolution screening of large numbers of samples in order to accelerate identification of (emerging) endocrine disruptors. PMID:29547277

Factor structure and construct validity of the Anxiety Sensitivity Index among island Puerto Ricans.

PubMed

Cintrón, Jennifer A; Carter, Michele M; Suchday, Sonia; Sbrocco, Tracy; Gray, James

2005-01-01

The factor structure and convergent and discriminant validity of the Anxiety Sensitivity Index (ASI) were examined among a sample of 275 island Puerto Ricans. Results from a confirmatory factor analysis (CFA) comparing our data to factor solutions commonly reported as representative of European American and Spanish populations indicated a poor fit. A subsequent exploratory factor analysis (EFA) indicated that a two-factor solution (Factor 1, Anxiety Sensitivity; Factor 2, Emotional Concerns) provided the best fit. Correlations between the ASI and anxiety measures were moderately high providing evidence of convergent validity, while correlations between the ASI and BDI were significantly lower providing evidence of discriminant validity. Scores on all measures were positively correlated with acculturation, suggesting that those who ascribe to more traditional Hispanic culture report elevated anxiety.

Application of the High Resolution Melting analysis for genetic mapping of Sequence Tagged Site markers in narrow-leafed lupin (Lupinus angustifolius L.).

PubMed

Kamel, Katarzyna A; Kroc, Magdalena; Święcicki, Wojciech

2015-01-01

Sequence tagged site (STS) markers are valuable tools for genetic and physical mapping that can be successfully used in comparative analyses among related species. Current challenges for molecular markers genotyping in plants include the lack of fast, sensitive and inexpensive methods suitable for sequence variant detection. In contrast, high resolution melting (HRM) is a simple and high-throughput assay, which has been widely applied in sequence polymorphism identification as well as in the studies of genetic variability and genotyping. The present study is the first attempt to use the HRM analysis to genotype STS markers in narrow-leafed lupin (Lupinus angustifolius L.). The sensitivity and utility of this method was confirmed by the sequence polymorphism detection based on melting curve profiles in the parental genotypes and progeny of the narrow-leafed lupin mapping population. Application of different approaches, including amplicon size and a simulated heterozygote analysis, has allowed for successful genetic mapping of 16 new STS markers in the narrow-leafed lupin genome.

Dietary patterns, insulin sensitivity and inflammation in older adults

PubMed Central

Anderson, Amy L.; Harris, Tamara B.; Tylavsky, Frances A.; Perry, Sara E.; Houston, Denise K.; Lee, Jung Sun; Kanaya, Alka M.; Sahyoun, Nadine R.

2011-01-01

Background/Objectives Several studies have linked dietary patterns to insulin sensitivity and systemic inflammation, which affect risk of multiple chronic diseases. The purpose of this study was to investigate the dietary patterns of a cohort of older adults, and examine relationships of dietary patterns with markers of insulin sensitivity and systemic inflammation. Subjects/Methods The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3075 older adults. In Health ABC, multiple indicators of glucose metabolism and systemic inflammation were assessed. Food intake was estimated with a modified Block food frequency questionnaire (FFQ). In this study, dietary patterns of 1751 participants with complete data were derived by cluster analysis. Results Six clusters were identified, including a ‘Healthy foods’ cluster, characterized by higher intake of lowfat dairy products, fruit, whole grains, poultry, fish and vegetables. In the main analysis, the ‘Healthy foods’ cluster had significantly lower fasting insulin and HOMA-IR than the ‘Breakfast cereal’ and ‘High-fat dairy products’ clusters, and lower fasting glucose than the ‘High-fat dairy products’ cluster (P ≤ 0.05). No differences were found in 2-hour glucose. With respect to inflammation, the ‘Healthy foods’ cluster had lower IL-6 than the ‘Sweets and desserts’ and ‘High-fat dairy products’ clusters, and no differences were seen in CRP or TNF-α. Conclusions A dietary pattern high in lowfat dairy products, fruit, whole grains, poultry, fish and vegetables may be associated with greater insulin sensitivity and lower systemic inflammation in older adults. PMID:21915138

Sensitivity enhancement by chromatographic peak concentration with ultra-high performance liquid chromatography-nuclear magnetic resonance spectroscopy for minor impurity analysis.

PubMed

Tokunaga, Takashi; Akagi, Ken-Ichi; Okamoto, Masahiko

2017-07-28

High performance liquid chromatography can be coupled with nuclear magnetic resonance (NMR) spectroscopy to give a powerful analytical method known as liquid chromatography-nuclear magnetic resonance (LC-NMR) spectroscopy, which can be used to determine the chemical structures of the components of complex mixtures. However, intrinsic limitations in the sensitivity of NMR spectroscopy have restricted the scope of this procedure, and resolving these limitations remains a critical problem for analysis. In this study, we coupled ultra-high performance liquid chromatography (UHPLC) with NMR to give a simple and versatile analytical method with higher sensitivity than conventional LC-NMR. UHPLC separation enabled the concentration of individual peaks to give a volume similar to that of the NMR flow cell, thereby maximizing the sensitivity to the theoretical upper limit. The UHPLC concentration of compound peaks present at typical impurity levels (5.0-13.1 nmol) in a mixture led to at most three-fold increase in the signal-to-noise ratio compared with LC-NMR. Furthermore, we demonstrated the use of UHPLC-NMR for obtaining structural information of a minor impurity in a reaction mixture in actual laboratory-scale development of a synthetic process. Using UHPLC-NMR, the experimental run times for chromatography and NMR were greatly reduced compared with LC-NMR. UHPLC-NMR successfully overcomes the difficulties associated with analyses of minor components in a complex mixture by LC-NMR, which are problematic even when an ultra-high field magnet and cryogenic probe are used. Copyright © 2017 Elsevier B.V. All rights reserved.

Infrared diagnosis using liquid crystal detectors

NASA Technical Reports Server (NTRS)

Hugenschmidt, M.; Vollrath, K.

1986-01-01

The possible uses of pulsed carbon dioxide lasers for analysis of plasmas and flows need appropriate infrared image converters. Emphasis was placed on liquid crystal detectors and their operational modes. Performance characterstics and selection criteria, such as high sensitivity, short reaction time, and high spatial resolution are discussed.

A Multidisciplinary Approach to High Throughput Nuclear Magnetic Resonance Spectroscopy

PubMed Central

Pourmodheji, Hossein; Ghafar-Zadeh, Ebrahim; Magierowski, Sebastian

2016-01-01

Nuclear Magnetic Resonance (NMR) is a non-contact, powerful structure-elucidation technique for biochemical analysis. NMR spectroscopy is used extensively in a variety of life science applications including drug discovery. However, existing NMR technology is limited in that it cannot run a large number of experiments simultaneously in one unit. Recent advances in micro-fabrication technologies have attracted the attention of researchers to overcome these limitations and significantly accelerate the drug discovery process by developing the next generation of high-throughput NMR spectrometers using Complementary Metal Oxide Semiconductor (CMOS). In this paper, we examine this paradigm shift and explore new design strategies for the development of the next generation of high-throughput NMR spectrometers using CMOS technology. A CMOS NMR system consists of an array of high sensitivity micro-coils integrated with interfacing radio-frequency circuits on the same chip. Herein, we first discuss the key challenges and recent advances in the field of CMOS NMR technology, and then a new design strategy is put forward for the design and implementation of highly sensitive and high-throughput CMOS NMR spectrometers. We thereafter discuss the functionality and applicability of the proposed techniques by demonstrating the results. For microelectronic researchers starting to work in the field of CMOS NMR technology, this paper serves as a tutorial with comprehensive review of state-of-the-art technologies and their performance levels. Based on these levels, the CMOS NMR approach offers unique advantages for high resolution, time-sensitive and high-throughput bimolecular analysis required in a variety of life science applications including drug discovery. PMID:27294925

HF Propagation sensitivity study and system performance analysis with the Air Force Coverage Analysis Program (AFCAP)

NASA Astrophysics Data System (ADS)

Caton, R. G.; Colman, J. J.; Parris, R. T.; Nickish, L.; Bullock, G.

2017-12-01

The Air Force Research Laboratory, in collaboration with NorthWest Research Associates, is developing advanced software capabilities for high fidelity simulations of high frequency (HF) sky wave propagation and performance analysis of HF systems. Based on the HiCIRF (High-frequency Channel Impulse Response Function) platform [Nickisch et. al, doi:10.1029/2011RS004928], the new Air Force Coverage Analysis Program (AFCAP) provides the modular capabilities necessary for a comprehensive sensitivity study of the large number of variables which define simulations of HF propagation modes. In this paper, we report on an initial exercise of AFCAP to analyze the sensitivities of the tool to various environmental and geophysical parameters. Through examination of the channel scattering function and amplitude-range-Doppler output on two-way propagation paths with injected target signals, we will compare simulated returns over a range of geophysical conditions as well as varying definitions for environmental noise, meteor clutter, and sea state models for Bragg backscatter. We also investigate the impacts of including clutter effects due to field-aligned backscatter from small scale ionization structures at varied levels of severity as defined by the climatologically WideBand Model (WBMOD). In the absence of additional user provided information, AFCAP relies on International Reference Ionosphere (IRI) model to define the ionospheric state for use in 2D ray tracing algorithms. Because the AFCAP architecture includes the option for insertion of a user defined gridded ionospheric representation, we compare output from the tool using the IRI and ionospheric definitions from assimilative models such as GPSII (GPS Ionospheric Inversion).

Co-acting gene networks predict TRAIL responsiveness of tumour cells with high accuracy.

PubMed

O'Reilly, Paul; Ortutay, Csaba; Gernon, Grainne; O'Connell, Enda; Seoighe, Cathal; Boyce, Susan; Serrano, Luis; Szegezdi, Eva

2014-12-19

Identification of differentially expressed genes from transcriptomic studies is one of the most common mechanisms to identify tumor biomarkers. This approach however is not well suited to identify interaction between genes whose protein products potentially influence each other, which limits its power to identify molecular wiring of tumour cells dictating response to a drug. Due to the fact that signal transduction pathways are not linear and highly interlinked, the biological response they drive may be better described by the relative amount of their components and their functional relationships than by their individual, absolute expression. Gene expression microarray data for 109 tumor cell lines with known sensitivity to the death ligand cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was used to identify genes with potential functional relationships determining responsiveness to TRAIL-induced apoptosis. The machine learning technique Random Forest in the statistical environment "R" with backward elimination was used to identify the key predictors of TRAIL sensitivity and differentially expressed genes were identified using the software GeneSpring. Gene co-regulation and statistical interaction was assessed with q-order partial correlation analysis and non-rejection rate. Biological (functional) interactions amongst the co-acting genes were studied with Ingenuity network analysis. Prediction accuracy was assessed by calculating the area under the receiver operator curve using an independent dataset. We show that the gene panel identified could predict TRAIL-sensitivity with a very high degree of sensitivity and specificity (AUC=0·84). The genes in the panel are co-regulated and at least 40% of them functionally interact in signal transduction pathways that regulate cell death and cell survival, cellular differentiation and morphogenesis. Importantly, only 12% of the TRAIL-predictor genes were differentially expressed highlighting the importance of functional interactions in predicting the biological response. The advantage of co-acting gene clusters is that this analysis does not depend on differential expression and is able to incorporate direct- and indirect gene interactions as well as tissue- and cell-specific characteristics. This approach (1) identified a descriptor of TRAIL sensitivity which performs significantly better as a predictor of TRAIL sensitivity than any previously reported gene signatures, (2) identified potential novel regulators of TRAIL-responsiveness and (3) provided a systematic view highlighting fundamental differences between the molecular wiring of sensitive and resistant cell types.

Development of a highly sensitive and specific immunoassay for enrofloxacin based on heterologous coating haptens.

PubMed

Wang, Zhanhui; Zhang, Huiyan; Ni, Hengjia; Zhang, Suxia; Shen, Jianzhong

2014-04-11

In the paper, an enzyme-linked immunosorbent immunoassay (ELISA) for detection of enrofloxacin was described using one new derivative of enrofloxacin as coating hapten, resulting in surprisingly high sensitivity and specificity. Incorporation of aminobutyric acid (AA) in the new derivative of enrofloxacin had decreased the IC50 of the ELISA for enrofloxacin from 1.3 μg L(-1) to as low as 0.07 μg L(-1). The assay showed neglect cross-reactivity for other fluoroquinolones but ofloxacin (8.23%), marbofloxacin (8.97%) and pefloxacin (7.29%). Analysis of enrofloxacin fortified chicken muscle showed average recoveries from 81 to 115%. The high sensitivity and specificity of the assay makes it a suitable screening method for the determination of low levels of enrofloxacin in chicken muscle without clean-up step. Copyright © 2014 Elsevier B.V. All rights reserved.

Hollow fiber surface plasmon resonance sensor for the detection of liquid with high refractive index.

PubMed

Liu, Bing-Hong; Jiang, Yong-Xiang; Zhu, Xiao-Song; Tang, Xiao-Li; Shi, Yi-Wei

2013-12-30

A new kind of surface plasmon resonance (SPR) sensor based on silver-coated hollow fiber (HF) structure for the detection of liquids with high refractive index (RI) is presented. Liquid sensed medium with high RI is filled in the hollow core of the HF and its RI can be detected by measuring the transmission spectra of the HF SPR sensor. The designed sensors with different silver thicknesses are fabricated and the transmission spectra for filled liquids with different RI are measured to investigate the performances of the sensors. Theoretical analysis is also carried out to evaluate the performance. The simulation results agree well with the experimental results. Factors that might affect sensitivity and detection accuracy of the sensor are discussed. The highest sensitivity achieved is 6,607 nm/RIU, which is comparable to the sensitivities of the other reported fiber SPR sensors.

Aeroelastic optimization methodology for viscous and turbulent flows

NASA Astrophysics Data System (ADS)

Barcelos Junior, Manuel Nascimento Dias

2007-12-01

In recent years, the development of faster computers and parallel processing allowed the application of high-fidelity analysis methods to the aeroelastic design of aircraft. However, these methods are restricted to the final design verification, mainly due to the computational cost involved in iterative design processes. Therefore, this work is concerned with the creation of a robust and efficient aeroelastic optimization methodology for inviscid, viscous and turbulent flows by using high-fidelity analysis and sensitivity analysis techniques. Most of the research in aeroelastic optimization, for practical reasons, treat the aeroelastic system as a quasi-static inviscid problem. In this work, as a first step toward the creation of a more complete aeroelastic optimization methodology for realistic problems, an analytical sensitivity computation technique was developed and tested for quasi-static aeroelastic viscous and turbulent flow configurations. Viscous and turbulent effects are included by using an averaged discretization of the Navier-Stokes equations, coupled with an eddy viscosity turbulence model. For quasi-static aeroelastic problems, the traditional staggered solution strategy has unsatisfactory performance when applied to cases where there is a strong fluid-structure coupling. Consequently, this work also proposes a solution methodology for aeroelastic and sensitivity analyses of quasi-static problems, which is based on the fixed point of an iterative nonlinear block Gauss-Seidel scheme. The methodology can also be interpreted as the solution of the Schur complement of the aeroelastic and sensitivity analyses linearized systems of equations. The methodologies developed in this work are tested and verified by using realistic aeroelastic systems.

Use of a Smartphone as a Colorimetric Analyzer in Paper-based Devices for Sensitive and Selective Determination of Mercury in Water Samples.

PubMed

Jarujamrus, Purim; Meelapsom, Rattapol; Pencharee, Somkid; Obma, Apinya; Amatatongchai, Maliwan; Ditcharoen, Nadh; Chairam, Sanoe; Tamuang, Suparb

2018-01-01

A smartphone application, called CAnal, was developed as a colorimetric analyzer in paper-based devices for sensitive and selective determination of mercury(II) in water samples. Measurement on the double layer of a microfluidic paper-based analytical device (μPAD) fabricated by alkyl ketene dimer (AKD)-inkjet printing technique with special design doped with unmodified silver nanoparticles (AgNPs) onto the detection zones was performed by monitoring the gray intensity in the blue channel of AgNPs, which disintegrated when exposed to mercury(II) on μPAD. Under the optimized conditions, the developed approach showed high sensitivity, low limit of detection (0.003 mg L -1 , 3SD blank/slope of the calibration curve), small sample volume uptake (two times of 2 μL), and short analysis time. The linearity range of this technique ranged from 0.01 to 10 mg L -1 (r 2 = 0.993). Furthermore, practical analysis of various water samples was also demonstrated to have acceptable performance that was in agreement with the data from cold vapor atomic absorption spectrophotometry (CV-AAS), a conventional method. The proposed technique allows for a rapid, simple (instant report of the final mercury(II) concentration in water samples via smartphone display), sensitive, selective, and on-site analysis with high sample throughput (48 samples h -1 , n = 3) of trace mercury(II) in water samples, which is suitable for end users who are unskilled in analyzing mercury(II) in water samples.

Comparative study on ambient ionization methods for direct analysis of navel orange tissues by mass spectrometry.

PubMed

Zhang, Hua; Bibi, Aisha; Lu, Haiyan; Han, Jing; Chen, Huanwen

2017-08-01

It is of sustainable interest to improve the sensitivity and selectivity of the ionization process, especially for direct analysis of complex samples without matrix separation. Herein, four ambient ionization methods including desorption atmospheric pressure chemical ionization (DAPCI), heat-assisted desorption atmospheric pressure chemical ionization (heat-assisted DAPCI), microwave plasma torch (MPT) and internal extractive electrospray ionization (iEESI) were employed for comparative analysis of the navel orange tissue samples by mass spectrometry. The volatile organic compounds (e.g. ethanol, vanillin, leaf alcohol and jasmine lactone) were successfully detected by non-heat-assisted DAPCI-MS, while semi-volatile organic compounds (e.g. 1-nonanol and ethyl nonanoate) together with low abundance of non-volatile organic compounds (e.g. sinensetin and nobiletin) were obtained by heat-assisted DAPCI-MS. Typical nonvolatile organic compounds [e.g. 5-(hydroxymethyl)furfural and glucosan] were sensitively detected with MPT-MS. Compounds of high polarity (e.g. amino acids, alkaloids and sugars) were easily profiled with iEESI-MS. Our data showed that more analytes could be detected when more energy was delivered for the desorption ionization purpose; however, heat-sensitive analytes would not be detected once the energy input exceeded the dissociation barriers of the analytes. For the later cases, soft ionization methods such as iEESI were recommended to sensitively profile the bioanalytes of high polarity. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

High sensitivity phase retrieval method in grating-based x-ray phase contrast imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Zhao; Gao, Kun; Chen, Jian

2015-02-15

Purpose: Grating-based x-ray phase contrast imaging is considered as one of the most promising techniques for future medical imaging. Many different methods have been developed to retrieve phase signal, among which the phase stepping (PS) method is widely used. However, further practical implementations are hindered, due to its complex scanning mode and high radiation dose. In contrast, the reverse projection (RP) method is a novel fast and low dose extraction approach. In this contribution, the authors present a quantitative analysis of the noise properties of the refraction signals retrieved by the two methods and compare their sensitivities. Methods: Using themore » error propagation formula, the authors analyze theoretically the signal-to-noise ratios (SNRs) of the refraction images retrieved by the two methods. Then, the sensitivities of the two extraction methods are compared under an identical exposure dose. Numerical experiments are performed to validate the theoretical results and provide some quantitative insight. Results: The SNRs of the two methods are both dependent on the system parameters, but in different ways. Comparison between their sensitivities reveals that for the refraction signal, the RP method possesses a higher sensitivity, especially in the case of high visibility and/or at the edge of the object. Conclusions: Compared with the PS method, the RP method has a superior sensitivity and provides refraction images with a higher SNR. Therefore, one can obtain highly sensitive refraction images in grating-based phase contrast imaging. This is very important for future preclinical and clinical implementations.« less

Application of uncertainty and sensitivity analysis to the air quality SHERPA modelling tool

NASA Astrophysics Data System (ADS)

Pisoni, E.; Albrecht, D.; Mara, T. A.; Rosati, R.; Tarantola, S.; Thunis, P.

2018-06-01

Air quality has significantly improved in Europe over the past few decades. Nonetheless we still find high concentrations in measurements mainly in specific regions or cities. This dimensional shift, from EU-wide to hot-spot exceedances, calls for a novel approach to regional air quality management (to complement EU-wide existing policies). The SHERPA (Screening for High Emission Reduction Potentials on Air quality) modelling tool was developed in this context. It provides an additional tool to be used in support to regional/local decision makers responsible for the design of air quality plans. It is therefore important to evaluate the quality of the SHERPA model, and its behavior in the face of various kinds of uncertainty. Uncertainty and sensitivity analysis techniques can be used for this purpose. They both reveal the links between assumptions and forecasts, help in-model simplification and may highlight unexpected relationships between inputs and outputs. Thus, a policy steered SHERPA module - predicting air quality improvement linked to emission reduction scenarios - was evaluated by means of (1) uncertainty analysis (UA) to quantify uncertainty in the model output, and (2) by sensitivity analysis (SA) to identify the most influential input sources of this uncertainty. The results of this study provide relevant information about the key variables driving the SHERPA output uncertainty, and advise policy-makers and modellers where to place their efforts for an improved decision-making process.

Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts.

PubMed

Hose, Alexander J; Depner, Martin; Illi, Sabina; Lau, Susanne; Keil, Thomas; Wahn, Ulrich; Fuchs, Oliver; Pfefferle, Petra Ina; Schmaußer-Hechfellner, Elisabeth; Genuneit, Jon; Lauener, Roger; Karvonen, Anne M; Roduit, Caroline; Dalphin, Jean-Charles; Riedler, Josef; Pekkanen, Juha; von Mutius, Erika; Ege, Markus J

2017-06-01

Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Persistent oscillations and backward bifurcation in a malaria model with varying human and mosquito populations: implications for control.

PubMed

Ngonghala, Calistus N; Teboh-Ewungkem, Miranda I; Ngwa, Gideon A

2015-06-01

We derive and study a deterministic compartmental model for malaria transmission with varying human and mosquito populations. Our model considers disease-related deaths, asymptomatic immune humans who are also infectious, as well as mosquito demography, reproduction and feeding habits. Analysis of the model reveals the existence of a backward bifurcation and persistent limit cycles whose period and size is determined by two threshold parameters: the vectorial basic reproduction number Rm, and the disease basic reproduction number R0, whose size can be reduced by reducing Rm. We conclude that malaria dynamics are indeed oscillatory when the methodology of explicitly incorporating the mosquito's demography, feeding and reproductive patterns is considered in modeling the mosquito population dynamics. A sensitivity analysis reveals important control parameters that can affect the magnitudes of Rm and R0, threshold quantities to be taken into consideration when designing control strategies. Both Rm and the intrinsic period of oscillation are shown to be highly sensitive to the mosquito's birth constant λm and the mosquito's feeding success probability pw. Control of λm can be achieved by spraying, eliminating breeding sites or moving them away from human habitats, while pw can be controlled via the use of mosquito repellant and insecticide-treated bed-nets. The disease threshold parameter R0 is shown to be highly sensitive to pw, and the intrinsic period of oscillation is also sensitive to the rate at which reproducing mosquitoes return to breeding sites. A global sensitivity and uncertainty analysis reveals that the ability of the mosquito to reproduce and uncertainties in the estimations of the rates at which exposed humans become infectious and infectious humans recover from malaria are critical in generating uncertainties in the disease classes.

Thermal comfort in Quebec City, Canada: sensitivity analysis of the UTCI and other popular thermal comfort indices in a mid-latitude continental city.

PubMed

Provençal, Simon; Bergeron, Onil; Leduc, Richard; Barrette, Nathalie

2016-04-01

The newly developed Universal Thermal Climate Index (UTCI), along with the physiological equivalent temperature (PET), the humidex (HX) and the wind chill index (WC), was calculated in Quebec City, Canada, a city with a strong seasonal climatic variability, over a 1-year period. The objective of this study is twofold: evaluate the operational benefits of implementing the UTCI for a climate monitoring program of public comfort and health awareness as opposed to relying on traditional and simple indices, and determine whether thermal comfort monitoring specific to dense urban neighborhoods is necessary to adequately fulfill the goals of the program. In order to do so, an analysis is performed to evaluate each of these indices' sensitivity to the meteorological variables that regulate them in different environments. Overall, the UTCI was found to be slightly more sensitive to mean radiant temperature, moderately more sensitive to humidity and much more sensitive to wind speed than the PET. This dynamic changed slightly depending on the environment and the season. In hot weather, the PET was found to be more sensitive to mean radiant temperature and therefore reached high values that could potentially be hazardous more frequently than the UTCI and the HX. In turn, the UTCI's stronger sensitivity to wind speed makes it a superior index to identify potentially hazardous weather in winter compared to the PET and the WC. Adopting the UTCI broadly would be an improvement over the traditionally popular HX and WC indices. The urban environment produced favorable conditions to sustain heat stress conditions, where the indices reached high values more frequently there than in suburban locations, which advocates for weather monitoring specific to denser urban areas.

Thermal comfort in Quebec City, Canada: sensitivity analysis of the UTCI and other popular thermal comfort indices in a mid-latitude continental city

NASA Astrophysics Data System (ADS)

Provençal, Simon; Bergeron, Onil; Leduc, Richard; Barrette, Nathalie

2016-04-01

The newly developed Universal Thermal Climate Index (UTCI), along with the physiological equivalent temperature (PET), the humidex (HX) and the wind chill index (WC), was calculated in Quebec City, Canada, a city with a strong seasonal climatic variability, over a 1-year period. The objective of this study is twofold: evaluate the operational benefits of implementing the UTCI for a climate monitoring program of public comfort and health awareness as opposed to relying on traditional and simple indices, and determine whether thermal comfort monitoring specific to dense urban neighborhoods is necessary to adequately fulfill the goals of the program. In order to do so, an analysis is performed to evaluate each of these indices' sensitivity to the meteorological variables that regulate them in different environments. Overall, the UTCI was found to be slightly more sensitive to mean radiant temperature, moderately more sensitive to humidity and much more sensitive to wind speed than the PET. This dynamic changed slightly depending on the environment and the season. In hot weather, the PET was found to be more sensitive to mean radiant temperature and therefore reached high values that could potentially be hazardous more frequently than the UTCI and the HX. In turn, the UTCI's stronger sensitivity to wind speed makes it a superior index to identify potentially hazardous weather in winter compared to the PET and the WC. Adopting the UTCI broadly would be an improvement over the traditionally popular HX and WC indices. The urban environment produced favorable conditions to sustain heat stress conditions, where the indices reached high values more frequently there than in suburban locations, which advocates for weather monitoring specific to denser urban areas.

