[Evaluation of the role of combined TES-MEP and CSEP monitoring during the spinal surgery].

PubMed

Chen, Yu-guang; Peng, Xin-sheng; Wan, Yong; Yang, Jun-lin; Zheng, Zhao-min; Zou, Xue-nong; Li, Fo-bao; Shu, Hai-hua; Xia, Jie-hua; Dou, Yun-ling

2010-02-01

To evaluate of the role of transcranial electrical stimulation motor evoked potential (TES-MEP) in combination with cortical somatosensory evoked potential (CSEP) monitoring during the spinal surgery. TES-MEP on bilateral anterior tibial muscle and flexor hallucal brevis and CSEP on bilateral posterior tibial nerve were observed simultaneously on 293 patients during spinal surgery from July 2006 to April 2009. Intravenous anesthesia was employed in all the patients, a part of which were added low dose of sevoflurane or muscle relaxant. The results of TES-MEP, CSEP and combined monitoring were analyzed statistically. Pre-operative and post-operative motor and sensory functions of spinal cord were compared. Success rate of TES-MEP, CSEP and combined monitoring was 90.8%, 96.9% and 100% respectively. For the judgment of motor function of spinal cord, the sensitivity of TES-MEP and CSEP was 100% and 89.3% respectively and the specificity of 98.4% and 96.9%. The Youden index of the two methods was 0.984 and 0.862. For sensory function, the sensitivity of them was 76.7% and 93.3% respectively and the specificity of 98.7% and 98.0%. The Youden index was 0.754 and 0.913. The sensitivity of combined monitoring was 100%, with the specificity of 96.9%. The Youden index was 0.969. The precision of monitoring motor function of spinal cord with TES-MEP is higher than that with CSEP, however, for sensory function, CSEP is more precise. The sensitivity and precision of combined monitoring for spinal cord function were apparently better than that of unitary TES-MEP or CSEP. The combined TES-MEP and CSEP monitoring is a relatively ideal method.

Relationship between the surrogate anthropometric measures, foot length and chest circumference and birth weight among newborns of Sarlahi, Nepal.

PubMed

Mullany, L C; Darmstadt, G L; Khatry, S K; Leclerq, S C; Tielsch, J M

2007-01-01

Classification of infants into low birth weight (LBW, <2500 g) or very low birth weight (VLBW, <2000 g) categories is a crucial step in targeting interventions to high-risk infants. To compare the validity of chest circumference and foot length as surrogate anthropometric measures for the identification of LBW and VLBW infants. Newborn infants (n=1640) born between March and June 2004 in 30 Village Development Committees of Sarlahi district, Nepal. Chest circumference, foot length and weight (SECA 727, precise to 2 g) of newborns were measured within 72 h after birth. The sensitivity, specificity and predictive values for a range of cutoff points of the anthropometric measures were estimated using the digital scale measurements as the gold standard. Among LBW infants (469/1640, 28.6%), chest circumference measures <30.3 cm were 91% sensitive and 83% specific. Similar levels of sensitivity for foot length were achieved only with considerable loss of specificity (<45%). Foot length measurements <6.9 cm were 88% sensitive and 86% specific for the identification of VLBW infants. Chest circumference was superior to foot length in classification of infants into birth weight categories. For the identification of VLBW infants, foot length performed well, and may be preferable to chest circumference, as the former measure does not require removal of infant swaddling clothes. In the absence of more precise direct measures of birth weight, chest circumference is recommended over foot length for the identification of LBW infants.

Validation of a commercial 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester lipase assay for diagnosis of canine pancreatitis.

PubMed

Goodband, Emily L; Serrano, Gonçalo; Constantino-Casas, Fernando; Archer, Joy; Watson, Penny J; Williams, Tim L

2018-01-01

The objectives of this study were fourfold: technical validation of a commercial canine 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase assay, to calculate a reference interval for DGGR lipase by the indirect a posteriori method, to establish biological validity of the assay, and to assess agreement between DGGR lipase and specific canine pancreatic lipase (Spec cPL) assays. Dogs with histologically confirmed acute pancreatitis (n=3), chronic pancreatitis (n=8) and normal pancreatic tissue (n=7) with stored (-80°C) serum samples were identified. Relevant controls were selected. Precision, reproducibility and linearity of DGGR lipase, and the effect of sample haemolysis and freezing, were assessed. Sensitivity and specificity of DGGR lipase and Spec cPL were determined. Agreement between these two parameters was calculated using Cohen's kappa coefficient (κ). The DGGR lipase assay demonstrated excellent precision, reproducibility and linearity. Sample haemolysis and storage at -80°C for 12 months did not influence the assay. DGGR lipase (>245IU/l) and Spec cPL (>400µg/l) both showed poor sensitivity but excellent specificity for acute pancreatitis, and poor to moderate sensitivity but excellent specificity for chronic pancreatitis. Substantial agreement (κ=0.679) was found between DGGR lipase and Spec cPL. The validated DGGR lipase assay had similar sensitivity and specificity for the diagnosis of acute and chronic pancreatitis to Spec cPL. DGGR lipase is a reliable alternative to Spec cPL for the diagnosis of pancreatitis.

Targeted Quantitation of Proteins by Mass Spectrometry

PubMed Central

2013-01-01

Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement. PMID:23517332

Targeted quantitation of proteins by mass spectrometry.

PubMed

Liebler, Daniel C; Zimmerman, Lisa J

2013-06-04

Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement.

Evaluation Methodology between Globalization and Localization Features Approaches for Skin Cancer Lesions Classification

NASA Astrophysics Data System (ADS)

Ahmed, H. M.; Al-azawi, R. J.; Abdulhameed, A. A.

2018-05-01

Huge efforts have been put in the developing of diagnostic methods to skin cancer disease. In this paper, two different approaches have been addressed for detection the skin cancer in dermoscopy images. The first approach uses a global method that uses global features for classifying skin lesions, whereas the second approach uses a local method that uses local features for classifying skin lesions. The aim of this paper is selecting the best approach for skin lesion classification. The dataset has been used in this paper consist of 200 dermoscopy images from Pedro Hispano Hospital (PH2). The achieved results are; sensitivity about 96%, specificity about 100%, precision about 100%, and accuracy about 97% for globalization approach while, sensitivity about 100%, specificity about 100%, precision about 100%, and accuracy about 100% for Localization Approach, these results showed that the localization approach achieved acceptable accuracy and better than globalization approach for skin cancer lesions classification.

Analysis of feline and canine allergen components in patients sensitized to pets.

PubMed

Ukleja-Sokołowska, Natalia; Gawrońska-Ukleja, Ewa; Żbikowska-Gotz, Magdalena; Socha, Ewa; Lis, Kinga; Sokołowski, Łukasz; Kuźmiński, Andrzej; Bartuzi, Zbigniew

2016-01-01

Component resolved allergen diagnosis allows for a precise evaluation of the sensitization profiles of patients sensitized to felines and canines. An accurate interpretation of these results allows better insight into the evolution of a given patients sensitizations, and allows for a more precise evaluation of their prognoses. 70 patients (42 women and 28 men, aged 18-65, with the average of 35.5) with a positive feline or canine allergy diagnosis were included in the research group. 30 patients with a negative allergy diagnosis were included in the control group. The total IgE levels of all patients with allergies as well as their allergen-specific IgE to feline and canine allergens were measured. Specific IgE levels to canine (Can f 1, Can f 2, Can f 3, Can f 5) and feline (Fel d 1, Fel d 2, Fel d 4) allergen components were also measured with the use of the ImmunoCap method. Monosensitization for only one canine or feline component was found in 30% of patients. As predicted, the main feline allergen was Fel d 1, which sensitized as many as 93.9% of patients sensitized to felines. Among 65 patients sensitized to at least one feline component, for 30 patients (46.2%) the only sensitizing feline component was Fel d 1. Only 19 patients in that group (63.3%) were not simultaneously sensitized to dogs and 11 (36.7%), the isolated sensitization to feline Fel d 1 notwithstanding, displayed concurrent sensitizations to one of the canine allergen components. Fel d 4 sensitized 49.2% of the research group.64.3% of patients sensitized to canine components had heightened levels of specific IgE to Can f 1. Monosensitization in that group occurred for 32.1% of the patients. Sensitization to Can f 5 was observed among 52.4% of the patients. Concurrent sensitizations to a few allergic components, not only cross-reactive but also originating in different protein families, are a significant problem for patients sensitized to animals.

Raman spectroscopy

USDA-ARS?s Scientific Manuscript database

Raman spectroscopy has gained increased use and importance in recent years for accurate and precise detection of physical and chemical properties of food materials, due to the greater specificity and sensitivity of Raman techniques over other analytical techniques. This book chapter presents Raman s...

Grasp posture alters visual processing biases near the hands

PubMed Central

Thomas, Laura E.

2015-01-01

Observers experience biases in visual processing for objects within easy reach of their hands that may assist them in evaluating items that are candidates for action. I investigated the hypothesis that hand postures affording different types of actions differentially bias vision. Across three experiments, participants performed global motion detection and global form perception tasks while their hands were positioned a) near the display in a posture affording a power grasp, b) near the display in a posture affording a precision grasp, or c) in their laps. Although the power grasp posture facilitated performance on the motion task, the precision grasp posture instead facilitated performance on the form task. These results suggest that the visual system weights processing based on an observer’s current affordances for specific actions: fast and forceful power grasps enhance temporal sensitivity, while detail-oriented precision grasps enhance spatial sensitivity. PMID:25862545

Quantitative optical metrology with CMOS cameras

NASA Astrophysics Data System (ADS)

Furlong, Cosme; Kolenovic, Ervin; Ferguson, Curtis F.

2004-08-01

Recent advances in laser technology, optical sensing, and computer processing of data, have lead to the development of advanced quantitative optical metrology techniques for high accuracy measurements of absolute shapes and deformations of objects. These techniques provide noninvasive, remote, and full field of view information about the objects of interest. The information obtained relates to changes in shape and/or size of the objects, characterizes anomalies, and provides tools to enhance fabrication processes. Factors that influence selection and applicability of an optical technique include the required sensitivity, accuracy, and precision that are necessary for a particular application. In this paper, sensitivity, accuracy, and precision characteristics in quantitative optical metrology techniques, and specifically in optoelectronic holography (OEH) based on CMOS cameras, are discussed. Sensitivity, accuracy, and precision are investigated with the aid of National Institute of Standards and Technology (NIST) traceable gauges, demonstrating the applicability of CMOS cameras in quantitative optical metrology techniques. It is shown that the advanced nature of CMOS technology can be applied to challenging engineering applications, including the study of rapidly evolving phenomena occurring in MEMS and micromechatronics.

Identifying the Genotypes of Hepatitis B Virus (HBV) with DNA Origami Label.

PubMed

Liu, Ke; Pan, Dun; Wen, Yanqin; Zhang, Honglu; Chao, Jie; Wang, Lihua; Song, Shiping; Fan, Chunhai; Shi, Yongyong

2018-02-01

The hepatitis B virus (HBV) genotyping may profoundly affect the accurate diagnosis and antiviral treatment of viral hepatitis. Existing genotyping methods such as serological, immunological, or molecular testing are still suffered from substandard specificity and low sensitivity in laboratory or clinical application. In a previous study, a set of high-efficiency hybridizable DNA origami-based shape ID probes to target the templates through which genetic variation could be determined in an ultrahigh resolution of atomic force microscopy (AFM) nanomechanical imaging are established. Here, as a further confirmatory research to explore the sensitivity and applicability of this assay, differentially predesigned DNA origami shape ID probes are also developed for precisely HBV genotyping. Through the specific identification of visualized DNA origami nanostructure with clinical HBV DNA samples, the genetic variation information of genotypes can be directly identified under AFM. As a proof-of-concept, five genotype B and six genotype C are detected in 11 HBV-infected patients' blood DNA samples of Han Chinese population in the single-blinded test. The AFM image-based DNA origami shape ID genotyping approach shows high specificity and sensitivity, which could be promising for virus infection diagnosis and precision medicine in the future. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estimating sensitivity and specificity for technology assessment based on observer studies.

PubMed

Nishikawa, Robert M; Pesce, Lorenzo L

2013-07-01

The goal of this study was to determine the accuracy and precision of using scores from a receiver operating characteristic rating scale to estimate sensitivity and specificity. We used data collected in a previous study that measured the improvements in radiologists' ability to classify mammographic microcalcification clusters as benign or malignant with and without the use of a computer-aided diagnosis scheme. Sensitivity and specificity were estimated from the rating data from a question that directly asked the radiologists their biopsy recommendations, which was used as the "truth," because it is the actual recall decision, thus it is their subjective truth. By thresholding the rating data, sensitivity and specificity were estimated for different threshold values. Because of interreader and intrareader variability, estimated sensitivity and specificity values for individual readers could be as much as 100% in error when using rating data compared to using the biopsy recommendation data. When pooled together, the estimates using thresholding the rating data were in good agreement with sensitivity and specificity estimated from the recommendation data. However, the statistical power of the rating data estimates was lower. By simply asking the observer his or her explicit recommendation (eg, biopsy or no biopsy), sensitivity and specificity can be measured directly, giving a more accurate description of empirical variability and the power of the study can be maximized. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

Validation of a motor activity system by a robotically controlled vehicle and using standard reference compounds.

PubMed

Patterson, John P; Markgraf, Carrie G; Cirino, Maria; Bass, Alan S

2005-01-01

A series of experiments were undertaken to evaluate the accuracy, precision, specificity, and sensitivity of an automated, infrared photo beam-based open field motor activity system, the MotorMonitor v. 4.01, Hamilton-Kinder, LLC, for use in a good laboratory practices (GLP) Safety Pharmacology laboratory. This evaluation consisted of two phases: (1) system validation, employing known inputs using the EM-100 Controller Photo Beam Validation System, a robotically controlled vehicle representing a rodent and (2) biologic validation, employing groups of rats treated with the standard pharmacologic agents diazepam or D-amphetamine. The MotorMonitor's parameters that described the open-field activity of a subject were: basic movements, total distance, fine movements, x/y horizontal ambulations, rearing, and total rest time. These measurements were evaluated over a number of zones within each enclosure. System validation with the EM-100 Controller Photo Beam Validation System showed that all the parameters accurately and precisely measured what they were intended to measure, with the exception of fine movements and x/y ambulations. Biologic validation using the central nervous system depressant diazepam at 1, 2, or 5 mg/kg, i.p. produced the expected dose-dependent reduction in rat motor activity. In contrast, the central nervous system stimulant D-amphetamine produced the expected increases in rat motor activity at 0.1 and 1 mg/kg, i.p, demonstrating the specificity and sensitivity of the system. Taken together, these studies of the accuracy, precision, specificity, and sensitivity show the importance of both system and biologic validation in the evaluation of an automated open field motor activity system for use in a GLP compliant laboratory.

Advances in tumor diagnosis using OCT and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Zakharov, V. P.; Bratchenko, I. A.; Kozlov, S. V.; Moryatov, A. A.; Kornilin, D. V.; Myakinin, O. O.; Artemyev, D. N.

2014-05-01

Complex investigation of malignant tumors was performed with combined optical coherence tomography (OCT) and Raman spectroscopy (RS) setup: 22 ex vivo lung tissue samples and 23 in vivo experiments with skin tumors. It was shown that combined RS-OCT unit may be used for precise tissue morphology visualization with simultaneous tumor type determination (BCC, malignant melanoma of skin tissues, adenocarcinoma and squamous cell carcinoma of lung). Fast RS phase method for skin and lung tumors identification was proposed. It is based on alteration of Raman spectral intensity in 1300-1340, 1440-1460 and 1640-1680 cm-1 bands for healthy and malignant tissue. Complex method could identify: malignant melanoma with 88.9% sensitivity and 87.8% specificity; adenocarcinoma with 100% sensitivity and 81.5% specificity; squamous cell carcinomas with 90.9% sensitivity and 77.8% specificity.

European Multicenter Study on Analytical Performance of DxN Veris System HCV Assay.

PubMed

Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Gismondo, Maria Rita; Hofmann, Jörg; Izopet, Jacques; Kühn, Sebastian; Lombardi, Alessandra; Marcos, Maria Angeles; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel W

2017-04-01

The analytical performance of the Veris HCV Assay for use on the new and fully automated Beckman Coulter DxN Veris Molecular Diagnostics System (DxN Veris System) was evaluated at 10 European virology laboratories. Precision, analytical sensitivity, specificity, and performance with negative samples, linearity, and performance with hepatitis C virus (HCV) genotypes were evaluated. Precision for all sites showed a standard deviation (SD) of 0.22 log 10 IU/ml or lower for each level tested. Analytical sensitivity determined by probit analysis was between 6.2 and 9.0 IU/ml. Specificity on 94 unique patient samples was 100%, and performance with 1,089 negative samples demonstrated 100% not-detected results. Linearity using patient samples was shown from 1.34 to 6.94 log 10 IU/ml. The assay demonstrated linearity upon dilution with all HCV genotypes. The Veris HCV Assay demonstrated an analytical performance comparable to that of currently marketed HCV assays when tested across multiple European sites. Copyright © 2017 American Society for Microbiology.

A multifaceted FISH approach to study endogenous RNAs and DNAs in native nuclear and cell structures.

PubMed

Byron, Meg; Hall, Lisa L; Lawrence, Jeanne B

2013-01-01

Fluorescence in situ hybridization (FISH) is not a singular technique, but a battery of powerful and versatile tools for examining the distribution of endogenous genes and RNAs in precise context with each other and in relation to specific proteins or cell structures. This unit offers the details of highly sensitive and successful protocols that were initially developed largely in our lab and honed over a number of years. Our emphasis is on analysis of nuclear RNAs and DNA to address specific biological questions about nuclear structure, pre-mRNA metabolism, or the role of noncoding RNAs; however, cytoplasmic RNA detection is also discussed. Multifaceted molecular cytological approaches bring precise resolution and sensitive multicolor detection to illuminate the organization and functional roles of endogenous genes and their RNAs within the native structure of fixed cells. Solutions to several common technical pitfalls are discussed, as are cautions regarding the judicious use of digital imaging and the rigors of analyzing and interpreting complex molecular cytological results.

Rapid Debris Analysis Project Task 3 Final Report - Sensitivity of Fallout to Source Parameters, Near-Detonation Environment Material Properties, Topography, and Meteorology

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

Goldstein, Peter

2014-01-24

This report describes the sensitivity of predicted nuclear fallout to a variety of model input parameters, including yield, height of burst, particle and activity size distribution parameters, wind speed, wind direction, topography, and precipitation. We investigate sensitivity over a wide but plausible range of model input parameters. In addition, we investigate a specific example with a relatively narrow range to illustrate the potential for evaluating uncertainties in predictions when there are more precise constraints on model parameters.

Simultaneous Determination of Potassium Clavulanate and Amoxicillin Trihydrate in Bulk, Pharmaceutical Formulations and in Human Urine Samples by UV Spectrophotometry

PubMed Central

Gujral, Rajinder Singh; Haque, Sk Manirul

2010-01-01

A simple and sensitive UV spectrophotometric method was developed and validated for the simultaneous determination of Potassium Clavulanate (PC) and Amoxicillin Trihydrate (AT) in bulk, pharmaceutical formulations and in human urine samples. The method was linear in the range of 0.2–8.5 μg/ml for PC and 6.4–33.6 μg/ml for AT. The absorbance was measured at 205 and 271 nm for PC and AT respectively. The method was validated with respect to accuracy, precision, specificity, ruggedness, robustness, limit of detection and limit of quantitation. This method was used successfully for the quality assessment of four PC and AT drug products and in human urine samples with good precision and accuracy. This is found to be simple, specific, precise, accurate, reproducible and low cost UV Spectrophotometric method. PMID:23675211

Uncertainty for Part Density Determination: An Update

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

Valdez, Mario Orlando

2016-12-14

Accurate and precise density measurements by hydrostatic weighing requires the use of an analytical balance, configured with a suspension system, to both measure the weight of a part in water and in air. Additionally, the densities of these liquid media (water and air) must be precisely known for the part density determination. To validate the accuracy and precision of these measurements, uncertainty statements are required. The work in this report is a revision of an original report written more than a decade ago, specifically applying principles and guidelines suggested by the Guide to the Expression of Uncertainty in Measurement (GUM)more » for determining the part density uncertainty through sensitivity analysis. In this work, updated derivations are provided; an original example is revised with the updated derivations and appendix, provided solely to uncertainty evaluations using Monte Carlo techniques, specifically using the NIST Uncertainty Machine, as a viable alternative method.« less

Relationship between the surrogate anthropometric measures, foot length and chest circumference and birth weight among newborns of Sarlahi, Nepal

PubMed Central

Mullany, LC; Darmstadt, GL; Khatry, SK; LeClerq, SC; Tielsch, JM

2008-01-01

Background Classification of infants into low birth weight (LBW, <2500 g) or very low birth weight (VLBW, <2000 g) categories is a crucial step in targeting interventions to high-risk infants. Objective To compare the validity of chest circumference and foot length as surrogate anthropometric measures for the identification of LBW and VLBW infants. Subjects and setting Newborn infants (n = 1640) born between March and June 2004 in 30 Village Development Committees of Sarlahi district, Nepal. Design Chest circumference, foot length and weight (SECA 727, precise to 2 g) of newborns were measured within 72 h after birth. The sensitivity, specificity and predictive values for a range of cutoff points of the anthropometric measures were estimated using the digital scale measurements as the gold standard. Results Among LBW infants (469/1640, 28.6%), chest circumference measures <30.3 cm were 91% sensitive and 83% specific. Similar levels of sensitivity for foot length were achieved only with considerable loss of specificity (<45%). Foot length measurements <6.9 cm were 88% sensitive and 86% specific for the identification of VLBW infants. Conclusion Chest circumference was superior to foot length in classification of infants into birth weight categories. For the identification of VLBW infants, foot length performed well, and may be preferable to chest circumference, as the former measure does not require removal of infant swaddling clothes. In the absence of more precise direct measures of birth weight, chest circumference is recommended over foot length for the identification of LBW infants. Sponsorship The National Institute of Child Health and Human Development; the Saving Newborn Lives Initiative, Save the Children – US and the Office of Heath and Nutrition, United States Agency for International Development (see Acknowledgements). PMID:16885929

Development and performance evaluation of a novel immunofluorescence chromatographic assay for histidine-rich protein 2 of Plasmodium falciparum.

PubMed

Kang, Keren; Dzakah, Emmanuel E; Huang, Yongping; Xie, Mingquan; Luo, Xiaochun; Li, Wenmei; Wang, Jihua

2015-05-30

The low sensitivity and specificity of Plasmodium falciparum diagnostic tests pose a serious health threat to people living in endemic areas. The objective of the study was to develop a rapid assay for the detection of histidine-rich protein 2 (HRP2) of P. falciparum in whole blood by immunofluorescence chromatographic technology. A total of 1163 positive and negative blood samples were screened. The double-antibody sandwich assay was used to establish the kit and its performance was evaluated for sensitivity, specificity, accuracy, precision, stability, and clinical effectiveness. The cut-off level of detection of the kit was 25 parasites/μl. Common interfering substances in human blood specimens, such as bilirubin, triglyceride and cholesterol had no significant effect on HRP2 antigen detection. The precision of the kit was run with different concentration of standard calibrators and the values were less than 10 %. The performance of this diagnostic kit in the detection of the calibrators has shown that a shelf life of about 12 months gives a more reliable result. Among clinical samples tested, the HRP2 test kit and the reference products had good coincidence rate in a parallel experiment and this test kit had a more sensitive detecting level to the target protein than the reference kits used in this study. The specificity and sensitivity for this test were 99.6 % (800/803) and 99.7 % (1160/1163), respectively. A novel HRP2 immunofluorescence detection method was developed in this study. Overall performance evaluation indicated that the kit has a rapid, high sensitivity and on-spot method for detecting P. falciparum.

Secondary node analysis as an indicator for axillary lymphadenectomy in breast cancer patients.

PubMed

Cremades, Manel; Torres, Mireia; Solà, Montse; Navinés, Jordi; Pascual, Icíar; Mariscal, Antonio; Caballero, Albert; Castellà, Eva; Luna, Miguel Ángel; Julián, Joan Francesc

2017-11-01

Currently, there is no agreement regarding if it would be necessary to perform an axillary lymph node dissection (ALND) in patients who have macrometastases in the sentinel lymph node (SLN). We studied the utility of the secondary node analysis (SN), defined as the following node after the SLN in an anatomical and lymphatic pathway, as a sign of malignant axillary involvement. An observational, retrospective and multicentre study was designed to assess the utility of the SN as a sign of axillary involvement. Among 2273 patients with breast cancer, a valid sample of 283 was obtained representing those who had the SN studied. Main endpoints of our study were: the SLN, the SN and the ALND histological pattern. Sensitivity, specificity and precision of the test were also calculated. SN test, in cases with positive SLN, has a sensitivity of 61.1%, a specificity of 78.7%, a positive predictive value of 45.8% and a negative predictive value of 87.3% with a precision of 74.7%. The study of the SN together with the technique of the SLN allows a more precise staging of the axillary involvement, in patients with breast cancer, than just the SLN technique. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Notes From the Field: Secondary Task Precision for Cognitive Load Estimation During Virtual Reality Surgical Simulation Training.

PubMed

Rasmussen, Sebastian R; Konge, Lars; Mikkelsen, Peter T; Sørensen, Mads S; Andersen, Steven A W

2016-03-01

Cognitive load (CL) theory suggests that working memory can be overloaded in complex learning tasks such as surgical technical skills training, which can impair learning. Valid and feasible methods for estimating the CL in specific learning contexts are necessary before the efficacy of CL-lowering instructional interventions can be established. This study aims to explore secondary task precision for the estimation of CL in virtual reality (VR) surgical simulation and also investigate the effects of CL-modifying factors such as simulator-integrated tutoring and repeated practice. Twenty-four participants were randomized for visual assistance by a simulator-integrated tutor function during the first 5 of 12 repeated mastoidectomy procedures on a VR temporal bone simulator. Secondary task precision was found to be significantly lower during simulation compared with nonsimulation baseline, p < .001. Contrary to expectations, simulator-integrated tutoring and repeated practice did not have an impact on secondary task precision. This finding suggests that even though considerable changes in CL are reflected in secondary task precision, it lacks sensitivity. In contrast, secondary task reaction time could be more sensitive, but requires substantial postprocessing of data. Therefore, future studies on the effect of CL modifying interventions should weigh the pros and cons of the various secondary task measurements. © The Author(s) 2015.

Assessing behavioural changes in ALS: cross-validation of ALS-specific measures.

PubMed

Pinto-Grau, Marta; Costello, Emmet; O'Connor, Sarah; Elamin, Marwa; Burke, Tom; Heverin, Mark; Pender, Niall; Hardiman, Orla

2017-07-01

The Beaumont Behavioural Inventory (BBI) is a behavioural proxy report for the assessment of behavioural changes in ALS. This tool has been validated against the FrSBe, a non-ALS-specific behavioural assessment, and further comparison of the BBI against a disease-specific tool was considered. This study cross-validates the BBI against the ALS-FTD-Q. Sixty ALS patients, 8% also meeting criteria for FTD, were recruited. All patients were evaluated using the BBI and the ALS-FTD-Q, completed by a carer. Correlational analysis was performed to assess construct validity. Precision, sensitivity, specificity, and overall accuracy of the BBI when compared to the ALS-FTD-Q, were obtained. The mean score of the whole sample on the BBI was 11.45 ± 13.06. ALS-FTD patients scored significantly higher than non-demented ALS patients (31.6 ± 14.64, 9.62 ± 11.38; p < 0.0001). A significant large positive correlation between the BBI and the ALS-FTD-Q was observed (r = 0.807, p < 0.0001), and no significant correlations between the BBI and other clinical/demographic characteristics indicate good convergent and discriminant validity, respectively. 72% of overall concordance was observed. Precision, sensitivity, and specificity for the classification of severely impaired patients were adequate. However, lower concordance in the classification of mild behavioural changes was observed, with higher sensitivity using the BBI, most likely secondary to BBI items which endorsed behavioural aspects not measured by the ALS-FTD-Q. Good construct validity has been further confirmed when the BBI is compared to an ALS-specific tool. Furthermore, the BBI is a more comprehensive behavioural assessment for ALS, as it measures the whole behavioural spectrum in this condition.

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

Probing New Long-Range Interactions by Isotope Shift Spectroscopy

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

Berengut, Julian C.; Budker, Dmitry; Delaunay, Cédric

We explore a method to probe new long- and intermediate-range interactions using precision atomic isotope shift spectroscopy. We develop a formalism to interpret linear King plots as bounds on new physics with minimal theory inputs. We focus only on bounding the new physics contributions that can be calculated independently of the standard model nuclear effects. We apply our method to existing Ca + data and project its sensitivity to conjectured new bosons with spin-independent couplings to the electron and the neutron using narrow transitions in other atoms and ions, specifically, Sr and Yb. Future measurements are expected to improve themore » relative precision by 5 orders of magnitude, and they can potentially lead to an unprecedented sensitivity for bosons within the 0.3 to 10 MeV mass range.« less

Probing New Long-Range Interactions by Isotope Shift Spectroscopy.

PubMed

Berengut, Julian C; Budker, Dmitry; Delaunay, Cédric; Flambaum, Victor V; Frugiuele, Claudia; Fuchs, Elina; Grojean, Christophe; Harnik, Roni; Ozeri, Roee; Perez, Gilad; Soreq, Yotam

2018-03-02

We explore a method to probe new long- and intermediate-range interactions using precision atomic isotope shift spectroscopy. We develop a formalism to interpret linear King plots as bounds on new physics with minimal theory inputs. We focus only on bounding the new physics contributions that can be calculated independently of the standard model nuclear effects. We apply our method to existing Ca^{+} data and project its sensitivity to conjectured new bosons with spin-independent couplings to the electron and the neutron using narrow transitions in other atoms and ions, specifically, Sr and Yb. Future measurements are expected to improve the relative precision by 5 orders of magnitude, and they can potentially lead to an unprecedented sensitivity for bosons within the 0.3 to 10 MeV mass range.