Long-term effects of low-fat diets either low or high in protein on cardiovascular and metabolic risk factors: a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Meta-analyses of short-term studies indicate favorable effects of higher protein vs. lower protein diets on health outcomes like adiposity or cardiovascular risk factors, but their long-term effects are unknown. Methods Electronic databases (MEDLINE, EMBASE, Cochrane Trial Register) were searched up to August 2012 with no restriction to language or calendar date. A random effect meta-analysis was performed using the Software package by the Cochrane Collaboration Review Manager 5.1. Sensitivity analysis was performed for RCTs with a Jadad Score ≥3, and excluding type 2 diabetic subjects (T2D). Results 15 RCTs met all objectives and were included in the present meta-analysis. No significant differences were observed for weight, waist circumference, fat mass, blood lipids (i.e. total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerols), C-reactive protein, diastolic and systolic blood pressure, fasting glucose and glycosylated hemoglobin. In contrast, improvements of fasting insulin was significantly more pronounced following high protein diets as compared to the low protein counterparts (weighted mean difference: -0.71 μIU/ml, 95% CI -1.36 to -0.05, p = 0.03). Sensitivity analysis of high quality RCTs confirmed the data of the primary analyses, while exclusion of studies with diabetic subjects resulted in an additional benefit of high-protein diets with respect to a more marked increase in HDL-cholesterol. Conclusion According to the present meta-analysis of long-term RCTs, high-protein diets exerted neither specific beneficial nor detrimental effects on outcome markers of obesity, cardiovascular disease or glycemic control. Thus, it seems premature to recommend high-protein diets in the management of overweight and obesity. PMID:23587198

Modeling and sensitivity analysis on the transport of aluminum oxide nanoparticles in saturated sand: effects of ionic strength, flow rate, and nanoparticle concentration.

PubMed

Rahman, Tanzina; Millwater, Harry; Shipley, Heather J

2014-11-15

Aluminum oxide nanoparticles have been widely used in various consumer products and there are growing concerns regarding their exposure in the environment. This study deals with the modeling, sensitivity analysis and uncertainty quantification of one-dimensional transport of nano-sized (~82 nm) aluminum oxide particles in saturated sand. The transport of aluminum oxide nanoparticles was modeled using a two-kinetic-site model with a blocking function. The modeling was done at different ionic strengths, flow rates, and nanoparticle concentrations. The two sites representing fast and slow attachments along with a blocking term yielded good agreement with the experimental results from the column studies of aluminum oxide nanoparticles. The same model was used to simulate breakthrough curves under different conditions using experimental data and calculated 95% confidence bounds of the generated breakthroughs. The sensitivity analysis results showed that slow attachment was the most sensitive parameter for high influent concentrations (e.g. 150 mg/L Al2O3) and the maximum solid phase retention capacity (related to blocking function) was the most sensitive parameter for low concentrations (e.g. 50 mg/L Al2O3). Copyright © 2014 Elsevier B.V. All rights reserved.

Development of rapid and sensitive high throughput pharmacologic assays for marine phycotoxins.

PubMed

Van Dolah, F M; Finley, E L; Haynes, B L; Doucette, G J; Moeller, P D; Ramsdell, J S

1994-01-01

The lack of rapid, high throughput assays is a major obstacle to many aspects of research on marine phycotoxins. Here we describe the application of microplate scintillation technology to develop high throughput assays for several classes of marine phycotoxin based on their differential pharmacologic actions. High throughput "drug discovery" format microplate receptor binding assays developed for brevetoxins/ciguatoxins and for domoic acid are described. Analysis for brevetoxins/ciguatoxins is carried out by binding competition with [3H] PbTx-3 for site 5 on the voltage dependent sodium channel in rat brain synaptosomes. Analysis of domoic acid is based on binding competition with [3H] kainic acid for the kainate/quisqualate glutamate receptor using frog brain synaptosomes. In addition, a high throughput microplate 45Ca flux assay for determination of maitotoxins is described. These microplate assays can be completed within 3 hours, have sensitivities of less than 1 ng, and can analyze dozens of samples simultaneously. The assays have been demonstrated to be useful for assessing algal toxicity and for assay-guided purification of toxins, and are applicable to the detection of biotoxins in seafood.

Cost-effectiveness Analysis of Nutritional Support for the Prevention of Pressure Ulcers in High-Risk Hospitalized Patients.

PubMed

Tuffaha, Haitham W; Roberts, Shelley; Chaboyer, Wendy; Gordon, Louisa G; Scuffham, Paul A

2016-06-01

To evaluate the cost-effectiveness of nutritional support compared with standard care in preventing pressure ulcers (PrUs) in high-risk hospitalized patients. An economic model using data from a systematic literature review. A meta-analysis of randomized controlled trials on the efficacy of nutritional support in reducing the incidence of PrUs was conducted. Modeled cohort of hospitalized patients at high risk of developing PrUs and malnutrition simulated during their hospital stay and up to 1 year. Standard care included PrU prevention strategies, such as redistribution surfaces, repositioning, and skin protection strategies, along with standard hospital diet. In addition to the standard care, the intervention group received nutritional support comprising patient education, nutrition goal setting, and the consumption of high-protein supplements. The analysis was from a healthcare payer perspective. Key outcomes of the model included the average costs and quality-adjusted life years. Model results were tested in univariate sensitivity analyses, and decision uncertainty was characterized using a probabilistic sensitivity analysis. Compared with standard care, nutritional support was cost saving at AU $425 per patient and marginally more effective with an average 0.005 quality-adjusted life years gained. The probability of nutritional support being cost-effective was 87%. Nutritional support to prevent PrUs in high-risk hospitalized patients is cost-effective with substantial cost savings predicted. Hospitals should implement the recommendations from the current PrU practice guidelines and offer nutritional support to high-risk patients.

High-resolution melting analysis for bird sexing: a successful approach to molecular sex identification using different biological samples.

PubMed

Morinha, Francisco; Travassos, Paulo; Seixas, Fernanda; Santos, Nuno; Sargo, Roberto; Sousa, Luís; Magalhães, Paula; Cabral, João A; Bastos, Estela

2013-05-01

High-resolution melting (HRM) analysis is a very attractive and flexible advanced post-PCR method with high sensitivity/specificity for simple, fast and cost-effective genotyping based on the detection of specific melting profiles of PCR products. Next generation real-time PCR systems, along with improved saturating DNA-binding dyes, enable the direct acquisition of HRM data after quantitative PCR. Melting behaviour is particularly influenced by the length, nucleotide sequence and GC content of the amplicons. This method is expanding rapidly in several research areas such as human genetics, reproductive biology, microbiology and ecology/conservation of wild populations. Here we have developed a successful HRM protocol for avian sex identification based on the amplification of sex-specific CHD1 fragments. The melting curve patterns allowed efficient sexual differentiation of 111 samples analysed (plucked feathers, muscle tissues, blood and oral cavity epithelial cells) of 14 bird species. In addition, we sequenced the amplified regions of the CHD1 gene and demonstrated the usefulness of this strategy for the genotype discrimination of various amplicons (CHD1Z and CHD1W), which have small size differences, ranging from 2 bp to 44 bp. The established methodology clearly revealed the advantages (e.g. closed-tube system, high sensitivity and rapidity) of a simple HRM assay for accurate sex differentiation of the species under study. The requirements, strengths and limitations of the method are addressed to provide a simple guide for its application in the field of molecular sexing of birds. The high sensitivity and resolution relative to previous real-time PCR methods makes HRM analysis an excellent approach for improving advanced molecular methods for bird sexing. © 2013 Blackwell Publishing Ltd.

Assessing the sensitivity of bovine tuberculosis surveillance in Canada's cattle population, 2009-2013.

PubMed

El Allaki, Farouk; Harrington, Noel; Howden, Krista

2016-11-01

The objectives of this study were (1) to estimate the annual sensitivity of Canada's bTB surveillance system and its three system components (slaughter surveillance, export testing and disease investigation) using a scenario tree modelling approach, and (2) to identify key model parameters that influence the estimates of the surveillance system sensitivity (SSSe). To achieve these objectives, we designed stochastic scenario tree models for three surveillance system components included in the analysis. Demographic data, slaughter data, export testing data, and disease investigation data from 2009 to 2013 were extracted for input into the scenario trees. Sensitivity analysis was conducted to identify key influential parameters on SSSe estimates. The median annual SSSe estimates generated from the study were very high, ranging from 0.95 (95% probability interval [PI]: 0.88-0.98) to 0.97 (95% PI: 0.93-0.99). Median annual sensitivity estimates for the slaughter surveillance component ranged from 0.95 (95% PI: 0.88-0.98) to 0.97 (95% PI: 0.93-0.99). This shows that slaughter surveillance to be the major contributor to overall surveillance system sensitivity with a high probability to detect M. bovis infection if present at a prevalence of 0.00028% or greater during the study period. The export testing and disease investigation components had extremely low component sensitivity estimates-the maximum median sensitivity estimates were 0.02 (95% PI: 0.014-0.023) and 0.0061 (95% PI: 0.0056-0.0066) respectively. The three most influential input parameters on the model's output (SSSe) were the probability of a granuloma being detected at slaughter inspection, the probability of a granuloma being present in older animals (≥12 months of age), and the probability of a granuloma sample being submitted to the laboratory. Additional studies are required to reduce the levels of uncertainty and variability associated with these three parameters influencing the surveillance system sensitivity. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates

PubMed Central

Yabu, Julie M.; Siebert, Janet C.; Maecker, Holden T.

2016-01-01

Background Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Methods and Findings Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Conclusions Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates. PMID:27078882

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates.

PubMed

Yabu, Julie M; Siebert, Janet C; Maecker, Holden T

2016-01-01

Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates.

Cost-effectiveness of WHO-Recommended Algorithms for TB Case Finding at Ethiopian HIV Clinics.

PubMed

Adelman, Max W; McFarland, Deborah A; Tsegaye, Mulugeta; Aseffa, Abraham; Kempker, Russell R; Blumberg, Henry M

2018-01-01

The World Health Organization (WHO) recommends active tuberculosis (TB) case finding and a rapid molecular diagnostic test (Xpert MTB/RIF) to detect TB among people living with HIV (PLHIV) in high-burden settings. Information on the cost-effectiveness of these recommended strategies is crucial for their implementation. We conducted a model-based cost-effectiveness analysis comparing 2 algorithms for TB screening and diagnosis at Ethiopian HIV clinics: (1) WHO-recommended symptom screen combined with Xpert for PLHIV with a positive symptom screen and (2) current recommended practice algorithm (CRPA; based on symptom screening, smear microscopy, and clinical TB diagnosis). Our primary outcome was US$ per disability-adjusted life-year (DALY) averted. Secondary outcomes were additional true-positive diagnoses, and false-negative and false-positive diagnoses averted. Compared with CRPA, combining a WHO-recommended symptom screen with Xpert was highly cost-effective (incremental cost of $5 per DALY averted). Among a cohort of 15 000 PLHIV with a TB prevalence of 6% (900 TB cases), this algorithm detected 8 more true-positive cases than CRPA, and averted 2045 false-positive and 8 false-negative diagnoses compared with CRPA. The WHO-recommended algorithm was marginally costlier ($240 000) than CRPA ($239 000). In sensitivity analysis, the symptom screen/Xpert algorithm was dominated at low Xpert sensitivity (66%). In this model-based analysis, combining a WHO-recommended symptom screen with Xpert for TB diagnosis among PLHIV was highly cost-effective ($5 per DALY averted) and more sensitive than CRPA in a high-burden, resource-limited setting.

Analyzing Single Giant Unilamellar Vesicles With a Slotline-Based RF Nanometer Sensor

DOE PAGES

Cui, Yan; Kenworthy, Anne K.; Edidin, Michael; ...

2016-03-11

Novel techniques that enable reagent free detection and analysis of single cells are of great interest for the development of biological and medical sciences, as well as point-of-care health service technologies. Highly sensitive and broadband RF sensors are promising candidates for such a technique. In this paper, we present a highly sensitive and tunable RF sensor, which is based on interference processes and built with a 100-nm slotline structure. The highly concentrated RF fields, up to ~ 1.76×10 7 V/m, enable strong interactions between giant unilamellar vesicles (GUVs) and fields for high-sensitivity operations. We also provide two modeling approaches tomore » extract cell dielectric properties from measured scattering parameters. GUVs of different molecular compositions are synthesized and analyzed with the RF sensor at ~ 2, ~ 2.5, and ~ 2.8 GHz with an initial |S 21| min of ~ -100 dB. Corresponding GUV dielectric properties are obtained. Finally, a one-dimensional scanning of single GUV is also demonstrated.« less

Comparison of the sensitivity of mass spectrometry atmospheric pressure ionization techniques in the analysis of porphyrinoids.

PubMed

Swider, Paweł; Lewtak, Jan P; Gryko, Daniel T; Danikiewicz, Witold

2013-10-01

The porphyrinoids chemistry is greatly dependent on the data obtained in mass spectrometry. For this reason, it is essential to determine the range of applicability of mass spectrometry ionization methods. In this study, the sensitivity of three different atmospheric pressure ionization techniques, electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization, was tested for several porphyrinods and their metallocomplexes. Electrospray ionization method was shown to be the best ionization technique because of its high sensitivity for derivatives of cyanocobalamin, free-base corroles and porphyrins. In the case of metallocorroles and metalloporphyrins, atmospheric pressure photoionization with dopant proved to be the most sensitive ionization method. It was also shown that for relatively acidic compounds, particularly for corroles, the negative ion mode provides better sensitivity than the positive ion mode. The results supply a lot of relevant information on the methodology of porphyrinoids analysis carried out by mass spectrometry. The information can be useful in designing future MS or liquid chromatography-MS experiments. Copyright © 2013 John Wiley & Sons, Ltd.

Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study.

PubMed

Chen, Jing; Gu, Dongfeng; Huang, Jianfeng; Rao, Dabeeru C; Jaquish, Cashell E; Hixson, James E; Chen, Chung-Shiuan; Chen, Jichun; Lu, Fanghong; Hu, Dongsheng; Rice, Treva; Kelly, Tanika N; Hamm, L Lee; Whelton, Paul K; He, Jiang

2009-03-07

Since insulin resistance is thought to be the underlying mechanism for metabolic syndrome, affected individuals might be sensitive to a dietary sodium intervention. We aimed to examine the association between metabolic syndrome and salt sensitivity of blood pressure. 1906 Chinese participants without diabetes, aged 16 years or more, were selected to receive a low-sodium diet (51.3 mmol per day) for 7 days followed by a high-sodium diet (307.8 mmol per day) for an additional 7 days. Participants were excluded from the analysis if metabolic risk factor information was missing or if they did not complete their dietary interventions. Blood pressure was measured at baseline and on days 2, 5, 6, and 7 of each intervention. Metabolic syndrome was defined as the presence of three or more of: abdominal obesity, raised blood pressure, high triglyceride concentration, low HDL cholesterol, or high glucose. High salt sensitivity was defined as a decrease in mean arterial blood pressure of more than 5 mm Hg during low-sodium or an increase of more than 5 mm Hg during high-sodium intervention. This study is registered with ClinicalTrials.gov, number NCT00721721. Of the 1881 participants with information regarding metabolic syndrome, 283 had metabolic syndrome. 1853 participants completed the low-sodium diet and 1845 completed the high-sodium diet. Multivariable-adjusted mean changes in blood pressure were significantly greater in participants with metabolic syndrome than in those without on both low-sodium and high-sodium diets (p<0.0001 for all comparisons). Additionally, risk of salt sensitivity rose with increasing numbers of risk factors for metabolic syndrome. Compared with those with no risk factors, participants with four or five had a 3.54-fold increased odds (95% CI 2.05-6.11) of high salt-sensitivity during the low-sodium and a 3.13-fold increased odds (1.80-5.43) of high salt-sensitivity during the high-sodium intervention. These results suggest that metabolic syndrome enhances blood pressure response to sodium intake. Reduction in sodium intake could be an especially important component in reducing blood pressure in patients with multiple risk factors for metabolic syndrome.

A highly sensitive and specific capacitive aptasensor for rapid and label-free trace analysis of Bisphenol A (BPA) in canned foods.

PubMed

Mirzajani, Hadi; Cheng, Cheng; Wu, Jayne; Chen, Jiangang; Eda, Shigotoshi; Najafi Aghdam, Esmaeil; Badri Ghavifekr, Habib

2017-03-15

A rapid, highly sensitive, specific and low-cost capacitive affinity biosensor is presented here for label-free and single step detection of Bisphenol A (BPA). The sensor design allows rapid prototyping at low-cost using printed circuit board material by benchtop equipment. High sensitivity detection is achieved through the use of a BPA-specific aptamer as probe molecule and large electrodes to enhance AC-electroelectrothermal effect for long-range transport of BPA molecules toward electrode surface. Capacitive sensing technique is used to determine the bounded BPA level by measuring the sample/electrode interfacial capacitance of the sensor. The developed biosensor can detect BPA level in 20s and exhibits a large linear range from 1 fM to 10 pM, with a limit of detection (LOD) of 152.93 aM. This biosensor was applied to test BPA in canned food samples and could successfully recover the levels of spiked BPA. This sensor technology is demonstrated to be highly promising and reliable for rapid, sensitive and on-site monitoring of BPA in food samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Guided-Mode-Leaky-Mode-Guided-Mode Fiber Interferometer and Its High Sensitivity Refractive Index Sensing Technology.

PubMed

Wang, Qi; Li, Chunyue; Zhao, Chengwu; Li, Weizheng

2016-06-01

A cascaded symmetrical dual-taper Mach-Zehnder interferometer structure based on guided-mode and leaky-mode interference is proposed in this paper. Firstly, the interference spectrum characteristics of interferometer has been analyzed by the Finite Difference-Beam Propagation Method (FD-BPM). When the diameter of taper waist is 20 μm-30 μm, dual-taper length is 1 mm and taper distance is 4 cm-6 cm, the spectral contrast is higher, which is suitable for sensing. Secondly, experimental research on refractive index sensitivity is carried out. A refractive index sensitivity of 62.78 nm/RIU (refractive index unit) can achieved in the RI range of 1.3333-1.3792 (0%~25% NaCl solution), when the sensor structure parameters meet the following conditions: diameter of taper waist is 24 μm, dual-taper length is 837 μm and taper distance is 5.5 cm. The spectrum contrast is 0.8 and measurement resolution is 1.6 × 10(-5) RIU. The simulation analysis is highly consistent with experimental results. Research shows that the sensor has promising application in low RI fields where high-precision measurement is required due to its high sensitivity and stability.

A highly sensitive magnetic biosensor for detection and quantification of anticancer drugs tagged to superparamagnetic nanoparticles

NASA Astrophysics Data System (ADS)

Devkota, J.; Wingo, J.; Mai, T. T. T.; Nguyen, X. P.; Huong, N. T.; Mukherjee, P.; Srikanth, H.; Phan, M. H.

2014-05-01

We report on a highly sensitive magnetic biosensor based on the magneto-reactance (MX) effect of a Co65Fe4Ni2Si15B14 amorphous ribbon with a nanohole-patterned surface for detection and quantification of anticancer drugs (Curcumin) tagged to superparamagnetic (Fe3O4) nanoparticles. Fe3O4 nanoparticles (mean size, ˜10 nm) were first coated with Alginate, and Curcumin was then tagged to the nanoparticles. The detection and quantification of Curcumin were assessed by the change in MX of the ribbon subject to varying concentrations of the Fe3O4 nanoparticles to which Curcumin was tagged. A high capacity of the MX-based biosensor in quantitative analysis of Curcumin-loaded Fe3O4 nanoparticles was achieved in the range of 0-50 ng/ml, beyond which the detection sensitivity of the sensor remained unchanged. The detection sensitivity of the biosensor reached an extremely high value of 30%, which is about 4-5 times higher than that of a magneto-impedance (MI) based biosensor. This biosensor is well suited for detection of low-concentration magnetic biomarkers in biological systems.

Improved Sensitivity for Molecular Detection of Bacterial and Candida Infections in Blood

PubMed Central

Bacconi, Andrea; Richmond, Gregory S.; Baroldi, Michelle A.; Laffler, Thomas G.; Blyn, Lawrence B.; Carolan, Heather E.; Frinder, Mark R.; Toleno, Donna M.; Metzgar, David; Gutierrez, Jose R.; Massire, Christian; Rounds, Megan; Kennel, Natalie J.; Rothman, Richard E.; Peterson, Stephen; Carroll, Karen C.; Wakefield, Teresa; Ecker, David J.

2014-01-01

The rapid identification of bacteria and fungi directly from the blood of patients with suspected bloodstream infections aids in diagnosis and guides treatment decisions. The development of an automated, rapid, and sensitive molecular technology capable of detecting the diverse agents of such infections at low titers has been challenging, due in part to the high background of genomic DNA in blood. PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) allows for the rapid and accurate identification of microorganisms but with a sensitivity of about 50% compared to that of culture when using 1-ml whole-blood specimens. Here, we describe a new integrated specimen preparation technology that substantially improves the sensitivity of PCR/ESI-MS analysis. An efficient lysis method and automated DNA purification system were designed for processing 5 ml of whole blood. In addition, PCR amplification formulations were optimized to tolerate high levels of human DNA. An analysis of 331 specimens collected from patients with suspected bloodstream infections resulted in 35 PCR/ESI-MS-positive specimens (10.6%) compared to 18 positive by culture (5.4%). PCR/ESI-MS was 83% sensitive and 94% specific compared to culture. Replicate PCR/ESI-MS testing from a second aliquot of the PCR/ESI-MS-positive/culture-negative specimens corroborated the initial findings in most cases, resulting in increased sensitivity (91%) and specificity (99%) when confirmed detections were considered true positives. The integrated solution described here has the potential to provide rapid detection and identification of organisms responsible for bloodstream infections. PMID:24951806

How sensitive and specific is urinalysis 'dipstick' testing for detection of hyperglycaemia and ketosis? An audit of findings from coronial autopsies.

PubMed

Mitchell, Rebecca; Thomas, Sunethra Devika; Langlois, Neil E I

2013-10-01

Biochemical analysis of glucose and ketones in the vitreous humour obtained at post-mortem examination is representative of the levels in the blood prior to death. Elevated levels can be indicative of conditions including diabetic ketoacidosis, which can be a cause for unexpected death. A rapid screening test for such conditions can be performed during the autopsy through urinalysis using test strips (urine 'dipstick' testing). The aim of this study was to assess the utility of urinalysis testing for post-mortem detection of derangements of glucose and ketone levels. The results of vitreous biochemical analysis and urinalysis were collated from 188 forensic autopsy cases. A vitreous glucose result of above 10 mmol/L was regarded as high. When this was compared to urinalysis results it was found that any urinalysis result above negative had a sensitivity of 0.83 and a specificity of 0.93. A vitreous ketone level of above 5 mmol/L was regarded as significantly elevated; a urinalysis result above negative had a sensitivity of 1, but a specificity of 0.12. Urinalysis ('dipstick' testing) for glucose has a good sensitivity and specificity for high vitreous glucose levels, which are regarded as indicative of pathological hyperglycaemia during life. It was found that urine testing for ketones either has an excellent sensitivity with low specificity or a poor sensitivity with a good specificity; however, this finding has to be viewed in the context of uncertainty of the biochemical level of significant ketosis.

Automated Morphological Analysis of Microglia After Stroke.

PubMed

Heindl, Steffanie; Gesierich, Benno; Benakis, Corinne; Llovera, Gemma; Duering, Marco; Liesz, Arthur

2018-01-01

Microglia are the resident immune cells of the brain and react quickly to changes in their environment with transcriptional regulation and morphological changes. Brain tissue injury such as ischemic stroke induces a local inflammatory response encompassing microglial activation. The change in activation status of a microglia is reflected in its gradual morphological transformation from a highly ramified into a less ramified or amoeboid cell shape. For this reason, the morphological changes of microglia are widely utilized to quantify microglial activation and studying their involvement in virtually all brain diseases. However, the currently available methods, which are mainly based on manual rating of immunofluorescent microscopic images, are often inaccurate, rater biased, and highly time consuming. To address these issues, we created a fully automated image analysis tool, which enables the analysis of microglia morphology from a confocal Z-stack and providing up to 59 morphological features. We developed the algorithm on an exploratory dataset of microglial cells from a stroke mouse model and validated the findings on an independent data set. In both datasets, we could demonstrate the ability of the algorithm to sensitively discriminate between the microglia morphology in the peri-infarct and the contralateral, unaffected cortex. Dimensionality reduction by principal component analysis allowed to generate a highly sensitive compound score for microglial shape analysis. Finally, we tested for concordance of results between the novel automated analysis tool and the conventional manual analysis and found a high degree of correlation. In conclusion, our novel method for the fully automatized analysis of microglia morphology shows excellent accuracy and time efficacy compared to traditional analysis methods. This tool, which we make openly available, could find application to study microglia morphology using fluorescence imaging in a wide range of brain disease models.