Probing New Long-Range Interactions by Isotope Shift Spectroscopy

DOE PAGES

Berengut, Julian C.; Budker, Dmitry; Delaunay, Cédric; ...

2018-02-26

We explore a method to probe new long- and intermediate-range interactions using precision atomic isotope shift spectroscopy. We develop a formalism to interpret linear King plots as bounds on new physics with minimal theory inputs. We focus only on bounding the new physics contributions that can be calculated independently of the standard model nuclear effects. We apply our method to existing Ca + data and project its sensitivity to conjectured new bosons with spin-independent couplings to the electron and the neutron using narrow transitions in other atoms and ions, specifically, Sr and Yb. Future measurements are expected to improve themore » relative precision by 5 orders of magnitude, and they can potentially lead to an unprecedented sensitivity for bosons within the 0.3 to 10 MeV mass range.« 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.

Inequality across Consonantal Contrasts in Speech Perception: Evidence from Mismatch Negativity

ERIC Educational Resources Information Center

Cornell, Sonia A.; Lahiri, Aditi; Eulitz, Carsten

2013-01-01

The precise structure of speech sound representations is still a matter of debate. In the present neurobiological study, we compared predictions about differential sensitivity to speech contrasts between models that assume full specification of all phonological information in the mental lexicon with those assuming sparse representations (only…

Sensitivity, Specificity, PPV, and NPV for Predictive Biomarkers.

PubMed

Simon, Richard

2015-08-01

Molecularly targeted cancer drugs are often developed with companion diagnostics that attempt to identify which patients will have better outcome on the new drug than the control regimen. Such predictive biomarkers are playing an increasingly important role in precision oncology. For diagnostic tests, sensitivity, specificity, positive predictive value, and negative predictive are usually used as performance measures. This paper discusses these indices for predictive biomarkers, provides methods for their calculation with survival or response endpoints, and describes assumptions involved in their use. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Raman fingerprints of atomically precise graphene nanoribbons

DOE PAGES

Verzhbitskiy, Ivan A.; Corato, Marzio De; Ruini, Alice; ...

2016-02-23

Bottom-up approaches allow the production of ultranarrow and atomically precise graphene nanoribbons (GNRs) with electronic and optical properties controlled by the specific atomic structure. Combining Raman spectroscopy and ab initio simulations, we show that GNR width, edge geometry, and functional groups all influence their Raman spectra. As a result, the low-energy spectral region below 1000 cm –1 is particularly sensitive to edge morphology and functionalization, while the D peak dispersion can be used to uniquely fingerprint the presence of GNRs and differentiates them from other sp 2 carbon nanostructures.

Search Filter Precision Can Be Improved By NOTing Out Irrelevant Content

PubMed Central

Wilczynski, Nancy L.; McKibbon, K. Ann; Haynes, R. Brian

2011-01-01

Background: Most methodologic search filters developed for use in large electronic databases such as MEDLINE have low precision. One method that has been proposed but not tested for improving precision is NOTing out irrelevant content. Objective: To determine if search filter precision can be improved by NOTing out the text words and index terms assigned to those articles that are retrieved but are off-target. Design: Analytic survey. Methods: NOTing out unique terms in off-target articles and testing search filter performance in the Clinical Hedges Database. Main Outcome Measures: Sensitivity, specificity, precision and number needed to read (NNR). Results: For all purpose categories (diagnosis, prognosis and etiology) except treatment and for all databases (MEDLINE, EMBASE, CINAHL and PsycINFO), constructing search filters that NOTed out irrelevant content resulted in substantive improvements in NNR (over four-fold for some purpose categories and databases). Conclusion: Search filter precision can be improved by NOTing out irrelevant content. PMID:22195215

Commentary: Early father-infant interaction and externalizing behaviors--a response to Ramchandani et al. (2013).

PubMed

Shaw, Daniel S

2013-01-01

Many researchers have attempted to uncover the precise contribution of fathers to childrearing in relation to both young and older children's development during the past five decades (Lamb, 1975), including during the infancy period (Parke & O'Leary. S, 1975). However, few have been able to isolate precise mechanisms by which specific types of paternal childrearing practices may be linked to specific types of prosocial and problem behavior. The current paper by Ramchandani et al. (2013) breaks new ground in identifying a precise dimension of paternal parenting during early infancy--engagement--and linking it to maternal reports of infant externalizing problem behavior. Importantly, this association was found after accounting for the influence of several child, paternal, and maternal characteristics, including observed maternal sensitivity. Specifically, the authors found that fathers observed to be less engaging with their 3-month olds were reported by mothers to show fewer disruptive problems 9 months later. © 2012 The Author. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Simple and ultra-fast recognition and quantitation of compounded monoclonal antibodies: Application to flow injection analysis combined to UV spectroscopy and matching method.

PubMed

Jaccoulet, E; Schweitzer-Chaput, A; Toussaint, B; Prognon, P; Caudron, E

2018-09-01

Compounding of monoclonal antibody (mAbs) constantly increases in hospital. Quality control (QC) of the compounded mAbs based on quantification and identification is required to prevent potential errors and fast method is needed to manage outpatient chemotherapy administration. A simple and ultra-fast (less than 30 s) method using flow injection analysis associated to least square matching method issued from the analyzer software was performed and evaluated for the routine hospital QC of three compounded mAbs: bevacizumab, infliximab and rituximab. The method was evaluated through qualitative and quantitative parameters. Preliminary analysis of the UV absorption and second derivative spectra of the mAbs allowed us to adapt analytical conditions according to the therapeutic range of the mAbs. In terms of quantitative QC, linearity, accuracy and precision were assessed as specified in ICH guidelines. Very satisfactory recovery was achieved and the RSD (%) of the intermediate precision were less than 1.1%. Qualitative analytical parameters were also evaluated in terms of specificity, sensitivity and global precision through a matrix of confusion. Results showed to be concentration and mAbs dependant and excellent (100%) specificity and sensitivity were reached within specific concentration range. Finally, routine application on "real life" samples (n = 209) from different batch of the three mAbs complied with the specifications of the quality control i.e. excellent identification (100%) and ± 15% of targeting concentration belonging to the calibration range. The successful use of the combination of second derivative spectroscopy and partial least square matching method demonstrated the interest of FIA for the ultra-fast QC of mAbs after compounding using matching method. Copyright © 2018 Elsevier B.V. All rights reserved.

Optimal search strategies for detecting health services research studies in MEDLINE

PubMed Central

Wilczynski, Nancy L.; Haynes, R. Brian; Lavis, John N.; Ramkissoonsingh, Ravi; Arnold-Oatley, Alexandra E.

2004-01-01

Background Evidence from health services research (HSR) is currently thinly spread through many journals, making it difficult for health services researchers, managers and policy-makers to find research on clinical practice guidelines and the appropriateness, process, outcomes, cost and economics of health care services. We undertook to develop and test search terms to retrieve from the MEDLINE database HSR articles meeting minimum quality standards. Methods The retrieval performance of 7445 methodologic search terms and phrases in MEDLINE (the test) were compared with a hand search of the literature (the gold standard) for each issue of 68 journal titles for the year 2000 (a total of 25 936 articles). We determined sensitivity, specificity and precision (the positive predictive value) of the MEDLINE search strategies. Results A majority of the articles that were classified as outcome assessment, but fewer than half of those in the other categories, were considered methodologically acceptable (no methodologic criteria were applied for cost studies). Combining individual search terms to maximize sensitivity, while keeping specificity at 50% or more, led to sensitivities in the range of 88.1% to 100% for several categories (specificities ranged from 52.9% to 97.4%). When terms were combined to maximize specificity while keeping sensitivity at 50% or more, specificities of 88.8% to 99.8% were achieved. When terms were combined to maximize sensitivity and specificity while minimizing the differences between the 2 measurements, most strategies for HSR categories achieved sensitivity and specificity of at least 80%. Interpretation Sensitive and specific search strategies were validated for retrieval of HSR literature from MEDLINE. These strategies have been made available for public use by the US National Library of Medicine at www.nlm.nih.gov/nichsr/hedges/search.html. PMID:15534310

Half-Unit Insulin Pens: Disease Management in Patients With Diabetes Who Are Sensitive to Insulin.

PubMed

Klonoff, David C; Nayberg, Irina; Stauder, Udo; Oualali, Hamid; Domenger, Catherine

2017-05-01

Insulin pens represent a significant technological advancement in diabetes management. While the vast majority have been designed with 1U-dosing increments, improved accuracy and precision facilitated by half-unit increments may be particularly significant in specific patients who are sensitive to insulin. These include patients with low insulin requirements and in those requiring more precise dose adjustments, such as the pediatric patient population. This review summarized functional characteristics of insulin half-unit pens (HUPs) and their effect on user experience. The literature search was restricted to articles published in English between January 1, 2000, and January 1, 2015. A total of 17 publications met the set criteria and were included in the review. Overall, studies outlined characteristics for 4 insulin HUPs. Based on their functionality, the pens were generally similar and all met the ISO 11608-1 criteria for accuracy. However, some had specific advantageous features in terms of size, weight, design, dialing torque, and injection force. Although limited, the currently available user preference studies in children and adolescents with diabetes and their carers suggest that the selection of an HUP is likely to be influenced by a combination of factors such as these, in addition to the prescribed insulin and dosing regimen. Insulin HUPs are likely to be a key diabetes management tool for patients who are sensitive to insulin; specific pen features may further advance diabetes management in these populations.

Analytical Validation of Accelerator Mass Spectrometry for Pharmaceutical Development: the Measurement of Carbon-14 Isotope Ratio.

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

Keck, B D; Ognibene, T; Vogel, J S

2010-02-05

Accelerator mass spectrometry (AMS) is an isotope based measurement technology that utilizes carbon-14 labeled compounds in the pharmaceutical development process to measure compounds at very low concentrations, empowers microdosing as an investigational tool, and extends the utility of {sup 14}C labeled compounds to dramatically lower levels. It is a form of isotope ratio mass spectrometry that can provide either measurements of total compound equivalents or, when coupled to separation technology such as chromatography, quantitation of specific compounds. The properties of AMS as a measurement technique are investigated here, and the parameters of method validation are shown. AMS, independent of anymore » separation technique to which it may be coupled, is shown to be accurate, linear, precise, and robust. As the sensitivity and universality of AMS is constantly being explored and expanded, this work underpins many areas of pharmaceutical development including drug metabolism as well as absorption, distribution and excretion of pharmaceutical compounds as a fundamental step in drug development. The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of {sup 14}C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the {sup 14}C label), stable across samples storage conditions for at least one year, linear over 4 orders of magnitude with an analytical range from one tenth Modern to at least 2000 Modern (instrument specific). Further, accuracy was excellent between 1 and 3 percent while precision expressed as coefficient of variation is between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of carbon-14 (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with {sup 14}C corresponds to 30 fg equivalents. AMS provides an sensitive, accurate and precise method of measuring drug compounds in biological matrices.« less

Prediction of parturition in bitches utilizing continuous vaginal temperature measurement.

PubMed

Geiser, B; Burfeind, O; Heuwieser, W; Arlt, S

2014-02-01

The objective of this study was to determine sensitivity and specificity of a body temperature decline in bitches to predict parturition. Temperature loggers were placed into the vaginal cavity of 16 pregnant bitches on day 56-61 after estimated ovulation or first mating. This measurement technique has been validated previously and enabled continuous sampling of body temperature. The temperature loggers were expelled from the vagina before delivery of the first pup. The computed values for specificity (77-92%) were higher than sensitivity (53-69%), indicating a more precise prognosis of parturition not occurring. In conclusion, our findings may assist interpreting vaginal temperature measurements in order to predict parturition in bitches. © 2013 Blackwell Verlag GmbH.

A systematic review and meta-analysis of the diagnostic accuracy of point-of-care tests for the detection of hyperketonemia in dairy cows.

PubMed

Tatone, Elise H; Gordon, Jessica L; Hubbs, Jessie; LeBlanc, Stephen J; DeVries, Trevor J; Duffield, Todd F

2016-08-01

Several rapid tests for use on farm have been validated for the detection of hyperketonemia (HK) in dairy cattle, however the reported sensitivity and specificity of each method varies and no single study has compared them all. Meta-analysis of diagnostic test accuracy is becoming more common in human medical literature but there are few veterinary examples. The objective of this work was to perform a systematic review and meta-analysis to determine the point-of-care testing method with the highest combined sensitivity and specificity, the optimal threshold for each method, and to identify gaps in the literature. A comprehensive literature search resulted in 5196 references. After removing duplicates and performing relevance screening, 23 studies were included for the qualitative synthesis and 18 for the meta-analysis. The three index tests evaluated in the meta-analysis were: the Precision Xtra(®) handheld device measuring beta-hydroxybutyrate (BHB) concentration in whole blood, and Ketostix(®) and KetoTest(®) semi-quantitative strips measuring the concentration of acetoacetate in urine and BHB in milk, respectively. The diagnostic accuracy of the 3 index tests relative to the reference standard measurement of BHB in serum or whole blood between 1.0-1.4mmol/L was compared using the hierarchical summary receiver operator characteristic (HSROC) method. Subgroup analysis was conducted for each index test to examine the accuracy at different thresholds. The impact of the reference standard threshold, the reference standard method, the prevalence of HK in the population, the primary study source and risk of bias of the primary study was explored using meta-regression. The Precision Xtra(®) device had the highest summary sensitivity in whole blood BHB at 1.2mmol/L, 94.8% (CI95%: 92.6-97.0), and specificity, 97.5% (CI95%: 96.9-98.1). The threshold employed (1.2-1.4mmol/L) did not impact the diagnostic accuracy of the test. The Ketostix(®) and KetoTest(®) strips had the highest summary sensitivity and specificity when the trace and weak positive thresholds were used, respectively. Controlling for the source of publication, HK prevalence and reference standard employed did not impact the estimated sensitivity and specificity of the tests. Including only peer-reviewed studies reduced the number of primary studies evaluating the Precision Xtra(®) by 43% and Ketostix(®) by 33%. Diagnosing HK with blood, urine or milk are valid options, however, the diagnostic inaccuracy of urine and milk should be considered when making economic and treatment decisions. Copyright © 2016 Elsevier B.V. All rights reserved.

Comprehensive benchmarking of SNV callers for highly admixed tumor data

PubMed Central

Bohnert, Regina; Vivas, Sonia

2017-01-01

Precision medicine attempts to individualize cancer therapy by matching tumor-specific genetic changes with effective targeted therapies. A crucial first step in this process is the reliable identification of cancer-relevant variants, which is considerably complicated by the impurity and heterogeneity of clinical tumor samples. We compared the impact of admixture of non-cancerous cells and low somatic allele frequencies on the sensitivity and precision of 19 state-of-the-art SNV callers. We studied both whole exome and targeted gene panel data and up to 13 distinct parameter configurations for each tool. We found vast differences among callers. Based on our comprehensive analyses we recommend joint tumor-normal calling with MuTect, EBCall or Strelka for whole exome somatic variant calling, and HaplotypeCaller or FreeBayes for whole exome germline calling. For targeted gene panel data on a single tumor sample, LoFreqStar performed best. We further found that tumor impurity and admixture had a negative impact on precision, and in particular, sensitivity in whole exome experiments. At admixture levels of 60% to 90% sometimes seen in pathological biopsies, sensitivity dropped significantly, even when variants were originally present in the tumor at 100% allele frequency. Sensitivity to low-frequency SNVs improved with targeted panel data, but whole exome data allowed more efficient identification of germline variants. Effective somatic variant calling requires high-quality pathological samples with minimal admixture, a consciously selected sequencing strategy, and the appropriate variant calling tool with settings optimized for the chosen type of data. PMID:29020110

Performance of search strategies to retrieve systematic reviews of diagnostic test accuracy from the Cochrane Library.

PubMed

Huang, Yuansheng; Yang, Zhirong; Wang, Jing; Zhuo, Lin; Li, Zhixia; Zhan, Siyan

2016-05-06

To compare the performance of search strategies to retrieve systematic reviews of diagnostic test accuracy from The Cochrane Library. Databases of CDSR and DARE in the Cochrane Library were searched for systematic reviews of diagnostic test accuracy published between 2008 and 2012 through nine search strategies. Each strategy consists of one group or combination of groups of searching filters about diagnostic test accuracy. Four groups of diagnostic filters were used. The Strategy combing all the filters was used as the reference to determine the sensitivity, precision, and the sensitivity x precision product for another eight Strategies. The reference Strategy retrieved 8029 records, of which 832 were eligible. The strategy only composed of MeSH terms about "accuracy measures" achieved the highest values in both precision (69.71%) and product (52.45%) with a moderate sensitivity (75.24%). The combination of MeSH terms and free text words about "accuracy measures" contributed little to increasing the sensitivity. Strategies composed of filters about "diagnosis" had similar sensitivity but lower precision and product to those composed of filters about "accuracy measures". MeSH term "exp'diagnosis' " achieved the lowest precision (9.78%) and product (7.91%), while its hyponym retrieved only half the number of records at the expense of missing 53 target articles. The precision was negatively correlated with sensitivities among the nine strategies. Compared to the filters about "diagnosis", the filters about "accuracy measures" achieved similar sensitivities but higher precision. When combining both terms, sensitivity of the strategy was enhanced obviously. The combination of MeSH terms and free text words about the same concept seemed to be meaningless for enhancing sensitivity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

How Advances in Imaging Will Affect Precision Radiation Oncology.

PubMed

Jaffray, David A; Das, Shiva; Jacobs, Paula M; Jeraj, Robert; Lambin, Philippe

2018-06-01

Radiation oncology is 1 of the most structured disciplines in medicine. It is of a highly technical nature with reliance on robotic systems to deliver intervention, engagement of diverse expertise, and early adoption of digital approaches to optimize and execute the application of this highly effective cancer treatment. As a localized intervention, the dependence on sensitive, specific, and accurate imaging to define the extent of disease, its heterogeneity, and adjacency to normal tissues directly affects the therapeutic ratio. Image-based in vivo temporal monitoring of the response to treatment enables adaptation and further affects the therapeutic ratio. Thus, more precise intervention will enable fractionation schedules that better interoperate with advances such as immunotherapy. In the data set-rich era that promises precision and personalized medicine, the radiation oncology field will integrate these new data into highly protocoled pathways of care that begin with multimodality prediction and enable patient-specific adaptation of therapy based on quantitative measures of the individual's dose-volume temporal trajectory and midtherapy predictions of response. In addition to advancements in computed tomography imaging, emerging technologies, such as ultra-high-field magnetic resonance and molecular imaging will bring new information to the design of treatments. Next-generation image guided radiation therapy systems will inject high specificity and sensitivity data and stimulate adaptive replanning. In addition, a myriad of pre- and peritherapeutic markers derived from advances in molecular pathology (eg, tumor genomics), automated and comprehensive imaging analytics (eg, radiomics, tumor microenvironment), and many other emerging biomarkers (eg, circulating tumor cell assays) will need to be integrated to maximize the benefit of radiation therapy for an individual patient. We present a perspective on the promise and challenges of fully exploiting imaging data in the pursuit of personalized radiation therapy, drawing from the presentations and broader discussions at the 2016 American Society of Therapeutic Radiation Oncology-National Cancer Institute workshop on Precision Medicine in Radiation Oncology (Bethesda, MD). Copyright © 2018. Published by Elsevier Inc.

Finding knowledge translation articles in CINAHL.

PubMed

Lokker, Cynthia; McKibbon, K Ann; Wilczynski, Nancy L; Haynes, R Brian; Ciliska, Donna; Dobbins, Maureen; Davis, David A; Straus, Sharon E

2010-01-01

The process of moving research into practice has a number of names including knowledge translation (KT). Researchers and decision makers need to be able to readily access the literature on KT for the field to grow and to evaluate the existing evidence. To develop and validate search filters for finding KT articles in the database Cumulative Index to Nursing and Allied Health (CINAHL). A gold standard database was constructed by hand searching and classifying articles from 12 journals as KT Content, KT Applications and KT Theory. Sensitivity, specificity, precision, and accuracy of the search filters. Optimized search filters had fairly low sensitivity and specificity for KT Content (58.4% and 64.9% respectively), while sensitivity and specificity increased for retrieving KT Application (67.5% and 70.2%) and KT Theory articles (70.4% and 77.8%). Search filter performance was suboptimal marking the broad base of disciplines and vocabularies used by KT researchers. Such diversity makes retrieval of KT studies in CINAHL difficult.

Water vapor δ(2) H, δ(18) O and δ(17) O measurements using an off-axis integrated cavity output spectrometer - sensitivity to water vapor concentration, delta value and averaging-time.

PubMed

Tian, Chao; Wang, Lixin; Novick, Kimberly A

2016-10-15

High-precision analysis of atmospheric water vapor isotope compositions, especially δ(17) O values, can be used to improve our understanding of multiple hydrological and meteorological processes (e.g., differentiate equilibrium or kinetic fractionation). This study focused on assessing, for the first time, how the accuracy and precision of vapor δ(17) O laser spectroscopy measurements depend on vapor concentration, delta range, and averaging-time. A Triple Water Vapor Isotope Analyzer (T-WVIA) was used to evaluate the accuracy and precision of δ(2) H, δ(18) O and δ(17) O measurements. The sensitivity of accuracy and precision to water vapor concentration was evaluated using two international standards (GISP and SLAP2). The sensitivity of precision to delta value was evaluated using four working standards spanning a large delta range. The sensitivity of precision to averaging-time was assessed by measuring one standard continuously for 24 hours. Overall, the accuracy and precision of the δ(2) H, δ(18) O and δ(17) O measurements were high. Across all vapor concentrations, the accuracy of δ(2) H, δ(18) O and δ(17) O observations ranged from 0.10‰ to 1.84‰, 0.08‰ to 0.86‰ and 0.06‰ to 0.62‰, respectively, and the precision ranged from 0.099‰ to 0.430‰, 0.009‰ to 0.080‰ and 0.022‰ to 0.054‰, respectively. The accuracy and precision of all isotope measurements were sensitive to concentration, with the higher accuracy and precision generally observed under moderate vapor concentrations (i.e., 10000-15000 ppm) for all isotopes. The precision was also sensitive to the range of delta values, although the effect was not as large compared with the sensitivity to concentration. The precision was much less sensitive to averaging-time than the concentration and delta range effects. The accuracy and precision performance of the T-WVIA depend on concentration but depend less on the delta value and averaging-time. The instrument can simultaneously and continuously measure δ(2) H, δ(18) O and δ(17) O values in water vapor, opening a new window to better understand ecological, hydrological and meteorological processes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Precision forging technology for aluminum alloy

NASA Astrophysics Data System (ADS)

Deng, Lei; Wang, Xinyun; Jin, Junsong; Xia, Juchen

2018-03-01

Aluminum alloy is a preferred metal material for lightweight part manufacturing in aerospace, automobile, and weapon industries due to its good physical properties, such as low density, high specific strength, and good corrosion resistance. However, during forging processes, underfilling, folding, broken streamline, crack, coarse grain, and other macro- or microdefects are easily generated because of the deformation characteristics of aluminum alloys, including narrow forgeable temperature region, fast heat dissipation to dies, strong adhesion, high strain rate sensitivity, and large flow resistance. Thus, it is seriously restricted for the forged part to obtain precision shape and enhanced property. In this paper, progresses in precision forging technologies of aluminum alloy parts were reviewed. Several advanced precision forging technologies have been developed, including closed die forging, isothermal die forging, local loading forging, metal flow forging with relief cavity, auxiliary force or vibration loading, casting-forging hybrid forming, and stamping-forging hybrid forming. High-precision aluminum alloy parts can be realized by controlling the forging processes and parameters or combining precision forging technologies with other forming technologies. The development of these technologies is beneficial to promote the application of aluminum alloys in manufacturing of lightweight parts.

Simultaneous Determination of Eight Hypotensive Drugs of Various Chemical Groups in Pharmaceutical Preparations by HPLC-DAD.

PubMed

Stolarczyk, Mariusz; Hubicka, Urszula; Żuromska-Witek, Barbara; Krzek, Jan

2015-01-01

A new sensitive, simple, rapid, and precise HPLC method with diode array detection has been developed for separation and simultaneous determination of hydrochlorothiazide, furosemide, torasemide, losartane, quinapril, valsartan, spironolactone, and canrenone in combined pharmaceutical dosage forms. The chromatographic analysis of the tested drugs was performed on an ACE C18, 100 Å, 250×4.6 mm, 5 μm particle size column with 0.0.05 M phosphate buffer (pH=3.00)-acetonitrile-methanol (30+20+50 v/v/v) mobile phase at a flow rate of 1.0 mL/min. The column was thermostatted at 25°C. UV detection was performed at 230 nm. Analysis time was 10 min. The elaborated method meets the acceptance criteria for specificity, linearity, sensitivity, accuracy, and precision. The proposed method was successfully applied for the determination of the studied drugs in the selected combined dosage forms.

Optogenetic Functional MRI

PubMed Central

Lin, Peter; Fang, Zhongnan; Liu, Jia; Lee, Jin Hyung

2016-01-01

The investigation of the functional connectivity of precise neural circuits across the entire intact brain can be achieved through optogenetic functional magnetic resonance imaging (ofMRI), which is a novel technique that combines the relatively high spatial resolution of high-field fMRI with the precision of optogenetic stimulation. Fiber optics that enable delivery of specific wavelengths of light deep into the brain in vivo are implanted into regions of interest in order to specifically stimulate targeted cell types that have been genetically induced to express light-sensitive trans-membrane conductance channels, called opsins. fMRI is used to provide a non-invasive method of determining the brain's global dynamic response to optogenetic stimulation of specific neural circuits through measurement of the blood-oxygen-level-dependent (BOLD) signal, which provides an indirect measurement of neuronal activity. This protocol describes the construction of fiber optic implants, the implantation surgeries, the imaging with photostimulation and the data analysis required to successfully perform ofMRI. In summary, the precise stimulation and whole-brain monitoring ability of ofMRI are crucial factors in making ofMRI a powerful tool for the study of the connectomics of the brain in both healthy and diseased states. PMID:27167840

Sonophoresis for Rapid Assessment of Interstitial Fluid and Drug Delivery

DTIC Science & Technology

2007-10-01

sensitive indicator of local diseases, for example skin cancer, psoriasis and eczema , but also of certain systemic diseases such as cardiovascular disease...cytokine " functionality -map" that precisely represents skin’s specific diseased milieu (Fig. 2b-CI and Fig. 3a-AD and PS, 3 additional data in. Supp...yielded a unique cytokine " functionality map", which correlates with the specific diseased state (figure 2d and 3a). A striking, rapid upregulation was

An optimal search filter for retrieving systematic reviews and meta-analyses

PubMed Central

2012-01-01

Background Health-evidence.ca is an online registry of systematic reviews evaluating the effectiveness of public health interventions. Extensive searching of bibliographic databases is required to keep the registry up to date. However, search filters have been developed to assist in searching the extensive amount of published literature indexed. Search filters can be designed to find literature related to a certain subject (i.e. content-specific filter) or particular study designs (i.e. methodological filter). The objective of this paper is to describe the development and validation of the health-evidence.ca Systematic Review search filter and to compare its performance to other available systematic review filters. Methods This analysis of search filters was conducted in MEDLINE, EMBASE, and CINAHL. The performance of thirty-one search filters in total was assessed. A validation data set of 219 articles indexed between January 2004 and December 2005 was used to evaluate performance on sensitivity, specificity, precision and the number needed to read for each filter. Results Nineteen of 31 search filters were effective in retrieving a high level of relevant articles (sensitivity scores greater than 85%). The majority achieved a high degree of sensitivity at the expense of precision and yielded large result sets. The main advantage of the health-evidence.ca Systematic Review search filter in comparison to the other filters was that it maintained the same level of sensitivity while reducing the number of articles that needed to be screened. Conclusions The health-evidence.ca Systematic Review search filter is a useful tool for identifying published systematic reviews, with further screening to identify those evaluating the effectiveness of public health interventions. The filter that narrows the focus saves considerable time and resources during updates of this online resource, without sacrificing sensitivity. PMID:22512835

Evaluation of a Commercial Glycoprotein Enzyme-Linked Immunosorbent Assay for Measuring Vaccine Immunity to Varicella

PubMed Central

Kim, Yun Hwa; Hwang, Ji Young; Shim, Hye Min; Lee, Eunsil; Park, Songyong

2014-01-01

Purpose To evaluate a recently marketed commercial glycoprotein enzyme-linked immunosorbent assay (gpEIA) kit, the VaccZyme™ VZV gpEIA, for measuring the immunity of varicella-vaccinated children. Materials and Methods We investigated the accuracy and reproducibility of the VaccZyme™ VZV gpEIA kit for the detection of antibodies to VZV. We also examined the sensitivity, specificity, and correlation between antibody titers calculated with gpEIA versus fluorescent antibody to membrane antigen (FAMA) by using sera of 349 children, ranging from 1 to 6 years old. Results VaccZyme™ VZV gpEIA gave precise and reproducible intra- and inter-assay results. FAMA and gpEIA titers showed a linear correlation (Pearson correlation coefficient=0.987). The sensitivity and specificity of the VaccZyme™ gpEIA was 31.4% and 100%, respectively, when the guidelines of the gpEIA (<100 mIU/mL) and FAMA 1:4 were adopted as cutoff values. However, the maximum sensitivity and specificity were 88.9% and 95.1%, respectively, with the highest correlation (κ=0.840), if the cutoff values were set with gpEIA at 49.7 mIU/mL and FAMA 1:16. Conclusion These results demonstrate that the VaccZyme™ VZV gpEIA kit gave precise and reproducible data for measuring antibody titer after varicella vaccination. The results also showed that the antibody titer calculated with the VaccZyme™ gpEIA kit strongly correlated with the FAMA titer. However, cutoff values should be re-optimized for the evaluation of vaccine immunity. PMID:24532518

A novel high sensitivity HPLC assay for topiramate, using 4-chloro-7-nitrobenzofurazan as pre-column fluorescence derivatizing agent.

PubMed

Bahrami, Gholamreza; Mohammadi, Bahareh

2007-05-01

A new, sensitive and simple high-performance liquid chromatographic method for analysis of topiramate, an antiepileptic agent, using 4-chloro-7-nitrobenzofurazan as pre-column derivatization agent is described. Following liquid-liquid extraction of topiramate and an internal standard (amlodipine) from human serum, derivatization of the drugs was performed by the labeling agent in the presence of dichloromethane, methanol, acetonitrile and borate buffer (0.05 M; pH 10.6). A mixture of sodium phosphate buffer (0.05 M; pH 2.4): methanol (35:65 v/v) was eluted as mobile phase and chromatographic separation was achieved using a Shimpack CLC-C18 (150 x 4.6 mm) column. In this method the limit of quantification of 0.01 microg/mL was obtained and the procedure was validated over the concentration range of 0.01 to 12.8 microg/mL. No interferences were found from commonly co-administrated antiepileptic drugs including phenytoin, phenobarbital carbamazepine, lamotrigine, zonisamide, primidone, gabapentin, vigabatrin, and ethosuximide. The analysis performance was carried-out in terms of specificity, sensitivity, linearity, precision, accuracy and stability and the method was shown to be accurate, with intra-day and inter-day accuracy from -3.4 to 10% and precise, with intra-day and inter-day precision from 1.1 to 18%.

[Usefulness of scoring risk for adverse outcomes in older patients with the Identification of Seniors at Risk scale and the Triage Risk Screening Tool: a meta-analysis].

PubMed

Rivero-Santana, Amado; Del Pino-Sedeño, Tasmania; Ramallo-Fariña, Yolanda; Vergara, Itziar; Serrano-Aguilar, Pedro

2017-02-01

A considerable proportion of the geriatric population experiences unfavorable outcomes of hospital emergency department care. An assessment of risk for adverse outcomes would facilitate making changes in clinical management by adjusting available resources to needs according to an individual patient's risk. Risk assessment tools are available, but their prognostic precision varies. This systematic review sought to quantify the prognostic precision of 2 geriatric screening and risk assessment tools commonly used in emergency settings for patients at high risk of adverse outcomes (revisits, functional deterioration, readmissions, or death): the Identification of Seniors at Risk (ISAR) scale and the Triage Risk Screening Tool (TRST). We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and SCOPUS, with no date limits, to find relevant studies. Quality was assessed with the QUADAS-2 checklist (for quality assessment of diagnostic accuracy studies). We pooled data for prognostic yield reported for the ISAR and TRST scores for each short- and medium-term outcome using bivariate random-effects modeling. The sensitivity of the ISAR scoring system as a whole ranged between 67% and 99%; specificity fell between 21% and 41%. TRST sensitivity ranged between 52% and 75% and specificity between 39% and 51%.We conclude that the tools currently used to assess risk of adverse outcomes in patients of advanced age attended in hospital emergency departments do not have adequate prognostic precision to be clinically useful.

Improving 14C dating precision in dynamic, brackish waters by one order of magnitude: 87Sr/86Sr isotopes as a quantitative proxy for 14C reservoir age.

NASA Astrophysics Data System (ADS)

Lougheed, B.; Davies, G.; Filipsson, H. L.; van der Lubbe, J.; Snowball, I.

2016-12-01

Accurate geochronologies are crucial for reconstructing the sensitivity of brackish and estuarine environments to external impacts. A common geochronological method used for such studies is radiocarbon (14C) dating, but its application in brackish environments is severely limited by an inability to quantify spatiotemporal variations in 14C reservoir age, or R(t), due to dynamic interplay between river runoff and marine water in these environments. Additionally, old carbon effects and species-specific behavioural processes also influence 14C ages. Using the world's largest brackish water body (the estuarine Baltic Sea) as a test-bed, combined with a comprehensive approach that objectively excludes both old carbon and species-specific effects, we demonstrate that it is possible to use 87Sr/86Sr ratios to quantify R(t) in ubiquitous mollusc shell material, leading to an almost one order of magnitude increase in Baltic Sea 14C geochronological precision over the current state-of-the-art. We propose that this novel proxy method can be developed for other brackish water bodies worldwide, thereby improving geochronological control in these climate sensitive, near-coastal environments.

Understanding and comparisons of different sampling approaches for the Fourier Amplitudes Sensitivity Test (FAST)

PubMed Central

Xu, Chonggang; Gertner, George

2013-01-01

Fourier Amplitude Sensitivity Test (FAST) is one of the most popular uncertainty and sensitivity analysis techniques. It uses a periodic sampling approach and a Fourier transformation to decompose the variance of a model output into partial variances contributed by different model parameters. Until now, the FAST analysis is mainly confined to the estimation of partial variances contributed by the main effects of model parameters, but does not allow for those contributed by specific interactions among parameters. In this paper, we theoretically show that FAST analysis can be used to estimate partial variances contributed by both main effects and interaction effects of model parameters using different sampling approaches (i.e., traditional search-curve based sampling, simple random sampling and random balance design sampling). We also analytically calculate the potential errors and biases in the estimation of partial variances. Hypothesis tests are constructed to reduce the effect of sampling errors on the estimation of partial variances. Our results show that compared to simple random sampling and random balance design sampling, sensitivity indices (ratios of partial variances to variance of a specific model output) estimated by search-curve based sampling generally have higher precision but larger underestimations. Compared to simple random sampling, random balance design sampling generally provides higher estimation precision for partial variances contributed by the main effects of parameters. The theoretical derivation of partial variances contributed by higher-order interactions and the calculation of their corresponding estimation errors in different sampling schemes can help us better understand the FAST method and provide a fundamental basis for FAST applications and further improvements. PMID:24143037

Understanding and comparisons of different sampling approaches for the Fourier Amplitudes Sensitivity Test (FAST).

PubMed

Xu, Chonggang; Gertner, George

2011-01-01

Fourier Amplitude Sensitivity Test (FAST) is one of the most popular uncertainty and sensitivity analysis techniques. It uses a periodic sampling approach and a Fourier transformation to decompose the variance of a model output into partial variances contributed by different model parameters. Until now, the FAST analysis is mainly confined to the estimation of partial variances contributed by the main effects of model parameters, but does not allow for those contributed by specific interactions among parameters. In this paper, we theoretically show that FAST analysis can be used to estimate partial variances contributed by both main effects and interaction effects of model parameters using different sampling approaches (i.e., traditional search-curve based sampling, simple random sampling and random balance design sampling). We also analytically calculate the potential errors and biases in the estimation of partial variances. Hypothesis tests are constructed to reduce the effect of sampling errors on the estimation of partial variances. Our results show that compared to simple random sampling and random balance design sampling, sensitivity indices (ratios of partial variances to variance of a specific model output) estimated by search-curve based sampling generally have higher precision but larger underestimations. Compared to simple random sampling, random balance design sampling generally provides higher estimation precision for partial variances contributed by the main effects of parameters. The theoretical derivation of partial variances contributed by higher-order interactions and the calculation of their corresponding estimation errors in different sampling schemes can help us better understand the FAST method and provide a fundamental basis for FAST applications and further improvements.

Molecular Detection of 10 of the Most Unwanted Alien Forest Pathogens in Canada Using Real-Time PCR

PubMed Central

Lamarche, Josyanne; Potvin, Amélie; Pelletier, Gervais; Stewart, Don; Feau, Nicolas; Alayon, Dario I. O.; Dale, Angela L.; Coelho, Aaron; Uzunovic, Adnan; Bilodeau, Guillaume J.; Brière, Stephan C.; Hamelin, Richard C.; Tanguay, Philippe

2015-01-01

Invasive alien tree pathogens can cause significant economic losses as well as large-scale damage to natural ecosystems. Early detection to prevent their establishment and spread is an important approach used by several national plant protection organizations (NPPOs). Molecular detection tools targeting 10 of the most unwanted alien forest pathogens in Canada were developed as part of the TAIGA project (http://taigaforesthealth.com/). Forest pathogens were selected following an independent prioritization. Specific TaqMan real-time PCR detection assays were designed to function under homogeneous conditions so that they may be used in 96- or 384-well plate format arrays for high-throughput testing of large numbers of samples against multiple targets. Assays were validated for 1) specificity, 2) sensitivity, 3) precision, and 4) robustness on environmental samples. All assays were highly specific when evaluated against a panel of pure cultures of target and phylogenetically closely-related species. Sensitivity, evaluated by assessing the limit of detection (with a threshold of 95% of positive samples), was found to be between one and ten target gene region copies. Precision or repeatability of each assay revealed a mean coefficient of variation of 3.4%. All assays successfully allowed detection of target pathogen on positive environmental samples, without any non-specific amplification. These molecular detection tools will allow for rapid and reliable detection of 10 of the most unwanted alien forest pathogens in Canada. PMID:26274489

Identifying nurse staffing research in Medline: development and testing of empirically derived search strategies with the PubMed interface

PubMed Central

2010-01-01

Background The identification of health services research in databases such as PubMed/Medline is a cumbersome task. This task becomes even more difficult if the field of interest involves the use of diverse methods and data sources, as is the case with nurse staffing research. This type of research investigates the association between nurse staffing parameters and nursing and patient outcomes. A comprehensively developed search strategy may help identify nurse staffing research in PubMed/Medline. Methods A set of relevant references in PubMed/Medline was identified by means of three systematic reviews. This development set was used to detect candidate free-text and MeSH terms. The frequency of these terms was compared to a random sample from PubMed/Medline in order to identify terms specific to nurse staffing research, which were then used to develop a sensitive, precise and balanced search strategy. To determine their precision, the newly developed search strategies were tested against a) the pool of relevant references extracted from the systematic reviews, b) a reference set identified from an electronic journal screening, and c) a sample from PubMed/Medline. Finally, all newly developed strategies were compared to PubMed's Health Services Research Queries (PubMed's HSR Queries). Results The sensitivities of the newly developed search strategies were almost 100% in all of the three test sets applied; precision ranged from 6.1% to 32.0%. PubMed's HSR queries were less sensitive (83.3% to 88.2%) than the new search strategies. Only minor differences in precision were found (5.0% to 32.0%). Conclusions As with other literature on health services research, nurse staffing studies are difficult to identify in PubMed/Medline. Depending on the purpose of the search, researchers can choose between high sensitivity and retrieval of a large number of references or high precision, i.e. and an increased risk of missing relevant references, respectively. More standardized terminology (e.g. by consistent use of the term "nurse staffing") could improve the precision of future searches in this field. Empirically selected search terms can help to develop effective search strategies. The high consistency between all test sets confirmed the validity of our approach. PMID:20731858

Identifying nurse staffing research in Medline: development and testing of empirically derived search strategies with the PubMed interface.

PubMed

Simon, Michael; Hausner, Elke; Klaus, Susan F; Dunton, Nancy E

2010-08-23

The identification of health services research in databases such as PubMed/Medline is a cumbersome task. This task becomes even more difficult if the field of interest involves the use of diverse methods and data sources, as is the case with nurse staffing research. This type of research investigates the association between nurse staffing parameters and nursing and patient outcomes. A comprehensively developed search strategy may help identify nurse staffing research in PubMed/Medline. A set of relevant references in PubMed/Medline was identified by means of three systematic reviews. This development set was used to detect candidate free-text and MeSH terms. The frequency of these terms was compared to a random sample from PubMed/Medline in order to identify terms specific to nurse staffing research, which were then used to develop a sensitive, precise and balanced search strategy. To determine their precision, the newly developed search strategies were tested against a) the pool of relevant references extracted from the systematic reviews, b) a reference set identified from an electronic journal screening, and c) a sample from PubMed/Medline. Finally, all newly developed strategies were compared to PubMed's Health Services Research Queries (PubMed's HSR Queries). The sensitivities of the newly developed search strategies were almost 100% in all of the three test sets applied; precision ranged from 6.1% to 32.0%. PubMed's HSR queries were less sensitive (83.3% to 88.2%) than the new search strategies. Only minor differences in precision were found (5.0% to 32.0%). As with other literature on health services research, nurse staffing studies are difficult to identify in PubMed/Medline. Depending on the purpose of the search, researchers can choose between high sensitivity and retrieval of a large number of references or high precision, i.e. and an increased risk of missing relevant references, respectively. More standardized terminology (e.g. by consistent use of the term "nurse staffing") could improve the precision of future searches in this field. Empirically selected search terms can help to develop effective search strategies. The high consistency between all test sets confirmed the validity of our approach.

Solar neutrino detection in a large volume double-phase liquid argon experiment

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

Franco, D.; Agnes, P.; Giganti, C.

2016-08-01

Precision measurements of solar neutrinos emitted by specific nuclear reaction chains in the Sun are of great interest for developing an improved understanding of star formation and evolution. Given the expected neutrino fluxes and known detection reactions, such measurements require detectors capable of collecting neutrino-electron scattering data in exposures on the order of 1 ktonne-yr, with good energy resolution and extremely low background. Two-phase liquid argon time projection chambers (LAr TPCs) are under development for direct Dark Matter WIMP searches, which possess very large sensitive mass, high scintillation light yield, good energy resolution, and good spatial resolution in all threemore » cartesian directions. While enabling Dark Matter searches with sensitivity extending to the ''neutrino floor'' (given by the rate of nuclear recoil events from solar neutrino coherent scattering), such detectors could also enable precision measurements of solar neutrino fluxes using the neutrino-electron elastic scattering events. Modeling results are presented for the cosmogenic and radiogenic backgrounds affecting solar neutrino detection in a 300 tonne (100 tonne fiducial) LAr TPC operating at LNGS depth (3,800 meters of water equivalent). The results show that such a detector could measure the CNO neutrino rate with ∼15% precision, and significantly improve the precision of the {sup 7}Be and pep neutrino rates compared to the currently available results from the Borexino organic liquid scintillator detector.« less

Simultaneous ultramicroanalysis of both 17-keto-and 17beta-hydroxy androgens in biological fluids.

PubMed

Ganjam, V K

1976-11-01

Sensitive methods for quantifying androgens were lacking. Therefore, a relatively simple procedure for separating steroids was combined with highly specific assay methods so that eight androgens could be measured with high accuracy, precision and sensitivity. Semi-automated separations on Sephadex LH-20 columns used heptane:methylene chloride:ethanol:water (50:50:1:0.12) and a flow rate of 17.0 min/ml. The six peaks eluted contained androstenedine; androsterone, epiandrosterone and dihydrotestosterone; testosterone and dehydroepiandrosterone; 3alpha-androstanediol; 3beta-androstanediol; and androstenediol. Androstenedione, dehydroepiandrosterone and androstenediol were quantified using specific antisera (sensitivity less than or equal to 75 pg). Testosterone and dihydrotestosterone were measured by competitive protein-binding assays using rabbit TeBG (sensitivity less than or equal to 150 pg). 3alpha- and 3beta-androstanediol were similarly assayed using human TeBG (sensitivity approximately 150 pg). Androsterone was reduced with NaBH4 and the resulting 3alpha-androstanediol was assayed using human TeBG (sensitivity approximately 200 pg). Inter- and intra-assay variations were less than 10% for radioimmunoassays and less than 16% for competitive protein-binding assays over the entire dose response curve.

Simultaneous quantification of withanolides in Withania somnifera by a validated high-performance thin-layer chromatographic method.

PubMed

Srivastava, Pooja; Tiwari, Neerja; Yadav, Akhilesh K; Kumar, Vijendra; Shanker, Karuna; Verma, Ram K; Gupta, Madan M; Gupta, Anil K; Khanuja, Suman P S

2008-01-01

This paper describes a sensitive, selective, specific, robust, and validated densitometric high-performance thin-layer chromatographic (HPTLC) method for the simultaneous determination of 3 key withanolides, namely, withaferin-A, 12-deoxywithastramonolide, and withanolide-A, in Ashwagandha (Withania somnifera) plant samples. The separation was performed on aluminum-backed silica gel 60F254 HPTLC plates using dichloromethane-methanol-acetone-diethyl ether (15 + 1 + 1 + 1, v/v/v/v) as the mobile phase. The withanolides were quantified by densitometry in the reflection/absorption mode at 230 nm. Precise and accurate quantification could be performed in the linear working concentration range of 66-330 ng/band with good correlation (r2 = 0.997, 0.999, and 0.996, respectively). The method was validated for recovery, precision, accuracy, robustness, limit of detection, limit of quantitation, and specificity according to International Conference on Harmonization guidelines. Specificity of quantification was confirmed using retention factor (Rf) values, UV-Vis spectral correlation, and electrospray ionization mass spectra of marker compounds in sample tracks.

Utility of ultrasonography for diagnosis of superficial swellings in buffalo (Bubalus bubalis)

PubMed Central

ABOUELNASR, Khaled; EL-SHAFAEY, El-Sayed; MOSBAH, Esam; EL-KHODERY, Sabry

2016-01-01

We studied 72 buffalo with superficial swellings in the head (n=4), neck (n=5), chest wall (n=4), abdominal wall (n=28), limbs (n=16), gluteal region (n=8), perineal region (n=6) and udder (n=1). Ultrasonographically, the swellings varied according to type, duration, content and location. The clinical use of ultrasound to assess these superficial swellings allowed diagnosis of abscesses (n=21), hematomas (n=11), hernias (n=17), bursitis (n=13), urethral diverticula (n=6) and tumors (n=4). Ultrasonography could precisely discriminate each lesion type (sensitivity, 71–100%; specificity, 75–100%; odds ratio, 1.0–8.4; Confidence Interval, 74.2–20; and P value 0.001). The specificity for ultrasonographic evaluation of superficial swellings was 100% for hernias, urethral diverticula and tumors, whilst the lowest specificity was recorded for hematomas (75%) and abscesses (92%). In conclusion, ultrasonography provides a precise, non-invasive and fast technique for the evaluation, classification and subsequent treatment of a variety of superficial swellings in buffalo. PMID:27181085

Accounting for regional variation in both natural environment and human disturbance to improve performance of multimetric indices of lotic benthic diatoms.

PubMed

Tang, Tao; Stevenson, R Jan; Infante, Dana M

2016-10-15

Regional variation in both natural environment and human disturbance can influence performance of ecological assessments. In this study we calculated 5 types of benthic diatom multimetric indices (MMIs) with 3 different approaches to account for variation in ecological assessments. We used: site groups defined by ecoregions or diatom typologies; the same or different sets of metrics among site groups; and unmodeled or modeled MMIs, where models accounted for natural variation in metrics within site groups by calculating an expected reference condition for each metric and each site. We used data from the USEPA's National Rivers and Streams Assessment to calculate the MMIs and evaluate changes in MMI performance. MMI performance was evaluated with indices of precision, bias, responsiveness, sensitivity and relevancy which were respectively measured as MMI variation among reference sites, effects of natural variables on MMIs, difference between MMIs at reference and highly disturbed sites, percent of highly disturbed sites properly classified, and relation of MMIs to human disturbance and stressors. All 5 types of MMIs showed considerable discrimination ability. Using different metrics among ecoregions sometimes reduced precision, but it consistently increased responsiveness, sensitivity, and relevancy. Site specific metric modeling reduced bias and increased responsiveness. Combined use of different metrics among site groups and site specific modeling significantly improved MMI performance irrespective of site grouping approach. Compared to ecoregion site classification, grouping sites based on diatom typologies improved precision, but did not improve overall performance of MMIs if we accounted for natural variation in metrics with site specific models. We conclude that using different metrics among ecoregions and site specific metric modeling improve MMI performance, particularly when used together. Applications of these MMI approaches in ecological assessments introduced a tradeoff with assessment consistency when metrics differed across site groups, but they justified the convenient and consistent use of ecoregions. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid and specific detection of Asian- and African-lineage Zika viruses

PubMed Central

Chotiwan, Nunya; Brewster, Connie D.; Magalhaes, Tereza; Weger-Lucarelli, James; Duggal, Nisha K.; Rückert, Claudia; Nguyen, Chilinh; Garcia Luna, Selene M.; Fauver, Joseph R.; Andre, Barb; Gray, Meg; Black, William C.; Kading, Rebekah C.; Ebel, Gregory D.; Kuan, Guillermina; Balmaseda, Angel; Jaenisch, Thomas; Marques, Ernesto T. A.; Brault, Aaron C.; Harris, Eva; Foy, Brian D.; Quackenbush, Sandra L.; Perera, Rushika; Rovnak, Joel

2017-01-01

Understanding the dynamics of Zika virus transmission and formulating rational strategies for its control require precise diagnostic tools that are also appropriate for resource-poor environments. We have developed a rapid and sensitive loop-mediated isothermal amplification (LAMP) assay that distinguishes Zika viruses of Asian and African lineages. The assay does not detect chikungunya virus or flaviviruses such as dengue, yellow fever, or West Nile viruses. The assay conditions allowed direct detection of Zika virus RNA in cultured infected cells; in mosquitoes; in virus-spiked samples of human blood, plasma, saliva, urine, and semen; and in infected patient serum, plasma, and semen samples without the need for RNA isolation or reverse transcription. The assay offers rapid, specific, sensitive, and inexpensive detection of the Asian-lineage Zika virus strain that is currently circulating in the Western hemisphere, and can also detect the African-lineage Zika virus strain using separate, specific primers. PMID:28469032

Evaluation of the Q analyzer, a new cap-piercing fully automated coagulometer with clotting, chromogenic, and immunoturbidometric capability.

PubMed

Kitchen, Steve; Woolley, Anita

2013-01-01

The Q analyzer is a recently launched fully automated photo-optical analyzer equipped with primary tube cap-piercing and capable of clotting, chromogenic, and immunoturbidometric tests. The purpose of the present study was to evaluate the performance characteristics of the Q analyzer with reagents from the instrument manufacturer. We assessed precision and throughput when performing coagulation screening tests, prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen assay by Clauss assay. We compared results with established reagent instrument combinations in widespread use. Precision of PT/INR and APTT was acceptable as indicated by total precision of around 3%. The time to first result was 3  min for an INR and 5  min for PT/APTT. The system produced 115 completed samples per hour when processing only INRs and 60 samples (120 results) per hour for PT/APTT combined. The sensitivity of the DG-APTT Synth/Q method to mild deficiency of factor VIII (FVIII), IX, and XI was excellent (as indicated by APTTs being prolonged above the upper limit of the reference range). The Q analyzer was associated with high precision, acceptable throughput, and good reliability. When used in combination with DG-PT reagent and manufacturer's instrument-specific international sensitivity index, the INRs obtained were accurate. The Q analyzer with DG-APTT Synth reagent demonstrated good sensitivity to isolated mild deficiency of FVIII, IX, and XI and had the advantage of relative insensitivity to mild FXII deficiency. Taken together, our data indicate that the Q hemostasis analyzer was suitable for routine use in combination with the reagents evaluated.

Attaining the Photometric Precision Required by Future Dark Energy Projects

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

Stubbs, Christopher

2013-01-21

This report outlines our progress towards achieving the high-precision astronomical measurements needed to derive improved constraints on the nature of the Dark Energy. Our approach to obtaining higher precision flux measurements has two basic components: 1) determination of the optical transmission of the atmosphere, and 2) mapping out the instrumental photon sensitivity function vs. wavelength, calibrated by referencing the measurements to the known sensitivity curve of a high precision silicon photodiode, and 3) using the self-consistency of the spectrum of stars to achieve precise color calibrations.

Search Strategy to Identify Dental Survival Analysis Articles Indexed in MEDLINE.

PubMed

Layton, Danielle M; Clarke, Michael

2016-01-01

Articles reporting survival outcomes (time-to-event outcomes) in patients over time are challenging to identify in the literature. Research shows the words authors use to describe their dental survival analyses vary, and that allocation of medical subject headings by MEDLINE indexers is inconsistent. Together, this undermines accurate article identification. The present study aims to develop and validate a search strategy to identify dental survival analyses indexed in MEDLINE (Ovid). A gold standard cohort of articles was identified to derive the search terms, and an independent gold standard cohort of articles was identified to test and validate the proposed search strategies. The first cohort included all 6,955 articles published in the 50 dental journals with the highest impact factors in 2008, of which 95 articles were dental survival articles. The second cohort included all 6,514 articles published in the 50 dental journals with the highest impact factors for 2012, of which 148 were dental survival articles. Each cohort was identified by a systematic hand search. Performance parameters of sensitivity, precision, and number needed to read (NNR) for the search strategies were calculated. Sensitive, precise, and optimized search strategies were developed and validated. The performances of the search strategy maximizing sensitivity were 92% sensitivity, 14% precision, and 7.11 NNR; the performances of the strategy maximizing precision were 93% precision, 10% sensitivity, and 1.07 NNR; and the performances of the strategy optimizing the balance between sensitivity and precision were 83% sensitivity, 24% precision, and 4.13 NNR. The methods used to identify search terms were objective, not subjective. The search strategies were validated in an independent group of articles that included different journals and different publication years. Across the three search strategies, dental survival articles can be identified with sensitivity up to 92%, precision up to 93%, and NNR of less than two articles to identify relevant records. This research has highlighted the impact that variation in reporting and indexing has on article identification and has improved researchers' ability to identify dental survival articles.

Synthetic Gene Expression Circuits for Designing Precision Tools in Oncology

PubMed Central

Re, Angela

2017-01-01

Precision medicine in oncology needs to enhance its capabilities to match diagnostic and therapeutic technologies to individual patients. Synthetic biology streamlines the design and construction of functionalized devices through standardization and rational engineering of basic biological elements decoupled from their natural context. Remarkable improvements have opened the prospects for the availability of synthetic devices of enhanced mechanism clarity, robustness, sensitivity, as well as scalability and portability, which might bring new capabilities in precision cancer medicine implementations. In this review, we begin by presenting a brief overview of some of the major advances in the engineering of synthetic genetic circuits aimed to the control of gene expression and operating at the transcriptional, post-transcriptional/translational, and post-translational levels. We then focus on engineering synthetic circuits as an enabling methodology for the successful establishment of precision technologies in oncology. We describe significant advancements in our capabilities to tailor synthetic genetic circuits to specific applications in tumor diagnosis, tumor cell- and gene-based therapy, and drug delivery. PMID:28894736

Cognitive and Neural Bases of Skilled Performance.

DTIC Science & Technology

1987-10-04

advantage is that this method is not computationally demanding, and model -specific analyses such as high -precision source localization with realistic...and a two- < " high -threshold model satisfy theoretical and pragmatic independence. Discrimination and bias measures from these two models comparing...recognition memory of patients with dementing diseases, amnesics, and normal controls. We found the two- high -threshold model to be more sensitive Lloyd

Quantitative molecular analysis in mantle cell lymphoma.

PubMed

Brízová, H; Hilská, I; Mrhalová, M; Kodet, R

2011-07-01

A molecular analysis has three major roles in modern oncopathology--as an aid in the differential diagnosis, in molecular monitoring of diseases, and in estimation of the potential prognosis. In this report we review the application of the molecular analysis in a group of patients with mantle cell lymphoma (MCL). We demonstrate that detection of the cyclin D1 mRNA level is a molecular marker in 98% of patients with MCL. Cyclin D1 quantitative monitoring is specific and sensitive for the differential diagnosis and for the molecular monitoring of the disease in the bone marrow. Moreover, the dynamics of cyclin D1 in bone marrow reflects the disease development and it predicts the clinical course. We employed the molecular analysis for a precise quantitative detection of proliferation markers, Ki-67, topoisomerase IIalpha, and TPX2, that are described as effective prognostic factors. Using the molecular approach it is possible to measure the proliferation rate in a reproducible, standard way which is an essential prerequisite for using the proliferation activity as a routine clinical tool. Comparing with immunophenotyping we may conclude that the quantitative PCR-based analysis is a useful, reliable, rapid, reproducible, sensitive and specific method broadening our diagnostic tools in hematopathology. In comparison to interphase FISH in paraffin sections quantitative PCR is less technically demanding and less time-consuming and furthermore it is more sensitive in detecting small changes in the mRNA level. Moreover, quantitative PCR is the only technology which provides precise and reproducible quantitative information about the expression level. Therefore it may be used to demonstrate the decrease or increase of a tumor-specific marker in bone marrow in comparison with a previously aspirated specimen. Thus, it has a powerful potential to monitor the course of the disease in correlation with clinical data.

Development and validation of sensitive LC/MS/MS method for quantitative bioanalysis of levonorgestrel in rat plasma and application to pharmacokinetics study.

PubMed

Ananthula, Suryatheja; Janagam, Dileep R; Jamalapuram, Seshulatha; Johnson, James R; Mandrell, Timothy D; Lowe, Tao L

2015-10-15

Rapid, sensitive, selective and accurate LC/MS/MS method was developed for quantitative determination of levonorgestrel (LNG) in rat plasma and further validated for specificity, linearity, accuracy, precision, sensitivity, matrix effect, recovery efficiency and stability. Liquid-liquid extraction procedure using hexane:ethyl acetate mixture at 80:20 v:v ratio was employed to efficiently extract LNG from rat plasma. Reversed phase Luna column C18(2) (50×2.0mm i.d., 3μM) installed on a AB SCIEX Triple Quad™ 4500 LC/MS/MS system was used to perform chromatographic separation. LNG was identified within 2min with high specificity. Linear calibration curve was drawn within 0.5-50ng·mL(-1) concentration range. The developed method was validated for intra-day and inter-day accuracy and precision whose values fell in the acceptable limits. Matrix effect was found to be minimal. Recovery efficiency at three quality control (QC) concentrations 0.5 (low), 5 (medium) and 50 (high) ng·mL(-1) was found to be >90%. Stability of LNG at various stages of experiment including storage, extraction and analysis was evaluated using QC samples, and the results showed that LNG was stable at all the conditions. This validated method was successfully used to study the pharmacokinetics of LNG in rats after SubQ injection, providing its applicability in relevant preclinical studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Research progress of on-the-go soil parameter sensors based on NIRS

NASA Astrophysics Data System (ADS)

An, Xiaofei; Meng, Zhijun; Wu, Guangwei; Guo, Jianhua

2014-11-01

Both the ever-increasing prices of fertilizer and growing ecological concern over chemical run-off into sources of drinking water have brought the issues of precision agriculture and site-specific management to the forefront of present technological development within agriculture and ecology. Soil is an important and basic element in agriculture production. Acquisition of soil information plays an important role in precision agriculture. The soil parameters include soil total nitrogen, phosporus, potassium, soil organic matter, soil moisture, electrical conductivity and pH value and so on. Field rapid acquisition to all the kinds of soil physical and chemical parameters is one of the most important research directions. And soil parameter real-time monitoring is also the trend of future development in precision agriculture. While developments in precision agriculture and site-specific management procedures have made significant in-roads on these issues and many researchers have developed effective means to determine soil properties, routinely obtaining robust on-the-go measurements of soil properties which are reliable enough to drive effective fertilizer application remains a challenge. NIRS technology provides a new method to obtain soil parameter with low cost and rapid advantage. In this paper, research progresses of soil on-the-go spectral sensors at domestic and abroad was combed and analyzed. There is a need for the sensing system to perform at least six key indexes for any on-the-go soil spectral sensor to be successful. The six indexes are detection limit, specificity, robustness, accuracy, cost and easy-to-use. Both the research status and problems were discussed. Finally, combining the national conditions of china, development tendency of on-the-go soil spectral sensors was proposed. In the future, on-the-go soil spectral sensors with reliable enough, sensitive enough and continuous detection would become popular in precision agriculture.