Sensitivity field distributions for segmental bioelectrical impedance analysis based on real human anatomy

NASA Astrophysics Data System (ADS)

Danilov, A. A.; Kramarenko, V. K.; Nikolaev, D. V.; Rudnev, S. G.; Salamatova, V. Yu; Smirnov, A. V.; Vassilevski, Yu V.

2013-04-01

In this work, an adaptive unstructured tetrahedral mesh generation technology is applied for simulation of segmental bioimpedance measurements using high-resolution whole-body model of the Visible Human Project man. Sensitivity field distributions for a conventional tetrapolar, as well as eight- and ten-electrode measurement configurations are obtained. Based on the ten-electrode configuration, we suggest an algorithm for monitoring changes in the upper lung area.

Highly sensitive solids mass spectrometer uses inert-gas ion source

NASA Technical Reports Server (NTRS)

1966-01-01

Mass spectrometer provides a recorded analysis of solid material surfaces and bulk. A beam of high-energy inert-gas ions bombards the surface atoms of a sample and converts a percentage into an ionized vapor. The mass spectrum analyzer separates the vapor ionic constituents by mass-to-charge ratio.

HIGHLY SENSITIVE DIOXIN IMMUNOASSAY AND ITS APPLICATIONS TO SOIL AND BIOTA SAMPLES. (R825433)

EPA Science Inventory

Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known highly toxic compound that is present in nearly all components of the global ecosystem, including air, soil, sediment, fish and humans. Dioxin analysis is equipment intensive and expensive requiring low ppt or even ppq ...

Development of a reagentless electrochemiluminescent electrode for flow injection analysis using copolymerised luminol/aniline on nano-TiO2 functionalised indium-tin oxide glass.

PubMed

Liu, Chao; Wei, Xiuhua; Tu, Yifeng

2013-07-15

In this study, a nano-structured copolymer of luminol/aniline (PLA) was deposited onto nano-TiO2-functionalised indium tin oxide (ITO)-coated glass by electrochemical polymerisation using cyclic voltammetry (CV). The resulting reagentless electrochemiluminescent (ECL) electrode (ECLode) can be used for flow injection analysis (FIA). The properties of the ECLode were characterised by CV, electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM). The ECLode has high background ECL emission as well as excellent stability and reproducibility, and yielding sensitive response towards target analytes. The ECL emissions of the ECLode were 50 times higher than PLA/ITO, and 500 times higher than polyluminol (PL)/ITO. The ECLode showed sensitive responses to reactive oxygen species (ROSs), permitting its application for determination of antioxidants by quenching. Under optimised conditions, an absolute detection limit of 69.9 pg was obtained for resveratrol, comparable to the highest levels of sensitivity achieved by other methods. Thus, the gross antioxidant content of red wine was determined, with satisfactory recoveries between 87.6% and 108.3%. These results suggest a bright future for the use of the ECLode for single-channel FIA due to its high sensitivity, accuracy and reproducibility. Copyright © 2013 Elsevier B.V. All rights reserved.

Identification of Proteus mirabilis Mutants with Increased Sensitivity to Antimicrobial Peptides

PubMed Central

McCoy, Andrea J.; Liu, Hongjian; Falla, Timothy J.; Gunn, John S.

2001-01-01

Antimicrobial peptides (APs) are important components of the innate defenses of animals, plants, and microorganisms. However, some bacterial pathogens are resistant to the action of APs. For example, Proteus mirabilis is highly resistant to the action of APs, such as polymyxin B (PM), protegrin, and the synthetic protegrin analog IB-367. To better understand this resistance, a transposon mutagenesis approach was used to generate P. mirabilis mutants sensitive to APs. Four unique PM-sensitive mutants of P. mirabilis were identified (these mutants were >2 to >128 times more sensitive than the wild type). Two of these mutants were also sensitive to IB-367 (16 and 128 times more sensitive than the wild type). Lipopolysaccharide (LPS) profiles of the PM- and protegrin-sensitive mutants demonstrated marked differences in both the lipid A and O-antigen regions, while the PM-sensitive mutants appeared to have alterations of either lipid A or O antigen. Matrix-assisted laser desorption ionization–time of flight mass spectrometry analysis of the wild-type and PM-sensitive mutant lipid A showed species with one or two aminoarabinose groups, while lipid A from the PM- and protegrin-sensitive mutants was devoid of aminoarabinose. When the mutants were streaked on an agar-containing medium, the swarming motility of the PM- and protegrin-sensitive mutants was completely inhibited and the swarming motility of the mutants sensitive to only PM was markedly decreased. DNA sequence analysis of the mutagenized loci revealed similarities to an O-acetyltransferase (PM and protegrin sensitive) and ATP synthase and sap loci (PM sensitive). These data further support the role of LPS modifications as an elaborate mechanism in the resistance of certain bacterial species to APs and suggest that LPS surface charge alterations may play a role in P. mirabilis swarming motility. PMID:11408219

Low-Temperature Photochemically Activated Amorphous Indium-Gallium-Zinc Oxide for Highly Stable Room-Temperature Gas Sensors.

PubMed

Jaisutti, Rawat; Kim, Jaeyoung; Park, Sung Kyu; Kim, Yong-Hoon

2016-08-10

We report on highly stable amorphous indium-gallium-zinc oxide (IGZO) gas sensors for ultraviolet (UV)-activated room-temperature detection of volatile organic compounds (VOCs). The IGZO sensors fabricated by a low-temperature photochemical activation process and exhibiting two orders higher photocurrent compared to conventional zinc oxide sensors, allowed high gas sensitivity against various VOCs even at room temperature. From a systematic analysis, it was found that by increasing the UV intensity, the gas sensitivity, response time, and recovery behavior of an IGZO sensor were strongly enhanced. In particular, under an UV intensity of 30 mW cm(-2), the IGZO sensor exhibited gas sensitivity, response time and recovery time of 37%, 37 and 53 s, respectively, against 750 ppm concentration of acetone gas. Moreover, the IGZO gas sensor had an excellent long-term stability showing around 6% variation in gas sensitivity over 70 days. These results strongly support a conclusion that a low-temperature solution-processed amorphous IGZO film can serve as a good candidate for room-temperature VOCs sensors for emerging wearable electronics.

Facile and sensitive determination of N-nitrosamines in food samples by high-performance liquid chromatography via combining fluorescent labeling with dispersive liquid-liquid microextraction.

PubMed

Lu, Shuaimin; Wu, Di; Li, Guoliang; Lv, Zhengxian; Gong, Peiwei; Xia, Lian; Sun, Zhiwei; Chen, Guang; Chen, Xuefeng; You, Jinmao; Wu, Yongning

2017-11-01

The intake of N-nitrosamines (NAs) from foodstuffs is considered to be an important influence factor for several cancers. But the rapid and sensitive screening of NAs remains a challenge in the field of food safety. Inspired by that, a sensitive and rapid method was demonstrated for determination of five NAs (Nitrosopyrrolidine, Nitrosodimethylamine, Nitrosodiethylamine, Nitrosodipropylamine and Nitrosodibutylamine) using dispersive liquid-liquid microextraction (DLLME) followed by high-performance liquid chromatography with fluorescence detection (HPLC-FLD). The NAs were firstly denitrosated and labeled by 2-(11H-benzo[a]carbazol-11-yl) ethyl carbonochloridate (BCEC-Cl) and finally enriched by DLLME. Furthermore, the main DLLME conditions were optimized systematically. Under the optimal conditions, satisfactory limits of detection (LODs) were obtained with a range of 0.01-0.07ngg -1 , which were significantly lower than the reported methods. The developed method showed many merits including rapidity, simplicity, high sensitivity and excellent selectivity, which shows a broad prospect in food safety analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Statistical sensitivity on right-handed currents in presence of eV scale sterile neutrinos with KATRIN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinbrink, Nicholas M.N.; Weinheimer, Christian; Glück, Ferenc

The KATRIN experiment aims to determine the absolute neutrino mass by measuring the endpoint region of the tritium β-spectrum. As a large-scale experiment with a sharp energy resolution, high source luminosity and low background it may also be capable of testing certain theories of neutrino interactions beyond the standard model (SM). An example of a non-SM interaction are right-handed currents mediated by right-handed W bosons in the left-right symmetric model (LRSM). In this extension of the SM, an additional SU(2){sub R} symmetry in the high-energy limit is introduced, which naturally includes sterile neutrinos and predicts the seesaw mechanism. In tritiummore » β decay, this leads to an additional term from interference between left- and right-handed interactions, which enhances or suppresses certain regions near the endpoint of the beta spectrum. In this work, the sensitivity of KATRIN to right-handed currents is estimated for the scenario of a light sterile neutrino with a mass of some eV. This analysis has been performed with a Bayesian analysis using Markov Chain Monte Carlo (MCMC). The simulations show that, in principle, KATRIN will be able to set sterile neutrino mass-dependent limits on the interference strength. The sensitivity is significantly increased if the Q value of the β decay can be sufficiently constrained. However, the sensitivity is not high enough to improve current upper limits from right-handed W boson searches at the LHC.« less

OPTIMA: sensitive and accurate whole-genome alignment of error-prone genomic maps by combinatorial indexing and technology-agnostic statistical analysis.

PubMed

Verzotto, Davide; M Teo, Audrey S; Hillmer, Axel M; Nagarajan, Niranjan

2016-01-01

Resolution of complex repeat structures and rearrangements in the assembly and analysis of large eukaryotic genomes is often aided by a combination of high-throughput sequencing and genome-mapping technologies (for example, optical restriction mapping). In particular, mapping technologies can generate sparse maps of large DNA fragments (150 kilo base pairs (kbp) to 2 Mbp) and thus provide a unique source of information for disambiguating complex rearrangements in cancer genomes. Despite their utility, combining high-throughput sequencing and mapping technologies has been challenging because of the lack of efficient and sensitive map-alignment algorithms for robustly aligning error-prone maps to sequences. We introduce a novel seed-and-extend glocal (short for global-local) alignment method, OPTIMA (and a sliding-window extension for overlap alignment, OPTIMA-Overlap), which is the first to create indexes for continuous-valued mapping data while accounting for mapping errors. We also present a novel statistical model, agnostic with respect to technology-dependent error rates, for conservatively evaluating the significance of alignments without relying on expensive permutation-based tests. We show that OPTIMA and OPTIMA-Overlap outperform other state-of-the-art approaches (1.6-2 times more sensitive) and are more efficient (170-200 %) and precise in their alignments (nearly 99 % precision). These advantages are independent of the quality of the data, suggesting that our indexing approach and statistical evaluation are robust, provide improved sensitivity and guarantee high precision.

Development of a highly sensitive and specific ELISA method for the determination of l-corydalmine in SD rats with monoclonal antibody.

PubMed

Zhang, Hongwei; Gao, Lan; Shu, Menglin; Liu, Jihua; Yu, Boyang

2018-01-15

l-Corydalmine (l-CDL) is a potent analgesic constituent of the traditional Chinese medicine, Rhizoma Corydalis. However, the pharmacokinetic process and tissue distribution of l-CDL in vivo are still unknown. Therefore, it is necessary to establish a simple and sensitive method to detect l-CDL, which will be helpful to study its distribution and pharmacokinetic process. To determine this compound in biological samples, a monoclonal antibody (mAb) against l-CDL was produced and a fast and highly sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed in this study. The icELISA was applied to determine l-CDL in biological samples. The limit of detection (LOD) of the method was 0.015 ng/mL with a liner range of 1-1000 ng/mL (R 2  = 0.9912). The intra- and inter-day precision were below 15% and the recoveries were within 80-117%. Finally, the developed immunoassay was successfully applied to the analysis of the distribution of l-CDL in SD rats. In conclusion, the icELISA based on the anti-l-CDL mAb could be considered as a highly sensitive and rapid method for the determination of l-CDL in biological samples. The ELISA approach may provide a valuable tool for the analysis of small molecules in biological samples. Copyright © 2017. Published by Elsevier B.V.

Statistical sensitivity on right-handed currents in presence of eV scale sterile neutrinos with KATRIN

NASA Astrophysics Data System (ADS)

Steinbrink, Nicholas M. N.; Glück, Ferenc; Heizmann, Florian; Kleesiek, Marco; Valerius, Kathrin; Weinheimer, Christian; Hannestad, Steen

2017-06-01

The KATRIN experiment aims to determine the absolute neutrino mass by measuring the endpoint region of the tritium β-spectrum. As a large-scale experiment with a sharp energy resolution, high source luminosity and low background it may also be capable of testing certain theories of neutrino interactions beyond the standard model (SM). An example of a non-SM interaction are right-handed currents mediated by right-handed W bosons in the left-right symmetric model (LRSM). In this extension of the SM, an additional SU(2)R symmetry in the high-energy limit is introduced, which naturally includes sterile neutrinos and predicts the seesaw mechanism. In tritium β decay, this leads to an additional term from interference between left- and right-handed interactions, which enhances or suppresses certain regions near the endpoint of the beta spectrum. In this work, the sensitivity of KATRIN to right-handed currents is estimated for the scenario of a light sterile neutrino with a mass of some eV. This analysis has been performed with a Bayesian analysis using Markov Chain Monte Carlo (MCMC). The simulations show that, in principle, KATRIN will be able to set sterile neutrino mass-dependent limits on the interference strength. The sensitivity is significantly increased if the Q value of the β decay can be sufficiently constrained. However, the sensitivity is not high enough to improve current upper limits from right-handed W boson searches at the LHC.

Multi-scale Modeling of the Impact Response of a Strain Rate Sensitive High-Manganese Austenitic Steel

NASA Astrophysics Data System (ADS)

Önal, Orkun; Ozmenci, Cemre; Canadinc, Demircan

2014-09-01

A multi-scale modeling approach was applied to predict the impact response of a strain rate sensitive high-manganese austenitic steel. The roles of texture, geometry and strain rate sensitivity were successfully taken into account all at once by coupling crystal plasticity and finite element (FE) analysis. Specifically, crystal plasticity was utilized to obtain the multi-axial flow rule at different strain rates based on the experimental deformation response under uniaxial tensile loading. The equivalent stress - equivalent strain response was then incorporated into the FE model for the sake of a more representative hardening rule under impact loading. The current results demonstrate that reliable predictions can be obtained by proper coupling of crystal plasticity and FE analysis even if the experimental flow rule of the material is acquired under uniaxial loading and at moderate strain rates that are significantly slower than those attained during impact loading. Furthermore, the current findings also demonstrate the need for an experiment-based multi-scale modeling approach for the sake of reliable predictions of the impact response.

Standardization of a fluconazole bioassay and correlation of results with those obtained by high-pressure liquid chromatography.

PubMed Central

Rex, J H; Hanson, L H; Amantea, M A; Stevens, D A; Bennett, J E

1991-01-01

An improved bioassay for fluconazole was developed. This assay is sensitive in the clinically relevant range (2 to 40 micrograms/ml) and analyzes plasma, serum, and cerebrospinal fluid specimens; bioassay results correlate with results obtained by high-pressure liquid chromatography (HPLC). Bioassay and HPLC analyses of spiked plasma, serum, and cerebrospinal fluid samples (run as unknowns) gave good agreement with expected values. Analysis of specimens from patients gave equivalent results by both HPLC and bioassay. HPLC had a lower within-run coefficient of variation (less than 2.5% for HPLC versus less than 11% for bioassay) and a lower between-run coefficient of variation (less than 5% versus less than 12% for bioassay) and was more sensitive (lower limit of detection, 0.1 micrograms/ml [versus 2 micrograms/ml for bioassay]). The bioassay is, however, sufficiently accurate and sensitive for clinical specimens, and its relative simplicity, low sample volume requirement, and low equipment cost should make it the technique of choice for analysis of routine clinical specimens. PMID:1854166

High order statistical signatures from source-driven measurements of subcritical fissile systems

NASA Astrophysics Data System (ADS)

Mattingly, John Kelly

1998-11-01

This research focuses on the development and application of high order statistical analyses applied to measurements performed with subcritical fissile systems driven by an introduced neutron source. The signatures presented are derived from counting statistics of the introduced source and radiation detectors that observe the response of the fissile system. It is demonstrated that successively higher order counting statistics possess progressively higher sensitivity to reactivity. Consequently, these signatures are more sensitive to changes in the composition, fissile mass, and configuration of the fissile assembly. Furthermore, it is shown that these techniques are capable of distinguishing the response of the fissile system to the introduced source from its response to any internal or inherent sources. This ability combined with the enhanced sensitivity of higher order signatures indicates that these techniques will be of significant utility in a variety of applications. Potential applications include enhanced radiation signature identification of weapons components for nuclear disarmament and safeguards applications and augmented nondestructive analysis of spent nuclear fuel. In general, these techniques expand present capabilities in the analysis of subcritical measurements.

Local sensitivity analysis for inverse problems solved by singular value decomposition

USGS Publications Warehouse

Hill, M.C.; Nolan, B.T.

2010-01-01

Local sensitivity analysis provides computationally frugal ways to evaluate models commonly used for resource management, risk assessment, and so on. This includes diagnosing inverse model convergence problems caused by parameter insensitivity and(or) parameter interdependence (correlation), understanding what aspects of the model and data contribute to measures of uncertainty, and identifying new data likely to reduce model uncertainty. Here, we consider sensitivity statistics relevant to models in which the process model parameters are transformed using singular value decomposition (SVD) to create SVD parameters for model calibration. The statistics considered include the PEST identifiability statistic, and combined use of the process-model parameter statistics composite scaled sensitivities and parameter correlation coefficients (CSS and PCC). The statistics are complimentary in that the identifiability statistic integrates the effects of parameter sensitivity and interdependence, while CSS and PCC provide individual measures of sensitivity and interdependence. PCC quantifies correlations between pairs or larger sets of parameters; when a set of parameters is intercorrelated, the absolute value of PCC is close to 1.00 for all pairs in the set. The number of singular vectors to include in the calculation of the identifiability statistic is somewhat subjective and influences the statistic. To demonstrate the statistics, we use the USDA’s Root Zone Water Quality Model to simulate nitrogen fate and transport in the unsaturated zone of the Merced River Basin, CA. There are 16 log-transformed process-model parameters, including water content at field capacity (WFC) and bulk density (BD) for each of five soil layers. Calibration data consisted of 1,670 observations comprising soil moisture, soil water tension, aqueous nitrate and bromide concentrations, soil nitrate concentration, and organic matter content. All 16 of the SVD parameters could be estimated by regression based on the range of singular values. Identifiability statistic results varied based on the number of SVD parameters included. Identifiability statistics calculated for four SVD parameters indicate the same three most important process-model parameters as CSS/PCC (WFC1, WFC2, and BD2), but the order differed. Additionally, the identifiability statistic showed that BD1 was almost as dominant as WFC1. The CSS/PCC analysis showed that this results from its high correlation with WCF1 (-0.94), and not its individual sensitivity. Such distinctions, combined with analysis of how high correlations and(or) sensitivities result from the constructed model, can produce important insights into, for example, the use of sensitivity analysis to design monitoring networks. In conclusion, the statistics considered identified similar important parameters. They differ because (1) with CSS/PCC can be more awkward because sensitivity and interdependence are considered separately and (2) identifiability requires consideration of how many SVD parameters to include. A continuing challenge is to understand how these computationally efficient methods compare with computationally demanding global methods like Markov-Chain Monte Carlo given common nonlinear processes and the often even more nonlinear models.

Sensitivity analysis and approximation methods for general eigenvalue problems

NASA Technical Reports Server (NTRS)

Murthy, D. V.; Haftka, R. T.

1986-01-01

Optimization of dynamic systems involving complex non-hermitian matrices is often computationally expensive. Major contributors to the computational expense are the sensitivity analysis and reanalysis of a modified design. The present work seeks to alleviate this computational burden by identifying efficient sensitivity analysis and approximate reanalysis methods. For the algebraic eigenvalue problem involving non-hermitian matrices, algorithms for sensitivity analysis and approximate reanalysis are classified, compared and evaluated for efficiency and accuracy. Proper eigenvector normalization is discussed. An improved method for calculating derivatives of eigenvectors is proposed based on a more rational normalization condition and taking advantage of matrix sparsity. Important numerical aspects of this method are also discussed. To alleviate the problem of reanalysis, various approximation methods for eigenvalues are proposed and evaluated. Linear and quadratic approximations are based directly on the Taylor series. Several approximation methods are developed based on the generalized Rayleigh quotient for the eigenvalue problem. Approximation methods based on trace theorem give high accuracy without needing any derivatives. Operation counts for the computation of the approximations are given. General recommendations are made for the selection of appropriate approximation technique as a function of the matrix size, number of design variables, number of eigenvalues of interest and the number of design points at which approximation is sought.

HPAEC-PAD for oligosaccharide analysis-novel insights into analyte sensitivity and response stability.

PubMed

Mechelke, Matthias; Herlet, Jonathan; Benz, J Philipp; Schwarz, Wolfgang H; Zverlov, Vladimir V; Liebl, Wolfgang; Kornberger, Petra

2017-12-01

The rising importance of accurately detecting oligosaccharides in biomass hydrolyzates or as ingredients in food, such as in beverages and infant milk products, demands for the availability of tools to sensitively analyze the broad range of available oligosaccharides. Over the last decades, HPAEC-PAD has been developed into one of the major technologies for this task and represents a popular alternative to state-of-the-art LC-MS oligosaccharide analysis. This work presents the first comprehensive study which gives an overview of the separation of 38 analytes as well as enzymatic hydrolyzates of six different polysaccharides focusing on oligosaccharides. The high sensitivity of the PAD comes at cost of its stability due to recession of the gold electrode. By an in-depth analysis of the sensitivity drop over time for 35 analytes, including xylo- (XOS), arabinoxylo- (AXOS), laminari- (LOS), manno- (MOS), glucomanno- (GMOS), and cellooligosaccharides (COS), we developed an analyte-specific one-phase decay model for this effect over time. Using this model resulted in significantly improved data normalization when using an internal standard. Our results thereby allow a quantification approach which takes the inevitable and analyte-specific PAD response drop into account. Graphical abstract HPAEC-PAD analysis of oligosaccharides and determination of PAD response drop leading to an improved data normalization.

A nano-patterned self assembled monolayer (SAM) rutile titania cancer chip for rapid, low cost, highly sensitive, direct cancer analysis in MALDI-MS.

PubMed

Manikandan, M; Gopal, Judy; Hasan, Nazim; Wu, Hui-Fen

2014-12-01

We developed a cancer chip by nano-patterning a highly sensitive SAM titanium surface capable of capturing and sensing concentrations as low as 10 cancer cells/mL from the environment by Matrix Assisted Laser Desorption and Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). The current approach evades any form of pretreatment and sample preparation processes; it is time saving and does not require the (expensive) conventional MALDI target plate. The home made aluminium (Al) target holder cost, on which we loaded the cancer chips for MALDI-TOF MS analysis, is about 60 USD. While the conventional stainless steel MALDI target plate is more than 700 USD. The SAM surface was an effective platform leading to on-chip direct MALDI-MS detection of cancer cells. We compared the functionality of this chip with the unmodified titanium surfaces and thermally oxidized (TO) titanium surfaces. The lowest detectable concentration of the TO chip was 10(3) cells/mL, while the lowest detectable concentration of the control or unmodified titanium chips was 10(6) cells/mL. Compared to the control surface, the SAM cancer chip showed 100,000 times of enhanced sensitivity and compared with the TO chip, 1000 times of increased sensitivity. The high sensitivity of the SAM surfaces is attributed to the presence of the rutile SAM, surface roughness and surface wettability as confirmed by AFM, XRD, contact angle microscope and FE-SEM. This study opens a new avenue for the potent application of the SAM cancer chip for direct cancer diagnosis by MALDI-TOF MS in the near future. Copyright © 2014. Published by Elsevier B.V.

Molecular tools for diagnosis of visceral leishmaniasis: systematic review and meta-analysis of diagnostic test accuracy.

PubMed

de Ruiter, C M; van der Veer, C; Leeflang, M M G; Deborggraeve, S; Lucas, C; Adams, E R

2014-09-01

Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Resonance analysis of a high temperature piezoelectric disc for sensitivity characterization.

PubMed

Bilgunde, Prathamesh N; Bond, Leonard J

2018-07-01

Ultrasonic transducers for high temperature (200 °C+) applications are a key enabling technology for advanced nuclear power systems and in a range of chemical and petro-chemical industries. Design, fabrication and optimization of such transducers using piezoelectric materials remains a challenge. In this work, experimental data-based analysis is performed to investigate the fundamental causal factors for the resonance characteristics of a piezoelectric disc at elevated temperatures. The effect of all ten temperature-dependent piezoelectric constants (ε 33 , ε 11 , d 33 , d 31 , d 15 , s 11 , s 12 , s 13 , s 33 , s 44 ) is studied numerically on both the radial and thickness mode resonances of a piezoelectric disc. A sensitivity index is defined to quantify the effect of each of the temperature-dependent coefficients on the resonance modes of the modified lead zirconium titanate disc. The temperature dependence of s 33 showed highest sensitivity towards the thickness resonance mode followed by ε 33 , s 11 , s 13 , s 12 , d 31 , d 33 , s 44 , ε 11 , and d 15 in the decreasing order of the sensitivity index. For radial resonance modes, the temperature dependence of ε 33 showed highest sensitivity index followed by s 11 , s 12 and d 31 coefficient. This numerical study demonstrates that the magnitude of d 33 is not the sole factor that affects the resonance characteristics of the piezoelectric disc at high temperatures. It appears that there exists a complex interplay between various temperature dependent piezoelectric coefficients that causes reduction in the thickness mode resonance frequencies which is found to be agreement in with the experimental data at an elevated temperature. Copyright © 2018 Elsevier B.V. All rights reserved.

Recent Results from the 2015 flight of Spider

NASA Astrophysics Data System (ADS)

Jones, William C.

2016-06-01

Spider is a balloon borne mm-wave polarimeter designed to provide high fidelity measurements of the large scale polarization of the microwave sky. Spider flew a 17 day mission in January 2015, mapping roughly 10% of the full sky (4500 square degrees) in the southern Galactic hemisphere at each of 94 and 150 GHz. Spider achieved an instrumental sensitivity of 4 μ K_{CMB}√{s}, providing maps that exceed the sensitivity of the Planck data. We discuss these data, the current status of our science analysis, and our understanding of the Galacticforeground emission in this high latitude region.

Quantitative polarized light microscopy using spectral multiplexing interferometry.

PubMed

Li, Chengshuai; Zhu, Yizheng

2015-06-01

We propose an interferometric spectral multiplexing method for measuring birefringent specimens with simple configuration and high sensitivity. The retardation and orientation of sample birefringence are simultaneously encoded onto two spectral carrier waves, generated interferometrically by a birefringent crystal through polarization mixing. A single interference spectrum hence contains sufficient information for birefringence determination, eliminating the need for mechanical rotation or electrical modulation. The technique is analyzed theoretically and validated experimentally on cellulose film. System simplicity permits the possibility of mitigating system birefringence background. Further analysis demonstrates the technique's exquisite sensitivity as high as ∼20  pm for retardation measurement.

In-line microfluidic refractometer based on C-shaped fiber assisted photonic crystal fiber Sagnac interferometer.

PubMed

Wu, Chuang; Tse, Ming-Leung Vincent; Liu, Zhengyong; Guan, Bai-Ou; Lu, Chao; Tam, Hwa-Yaw

2013-09-01

We propose and demonstrate a highly sensitive in-line photonic crystal fiber (PCF) microfluidic refractometer. Ultrathin C-shaped fibers are spliced in-between the PCF and standard single-mode fibers. The C-shaped fibers provide openings for liquid to flow in and out of the PCF. Based on a Sagnac interferometer, the refractive index (RI) response of the device is investigated theoretically and experimentally. A high sensitivity of 6621 nm/RIU for liquid RI from 1.330 to 1.333 is achieved in the experiment, which agrees well with the theoretical analysis.

Climate change projected fire weather sensitivity: CaliforniaSanta Ana wind occurrence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Norman L.; Schlegel, Nicole J.

2006-01-01

A new methodbased on global climate model pressuregradients was developed for identifying coastal high-wind fire weatherconditions, such as the Santa Ana Occurrence (SAO). Application of thismethod for determining southern California Santa Ana wind occurrenceresulted in a good correlation between derived large-scale SAOs andobserved offshore winds during periods of low humidity. The projectedchange in the number of SAOs was analyzed using two global climatemodels, one a low temperature sensitivity and the other amiddle-temperature sensitivity, both forced with low and high emissionscenarios, for three future time periods. This initial analysis showsconsistent shifts in SAO events from earlier (September-October) to later(November-December) in themore » season, suggesting that SAOs may significantlyincrease the extent of California coastal areas burned by wildfires, lossof life, and property.« less

Fabrication and Structural Design of Micro Pressure Sensors for Tire Pressure Measurement Systems (TPMS).

PubMed

Tian, Bian; Zhao, Yulong; Jiang, Zhuangde; Zhang, Ling; Liao, Nansheng; Liu, Yuanhao; Meng, Chao

2009-01-01

In this paper we describe the design and testing of a micro piezoresistive pressure sensor for a Tire Pressure Measurement System (TPMS) which has the advantages of a minimized structure, high sensitivity, linearity and accuracy. Through analysis of the stress distribution of the diaphragm using the ANSYS software, a model of the structure was established. The fabrication on a single silicon substrate utilizes the technologies of anisotropic chemical etching and packaging through glass anodic bonding. The performance of this type of piezoresistive sensor, including size, sensitivity, and long-term stability, were investigated. The results indicate that the accuracy is 0.5% FS, therefore this design meets the requirements for a TPMS, and not only has a smaller size and simplicity of preparation, but also has high sensitivity and accuracy.

Studentized continuous wavelet transform (t-CWT) in the analysis of individual ERPs: real and simulated EEG data

PubMed Central

Real, Ruben G. L.; Kotchoubey, Boris; Kübler, Andrea

2014-01-01

This study aimed at evaluating the performance of the Studentized Continuous Wavelet Transform (t-CWT) as a method for the extraction and assessment of event-related brain potentials (ERP) in data from a single subject. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the t-CWT were assessed and compared to a variety of competing procedures using simulated EEG data at six low signal-to-noise ratios. Results show that the t-CWT combines high sensitivity and specificity with favorable PPV and NPV. Applying the t-CWT to authentic EEG data obtained from 14 healthy participants confirmed its high sensitivity. The t-CWT may thus be well suited for the assessment of weak ERPs in single-subject settings. PMID:25309308

Studentized continuous wavelet transform (t-CWT) in the analysis of individual ERPs: real and simulated EEG data.

PubMed

Real, Ruben G L; Kotchoubey, Boris; Kübler, Andrea

2014-01-01

This study aimed at evaluating the performance of the Studentized Continuous Wavelet Transform (t-CWT) as a method for the extraction and assessment of event-related brain potentials (ERP) in data from a single subject. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the t-CWT were assessed and compared to a variety of competing procedures using simulated EEG data at six low signal-to-noise ratios. Results show that the t-CWT combines high sensitivity and specificity with favorable PPV and NPV. Applying the t-CWT to authentic EEG data obtained from 14 healthy participants confirmed its high sensitivity. The t-CWT may thus be well suited for the assessment of weak ERPs in single-subject settings.

Global sensitivity analysis for urban water quality modelling: Terminology, convergence and comparison of different methods

NASA Astrophysics Data System (ADS)

Vanrolleghem, Peter A.; Mannina, Giorgio; Cosenza, Alida; Neumann, Marc B.

2015-03-01

Sensitivity analysis represents an important step in improving the understanding and use of environmental models. Indeed, by means of global sensitivity analysis (GSA), modellers may identify both important (factor prioritisation) and non-influential (factor fixing) model factors. No general rule has yet been defined for verifying the convergence of the GSA methods. In order to fill this gap this paper presents a convergence analysis of three widely used GSA methods (SRC, Extended FAST and Morris screening) for an urban drainage stormwater quality-quantity model. After the convergence was achieved the results of each method were compared. In particular, a discussion on peculiarities, applicability, and reliability of the three methods is presented. Moreover, a graphical Venn diagram based classification scheme and a precise terminology for better identifying important, interacting and non-influential factors for each method is proposed. In terms of convergence, it was shown that sensitivity indices related to factors of the quantity model achieve convergence faster. Results for the Morris screening method deviated considerably from the other methods. Factors related to the quality model require a much higher number of simulations than the number suggested in literature for achieving convergence with this method. In fact, the results have shown that the term "screening" is improperly used as the method may exclude important factors from further analysis. Moreover, for the presented application the convergence analysis shows more stable sensitivity coefficients for the Extended-FAST method compared to SRC and Morris screening. Substantial agreement in terms of factor fixing was found between the Morris screening and Extended FAST methods. In general, the water quality related factors exhibited more important interactions than factors related to water quantity. Furthermore, in contrast to water quantity model outputs, water quality model outputs were found to be characterised by high non-linearity.

A method for high-throughput, sensitive analysis of IgG Fc and Fab glycosylation by capillary electrophoresis.

PubMed

Mahan, Alison E; Tedesco, Jacquelynne; Dionne, Kendall; Baruah, Kavitha; Cheng, Hao D; De Jager, Philip L; Barouch, Dan H; Suscovich, Todd; Ackerman, Margaret; Crispin, Max; Alter, Galit

2015-02-01

The N-glycan of the IgG constant region (Fc) plays a central role in tuning and directing multiple antibody functions in vivo, including antibody-dependent cellular cytotoxicity, complement deposition, and the regulation of inflammation, among others. However, traditional methods of N-glycan analysis, including HPLC and mass spectrometry, are technically challenging and ill suited to handle the large numbers of low concentration samples analyzed in clinical or animal studies of the N-glycosylation of polyclonal IgG. Here we describe a capillary electrophoresis-based technique to analyze plasma-derived polyclonal IgG-glycosylation quickly and accurately in a cost-effective, sensitive manner that is well suited for high-throughput analyses. Additionally, because a significant fraction of polyclonal IgG is glycosylated on both Fc and Fab domains, we developed an approach to separate and analyze domain-specific glycosylation in polyclonal human, rhesus and mouse IgGs. Overall, this protocol allows for the rapid, accurate, and sensitive analysis of Fc-specific IgG glycosylation, which is critical for population-level studies of how antibody glycosylation may vary in response to vaccination or infection, and across disease states ranging from autoimmunity to cancer in both clinical and animal studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Determination of fluorine concentrations using wavelength dispersive X-ray fluorescence (WDXRF) spectrometry to analyze fluoride precipitates.

NASA Astrophysics Data System (ADS)

Lee, H. A.; Lee, J.; Kwon, E.; Kim, D.; Yoon, H. O.

2015-12-01

In recent times, fluorine has been receiving increasing attention due to the possibility for chemical (HF) leakage accidents and its high toxicity to human and environment. In this respect, a novel approach for the determination of fluorine concentrations in water samples using wavelength dispersive X-ray fluorescence (WDXRF) spectrometry was investigated in this study. The main disadvantage of WDXRF technique for fluorine analysis is low analytical sensitivity for light elements with atomic number (Z) less than 15. To overcome this problem, we employed the precipitation reaction which fluoride is reacted with cation such as Al3+ and/or Ca2+ prior to WDXRF analysis because of their high analytical sensitivity. The cation was added in fluoride solutions to form precipitate (AlF3 and/or CaF2) and then the solution was filtered through Whatman filter. After drying at 60 °C for 5 min, the filter was coated with X-ray film and directly analyzed using WDXRF spectrometry. Consequently, we analyzed the cation on filter and subsequently fluorine concentration was calculated inversely based on chemical form of precipitate. This method can improve the analytical sensitivity of WDXRF technique for fluorine analysis and be applicable to various elements that can make precipitate.

Effect of different transport observations on inverse modeling results: case study of a long-term groundwater tracer test monitored at high resolution

NASA Astrophysics Data System (ADS)

Rasa, Ehsan; Foglia, Laura; Mackay, Douglas M.; Scow, Kate M.

2013-11-01

Conservative tracer experiments can provide information useful for characterizing various subsurface transport properties. This study examines the effectiveness of three different types of transport observations for sensitivity analysis and parameter estimation of a three-dimensional site-specific groundwater flow and transport model: conservative tracer breakthrough curves (BTCs), first temporal moments of BTCs ( m 1), and tracer cumulative mass discharge ( M d) through control planes combined with hydraulic head observations ( h). High-resolution data obtained from a 410-day controlled field experiment at Vandenberg Air Force Base, California (USA), have been used. In this experiment, bromide was injected to create two adjacent plumes monitored at six different transects (perpendicular to groundwater flow) with a total of 162 monitoring wells. A total of 133 different observations of transient hydraulic head, 1,158 of BTC concentration, 23 of first moment, and 36 of mass discharge were used for sensitivity analysis and parameter estimation of nine flow and transport parameters. The importance of each group of transport observations in estimating these parameters was evaluated using sensitivity analysis, and five out of nine parameters were calibrated against these data. Results showed the advantages of using temporal moment of conservative tracer BTCs and mass discharge as observations for inverse modeling.

Two sensitizing oxidation products of p-phenylenediamine patch tested in patients allergic to p-phenylenediamine.

PubMed

Young, Ewa; Zimerson, Erik; Bruze, Magnus; Svedman, Cecilia

2016-02-01

The results from a previous study indicated the presence of several possible sensitizers formed during oxidation of the potent sensitizer p-phenylenediamine (PPD) to which PPD-sensitized patients might react, in various patterns. To extract and analyse a yellow spot from a thin-layer chromatogram with oxidized PPD, to which 6 of 14 (43%) PPD-positive patients had reacted in a previous study, in order to identify potential sensitizer(s) and to patch test this/these substance(s) in the 14 PPD-positive patients. The yellow spot was extracted from a thin-layer chromatogram of oxidized PPD, and two substances, suspected to be allergens, were identified by analysis with gas chromatography mass spectrometry (GCMS). The 14 PPD-positive patients, who had been previously tested with the thin-layer chromatogram of oxidized PPD, participated in the investigation, and were tested with dilutions of the two substances. GCMS analysis identified 4-nitroaniline and 4,4'-azodianiline in the yellow spot. Of the 14 PPD-positive test patients, 5 (36%) reacted to 4-nitroaniline and 9 (64%) reacted to 4,4'-azodianiline. The results show that 4-nitroaniline and 4,4'-azodianiline, formed during oxidation of PPD, are potent sensitizers. PPD-sensitized patients react to a high extent to concentrations equimolar to PPD of 4-nitroaniline and 4,4'-azodianiline. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fourier analysis for hydrostatic pressure sensing in a polarization-maintaining photonic crystal fiber.

PubMed

Childs, Paul; Wong, Allan C L; Fu, H Y; Liao, Yanbiao; Tam, Hwayaw; Lu, Chao; Wai, P K A

2010-12-20

We measured the hydrostatic pressure dependence of the birefringence and birefringent dispersion of a Sagnac interferometric sensor incorporating a length of highly birefringent photonic crystal fiber using Fourier analysis. Sensitivity of both the phase and chirp spectra to hydrostatic pressure is demonstrated. Using this analysis, phase-based measurements showed a good linearity with an effective sensitivity of 9.45 nm/MPa and an accuracy of ±7.8 kPa using wavelength-encoded data and an effective sensitivity of -55.7 cm(-1)/MPa and an accuracy of ±4.4 kPa using wavenumber-encoded data. Chirp-based measurements, though nonlinear in response, showed an improvement in accuracy at certain pressure ranges with an accuracy of ±5.5 kPa for the full range of measured pressures using wavelength-encoded data and dropping to within ±2.5 kPa in the range of 0.17 to 0.4 MPa using wavenumber-encoded data. Improvements of the accuracy demonstrated the usefulness of implementing chirp-based analysis for sensing purposes.

A review of promising new immunoassay technology for monitoring forest herbicides

Treesearch

Charles K. McMahon

1993-01-01

Rising costs of classical instrumental methods of chemical analysis coupled with an increasing need for environmental monitoring has lead to the development of highly sensitive, low-cost immunochemical methods of analysis for the detection of environmental contaminants. These methods known simply as immunoassays are chemical assays which use antibodies as reagents. A...

The FAQUIRE Approach: FAst, QUantitative, hIghly Resolved and sEnsitivity Enhanced 1H, 13C Data.

PubMed

Farjon, Jonathan; Milande, Clément; Martineau, Estelle; Akoka, Serge; Giraudeau, Patrick

2018-02-06

The targeted analysis of metabolites in complex mixtures is a challenging issue. NMR is one of the major tools in this field, but there is a strong need for more sensitive, better-resolved, and faster quantitative methods. In this framework, we introduce the concept of FAst, QUantitative, hIghly Resolved and sEnsitivity enhanced (FAQUIRE) NMR to push forward the limits of metabolite NMR analysis. 2D 1 H, 13 C 2D quantitative maps are promising alternatives for enhancing the spectral resolution but are highly time-consuming because of (i) the intrinsic nature of 2D, (ii) the longer recycling times required for quantitative conditions, and (iii) the higher number of scans needed to reduce the level of detection/quantification to access low concentrated metabolites. To reach this aim, speeding up the recently developed QUantItative Perfected and pUre shifted HSQC (QUIPU HSQC) is an interesting attempt to develop the FAQUIRE concept. Thanks to the combination of spectral aliasing, nonuniform sampling, and variable repetition time, the acquisition time of 2D quantitative maps is reduced by a factor 6 to 9, while conserving a high spectral resolution thanks to a pure shift approach. The analytical potential of the new Quick QUIPU HSQC (Q QUIPU HSQC) is evaluated on a model metabolite sample, and its potential is shown on breast-cell extracts embedding metabolites at millimolar to submillimolar concentrations.

Evaluation of high throughput gene expression platforms using a genomic biomarker signature for prediction of skin sensitization.

PubMed

Forreryd, Andy; Johansson, Henrik; Albrekt, Ann-Sofie; Lindstedt, Malin

2014-05-16

Allergic contact dermatitis (ACD) develops upon exposure to certain chemical compounds termed skin sensitizers. To reduce the occurrence of skin sensitizers, chemicals are regularly screened for their capacity to induce sensitization. The recently developed Genomic Allergen Rapid Detection (GARD) assay is an in vitro alternative to animal testing for identification of skin sensitizers, classifying chemicals by evaluating transcriptional levels of a genomic biomarker signature. During assay development and biomarker identification, genome-wide expression analysis was applied using microarrays covering approximately 30,000 transcripts. However, the microarray platform suffers from drawbacks in terms of low sample throughput, high cost per sample and time consuming protocols and is a limiting factor for adaption of GARD into a routine assay for screening of potential sensitizers. With the purpose to simplify assay procedures, improve technical parameters and increase sample throughput, we assessed the performance of three high throughput gene expression platforms--nCounter®, BioMark HD™ and OpenArray®--and correlated their performance metrics against our previously generated microarray data. We measured the levels of 30 transcripts from the GARD biomarker signature across 48 samples. Detection sensitivity, reproducibility, correlations and overall structure of gene expression measurements were compared across platforms. Gene expression data from all of the evaluated platforms could be used to classify most of the sensitizers from non-sensitizers in the GARD assay. Results also showed high data quality and acceptable reproducibility for all platforms but only medium to poor correlations of expression measurements across platforms. In addition, evaluated platforms were superior to the microarray platform in terms of cost efficiency, simplicity of protocols and sample throughput. We evaluated the performance of three non-array based platforms using a limited set of transcripts from the GARD biomarker signature. We demonstrated that it was possible to achieve acceptable discriminatory power in terms of separation between sensitizers and non-sensitizers in the GARD assay while reducing assay costs, simplify assay procedures and increase sample throughput by using an alternative platform, providing a first step towards the goal to prepare GARD for formal validation and adaption of the assay for industrial screening of potential sensitizers.

Cost effectiveness analysis of screening for sight threatening diabetic eye disease

PubMed Central

James, Marilyn; Turner, David A; Broadbent, Deborah M; Vora, Jiten; Harding, Simon P

2000-01-01

Objective To measure the cost effectiveness of systematic photographic screening for sight threatening diabetic eye disease compared with existing practice. Design Cost effectiveness analysis Setting Liverpool. Subjects A target population of 5000 diabetic patients invited for screening. Main outcome measures Cost effectiveness (cost per true positive) of systematic and opportunistic programmes; incremental cost effectiveness of replacing opportunistic with systematic screening. Results Baseline prevalence of sight threatening eye disease was 14.1%. The cost effectiveness of the systematic programme was £209 (sensitivity 89%, specificity 86%, compliance 80%, annual cost £104 996) and of the opportunistic programme was £289 (combined sensitivity 63%, specificity 92%, compliance 78%, annual cost £99 981). The incremental cost effectiveness of completely replacing the opportunistic programme was £32. Absolute values of cost effectiveness were highly sensitive to varying prevalence, sensitivity and specificity, compliance, and programme size. Conclusion Replacing existing programmes with systematic screening for diabetic eye disease is justified. PMID:10856062

Application of positron annihilation lineshape analysis to fatigue damage and thermal embrittlement for nuclear plant materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uchida, M.; Ohta, Y.; Nakamura, N.

1995-08-01

Positron annihilation (PA) lineshape analysis is sensitive to detect microstructural defects such as vacancies and dislocations. The authors are developing a portable system and applying this technique to nuclear power plant material evaluations; fatigue damage in type 316 stainless steel and SA508 low alloy steel, and thermal embrittlement in duplex stainless steel. The PA technique was found to be sensitive in the early fatigue life (up to 10%), but showed a little sensitivity for later stages of the fatigue life in both type 316 stainless steel and SA508 ferritic steel. Type 316 steel showed a higher PA sensitivity than SA508more » since the initial SA508 microstructure already contained a high dislocation density in the as-received state. The PA parameter increased as a fraction of aging time in CF8M samples aged at 350 C and 400 C, but didn`t change much in CF8 samples.« less

Performance analysis of higher mode spoof surface plasmon polariton for terahertz sensing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Haizi; Tu, Wanli; Zhong, Shuncong, E-mail: zhongshuncong@hotmail.com

2015-04-07

We investigated the spoof surface plasmon polaritons (SSPPs) on 1D grooved metal surface for terahertz sensing of refractive index of the filling analyte through a prism-coupling attenuated total reflection setup. From the dispersion relation analysis and the finite element method-based simulation, we revealed that the dispersion curve of SSPP got suppressed as the filling refractive index increased, which cause the coupling resonance frequency redshifting in the reflection spectrum. The simulated results for testing various refractive indexes demonstrated that the incident angle of terahertz radiation has a great effect on the performance of sensing. Smaller incident angle will result in amore » higher sensitive sensing with a narrower detection range. In the meanwhile, the higher order mode SSPP-based sensing has a higher sensitivity with a narrower detection range. The maximum sensitivity is 2.57 THz/RIU for the second-order mode sensing at 45° internal incident angle. The proposed SSPP-based method has great potential for high sensitive terahertz sensing.« less

Assessment of nodal involvement in non-small-cell lung cancer with 18F-FDG-PET/CT: mediastinal blood pool cut-off has the highest sensitivity and tumour SUVmax/2 has the highest specificity.

PubMed

Mallorie, Amy; Goldring, James; Patel, Anant; Lim, Eric; Wagner, Thomas

2017-08-01

Lymph node involvement in non-small-cell lung cancer (NSCLC) is a major factor in determining management and prognosis. We aimed to evaluate the accuracy of fluorine-18-fluorodeoxyglucose-PET/computed tomography (CT) for the assessment of nodal involvement in patients with NSCLC. In this retrospective study, we included 61 patients with suspected or confirmed resectable NSCLC over a 2-year period from April 2013 to April 2015. 221 nodes with pathological staging from surgery or endobronchial ultrasound-guided transbronchial needle aspiration were assessed using a nodal station-based analysis with original clinical reports and three different cut-offs: mediastinal blood pool (MBP), liver background and tumour standardized uptake value maximal (SUVmax)/2. Using nodal station-based analysis for activity more than tumour SUVmax/2, the sensitivity was 45%, the specificity was 89% and the negative predictive value (NPV) was 87%. For activity more than MBP, the sensitivity was 93%, the specificity was 72% and NPV was 98%. For activity more than liver background, the sensitivity was 83%, the specificity was 84% and NPV was 96%. Using a nodal staging-based analysis for accuracy at detecting N2/3 disease, for activity more than tumour SUVmax/2, the sensitivity was 59%, the specificity was 85% and NPV was 80%. For activity more than MBP, the sensitivity was 95%, the specificity was 61% and NPV was 96%. For activity more than liver background, the sensitivity was 86%, the specificity was 81% and NPV was 92%. Receiver-operating characteristic analysis showed the optimal nodal SUVmax to be more than 6.4 with a sensitivity of 45% and a specificity of 95%, with an area under the curve of 0.85. Activity more than MBP was the most sensitive cut-off with the highest sensitivity and NPV. Activity more than primary tumour SUVmax/2 was the most specific cut-off. Nodal SUVmax more than 6.4 has a high specificity of 95%.

Propensity Score Analysis Comparing Videothoracoscopic Lobectomy With Thoracotomy: A French Nationwide Study.

PubMed

Pagès, Pierre-Benoit; Delpy, Jean-Philippe; Orsini, Bastien; Gossot, Dominique; Baste, Jean-Marc; Thomas, Pascal; Dahan, Marcel; Bernard, Alain

2016-04-01

Video-assisted thoracoscopic surgery (VATS) lobectomy has recently become the recommended approach for stage I non-small cell lung cancer. However, these guidelines are not based on any large randomized control trial. Our study used propensity scores and a sensitivity analysis to compare VATS lobectomy with open thoracotomy. From 2005 to 2012, 24,811 patients (95.1%) were operated on by open thoracotomy and 1,278 (4.9%) by VATS. The end points were 30-day postoperative death, postoperative complications, hospital stay, overall survival, and disease-free survival. Two propensity scores analyses were performed: matching and inverse probability of treatment weighting, and one sensitivity analysis to unmask potential hidden bias. A subgroup analysis was performed to compare "high-risk" with "low-risk" patients. Results are reported by odds ratios or hazard ratios and their 95% confidence intervals. Postoperative death was not significantly reduced by VATS whatever the analysis. Concerning postoperative complications, VATS significantly decreased the occurrence of atelectasis and pneumopathy with both analysis methods, but there were no differences in the occurrence of other postoperative complications. VATS did not provide a benefit for high-risk patients. The VATS approach decreased the hospital length of stay from 2.4 days (95% confidence interval, -1.7 to -3 days) to -4.68 days (95% confidence interval, -8.5 to 0.9 days). Overall survival and disease-free survival were not influenced by the surgical approach. The sensitivity analysis showed potential biases. The results must be interpreted carefully because of the differences observed according to the propensity scores method used. A multicenter randomized controlled trial is necessary to limit the biases. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Semi-micro high-performance liquid chromatographic analysis of tiropramide in human plasma using column-switching.

PubMed

Baek, Soo Kyoung; Lee, Seung Seok; Park, Eun Jeon; Sohn, Dong Hwan; Lee, Hye Suk

2003-02-05

A rapid and sensitive column-switching semi-micro high-performance liquid chromatography method was developed for the direct analysis of tiropramide in human plasma. The plasma sample (100 microl) was directly injected onto Capcell Pak MF Ph-1 precolumn where deproteinization and analyte fractionation occurred. Tiropramide was then eluted into an enrichment column (Capcell Pak UG C(18)) using acetonitrile-potassium phosphate (pH 7.0, 50 mM) (12:88, v/v) and was analyzed on a semi-micro C(18) analytical column using acetonitrile-potassium phosphate (pH 7.0, 10 mM) (50:50, v/v). The method showed excellent sensitivity (limit of quantification 5 ng/ml), and good precision (C.V.