Precision and sensitivity of the measurement of 15N enrichment in D-alanine from bacterial cell walls using positive/negative ion mass spectrometry

NASA Technical Reports Server (NTRS)

Tunlid, A.; Odham, G.; Findlay, R. H.; White, D. C.

1985-01-01

Sensitive detection of cellular components from specific groups of microbes can be utilized as 'signatures' in the examination of microbial consortia from soils, sediments or biofilms. Utilizing capillary gas chromatography/mass spectrometry and stereospecific derivatizing agents, D-alanine, a component localized in the prokaryotic (bacterial) cell wall, can be detected reproducibly. Enrichments of D-[15N]alanine determined in E. coli grown with [15N]ammonia can be determined with precision at 1.0 atom%. Chemical ionization with methane gas and the detection of negative ions (M - HF)- and (M - F or M + H - HF)- formed from the heptafluorobutyryl D-2 butanol ester of D-alanine allowed as little as 8 pg (90 fmol) to be detected reproducibly. This method can be utilized to define the metabolic activity in terms of 15N incorporation at the level of 10(3)-10(4) cells, as a function of the 15N-14N ratio.

Can we use high precision metal isotope analysis to improve our understanding of cancer?

PubMed

Larner, Fiona

2016-01-01

High precision natural isotope analyses are widely used in geosciences to trace elemental transport pathways. The use of this analytical tool is increasing in nutritional and disease-related research. In recent months, a number of groups have shown the potential this technique has in providing new observations for various cancers when applied to trace metal metabolism. The deconvolution of isotopic signatures, however, relies on mathematical models and geochemical data, which are not representative of the system under investigation. In addition to relevant biochemical studies of protein-metal isotopic interactions, technological development both in terms of sample throughput and detection sensitivity of these elements is now needed to translate this novel approach into a mainstream analytical tool. Following this, essential background healthy population studies must be performed, alongside observational, cross-sectional disease-based studies. Only then can the sensitivity and specificity of isotopic analyses be tested alongside currently employed methods, and important questions such as the influence of cancer heterogeneity and disease stage on isotopic signatures be addressed.

Effect of household pet ownership on infant immune response and subsequent sensitization

PubMed Central

Simpson, Angela

2010-01-01

Sensitization to pets is a major risk factor for asthma. There are many reports on the relationship between household pets, sensitization to the pet, and sensitization to other allergens, often with conflicting results. Pet ownership is not random, and household pets are associated with exposures other than pet allergens. We will review some of the evidence regarding the effects of household pets on infant immune responses, focusing on data from birth cohort studies. It remains unclear precisely why some children develop specific sensitizations to pets whilst others do not in the face of equivalent exposures, but it is likely to be due to gene-environment interactions. Further long-term follow-up of children in whom neonatal and infant immune responses have been measured is necessary to understand how these events occur and how they relate to subsequent disease. PMID:21437047

Validation of the Six Sigma Z-score for the quality assessment of clinical laboratory timeliness.

PubMed

Ialongo, Cristiano; Bernardini, Sergio

2018-03-28

The International Federation of Clinical Chemistry and Laboratory Medicine has introduced in recent times the turnaround time (TAT) as mandatory quality indicator for the postanalytical phase. Classic TAT indicators, namely, average, median, 90th percentile and proportion of acceptable test (PAT), are in use since almost 40 years and to date represent the mainstay for gauging the laboratory timeliness. In this study, we investigated the performance of the Six Sigma Z-score, which was previously introduced as a device for the quantitative assessment of timeliness. A numerical simulation was obtained modeling the actual TAT data set using the log-logistic probability density function. Five thousand replicates for each size of the artificial TAT random sample (n=20, 50, 250 and 1000) were generated, and different laboratory conditions were simulated manipulating the PDF in order to generate more or less variable data. The Z-score and the classic TAT indicators were assessed for precision (%CV), robustness toward right-tailing (precision at different sample variability), sensitivity and specificity. Z-score showed sensitivity and specificity comparable to PAT (≈80% with n≥250), but superior precision that ranged within 20% by moderately small sized samples (n≥50); furthermore, Z-score was less affected by the value of the cutoff used for setting the acceptable TAT, as well as by the sample variability that reflected into the magnitude of right-tailing. The Z-score was a valid indicator of laboratory timeliness and a suitable device to improve as well as to maintain the achieved quality level.

Validation of high throughput screening of human sera for detection of anti-PA IgG by Enzyme-Linked Immunosorbent Assay (ELISA) as an emergency response to an anthrax incident

PubMed Central

Semenova, Vera A.; Steward-Clark, Evelene; Maniatis, Panagiotis; Epperson, Monica; Sabnis, Amit; Schiffer, Jarad

2017-01-01

To improve surge testing capability for a response to a release of Bacillus anthracis, the CDC anti-Protective Antigen (PA) IgG Enzyme-Linked Immunosorbent Assay (ELISA) was re-designed into a high throughput screening format. The following assay performance parameters were evaluated: goodness of fit (measured as the mean reference standard r2), accuracy (measured as percent error), precision (measured as coefficient of variance (CV)), lower limit of detection (LLOD), lower limit of quantification (LLOQ), dilutional linearity, diagnostic sensitivity (DSN) and diagnostic specificity (DSP). The paired sets of data for each sample were evaluated by Concordance Correlation Coefficient (CCC) analysis. The goodness of fit was 0.999; percent error between the expected and observed concentration for each sample ranged from −4.6% to 14.4%. The coefficient of variance ranged from 9.0% to 21.2%. The assay LLOQ was 2.6 μg/mL. The regression analysis results for dilutional linearity data were r2 = 0.952, slope = 1.02 and intercept = −0.03. CCC between assays was 0.974 for the median concentration of serum samples. The accuracy and precision components of CCC were 0.997 and 0.977, respectively. This high throughput screening assay is precise, accurate, sensitive and specific. Anti-PA IgG concentrations determined using two different assays proved high levels of agreement. The method will improve surge testing capability 18-fold from 4 to 72 sera per assay plate. PMID:27814939

Validation of high throughput screening of human sera for detection of anti-PA IgG by Enzyme-Linked Immunosorbent Assay (ELISA) as an emergency response to an anthrax incident.

PubMed

Semenova, Vera A; Steward-Clark, Evelene; Maniatis, Panagiotis; Epperson, Monica; Sabnis, Amit; Schiffer, Jarad

2017-01-01

To improve surge testing capability for a response to a release of Bacillus anthracis, the CDC anti-Protective Antigen (PA) IgG Enzyme-Linked Immunosorbent Assay (ELISA) was re-designed into a high throughput screening format. The following assay performance parameters were evaluated: goodness of fit (measured as the mean reference standard r 2 ), accuracy (measured as percent error), precision (measured as coefficient of variance (CV)), lower limit of detection (LLOD), lower limit of quantification (LLOQ), dilutional linearity, diagnostic sensitivity (DSN) and diagnostic specificity (DSP). The paired sets of data for each sample were evaluated by Concordance Correlation Coefficient (CCC) analysis. The goodness of fit was 0.999; percent error between the expected and observed concentration for each sample ranged from -4.6% to 14.4%. The coefficient of variance ranged from 9.0% to 21.2%. The assay LLOQ was 2.6 μg/mL. The regression analysis results for dilutional linearity data were r 2  = 0.952, slope = 1.02 and intercept = -0.03. CCC between assays was 0.974 for the median concentration of serum samples. The accuracy and precision components of CCC were 0.997 and 0.977, respectively. This high throughput screening assay is precise, accurate, sensitive and specific. Anti-PA IgG concentrations determined using two different assays proved high levels of agreement. The method will improve surge testing capability 18-fold from 4 to 72 sera per assay plate. Published by Elsevier Ltd.

Beyond MEDLINE for literature searches.

PubMed

Conn, Vicki S; Isaramalai, Sang-arun; Rath, Sabyasachi; Jantarakupt, Peeranuch; Wadhawan, Rohini; Dash, Yashodhara

2003-01-01

To describe strategies for a comprehensive literature search. MEDLINE searches result in limited numbers of studies that are often biased toward statistically significant findings. Diversified search strategies are needed. Empirical evidence about the recall and precision of diverse search strategies is presented. Challenges and strengths of each search strategy are identified. Search strategies vary in recall and precision. Often sensitivity and specificity are inversely related. Valuable search strategies include examination of multiple diverse computerized databases, ancestry searches, citation index searches, examination of research registries, journal hand searching, contact with the "invisible college," examination of abstracts, Internet searches, and contact with sources of synthesized information. Extending searches beyond MEDLINE enables researchers to conduct more systematic comprehensive searches.

Large-Scale Interlaboratory Study to Develop, Analytically Validate and Apply Highly Multiplexed, Quantitative Peptide Assays to Measure Cancer-Relevant Proteins in Plasma*

PubMed Central

Abbatiello, Susan E.; Schilling, Birgit; Mani, D. R.; Zimmerman, Lisa J.; Hall, Steven C.; MacLean, Brendan; Albertolle, Matthew; Allen, Simon; Burgess, Michael; Cusack, Michael P.; Gosh, Mousumi; Hedrick, Victoria; Held, Jason M.; Inerowicz, H. Dorota; Jackson, Angela; Keshishian, Hasmik; Kinsinger, Christopher R.; Lyssand, John; Makowski, Lee; Mesri, Mehdi; Rodriguez, Henry; Rudnick, Paul; Sadowski, Pawel; Sedransk, Nell; Shaddox, Kent; Skates, Stephen J.; Kuhn, Eric; Smith, Derek; Whiteaker, Jeffery R.; Whitwell, Corbin; Zhang, Shucha; Borchers, Christoph H.; Fisher, Susan J.; Gibson, Bradford W.; Liebler, Daniel C.; MacCoss, Michael J.; Neubert, Thomas A.; Paulovich, Amanda G.; Regnier, Fred E.; Tempst, Paul; Carr, Steven A.

2015-01-01

There is an increasing need in biology and clinical medicine to robustly and reliably measure tens to hundreds of peptides and proteins in clinical and biological samples with high sensitivity, specificity, reproducibility, and repeatability. Previously, we demonstrated that LC-MRM-MS with isotope dilution has suitable performance for quantitative measurements of small numbers of relatively abundant proteins in human plasma and that the resulting assays can be transferred across laboratories while maintaining high reproducibility and quantitative precision. Here, we significantly extend that earlier work, demonstrating that 11 laboratories using 14 LC-MS systems can develop, determine analytical figures of merit, and apply highly multiplexed MRM-MS assays targeting 125 peptides derived from 27 cancer-relevant proteins and seven control proteins to precisely and reproducibly measure the analytes in human plasma. To ensure consistent generation of high quality data, we incorporated a system suitability protocol (SSP) into our experimental design. The SSP enabled real-time monitoring of LC-MRM-MS performance during assay development and implementation, facilitating early detection and correction of chromatographic and instrumental problems. Low to subnanogram/ml sensitivity for proteins in plasma was achieved by one-step immunoaffinity depletion of 14 abundant plasma proteins prior to analysis. Median intra- and interlaboratory reproducibility was <20%, sufficient for most biological studies and candidate protein biomarker verification. Digestion recovery of peptides was assessed and quantitative accuracy improved using heavy-isotope-labeled versions of the proteins as internal standards. Using the highly multiplexed assay, participating laboratories were able to precisely and reproducibly determine the levels of a series of analytes in blinded samples used to simulate an interlaboratory clinical study of patient samples. Our study further establishes that LC-MRM-MS using stable isotope dilution, with appropriate attention to analytical validation and appropriate quality control measures, enables sensitive, specific, reproducible, and quantitative measurements of proteins and peptides in complex biological matrices such as plasma. PMID:25693799

Complexity in estimation of esomeprazole and its related impurities' stability in various stress conditions in low-dose aspirin and esomeprazole magnesium capsules.

PubMed

Reddy, Palavai Sripal; Hotha, Kishore Kumar; Sait, Shakil

2013-01-01

A complex, sensitive, and precise high-performance liquid chromatographic method for the profiling of impurities of esomeprazole in low-dose aspirin and esomeprazole capsules has been developed, validated, and used for the determination of impurities in pharmaceutical products. Esomeprazole and its related impurities' development in the presence of aspirin was traditionally difficult due to aspirin's sensitivity to basic conditions and esomeprazole's sensitivity to acidic conditions. When aspirin is under basic, humid, and extreme temperature conditions, it produces salicylic acid and acetic acid moieties. These two byproducts create an acidic environment for the esomeprazole. Due to the volatility and migration phenomenon of the produced acetic acid and salicylic acid from aspirin in the capsule dosage form, esomeprazole's purity, stability, and quantification are affected. The objective of the present research work was to develop a gradient reversed-phase liquid chromatographic method to separate all the degradation products and process-related impurities from the main peak. The impurities were well-separated on a RP8 column (150 mm × 4.6mm, X-terra, RP8, 3.5μm) by the gradient program using a glycine buffer (0.08 M, pH adjusted to 9.0 with 50% NaOH), acetonitrile, and methanol at a flow rate of 1.0 mL min(-1) with detection wavelength at 305 nm and column temperature at 30°C. The developed method was found to be specific, precise, linear, accurate, rugged, and robust. LOQ values for all of the known impurities were below reporting thresholds. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation in the presence of aspirin. The developed RP-HPLC method was validated according to the present ICH guidelines for specificity, linearity, accuracy, precision, limit of detection, limit of quantification, ruggedness, and robustness.

Potential transducers based man-tailored biomimetic sensors for selective recognition of dextromethorphan as an antitussive drug.

PubMed

El-Naby, Eman H; Kamel, Ayman H

2015-09-01

A biomimetic potentiometric sensor for specific recognition of dextromethorphan (DXM), a drug classified according to the Drug Enforcement Administration (DEA) as a "drug of concern", is designed and characterized. A molecularly imprinted polymer (MIP), with special molecular recognition properties of DXM, was prepared by thermal polymerization in which DXM acted as template molecule, methacrylic acid (MAA) and acrylonitrile (AN) acted as functional monomers in the presence of ethylene glycol dimethacrylate (EGDMA) as crosslinker. The sensors showed a high selectivity and a sensitive response to the template in aqueous system. Electrochemical evaluation of these sensors revealed near-Nernstian response with slopes of 49.6±0.5 and 53.4±0.5 mV decade(-1) with a detection limit of 1.9×10(-6), and 1.0×10(-6) mol L(-1) DXM with MIP/MAA and MIP/AN membrane based sensors, respectively. Significantly improved accuracy, precision, response time, stability, selectivity and sensitivity were offered by these simple and cost-effective potentiometric sensors compared with other standard techniques. The method has the requisite accuracy, sensitivity and precision to assay DXM in pharmaceutical products. Copyright © 2015 Elsevier B.V. All rights reserved.

Digital PCR: A Sensitive and Precise Method for KIT D816V Quantification in Mastocytosis.

PubMed

Greiner, Georg; Gurbisz, Michael; Ratzinger, Franz; Witzeneder, Nadine; Simonitsch-Klupp, Ingrid; Mitterbauer-Hohendanner, Gerlinde; Mayerhofer, Matthias; Müllauer, Leonhard; Sperr, Wolfgang R; Valent, Peter; Hoermann, Gregor

2018-03-01

The analytically sensitive detection of KIT D816V in blood and bone marrow is important for diagnosing systemic mastocytosis (SM). Additionally, precise quantification of the KIT D816V variant allele fraction (VAF) is relevant clinically because it helps to predict multilineage involvement and prognosis in cases of advanced SM. Digital PCR (dPCR) is a promising new method for sensitive detection and accurate quantification of somatic mutations. We performed a validation study of dPCR for KIT D816V on 302 peripheral blood and bone marrow samples from 156 patients with mastocytosis for comparison with melting curve analysis after peptide nucleic acid-mediated PCR clamping (clamp-PCR) and allele-specific quantitative real-time PCR (qPCR). dPCR showed a limit of detection of 0.01% VAF with a mean CV of 8.5% and identified the mutation in 90% of patients compared with 70% for clamp-PCR ( P < 0.001). Moreover, dPCR for KIT D816V was highly concordant with qPCR without systematic deviation of results, and confirmed the clinical value of KIT D816V VAF measurements. Thus, patients with advanced SM showed a significantly higher KIT D816V VAF (median, 2.43%) compared with patients with indolent SM (median, 0.14%; P < 0.001). Moreover, dPCR confirmed the prognostic significance of a high KIT D816V VAF regarding survival ( P < 0.001). dPCR for KIT D816V provides a high degree of precision and sensitivity combined with the potential for interlaboratory standardization, which is crucial for the implementation of KIT D816V allele burden measurement. Thus, dPCR is suitable as a new method for KIT D816V testing in patients with mastocytosis. © 2017 American Association for Clinical Chemistry.

Modeling Canadian Quality Control Test Program for Steroid Hormone Receptors in Breast Cancer: Diagnostic Accuracy Study.

PubMed

Pérez, Teresa; Makrestsov, Nikita; Garatt, John; Torlakovic, Emina; Gilks, C Blake; Mallett, Susan

The Canadian Immunohistochemistry Quality Control program monitors clinical laboratory performance for estrogen receptor and progesterone receptor tests used in breast cancer treatment management in Canada. Current methods assess sensitivity and specificity at each time point, compared with a reference standard. We investigate alternative performance analysis methods to enhance the quality assessment. We used 3 methods of analysis: meta-analysis of sensitivity and specificity of each laboratory across all time points; sensitivity and specificity at each time point for each laboratory; and fitting models for repeated measurements to examine differences between laboratories adjusted by test and time point. Results show 88 laboratories participated in quality control at up to 13 time points using typically 37 to 54 histology samples. In meta-analysis across all time points no laboratories have sensitivity or specificity below 80%. Current methods, presenting sensitivity and specificity separately for each run, result in wide 95% confidence intervals, typically spanning 15% to 30%. Models of a single diagnostic outcome demonstrated that 82% to 100% of laboratories had no difference to reference standard for estrogen receptor and 75% to 100% for progesterone receptor, with the exception of 1 progesterone receptor run. Laboratories with significant differences to reference standard identified with Generalized Estimating Equation modeling also have reduced performance by meta-analysis across all time points. The Canadian Immunohistochemistry Quality Control program has a good design, and with this modeling approach has sufficient precision to measure performance at each time point and allow laboratories with a significantly lower performance to be targeted for advice.

The use of capillary electrophoresis as part of a specificity testing strategy for mitoguazone dihydrochloride HPLC methods.

PubMed

Thomson, C E; Gray, M R; Baxter, M P

1997-05-01

Capillary electrophoresis (CE) has been used as part of a validation experiment designed to prove the specificity of high performance liquid chromatography (HPLC) methods used for analysis of mitoguazone dihydrochloride drug substance. Data regarding accuracy, precision and sensitivity of the CE methods are presented as well as a comparison of results obtained from CE, HPLC and thin-layer chromatography (TLC) analysis of samples stressed under a variety of conditions. It was concluded that, not only were the HPLC methods being investigated specific, but that CE could potentially be used to replace HPLC for the routine assay of mitoguazone dihydrochloride.

Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration.

PubMed

Zhang, Boyang; Huang, Kunlun; Zhu, Liye; Luo, Yunbo; Xu, Wentao

2017-07-01

In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology.

Validation of the VitaBit Sit–Stand Tracker: Detecting Sitting, Standing, and Activity Patterns

PubMed Central

Plasqui, Guy

2018-01-01

Sedentary behavior (SB) has detrimental consequences and cannot be compensated for through moderate-to-vigorous physical activity (PA). In order to understand and mitigate SB, tools for measuring and monitoring SB are essential. While current direct-to-customer wearables focus on PA, the VitaBit validated in this study was developed to focus on SB. It was tested in a laboratory and in a free-living condition, comparing it to direct observation and to a current best-practice device, the ActiGraph, on a minute-by-minute basis. In the laboratory, the VitaBit yielded specificity and negative predictive rates (NPR) of above 91.2% for sitting and standing, while sensitivity and precision ranged from 74.6% to 85.7%. For walking, all performance values exceeded 97.3%. In the free-living condition, the device revealed performance of over 72.6% for sitting with the ActiGraph as criterion. While sensitivity and precision for standing and walking ranged from 48.2% to 68.7%, specificity and NPR exceeded 83.9%. According to the laboratory findings, high performance for sitting, standing, and walking makes the VitaBit eligible for SB monitoring. As the results are not transferrable to daily life activities, a direct observation study in a free-living setting is recommended. PMID:29543766

Optical Control of Dopamine Receptors Using a Photoswitchable Tethered Inverse Agonist.

PubMed

Donthamsetti, Prashant C; Winter, Nils; Schönberger, Matthias; Levitz, Joshua; Stanley, Cherise; Javitch, Jonathan A; Isacoff, Ehud Y; Trauner, Dirk

2017-12-27

Family A G protein-coupled receptors (GPCRs) control diverse biological processes and are of great clinical relevance. Their archetype rhodopsin becomes naturally light sensitive by binding covalently to the photoswitchable tethered ligand (PTL) retinal. Other GPCRs, however, neither bind covalently to ligands nor are light sensitive. We sought to impart the logic of rhodopsin to light-insensitive Family A GPCRs in order to enable their remote control in a receptor-specific, cell-type-specific, and spatiotemporally precise manner. Dopamine receptors (DARs) are of particular interest for their roles in motor coordination, appetitive, and aversive behavior, as well as neuropsychiatric disorders such as Parkinson's disease, schizophrenia, mood disorders, and addiction. Using an azobenzene derivative of the well-known DAR ligand 2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin (PPHT), we were able to rapidly, reversibly, and selectively block dopamine D1 and D2 receptors (D1R and D2R) when the PTL was conjugated to an engineered cysteine near the dopamine binding site. Depending on the site of tethering, the ligand behaved as either a photoswitchable tethered neutral antagonist or inverse agonist. Our results indicate that DARs can be chemically engineered for selective remote control by light and provide a template for precision control of Family A GPCRs.

Detection of PCT and urinary β2 -MG enhances the accuracy for localization diagnosing pediatric urinary tract infection.

PubMed

Fang, Jian; Luan, Jiangwei; Zhu, Gaohong; Qi, Chang; Wang, Dandan

2017-09-01

The purpose of this article was to investigate whether the combination of urinary beta 2 microglobulin (urinary β 2 -MG) and procalcitonin (PCT) diagnosis could enhance the localization diagnostic precision of pediatric urinary tract infection comparing with single diagnosis. A study was conducted in the Nephrology Department of Wuhan women and children's health care centre. This study incorporated 85 participants, including 35 children who were diagnosed as upper urinary tract infection (UUTI) with the symptom of fever and 50 children who conducted lower urinary tract infection (LUTI). Levels of PCT and urinary β 2 -MG in both UUTI and LUTI patients were measured and compared. The level of PCT and β 2 -MG were both significantly higher in UUTI group compared with in LUTI group. AUC of urinary β 2 -MG ROC (sensitivity of 71.4%, specificity of 90.0%) was significantly smaller than that of PCT ROC (sensitivity of 77.1%, specificity of 96.0%) in the single diagnosis. Although in the combined diagnosis, the sensitivity and specificity increased to 88.6% and 98%, respectively. Both PCT and β 2 -MG could be used to localize the UTI. Introducing urinary β 2 -MG into PCT diagnosis could increase the sensitivity and specificity of UTI lesion diagnosis in clinical practice. © 2016 The Authors Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.

Urinalysis: The Automated Versus Manual Techniques; Is It Time To Change?.

PubMed

Ahmed, Asmaa Ismail; Baz, Heba; Lotfy, Sarah

2016-01-01

Urinalysis is the third major test in clinical laboratory. Manual technique imprecision urges the need for a rapid reliable automated test. We evaluated the H800-FUSIOO automatic urine sediment analyzer and compared it to the manual urinalysis technique to determine if it may be a competitive substitute in laboratories of central hospitals. 1000 urine samples were examined by the two methods in parallel. Agreement, precision, carryover, drift, sensitivity, specificity, and practicability criteria were tested. Agreement ranged from excellent to good for all urine semi-quantitative components (K > 0.4, p = 0.000), except for granular casts (K = 0.317, p = 0.000). Specific gravity results correlated well between the two methods (r = 0.884, p = 0.000). RBCS and WBCs showed moderate correlation (r = 0.42, p = 0.000) and (r = 0.44, p = 0.000), respectively. The auto-analyzer's within-run precision was > 75% for all semi-quantitative components except for proteins (50% precision). This finding in addition to the granular casts poor agreement indicate the necessity of operator interference at the critical cutoff values. As regards quantitative contents, RBCs showed a mean of 69.8 +/- 3.95, C.V. = 5.7, WBCs showed a mean of 38.9 +/- 1.9, C.V. = 4.9). Specific gravity, pH, microalbumin, and creatinine also showed good precision results with C.Vs of 0.000, 2.6, 9.1, and 0.00 respectively. In the between run precision, positive control showed good precision (C.V. = 2.9), while negative control's C.V. was strikingly high (C.V. = 127). Carryover and drift studies were satisfactory. Manual examination of inter-observer results showed major discrepancies (< 60% similar readings), while intra-observer's results correlated well with each other (r = 0.99, p = 0.000). Automation of urinalysis decreases observer-associated variation and offers prompt competitive results when standardized for screening away from the borderline cutoffs.

HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised classification of superfamily protein sequences with a reliable cut-off threshold.

PubMed

Pagnuco, Inti Anabela; Revuelta, María Victoria; Bondino, Hernán Gabriel; Brun, Marcel; Ten Have, Arjen

2018-01-01

Protein superfamilies can be divided into subfamilies of proteins with different functional characteristics. Their sequences can be classified hierarchically, which is part of sequence function assignation. Typically, there are no clear subfamily hallmarks that would allow pattern-based function assignation by which this task is mostly achieved based on the similarity principle. This is hampered by the lack of a score cut-off that is both sensitive and specific. HMMER Cut-off Threshold Tool (HMMERCTTER) adds a reliable cut-off threshold to the popular HMMER. Using a high quality superfamily phylogeny, it clusters a set of training sequences such that the cluster-specific HMMER profiles show cluster or subfamily member detection with 100% precision and recall (P&R), thereby generating a specific threshold as inclusion cut-off. Profiles and thresholds are then used as classifiers to screen a target dataset. Iterative inclusion of novel sequences to groups and the corresponding HMMER profiles results in high sensitivity while specificity is maintained by imposing 100% P&R self detection. In three presented case studies of protein superfamilies, classification of large datasets with 100% precision was achieved with over 95% recall. Limits and caveats are presented and explained. HMMERCTTER is a promising protein superfamily sequence classifier provided high quality training datasets are used. It provides a decision support system that aids in the difficult task of sequence function assignation in the twilight zone of sequence similarity. All relevant data and source codes are available from the Github repository at the following URL: https://github.com/BBCMdP/HMMERCTTER.

HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised classification of superfamily protein sequences with a reliable cut-off threshold

PubMed Central

Pagnuco, Inti Anabela; Revuelta, María Victoria; Bondino, Hernán Gabriel; Brun, Marcel

2018-01-01

Background Protein superfamilies can be divided into subfamilies of proteins with different functional characteristics. Their sequences can be classified hierarchically, which is part of sequence function assignation. Typically, there are no clear subfamily hallmarks that would allow pattern-based function assignation by which this task is mostly achieved based on the similarity principle. This is hampered by the lack of a score cut-off that is both sensitive and specific. Results HMMER Cut-off Threshold Tool (HMMERCTTER) adds a reliable cut-off threshold to the popular HMMER. Using a high quality superfamily phylogeny, it clusters a set of training sequences such that the cluster-specific HMMER profiles show cluster or subfamily member detection with 100% precision and recall (P&R), thereby generating a specific threshold as inclusion cut-off. Profiles and thresholds are then used as classifiers to screen a target dataset. Iterative inclusion of novel sequences to groups and the corresponding HMMER profiles results in high sensitivity while specificity is maintained by imposing 100% P&R self detection. In three presented case studies of protein superfamilies, classification of large datasets with 100% precision was achieved with over 95% recall. Limits and caveats are presented and explained. Conclusions HMMERCTTER is a promising protein superfamily sequence classifier provided high quality training datasets are used. It provides a decision support system that aids in the difficult task of sequence function assignation in the twilight zone of sequence similarity. All relevant data and source codes are available from the Github repository at the following URL: https://github.com/BBCMdP/HMMERCTTER. PMID:29579071

[Enzymatic methods in the analysis of musts and wines].

PubMed

Lafon-Lafourcade, S

1978-01-01

The enzymatic methods are based on the property of the enzymes to catalyse specifically and reversibly the conversion of certain metabolites. These methods, developed thanks to the industrial preparation of enzymes, can be applied with no major modification to the analysis of drinks. About 15 constituants of musts and wines can now be determined by these methods. If their cost price was not relatively high, their specificity, sensitivity and rapidity would enable them to compete with the most precise of chemical methods. This is why they are only used in analytic oenology when chemical analysis is most specific enough or too laborious. Enzymatic measurement allows one by its specificity to determine the amount of residual sugar that is fermentable in a dry wine and by its sensitivity to verifie the total disappearance of the malic acid of the wine. Its rapidity must make it preferable to the long and not very specific chemical measurement, especially concerning the determination of citric acid. But glycerol, ethanol and acetic acid can be measured by chemical or chromatographical means with sufficient precision and for a more modest price. In oenology the methods are essentially used for research. They have permitted the study of the combinations of sulphur anhydride in wines (measurement of cetonic acids). The determination of the isomeric nature of the lactic acid produced from sugars by lactic bacteria is based on their application; this determination is a criterium for the identification and classification of these microorganisms. The measurement of the lactic acid during vinification allows the early disclosure of the first effects of a bacterial development; inversely it permits the invalidation of the existence of a lactic sourness, which a high volatile acidity might point to. Lastly, the enzymatic measurement of gluconic acid allows the health of the crop to be controlled.

A NEW SENSITIVE ASSAY FOR ANTIBODY AGAINST CELL SURFACE ANTIGENS BASED ON INHIBITION OF CELL-DEPENDENT ANTIBODY-MEDIATED CYTOTOXICITY

PubMed Central

Halloran, Phil; Schirrmacher, Volker; Festenstein, Hilliard

1974-01-01

Inhibition of cell-dependent antibody-mediated cytotoxicity has been investigated as a new assay for antibody against cell surface antigens. The cytotoxicity system consisted of effector cells (normal mouse spleen cells), target cells (61Cr-labeled chicken erythrocytes), and antitarget cell antibody. Addition of antibody against cell surface antigens in the effector cell population regularly inhibited the cytotoxicity measured in this system. This cytotoxicity inhibition assay (CIA) detected antibody with a variety of specificities: anti-H-2, anti-Thy 1.2, anti-immunoglobulin, and antimouse bone marrow-derived lymphocyte antigen. When the inhibition by anti-H-2 sera was analyzed using effector cells from congenic mice, the activity was found to be directed against specificities mapping in the H-2K, H-2D, and I regions of the H-2 complex, correlating well with the specificities characterized by complement-dependent assays. A comparison between the sensitivity of the CIA and complement-dependent lysis revealed that the CIA was 2–11 times more sensitive for anti-H-2 antisera and 20–780 times more sensitive for certain antisera against subpopulations of the spleen cells (i.e., T cells or B cells). The CIA proved to be precise, sensitive, and reliable. It may become a very useful antibody assay in various species including man. PMID:4547657

Outlier analysis of functional genomic profiles enriches for oncology targets and enables precision medicine.

PubMed

Zhu, Zhou; Ihle, Nathan T; Rejto, Paul A; Zarrinkar, Patrick P

2016-06-13

Genome-scale functional genomic screens across large cell line panels provide a rich resource for discovering tumor vulnerabilities that can lead to the next generation of targeted therapies. Their data analysis typically has focused on identifying genes whose knockdown enhances response in various pre-defined genetic contexts, which are limited by biological complexities as well as the incompleteness of our knowledge. We thus introduce a complementary data mining strategy to identify genes with exceptional sensitivity in subsets, or outlier groups, of cell lines, allowing an unbiased analysis without any a priori assumption about the underlying biology of dependency. Genes with outlier features are strongly and specifically enriched with those known to be associated with cancer and relevant biological processes, despite no a priori knowledge being used to drive the analysis. Identification of exceptional responders (outliers) may not lead only to new candidates for therapeutic intervention, but also tumor indications and response biomarkers for companion precision medicine strategies. Several tumor suppressors have an outlier sensitivity pattern, supporting and generalizing the notion that tumor suppressors can play context-dependent oncogenic roles. The novel application of outlier analysis described here demonstrates a systematic and data-driven analytical strategy to decipher large-scale functional genomic data for oncology target and precision medicine discoveries.

Asymmetric exponential amplification reaction on a toehold/biotin featured template: an ultrasensitive and specific strategy for isothermal microRNAs analysis

PubMed Central

Chen, Jun; Zhou, Xueqing; Ma, Yingjun; Lin, Xiulian; Dai, Zong; Zou, Xiaoyong

2016-01-01

The sensitive and specific analysis of microRNAs (miRNAs) without using a thermal cycler instrument is significant and would greatly facilitate biological research and disease diagnostics. Although exponential amplification reaction (EXPAR) is the most attractive strategy for the isothermal analysis of miRNAs, its intrinsic limitations of detection efficiency and inevitable non-specific amplification critically restrict its use in analytical sensitivity and specificity. Here, we present a novel asymmetric EXPAR based on a new biotin/toehold featured template. A biotin tag was used to reduce the melting temperature of the primer/template duplex at the 5′ terminus of the template, and a toehold exchange structure acted as a filter to suppress the non-specific trigger of EXPAR. The asymmetric EXPAR exhibited great improvements in amplification efficiency and specificity as well as a dramatic extension of dynamic range. The limit of detection for the let-7a analysis was decreased to 6.02 copies (0.01 zmol), and the dynamic range was extended to 10 orders of magnitude. The strategy enabled the sensitive and accurate analysis of let-7a miRNA in human cancer tissues with clearly better precision than both standard EXPAR and RT-qPCR. Asymmetric EXPAR is expected to have an important impact on the development of simple and rapid molecular diagnostic applications for short oligonucleotides. PMID:27257058

Identification of 11-Nor-delta9-tetrahydrocannabinol-9-carboxylic acid in urine by ion trap GC-MS-MS in the context of doping analysis.

PubMed

Caballero, Gerardo M; D'Angelo, Carlos; Fraguío, Mariá Sol; Centurión, Osvaldo Teme

2004-01-01

The purpose of this study is to develop a sensitive and specific alternative to current gas chromatography (GC)-mass spectrometry (MS) selected ion monitoring confirmation methods of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (cTHC) in human urine samples, in the context of doping analysis. An identification procedure based on the comparison, among suspicious and control samples, of the relative abundances of cTHC selected product ions obtained by GC-tandem MS in an ion trap is presented. The method complies with the identification criteria for qualitative assays established by sports authorities; the comparison procedure is precise, reproducible, specific, and sensitive, thus indicating that it is fit for the purpose of identification accordingly to World Antidoping Agency requirements.

Relationship between the caregiver's report on the patient's spontaneous-speech and the Brief Aphasia Evaluation.

PubMed

Vigliecca, Nora Silvana

2017-11-09

To study the relationship between the caregiver's perception about the patient's impairment in spontaneous speech, according to an item of four questions administered by semi-structured interview, and the patient's performance in the Brief Aphasia Evaluation (BAE). 102 right-handed patients with focal brain lesions of different types and location were examined. BAE is a valid and reliable instrument to assess aphasia. The caregiver's perception was correlated with the item of spontaneous speech, the total score and the three main factors of the BAE: Expression, Comprehension and Complementary factors. The precision (sensitivity/ specificity) about the caregiver's perception of the patient's spontaneous speech was analyzed with reference to the presence or absence of disorder, according to the professional, on the BAE item of spontaneous speech. The studied correlation was satisfactory, being greater (higher than 80%) for the following indicators: the item of spontaneous speech, the Expression factor and the total score of the scale; the correlation was a little smaller (higher than 70%) for the Comprehension and Complementary factors. Comparing two cut-off points that evaluated the precision of the caregiver's perception, satisfactory results were observed in terms of sensitivity and specificity (>70%) with likelihood ratios higher than three. By using the median as the cut-off point, more satisfactory diagnostic discriminations were obtained. Interviewing the caregiver specifically on the patient's spontaneous speech, in an abbreviated form, provides relevant information for the aphasia diagnosis.

A validated ultra high-pressure liquid chromatography method for separation of candesartan cilexetil impurities and its degradents in drug product

PubMed Central

Kumar, Namala Durga Atchuta; Babu, K. Sudhakar; Gosada, Ullas; Sharma, Nitish

2012-01-01

Introduction: A selective, specific, and sensitive “Ultra High-Pressure Liquid Chromatography” (UPLC) method was developed for determination of candesartan cilexetil impurities as well asits degradent in tablet formulation. Materials and Methods: The chromatographic separation was performed on Waters Acquity UPLC system and BEH Shield RP18 column using gradient elution of mobile phase A and B. 0.01 M phosphate buffer adjusted pH 3.0 with Orthophosphoric acid was used as mobile phase A and 95% acetonitrile with 5% Milli Q Water was used as mobile phase B. Ultraviolet (UV) detection was performed at 254 nm and 210 nm, where (CDS-6), (CDS-5), (CDS-7), (Ethyl Candesartan), (Desethyl CCX), (N-Ethyl), (CCX-1), (1 N Ethyl Oxo CCX), (2 N Ethyl Oxo CCX), (2 N Ethyl) and any unknown impurity were monitored at 254 nm wavelength, and two process-related impurities, trityl alcohol and MTE impurity, were estimated at 210 nm. Candesartan cilexetil andimpurities were chromatographed with a total run time of 20 min. Results: Calibration showed that the response of impurity was a linear function of concentration over the range limit of quantification to 2 μg/mL (r2≥0.999) and the method was validated over this range for precision, intermediate precision, accuracy, linearity, and specificity. For the precision study, percentage relative standard deviation of each impurity was <15% (n=6). Conclusion: The method was found to be precise, accurate, linear, and specific. The proposed method was successfully employed for estimation of candesartan cilexetil impurities in pharmaceutical preparations. PMID:23781475

Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

NASA Astrophysics Data System (ADS)

VanNasdale, Dean Allan, Jr.

2011-12-01

The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology was present. We found that normal aging changes could be distinguished from pathology associated with AMD and that polarization sensitive imaging can be used to delineate large extents of retinal damage. We found that various types of AMD pathology can also be differentiated based on scattering and polarization altering properties. Our findings demonstrate that polarization sensitive imaging is a useful modality in the evaluation of changes occurring in the normal human macula as well as changes associated with serious macular disease.

Added Value of SPECT/CT in the Evaluation of Benign Bone Diseases of the Appendicular Skeleton.

PubMed

Abikhzer, Gad; Srour, Saher; Keidar, Zohar; Bar-Shalom, Rachel; Kagna, Olga; Israel, Ora; Militianu, Daniela

2016-04-01

Bone scintigraphy is a sensitive technique to detect altered bone mineralization but has limited specificity. The use of SPECT/CT has improved significantly the diagnostic accuracy of bone scintigraphy, in patients with cancer as well as in evaluation of benign bone disease. It provides precise localization and characterization of tracer-avid foci, shortens the diagnostic workup, and decreases patient anxiety. Through both the SPECT and the CT components, SPECT/CT has an incremental value in characterizing benign bone lesions, specifically in the appendicular skeleton, as illustrated by present case series.

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

PubMed

Iannaccone, Mario; Gili, Sebastiano; De Filippo, Ovidio; D'Amico, Salvatore; Gagliardi, Marco; Bertaina, Maurizio; Mazzilli, Silvia; Rettegno, Sara; Bongiovanni, Federica; Gatti, Paolo; Ugo, Fabrizio; Boccuzzi, Giacomo G; Colangelo, Salvatore; Prato, Silvia; Moretti, Claudio; D'Amico, Maurizio; Noussan, Patrizia; Garbo, Roberto; Hildick-Smith, David; Gaita, Fiorenzo; D'Ascenzo, Fabrizio

2018-01-01

Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

Improving the sensitivity and specificity of a bioanalytical assay for the measurement of certolizumab pegol.

PubMed

Smeraglia, John; Silva, John-Paul; Jones, Kieran

2017-08-01

In order to evaluate placental transfer of certolizumab pegol (CZP), a more sensitive and selective bioanalytical assay was required to accurately measure low CZP concentrations in infant and umbilical cord blood. Results & methodology: A new electrochemiluminescence immunoassay was developed to measure CZP levels in human plasma. Validation experiments demonstrated improved selectivity (no matrix interference observed) and a detection range of 0.032-5.0 μg/ml. Accuracy and precision met acceptance criteria (mean total error ≤20.8%). Dilution linearity and sample stability were acceptable and sufficient to support the method. The electrochemiluminescence immunoassay was validated for measuring low CZP concentrations in human plasma. The method demonstrated a more than tenfold increase in sensitivity compared with previous assays, and improved selectivity for intact CZP.

Rapid and specific detection of Asian- and African-lineage Zika viruses.

PubMed

Chotiwan, Nunya; Brewster, Connie D; Magalhaes, Tereza; Weger-Lucarelli, James; Duggal, Nisha K; Rückert, Claudia; Nguyen, Chilinh; Garcia Luna, Selene M; Fauver, Joseph R; Andre, Barb; Gray, Meg; Black, William C; Kading, Rebekah C; Ebel, Gregory D; Kuan, Guillermina; Balmaseda, Angel; Jaenisch, Thomas; Marques, Ernesto T A; Brault, Aaron C; Harris, Eva; Foy, Brian D; Quackenbush, Sandra L; Perera, Rushika; Rovnak, Joel

2017-05-03

Understanding the dynamics of Zika virus transmission and formulating rational strategies for its control require precise diagnostic tools that are also appropriate for resource-poor environments. We have developed a rapid and sensitive loop-mediated isothermal amplification (LAMP) assay that distinguishes Zika viruses of Asian and African lineages. The assay does not detect chikungunya virus or flaviviruses such as dengue, yellow fever, or West Nile viruses. The assay conditions allowed direct detection of Zika virus RNA in cultured infected cells; in mosquitoes; in virus-spiked samples of human blood, plasma, saliva, urine, and semen; and in infected patient serum, plasma, and semen samples without the need for RNA isolation or reverse transcription. The assay offers rapid, specific, sensitive, and inexpensive detection of the Asian-lineage Zika virus strain that is currently circulating in the Western hemisphere, and can also detect the African-lineage Zika virus strain using separate, specific primers. Copyright © 2017, American Association for the Advancement of Science.

Development of real-time PCR assays for the detection of Moraxella macacae associated with bloody nose syndrome in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques

PubMed Central

Whitehouse, Chris A.; Chase, Kitty; Embers, Monica E.; Kulesh, David A.; Ladner, Jason T.; Palacios, Gustavo F.; Minogue, Timothy D.

2016-01-01

Background Moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. The aim of this study was to develop specific molecular diagnostic assays for M. macacae and to determine their performance characteristics. Methods We developed six real-time PCR assays on the Roche LightCycler. The accuracy, precision, selectivity, and limit of detection (LOD) were determined for each assay, in addition to further validation by testing nasal swabs from macaques presenting with epistaxis at the Tulane National Primate Research Center. Results All assays exhibited 100% specificity and were highly sensitive with an LOD of 10 fg for chromosomal assays and 1 fg for the plasmid assay. Testing of nasal swabs from 10 symptomatic macaques confirmed the presence of M. macacae in these animals. Conclusions We developed several accurate, sensitive, and species-specific real-time PCR assays for the detection of M. macacae in captive macaques. PMID:26365904

Artificial neural networks: Predicting head CT findings in elderly patients presenting with minor head injury after a fall.

PubMed

Dusenberry, Michael W; Brown, Charles K; Brewer, Kori L

2017-02-01

To construct an artificial neural network (ANN) model that can predict the presence of acute CT findings with both high sensitivity and high specificity when applied to the population of patients≥age 65years who have incurred minor head injury after a fall. An ANN was created in the Python programming language using a population of 514 patients ≥ age 65 years presenting to the ED with minor head injury after a fall. The patient dataset was divided into three parts: 60% for "training", 20% for "cross validation", and 20% for "testing". Sensitivity, specificity, positive and negative predictive values, and accuracy were determined by comparing the model's predictions to the actual correct answers for each patient. On the "cross validation" data, the model attained a sensitivity ("recall") of 100.00%, specificity of 78.95%, PPV ("precision") of 78.95%, NPV of 100.00%, and accuracy of 88.24% in detecting the presence of positive head CTs. On the "test" data, the model attained a sensitivity of 97.78%, specificity of 89.47%, PPV of 88.00%, NPV of 98.08%, and accuracy of 93.14% in detecting the presence of positive head CTs. ANNs show great potential for predicting CT findings in the population of patients ≥ 65 years of age presenting with minor head injury after a fall. As a good first step, the ANN showed comparable sensitivity, predictive values, and accuracy, with a much higher specificity than the existing decision rules in clinical usage for predicting head CTs with acute intracranial findings. Copyright © 2016 Elsevier Inc. All rights reserved.

Digital PCR Modeling for Maximal Sensitivity, Dynamic Range and Measurement Precision

PubMed Central

Majumdar, Nivedita; Wessel, Thomas; Marks, Jeffrey

2015-01-01

The great promise of digital PCR is the potential for unparalleled precision enabling accurate measurements for genetic quantification. A challenge associated with digital PCR experiments, when testing unknown samples, is to perform experiments at dilutions allowing the detection of one or more targets of interest at a desired level of precision. While theory states that optimal precision (Po) is achieved by targeting ~1.59 mean copies per partition (λ), and that dynamic range (R) includes the space spanning one positive (λL) to one negative (λU) result from the total number of partitions (n), these results are tempered for the practitioner seeking to construct digital PCR experiments in the laboratory. A mathematical framework is presented elucidating the relationships between precision, dynamic range, number of partitions, interrogated volume, and sensitivity in digital PCR. The impact that false reaction calls and volumetric variation have on sensitivity and precision is next considered. The resultant effects on sensitivity and precision are established via Monte Carlo simulations reflecting the real-world likelihood of encountering such scenarios in the laboratory. The simulations provide insight to the practitioner on how to adapt experimental loading concentrations to counteract any one of these conditions. The framework is augmented with a method of extending the dynamic range of digital PCR, with and without increasing n, via the use of dilutions. An example experiment demonstrating the capabilities of the framework is presented enabling detection across 3.33 logs of starting copy concentration. PMID:25806524

New Class of Precision Antimicrobials Redefines Role of Clostridium difficile S-layer in Virulence and Viability

PubMed Central

Kirk, Joseph A.; Gebhart, Dana; Buckley, Anthony M.; Lok, Stephen; Scholl, Dean; Douce, Gillian R.; Govoni, Gregory R.; Fagan, Robert P.

2017-01-01

Avidocin-CDs are a new class of precision bactericidal agents that do not damage resident gut microbiota and are unlikely to promote the spread of antibiotic resistance. The precision killing properties result from the fusion of bacteriophage receptor binding proteins (RBPs) to a lethal contractile scaffold from an R-type bacteriocin. We recently described the prototypic Avidocin-CD, Av-CD291.2, that specifically kills C. difficile ribotype 027 strains and prevents colonization of mice. We have since selected two rare Av-CD291.2 resistant mutants of strain R20291 (RT027; S-layer cassette type-4, SCLT-4). These mutants have distinct point mutations in the slpA gene that result in an S-layer null phenotype. Reversion of the mutations to wild-type restored normal SLCT-4 S-layer formation and Av-CD291.2 sensitivity; however, complementation with other SCLT alleles did not restore Av-CD291.2 sensitivity despite restoring S-layer formation. Using newly identified phage RBPs, we constructed a panel of new Avidocin-CDs that kill C. difficile isolates in an SLCT-dependent manner, confirming the S-layer as the receptor in every case. In addition to bacteriophage adsorption, characterization of the S-layer null mutant also uncovered important roles for SlpA in sporulation, resistance to lysozyme and LL-37, and toxin production. Surprisingly, the S-layer-null mutant was found to persist in the hamster gut despite its completely attenuated virulence. Avidocin-CDs have significant therapeutic potential for the treatment and prevention of C. difficile Infection (CDI) given their exquisite specificity for the pathogen. Furthermore, the emergence of resistance forces mutants to trade virulence for continued viability and, therefore, greatly reduce their potential clinical impact. PMID:28878013

How the impact of median neuropathy on sensorimotor control capability of hands for diabetes: an achievable assessment from functional perspectives.

PubMed

Chiu, Haw-Yen; Hsu, Hsiu-Yun; Kuo, Li-Chieh; Su, Fong-Chin; Yu, Hui-I; Hua, Shih-Che; Lu, Chieh-Hsiang

2014-01-01

To comprehend the sensorimotor control ability in diabetic hands, this study investigated the sensation, motor function and precision pinch performances derived from a pinch-holding-up activity (PHUA) test of the hands of diabetic patients and healthy subjects. The precision, sensitivity and specificity of the PHUA test in the measurements of diabetic patients were also analyzed. We hypothesized that the diabetic hands would have impacts on the sensorimotor functions of the hand performances under functionally quantitative measurements. One hundred and fifty-nine patients with clinically defined diabetes mellitus (DM) and 95 age- and gender-matched healthy controls were included. Semmes-Weinstein monofilament (SWM), static and moving two-point discrimination (S2PD and M2PD), maximal pinch strength and precision pinch performance tests were conducted to evaluate the sensation, motor and sensorimotor status of the recruited hands. The results showed that there were significant differences (all p<0.05) in SWM, S2PD, M2PD and maximum pinch strength between the DM and control groups. A higher force ratio in the DM patients than in the controls (p<0.001) revealed a poor ability of pinch force adjustment in the DM patients. The percentage of maximal pinch strength was also significantly different (p<0.001) between the DM and control groups. The sensitivity, specificity and area under the receiver operating characteristic curve were 0.85, 0.51, and 0.724, respectively, for the PHUA test. Statistically significant degradations in sensory and motor functions and sensorimotor control ability were observed in the hands of the diabetic patients. The PHUA test could be feasibly used as a clinical tool to determine the sensorimotor function of the hands of diabetic patients from a functional perspective.

Locating qualitative studies in dementia on MEDLINE, EMBASE, CINAHL, and PsycINFO: A comparison of search strategies.

PubMed

Rogers, Morwenna; Bethel, Alison; Abbott, Rebecca

2017-10-28

Qualitative research in dementia improves understanding of the experience of people affected by dementia. Searching databases for qualitative studies is problematic. Qualitative-specific search strategies might help with locating studies. To examine the effectiveness (sensitivity and precision) of 5 qualitative strategies on locating qualitative research studies in dementia in 4 major databases (MEDLINE, EMBASE, PsycINFO, and CINAHL). Qualitative dementia studies were checked for inclusion on MEDLINE, EMBASE, PsycINFO, and CINAHL. Five qualitative search strategies (subject headings, simple free-text terms, complex free-text terms, and 2 broad-based strategies) were tested for study retrieval. Specificity, precision and number needed to read were calculated. Two hundred fourteen qualitative studies in dementia were included. PsycINFO and CINAHL held the most qualitative studies out the 4 databases studied (N = 171 and 166, respectively) and both held unique records (N = 14 and 7, respectively). The controlled vocabulary strategy in CINAHL returned 96% (N = 192) of studies held; by contrast, controlled vocabulary in PsycINFO returned 7% (N = 13) of studies held. The broad-based strategies returned more studies (93-99%) than the other free-text strategies (22-82%). Precision ranged from 0.061 to 0.004 resulting in a number needed to read to obtain 1 relevant study ranging from 16 (simple free-text search in CINAHL) to 239 (broad-based search in EMBASE). Qualitative search strategies using 3 broad terms were more sensitive than long complex searches. The controlled vocabulary for qualitative research in CINAHL was particularly effective. Furthermore, results indicate that MEDLINE and EMBASE offer little benefit for locating qualitative dementia research if CINAHL and PSYCINFO are also searched. Copyright © 2017 John Wiley & Sons, Ltd.

How the Impact of Median Neuropathy on Sensorimotor Control Capability of Hands for Diabetes: An Achievable Assessment from Functional Perspectives

PubMed Central

Chiu, Haw-Yen; Hsu, Hsiu-Yun; Kuo, Li-Chieh; Su, Fong-Chin; Yu, Hui-I; Hua, Shih-Che; Lu, Chieh-Hsiang

2014-01-01

To comprehend the sensorimotor control ability in diabetic hands, this study investigated the sensation, motor function and precision pinch performances derived from a pinch-holding-up activity (PHUA) test of the hands of diabetic patients and healthy subjects. The precision, sensitivity and specificity of the PHUA test in the measurements of diabetic patients were also analyzed. We hypothesized that the diabetic hands would have impacts on the sensorimotor functions of the hand performances under functionally quantitative measurements. One hundred and fifty-nine patients with clinically defined diabetes mellitus (DM) and 95 age- and gender-matched healthy controls were included. Semmes-Weinstein monofilament (SWM), static and moving two-point discrimination (S2PD and M2PD), maximal pinch strength and precision pinch performance tests were conducted to evaluate the sensation, motor and sensorimotor status of the recruited hands. The results showed that there were significant differences (all p<0.05) in SWM, S2PD, M2PD and maximum pinch strength between the DM and control groups. A higher force ratio in the DM patients than in the controls (p<0.001) revealed a poor ability of pinch force adjustment in the DM patients. The percentage of maximal pinch strength was also significantly different (p<0.001) between the DM and control groups. The sensitivity, specificity and area under the receiver operating characteristic curve were 0.85, 0.51, and 0.724, respectively, for the PHUA test. Statistically significant degradations in sensory and motor functions and sensorimotor control ability were observed in the hands of the diabetic patients. The PHUA test could be feasibly used as a clinical tool to determine the sensorimotor function of the hands of diabetic patients from a functional perspective. PMID:24722361

Validation of Medicaid claims-based diagnosis of myocardial infarction using an HIV clinical cohort

PubMed Central

Brouwer, Emily S.; Napravnik, Sonia; Eron, Joseph J; Simpson, Ross J; Brookhart, M. Alan; Stalzer, Brant; Vinikoor, Michael; Floris-Moore, Michelle; Stürmer, Til

2014-01-01

Background In non-experimental comparative effectiveness research using healthcare databases, outcome measurements must be validated to evaluate and potentially adjust for misclassification bias. We aimed to validate claims-based myocardial infarction algorithms in a Medicaid population using an HIV clinical cohort as the gold standard. Methods Medicaid administrative data were obtained for the years 2002–2008 and linked to the UNC CFAR HIV Clinical Cohort based on social security number, first name and last name and myocardial infarction were adjudicated. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results There were 1,063 individuals included. Over a median observed time of 2.5 years, 17 had a myocardial infarction. Specificity ranged from 0.979–0.993 with the highest specificity obtained using criteria with the ICD-9 code in the primary and secondary position and a length of stay ≥ 3 days. Sensitivity of myocardial infarction ascertainment varied from 0.588–0.824 depending on algorithm. Conclusion: Specificities of varying claims-based myocardial infarction ascertainment criteria are high but small changes impact positive predictive value in a cohort with low incidence. Sensitivities vary based on ascertainment criteria. Type of algorithm used should be prioritized based on study question and maximization of specific validation parameters that will minimize bias while also considering precision. PMID:23604043

High spatial precision nano-imaging of polarization-sensitive plasmonic particles

NASA Astrophysics Data System (ADS)

Liu, Yunbo; Wang, Yipei; Lee, Somin Eunice

2018-02-01

Precise polarimetric imaging of polarization-sensitive nanoparticles is essential for resolving their accurate spatial positions beyond the diffraction limit. However, conventional technologies currently suffer from beam deviation errors which cannot be corrected beyond the diffraction limit. To overcome this issue, we experimentally demonstrate a spatially stable nano-imaging system for polarization-sensitive nanoparticles. In this study, we show that by integrating a voltage-tunable imaging variable polarizer with optical microscopy, we are able to suppress beam deviation errors. We expect that this nano-imaging system should allow for acquisition of accurate positional and polarization information from individual nanoparticles in applications where real-time, high precision spatial information is required.

Improved group-specific primers based on the full SILVA 16S rRNA gene reference database.

PubMed

Pfeiffer, Stefan; Pastar, Milica; Mitter, Birgit; Lippert, Kathrin; Hackl, Evelyn; Lojan, Paul; Oswald, Andreas; Sessitsch, Angela

2014-08-01

Quantitative PCR (qPCR) and community fingerprinting methods, such as the Terminal Restriction Fragment Length Polymorphism (T-RFLP) analysis,are well-suited techniques for the examination of microbial community structures. The use of phylum and class-specific primers can provide enhanced sensitivity and phylogenetic resolution as compared with domain-specific primers. To date, several phylum- and class-specific primers targeting the 16S ribosomal RNA gene have been published. However, many of these primers exhibit low discriminatory power against non-target bacteria in PCR. In this study, we evaluated the precision of certain published primers in silico and via specific PCR. We designed new qPCR and T-RFLP primer pairs (for the classes Alphaproteobacteria and Betaproteobacteria, and the phyla Bacteroidetes, Firmicutes and Actinobacteria) by combining the sequence information from a public dataset (SILVA SSU Ref 102 NR) with manual primer design. We evaluated the primer pairs via PCR using isolates of the above-mentioned groups and via screening of clone libraries from environmental soil samples and human faecal samples. As observed through theoretical and practical evaluation, the primers developed in this study showed a higher level of precision than previously published primers, thus allowing a deeper insight into microbial community dynamics.

Scientific investigations with the data base HEAO-1 scanning modulator collimator

NASA Technical Reports Server (NTRS)

Schwartz, Daniel A.

1992-01-01

The hardware specification for the Scanning Modulation Collimator (MC) experiment on HEAO-1 was to measure positions of bright (greater than 10(exp -11) ergs/cm(exp 2)s), hard (1 to 15 keV) x-ray sources to 5-10 arcsec, and to measure their size and structure in three energy bands down to 10 arcsec resolution. The scientific purpose of this specification was to enable the identification of these x-ray sources with optical and radio objects in order to elucidate the x-ray emission mechanism and the nature of the candidate astronomical system. The experiment was an outstanding success. Hardware systems functioned perfectly although loss of one (out of eight) proportional counters degraded our sensitivity by about 10 percent. Our aspect solution of 7 arcsec precision, allowed us to achieve statistic-limited location precision for all but the strongest sources. We vigorously pursued a strategy of determining the scientific importance of each identification, and of publishing each scientific result as it came along.