Analysis of imazaquin in soybeans by solid-phase extraction and high-performance liquid chromatography.

PubMed

Guo, C; Hu, J-Y; Chen, X-Y; Li, J-Z

2008-02-01

An analytical method for the determination imazaquin residues in soybeans was developed. The developed liquid/liquid partition and strong anion exchange solid-phase extraction procedures provide the effective cleanup, removing the greatest number of sample matrix interferences. By optimizing mobile-phase pH water/acetonitrile conditions with phosphoric acid, using a C-18 reverse-phase chromatographic column and employing ultraviolet detection, excellent peak resolution was achieved. The combined cleanup and chromatographic method steps reported herein were sensitive and reliable for determining the imazaquin residues in soybean samples. This method is characterized by recovery >88.4%, precision <6.7% CV, and sensitivity of 0.005 ppm, in agreement with directives for method validation in residue analysis. Imazaquin residues in soybeans were further confirmed by high performance liquid chromatography-mass spectrometry (LC-MS). The proposed method was successfully applied to the analysis of imazaquin residues in soybean samples grown in an experimental field after treatments of imazaquin formulation.

Determination of Curcuminoids in Curcuma longa Linn. by UPLC/Q-TOF-MS: An Application in Turmeric Cultivation.

PubMed

Ashraf, Kamran; Mujeeb, Mohd; Ahmad, Altaf; Ahmad, Niyaz; Amir, Mohd

2015-09-01

Cucuma longa Linn. (Fam-Zingiberaceae) is a valued medicinal plant contains curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) as major bioactive constituents. Previously reported analytical methods for analysis of curcuminoids were found to suffer from low resolution, lower sensitivity and longer analytical times. In this study, a rapid, sensitive, selective high-throughput ultra high performance liquid chromatography-tandem mass spectrometry (UPLC/Q-TOF-MS) method was developed and validated for the quantification of curcuminoids with an aim to reduce analysis time and enhance efficiency. UPLC/Q-TOF-MS analysis showed large variation (1.408-5.027% w/w) of curcuminoids among different samples with respect to their occurrence of metabolite and their concentration. The results showed that Erode (south province) contains highest quantity of curcuminoids and concluded to be the superior varieties. The results obtained here could be valuable for devising strategies for cultivating this medicinal plant. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Systematic exploration of essential yeast gene function with temperature-sensitive mutants

PubMed Central

Li, Zhijian; Vizeacoumar, Franco J; Bahr, Sondra; Li, Jingjing; Warringer, Jonas; Vizeacoumar, Frederick S; Min, Renqiang; VanderSluis, Benjamin; Bellay, Jeremy; DeVit, Michael; Fleming, James A; Stephens, Andrew; Haase, Julian; Lin, Zhen-Yuan; Baryshnikova, Anastasia; Lu, Hong; Yan, Zhun; Jin, Ke; Barker, Sarah; Datti, Alessandro; Giaever, Guri; Nislow, Corey; Bulawa, Chris; Myers, Chad L; Costanzo, Michael; Gingras, Anne-Claude; Zhang, Zhaolei; Blomberg, Anders; Bloom, Kerry; Andrews, Brenda; Boone, Charles

2012-01-01

Conditional temperature-sensitive (ts) mutations are valuable reagents for studying essential genes in the yeast Saccharomyces cerevisiae. We constructed 787 ts strains, covering 497 (~45%) of the 1,101 essential yeast genes, with ~30% of the genes represented by multiple alleles. All of the alleles are integrated into their native genomic locus in the S288C common reference strain and are linked to a kanMX selectable marker, allowing further genetic manipulation by synthetic genetic array (SGA)–based, high-throughput methods. We show two such manipulations: barcoding of 440 strains, which enables chemical-genetic suppression analysis, and the construction of arrays of strains carrying different fluorescent markers of subcellular structure, which enables quantitative analysis of phenotypes using high-content screening. Quantitative analysis of a GFP-tubulin marker identified roles for cohesin and condensin genes in spindle disassembly. This mutant collection should facilitate a wide range of systematic studies aimed at understanding the functions of essential genes. PMID:21441928

MDS1, a dosage suppressor of an mck1 mutant, encodes a putative yeast homolog of glycogen synthase kinase 3.

PubMed Central

Puziss, J W; Hardy, T A; Johnson, R B; Roach, P J; Hieter, P

1994-01-01

The yeast gene MCK1 encodes a serine/threonine protein kinase that is thought to function in regulating kinetochore activity and entry into meiosis. Disruption of MCK1 confers a cold-sensitive phenotype, a temperature-sensitive phenotype, and sensitivity to the microtubule-destabilizing drug benomyl and leads to loss of chromosomes during growth on benomyl. A dosage suppression selection was used to identify genes that, when present at high copy number, could suppress the cold-sensitive phenotype of mck1::HIS3 mutant cells. Several unique classes of clones were identified, and one of these, designated MDS1, has been characterized in some detail. Nucleotide sequence data reveal that MDS1 encodes a serine/threonine protein kinase that is highly homologous to the shaggy/zw3 kinase in Drosophila melanogaster and its functional homolog, glycogen synthase kinase 3, in rats. The presence of MDS1 in high copy number rescues both the cold-sensitive and the temperature-sensitive phenotypes, but not the benomyl-sensitive phenotype, associated with the disruption of MCK1. Analysis of strains harboring an mds1 null mutation demonstrates that MDS1 is not essential during normal vegetative growth but appears to be required for meiosis. Finally, in vitro experiments indicate that the proteins encoded by both MCK1 and MDS1 possess protein kinase activity with substrate specificity similar to that of mammalian glycogen synthase kinase 3. Images PMID:8264650

Connectome sensitivity or specificity: which is more important?

PubMed

Zalesky, Andrew; Fornito, Alex; Cocchi, Luca; Gollo, Leonardo L; van den Heuvel, Martijn P; Breakspear, Michael

2016-11-15

Connectomes with high sensitivity and high specificity are unattainable with current axonal fiber reconstruction methods, particularly at the macro-scale afforded by magnetic resonance imaging. Tensor-guided deterministic tractography yields sparse connectomes that are incomplete and contain false negatives (FNs), whereas probabilistic methods steered by crossing-fiber models yield dense connectomes, often with low specificity due to false positives (FPs). Densely reconstructed probabilistic connectomes are typically thresholded to improve specificity at the cost of a reduction in sensitivity. What is the optimal tradeoff between connectome sensitivity and specificity? We show empirically and theoretically that specificity is paramount. Our evaluations of the impact of FPs and FNs on empirical connectomes indicate that specificity is at least twice as important as sensitivity when estimating key properties of brain networks, including topological measures of network clustering, network efficiency and network modularity. Our asymptotic analysis of small-world networks with idealized modular structure reveals that as the number of nodes grows, specificity becomes exactly twice as important as sensitivity to the estimation of the clustering coefficient. For the estimation of network efficiency, the relative importance of specificity grows linearly with the number of nodes. The greater importance of specificity is due to FPs occurring more prevalently between network modules rather than within them. These spurious inter-modular connections have a dramatic impact on network topology. We argue that efforts to maximize the sensitivity of connectome reconstruction should be realigned with the need to map brain networks with high specificity. Copyright © 2016 Elsevier Inc. All rights reserved.

Emerging spectra of singular correlation matrices under small power-map deformations

NASA Astrophysics Data System (ADS)

Vinayak; Schäfer, Rudi; Seligman, Thomas H.

2013-09-01

Correlation matrices are a standard tool in the analysis of the time evolution of complex systems in general and financial markets in particular. Yet most analysis assume stationarity of the underlying time series. This tends to be an assumption of varying and often dubious validity. The validity of the assumption improves as shorter time series are used. If many time series are used, this implies an analysis of highly singular correlation matrices. We attack this problem by using the so-called power map, which was introduced to reduce noise. Its nonlinearity breaks the degeneracy of the zero eigenvalues and we analyze the sensitivity of the so-emerging spectra to correlations. This sensitivity will be demonstrated for uncorrelated and correlated Wishart ensembles.

Emerging spectra of singular correlation matrices under small power-map deformations.

PubMed

Vinayak; Schäfer, Rudi; Seligman, Thomas H

2013-09-01

Correlation matrices are a standard tool in the analysis of the time evolution of complex systems in general and financial markets in particular. Yet most analysis assume stationarity of the underlying time series. This tends to be an assumption of varying and often dubious validity. The validity of the assumption improves as shorter time series are used. If many time series are used, this implies an analysis of highly singular correlation matrices. We attack this problem by using the so-called power map, which was introduced to reduce noise. Its nonlinearity breaks the degeneracy of the zero eigenvalues and we analyze the sensitivity of the so-emerging spectra to correlations. This sensitivity will be demonstrated for uncorrelated and correlated Wishart ensembles.

Barcoding T Cell Calcium Response Diversity with Methods for Automated and Accurate Analysis of Cell Signals (MAAACS)

PubMed Central

Sergé, Arnauld; Bernard, Anne-Marie; Phélipot, Marie-Claire; Bertaux, Nicolas; Fallet, Mathieu; Grenot, Pierre; Marguet, Didier; He, Hai-Tao; Hamon, Yannick

2013-01-01

We introduce a series of experimental procedures enabling sensitive calcium monitoring in T cell populations by confocal video-microscopy. Tracking and post-acquisition analysis was performed using Methods for Automated and Accurate Analysis of Cell Signals (MAAACS), a fully customized program that associates a high throughput tracking algorithm, an intuitive reconnection routine and a statistical platform to provide, at a glance, the calcium barcode of a population of individual T-cells. Combined with a sensitive calcium probe, this method allowed us to unravel the heterogeneity in shape and intensity of the calcium response in T cell populations and especially in naive T cells, which display intracellular calcium oscillations upon stimulation by antigen presenting cells. PMID:24086124

Recent advances in chemiluminescence detection coupled with capillary electrophoresis and microchip capillary electrophoresis.

PubMed

Liu, Yuxuan; Huang, Xiangyi; Ren, Jicun

2016-01-01

CE is an ideal analytical method for extremely volume-limited biological microenvironments. However, the small injection volume makes it a challenge to achieve highly sensitive detection. Chemiluminescence (CL) detection is characterized by providing low background with excellent sensitivity because of requiring no light source. The coupling of CL with CE and MCE has become a powerful analytical method. So far, this method has been widely applied to chemical analysis, bioassay, drug analysis, and environment analysis. In this review, we first introduce some developments for CE-CL and MCE-CL systems, and then put the emphasis on the applications in the last 10 years. Finally, we discuss the future prospects. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preoperative Staging With 11C-Choline PET/CT Is Adequately Accurate in Patients With Very High-Risk Prostate Cancer.

PubMed

Schiavina, Riccardo; Bianchi, Lorenzo; Mineo Bianchi, Federico; Borghesi, Marco; Pultrone, Cristian Vincenzo; Dababneh, Hussam; Castellucci, Paolo; Ceci, Francesco; Nanni, Cristina; Gaudiano, Caterina; Fiorentino, Michelangelo; Porreca, Angelo; Chessa, Francesco; Minervini, Andrea; Fanti, Stefano; Brunocilla, Eugenio

2018-05-30

To evaluate the accuracy of 11 C-choline positron emission tomography (PET)/computed tomography (CT) for nodal staging of prostate cancer (PCa) in different populations of high-risk patients. We evaluated 262 individuals with intermediate- or high-risk PCa submitted to radical prostatectomy and extended pelvic lymph node dissection. Within men with high-risk disease, we identified a subgroup of individuals harboring very high-risk (VHR, n = 28) disease: clinical stage ≥ T2c and more than 5 cores with Gleason score 8-10; primary biopsy Gleason score of 5; 3 high-risk features; or prostate-specific antigen ≥ 30 ng/mL. The diagnostic accuracy of PET/CT and contrast-enhanced CT (CECT) was assessed after stratifying patients according to risk group classification on a patient- and anatomic region-based analysis. On patient-based analysis, considering high-risk patients (n = 155), 11 C-choline PET/CT versus CECT had sensitivity and specificity of 50% and 76% versus 21% and 92%, respectively. Considering VHR men as separate subgroups (n = 28), 11 C-choline PET/CT versus CECT had sensitivity and specificity of 71% and 93% versus 25% and 79%, respectively. Accordingly, in the VHR category, the area under the curve of 11 C-choline PET/CT versus CECT was 0.86 (95% confidence interval, 0.71-1.0) versus 0.69 (95% confidence interval, 0.52-0.86), respectively. On anatomic region-based analysis, considering the VHR group, 11 C-choline PET/CT versus CECT had sensitivity and specificity of 70.6% and 95.5% versus 35.3% and 98.5%, respectively. Patients with VHR characteristics could represent the ideal candidate to undergo disease staging with PET/CT before surgery with the highest cost efficacy. Copyright © 2018 Elsevier Inc. All rights reserved.

Simple Electrolyzer Model Development for High-Temperature Electrolysis System Analysis Using Solid Oxide Electrolysis Cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

JaeHwa Koh; DuckJoo Yoon; Chang H. Oh

2010-07-01

An electrolyzer model for the analysis of a hydrogen-production system using a solid oxide electrolysis cell (SOEC) has been developed, and the effects for principal parameters have been estimated by sensitivity studies based on the developed model. The main parameters considered are current density, area specific resistance, temperature, pressure, and molar fraction and flow rates in the inlet and outlet. Finally, a simple model for a high-temperature hydrogen-production system using the solid oxide electrolysis cell integrated with very high temperature reactors is estimated.

NAVIGATION PERFORMANCE IN HIGH EARTH ORBITS USING NAVIGATOR GPS RECEIVER

NASA Technical Reports Server (NTRS)

Bamford, William; Naasz, Bo; Moreau, Michael C.

2006-01-01

NASA GSFC has developed a GPS receiver that can acquire and track GPS signals with sensitivity significantly lower than conventional GPS receivers. This opens up the possibility of using GPS based navigation for missions in high altitude orbit, such as Geostationary Operational Environmental Satellites (GOES) in a geostationary orbit, and the Magnetospheric MultiScale (MMS) Mission, in highly eccentric orbits extending to 12 Earth radii and higher. Indeed much research has been performed to study the feasibility of using GPS navigation in high Earth orbits and the performance achievable. Recently, GSFC has conducted a series of hardware in-the-loop tests to assess the performance of this new GPS receiver in various high Earth orbits of interest. Tracking GPS signals to down to approximately 22-25 dB-Hz, including signals from the GPS transmitter side-lobes, steady-state navigation performance in a geostationary orbit is on the order of 10 meters. This paper presents the results of these tests, as well as sensitivity analysis to such factors as ionosphere masks, use of GPS side-lobe signals, and GPS receiver sensitivity.

Tonic blood pressure modulates the relationship between baroreceptor cardiac reflex sensitivity and cognitive performance.

PubMed

Del Paso, Gustavo A Reyes; González, M Isabel; Hernández, José Antonio; Duschek, Stefan; Gutiérrez, Nicolás

2009-09-01

This study explored the effects of tonic blood pressure on the association between baroreceptor cardiac reflex sensitivity and cognitive performance. Sixty female participants completed a mental arithmetic task. Baroreceptor reflex sensitivity was assessed using sequence analysis. An interaction was found, indicating that the relationship between baroreceptor reflex sensitivity and cognitive performance is modulated by blood pressure levels. Reflex sensitivity was inversely associated to performance indices in the subgroup of participants with systolic blood pressure above the mean, whereas the association was positive in participants with systolic values below the mean. These results are in accordance with the findings in the field of pain perception and suggest that tonic blood pressure modulates the inhibitory effects of baroreceptor stimulation on high central nervous functions.

Evaluation of Uncertainty and Sensitivity in Environmental Modeling at a Radioactive Waste Management Site

NASA Astrophysics Data System (ADS)

Stockton, T. B.; Black, P. K.; Catlett, K. M.; Tauxe, J. D.

2002-05-01

Environmental modeling is an essential component in the evaluation of regulatory compliance of radioactive waste management sites (RWMSs) at the Nevada Test Site in southern Nevada, USA. For those sites that are currently operating, further goals are to support integrated decision analysis for the development of acceptance criteria for future wastes, as well as site maintenance, closure, and monitoring. At these RWMSs, the principal pathways for release of contamination to the environment are upward towards the ground surface rather than downwards towards the deep water table. Biotic processes, such as burrow excavation and plant uptake and turnover, dominate this upward transport. A combined multi-pathway contaminant transport and risk assessment model was constructed using the GoldSim modeling platform. This platform facilitates probabilistic analysis of environmental systems, and is especially well suited for assessments involving radionuclide decay chains. The model employs probabilistic definitions of key parameters governing contaminant transport, with the goals of quantifying cumulative uncertainty in the estimation of performance measures and providing information necessary to perform sensitivity analyses. This modeling differs from previous radiological performance assessments (PAs) in that the modeling parameters are intended to be representative of the current knowledge, and the uncertainty in that knowledge, of parameter values rather than reflective of a conservative assessment approach. While a conservative PA may be sufficient to demonstrate regulatory compliance, a parametrically honest PA can also be used for more general site decision-making. In particular, a parametrically honest probabilistic modeling approach allows both uncertainty and sensitivity analyses to be explicitly coupled to the decision framework using a single set of model realizations. For example, sensitivity analysis provides a guide for analyzing the value of collecting more information by quantifying the relative importance of each input parameter in predicting the model response. However, in these complex, high dimensional eco-system models, represented by the RWMS model, the dynamics of the systems can act in a non-linear manner. Quantitatively assessing the importance of input variables becomes more difficult as the dimensionality, the non-linearities, and the non-monotonicities of the model increase. Methods from data mining such as Multivariate Adaptive Regression Splines (MARS) and the Fourier Amplitude Sensitivity Test (FAST) provide tools that can be used in global sensitivity analysis in these high dimensional, non-linear situations. The enhanced interpretability of model output provided by the quantitative measures estimated by these global sensitivity analysis tools will be demonstrated using the RWMS model.

High-resolution spectral analysis of ammonia near 6.2 μm using a cw EC-QCL coupled with cavity ring-down spectroscopy.

PubMed

Maithani, Sanchi; Mandal, Santanu; Maity, Abhijit; Pal, Mithun; Pradhan, Manik

2018-04-30

We report on the development of a mid-infrared cavity ring-down spectrometer (CRDS) coupled with a continuous wave (cw) external cavity quantum cascade laser (EC-QCL), operating between 6.0 μm and 6.3 μm, for high-resolution spectroscopic studies of ammonia (NH3) which served as a bench-mark molecule in this spectral region. We characterized the EC-QCL based CRDS system in detail and achieved a noise-equivalent absorption (NEA) coefficient of 2.11 × 10-9 cm-1 Hz-1/2 for a 100 Hz data acquisition rate. We thereafter exploited the system for high-resolution spectroscopic analysis of interference-free 10 transition lines of the ν4 fundamental vibrational band of NH3 centred at ∼6.2 μm. We probed the strongest interference-free absorption line RQ(4,3) of ν4, centred at 1613.370 cm-1 for highly-sensitive trace detection of NH3 and subsequently achieved a minimum detection sensitivity (1σ) of 2.78 × 109 molecules per cm3 which translated into the detection limit of 740 parts-per-trillion by volume (pptv/10-12) at a pressure of 115 Torr for an integration time of ∼167 seconds. To demonstrate the efficacy of the present system in real-life applications, we finally measured the mixing ratios of NH3 present in ambient air and human exhaled breath with high sensitivity and molecular specificity.

Are quantitative sensitivity analysis methods always reliable?

NASA Astrophysics Data System (ADS)

Huang, X.

2016-12-01

Physical parameterizations developed to represent subgrid-scale physical processes include various uncertain parameters, leading to large uncertainties in today's Earth System Models (ESMs). Sensitivity Analysis (SA) is an efficient approach to quantitatively determine how the uncertainty of the evaluation metric can be apportioned to each parameter. Also, SA can identify the most influential parameters, as a result to reduce the high dimensional parametric space. In previous studies, some SA-based approaches, such as Sobol' and Fourier amplitude sensitivity testing (FAST), divide the parameters into sensitive and insensitive groups respectively. The first one is reserved but the other is eliminated for certain scientific study. However, these approaches ignore the disappearance of the interactive effects between the reserved parameters and the eliminated ones, which are also part of the total sensitive indices. Therefore, the wrong sensitive parameters might be identified by these traditional SA approaches and tools. In this study, we propose a dynamic global sensitivity analysis method (DGSAM), which iteratively removes the least important parameter until there are only two parameters left. We use the CLM-CASA, a global terrestrial model, as an example to verify our findings with different sample sizes ranging from 7000 to 280000. The result shows DGSAM has abilities to identify more influential parameters, which is confirmed by parameter calibration experiments using four popular optimization methods. For example, optimization using Top3 parameters filtered by DGSAM could achieve substantial improvement against Sobol' by 10%. Furthermore, the current computational cost for calibration has been reduced to 1/6 of the original one. In future, it is necessary to explore alternative SA methods emphasizing parameter interactions.

In silico designing of power conversion efficient organic lead dyes for solar cells using todays innovative approaches to assure renewable energy for future

NASA Astrophysics Data System (ADS)

Kar, Supratik; Roy, Juganta K.; Leszczynski, Jerzy

2017-06-01

Advances in solar cell technology require designing of new organic dye sensitizers for dye-sensitized solar cells with high power conversion efficiency to circumvent the disadvantages of silicon-based solar cells. In silico studies including quantitative structure-property relationship analysis combined with quantum chemical analysis were employed to understand the primary electron transfer mechanism and photo-physical properties of 273 arylamine organic dyes from 11 diverse chemical families explicit to iodine electrolyte. The direct quantitative structure-property relationship models enable identification of the essential electronic and structural attributes necessary for quantifying the molecular prerequisites of 11 classes of arylamine organic dyes, responsible for high power conversion efficiency of dye-sensitized solar cells. Tetrahydroquinoline, N,N'-dialkylaniline and indoline have been least explored classes under arylamine organic dyes for dye-sensitized solar cells. Therefore, the identified properties from the corresponding quantitative structure-property relationship models of the mentioned classes were employed in designing of "lead dyes". Followed by, a series of electrochemical and photo-physical parameters were computed for designed dyes to check the required variables for electron flow of dye-sensitized solar cells. The combined computational techniques yielded seven promising lead dyes each for all three chemical classes considered. Significant (130, 183, and 46%) increment in predicted %power conversion efficiency was observed comparing with the existing dye with highest experimental %power conversion efficiency value for tetrahydroquinoline, N,N'-dialkylaniline and indoline, respectively maintaining required electrochemical parameters.

Evidence in obese children: contribution of hyperlipidemia, obesity-inflammation, and insulin sensitivity.

PubMed

Chang, Chi-Jen; Jian, Deng-Yuan; Lin, Ming-Wei; Zhao, Jun-Zhi; Ho, Low-Tone; Juan, Chi-Chang

2015-01-01

Evidence shows a high incidence of insulin resistance, inflammation and dyslipidemia in adult obesity. The aim of this study was to assess the relevance of inflammatory markers, circulating lipids, and insulin sensitivity in overweight/obese children. We enrolled 45 male children (aged 6 to 13 years, lean control = 16, obese = 19, overweight = 10) in this study. The plasma total cholesterol, HDL cholesterol, triglyceride, glucose and insulin levels, the circulating levels of inflammatory factors, such as TNF-α, IL-6, and MCP-1, and the high-sensitive CRP level were determined using quantitative colorimetric sandwich ELISA kits. Compared with the lean control subjects, the obese subjects had obvious insulin resistance, abnormal lipid profiles, and low-grade inflammation. The overweight subjects only exhibited significant insulin resistance and low-grade inflammation. Both TNF-α and leptin levels were higher in the overweight/obese subjects. A concurrent correlation analysis showed that body mass index (BMI) percentile and fasting insulin were positively correlated with insulin resistance, lipid profiles, and inflammatory markers but negatively correlated with adiponectin. A factor analysis identified three domains that explained 74.08% of the total variance among the obese children (factor 1: lipid, 46.05%; factor 2: obesity-inflammation, 15.38%; factor 3: insulin sensitivity domains, 12.65%). Our findings suggest that lipid, obesity-inflammation, and insulin sensitivity domains predominantly exist among obese children. These factors might be applied to predict the outcomes of cardiovascular diseases in the future.

Sensitivity and specificity of the AdenoPlus point-of-care system in detecting adenovirus in conjunctivitis patients at an ophthalmic emergency department: a diagnostic accuracy study.

PubMed

Kam, K Y Ronald; Ong, Hon Shing; Bunce, Catey; Ogunbowale, Lola; Verma, Seema

2015-09-01

To estimate the diagnostic accuracy (sensitivity and specificity) of the AdenoPlus point-of-care adenoviral test compared to PCR in an ophthalmic accident and emergency service. These findings were compared with those of a previous study. This was a prospective diagnostic accuracy study on 121 patients presenting to an emergency eye unit with a clinical picture of acute adenoviral conjunctivitis. AdenoPlus testing was carried out on one eye of each patient and a PCR analysis was also performed on a swab taken from the same eye. AdenoPlus and PCR results were interpreted by masked personnel. Sensitivity and specificity for the AdenoPlus test were calculated using PCR results as the reference standard. 121 patients were enrolled and 109 met the inclusion criteria. 43 patients (39.4%) tested positive for adenovirus by PCR analysis. The sensitivity of the AdenoPlus swab in detecting adenovirus was 39.5% (17/43, 95% CI 26% to 54%) and specificity was 95.5% (63/66, 95% CI 87% to 98%) compared to PCR. The AdenoPlus test has a high specificity for diagnosing adenoviral conjunctivitis, but in this clinical setting, we could not reproduce the high sensitivity that has been previously published. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Quadrant photodetector sensitivity.