[The development and implementation of polymerase chain reaction to detect in real-time operation mode yersinia pestis in field material].

PubMed

Afanas'ev, M V; Chipanin, E V; Shestakov, V E; Denisov, A V; Fomina, L A; Ostiak, A S; Balakhonov, S V

2013-03-01

The article presents the results of development and practical implementation of system of polymerase chain reaction testing in real-time operation mode to detect agent of plague infield material. In laboratory conditions the system demonstrated good results and hence it was applied in conditions of field laboratory of epidemiologic team during planned epizootologic examination of Gorno-Altaisk hot spot of plague. The sampling consisted of more than 1400 objects. It was demonstrated that high sensitivity and specificity is immanent to proposed system. The adaptation of the system to the real time amplifier "Smart Cycler" (Cephid, USA) having some specific technical characteristics makes it possible to consider the proposed test-system as an effective sensitive and precise instrument for screening studies in the process of regular epizootologic examinations of hot spots of plague.

Recent advances in immunosensor for narcotic drug detection

PubMed Central

Gandhi, Sonu; Suman, Pankaj; Kumar, Ashok; Sharma, Prince; Capalash, Neena; Suri, C. Raman

2015-01-01

Introduction: Immunosensor for illicit drugs have gained immense interest and have found several applications for drug abuse monitoring. This technology has offered a low cost detection of narcotics; thereby, providing a confirmatory platform to compliment the existing analytical methods. Methods: In this minireview, we define the basic concept of transducer for immunosensor development that utilizes antibodies and low molecular mass hapten (opiate) molecules. Results: This article emphasizes on recent advances in immunoanalytical techniques for monitoring of opiate drugs. Our results demonstrate that high quality antibodies can be used for immunosensor development against target analyte with greater sensitivity, specificity and precision than other available analytical methods. Conclusion: In this review we highlight the fundamentals of different transducer technologies and its applications for immunosensor development currently being developed in our laboratory using rapid screening via immunochromatographic kit, label free optical detection via enzyme, fluorescence, gold nanoparticles and carbon nanotubes based immunosensing for sensitive and specific monitoring of opiates. PMID:26929925

Using the ADAP Learning Algorithm to Forecast the Onset of Diabetes Mellitus

PubMed Central

Smith, Jack W.; Everhart, J.E.; Dickson, W.C.; Knowler, W.C.; Johannes, R.S.

1988-01-01

Neural networks or connectionist models for parallel processing are not new. However, a resurgence of interest in the past half decade has occurred. In part, this is related to a better understanding of what are now referred to as hidden nodes. These algorithms are considered to be of marked value in pattern recognition problems. Because of that, we tested the ability of an early neural network model, ADAP, to forecast the onset of diabetes mellitus in a high risk population of Pima Indians. The algorithm's performance was analyzed using standard measures for clinical tests: sensitivity, specificity, and a receiver operating characteristic curve. The crossover point for sensitivity and specificity is 0.76. We are currently further examining these methods by comparing the ADAP results with those obtained from logistic regression and linear perceptron models using precisely the same training and forecasting sets. A description of the algorithm is included.

Evaluation of Raman spectroscopy in comparison to commonly performed dengue diagnostic tests

NASA Astrophysics Data System (ADS)

Khan, Saranjam; Ullah, Rahat; Khurram, Muhammad; Ali, Hina; Mahmood, Arshad; Khan, Ajmal; Ahmed, Mushtaq

2016-09-01

This study demonstrates the evaluation of Raman spectroscopy as a rapid diagnostic test in comparison to commonly performed tests for an accurate detection of dengue fever in human blood sera. Blood samples of 104 suspected dengue patients collected from Holy Family Hospital, Rawalpindi, Pakistan, have been used in this study. Out of 104 samples, 52 (50%) were positive based on immunoglobulin G (IgG), whereas 54 (52%) were positive based on immunoglobulin M (IgM) antibody tests. For the determination of the diagnostic capabilities of Raman spectroscopy, accuracy, sensitivity, specificity and false positive rate have been calculated in comparison to normally performed IgM and IgG captured enzyme-linked immunosorbent assay tests. Accuracy, precision, specificity, and sensitivity for Raman spectroscopy in comparison to IgM were found to be 66%, 70%, 72%, and 61%, whereas based on IgG they were 47%, 46%, 52%, and 43%, respectively.

Optimization and Validation of ELISA for Pre-Clinical Trials of Influenza Vaccine.

PubMed

Mitic, K; Muhandes, L; Minic, R; Petrusic, V; Zivkovic, I

2016-01-01

Testing of every new vaccine involves investigation of its immunogenicity, which is based on monitoring its ability to induce specific antibodies in animals. The fastest and most sensitive method used for this purpose is enzyme-linked immunosorbent assay (ELISA). However, commercial ELISA kits with whole influenza virus antigens are not available on the market, and it is therefore essential to establish an adequate assay for testing influenza virusspecific antibodies. We developed ELISA with whole influenza virus strains for the season 2011/2012 as antigens and validated it by checking its specificity, accuracy, linearity, range, precision, and sensitivity. The results show that we developed high-quality ELISA that can be used to test immunogenicity of newly produced seasonal or pandemic vaccines in mice. The pre-existence of validated ELISA enables shortening the time from the process of vaccine production to its use in patients, which is particularly important in the case of a pandemic.

Inflammatory bowel disease and patterns of volatile organic compounds in the exhaled breath of children: A case-control study using Ion Molecule Reaction-Mass Spectrometry.

PubMed

Monasta, Lorenzo; Pierobon, Chiara; Princivalle, Andrea; Martelossi, Stefano; Marcuzzi, Annalisa; Pasini, Francesco; Perbellini, Luigi

2017-01-01

Inflammatory bowel diseases (IBD) profoundly affect quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world, and in children in particular. Patients with suspected IBD require careful history and clinical examination, while definitive diagnosis relies on endoscopic and histological findings. The aim of the present study was to investigate whether the alveolar air of pediatric patients with IBD presents a specific volatile organic compounds' (VOCs) pattern when compared to controls. Patients 10-17 years of age, were divided into four groups: Crohn's disease (CD), ulcerative colitis (UC), controls with gastrointestinal symptomatology, and surgical controls with no evidence of gastrointestinal problems. Alveolar breath was analyzed by ion molecule reaction mass spectrometry. Four models were built starting from 81 molecules plus the age of subjects as independent variables, adopting a penalizing LASSO logistic regression approach: 1) IBDs vs. controls, finally based on 18 VOCs plus age (sensitivity = 95%, specificity = 69%, AUC = 0.925); 2) CD vs. UC, finally based on 13 VOCs plus age (sensitivity = 94%, specificity = 76%, AUC = 0.934); 3) IBDs vs. gastroenterological controls, finally based on 15 VOCs plus age (sensitivity = 94%, specificity = 65%, AUC = 0.918); 4) IBDs vs. controls, built starting from the 21 directly or indirectly calibrated molecules only, and finally based on 12 VOCs plus age (sensitivity = 94%, specificity = 71%, AUC = 0.888). The molecules identified by the models were carefully studied in relation to the concerned outcomes. This study, with the creation of models based on VOCs profiles, precise instrumentation and advanced statistical methods, can contribute to the development of new non-invasive, fast and relatively inexpensive diagnostic tools, with high sensitivity and specificity. It also represents a crucial step towards gaining further insights on the etiology of IBD through the analysis of specific molecules which are the expression of the particular metabolism that characterizes these patients.

Surface plasmon resonance spectroscopy sensor and methods for using same

DOEpatents

Anderson, Brian Benjamin; Nave, Stanley Eugene

2002-01-01

A surface plasmon resonance ("SPR") probe with a detachable sensor head and system and methods for using the same in various applications is described. The SPR probe couples fiber optic cables directly to an SPR substrate that has a generally planar input surface and a generally curved reflecting surface, such as a substrate formed as a hemisphere. Forming the SPR probe in this manner allows the probe to be miniaturized and operate without the need for high precision, expensive and bulky collimating or focusing optics. Additionally, the curved reflecting surface of the substrate can be coated with one or multiple patches of sensing medium to allow the probe to detect for multiple analytes of interest or to provide multiple readings for comparison and higher precision. Specific applications for the probe are disclosed, including extremely high sensitive relative humidity and dewpoint detection for, e.g., moisture-sensitive environment such as volatile chemical reactions. The SPR probe disclosed operates with a large dynamic range and provides extremely high quality spectra despite being robust enough for field deployment and readily manufacturable.

Rapid and Sensitive Quantification of Vibrio cholerae and Vibrio mimicus Cells in Water Samples by Use of Catalyzed Reporter Deposition Fluorescence In Situ Hybridization Combined with Solid-Phase Cytometry

PubMed Central

Schauer, Sonja; Sommer, Regina; Farnleitner, Andreas H.

2012-01-01

A new protocol for rapid, specific, and sensitive cell-based quantification of Vibrio cholerae/Vibrio mimicus in water samples was developed. The protocol is based on catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH) in combination with solid-phase cytometry. For pure cultures, we were able to quantify down to 6 V. cholerae cells on one membrane with a relative precision of 39% and down to 12 cells with a relative precision of 17% after hybridization with the horseradish peroxidase (HRP)-labeled probe Vchomim1276 (specific for V. cholerae and V. mimicus) and signal amplification. The corresponding position of the probe on the 16S rRNA is highly accessible even when labeled with HRP. For the first time, we were also able to successfully quantify V. cholerae/V. mimicus via solid-phase cytometry in extremely turbid environmental water samples collected in Austria. Cell numbers ranged from 4.5 × 101 cells ml−1 in the large saline lake Neusiedler See to 5.6 × 104 cells ml−1 in an extremely turbid shallow soda lake situated nearby. We therefore suggest CARD-FISH in combination with solid-phase cytometry as a powerful tool to quantify V. cholerae/V. mimicus in ecological studies as well as for risk assessment and monitoring programs. PMID:22885749

Optical coherence tomography allows for the reliable identification of laryngeal epithelial dysplasia and for precise biopsy: a clinicopathological study of 61 patients undergoing microlaryngoscopy.

PubMed

Just, Tino; Lankenau, Eva; Prall, Friedrich; Hüttmann, Gereon; Pau, Hans Wilhelm; Sommer, Konrad

2010-10-01

A newly developed microscope-based spectral-domain optical coherence tomography (SD-OCT) device and an endoscope-based time-domain OCT (TD-OCT) were used to assess the inter-rater reliability, sensitivity, specificity, and accuracy of benign and dysplastic laryngeal epithelial lesions. Prospective study. OCT during microlaryngoscopy was done on 35 patients with an endoscope-based TD-OCT, and on 26 patients by an SD-OCT system integrated into an operating microscope. Biopsies were taken from microscopically suspicious lesions allowing comparative study of OCT images and histology. Thickness of the epithelium was seen to be the main criterion for degree of dysplasia. The inter-rater reliability for two observers was found to be kappa = 0.74 (P <.001) for OCT. OCT provided test outcomes for differentiation between benign laryngeal lesions and dysplasia/CIS with sensitivity of 88%, specificity of 89%, PPV of 85%, NPV of 91%, and predictive accuracy of 88%. However, because of the limited penetration depth of the laser light primarily in hyperkeratotic lesions (thickness above 1.5 mm), the basal cell layer was no longer visible, precluding reliable assessment of such lesions. OCT allows for a fairly accurate assessment of benign and dysplastic laryngeal epithelial lesion and greatly facilitates the taking of precise biopsies. Laryngoscope, 2010.

Development and Preliminary Tests of an Open-Path Airborne Diode Laser Absorption Instrument for Carbon Dioxide

NASA Technical Reports Server (NTRS)

Diskin, Glenn S.; DiGangi, Joshua P.; Yang, Melissa; Slate, Thomas A.; Rana, Mario

2015-01-01

Carbon dioxide (CO2) is well known for its importance as an atmospheric greenhouse gas, with many sources and sinks around the globe. Understanding the fluxes of carbon into and out of the atmosphere is a complex and daunting challenge. One tool applied by scientists to measure the vertical flux of CO2 near the surface uses the eddy covariance technique, most often from towers but also from aircraft flying specific patterns over the study area. In this technique, variations of constituents of interest are correlated with fluctuations in the local vertical wind velocity. Measurement requirements are stringent, particularly with regard to precision, sensitivity to small changes, and temporal sampling rate. In addition, many aircraft have limited payload capability, so instrument size, weight, and power consumption are also important considerations. We report on the development and preliminary application of an airborne sensor for the measurement of atmospheric CO2. The instrument, modeled on the successful DLH (Diode Laser Hygrometer) series of instruments, has been tested in the laboratory and on the NASA DC-8 aircraft. Performance parameters such as accuracy, precision, sensitivity, specificity, and temporal response are discussed in the context of typical atmospheric variability and suitability for flux measurement applications. On-aircraft, in-flight data have been obtained and are discussed as well. Performance of the instrument has been promising, and continued flight testing is planned during 2016.

A microfluidic system with integrated molecular imprinting polymer films for surface plasmon resonance detection

NASA Astrophysics Data System (ADS)

Huang, Shih-Chiang; Lee, Gwo-Bin; Chien, Fan-Ching; Chen, Shean-Jen; Chen, Wen-Janq; Yang, Ming-Chang

2006-07-01

This paper presents a novel microfluidic system with integrated molecular imprinting polymer (MIP) films designed for surface plasmon resonance (SPR) biosensing of multiple nanoscale biomolecules. The innovative microfluidic chip uses pneumatic microvalves and micropumps to transport a precise amount of the biosample through multiple microchannels to sensing regions containing the locally spin-coated MIP films. The signals of SPR biosensing are basically proportional to the number of molecules adsorbed on the MIP films. Hence, a precise control of flow rates inside microchannels is important to determine the adsorption amount of the molecules in the SPR/MIP chips. The integration of micropumps and microvalves can automate the sample introduction process and precisely control the amount of the sample injection to the microfluidic system. The proposed biochip enables the label-free biosensing of biomolecules in an automatic format, and provides a highly sensitive, highly specific and high-throughput detection performance. Three samples, i.e. progesterone, cholesterol and testosterone, are successfully detected using the developed system. The experimental results show that the proposed SPR/MIP microfluidic chip provides a comparable sensitivity to that of large-scale SPR techniques, but with reduced sample consumption and an automatic format. As such, the developed biochip has significant potential for a wide variety of nanoscale biosensing applications. The preliminary results of the current paper were presented at Transducers 2005, Seoul, Korea, 5-9 June 2005.

Nanoparticle imaging probes for molecular imaging with computed tomography and application to cancer imaging

NASA Astrophysics Data System (ADS)

Roeder, Ryan K.; Curtis, Tyler E.; Nallathamby, Prakash D.; Irimata, Lisa E.; McGinnity, Tracie L.; Cole, Lisa E.; Vargo-Gogola, Tracy; Cowden Dahl, Karen D.

2017-03-01

Precision imaging is needed to realize precision medicine in cancer detection and treatment. Molecular imaging offers the ability to target and identify tumors, associated abnormalities, and specific cell populations with overexpressed receptors. Nuclear imaging and radionuclide probes provide high sensitivity but subject the patient to a high radiation dose and provide limited spatiotemporal information, requiring combined computed tomography (CT) for anatomic imaging. Therefore, nanoparticle contrast agents have been designed to enable molecular imaging and improve detection in CT alone. Core-shell nanoparticles provide a powerful platform for designing tailored imaging probes. The composition of the core is chosen for enabling strong X-ray contrast, multi-agent imaging with photon-counting spectral CT, and multimodal imaging. A silica shell is used for protective, biocompatible encapsulation of the core composition, volume-loading fluorophores or radionuclides for multimodal imaging, and facile surface functionalization with antibodies or small molecules for targeted delivery. Multi-agent (k-edge) imaging and quantitative molecular imaging with spectral CT was demonstrated using current clinical agents (iodine and BaSO4) and a proposed spectral library of contrast agents (Gd2O3, HfO2, and Au). Bisphosphonate-functionalized Au nanoparticles were demonstrated to enhance sensitivity and specificity for the detection of breast microcalcifications by conventional radiography and CT in both normal and dense mammary tissue using murine models. Moreover, photon-counting spectral CT enabled quantitative material decomposition of the Au and calcium signals. Immunoconjugated Au@SiO2 nanoparticles enabled highly-specific targeting of CD133+ ovarian cancer stem cells for contrast-enhanced detection in model tumors.

Analytical characteristics and comparative evaluation of Aptima HIV-1 Quant Dx assay with Ampliprep/COBAS TaqMan HIV-1 test v2.0.

PubMed

Hatzakis, Angelos; Papachristou, Helen; Nair, Sangeetha J; Fortunko, Jacqueline; Foote, Tracy; Kim, HeeCheol; Peling, Tashi L; Worlock, Andrew J

2016-10-21

Quantitation of HIV-RNA is critically important for diagnosis, prognosis, treatment, monitoring and assessment of infectivity in HIV-1 infection. The objective of this study was to assess performance characteristics of the Aptima HIV-1 Quant Dx assay (Aptima), a new transcription mediated amplification (TMA), fully integrated and automated assay from Hologic Inc., San Diego, CA, USA. The analytical sensitivity, analytical specificity, precision and detection of HIV-1 subtypes were tested based on commercially available international standards or panels. A selected group of 244 anti-HIV-1 (+) plasma samples was used for comparison with Roche COBAS Ampliprep/COBAS TaqMan HIV- 1 test v2.0 (Roche CAP/CTM), (Roche Molecular Systems, Pleasanton, CA). The 50 and 95 % limit of detection were estimated at 4.9 (95 % CI 3.9-5.7) and 17.6 (15.2-21.2) IU/mL respectively. The specificity was found 99.83 (99.06-99.97) %. The standard deviations and coefficient of variations for panels with 50 and 100 copies/mL (1.7 and 2 log copies/mL) were 0.14 log copies/mL (8.67 %CV) and 0.18 log copies/mL (9.91 %CV) respectively. The detection rate for Aptima and Roche assays was 220/244 (90.2 %) and 217/244 (88.9 %) respectively. The Aptima assay is a sensitive, specific, precise and accurate test for measuring HIV-1 viral loads and for the detection of HIV-1 infections.

Development of a BK virus real-time quantitative assay using the bioMérieux analyte-specific reagents in plasma specimens.

PubMed

Rennert, Hanna; Fernandes, Helen; Gilani, Zahid; Sipley, John

2015-12-01

Viral load testing for BK virus (BKV) has become the standard of care for diagnosing BKV infection and monitoring therapy in kidney transplant patients. However, there are currently no US Food and Drug Administration-approved assays and no standardization among available tests. This study evaluated the performance of the analyte-specific reagent (ASR) BKV primers r-gene and probe r-gene reagents (bioMérieux, Marcy l'Étoile, France) soon to become available on the US market for accuracy, linearity, precision, analytical sensitivity, specificity, and correlation with the Qiagen (Germantown, MD) BKV ASR test using commercial material and patient plasma samples. The assay was linear from 204 to 3.92 million (2.31-6.6 log10) DNA copies/mL (coefficient of determination: R(2) =0.999). A dilution series demonstrated limits of detection and quantitation of 2.14 log10 and 2.30 log10 copies/mL (95% hit rate detection), respectively. Interrun precision was highly reproducible, with coefficients of variance ranging from 2.2% to 6.0%. A comparison of 34 matched samples showed a good agreement (R(2) = 0.87) between the bioMérieux BKV laboratory test and the Qiagen BKV ASR assay results, with an average negative bias (-0.28 log10 copies/mL). The laboratory-developed test with bioMérieux BKV reagents is a reliable and sensitive assay for BKV DNA quantitation compared with the Qiagen ASR test. Copyright© by the American Society for Clinical Pathology.

Combining Whispering-Gallery Mode Optical Biosensors with Microfluidics for Real-Time Detection of Protein Secretion from Living Cells in Complex Media.

PubMed

Chen, Ying-Jen; Schoeler, Ulrike; Huang, Chung-Hsuan Benjamin; Vollmer, Frank

2018-05-01

The noninvasive monitoring of protein secretion of cells responding to drug treatment is an effective and essential tool in latest drug development and for cytotoxicity assays. In this work, a surface functionalization method is demonstrated for specific detection of protein released from cells and a platform that integrates highly sensitive optical devices, called whispering-gallery mode biosensors, with precise microfluidics control to achieve label-free and real-time detection. Cell biomarker release is measured in real time and with nanomolar sensitivity. The surface functionalization method allows for antibodies to be immobilized on the surface for specific detection, while the microfluidics system enables detection in a continuous flow with a negligible compromise between sensitivity and flow control over stabilization and mixing. Cytochrome c detection is used to illustrate the merits of the system. Jurkat cells are treated with the toxin staurosporine to trigger cell apoptosis and cytochrome c released into the cell culture medium is monitored via the newly invented optical microfluidic platform. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Blood collected on filter paper for wildlife serology: detecting antibodies to Neospora caninum, West Nile virus, and five bovine viruses in reindeer.

PubMed

Curry, Patricia S; Ribble, Carl; Sears, William C; Hutchins, Wendy; Orsel, Karin; Godson, Dale; Lindsay, Robbin; Dibernardo, Antonia; Kutz, Susan J

2014-04-01

We compared Nobuto filter paper (FP) whole-blood samples to serum for detecting antibodies to seven pathogens in reindeer (Rangifer tarandus tarandus). Serum and FP samples were collected from captive reindeer in 2008-2009. Sample pairs (serum and FP eluates) were assayed in duplicate at diagnostic laboratories with the use of competitive enzyme-linked immunosorbent assays (cELISAs) for Neospora caninum and West Nile virus (WNV); indirect ELISA (iELISAs) for bovine herpesvirus type 1 (BHV-1), parainfluenza virus type 3 (PI-3), and bovine respiratory syncytial virus (BRSV); and virus neutralization (VN) for bovine viral diarrhea virus (BVDV) types I and II. Assay thresholds were evidence-based values employed by each laboratory. Comparable performance to serum was defined as FP sensitivity and specificity ≥ 80%. Filter-paper specificity estimates ranged from 92% in the cELISAs for N. caninum and WNV to 98% in the iELISAs for PI-3 and BRSV. Sensitivity was >85% for five tests (most ≥ 95%) but was insufficient (71-82%) for the PI-3 and BRSV iELISAs. Lowering the threshold for FP samples in these two ELISAs raised sensitivity to ≥ 87% and reduced specificity slightly (≥ 90% in three of the four test runs). Sample size limited the precision of some performance estimates. Based on the criteria of sensitivity and specificity ≥ 80%, and using adjusted FP thresholds for PI-3 and BRSV, FP sensitivity and specificity were comparable to serum in all seven assays. A potential limitation of FP is reduced sensitivity in tests that require undiluted serum (i.e., N. caninum cELISA and BVDV VNs). Possible toxicity to the assay cell layer in VN requires investigation. Results suggested that cELISA is superior to iELISA for detecting antibodies in FP samples from reindeer and other Rangifer tarandus subspecies. Our findings expand the potential utility of FP sampling from wildlife.

Light leptonic new physics at the precision frontier

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

Le Dall, Matthias, E-mail: mledall@uvic.ca

2016-06-21

Precision probes of new physics are often interpreted through their indirect sensitivity to short-distance scales. In this proceedings contribution, we focus on the question of which precision observables, at current sensitivity levels, allow for an interpretation via either short-distance new physics or consistent models of long-distance new physics, weakly coupled to the Standard Model. The electroweak scale is chosen to set the dividing line between these scenarios. In particular, we find that inverse see-saw models of neutrino mass allow for light new physics interpretations of most precision leptonic observables, such as lepton universality, lepton flavor violation, but not for themore » electron EDM.« less

High-depth, high-accuracy microsatellite genotyping enables precision lung cancer risk classification

PubMed Central

Velmurugan, K R; Varghese, R T; Fonville, N C; Garner, H R

2017-01-01

There remains a large discrepancy between the known genetic contributions to cancer and that which can be explained by genomic variants, both inherited and somatic. Recently, understudied repetitive DNA regions called microsatellites have been identified as genetic risk markers for a number of diseases including various cancers (breast, ovarian and brain). In this study, we demonstrate an integrated process for identifying and further evaluating microsatellite-based risk markers for lung cancer using data from the cancer genome atlas and the 1000 genomes project. Comparing whole-exome germline sequencing data from 488 TCGA lung cancer samples to germline exome data from 390 control samples from the 1000 genomes project, we identified 119 potentially informative microsatellite loci. These loci were found to be able to distinguish between cancer and control samples with sensitivity and specificity ratios over 0.8. Then these loci, supplemented with additional loci from other cancers and controls, were evaluated using a target enrichment kit and sample-multiplexed nextgen sequencing. Thirteen of the 119 risk markers were found to be informative in a well powered study (>0.99 for a 0.95 confidence interval) using high-depth (579x±315) nextgen sequencing of 30 lung cancer and 89 control samples, resulting in sensitivity and specificity ratios of 0.90 and 0.94, respectively. When 8 loci harvested from the bioinformatic analysis of other cancers are added to the classifier, then the sensitivity and specificity rise to 0.93 and 0.97, respectively. Analysis of the genes harboring these loci revealed two genes (ARID1B and REL) and two significantly enriched pathways (chromatin organization and cellular stress response) suggesting that the process of lung carcinogenesis is linked to chromatin remodeling, inflammation, and tumor microenvironment restructuring. We illustrate that high-depth sequencing enables a high-precision microsatellite-based risk classifier analysis approach. This microsatellite-based platform confirms the potential to create clinically actionable diagnostics for lung cancer. PMID:28759038

High-depth, high-accuracy microsatellite genotyping enables precision lung cancer risk classification.

PubMed

Velmurugan, K R; Varghese, R T; Fonville, N C; Garner, H R

2017-11-16

There remains a large discrepancy between the known genetic contributions to cancer and that which can be explained by genomic variants, both inherited and somatic. Recently, understudied repetitive DNA regions called microsatellites have been identified as genetic risk markers for a number of diseases including various cancers (breast, ovarian and brain). In this study, we demonstrate an integrated process for identifying and further evaluating microsatellite-based risk markers for lung cancer using data from the cancer genome atlas and the 1000 genomes project. Comparing whole-exome germline sequencing data from 488 TCGA lung cancer samples to germline exome data from 390 control samples from the 1000 genomes project, we identified 119 potentially informative microsatellite loci. These loci were found to be able to distinguish between cancer and control samples with sensitivity and specificity ratios over 0.8. Then these loci, supplemented with additional loci from other cancers and controls, were evaluated using a target enrichment kit and sample-multiplexed nextgen sequencing. Thirteen of the 119 risk markers were found to be informative in a well powered study (>0.99 for a 0.95 confidence interval) using high-depth (579x±315) nextgen sequencing of 30 lung cancer and 89 control samples, resulting in sensitivity and specificity ratios of 0.90 and 0.94, respectively. When 8 loci harvested from the bioinformatic analysis of other cancers are added to the classifier, then the sensitivity and specificity rise to 0.93 and 0.97, respectively. Analysis of the genes harboring these loci revealed two genes (ARID1B and REL) and two significantly enriched pathways (chromatin organization and cellular stress response) suggesting that the process of lung carcinogenesis is linked to chromatin remodeling, inflammation, and tumor microenvironment restructuring. We illustrate that high-depth sequencing enables a high-precision microsatellite-based risk classifier analysis approach. This microsatellite-based platform confirms the potential to create clinically actionable diagnostics for lung cancer.

Clinical value of real time 3D sonohysterography and 2D sonohysterography in comparison to hysteroscopy with subsequent histopathological examination in perimenopausal women with abnormal uterine bleeding.

PubMed

Kowalczyk, Dariusz; Guzikowski, Wojciech; Więcek, Jacek; Sioma-Markowska, Urszula

2012-01-01

In many publications the transvaginal ultrasound is regarded as the first step to diagnose the cause of uterine bleeding in perimenopausal women. In order to improve the sensitivity and specificity of the conventional ultrasound physiological saline solution was administered to the uterine cavity and after expansion of its walls the interior uterine cavity was examined. And this procedure is called 2D sonohysterography (SIS 2D). By the ultrasound scanners which enable to get 3D real time image a spatial evaluation of the uterine cavity is possible. Clinical value of the real time 3D sonohysterography and 2D sonohysterography compared to hysteroscopy with histopathological examination in perimenopausal women. The study concerned a group of 97 perimenopausal women with abnormal uterine bleeding. In all of them after a standard transvaginal ultrasonography a catheter was inserted into the uterine cavity. After expansion of the uterine walls by administering about 10 ml of 0,9% saline solution the uterine cavity was examined by conventional sonohysterography. Then a 3D imaging mode was activated and the uterine interior was examined by real time 3D ultrasonography. The ultrasound results were verified by hysteroscopy, the endometrial lesions were removed and underwent a histopathological examination. In two cases the SIS examination was impossible because of uterine cervix atresion. In the rest of examined group the SIS 2D sensitivity and specificity came up to 72 and 96% respectively. In the group of SIS 3D the sensitivity and specificity reached 83 and 99% respectively. Adding SIS 3D, a minimally invasive method, to conventional sonohysterography improves the precision of diagnosis of endometrial pathology, allows to get three-dimensional image of the uterine cavity and enables examination of endometrial lesions. The diagnostic precision of this procedure is similar to the results achieved by hysteroscopy.

An evaluation of the automated assay of urinary oestrogens in pregnant women

PubMed Central

Muir, G. G.; Ryan, M.; Conaill, D. U.

1970-01-01

An automated assay suitable for estimating urinary oestrogens in pregnant women has been investigated. Fluorimetry was found to have considerable advantages over colorimetry. The fluorimetric assay was simpler, more precise, more sensitive, and eliminated the need for correction for non-specific chromogens; in the assay of oestriol in pregnant women there was no need for correction for non-specific fluorescence. Spectrofluorimetric and photometric analyses, recoveries, and reproducibility show that the method offers a robust means of providing values for urinary oestrogen in pregnant women on a scale of up to 100 tests a day, the time of the assay being one and a half hours. PMID:5476876

Kindling of life stress in bipolar disorder: comparison of sensitization and autonomy models.

PubMed

Weiss, Rachel B; Stange, Jonathan P; Boland, Elaine M; Black, Shimrit K; LaBelle, Denise R; Abramson, Lyn Y; Alloy, Lauren B

2015-02-01

Research on life stress in bipolar disorder largely fails to account for the possibility of a dynamic relationship between psychosocial stress and episode initiation. The kindling hypothesis (Post, 1992) states that over the course of recurrent affective disorders, there is a weakening temporal relationship between major life stress and episode initiation that could reflect either a progressive sensitization or progressive autonomy to life stress. The present study involved a comprehensive and precise examination of the kindling hypothesis in 102 participants with bipolar II disorder that allowed for a direct comparison of sensitization and autonomy models. Polarity-specific tests were conducted across the continuum of event severity with respect to impact and frequency of life events. Hypotheses were polarity- and event-valence specific and were based on the stress sensitization model. Results were only partially consistent with the sensitization model: Individuals with more prior mood episodes had an increased frequency of minor negative events before depression and of minor positive events before hypomania. However, the number of past episodes did not moderate relationships between life events and time until prospective onset of mood episodes. These results are more consistent with a sensitization than an autonomy model, but several predictions of the sensitization model were not supported. Methodological strengths, limitations, and implications are discussed regarding putative changes in stress reactivity that may occur with repeated exposure to mood episodes in bipolar II disorder. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Water vapor δ17O measurements using an off-axis integrated cavity output spectrometer and seasonal variation in 17O-excess of precipitation in the east-central United States

NASA Astrophysics Data System (ADS)

Tian, C.; Wang, L.; Novick, K. A.

2016-12-01

High-precision triple oxygen isotope analysis can be used to improve our understanding of multiple hydrological and meteorological processes. Recent studies focus on understanding 17O-excess variation of tropical storms, high-latitude snow and ice-core as well as spatial distribution of meteoric water (tap water). The temporal scale of 17O-excess variation in middle-latitude precipitation is needed to better understand which processes control on the 17O-excess variations. This study focused on assessing how the accuracy and precision of vapor δ17O laser spectroscopy measurements depend on vapor concentration, delta range, and averaging-time. Meanwhile, we presented 17O-excess data from two-year, event based precipitation sampling in the east-central United States. A Triple Water Vapor Isotope Analyzer (T-WVIA) was used to evaluate the accuracy and precision of δ2H, δ18O and δ17O measurements. GISP and SLAP2 from IAEA and four working standards were used to evaluate the sensitivity in the three factors. Overall, the accuracy and precision of all isotope measurements were sensitive to concentration, with higher accuracy and precision generally observed under moderate vapor concentrations (i.e., 10000-15000 ppm) for all isotopes. Precision was also sensitive to the range of delta values, though the effect was not as large when compared to the sensitivity to concentration. The precision was much less sensitive to averaging time when compared with concentration and delta range effects. The preliminary results showed that 17O-excess variation was lower in summer (23±17 per meg) than in winter (34±16 per meg), whereas spring values (30±21 per meg) was similar to fall (29±13 per meg). That means kinetic fractionation influences the isotopic composition and 17O-excess in different seasons.

Measurement precision in a series of visual fields acquired by the standard and fast versions of the Swedish interactive thresholding algorithm: analysis of large-scale data from clinics.

PubMed

Saunders, Luke J; Russell, Richard A; Crabb, David P

2015-01-01

Swedish Interactive Thresholding Algorithm (SITA) testing strategies for the Humphrey Field Analyzer have become a clinical standard. Measurements from SITA Fast are thought to be more variable than SITA Standard, yet some clinics routinely use SITA Fast because it is quicker. To examine the measurement precision of the 2 SITA strategies across a range of sensitivities using a large number of visual field (VF) series from 4 glaucoma clinics in England. Retrospective cohort study at Moorfields Eye Hospital in London, England; Gloucestershire Eye Unit at Cheltenham General Hospital; Queen Alexandra Hospital in Portsmouth, England; and the Calderdale and Huddersfield National Health Service Foundation Trust that included 66,974 Humphrey 24-2 SITA Standard VFs (10,124 eyes) and 19,819 Humphrey 24-2 SITA Fast VFs (3654 eyes) recorded between May 20, 1997, and September 20, 2012. Pointwise ordinary least squares linear regression of measured sensitivity over time was conducted using VF series of 1 random eye from each patient. Residuals from the regression were pooled according to fitted sensitivities. For each sensitivity (decibel) level, the standard deviation of the residuals was used to estimate measurement precision and were compared for SITA Standard and SITA Fast. Simulations of progression from different VF baselines were used to evaluate how different levels of precision would affect time to detect VF progression. Median years required to detect progression. Median (interquartile range) patient age, follow-up, and series lengths for SITA Standard were 64 (53-72) years, 6.0 (4.0-8.5) years, and 6 (4-8) VFs, respectively; for SITA Fast, medians (interquartile range) were 70 (61-78) years, 5.1 (3.2-7.3) years, and 5 (4-6) VFs. Measurement precision worsened as sensitivity decreased for both test strategies. In the 20 to 5 dB range, SITA Fast was less precise than SITA Standard; this difference was largest between 15 to 10 dB, where variability in both methods peaked. Translated to median time to detection, differences in measurement precision were negligible, suggesting minimal effects on time to detect progression. Although SITA Standard is a more precise testing algorithm than SITA Fast at lower VF sensitivities, it is unlikely to make a sizeable difference to improving the time to detect VF progression.

Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

PubMed

Albers, Christian; Westkott, Maren; Pawelzik, Klaus

2016-01-01

Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity

PubMed Central

Albers, Christian; Westkott, Maren; Pawelzik, Klaus

2016-01-01

Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns. PMID:26900845

Detecting Tie2, an endothelial growth factor receptor, by using immunohistochemistry in mouse lungs.

PubMed

Guha, Prajna P; David, Sascha A; Ghosh, Chandra C

2014-01-01

Immunohistochemical (IHC) staining is an invaluable, sensitive, and effective method to detect the presence and localization of proteins in the cellular compartment in tissues. The basic concept of IHC is detecting the antigen in tissues by means of specific antibody binding, which is then demonstrated with a colored histochemical reaction that can be observed under a light microscope. The most challenging aspect of IHC techniques is optimizing the precise experimental conditions that are required to get a specific and a strong signal. The critical steps of IHC are specimen acquisition, fixation, permeabilization, detection system, and selection of the antigen specific antibody and its optimization. Here, we elaborate the technique using the endothelial growth factor binding receptor Tie2 in mouse lungs.

Quantification of Kryptofix 2.2.2 in [18F]fluorine-labelled radiopharmaceuticals by rapid-resolution liquid chromatography.

PubMed

Lao, Yexing; Yang, Cuiping; Zou, Wei; Gan, Manquan; Chen, Ping; Su, Weiwei

2012-05-01

The cryptand Kryptofix 2.2.2 is used extensively as a phase-transfer reagent in the preparation of [18F]fluoride-labelled radiopharmaceuticals. However, it has considerable acute toxicity. The aim of this study was to develop and validate a method for rapid (within 1 min), specific and sensitive quantification of Kryptofix 2.2.2 at trace levels. Chromatographic separations were carried out by rapid-resolution liquid chromatography (Agilent ZORBAX SB-C18 rapid-resolution column, 2.1 × 30 mm, 3.5 μm). Tandem mass spectra were acquired using a triple quadrupole mass spectrometer equipped with an electrospray ionization interface. Quantitative mass spectrometric analysis was conducted in positive ion mode and multiple reaction monitoring mode for the m/z 377.3 → 114.1 transition for Kryptofix 2.2.2. The external standard method was used for quantification. The method met the precision and efficiency requirements for PET radiopharmaceuticals, providing satisfactory results for specificity, matrix effect, stability, linearity (0.5-100 ng/ml, r(2)=0.9975), precision (coefficient of variation < 5%), accuracy (relative error < ± 3%), sensitivity (lower limit of quantification=0.5 ng) and detection time (<1 min). Fluorodeoxyglucose (n=6) was analysed, and the Kryptofix 2.2.2 content was found to be well below the maximum permissible levels approved by the US Food and Drug Administration. The developed method has a short analysis time (<1 min) and high sensitivity (lower limit of quantification=0.5 ng/ml) and can be successfully applied to rapid quantification of Kryptofix 2.2.2 at trace levels in fluorodeoxyglucose. This method could also be applied to other [18F]fluorine-labelled radiopharmaceuticals that use Kryptofix 2.2.2 as a phase-transfer reagent.

Efficient strategies to find diagnostic test accuracy studies in kidney journals.

PubMed

Rogerson, Thomas E; Ladhani, Maleeka; Mitchell, Ruth; Craig, Jonathan C; Webster, Angela C

2015-08-01

Nephrologists looking for quick answers to diagnostic clinical questions in MEDLINE can use a range of published search strategies or Clinical Query limits to improve the precision of their searches. We aimed to evaluate existing search strategies for finding diagnostic test accuracy studies in nephrology journals. We assessed the accuracy of 14 search strategies for retrieving diagnostic test accuracy studies from three nephrology journals indexed in MEDLINE. Two investigators hand searched the same journals to create a reference set of diagnostic test accuracy studies to compare search strategy results against. We identified 103 diagnostic test accuracy studies, accounting for 2.1% of all studies published. The most specific search strategy was the Narrow Clinical Queries limit (sensitivity: 0.20, 95% CI 0.13-0.29; specificity: 0.99, 95% CI 0.99-0.99). Using the Narrow Clinical Queries limit, a searcher would need to screen three (95% CI 2-6) articles to find one diagnostic study. The most sensitive search strategy was van der Weijden 1999 Extended (sensitivity: 0.95; 95% CI 0.89-0.98; specificity 0.55, 95% CI 0.53-0.56) but required a searcher to screen 24 (95% CI 23-26) articles to find one diagnostic study. Bachmann 2002 was the best balanced search strategy, which was sensitive (0.88, 95% CI 0.81-0.94), but also specific (0.74, 95% CI 0.73-0.75), with a number needed to screen of 15 (95% CI 14-17). Diagnostic studies are infrequently published in nephrology journals. The addition of a strategy for diagnostic studies to a subject search strategy in MEDLINE may reduce the records needed to screen while preserving adequate search sensitivity for routine clinical use. © 2015 Asian Pacific Society of Nephrology.

PreCisIon: PREdiction of CIS-regulatory elements improved by gene's positION.

PubMed

Elati, Mohamed; Nicolle, Rémy; Junier, Ivan; Fernández, David; Fekih, Rim; Font, Julio; Képès, François

2013-02-01

Conventional approaches to predict transcriptional regulatory interactions usually rely on the definition of a shared motif sequence on the target genes of a transcription factor (TF). These efforts have been frustrated by the limited availability and accuracy of TF binding site motifs, usually represented as position-specific scoring matrices, which may match large numbers of sites and produce an unreliable list of target genes. To improve the prediction of binding sites, we propose to additionally use the unrelated knowledge of the genome layout. Indeed, it has been shown that co-regulated genes tend to be either neighbors or periodically spaced along the whole chromosome. This study demonstrates that respective gene positioning carries significant information. This novel type of information is combined with traditional sequence information by a machine learning algorithm called PreCisIon. To optimize this combination, PreCisIon builds a strong gene target classifier by adaptively combining weak classifiers based on either local binding sequence or global gene position. This strategy generically paves the way to the optimized incorporation of any future advances in gene target prediction based on local sequence, genome layout or on novel criteria. With the current state of the art, PreCisIon consistently improves methods based on sequence information only. This is shown by implementing a cross-validation analysis of the 20 major TFs from two phylogenetically remote model organisms. For Bacillus subtilis and Escherichia coli, respectively, PreCisIon achieves on average an area under the receiver operating characteristic curve of 70 and 60%, a sensitivity of 80 and 70% and a specificity of 60 and 56%. The newly predicted gene targets are demonstrated to be functionally consistent with previously known targets, as assessed by analysis of Gene Ontology enrichment or of the relevant literature and databases.

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

Verzhbitskiy, Ivan A.; Corato, Marzio De; Ruini, Alice

Bottom-up approaches allow the production of ultranarrow and atomically precise graphene nanoribbons (GNRs) with electronic and optical properties controlled by the specific atomic structure. Combining Raman spectroscopy and ab initio simulations, we show that GNR width, edge geometry, and functional groups all influence their Raman spectra. As a result, the low-energy spectral region below 1000 cm –1 is particularly sensitive to edge morphology and functionalization, while the D peak dispersion can be used to uniquely fingerprint the presence of GNRs and differentiates them from other sp 2 carbon nanostructures.

Physics of chemoreception.

PubMed Central

Berg, H C; Purcell, E M

1977-01-01

Statistical fluctuations limit the precision with which a microorganism can, in a given time T, determine the concentration of a chemoattractant in the surrounding medium. The best a cell can do is to monitor continually the state of occupation of receptors distributed over its surface. For nearly optimum performance only a small fraction of the surface need be specifically adsorbing. The probability that a molecule that has collided with the cell will find a receptor is Ns/(Ns + pi a), if N receptors, each with a binding site of radius s, are evenly distributed over a cell of radius a. There is ample room for many indenpendent systems of specific receptors. The adsorption rate for molecules of moderate size cannot be significantly enhanced by motion of the cell or by stirring of the medium by the cell. The least fractional error attainable in the determination of a concentration c is approximately (TcaD) - 1/2, where D is diffusion constant of the attractant. The number of specific receptors needed to attain such precision is about a/s. Data on bacteriophage absorption, bacterial chemotaxis, and chemotaxis in a cellular slime mold are evaluated. The chemotactic sensitivity of Escherichia coli approaches that of the cell of optimum design. PMID:911982

Discrimination of Influenza Infection (A/2009 H1N1) from Prior Exposure by Antibody Protein Microarray Analysis

PubMed Central

te Beest, Dennis; de Bruin, Erwin; Imholz, Sandra; Wallinga, Jacco; Teunis, Peter; Koopmans, Marion; van Boven, Michiel

2014-01-01

Reliable discrimination of recent influenza A infection from previous exposure using hemagglutination inhibition (HI) or virus neutralization tests is currently not feasible. This is due to low sensitivity of the tests and the interference of antibody responses generated by previous infections. Here we investigate the diagnostic characteristics of a newly developed antibody (HA1) protein microarray using data from cross-sectional serological studies carried out before and after the pandemic of 2009. The data are analysed by mixture models, providing a probabilistic classification of sera (susceptible, prior-exposed, recently infected). Estimated sensitivity and specificity for identifying A/2009 infections are low using HI (66% and 51%), and high when using A/2009 microarray data alone or together with A/1918 microarray data (96% and 95%). As a heuristic, a high A/2009 to A/1918 antibody ratio (>1.05) is indicative of recent infection, while a low ratio is indicative of a pre-existing response, even if the A/2009 titer is high. We conclude that highly sensitive and specific classification of individual sera is possible using the protein microarray, thereby enabling precise estimation of age-specific infection attack rates in the population even if sample sizes are small. PMID:25405997

Diagnostic utility of a line probe assay for multidrug resistant-TB in smear-negative pulmonary tuberculosis.

PubMed

Singh, Binit Kumar; Sharma, Surendra K; Sharma, Rohini; Sreenivas, Vishnubhatla; Myneedu, Vithal P; Kohli, Mikashmi; Bhasin, Dinkar; Sarin, Sanjay

2017-01-01

To evaluate the performance of Genotype MTBDRplus VER 2.0 in the diagnosis of Mycobacterium tuberculosis (MTB) in sputum smear-negative pulmonary TB cases. A total of 572 Ziehl-Neelsen sputum smear-negative samples were selected and subjected to line probe assay (Genotype MTBDRplus VER 2.0), and culture in mycobacterial growth indicator tube (MGIT-960). Immunochromatographic test was used to confirm the MTB-complex (MTBC) in culture-positive samples and phenotypic drug-susceptibility testing was done using MGIT-960. The line probe assay was able to diagnose MTBC in 38.2% (213/558) of specimens after excluding 14 nontuberculous mycobacteria. Sensitivity and specificity of the assay were 68.4% and 89.3% respectively, considering MGIT-960 culture as gold standard after excluding contaminated and invalid results. On comparing with composite reference standard, the assay had 71.5% sensitivity and 100% specificity in the diagnosis of tuberculosis. The sensitivity and specificity for detecting resistance to rifampicin (RMP) were 100% and 99.24% respectively and for resistance to isoniazid (INH) were 97.62% and 98.55%, respectively. Genotype MTBDRplus VER 2.0 is a rapid and precise diagnostic tool for detection of MTB in sputum smear-negative samples. It also facilitates accurate diagnosis of RMP and INH resistance within turn around-time.

Identification of Sarcosine as a Target Molecule for the Canine Olfactory Detection of Prostate Carcinoma.

PubMed

Pacik, Dalibor; Plevova, Mariana; Urbanova, Lucie; Lackova, Zuzana; Strmiska, Vladislav; Necas, Alois; Heger, Zbynek; Adam, Vojtech

2018-03-21

The hypothesis that dogs can detect malignant tumours through the identification of specific molecules is nearly 30 years old. To date, several reports have described the successful detection of distinct types of cancer. However, is still a lack of data regarding the specific molecules that can be recognized by a dog's olfactory apparatus. Hence, we performed a study with artificially prepared, well-characterized urinary specimens that were enriched with sarcosine, a widely reported urinary biomarker for prostate cancer (PCa). For the purposes of the study, a German shepherd dog was utilized for analyses of 60 positive and 120 negative samples. Our study provides the first evidence that a sniffer dog specially trained for the olfactory detection of PCa can recognize sarcosine in artificial urine with a performance [sensitivity of 90%, specificity of 95%, and precision of 90% for the highest amount of sarcosine (10 µmol/L)] that is comparable to the identification of PCa-diagnosed subjects (sensitivity of 93.5% and specificity of 91.6%). This study casts light on the unrevealed phenomenon of PCa olfactory detection and opens the door for further studies with canine olfactory detection and cancer diagnostics.

Development of Electrochemiluminescent Serology Assays to Measure the Humoral Response to Antigens of Respiratory Syncytial Virus.

PubMed

Maifeld, Sarah V; Ro, Bodrey; Mok, Hoyin; Chu, Marla; Yu, Li; Yamagata, Ryan; Leonardson, Tansy; Chio, Vera; Parhy, Bandita; Park, Samuel; Carlson, Marcia; Machhi, Shushil; Ulbrandt, Nancy; Falsey, Ann R; Walsh, Edward E; Wang, C Kathy; Esser, Mark T; Zuo, Fengrong

2016-01-01

Sensitive and precise serology assays are needed to measure the humoral response to antigens of respiratory syncytial virus (RSV) following natural infection or vaccination. We developed and evaluated a collection of electrochemiluminescent (ECL) serology assays using four RSV antigens (F, N, Ga and Gb). To assess the merits of ECL technology, the four ECL serology assays were evaluated using a well-characterized "gold standard" panel of acute and convalescent serum samples from fifty-nine RSV-positive and thirty RSV-negative elderly subjects (≥65 years old). The combined results from the four ECL assays demonstrated good concordance to the "gold standard" diagnosis, reaching 95% diagnostic sensitivity and 100% diagnostic specificity. Additionally, a combination of ECL assays provided higher diagnostic sensitivity than a commercially available diagnostic ELISA or cell-based microneutralization assay. In summary, these data demonstrate the advantages of using ECL-based serology assays and highlight their use as a sensitive diagnostic approach to detect recent RSV infection in an elderly population.

Dendrochemical patterns of calcium, zinc, and potassium related to internal factors detected by energy dispersive X-ray fluorescence (EDXRF)

Treesearch

Kevin T. Smith; Jean Christophe Balouet; Walter C. Shortle; Michel Chalot; François Beaujard; Hakan Grudd; Don A. Vroblesky; Joel G. Burken

2014-01-01

Energy dispersive X-ray fluorescence (EDXRF) provides highly sensitive and precise spatial resolution of cation content in individual annual growth rings in trees. The sensitivity and precision have prompted successful applications to forensic dendrochemistry and the timing of environmental releases of contaminants. These applications have highlighted the need to...

Use of hexyl isocyanate antigen to detect antibodies to hexamethylene diisocyanate (HDI) in sensitized guinea pigs and in a sensitized worker.

PubMed

Karol, M H; Hauth, B A

1982-01-01

Hypersensitivity to hexamethylene diisocyanate (HDI) has been reported following occupational exposure. Diagnosis of sensitivity is usually made from clinical evaluation of symptomatology. An in vitro serologic assay for HDI sensitivity was developed by immunizing guinea pigs with HDI and with hexyl isocyanate (HMI). Animals injected intradermally with HMI produced hapten-specific antibodies whereas guinea pigs injected with HDI produced antibodies specific for larger determinants which included the HDI hapten. The larger determinants were assumed to be composed of portions of "self" molecules which reacted in vivo with HDI. Serum albumin appeared to be one such molecule. No cross reactions were noted between antibodies to HDI and another widely used industrial isocyanate, toluene diisocyanate (TDI). Antigens effective in detecting antibodies to HDI or HMI were tested for ability to detect reaginic antibodies in a worker with clinical "HDI" asthma. Using a radioimmunoassay (RAST), antibodies reacted with conjugates containing either HDI or HMI as haptens. In addition, the prevalance of HDI polyisocyanates (Desmodur N) in spray paints prompted its use as a hapten. Antibodies reacted with Desmodur N antigen conjugates in RAST. RAST inhibition further indicated that Desmodur N antigen reacted more readily with the patient's antibodies than did HDI or HMI antigens. These results suggest that the patient may have been exposed to HDI polyisocyanates in spray paint application. Use of Rast inhibition for diagnosis of sensitivity may indicate the precise sensitizing agent within a mixture.

Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity

PubMed Central

Tycko, Josh; Myer, Vic E.; Hsu, Patrick D.

2016-01-01

Summary Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance. PMID:27494557

SU-F-J-59: Assessment of Dose Response Distribution in Individual Human Tumor

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

Yan, D; Chen, S; Krauss, D

Purpose: To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. Methods: FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function ofmore » pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. Results: Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. Conclusion: Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.« less

Point of care hemoglobin testing in plateletpheresis donors: Noninvasive versus invasive methods.

PubMed

Mallhi, R S; Pawar, Amit; Kushwaha, Neerja; Kumar, Sudeep; Dimri, Ujjwal

2016-10-01

Predonation hemoglobin (Hb) for plateletpheresis donors is estimated by presently available invasive methods. Venous samples of only those donors whose Hb is more than 12.5 g/dl are screened for complete blood count and transfusion transmissible infections. There is a pressing need to substitute this invasive Hb test with noninvasive one to reduce donor discomfort and avoid further pricking the donor. We therefore went ahead with the aim of comparing a noninvasive Hb estimation method NBM 200 with the invasive method - Hemocue, taking SYSMEX KX-21 as a gold standard. 500 voluntary consenting plateletpheresis donors qualifying the laid down criteria for platelet donation were included in the study. Hb readings obtained by the NBM 200 and Hemocue were compared to those obtained from the fully automated hematology analyzer SYSMEX KX-21. Coefficients of correlation were found to be statistically significant at <0.0001 level of confidence. Results of Friedman's test on the three methods also showed significant difference in means. Bland-Altman plots and mountain plots also confirm the same. NBM 200 was found to be more sensitive, specific, and precise than Hemocue in detecting ineligible donors. NBM 200 was found to be more sensitive, specific, and precise as compared to Hemocue for predonation screening of Hb in plateletpheresis donors and the prime benefit it offers is that it is 'noninvasive' thereby assisting in stemming the platelet donor pool. The onus lies on the blood transfusion services to make use of appropriately validated gadgets that reduce the donor discomfort.

The Lumipulse G HBsAg-Quant assay for screening and quantification of the hepatitis B surface antigen.

PubMed

Yang, Ruifeng; Song, Guangjun; Guan, Wenli; Wang, Qian; Liu, Yan; Wei, Lai

2016-02-01

Qualitative HBsAg assay is used to screen HBV infection for decades. The utility of quantitative assay is also rejuvenated recently. We aimed to evaluate and compare the performance of a novel ultra-sensitive and quantitative assay, the Lumipulse assay, with the Architect and Elecsys assays. As screening methods, specificity was compared using 2043 consecutive clinical routine samples. As quantitative assays, precision and accuracy were assessed. Sera from 112 treatment-naïve chronic hepatitis B patients, four patients undergoing antiviral therapy and one patient with acute infection were tested to compare the correlations. Samples with concurrent HBsAg/anti-HBs were also quantified. The Lumipulse assay precisely quantified ultra-low level of HBsAg (0.004 IU/mL). It identified additional 0.98% (20/2043) clinical samples with trance amount of HBsAg. Three assays displayed excellent linear correlations irrespective of genotypes and S-gene mutations (R(2)>0.95, P<0.0001), while minor quantitative biases existed. The Lumipulse assay did not yield higher HBsAg concentrations in samples with concomitant anti-HBs. Compared with other assays, the Lumipulse assay is sensitive and specific for detecting HBsAg. The interpretation of the extremely low-level results, however, is challenging. Quantitative HBsAg results by different assays are highly correlated, but they should be interpreted interchangeably only after conversion to eliminate the biases. Copyright © 2015 Elsevier B.V. All rights reserved.

SigEMD: A powerful method for differential gene expression analysis in single-cell RNA sequencing data.

PubMed

Wang, Tianyu; Nabavi, Sheida

2018-04-24

Differential gene expression analysis is one of the significant efforts in single cell RNA sequencing (scRNAseq) analysis to discover the specific changes in expression levels of individual cell types. Since scRNAseq exhibits multimodality, large amounts of zero counts, and sparsity, it is different from the traditional bulk RNA sequencing (RNAseq) data. The new challenges of scRNAseq data promote the development of new methods for identifying differentially expressed (DE) genes. In this study, we proposed a new method, SigEMD, that combines a data imputation approach, a logistic regression model and a nonparametric method based on the Earth Mover's Distance, to precisely and efficiently identify DE genes in scRNAseq data. The regression model and data imputation are used to reduce the impact of large amounts of zero counts, and the nonparametric method is used to improve the sensitivity of detecting DE genes from multimodal scRNAseq data. By additionally employing gene interaction network information to adjust the final states of DE genes, we further reduce the false positives of calling DE genes. We used simulated datasets and real datasets to evaluate the detection accuracy of the proposed method and to compare its performance with those of other differential expression analysis methods. Results indicate that the proposed method has an overall powerful performance in terms of precision in detection, sensitivity, and specificity. Copyright © 2018 Elsevier Inc. All rights reserved.

Determination of 25-OH-PPD in rat plasma by high-performance liquid chromatography-mass spectrometry and its application in rat pharmacokinetic studies.

PubMed

Zhang, Xiangrong; Zhang, Dan; Xu, Jinghua; Gu, Jingkai; Zhao, Yuqing

2007-10-15

A sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the investigation of the pharmacokinetics of 20(R)-dammarane-3beta,12beta,20,25-tetrol (25-OH-PPD) in rat. Ginsenoside Rh(2) was employed as an internal standard. The plasma samples were pretreated by liquid-liquid extraction and analyzed using LC/MS/MS with an electrospray ionization interface. The mobile phase consisted of methanol-acetonitrile-10 mmol/l aqueous ammonium acetate (42.5:42.5:15, v:v:v), which was pumped at 0.4 ml/min. The analytical column (50 mm x 2.1 mm i.d.) was packed with Venusil XBP C8 material (3.5 microm). The standard curve was linear from 10 to 3000 ng/ml. The assay was specific, accurate (accuracy between -1.19 and 2.57% for all quality control samples), precise and reproducible (within- and between-day precisions measured as relative standard deviation were <5% and <7%, respectively). 25-OH-PPD in rat plasma was stable over three freeze-thaw cycles and at ambient temperatures for 6h. The method had a lower limit of quantitation of 10 ng/ml, which offered a satisfactory sensitivity for the determination of (25-OH-PPD) in plasma. This quantitation method was successfully applied to pharmacokinetic studies of 25-OH-PPD after both an oral and an intravenous administration to rats and the absolute bioavailability is 64.8+/-14.3%.

Development of a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of phenylethanolamine A in tissue and feed samples and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS).

PubMed

Cao, Biyun; He, Guangzhao; Yang, Hong; Chang, Huafang; Li, Shuqun; Deng, Anping

2013-10-15

Phenylethanolamine A (PA) is a new emerged β-adrenergic agonist illegally used as feed additives for growth promotion. In this study, a highly sensitive and specific indirect competitive enzyme-linked immunosorbent assay (ELISA) for the detection of PA in tissue and feed samples was developed and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS). By reduction of nitryl group to amino group, the PA derivative was synthesized and coupled to carrier proteins with diazobenzidine method. The antisera obtained from four immunized rabbits were characterized in terms of sensitivity and specificity. All antisera displayed high sensitivity with IC50 values lower than 0.48 ng mL(-1). The most sensitive ELISA was established with IC50 and limit of detection (LOD) values of 0.049 ng mL(-1) and 0.003 ng mL(-1), respectively. The cross-reactivity (CR) values of the antisera with three frequently used β-adrenergic agonists (clenbuterol, salbutamol and ractopamine) were lesser than 0.39%; there was no CR of the antisera with other six compounds including two structurally related substances (isoproterenol, phenylephrine). To investigate the accuracy and precision of the assay, swine kidney, liver, meat and feed samples were fortified with PA at different content and analyzed by ELISA. Acceptable recovery rates of 92.2-113.7% and intra-assay coefficients of variation of 3.8-10.9% (n=3) were achieved. Seven spiked samples were simultaneously analyzed by ELISA and LC-MS/MS. There was a high correlation coefficient of 0.9956 (n=7) between the two methods. The proposed ELISA proven to be a feasible quantitative/screening method for PA analysis in tissue and feed samples with the properties of high sensitivity and specificity, high sample throughput and low expensive. © 2013 Elsevier B.V. All rights reserved.