PubMed

Manojlović, Lazo M

2011-07-10

A quantitative theoretical analysis of the quadrant photodetector (QPD) sensitivity in position measurement is presented. The Gaussian light spot irradiance distribution on the QPD surface was assumed to meet most of the real-life applications of this sensor. As the result of the mathematical treatment of the problem, we obtained, in a closed form, the sensitivity function versus the ratio of the light spot 1/e radius and the QPD radius. The obtained result is valid for the full range of the ratios. To check the influence of the finite light spot radius on the interaxis cross talk and linearity, we also performed a mathematical analysis to quantitatively measure these types of errors. An optimal range of the ratio of light spot radius and QPD radius has been found to simultaneously achieve low interaxis cross talk and high linearity of the sensor. © 2011 Optical Society of America

[Study on the current situation and influential factors of anxiety sensitivity among middle school students in Chongqing].

PubMed

Li, Qian-Qian; Zhang, Da-Jun; Guo, Lan-Ting; Feng, Zheng-Zhi; Wu, Ming-Xia

2007-09-01

To explore the status and influencing factors on anxiety sensitivity among middle school students in Chongqing. 58 classes from 12 schools were randomly selected in four administrative districts of Chongqing city. A total number of 2700 students was included for final analysis including 48.5% from junior high school and 51.5% from senior high school students with 49.2% boys and 50.8% girls. The Chinese version of the Anxiety Sensitivity Index-Revision, Adolescent Self-Rating Life Events Check List (ASLEC) and State-Trait Anxiety Inventory (STAI) were used. (1) There was no significant difference between grade groups (P = 0.49). (2) The level of girl's anxiety sensitivity was always higher than boy's (P < 0.001). (3) Data from multiple linear regression showed that the influential factors to the degree of anxiety sensitivity were: state of anxiety, trait anxiety, life events, sex, stress from learning, etc (standard coefficients of regression were 0.258, 0.163, 0.112, 0.093, 0.124, -0.096, 0.096). The major influential factors of anxiety sensitivity would include: sex, stress from learning, life events, interpersonal relationship, state of anxiety and trait anxiety.

Role of Lipid Composition and Lipid Peroxidation in the Sensitivity of Fungal Plant Pathogens to Aluminum Chloride and Sodium Metabisulfite▿

PubMed Central

Avis, Tyler J.; Michaud, Mélanie; Tweddell, Russell J.

2007-01-01

Aluminum chloride and sodium metabisulfite have shown high efficacy at low doses in controlling postharvest pathogens on potato tubers. Direct effects of these two salts included the loss of cell membrane integrity in exposed pathogens. In this work, four fungal potato pathogens were studied in order to elucidate the role of membrane lipids and lipid peroxidation in the relative sensitivity of microorganisms exposed to these salts. Inhibition of mycelial growth in these fungi varied considerably and revealed sensitivity groups within the tested fungi. Analysis of fatty acids in these fungi demonstrated that sensitivity was related to high intrinsic fatty acid unsaturation. When exposed to the antifungal salts, sensitive fungi demonstrated a loss of fatty acid unsaturation, which was accompanied by an elevation in malondialdehyde content (a biochemical marker of lipid peroxidation). Our data suggest that aluminum chloride and sodium metabisulfite could induce lipid peroxidation in sensitive fungi, which may promote the ensuing loss of integrity in the plasma membrane. This direct effect on fungal membranes may contribute, at least in part, to the observed antimicrobial effects of these two salts. PMID:17337539

The Impact of Parametric Uncertainties on Biogeochemistry in the E3SM Land Model

NASA Astrophysics Data System (ADS)

Ricciuto, Daniel; Sargsyan, Khachik; Thornton, Peter

2018-02-01

We conduct a global sensitivity analysis (GSA) of the Energy Exascale Earth System Model (E3SM), land model (ELM) to calculate the sensitivity of five key carbon cycle outputs to 68 model parameters. This GSA is conducted by first constructing a Polynomial Chaos (PC) surrogate via new Weighted Iterative Bayesian Compressive Sensing (WIBCS) algorithm for adaptive basis growth leading to a sparse, high-dimensional PC surrogate with 3,000 model evaluations. The PC surrogate allows efficient extraction of GSA information leading to further dimensionality reduction. The GSA is performed at 96 FLUXNET sites covering multiple plant functional types (PFTs) and climate conditions. About 20 of the model parameters are identified as sensitive with the rest being relatively insensitive across all outputs and PFTs. These sensitivities are dependent on PFT, and are relatively consistent among sites within the same PFT. The five model outputs have a majority of their highly sensitive parameters in common. A common subset of sensitive parameters is also shared among PFTs, but some parameters are specific to certain types (e.g., deciduous phenology). The relative importance of these parameters shifts significantly among PFTs and with climatic variables such as mean annual temperature.

Reach-scale channel sensitivity to multiple human activities and natural events: Lower Santa Clara River, California, USA

NASA Astrophysics Data System (ADS)

Downs, Peter W.; Dusterhoff, Scott R.; Sears, William A.

2013-05-01

Understanding the cumulative impact of natural and human influences on the sensitivity of channel morphodynamics, a relative measure between the drivers for change and the magnitude of channel response, requires an approach that accommodates spatial and temporal variability in the suite of primary stressors. Multiple historical data sources were assembled to provide a reach-scale analysis of the lower Santa Clara River (LSCR) in Ventura County, California, USA. Sediment supply is naturally high due to tectonic activity, earthquake-generated landslides, wildfires, and high magnitude flow events during El Niño years. Somewhat typically for the region, the catchment has been subject to four reasonably distinct land use and resource management combinations since European-American settlement. When combined with analysis of channel morphological response (quantifiable since ca. 1930), reach-scale and temporal differences in channel sensitivity become apparent. Downstream reaches have incised on average 2.4 m and become narrower by almost 50% with changes focused in a period of highly sensitive response after about 1950 followed by forced insensitivity caused by structural flood embankments and a significant grade control structure. In contrast, the middle reaches have been responsive but are morphologically resilient, and the upstream reaches show a mildly sensitive aggradational trend. Superimposing the natural and human drivers for change reveals that large scale stressors (related to ranching and irrigation) have been replaced over time by a suite of stressors operating at multiple spatial scales. Lower reaches have been sensitive primarily to 'local' scale impacts (urban growth, flood control, and aggregate mining) whereas, upstream, catchment-scale influences still prevail (including flow regulation and climate-driven sediment supply factors). These factors illustrate the complexity inherent to cumulative impact assessment in fluvial systems, provide evidence for a distinct Anthropocene fluvial response, and underpin the enormity of the challenge faced in trying to sustainably manage and restore rivers.

Spatially Resolved Chemical Imaging for Biosignature Analysis: Terrestrial and Extraterrestrial Examples

NASA Astrophysics Data System (ADS)

Bhartia, R.; Wanger, G.; Orphan, V. J.; Fries, M.; Rowe, A. R.; Nealson, K. H.; Abbey, W. J.; DeFlores, L. P.; Beegle, L. W.

2014-12-01

Detection of in situ biosignatures on terrestrial and planetary missions is becoming increasingly more important. Missions that target the Earth's deep biosphere, Mars, moons of Jupiter (including Europa), moons of Saturn (Titan and Enceladus), and small bodies such as asteroids or comets require methods that enable detection of materials for both in-situ analysis that preserve context and as a means to select high priority sample for return to Earth. In situ instrumentation for biosignature detection spans a wide range of analytical and spectroscopic methods that capitalize on amino acid distribution, chirality, lipid composition, isotopic fractionation, or textures that persist in the environment. Many of the existing analytical instruments are bulk analysis methods and while highly sensitive, these require sample acquisition and sample processing. However, by combining with triaging spectroscopic methods, biosignatures can be targeted on a surface and preserve spatial context (including mineralogy, textures, and organic distribution). To provide spatially correlated chemical analysis at multiple spatial scales (meters to microns) we have employed a dual spectroscopic approach that capitalizes on high sensitivity deep UV native fluorescence detection and high specificity deep UV Raman analysis.. Recently selected as a payload on the Mars 2020 mission, SHERLOC incorporates these optical methods for potential biosignatures detection on Mars. We present data from both Earth analogs that operate as our only examples known biosignatures and meteorite samples that provide an example of abiotic organic formation, and demonstrate how provenance effects the spatial distribution and composition of organics.

An efficient method of reducing glass dispersion tolerance sensitivity

NASA Astrophysics Data System (ADS)

Sparrold, Scott W.; Shepard, R. Hamilton

2014-12-01

Constraining the Seidel aberrations of optical surfaces is a common technique for relaxing tolerance sensitivities in the optimization process. We offer an observation that a lens's Abbe number tolerance is directly related to the magnitude by which its longitudinal and transverse color are permitted to vary in production. Based on this observation, we propose a computationally efficient and easy-to-use merit function constraint for relaxing dispersion tolerance sensitivity. Using the relationship between an element's chromatic aberration and dispersion sensitivity, we derive a fundamental limit for lens scale and power that is capable of achieving high production yield for a given performance specification, which provides insight on the point at which lens splitting or melt fitting becomes necessary. The theory is validated by comparing its predictions to a formal tolerance analysis of a Cooke Triplet, and then applied to the design of a 1.5x visible linescan lens to illustrate optimization for reduced dispersion sensitivity. A selection of lenses in high volume production is then used to corroborate the proposed method of dispersion tolerance allocation.

Self-assembled two-dimensional gold nanoparticle film for sensitive nontargeted analysis of food additives with surface-enhanced Raman spectroscopy.

PubMed

Wu, Yiping; Yu, Wenfang; Yang, Benhong; Li, Pan

2018-05-15

The use of different food additives and their active metabolites has been found to cause serious problems to human health. Thus, considering the potential effects on human health, developing a sensitive and credible analytical method for different foods is important. Herein, the application of solvent-driven self-assembled Au nanoparticles (Au NPs) for the rapid and sensitive detection of food additives in different commercial products is reported. The assembled substrates are highly sensitive and exhibit excellent uniformity and reproducibility because of uniformly distributed and high-density hot spots. The sensitive analyses of ciprofloxacin (CF), diethylhexyl phthalate (DEHP), tartrazine and azodicarbonamide at the 0.1 ppm level using this surface-enhanced Raman spectroscopy (SERS) substrate are given, and the results show that Au NP arrays can serve as efficient SERS substrates for the detection of food additives. More importantly, SERS spectra of several commercial liquors and sweet drinks are obtained to evaluate the addition of illegal additives. This SERS active platform can be used as an effective strategy in the detection of prohibited additives in food.

Multiplexed transcriptome analysis to detect ALK, ROS1 and RET rearrangements in lung cancer

PubMed Central

Rogers, Toni-Maree; Arnau, Gisela Mir; Ryland, Georgina L.; Huang, Stephen; Lira, Maruja E.; Emmanuel, Yvette; Perez, Omar D.; Irwin, Darryl; Fellowes, Andrew P.; Wong, Stephen Q.; Fox, Stephen B.

2017-01-01

ALK, ROS1 and RET gene fusions are important predictive biomarkers for tyrosine kinase inhibitors in lung cancer. Currently, the gold standard method for gene fusion detection is Fluorescence In Situ Hybridization (FISH) and while highly sensitive and specific, it is also labour intensive, subjective in analysis, and unable to screen a large numbers of gene fusions. Recent developments in high-throughput transcriptome-based methods may provide a suitable alternative to FISH as they are compatible with multiplexing and diagnostic workflows. However, the concordance between these different methods compared with FISH has not been evaluated. In this study we compared the results from three transcriptome-based platforms (Nanostring Elements, Agena LungFusion panel and ThermoFisher NGS fusion panel) to those obtained from ALK, ROS1 and RET FISH on 51 clinical specimens. Overall agreement of results ranged from 86–96% depending on the platform used. While all platforms were highly sensitive, both the Agena panel and Thermo Fisher NGS fusion panel reported minor fusions that were not detectable by FISH. Our proof–of–principle study illustrates that transcriptome-based analyses are sensitive and robust methods for detecting actionable gene fusions in lung cancer and could provide a robust alternative to FISH testing in the diagnostic setting. PMID:28181564

Highly sensitive ;turn-on; fluorescent chemical sensor for trace analysis of Cr3 + using electro-synthesized poly(N-(9-fluorenylmethoxycarbonyl)-L-histidine)

NASA Astrophysics Data System (ADS)

Zhang, Hui; Zhang, Ge; Xu, Jingkun; Wen, Yangping; Ming, Shouli; Zhang, Jie; Ding, Wanchuan

2018-02-01

Trivalent chromium (Cr3 +) can cause severely environment pollution, declining quality of edible agro-products in plants and animals, and human diseases. Poly(N-(9-fluorenylmethoxycarbonyl)-L-histidine) (PFLH) synthesized by the direct electro-polymerization of its corresponding commercially available monomer in both boron trifluoride diethyl etherate and dichloromethane mixed system. The ;turn-on; type fluorescent sensor based on PFLH displayed high sensitivity and selectivity for Cr3 + detecting. The structure of PFLH was rationally proved by 1H NMR spectra, FT-IR spectra, quantum chemical calculations, and its optical properties were characterized. The electro-synthesized PFLH exhibited a ;turn-on; fluorescent response towards Cr3 +, which was employed as a sensing platform for the ;turn-on; fluorescent analysis of Cr3 + in a wide linear range from 5.1 nM to 25 μM with a low limit of detection as low as 1.7 nM. The possible mechanism of fluorescent ;turn-on; sensor based on PFLH for Cr3 + was proposed. The sensor displayed high sensitivity, good selectivity, satisfactory practicability, suggesting that PFLH has potential fluorescent application for ;turn-on; sensing Cr3 + in agricultural environments and edible agro-products of plants and animals.

Multi-Component Profiling of Trace Volatiles in Blood by Gas Chromatography/Mass Spectrometry with Dynamic Headspace Extraction

PubMed Central

Kakuta, Shoji; Yamashita, Toshiyuki; Nishiumi, Shin; Yoshida, Masaru; Fukusaki, Eiichiro; Bamba, Takeshi

2015-01-01

A dynamic headspace extraction method (DHS) with high-pressure injection is described. This dynamic extraction method has superior sensitivity to solid phase micro extraction, SPME and is capable of extracting the entire gas phase by purging the headspace of a vial. Optimization of the DHS parameters resulted in a highly sensitive volatile profiling system with the ability to detect various volatile components including alcohols at nanogram levels. The average LOD for a standard volatile mixture was 0.50 ng mL−1, and the average LOD for alcohols was 0.66 ng mL−1. This method was used for the analysis of volatile components from biological samples and compared with acute and chronic inflammation models. The method permitted the identification of volatiles with the same profile pattern as in vitro oxidized lipid-derived volatiles. In addition, the concentration of alcohols and aldehydes from the acute inflammation model samples were significantly higher than that for the chronic inflammation model samples. The different profiles between these samples could also be identified by this method. Finally, it was possible to analyze alcohols and low-molecular-weight volatiles that are difficult to analyze by SPME in high sensitivity and to show volatile profiling based on multi-volatile simultaneous analysis. PMID:26819905

Multi-Component Profiling of Trace Volatiles in Blood by Gas Chromatography/Mass Spectrometry with Dynamic Headspace Extraction.

PubMed

Kakuta, Shoji; Yamashita, Toshiyuki; Nishiumi, Shin; Yoshida, Masaru; Fukusaki, Eiichiro; Bamba, Takeshi

2015-01-01

A dynamic headspace extraction method (DHS) with high-pressure injection is described. This dynamic extraction method has superior sensitivity to solid phase micro extraction, SPME and is capable of extracting the entire gas phase by purging the headspace of a vial. Optimization of the DHS parameters resulted in a highly sensitive volatile profiling system with the ability to detect various volatile components including alcohols at nanogram levels. The average LOD for a standard volatile mixture was 0.50 ng mL(-1), and the average LOD for alcohols was 0.66 ng mL(-1). This method was used for the analysis of volatile components from biological samples and compared with acute and chronic inflammation models. The method permitted the identification of volatiles with the same profile pattern as in vitro oxidized lipid-derived volatiles. In addition, the concentration of alcohols and aldehydes from the acute inflammation model samples were significantly higher than that for the chronic inflammation model samples. The different profiles between these samples could also be identified by this method. Finally, it was possible to analyze alcohols and low-molecular-weight volatiles that are difficult to analyze by SPME in high sensitivity and to show volatile profiling based on multi-volatile simultaneous analysis.

High sensitivity pulse-counting mass spectrometer system for noble gas analysis

NASA Technical Reports Server (NTRS)

Hohenberg, C. M.

1980-01-01

A pulse-counting mass spectrometer is described which is comprised of a new ion source of cylindrical geometry, with exceptional optical properties (the Baur source), a dual focal plane externally adjustable collector slits, and a 17-stage Allen-type electron multiplier, all housed in a metal 21 cm radius, 90 deg magnetic sector flight tube. Mass discrimination of the instrument is less than 1 per mil per mass unit; the optical transmission is more than 90%; the source sensitivity (Faraday collection) is 4 ma/torr at 250 micron emission; and the abundance sensitivity is 30,000.

PAX1 methylation analysis by MS-HRM is useful in triage of high-grade squamous intraepithelial lesions.

PubMed

Wang, Zhen-Ming

2014-01-01

This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation- sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.

What to do with thyroid nodules showing benign cytology and BRAF(V600E) mutation? A study based on clinical and radiologic features using a highly sensitive analytic method.

PubMed

Kim, Soo-Yeon; Kim, Eun-Kyung; Kwak, Jin Young; Moon, Hee Jung; Yoon, Jung Hyun

2015-02-01

BRAF(V600E) mutation analysis has been used as a complementary diagnostic tool to ultrasonography-guided, fine-needle aspiration (US-FNA) in the diagnosis of thyroid nodule with high specificity reported up to 100%. When highly sensitive analytic methods are used, however, false-positive results of BRAF(V600E) mutation analysis have been reported. In this study, we investigated the clinical, US features, and outcome of patients with thyroid nodules with benign cytology but positive BRAF(V600E) mutation using highly sensitive analytic methods from US-FNA. This study included 22 nodules in 22 patients (3 men, 19 women; mean age, 53 years) with benign cytology but positive BRAF(V600E) mutation from US-FNA. US features were categorized according to the internal components, echogenicity, margin, calcifications, and shape. Suspicious US features included markedly hypoechogenicity, noncircumscribed margins, micro or mixed calcifications, and nonparallel shape. Nodules were considered to have either concordant or discordant US features to benign cytology. Medical records and imaging studies were reviewed for final cytopathology results and outcomes during follow-up. Among the 22 nodules, 17 nodules were reviewed. Fifteen of 17 nodules were malignant, and 2 were benign. The benign nodules were confirmed as adenomatous hyperplasia with underlying lymphocytic thyroiditis and a fibrotic nodule with dense calcification. Thirteen of the 15 malignant nodules had 2 or more suspicious US features, and all 15 nodules were considered to have discordant cytology considering suspicious US features. Five nodules had been followed with US or US-FNA without resection, and did not show change in size or US features on follow-up US examinations. BRAF(V600E) mutation analysis is a highly sensitive diagnostic tool in the diagnosis of papillary thyroid carcinomas. In the management of thyroid nodules with benign cytology but positive BRAF(V600E) mutation, thyroidectomy should be considered in nodules which have 2 or more suspicious US features and are considered discordant on image-cytology correlation. Copyright © 2015 Elsevier Inc. All rights reserved.

Image stacking approach to increase sensitivity of fluorescence detection using a low cost complementary metal-oxide-semiconductor (CMOS) webcam.

PubMed

Balsam, Joshua; Bruck, Hugh Alan; Kostov, Yordan; Rasooly, Avraham

2012-01-01

Optical technologies are important for biological analysis. Current biomedical optical analyses rely on high-cost, high-sensitivity optical detectors such as photomultipliers, avalanched photodiodes or cooled CCD cameras. In contrast, Webcams, mobile phones and other popular consumer electronics use lower-sensitivity, lower-cost optical components such as photodiodes or CMOS sensors. In order for consumer electronics devices, such as webcams, to be useful for biomedical analysis, they must have increased sensitivity. We combined two strategies to increase the sensitivity of CMOS-based fluorescence detector. We captured hundreds of low sensitivity images using a Webcam in video mode, instead of a single image typically used in cooled CCD devices.We then used a computational approach consisting of an image stacking algorithm to remove the noise by combining all of the images into a single image. While video mode is widely used for dynamic scene imaging (e.g. movies or time-lapse photography), it is not used to capture a single static image, which removes noise and increases sensitivity by more than thirty fold. The portable, battery-operated Webcam-based fluorometer system developed here consists of five modules: (1) a low cost CMOS Webcam to monitor light emission, (2) a plate to perform assays, (3) filters and multi-wavelength LED illuminator for fluorophore excitation, (4) a portable computer to acquire and analyze images, and (5) image stacking software for image enhancement. The samples consisted of various concentrations of fluorescein, ranging from 30 μM to 1000 μM, in a 36-well miniature plate. In the single frame mode, the fluorometer's limit-of-detection (LOD) for fluorescein is ∼1000 μM, which is relatively insensitive. However, when used in video mode combined with image stacking enhancement, the LOD is dramatically reduced to 30 μM, sensitivity which is similar to that of state-of-the-art ELISA plate photomultiplier-based readers. Numerous medical diagnostics assays rely on optical and fluorescence readers. Our novel combination of detection technologies, which is new to biodetection may enable the development of new low cost optical detectors based on an inexpensive Webcam (<$10). It has the potential to form the basis for high sensitivity, low cost medical diagnostics in resource-poor settings.

Image stacking approach to increase sensitivity of fluorescence detection using a low cost complementary metal-oxide-semiconductor (CMOS) webcam

PubMed Central

Balsam, Joshua; Bruck, Hugh Alan; Kostov, Yordan; Rasooly, Avraham

2013-01-01

Optical technologies are important for biological analysis. Current biomedical optical analyses rely on high-cost, high-sensitivity optical detectors such as photomultipliers, avalanched photodiodes or cooled CCD cameras. In contrast, Webcams, mobile phones and other popular consumer electronics use lower-sensitivity, lower-cost optical components such as photodiodes or CMOS sensors. In order for consumer electronics devices, such as webcams, to be useful for biomedical analysis, they must have increased sensitivity. We combined two strategies to increase the sensitivity of CMOS-based fluorescence detector. We captured hundreds of low sensitivity images using a Webcam in video mode, instead of a single image typically used in cooled CCD devices.We then used a computational approach consisting of an image stacking algorithm to remove the noise by combining all of the images into a single image. While video mode is widely used for dynamic scene imaging (e.g. movies or time-lapse photography), it is not used to capture a single static image, which removes noise and increases sensitivity by more than thirty fold. The portable, battery-operated Webcam-based fluorometer system developed here consists of five modules: (1) a low cost CMOS Webcam to monitor light emission, (2) a plate to perform assays, (3) filters and multi-wavelength LED illuminator for fluorophore excitation, (4) a portable computer to acquire and analyze images, and (5) image stacking software for image enhancement. The samples consisted of various concentrations of fluorescein, ranging from 30 μM to 1000 μM, in a 36-well miniature plate. In the single frame mode, the fluorometer's limit-of-detection (LOD) for fluorescein is ∼1000 μM, which is relatively insensitive. However, when used in video mode combined with image stacking enhancement, the LOD is dramatically reduced to 30 μM, sensitivity which is similar to that of state-of-the-art ELISA plate photomultiplier-based readers. Numerous medical diagnostics assays rely on optical and fluorescence readers. Our novel combination of detection technologies, which is new to biodetection may enable the development of new low cost optical detectors based on an inexpensive Webcam (<$10). It has the potential to form the basis for high sensitivity, low cost medical diagnostics in resource-poor settings. PMID:23990697

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hornemann, Andrea, E-mail: andrea.hornemann@ptb.de; Hoehl, Arne, E-mail: arne.hoehl@ptb.de; Ulm, Gerhard, E-mail: gerhard.ulm@ptb.de

Bio-diagnostic assays of high complexity rely on nanoscaled assay recognition elements that can provide unique selectivity and design-enhanced sensitivity features. High throughput performance requires the simultaneous detection of various analytes combined with appropriate bioassay components. Nanoparticle induced sensitivity enhancement, and subsequent multiplexed capability Surface-Enhanced InfraRed Absorption (SEIRA) assay formats are fitting well these purposes. SEIRA constitutes an ideal platform to isolate the vibrational signatures of targeted bioassay and active molecules. The potential of several targeted biolabels, here fluorophore-labeled antibody conjugates, chemisorbed onto low-cost biocompatible gold nano-aggregates substrates have been explored for their use in assay platforms. Dried films were analyzedmore » by synchrotron radiation based FTIR/SEIRA spectro-microscopy and the resulting complex hyperspectral datasets were submitted to automated statistical analysis, namely Principal Components Analysis (PCA). The relationships between molecular fingerprints were put in evidence to highlight their spectral discrimination capabilities. We demonstrate that robust spectral encoding via SEIRA fingerprints opens up new opportunities for fast, reliable and multiplexed high-end screening not only in biodiagnostics but also in vitro biochemical imaging.« less

Potential of far-ultraviolet absorption spectroscopy as a highly sensitive qualitative and quantitative analysis method for polymer films, part I: classification of commercial food wrap films.

PubMed

Sato, Harumi; Higashi, Noboru; Ikehata, Akifumi; Koide, Noriko; Ozaki, Yukihiro

2007-07-01

The aim of the present study is to propose a totally new technique for the utilization of far-ultraviolet (UV) spectroscopy in polymer thin film analysis. Far-UV spectra in the 120-300 nm region have been measured in situ for six kinds of commercial polymer wrap films by use of a novel type of far-UV spectrometer that does not need vacuum evaporation. These films can be straightforwardly classified into three groups, polyethylene (PE) films, polyvinyl chloride (PVC) films, and polyvinylidene chloride (PVDC) films, by using the raw spectra. The differences in the wavelength of the absorption band due to the sigma-sigma* transition of the C-C bond have been used for the classification of the six kinds of films. Using this method, it was easy to distinguish the three kinds of PE films and to separate the two kinds of PVDC films. Compared with other spectroscopic methods, the advantages of this technique include nondestructive analysis, easy spectral measurement, high sensitivity, and simple spectral analysis. The present study has demonstrated that far-UV spectroscopy is a very promising technique for polymer film analysis.

On understanding the relationship between structure in the potential surface and observables in classical dynamics: A functional sensitivity analysis approach

NASA Astrophysics Data System (ADS)

Judson, Richard S.; Rabitz, Herschel

1987-04-01

The relationship between structure in the potential surface and classical mechanical observables is examined by means of functional sensitivity analysis. Functional sensitivities provide maps of the potential surface, highlighting those regions that play the greatest role in determining the behavior of observables. A set of differential equations for the sensitivities of the trajectory components are derived. These are then solved using a Green's function method. It is found that the sensitivities become singular at the trajectory turning points with the singularities going as η-3/2, with η being the distance from the nearest turning point. The sensitivities are zero outside of the energetically and dynamically allowed region of phase space. A second set of equations is derived from which the sensitivities of observables can be directly calculated. An adjoint Green's function technique is employed, providing an efficient method for numerically calculating these quantities. Sensitivity maps are presented for a simple collinear atom-diatom inelastic scattering problem and for two Henon-Heiles type Hamiltonians modeling intramolecular processes. It is found that the positions of the trajectory caustics in the bound state problem determine regions of the highest potential surface sensitivities. In the scattering problem (which is impulsive, so that ``sticky'' collisions did not occur), the positions of the turning points of the individual trajectory components determine the regions of high sensitivity. In both cases, these lines of singularities are superimposed on a rich background structure. Most interesting is the appearance of classical interference effects. The interference features in the sensitivity maps occur most noticeably where two or more lines of turning points cross. The important practical motivation for calculating the sensitivities derives from the fact that the potential is a function, implying that any direct attempt to understand how local potential regions affect the behavior of the observables by repeatedly and systematically altering the potential will be prohibitively expensive. The functional sensitivity method enables one to perform this analysis at a fraction of the computational labor required for the direct method.

Non-volatile analysis in fruits by laser resonant ionization spectrometry: application to resveratrol (3,5,4'-trihydroxystilbene) in grapes

NASA Astrophysics Data System (ADS)

Montero, C.; Orea, J. M.; Soledad Muñoz, M.; Lobo, R. F. M.; González Ureña, A.

A laser desorption (LD) coupled with resonance-enhanced multiphoton ionisation (REMPI) and time-of-flight mass spectrometry (TOFMS) technique for non-volatile trace analysis compounds is presented. Essential features are: (a) an enhanced desorption yield due to the mixing of metal powder with the analyte in the sample preparation, (b) a high resolution, great sensitivity and low detection limit due to laser resonant ionisation and mass spectrometry detection. Application to resveratrol content in grapes demonstrated the capability of the analytical method with a sensitivity of 0.2 pg per single laser shot and a detection limit of 5 ppb.

Comparison between two methodologies for urban drainage decision aid.

PubMed

Moura, P M; Baptista, M B; Barraud, S

2006-01-01

The objective of the present work is to compare two methodologies based on multicriteria analysis for the evaluation of stormwater systems. The first methodology was developed in Brazil and is based on performance-cost analysis, the second one is ELECTRE III. Both methodologies were applied to a case study. Sensitivity and robustness analyses were then carried out. These analyses demonstrate that both methodologies have equivalent results, and present low sensitivity and high robustness. These results prove that the Brazilian methodology is consistent and can be used safely in order to select a good solution or a small set of good solutions that could be compared with more detailed methods afterwards.

Modified GMDH-NN algorithm and its application for global sensitivity analysis

NASA Astrophysics Data System (ADS)

Song, Shufang; Wang, Lu

2017-11-01

Global sensitivity analysis (GSA) is a very useful tool to evaluate the influence of input variables in the whole distribution range. Sobol' method is the most commonly used among variance-based methods, which are efficient and popular GSA techniques. High dimensional model representation (HDMR) is a popular way to compute Sobol' indices, however, its drawbacks cannot be ignored. We show that modified GMDH-NN algorithm can calculate coefficients of metamodel efficiently, so this paper aims at combining it with HDMR and proposes GMDH-HDMR method. The new method shows higher precision and faster convergent rate. Several numerical and engineering examples are used to confirm its advantages.

Comparison of Abbott RealTime High-Risk HPV and Hybrid Capture 2 Assays for Detection of HPV Infection.

PubMed

Ko, Kiwoong; Yu, Shinae; Lee, Eun Hee; Park, Hyosoon; Woo, Hee-Yeon; Kwon, Min-Jung

2016-09-01

Various assays for detecting high-risk human papillomavirus (HR HPV) have been introduced recently, including the Abbott RealTime High-Risk HPV assay. We sought to compare the performance of Abbott PCR to Hybrid Capture 2 for the detection of HR HPV. A total of 941 cervical swab specimens were obtained. We submitted all specimens for HR HPV detection with HC2 and Abbott PCR, and then additionally analyzed discordant and concordant positive results using restriction fragment mass polymorphism (RFMP) genotyping analysis. HC2 detected one of 13 HR HPV types in 12.3% (116/941) of cases, while Abbott PCR detected one of 14 detectable HR HPV types in 12.9% (121/941) of cases. The overall agreement rate was 97.3% with a kappa coefficient of 0.879. Discordant results between these two assays were observed in 25 cases. HC2 showed a sensitivity of 90.0% and specificity of 95.9%, while Abbott PCR showed a sensitivity of 98.0% and specificity of 96.8% when using RFMP results as the gold standard. For HPV 16/18 detection, Abbott PCR showed 95.8%/88.9% sensitivity and 99.2%/99.8% specificity, respectively. The overall coinfection rate between HPV 16, 18 and non-16/18 was 9.9% (12/121) in Abbott PCR analysis. Considering its high agreement rate with HC2, higher sensitivity/specificity compared to HC2, and ability to differentiate HPV 16/18 from other HPV types, Abbott PCR could be a reliable laboratory testing method for the screening of HPV infections. © 2016 by the Association of Clinical Scientists, Inc.

DHA-fluorescent probe is sensitive to membrane order and reveals molecular adaptation of DHA in ordered lipid microdomains☆

PubMed Central

Teague, Heather; Ross, Ron; Harris, Mitchel; Mitchell, Drake C.; Shaikh, Saame Raza

2012-01-01

Docosahexaenoic acid (DHA) disrupts the size and order of plasma membrane lipid microdomains in vitro and in vivo. However, it is unknown how the highly disordered structure of DHA mechanistically adapts to increase the order of tightly packed lipid microdomains. Therefore, we studied a novel DHA-Bodipy fluorescent probe to address this issue. We first determined if the DHA-Bodipy probe localized to the plasma membrane of primary B and immortal EL4 cells. Image analysis revealed that DHA-Bodipy localized into the plasma membrane of primary B cells more efficiently than EL4 cells. We then determined if the probe detected changes in plasma membrane order. Quantitative analysis of time-lapse movies established that DHA-Bodipy was sensitive to membrane molecular order. This allowed us to investigate how DHA-Bodipy physically adapted to ordered lipid microdomains. To accomplish this, we employed steady-state and time-resolved fluorescence anisotropy measurements in lipid vesicles of varying composition. Similar to cell culture studies, the probe was highly sensitive to membrane order in lipid vesicles. Moreover, these experiments revealed, relative to controls, that upon incorporation into highly ordered microdomains, DHA-Bodipy underwent an increase in its fluorescence lifetime and molecular order. In addition, the probe displayed a significant reduction in its rotational diffusion compared to controls. Altogether, DHA-Bodipy was highly sensitive to membrane order and revealed for the first time that DHA, despite its flexibility, could become ordered with less rotational motion inside ordered lipid microdomains. Mechanistically, this explains how DHA acyl chains can increase order upon formation of lipid microdomains in vivo. PMID:22841541

Field-effect sensors - from pH sensing to biosensing: sensitivity enhancement using streptavidin-biotin as a model system.

PubMed

Lowe, Benjamin M; Sun, Kai; Zeimpekis, Ioannis; Skylaris, Chris-Kriton; Green, Nicolas G

2017-11-06

Field-Effect Transistor sensors (FET-sensors) have been receiving increasing attention for biomolecular sensing over the last two decades due to their potential for ultra-high sensitivity sensing, label-free operation, cost reduction and miniaturisation. Whilst the commercial application of FET-sensors in pH sensing has been realised, their commercial application in biomolecular sensing (termed BioFETs) is hindered by poor understanding of how to optimise device design for highly reproducible operation and high sensitivity. In part, these problems stem from the highly interdisciplinary nature of the problems encountered in this field, in which knowledge of biomolecular-binding kinetics, surface chemistry, electrical double layer physics and electrical engineering is required. In this work, a quantitative analysis and critical review has been performed comparing literature FET-sensor data for pH-sensing with data for sensing of biomolecular streptavidin binding to surface-bound biotin systems. The aim is to provide the first systematic, quantitative comparison of BioFET results for a single biomolecular analyte, specifically streptavidin, which is the most commonly used model protein in biosensing experiments, and often used as an initial proof-of-concept for new biosensor designs. This novel quantitative and comparative analysis of the surface potential behaviour of a range of devices demonstrated a strong contrast between the trends observed in pH-sensing and those in biomolecule-sensing. Potential explanations are discussed in detail and surface-chemistry optimisation is shown to be a vital component in sensitivity-enhancement. Factors which can influence the response, yet which have not always been fully appreciated, are explored and practical suggestions are provided on how to improve experimental design.

Structure-matched Phthalocyanine Ion Pair as a Red-emitting Fluorescent Optical Probe for the Analysis of Sodium Dodecylbenzenesulfonate with High Specificity and Sensitivity.

PubMed

Yu, Fei; Guo, Menglin; Deng, Yabin; Lu, Yin; Chen, Lin; Huang, Ping; Li, Donghui

2016-01-01

We have found that a positively charged cationic copper phthalocyanine, Alcian blue (Alcian blue 8GX), can efficiently quench the fluorescence of an oppositely charged red fluorescent phthalocyanine compound with a matched molecular structure, tetrasulfonated aluminum phthalocyanine (AlS4Pc), because of the formation of an ion pair complex (AlS4Pc-Alcian blue 8GX) that exhibits almost no fluorescence. An investigation was carried out on the fluorescence recovery of AlS4Pc-Alcian blue 8GX caused by a series of anionic surfactants containing a sulfonic group (sodium dodecylbenzenesulfonate (SDBS), sodium lauryl sulfate (SLS), and sodium dodecyl sulfate (SDS)). The results showed that SDBS exhibited a significant response, and the highest sensitivity among the surfactants. Due to its high efficiency of fluorescence quenching and the high level of fluorescence recovery, direct observes can even be performed by the naked eye. The results revealed that the Alcian blue 8GX-AlS4Pc ion-pair complex fluorescent probe only responded to SDBS in the low-concentration range. Based on the new founding, this study proposed a novel principle and method of fluorescence enhancement to specifically measure the concentration of SDBS, thereby achieving a highly sensitive and highly specific determination of SDBS. Under the optimal conditions, the fluorescence intensity (I(f)) of the system and the concentration of SDBS in the range of 1 × 10(-7) - 1 × 10(-5) mol/dm(3) exhibited a good linear relationship. This method is highly sensitive, and the operation is simple and rapid. It had been applied for the quantitative analysis of SDBS in environmental water, while achieving satisfactory results compared with those of the standard method. This study developed a new application of the fluorescent phthalocyanine compounds used as molecular probes in analytical sciences.

Detection of Organophosphorus Pesticides with Colorimetry and Computer Image Analysis.

PubMed

Li, Yanjie; Hou, Changjun; Lei, Jincan; Deng, Bo; Huang, Jing; Yang, Mei

2016-01-01

Organophosphorus pesticides (OPs) represent a very important class of pesticides that are widely used in agriculture because of their relatively high-performance and moderate environmental persistence, hence the sensitive and specific detection of OPs is highly significant. Based on the inhibitory effect of acetylcholinesterase (AChE) induced by inhibitors, including OPs and carbamates, a colorimetric analysis was used for detection of OPs with computer image analysis of color density in CMYK (cyan, magenta, yellow and black) color space and non-linear modeling. The results showed that there was a gradually weakened trend of yellow intensity with the increase of the concentration of dichlorvos. The quantitative analysis of dichlorvos was achieved by Artificial Neural Network (ANN) modeling, and the results showed that the established model had a good predictive ability between training sets and predictive sets. Real cabbage samples containing dichlorvos were detected by colorimetry and gas chromatography (GC), respectively. The results showed that there was no significant difference between colorimetry and GC (P > 0.05). The experiments of accuracy, precision and repeatability revealed good performance for detection of OPs. AChE can also be inhibited by carbamates, and therefore this method has potential applications in real samples for OPs and carbamates because of high selectivity and sensitivity.

Sensitive determination of thiols in wine samples by a stable isotope-coded derivatization reagent d0/d4-acridone-10-ethyl-N-maleimide coupled with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis.

PubMed

Lv, Zhengxian; You, Jinmao; Lu, Shuaimin; Sun, Weidi; Ji, Zhongyin; Sun, Zhiwei; Song, Cuihua; Chen, Guang; Li, Guoliang; Hu, Na; Zhou, Wu; Suo, Yourui

2017-03-31

As the key aroma compounds, varietal thiols are the crucial odorants responsible for the flavor of wines. Quantitative analysis of thiols can provide crucial information for the aroma profiles of different wine styles. In this study, a rapid and sensitive method for the simultaneous determination of six thiols in wine using d 0 /d 4 -acridone-10-ethyl-N-maleimide (d 0 /d 4 -AENM) as stable isotope-coded derivatization reagent (SICD) by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) has been developed. Quantification of thiols was performed by using d 4 -AENM labeled thiols as the internal standards (IS), followed by stable isotope dilution HPLC-ESI-MS/MS analysis. The AENM derivatization combined with multiple reactions monitoring (MRM) not only allowed trace analysis of thiols due to the extremely high sensitivity, but also efficiently corrected the matrix effects during HPLC-MS/MS and the fluctuation in MS/MS signal intensity due to instrument. The obtained internal standard calibration curves for six thiols were linear over the range of 25-10,000pmol/L (R 2 ≥0.9961). Detection limits (LODs) for most of analytes were below 6.3pmol/L. The proposed method was successfully applied for the simultaneous determination of six kinds of thiols in wine samples with precisions ≤3.5% and recoveries ≥78.1%. In conclusion, the developed method is expected to be a promising tool for detection of trace thiols in wine and also in other complex matrix. Copyright © 2017 Elsevier B.V. All rights reserved.

Developing Vulnerability Analysis Method for Climate Change Adaptation on Agropolitan Region in Malang District

NASA Astrophysics Data System (ADS)

Sugiarto, Y.; Perdinan; Atmaja, T.; Wibowo, A.

2017-03-01

Agriculture plays a strategic role in strengthening sustainable development. Based on agropolitan concept, the village becomes the center of economic activities by combining agriculture, agro-industry, agribusiness and tourism that able to create high value-added economy. The impact of climate change on agriculture and water resources may increase the pressure on agropolitan development. The assessment method is required to measure the vulnerability of area-based communities in the agropolitan to climate change impact. An analysis of agropolitan vulnerability was conducted in Malang district based on four aspects and considering the availability and distribution of water as the problem. The indicators used to measure was vulnerability component which consisted of sensitivity and adaptive capacity and exposure component. The studies earned 21 indicators derived from the 115 village-based data. The results of vulnerability assessments showed that most of the villages were categorised at a moderate level. Around 20% of 388 villages were categorized at high to very high level of vulnerability due to low level of agricultural economic. In agropolitan region within the sub-district of Poncokusumo, the vulnerability of the villages varies between very low to very high. The most villages were vulnerable due to lower adaptive capacity, eventhough the level of sensitivity and exposure of all villages were relatively similar. The existence of water resources was the biggest contributor to the high exposure of the villages in Malang district, while the reception of credit facilities and source of family income were among the indicators that lead to high sensitivity component.

Interactional Effects of Instructional Quality and Teacher Judgement Accuracy on Achievement.

ERIC Educational Resources Information Center

Helmke, Andreas; Schrader, Friedrich-Wilhelm

1987-01-01

Analysis of predictions of 32 teachers regarding 690 fifth-graders' scores on a mathematics achievement test found that the combination of high judgement accuracy with varied instructional techniques was particularly favorable to students in contrast to a combination of high diagnostic sensitivity with a low frequency of cues or individual…

Reliability analysis of instrument design of noninvasive bone marrow disease detector

NASA Astrophysics Data System (ADS)

Su, Yu; Li, Ting; Sun, Yunlong

2016-02-01

Bone marrow is an important hematopoietic organ, and bone marrow lesions (BMLs) may cause a variety of complications with high death rate and short survival time. Early detection and follow up care are particularly important. But the current diagnosis methods rely on bone marrow biopsy/puncture, with significant limitations such as invasion, complex operation, high risk, and discontinuous. It is highly in need of a non-invasive, safe, easily operated, and continuous monitoring technology. So we proposed to design a device aimed for detecting bone marrow lesions, which was based on near infrared spectrum technology. Then we fully tested its reliabilities, including the sensitivity, specificity, signal-to-noise ratio (SNR), stability, and etc. Here, we reported this sequence of reliability test experiments, the experimental results, and the following data analysis. This instrument was shown to be very sensitive, with distinguishable concentration less than 0.002 and with good linearity, stability and high SNR. Finally, these reliability-test data supported the promising clinical diagnosis and surgery guidance of our novel instrument in detection of BMLs.

Highly sensitive protein detection by combination of atomic force microscopy fishing with charge generation and mass spectrometry analysis.

PubMed

Ivanov, Yuri D; Pleshakova, Tatyana; Malsagova, Krystina; Kozlov, Andrey; Kaysheva, Anna; Kopylov, Arthur; Izotov, Alexander; Andreeva, Elena; Kanashenko, Sergey; Usanov, Sergey; Archakov, Alexander

2014-10-01

An approach combining atomic force microscopy (AFM) fishing and mass spectrometry (MS) analysis to detect proteins at ultra-low concentrations is proposed. Fishing out protein molecules onto a highly oriented pyrolytic graphite surface coated with polytetrafluoroethylene film was carried out with and without application of an external electric field. After that they were visualized by AFM and identified by MS. It was found that injection of solution leads to charge generation in the solution, and an electric potential within the measuring cell is induced. It was demonstrated that without an external electric field in the rapid injection input of diluted protein solution the fishing is efficient, as opposed to slow fluid input. The high sensitivity of this method was demonstrated by detection of human serum albumin and human cytochrome b5 in 10(-17) -10(-18) m water solutions. It was shown that an external negative voltage applied to highly oriented pyrolytic graphite hinders the protein fishing. The efficiency of fishing with an external positive voltage was similar to that obtained without applying any voltage. © 2014 FEBS.

Clustering effects on postprandial insulin secretion and sensitivity in response to meals with different fatty acid compositions.

PubMed

Bermudez, Beatriz; Ortega-Gomez, Almudena; Varela, Lourdes M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G; Lopez, Sergio

2014-07-25

Dietary fatty acids play a role in glucose homeostasis. The aim of this study was to assess the individual relationship between dietary saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids with postprandial β-cell function and insulin sensitivity in subjects with normal and high fasting triglycerides. We assessed postprandial β-cell function (by the insulinogenic index and the ratio of the insulin to glucose areas under the time-concentration curve) and insulin sensitivity (by the oral glucose and the minimal model insulin sensitivity indices) over four nonconsecutive, randomly assigned, high-fat meals containing a panel of SFA (palmitic and stearic acids), MUFA (palmitoleic and oleic acids) and PUFA (linoleic and α-linolenic acids) in 14 subjects with normal and in 14 subjects with high fasting triglycerides. The proportions of each fatty acid in the meals and the values for surrogate measures of postprandial β-cell function and insulin sensitivity were subjected to a Pearson correlation and hierarchical cluster analysis, which revealed two classes of dietary fatty acids for regulating postprandial glucose homeostasis. We successfully discriminated the adverse effects of SFA palmitic acid from the beneficial effects of MUFA oleic acid on postprandial β-cell function (r ≥ 0.84 for SFA palmitic acid and r ≥ -0.71 for MUFA oleic acid; P < 0.05) and insulin sensitivity (r ≥ -0.92 for SFA palmitic acid and r ≥ 0.89 for MUFA oleic acid; P < 0.001) both in subjects with normal and high fasting triglycerides. In conclusion, dietary MUFA oleic acid, in contrast to SFA palmitic acid, favours the tuning towards better postprandial glycaemic control in subjects with normal and high fasting triglycerides.

Stereometric parameters change vs. Topographic Change Analysis (TCA) agreement in Heidelberg Retina Tomography III (HRT-3) early detection of clinical significant glaucoma progression.

PubMed

Dascalu, A M; Cherecheanu, A P; Stana, D; Voinea, L; Ciuluvica, R; Savlovschi, C; Serban, D

2014-01-01

to investigate the sensitivity and specificity of the stereometric parameters change analysis vs. Topographic Change Analysis in early detection of glaucoma progression. 81 patients with POAG were monitored for 4 years (GAT monthly, SAP at every 6 months, optic disc photographs and HRT3 yearly). The exclusion criteria were other optic disc or retinal pathology; topographic standard deviation (TSD>30; inter-test variation of reference height>25 μm. The criterion for structural progression was the following: at least 20 adjacent super-pixels with a clinically significant decrease in height (>5%). 16 patients of the total 81 presented structural progression on TCA. The most useful stereometric parameters for the early detection of glaucoma progression were the following: Rim Area change (sensitivity 100%, specificity 74.2% for a "cut-off " value of -0.05), C/D Area change (sensitivity 85.7%, specificity 71.5% for a "cut off " value of 0.02), C/D linear change (sensitivity 85.7%, specificity 71.5% for a "cut-off " value of 0.02), Rim Volume change (sensitivity 71.4%, specificity 88.8% for a "cut-off " value of -0.04). RNFL Thickness change (<0) was highly sensitive (82%), but less specific for glaucoma progression (45,2%). Changes of the other stereometric parameters have a limited diagnostic value for the early detection of glaucoma progression. TCA is a valuable tool for the assessment of the structural progression in glaucoma patients and its inter-test variability is low. On long-term, the quantitative analysis according to stereometric parameters change is also very important. The most relevant parameters to detect progression are RA, C/D Area, Linear C/D and RV.

Capillary moving-boundary isotachophoresis with electrospray ionization mass-spectrometric detection and hydrogen ion used as essential terminator: Methodology for sensitive analysis of hydroxyderivatives of s-triazine herbicides in waters.

PubMed

Malá, Zdena; Gebauer, Petr

2017-10-06

Capillary isotachophoresis (ITP) is an electrophoretic technique offering high sensitivity due to permanent stacking of the migrating analytes. Its combination with electrospray-ionization mass-spectrometric (ESI-MS) detection is limited by the narrow spectrum of ESI-compatible components but can be compensated by experienced system architecture. This work describes a methodology for sensitive analysis of hydroxyderivatives of s-triazine herbicides, based on implementation of the concepts of moving-boundary isotachophoresis and of H + as essential terminating component into cationic ITP with ESI-MS detection. Theoretical description of such kind of system is given and equations for zone-related boundary mobilities are derived, resulting in a much more general definition of the effective mobility of the terminating H + zone than used so far. Explicit equations allowing direct calculation for selected simple systems are derived. The presented theory allows prediction of stacking properties of particular systems and easy selection of suitable electrolyte setups. A simple ESI-compatible system composed of acetic acid and ammonium with H + and ammonium as a mixed terminator was selected for the analysis of 2-hydroxyatrazine and 2-hydroxyterbutylazine, degradation products of s-triazine herbicides. The proposed method was tested with direct injection without any sample pretreatment and provided excellent linearity and high sensitivity with limits of detection below 100ng/L (0.5nM). Example analyses of unspiked and spiked drinking and river water are shown. Copyright © 2017 Elsevier B.V. All rights reserved.

A sensitivity analysis of process design parameters, commodity prices and robustness on the economics of odour abatement technologies.

PubMed

Estrada, José M; Kraakman, N J R Bart; Lebrero, Raquel; Muñoz, Raúl

2012-01-01

The sensitivity of the economics of the five most commonly applied odour abatement technologies (biofiltration, biotrickling filtration, activated carbon adsorption, chemical scrubbing and a hybrid technology consisting of a biotrickling filter coupled with carbon adsorption) towards design parameters and commodity prices was evaluated. Besides, the influence of the geographical location on the Net Present Value calculated for a 20 years lifespan (NPV20) of each technology and its robustness towards typical process fluctuations and operational upsets were also assessed. This comparative analysis showed that biological techniques present lower operating costs (up to 6 times) and lower sensitivity than their physical/chemical counterparts, with the packing material being the key parameter affecting their operating costs (40-50% of the total operating costs). The use of recycled or partially treated water (e.g. secondary effluent in wastewater treatment plants) offers an opportunity to significantly reduce costs in biological techniques. Physical/chemical technologies present a high sensitivity towards H2S concentration, which is an important drawback due to the fluctuating nature of malodorous emissions. The geographical analysis evidenced high NPV20 variations around the world for all the technologies evaluated, but despite the differences in wage and price levels, biofiltration and biotrickling filtration are always the most cost-efficient alternatives (NPV20). When, in an economical evaluation, the robustness is as relevant as the overall costs (NPV20), the hybrid technology would move up next to BTF as the most preferred technologies. Copyright © 2012 Elsevier Inc. All rights reserved.

Sensitivity and Specificity of Eustachian Tube Function Tests in Adults

PubMed Central

Doyle, William J.; Swarts, J. Douglas; Banks, Julianne; Casselbrant, Margaretha L; Mandel, Ellen M; Alper, Cuneyt M.

2013-01-01

Objective Determine if Eustachian Tube (ET) function (ETF) tests can identify ears with physician-diagnosed ET dysfunction (ETD) in a mixed population at high sensitivity and specificity and define the inter-relatedness of ETF test parameters. Methods ETF was evaluated using the Forced-Response, Inflation-Deflation, Valsalva and Sniffing tests in 15 control ears of adult subjects after unilateral myringotomy (Group I) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (Group II). Data were analyzed using logistic regression including each parameter independently and then a step-down Discriminant Analysis including all ETF test parameters to predict group assignment. Factor Analysis operating over all parameters was used to explore relatedness. Results The Discriminant Analysis identified 4 ETF test parameters (Valsalva, ET opening pressure, dilatory efficiency and % positive pressure equilibrated) that together correctly assigned ears to Group II at a sensitivity of 95% and a specificity of 83%. Individual parameters representing the efficiency of ET opening during swallowing showed moderately accurate assignments of ears to their respective groups. Three factors captured approximately 98% of the variance among parameters, the first had negative loadings of the ETF structural parameters, the second had positive loadings of the muscle-assisted ET opening parameters and the third had negative loadings of the muscle-assisted ET opening parameters and positive loadings of the structural parameters. Discussion These results show that ETF tests can correctly assign individual ears to physician-diagnosed ETD with high sensitivity and specificity and that ETF test parameters can be grouped into structural-functional categories. PMID:23868429

Electrochemical Quartz Crystal Nanobalance (EQCN) Based Biosensor for Sensitive Detection of Antibiotic Residues in Milk.

PubMed

Bhand, Sunil; Mishra, Geetesh K

2017-01-01

An electrochemical quartz crystal nanobalance (EQCN), which provides real-time analysis of dynamic surface events, is a valuable tool for analyzing biomolecular interactions. EQCN biosensors are based on mass-sensitive measurements that can detect small mass changes caused by chemical binding to small piezoelectric crystals. Among the various biosensors, the piezoelectric biosensor is considered one of the most sensitive analytical techniques, capable of detecting antigens at picogram levels. EQCN is an effective monitoring technique for regulation of the antibiotics below the maximum residual limit (MRL). The analysis of antibiotic residues requires high sensitivity, rapidity, reliability and cost effectiveness. For analytical purposes the general approach is to take advantage of the piezoelectric effect by immobilizing a biosensing layer on top of the piezoelectric crystal. The sensing layer usually comprises a biological material such as an antibody, enzymes, or aptamers having high specificity and selectivity for the target molecule to be detected. The biosensing layer is usually functionalized using surface chemistry modifications. When these bio-functionalized quartz crystals are exposed to a particular substance of interest (e.g., a substrate, inhibitor, antigen or protein), binding interaction occurs. This causes a frequency or mass change that can be used to determine the amount of material interacted or bound. EQCN biosensors can easily be automated by using a flow injection analysis (FIA) setup coupled through automated pumps and injection valves. Such FIA-EQCN biosensors have great potential for the detection of different analytes such as antibiotic residues in various matrices such as water, waste water, and milk.

Temporal diagnostic analysis of the SWAT model to detect dominant periods of poor model performance

NASA Astrophysics Data System (ADS)

Guse, Björn; Reusser, Dominik E.; Fohrer, Nicola

2013-04-01

Hydrological models generally include thresholds and non-linearities, such as snow-rain-temperature thresholds, non-linear reservoirs, infiltration thresholds and the like. When relating observed variables to modelling results, formal methods often calculate performance metrics over long periods, reporting model performance with only few numbers. Such approaches are not well suited to compare dominating processes between reality and model and to better understand when thresholds and non-linearities are driving model results. We present a combination of two temporally resolved model diagnostic tools to answer when a model is performing (not so) well and what the dominant processes are during these periods. We look at the temporal dynamics of parameter sensitivities and model performance to answer this question. For this, the eco-hydrological SWAT model is applied in the Treene lowland catchment in Northern Germany. As a first step, temporal dynamics of parameter sensitivities are analyzed using the Fourier Amplitude Sensitivity test (FAST). The sensitivities of the eight model parameters investigated show strong temporal variations. High sensitivities were detected for two groundwater (GW_DELAY, ALPHA_BF) and one evaporation parameters (ESCO) most of the time. The periods of high parameter sensitivity can be related to different phases of the hydrograph with dominances of the groundwater parameters in the recession phases and of ESCO in baseflow and resaturation periods. Surface runoff parameters show high parameter sensitivities in phases of a precipitation event in combination with high soil water contents. The dominant parameters give indication for the controlling processes during a given period for the hydrological catchment. The second step included the temporal analysis of model performance. For each time step, model performance was characterized with a "finger print" consisting of a large set of performance measures. These finger prints were clustered into four reoccurring patterns of typical model performance, which can be related to different phases of the hydrograph. Overall, the baseflow cluster has the lowest performance. By combining the periods with poor model performance with the dominant model components during these phases, the groundwater module was detected as the model part with the highest potential for model improvements. The detection of dominant processes in periods of poor model performance enhances the understanding of the SWAT model. Based on this, concepts how to improve the SWAT model structure for the application in German lowland catchment are derived.

Maternal self-efficacy and experimentally manipulated infant difficulty effects on maternal sensory sensitivity: a signal detection analysis.

PubMed

Donovan, Wilberta; Leavitt, Lewis; Taylor, Nicole

2005-09-01

The impact of differences in maternal self-efficacy and infant difficulty on mothers' sensitivity to small changes in the fundamental frequency of an audiotaped infant's cry was explored in 2 experiments. The experiments share in common experimental manipulations of infant difficulty, a laboratory derived measure of maternal efficacy (low, moderate, and high illusory control), and the use of signal detection methodology to measure maternal sensory sensitivity. In Experiment 1 (N = 72), easy and difficult infant temperament was manipulated by varying the amount of crying (i.e., frequency of cry termination) in a simulated child-care task. In Experiment 2 (N = 51), easy and difficult infant temperament was manipulated via exposure to the solvable or unsolvable pretreatment of a learned helplessness task to mirror mothers' ability to soothe a crying infant. In both experiments, only mothers with high illusory control showed reduced sensory sensitivity under the difficult infant condition compared with the easy infant condition. Copyright 2005 APA, all rights reserved.

Immune biosensors based on the SPR and TIRE: efficiency of their application for bacteria determination

NASA Astrophysics Data System (ADS)

Starodub, N. F.; Ogorodniichuk, J.; Lebedeva, T.; Shpylovyy, P.

2013-11-01

In this work we have designed high-specific biosensors for Salmonella typhimurium detection based on the surface plasmon resonance (SPR) and total internal reflection ellipsometry (TIRE). It has been demonstrated high selectivity and sensitivity of analysis. As a registering part for our experiments the Spreeta (USA) and "Plasmonotest" (Ukraine) with flowing cell have been applied among of SPR device. Previous researches confirmed an efficiency of SPR biosensors using for detecting of specific antigen-antibody interactions therefore this type of reactions with some previous preparations of surface binding layer was used as reactive part. It has been defined that in case with Spreeta sensitivity was on the level 103 - 107 cells/ml. Another biosensor based on the SPR has shown the sensitivity within 101 - 106 cells/ml. Maximal sensitivity was on the level of several cells in 10 ml (up to the fact that less than 5 cells) which has been obtained using the biosensor based on TIRE.

A blood tumor marker combination assay produces high sensitivity and specificity for cancer according to the natural history.

PubMed

Kobayashi, Tsuneo

2018-03-01

Diagnosis using a specific tumor marker is difficult because the sensitivity of this detection method is under 20%. Herein, a tumor marker combination assay, combining growth-related tumor marker and associated tumor marker (Cancer, 73(7), 1994), was employed. This double-blind tumor marker combination assay (TMCA) showed 87.5% sensitivity as the results, but a low specificity, ranging from 30 to 76%. To overcome this low specificity, we exploited complex markers, a multivariate analysis and serum fractionation by biochemical biopsy. Thus, in this study, a combination of new techniques was used to re-evaluate these serum samples. Three serum panels, containing 90, 120, and 97 samples were obtained from the Mayo Clinic. The final results showed 80-90% sensitivity, 84-85% specificity, and 83-88% accuracy. We demonstrated a notable tumor marker combination assay with high accuracy. This TMCA should be applicable for primary cancer detection and recurrence prevention. © 2018 The Author. Cancer Medicine published by John Wiley & Sons Ltd.

Robust Optimization and Sensitivity Analysis with Multi-Objective Genetic Algorithms: Single- and Multi-Disciplinary Applications

DTIC Science & Technology

2007-01-01

multi-disciplinary optimization with uncertainty. Robust optimization and sensitivity analysis is usually used when an optimization model has...formulation is introduced in Section 2.3. We briefly discuss several definitions used in the sensitivity analysis in Section 2.4. Following in...2.5. 2.4 SENSITIVITY ANALYSIS In this section, we discuss several definitions used in Chapter 5 for Multi-Objective Sensitivity Analysis . Inner

Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*.

PubMed

Landesberg, Giora; Jaffe, Allan S; Gilon, Dan; Levin, Phillip D; Goodman, Sergey; Abu-Baih, Abed; Beeri, Ronen; Weissman, Charles; Sprung, Charles L; Landesberg, Amir

2014-04-01

Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis. Prospective, analytic cohort study. Tertiary academic institute. A cohort of ICU patients with severe sepsis or septic shock. Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock. Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e'-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and -2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s'-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e'-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e'-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively). Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

Lunar Exploration Architecture Level Key Drivers and Sensitivities

NASA Technical Reports Server (NTRS)

Goodliff, Kandyce; Cirillo, William; Earle, Kevin; Reeves, J. D.; Shyface, Hilary; Andraschko, Mark; Merrill, R. Gabe; Stromgren, Chel; Cirillo, Christopher

2009-01-01

Strategic level analysis of the integrated behavior of lunar transportation and lunar surface systems architecture options is performed to assess the benefit, viability, affordability, and robustness of system design choices. This analysis employs both deterministic and probabilistic modeling techniques so that the extent of potential future uncertainties associated with each option are properly characterized. The results of these analyses are summarized in a predefined set of high-level Figures of Merit (FOMs) so as to provide senior NASA Constellation Program (CxP) and Exploration Systems Mission Directorate (ESMD) management with pertinent information to better inform strategic level decision making. The strategic level exploration architecture model is designed to perform analysis at as high a level as possible but still capture those details that have major impacts on system performance. The strategic analysis methodology focuses on integrated performance, affordability, and risk analysis, and captures the linkages and feedbacks between these three areas. Each of these results leads into the determination of the high-level FOMs. This strategic level analysis methodology has been previously applied to Space Shuttle and International Space Station assessments and is now being applied to the development of the Constellation Program point-of-departure lunar architecture. This paper provides an overview of the strategic analysis methodology and the lunar exploration architecture analyses to date. In studying these analysis results, the strategic analysis team has identified and characterized key drivers affecting the integrated architecture behavior. These key drivers include inclusion of a cargo lander, mission rate, mission location, fixed-versus- variable costs/return on investment, and the requirement for probabilistic analysis. Results of sensitivity analysis performed on lunar exploration architecture scenarios are also presented.

Trace analysis of high-purity graphite by LA-ICP-MS.

PubMed

Pickhardt, C; Becker, J S

2001-07-01

Laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been established as a very efficient and sensitive technique for the direct analysis of solids. In this work the capability of LA-ICP-MS was investigated for determination of trace elements in high-purity graphite. Synthetic laboratory standards with a graphite matrix were prepared for the purpose of quantifying the analytical results. Doped trace elements, concentration 0.5 microg g(-1), in a laboratory standard were determined with an accuracy of 1% to +/- 7% and a relative standard deviation (RSD) of 2-13%. Solution-based calibration was also used for quantitative analysis of high-purity graphite. It was found that such calibration led to analytical results for trace-element determination in graphite with accuracy similar to that obtained by use of synthetic laboratory standards for quantification of analytical results. Results from quantitative determination of trace impurities in a real reactor-graphite sample, using both quantification approaches, were in good agreement. Detection limits for all elements of interest were determined in the low ng g(-1) concentration range. Improvement of detection limits by a factor of 10 was achieved for analyses of high-purity graphite with LA-ICP-MS under wet plasma conditions, because the lower background signal and increased element sensitivity.

Critical review and meta-analysis on the combination of heart-type fatty acid binding protein (H-FABP) and troponin for early diagnosis of acute myocardial infarction.

PubMed

Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco

2013-01-01

An early diagnosis is crucial for effective triage and management of patients with suspected acute myocardial infarction (AMI). Although troponin testing is the cornerstone of diagnosis, the sensitivity of this biomarker is still suboptimal at patient admission. The heart-type fatty acid binding protein (H-FABP) is an early and sensitive biomarker of myocardial ischemia, whose appropriate setting is in combination with troponin testing. We performed a systematic review and meta-analysis of articles that have assessed the combination of troponin and H-FABP in the early diagnosis of AMI. Eight studies, totaling 2735 patients, met the inclusion criteria but none of them used a high-sensitivity troponin immunoassay. The between-study variation was high (98.5%), and attributable to heterogeneity. When considered alone, troponin exhibited a significantly greater pooled area under the curve (AUC) than H-FABP alone (0.820 versus 0.784; p<0.001). The pooled specificity was also higher for troponin alone than for H-FABP alone (0.94 versus 0.83; p<0.001), whereas the cumulative sensitivity was lower for troponin than for H-FABP (0.73 versus 0.80; p=0.02). The combination of both biomarkers exhibited a greater AUC than troponin alone (0.881; p<0.001), as well as a higher pooled sensitivity (0.91; p<0.001), which was however counterbalanced by a lower specificity (0.82; p<0.001). These results attest that the combination of H-FABP with a conventional troponin immunoassay seems advantageous for increasing the sensitivity of the former biomarker, at the expense of a lower specificity. The introduction of H-FABP testing would hence require careful assessment of laboratory data or clinical signs and symptoms for excluding sources of elevation different from AMI. Further studies are needed to assess the diagnostic effectiveness of combining H-FABP with a high-sensitivity troponin immunoassay. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

PASTA: splice junction identification from RNA-Sequencing data

PubMed Central

2013-01-01

Background Next generation transcriptome sequencing (RNA-Seq) is emerging as a powerful experimental tool for the study of alternative splicing and its regulation, but requires ad-hoc analysis methods and tools. PASTA (Patterned Alignments for Splicing and Transcriptome Analysis) is a splice junction detection algorithm specifically designed for RNA-Seq data, relying on a highly accurate alignment strategy and on a combination of heuristic and statistical methods to identify exon-intron junctions with high accuracy. Results Comparisons against TopHat and other splice junction prediction software on real and simulated datasets show that PASTA exhibits high specificity and sensitivity, especially at lower coverage levels. Moreover, PASTA is highly configurable and flexible, and can therefore be applied in a wide range of analysis scenarios: it is able to handle both single-end and paired-end reads, it does not rely on the presence of canonical splicing signals, and it uses organism-specific regression models to accurately identify junctions. Conclusions PASTA is a highly efficient and sensitive tool to identify splicing junctions from RNA-Seq data. Compared to similar programs, it has the ability to identify a higher number of real splicing junctions, and provides highly annotated output files containing detailed information about their location and characteristics. Accurate junction data in turn facilitates the reconstruction of the splicing isoforms and the analysis of their expression levels, which will be performed by the remaining modules of the PASTA pipeline, still under development. Use of PASTA can therefore enable the large-scale investigation of transcription and alternative splicing. PMID:23557086

BreathDx - molecular analysis of exhaled breath as a diagnostic test for ventilator-associated pneumonia: protocol for a European multicentre observational study.

PubMed

van Oort, Pouline M P; Nijsen, Tamara; Weda, Hans; Knobel, Hugo; Dark, Paul; Felton, Timothy; Rattray, Nicholas J W; Lawal, Oluwasola; Ahmed, Waqar; Portsmouth, Craig; Sterk, Peter J; Schultz, Marcus J; Zakharkina, Tetyana; Artigas, Antonio; Povoa, Pedro; Martin-Loeches, Ignacio; Fowler, Stephen J; Bos, Lieuwe D J

2017-01-03

The diagnosis of ventilator-associated pneumonia (VAP) remains time-consuming and costly, the clinical tools lack specificity and a bedside test to exclude infection in suspected patients is unavailable. Breath contains hundreds to thousands of volatile organic compounds (VOCs) that result from host and microbial metabolism as well as the environment. The present study aims to use breath VOC analysis to develop a model that can discriminate between patients who have positive cultures and who have negative cultures with a high sensitivity. The Molecular Analysis of Exhaled Breath as Diagnostic Test for Ventilator-Associated Pneumonia (BreathDx) study is a multicentre observational study. Breath and bronchial lavage samples will be collected from 100 and 53 intubated and ventilated patients suspected of VAP. Breath will be analysed using Thermal Desorption - Gas Chromatography - Mass Spectrometry (TD-GC-MS). The primary endpoint is the accuracy of cross-validated prediction for positive respiratory cultures in patients that are suspected of VAP, with a sensitivity of at least 99% (high negative predictive value). To our knowledge, BreathDx is the first study powered to investigate whether molecular analysis of breath can be used to classify suspected VAP patients with and without positive microbiological cultures with 99% sensitivity. UKCRN ID number 19086, registered May 2015; as well as registration at www.trialregister.nl under the acronym 'BreathDx' with trial ID number NTR 6114 (retrospectively registered on 28 October 2016).

Interval analysis of interictal EEG: pathology of the alpha rhythm in focal epilepsy

NASA Astrophysics Data System (ADS)

Pyrzowski, Jan; Siemiński, Mariusz; Sarnowska, Anna; Jedrzejczak, Joanna; Nyka, Walenty M.

2015-11-01

The contemporary use of interictal scalp electroencephalography (EEG) in the context of focal epilepsy workup relies on the visual identification of interictal epileptiform discharges. The high-specificity performance of this marker comes, however, at a cost of only moderate sensitivity. Zero-crossing interval analysis is an alternative to Fourier analysis for the assessment of the rhythmic component of EEG signals. We applied this method to standard EEG recordings of 78 patients divided into 4 subgroups: temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), psychogenic nonepileptic seizures (PNES) and nonepileptic patients with headache. Interval-analysis based markers were capable of effectively discriminating patients with epilepsy from those in control subgroups (AUC~0.8) with diagnostic sensitivity potentially exceeding that of visual analysis. The identified putative epilepsy-specific markers were sensitive to the properties of the alpha rhythm and displayed weak or non-significant dependences on the number of antiepileptic drugs (AEDs) taken by the patients. Significant AED-related effects were concentrated in the theta interval range and an associated marker allowed for identification of patients on AED polytherapy (AUC~0.9). Interval analysis may thus, in perspective, increase the diagnostic yield of interictal scalp EEG. Our findings point to the possible existence of alpha rhythm abnormalities in patients with epilepsy.

Language evaluation protocol for children aged 2 months to 23 months: analysis of sensitivity and specificity.

PubMed

Labanca, Ludimila; Alves, Cláudia Regina Lindgren; Bragança, Lidia Lourenço Cunha; Dorim, Diego Dias Ramos; Alvim, Cristina Gonçalves; Lemos, Stela Maris Aguiar

2015-01-01

To establish cutoff points for the analysis of the Behavior Observation Form (BOF) of children in the ages of 2 to 23 months and evaluate the sensitivity and specificity by age group and domains (Emission, Reception, and Cognitive Aspects of Language). The sample consisted of 752 children who underwent BOF. Each child was classified as having appropriate language development for the age or having possible risk of language impairment. Performance Indicators (PI) were calculated in each domain as well as the overall PI in all domains. The values for sensitivity and specificity were also calculated. The cutoff points for possible risk of language impairment for each domain and each age group were obtained using the receiver operating characteristics curve. The results of the study revealed that one-third of the assessed children have a risk of language impairment in the first two years of life. The analysis of BOF showed high sensitivity (>90%) in all categories and in all age groups; however, the chance of false-positive results was higher than 20% in the majority of aspects evaluated. It was possible to establish the cutoff points for all categories and age groups with good correlation between sensitivity and specificity, except for the age group of 2 to 6 months. This study provides important contributions to the discussion on the evaluation of the language development of children younger than 2 years.

TBA PRODUCTION BY ACID HYDROLYSIS OF MTBE DURING HEATED HEADSPACE ANALYSIS & EVALUATION OF A BASE AS A PRESERVATIVE

EPA Science Inventory

At room temperature (20°±3°C), purge and trap samplers provide poor sensitivity for analysis of the fuel oxygenates that are alcohols, such as tertiary butyl alcohol (TBA). Because alcohols are miscible or highly soluble in water, they are not efficiently transferred to a gas chr...

Efficient estimators for likelihood ratio sensitivity indices of complex stochastic dynamics.

PubMed

Arampatzis, Georgios; Katsoulakis, Markos A; Rey-Bellet, Luc

2016-03-14

We demonstrate that centered likelihood ratio estimators for the sensitivity indices of complex stochastic dynamics are highly efficient with low, constant in time variance and consequently they are suitable for sensitivity analysis in long-time and steady-state regimes. These estimators rely on a new covariance formulation of the likelihood ratio that includes as a submatrix a Fisher information matrix for stochastic dynamics and can also be used for fast screening of insensitive parameters and parameter combinations. The proposed methods are applicable to broad classes of stochastic dynamics such as chemical reaction networks, Langevin-type equations and stochastic models in finance, including systems with a high dimensional parameter space and/or disparate decorrelation times between different observables. Furthermore, they are simple to implement as a standard observable in any existing simulation algorithm without additional modifications.

Efficient estimators for likelihood ratio sensitivity indices of complex stochastic dynamics

NASA Astrophysics Data System (ADS)

Arampatzis, Georgios; Katsoulakis, Markos A.; Rey-Bellet, Luc

2016-03-01

We demonstrate that centered likelihood ratio estimators for the sensitivity indices of complex stochastic dynamics are highly efficient with low, constant in time variance and consequently they are suitable for sensitivity analysis in long-time and steady-state regimes. These estimators rely on a new covariance formulation of the likelihood ratio that includes as a submatrix a Fisher information matrix for stochastic dynamics and can also be used for fast screening of insensitive parameters and parameter combinations. The proposed methods are applicable to broad classes of stochastic dynamics such as chemical reaction networks, Langevin-type equations and stochastic models in finance, including systems with a high dimensional parameter space and/or disparate decorrelation times between different observables. Furthermore, they are simple to implement as a standard observable in any existing simulation algorithm without additional modifications.

Efficient estimators for likelihood ratio sensitivity indices of complex stochastic dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arampatzis, Georgios; Katsoulakis, Markos A.; Rey-Bellet, Luc

2016-03-14

We demonstrate that centered likelihood ratio estimators for the sensitivity indices of complex stochastic dynamics are highly efficient with low, constant in time variance and consequently they are suitable for sensitivity analysis in long-time and steady-state regimes. These estimators rely on a new covariance formulation of the likelihood ratio that includes as a submatrix a Fisher information matrix for stochastic dynamics and can also be used for fast screening of insensitive parameters and parameter combinations. The proposed methods are applicable to broad classes of stochastic dynamics such as chemical reaction networks, Langevin-type equations and stochastic models in finance, including systemsmore » with a high dimensional parameter space and/or disparate decorrelation times between different observables. Furthermore, they are simple to implement as a standard observable in any existing simulation algorithm without additional modifications.« less

Fabrication and Structural Design of Micro Pressure Sensors for Tire Pressure Measurement Systems (TPMS)

PubMed Central

Tian, Bian; Zhao, Yulong; Jiang, Zhuangde; Zhang, Ling; Liao, Nansheng; Liu, Yuanhao; Meng, Chao

2009-01-01

In this paper we describe the design and testing of a micro piezoresistive pressure sensor for a Tire Pressure Measurement System (TPMS) which has the advantages of a minimized structure, high sensitivity, linearity and accuracy. Through analysis of the stress distribution of the diaphragm using the ANSYS software, a model of the structure was established. The fabrication on a single silicon substrate utilizes the technologies of anisotropic chemical etching and packaging through glass anodic bonding. The performance of this type of piezoresistive sensor, including size, sensitivity, and long-term stability, were investigated. The results indicate that the accuracy is 0.5% FS, therefore this design meets the requirements for a TPMS, and not only has a smaller size and simplicity of preparation, but also has high sensitivity and accuracy. PMID:22573960

Responses to auxin signals: an operating principle for dynamical sensitivity yet high resilience

PubMed Central

Bravi, B.; Martin, O. C.

2018-01-01

Plants depend on the signalling of the phytohormone auxin for their development and for responding to environmental perturbations. The associated biomolecular signalling network involves a negative feedback on Aux/IAA proteins which mediate the influence of auxin (the signal) on the auxin response factor (ARF) transcription factors (the drivers of the response). To probe the role of this feedback, we consider alternative in silico signalling networks implementing different operating principles. By a comparative analysis, we find that the presence of a negative feedback allows the system to have a far larger sensitivity in its dynamical response to auxin and that this sensitivity does not prevent the system from being highly resilient. Given this insight, we build a new biomolecular signalling model for quantitatively describing such Aux/IAA and ARF responses. PMID:29410878

Image encryption based on a delayed fractional-order chaotic logistic system

NASA Astrophysics Data System (ADS)

Wang, Zhen; Huang, Xia; Li, Ning; Song, Xiao-Na

2012-05-01

A new image encryption scheme is proposed based on a delayed fractional-order chaotic logistic system. In the process of generating a key stream, the time-varying delay and fractional derivative are embedded in the proposed scheme to improve the security. Such a scheme is described in detail with security analyses including correlation analysis, information entropy analysis, run statistic analysis, mean-variance gray value analysis, and key sensitivity analysis. Experimental results show that the newly proposed image encryption scheme possesses high security.