The Radiative Forcing Model Intercomparison Project (RFMIP): Assessment and characterization of forcing to enable feedback studies

NASA Astrophysics Data System (ADS)

Pincus, R.; Stevens, B. B.; Forster, P.; Collins, W.; Ramaswamy, V.

2014-12-01

The Radiative Forcing Model Intercomparison Project (RFMIP): Assessment and characterization of forcing to enable feedback studies An enormous amount of attention has been paid to the diversity of responses in the CMIP and other multi-model ensembles. This diversity is normally interpreted as a distribution in climate sensitivity driven by some distribution of feedback mechanisms. Identification of these feedbacks relies on precise identification of the forcing to which each model is subject, including distinguishing true error from model diversity. The Radiative Forcing Model Intercomparison Project (RFMIP) aims to disentangle the role of forcing from model sensitivity as determinants of varying climate model response by carefully characterizing the radiative forcing to which such models are subject and by coordinating experiments in which it is specified. RFMIP consists of four activities: 1) An assessment of accuracy in flux and forcing calculations for greenhouse gases under past, present, and future climates, using off-line radiative transfer calculations in specified atmospheres with climate model parameterizations and reference models 2) Characterization and assessment of model-specific historical forcing by anthropogenic aerosols, based on coordinated diagnostic output from climate models and off-line radiative transfer calculations with reference models 3) Characterization of model-specific effective radiative forcing, including contributions of model climatology and rapid adjustments, using coordinated climate model integrations and off-line radiative transfer calculations with a single fast model 4) Assessment of climate model response to precisely-characterized radiative forcing over the historical record, including efforts to infer true historical forcing from patterns of response, by direct specification of non-greenhouse-gas forcing in a series of coordinated climate model integrations This talk discusses the rationale for RFMIP, provides an overview of the four activities, and presents preliminary motivating results.

Analyzing Water's Optical Absorption

NASA Technical Reports Server (NTRS)

2002-01-01

A cooperative agreement between World Precision Instruments (WPI), Inc., and Stennis Space Center has led the UltraPath(TM) device, which provides a more efficient method for analyzing the optical absorption of water samples at sea. UltraPath is a unique, high-performance absorbance spectrophotometer with user-selectable light path lengths. It is an ideal tool for any study requiring precise and highly sensitive spectroscopic determination of analytes, either in the laboratory or the field. As a low-cost, rugged, and portable system capable of high- sensitivity measurements in widely divergent waters, UltraPath will help scientists examine the role that coastal ocean environments play in the global carbon cycle. UltraPath(TM) is a trademark of World Precision Instruments, Inc. LWCC(TM) is a trademark of World Precision Instruments, Inc.

Hot Spots in a Network of Functional Sites

PubMed Central

Ozbek, Pemra; Soner, Seren; Haliloglu, Turkan

2013-01-01

It is of significant interest to understand how proteins interact, which holds the key phenomenon in biological functions. Using dynamic fluctuations in high frequency modes, we show that the Gaussian Network Model (GNM) predicts hot spot residues with success rates ranging between S 8–58%, C 84–95%, P 5–19% and A 81–92% on unbound structures and S 8–51%, C 97–99%, P 14–50%, A 94–97% on complex structures for sensitivity, specificity, precision and accuracy, respectively. High specificity and accuracy rates with a single property on unbound protein structures suggest that hot spots are predefined in the dynamics of unbound structures and forming the binding core of interfaces, whereas the prediction of other functional residues with similar dynamic behavior explains the lower precision values. The latter is demonstrated with the case studies; ubiquitin, hen egg-white lysozyme and M2 proton channel. The dynamic fluctuations suggest a pseudo network of residues with high frequency fluctuations, which could be plausible for the mechanism of biological interactions and allosteric regulation. PMID:24023934

NCLscan: accurate identification of non-co-linear transcripts (fusion, trans-splicing and circular RNA) with a good balance between sensitivity and precision.

PubMed

Chuang, Trees-Juen; Wu, Chan-Shuo; Chen, Chia-Ying; Hung, Li-Yuan; Chiang, Tai-Wei; Yang, Min-Yu

2016-02-18

Analysis of RNA-seq data often detects numerous 'non-co-linear' (NCL) transcripts, which comprised sequence segments that are topologically inconsistent with their corresponding DNA sequences in the reference genome. However, detection of NCL transcripts involves two major challenges: removal of false positives arising from alignment artifacts and discrimination between different types of NCL transcripts (trans-spliced, circular or fusion transcripts). Here, we developed a new NCL-transcript-detecting method ('NCLscan'), which utilized a stepwise alignment strategy to almost completely eliminate false calls (>98% precision) without sacrificing true positives, enabling NCLscan outperform 18 other publicly-available tools (including fusion- and circular-RNA-detecting tools) in terms of sensitivity and precision, regardless of the generation strategy of simulated dataset, type of intragenic or intergenic NCL event, read depth of coverage, read length or expression level of NCL transcript. With the high accuracy, NCLscan was applied to distinguishing between trans-spliced, circular and fusion transcripts on the basis of poly(A)- and nonpoly(A)-selected RNA-seq data. We showed that circular RNAs were expressed more ubiquitously, more abundantly and less cell type-specifically than trans-spliced and fusion transcripts. Our study thus describes a robust pipeline for the discovery of NCL transcripts, and sheds light on the fundamental biology of these non-canonical RNA events in human transcriptome. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Purity assessment of recombinant human granulocyte colony-stimulating factor in finished drug product by capillary zone electrophoresis.

PubMed

Benković, Goran; Skrlin, Ana; Madić, Tomislav; Debeljak, Zeljko; Medić-Šarić, Marica

2014-09-01

Current methods for determination of impurities with different charge-to-volume ratio are limited especially in terms of sensitivity and precision. The main goal of this research was to establish a quantitative method for determination of impurities with charges differing from that of recombinant human granulocyte colony-stimulating factor (rhG-CSF, filgrastim) with superior precision and sensitivity compared to existing methods. A CZE method has been developed, optimized, and validated for a purity assessment of filgrastim in liquid pharmaceutical formulations. Optimal separation of filgrastim from the related impurities with different charges was achieved on a 50 μm id fused-silica capillary of a total length of 80.5 cm. A BGE that contains 100 mM phosphoric acid adjusted to pH 7.0 with triethanolamine was used. The applied voltage was 20 kV while the temperature was maintained at 25°C. UV detection was set to 200 nm. Method was validated in terms of selectivity/specificity, linearity, precision, LOD, LOQ, stability, and robustness. Linearity was observed in the concentration range of 6-600 μg/mL and the LOQ was determined to be 0.3% relative to the concentration of filgrastim of 0.6 mg/mL. Other validation parameters were also found to be acceptable; thus the method was successfully applied for a quantitative purity assessment of filgrastim in a finished drug product. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of plutonium in spent nuclear fuel using high resolution X-ray

DOE PAGES

McIntosh, Kathryn G.; Reilly, Sean D.; Havrilla, George J.

2015-05-30

Characterization of Pu is an essential aspect of safeguards operations at nuclear fuel reprocessing facilities. A novel analysis technique called hiRX (high resolution X-ray) has been developed for the direct measurement of Pu in spent nuclear fuel dissolver solutions. hiRX is based on monochromatic wavelength dispersive X-ray fluorescence (MWDXRF), which provides enhanced sensitivity and specificity compared with conventional XRF techniques. A breadboard setup of the hiRX instrument was calibrated using spiked surrogate spent fuel (SSF) standards prepared as dried residues. Samples of actual spent fuel were utilized to evaluate the performance of the hiRX. The direct detection of just 39more » ng of Pu is demonstrated. Initial quantitative results, with error of 4–27% and precision of 2% relative standard deviation (RSD), were obtained for spent fuel samples. The limit of detection for Pu (100 s) within an excitation spot of 200 μm diameter was 375 pg. This study demonstrates the potential for the hiRX technique to be utilized for the rapid, accurate, and precise determination of Pu. Moreover, the results highlight the analytical capability of hiRX for other applications requiring sensitive and selective nondestructive analyses.« less

Quantum metrology with a transmon qutrit

NASA Astrophysics Data System (ADS)

Shlyakhov, A. R.; Zemlyanov, V. V.; Suslov, M. V.; Lebedev, A. V.; Paraoanu, G. S.; Lesovik, G. B.; Blatter, G.

2018-02-01

Making use of coherence and entanglement as metrological quantum resources allows us to improve the measurement precision from the shot-noise or quantum limit to the Heisenberg limit. Quantum metrology then relies on the availability of quantum engineered systems that involve controllable quantum degrees of freedom which are sensitive to the measured quantity. Sensors operating in the qubit mode and exploiting their coherence in a phase-sensitive measurement have been shown to approach the Heisenberg scaling in precision. Here, we show that this result can be further improved by operating the quantum sensor in the qudit mode, i.e., by exploiting d rather than two levels. Specifically, we describe the metrological algorithm for using a superconducting transmon device operating in a qutrit mode as a magnetometer. The algorithm is based on the base-3 semiquantum Fourier transformation and enhances the quantum theoretical performance of the sensor by a factor of 2. Even more, the practical gain of our qutrit implementation is found in a reduction of the number of iteration steps of the quantum Fourier transformation by the factor ln(2 )/ln(3 )≈0.63 compared to the qubit mode. We show that a two-tone capacitively coupled radio-frequency signal is sufficient for implementation of the algorithm.

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

McIntosh, Kathryn G.; Reilly, Sean D.; Havrilla, George J.

Characterization of Pu is an essential aspect of safeguards operations at nuclear fuel reprocessing facilities. A novel analysis technique called hiRX (high resolution X-ray) has been developed for the direct measurement of Pu in spent nuclear fuel dissolver solutions. hiRX is based on monochromatic wavelength dispersive X-ray fluorescence (MWDXRF), which provides enhanced sensitivity and specificity compared with conventional XRF techniques. A breadboard setup of the hiRX instrument was calibrated using spiked surrogate spent fuel (SSF) standards prepared as dried residues. Samples of actual spent fuel were utilized to evaluate the performance of the hiRX. The direct detection of just 39more » ng of Pu is demonstrated. Initial quantitative results, with error of 4–27% and precision of 2% relative standard deviation (RSD), were obtained for spent fuel samples. The limit of detection for Pu (100 s) within an excitation spot of 200 μm diameter was 375 pg. This study demonstrates the potential for the hiRX technique to be utilized for the rapid, accurate, and precise determination of Pu. Moreover, the results highlight the analytical capability of hiRX for other applications requiring sensitive and selective nondestructive analyses.« less

Loss of heterozygosity assay for molecular detection of cancer using energy-transfer primers and capillary array electrophoresis.

PubMed

Medintz, I L; Lee, C C; Wong, W W; Pirkola, K; Sidransky, D; Mathies, R A

2000-08-01

Microsatellite DNA loci are useful markers for the detection of loss of heterozygosity (LOH) and microsatellite instability (MI) associated with primary cancers. To carry out large-scale studies of LOH and MI in cancer progression, high-throughput instrumentation and assays with high accuracy and sensitivity need to be validated. DNA was extracted from 26 renal tumor and paired lymphocyte samples and amplified with two-color energy-transfer (ET) fluorescent primers specific for loci associated with cancer-induced chromosomal changes. PCR amplicons were separated on the MegaBACE-1000 96 capillary array electrophoresis (CAE) instrument and analyzed with MegaBACE Genetic Profiler v.1.0 software. Ninety-six separations were achieved in parallel in 75 minutes. Loss of heterozygosity was easily detected in tumor samples as was the gain/loss of microsatellite core repeats. Allelic ratios were determined with a precision of +/- 10% or better. Prior analysis of these samples with slab gel electrophoresis and radioisotope labeling had not detected these changes with as much sensitivity or precision. This study establishes the validity of this assay and the MegaBACE instrument for large-scale, high-throughput studies of the molecular genetic changes associated with cancer.

A European multicenter study on the analytical performance of the VERIS HBV assay.

PubMed

Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Izopet, Jacques; Lombardi, Alessandra; Mancon, Alessandro; Marcos, Maria Angeles; Sauné, Karine; O Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel

Hepatitis B viral load monitoring is an essential part of managing patients with chronic Hepatits B infection. Beckman Coulter has developed the VERIS HBV Assay for use on the fully automated Beckman Coulter DxN VERIS Molecular Diagnostics System. 1 OBJECTIVES: To evaluate the analytical performance of the VERIS HBV Assay at multiple European virology laboratories. Precision, analytical sensitivity, negative sample performance, linearity and performance with major HBV genotypes/subtypes for the VERIS HBV Assay was evaluated. Precision showed an SD of 0.15 log 10 IU/mL or less for each level tested. Analytical sensitivity determined by probit analysis was between 6.8-8.0 IU/mL. Clinical specificity on 90 unique patient samples was 100.0%. Performance with 754 negative samples demonstrated 100.0% not detected results, and a carryover study showed no cross contamination. Linearity using clinical samples was shown from 1.23-8.23 log 10 IU/mL and the assay detected and showed linearity with major HBV genotypes/subtypes. The VERIS HBV Assay demonstrated comparable analytical performance to other currently marketed assays for HBV DNA monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

TRPV1 SUMOylation regulates nociceptive signaling in models of inflammatory pain.

PubMed

Wang, Yan; Gao, Yingwei; Tian, Quan; Deng, Qi; Wang, Yangbo; Zhou, Tian; Liu, Qiang; Mei, Kaidi; Wang, Yingping; Liu, Huiqing; Ma, Ruining; Ding, Yuqiang; Rong, Weifang; Cheng, Jinke; Yao, Jing; Xu, Tian-Le; Zhu, Michael X; Li, Yong

2018-04-18

Although TRPV1 channels represent a key player of noxious heat sensation, the precise mechanisms for thermal hyperalgesia remain unknown. We report here that conditional knockout of deSUMOylation enzyme, SENP1, in mouse dorsal root ganglion (DRG) neurons exacerbated thermal hyperalgesia in both carrageenan- and Complete Freund's adjuvant-induced inflammation models. TRPV1 is SUMOylated at a C-terminal Lys residue (K822), which specifically enhances the channel sensitivity to stimulation by heat, but not capsaicin, protons or voltage. TRPV1 SUMOylation is decreased by SENP1 but upregulated upon peripheral inflammation. More importantly, the reduced ability of TRPV1 knockout mice to develop inflammatory thermal hyperalgesia was rescued by viral infection of lumbar 3/4 DRG neurons of wild-type TRPV1, but not its SUMOylation-deficient mutant, K822R. These data suggest that TRPV1 SUMOylation is essential for the development of inflammatory thermal hyperalgesia, through a mechanism that involves sensitization of the channel response specifically to thermal stimulation.

Determinants of propranolol’s selective effect on loss aversion

PubMed Central

Sokol-Hessner, Peter; Lackovic, Sandra F.; Tobe, Russell H.; Camerer, Colin F.; Leventhal, Bennett L.; Phelps, Elizabeth A.

2015-01-01

Research on emotion and decision-making has suggested that arousal mediates risky decisions (e.g., Bechara et al., 1997), but several distinct and often confounded processes drive such choices. Here, we used econometric modeling to separate and quantify the unique contributions of loss aversion, risk sensitivity and choice consistency to risky decision-making. We administered the beta-blocker propranolol in a double-blind, placebo-controlled within-subjects study, targeting the neurohormonal basis of physiological arousal. Matching our intervention’s pharmacological specificity with a quantitative model delineating decision-making components allowed us to identify the causal relationships between arousal and decision-making that do and do not exist. Propranolol selectively reduced loss aversion in a baseline- and dose-dependent manner (i.e. as a function of initial loss aversion and body-mass index), and did not affect risk sensitivity or choice consistency. These findings provide evidence for a specific, modulatory, and causal relationship between precise components of both emotion and risky decision-making. PMID:26063441

Plasma thromboplastin antecedent (PTA, factor XI): a specific and sensitive radioimmunoassay. [/sup 125/I tracer technique

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

Saito, H.; Goldsmith, G.H. Jr.

A specific, sensitive, and reproducible radioimmunoassay for human plasma thromboplastin antecedent (PTA, factor XI) has been developed with purified PTA and monospecific rabbit antiserum. Precise measurements of PTA antigen were possible for concentrations as low as 0.3% of that in normal pooled plasma. Normal plasma contained approximately 6 ..mu..g PTA/ml. A good correlation (correlation coefficient 0.68) existed between the PTA procoagulant assays and radioimmunoassays among 50 normal adults (25 males and 25 females). PTA antigen was markedly reduced in plasma of 13 patients with congenital homozygous PTA deficiency (range <0.003-0.128 U/ml) and 9 patients with hepatic cirrhosis (0.35 +- 0.17more » U/ml), but was normal in those of 9 patients under treatment with warfarin, 8 patients with disseminated intravascular coagulation and 16 patients with other congenital clotting factor abnormalities, including prekallikrein deficiency (Fletcher trait) and high molecular weight kininogen deficiency (Fitzgerald trait).« less

A branch-migration based fluorescent probe for straightforward, sensitive and specific discrimination of DNA mutations

PubMed Central

Xiao, Xianjin; Wu, Tongbo; Xu, Lei; Chen, Wei

2017-01-01

Abstract Genetic mutations are important biomarkers for cancer diagnostics and surveillance. Preferably, the methods for mutation detection should be straightforward, highly specific and sensitive to low-level mutations within various sequence contexts, fast and applicable at room-temperature. Though some of the currently available methods have shown very encouraging results, their discrimination efficiency is still very low. Herein, we demonstrate a branch-migration based fluorescent probe (BM probe) which is able to identify the presence of known or unknown single-base variations at abundances down to 0.3%-1% within 5 min, even in highly GC-rich sequence regions. The discrimination factors between the perfect-match target and single-base mismatched target are determined to be 89–311 by measurement of their respective branch-migration products via polymerase elongation reactions. The BM probe not only enabled sensitive detection of two types of EGFR-associated point mutations located in GC-rich regions, but also successfully identified the BRAF V600E mutation in the serum from a thyroid cancer patient which could not be detected by the conventional sequencing method. The new method would be an ideal choice for high-throughput in vitro diagnostics and precise clinical treatment. PMID:28201758

Recombinase polymerase and enzyme-linked immunosorbent assay as a DNA amplification-detection strategy for food analysis.

PubMed

Santiago-Felipe, S; Tortajada-Genaro, L A; Puchades, R; Maquieira, A

2014-02-06

Polymerase chain reaction in conjunction with enzyme-linked immunosorbent assay (PCR-ELISA) is a well-established technique that provides a suitable rapid, sensitive, and selective method for a broad range of applications. However, the need for precise rapid temperature cycling of PCR is an important drawback that can be overcome by employing isothermal amplification reactions such as recombinase polymerase amplification (RPA). The RPA-ELISA combination is proposed for amplification at a low, constant temperature (40°C) in a short time (40 min), for the hybridisation of labelled products to specific 5'-biotinylated probes/streptavidin in coated microtiter plates at room temperature, and for detection by colorimetric immunoassay. RPA-ELISA was applied to screen common safety threats in foodstuffs, such as allergens (hazelnut, peanut, soybean, tomato, and maize), genetically modified organisms (P35S and TNOS), pathogenic bacteria (Salmonella sp. and Cronobacter sp.), and fungi (Fusarium sp.). Satisfactory sensitivity and reproducibility results were achieved for all the targets. The RPA-ELISA technique does away with thermocycling and provides a suitable sensitive, specific, and cost-effective method for routine applications, and proves particularly useful for resource-limited settings. Copyright © 2013 Elsevier B.V. All rights reserved.

Feasibility of a Novel Functional Sensibility Test as an Assisted Examination for Determining Precision Pinch Performance in Patients with Carpal Tunnel Syndrome

PubMed Central

Hsu, Hsiu-Yun; Kuo, Li-Chieh; Kuo, Yao-Lung; Chiu, Haw-Yen; Jou, I-Ming; Wu, Po-Ting; Su, Fong-Chin

2013-01-01

To understand the feasibility of a novel functional sensibility test for determining precision pinch performance in patients with carpal tunnel syndrome, this study investigates the validity, sensitivity and specificity of functional sensibility derived from a pinch-holding-up activity (PHUA) test. Participants include 70 clinically defined carpal tunnel syndrome (CTS) patients with 119 involved hands and 70 age- and gender-matched controls. To examine the discriminating ability of the functional sensibility test, the differences in the ability of pinch force adjustments to the inertial load of handling object between CTS and control subjects are analyzed. The results of functional sensibility are correlated with the severity of CTS to establish concurrent validity. The receiver operating characteristic (ROC) curve is constructed to demonstrate the accuracy of the proposed test. The functional sensibility score significantly discriminates the patients and control groups (respectively, 12.94±1.72 vs. 11.51±1.15N in peak pinch force (FPPeak), p<0.001; 2.92±0.41 vs. 2.52±0.24 in force ratio, p<0.001) and is moderately correlated (r = 0.42–0.54, p<0.001) with the results of traditional sensibility tests (touch-pressure threshold and two-point discrimination test). In addition, there is a statistical difference in the results of functional sensibility (p<0.001) among the subgroups of CTS severity based on electrophysiological study. The sensitivity and specificity are 0.79 and 0.76, respectively, for the functional sensibility test. The areas under the ROC curve are 0.85 and 0.80 for the force ratio and FPPeak, respectively. In conclusion, the functional sensibility test could be feasibly used as a clinical tool for determining both the sensibility and precision pinch performance of hands for the patients with CTS. PMID:23977209

National validation study of a swab protocol for the recovery of Bacillus anthracis spores from surfaces.

PubMed

Hodges, Lisa R; Rose, Laura J; O'Connell, Heather; Arduino, Matthew J

2010-05-01

Twelve Laboratory Response Network (LRN) affiliated laboratories participated in a validation study of a macrofoam swab protocol for the recovery, detection, and quantification of viable B. anthracis (BA) Sterne spores from steel surfaces. CDC personnel inoculated steel coupons (26cm(2)) with 1-4 log(10) BA spores and recovered them by sampling with pre-moistened macrofoam swabs. Phase 1 (P1) of the study evaluated swabs containing BA only, while dust and background organisms were added to swabs in Phase 2 (P2) to mimic environmental conditions. Laboratories processed swabs and enumerated spores by culturing eluted swab suspensions and counting colonies with morphology consistent with BA. Processed swabs were placed in enrichment broth, incubated 24h, and cultured by streaking for isolation. Real-time PCR was performed on selected colonies from P2 samples to confirm the identity of BA. Mean percent recovery (%R) of spores from the surface ranged from 15.8 to 31.0% (P1) and from 27.9 to 55.0% (P2). The highest mean percent recovery was 31.0% (sd 10.9%) for P1 (4 log(10) inoculum) and 55.0% (sd 27.6%) for P2 (1 log(10) inoculum). The overall %R was higher for P2 (44.6%) than P1 (24.1%), but the overall reproducibility (between-lab variability) was lower in P2 than in P1 (25.0 vs 16.5%CV, respectively). The overall precision (within-lab variability) was close to identical for P1 and P2 (44.0 and 44.1, respectively), but varied greatly between inoculum levels. The protocol demonstrated linearity in %R over the three inoculum levels and is able to detect between 26 and 5x10(6)spores/26cm(2). Sensitivity as determined by culture was >98.3% for both phases and all inocula, suggesting that the culture method maintains sensitivity in the presence of contaminants. The enrichment broth method alone was less sensitive for sampled swabs (66.4%) during P2, suggesting that the presence of background organisms inhibited growth or isolation of BA from the broth. The addition of real-time PCR testing to the assay increased specificity from >85.4% to >95.0% in P2. Although the precision was low at the 1 log(10) inoculum level in both phases (59.0 and 50.2%), this swab processing protocol, was sensitive, specific, precise, and reproducible at 2-4 log(10)/26cm(2) spore concentrations. Published by Elsevier B.V.

Calibration of gyro G-sensitivity coefficients with FOG monitoring on precision centrifuge

NASA Astrophysics Data System (ADS)

Lu, Jiazhen; Yang, Yanqiang; Li, Baoguo; Liu, Ming

2017-07-01

The advantages of mechanical gyros, such as high precision, endurance and reliability, make them widely used as the core parts of inertial navigation systems (INS) utilized in the fields of aeronautics, astronautics and underground exploration. In a high-g environment, the accuracy of gyros is degraded. Therefore, the calibration and compensation of the gyro G-sensitivity coefficients is essential when the INS operates in a high-g environment. A precision centrifuge with a counter-rotating platform is the typical equipment for calibrating the gyro, as it can generate large centripetal acceleration and keep the angular rate close to zero; however, its performance is seriously restricted by the angular perturbation in the high-speed rotating process. To reduce the dependence on the precision of the centrifuge and counter-rotating platform, an effective calibration method for the gyro g-sensitivity coefficients under fiber-optic gyroscope (FOG) monitoring is proposed herein. The FOG can efficiently compensate spindle error and improve the anti-interference ability. Harmonic analysis is performed for data processing. Simulations show that the gyro G-sensitivity coefficients can be efficiently estimated to up to 99% of the true value and compensated using a lookup table or fitting method. Repeated tests indicate that the G-sensitivity coefficients can be correctly calibrated when the angular rate accuracy of the precision centrifuge is as low as 0.01%. Verification tests are performed to demonstrate that the attitude errors can be decreased from 0.36° to 0.08° in 200 s. The proposed measuring technology is generally applicable in engineering, as it can reduce the accuracy requirements for the centrifuge and the environment.

Touch-down reverse transcriptase-PCR detection of IgV(H) rearrangement and Sybr-Green-based real-time RT-PCR quantitation of minimal residual disease in patients with chronic lymphocytic leukemia.

PubMed

Peková, Sona; Marková, Jana; Pajer, Petr; Dvorák, Michal; Cetkovský, Petr; Schwarz, Jirí

2005-01-01

Patients with chronic lymphocytic leukemia (CLL) can relapse even after aggressive therapy and autografts. It is commonly assumed that to prevent relapse the level of minimal residual disease (MRD) should be as low as possible. To evaluate MRD, highly sensitive quantitative assays are needed. The aim of the study was to develop a robust and sensitive method for detection of the clonal immunoglobulin heavy-chain variable (IgV(H)) rearrangement in CLL and to introduce a highly sensitive and specific methodology for MRD monitoring in patients with CLL who undergo intensive treatment. As a prerequisite for MRD detection, touch-down reverse transcriptase (RT)-PCR using degenerate primers were used for the diagnostic identification of (H) gene rearrangement(s). For quantitative MRD detection in 18 patients, we employed a real-time RT-PCR assay (RQ-PCR) making use of patient-specific primers and the cost-saving Sybr-Green reporter dye (SG). For precise calibration of RQ-PCR, patient-specific IgV(H) sequences were cloned. Touch-down RT-PCR with degenerate primers allowed the successful detection of IgV(H) clonal rearrangement(s) in 252 of 257 (98.1%) diagnostic samples. Biallelic rearrangements were found in 27 of 252 (10.7%) cases. Degenerate primers used for the identification of clonal expansion at diagnosis were not sensitive enough for MRD detection. In contrast, our RQ-PCR assay using patient-specific primers and SG reached the sensitivity of 10(-)(6). We demonstrated MRD in each patient tested, including four of four patients in complete remission following autologous hematopoietic stem cell transplantation (HSCT) and three of three following allogeneic 'mini'-HSCT. Increments in MRD might herald relapse; aggressive chemotherapy could induce molecular remission. Our touch-down RT-PCR has higher efficiency to detect clonal IgV(H) rearrangements including the biallelic ones. MRD quantitation of IgV(H) expression using SG-based RQ-PCR represents a highly specific, sensitive, and economic alternative to the current quantitative methods.

Polyadenylation site prediction using PolyA-iEP method.

PubMed

Kavakiotis, Ioannis; Tzanis, George; Vlahavas, Ioannis

2014-01-01

This chapter presents a method called PolyA-iEP that has been developed for the prediction of polyadenylation sites. More precisely, PolyA-iEP is a method that recognizes mRNA 3'ends which contain polyadenylation sites. It is a modular system which consists of two main components. The first exploits the advantages of emerging patterns and the second is a distance-based scoring method. The outputs of the two components are finally combined by a classifier. The final results reach very high scores of sensitivity and specificity.

Testing the effectiveness of simplified search strategies for updating systematic reviews.

PubMed

Rice, Maureen; Ali, Muhammad Usman; Fitzpatrick-Lewis, Donna; Kenny, Meghan; Raina, Parminder; Sherifali, Diana

2017-08-01

The objective of the study was to test the overall effectiveness of a simplified search strategy (SSS) for updating systematic reviews. We identified nine systematic reviews undertaken by our research group for which both comprehensive and SSS updates were performed. Three relevant performance measures were estimated, that is, sensitivity, precision, and number needed to read (NNR). The update reference searches for all nine included systematic reviews identified a total of 55,099 citations that were screened resulting in final inclusion of 163 randomized controlled trials. As compared with reference search, the SSS resulted in 8,239 hits and had a median sensitivity of 83.3%, while precision and NNR were 4.5 times better. During analysis, we found that the SSS performed better for clinically focused topics, with a median sensitivity of 100% and precision and NNR 6 times better than for the reference searches. For broader topics, the sensitivity of the SSS was 80% while precision and NNR were 5.4 times better compared with reference search. SSS performed well for clinically focused topics and, with a median sensitivity of 100%, could be a viable alternative to a conventional comprehensive search strategy for updating this type of systematic reviews particularly considering the budget constraints and the volume of new literature being published. For broader topics, 80% sensitivity is likely to be considered too low for a systematic review update in most cases, although it might be acceptable if updating a scoping or rapid review. Copyright © 2017 Elsevier Inc. All rights reserved.

Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of 64Cu-Au alloy nanoclusters

NASA Astrophysics Data System (ADS)

Zhao, Yongfeng; Sultan, Deborah; Detering, Lisa; Luehmann, Hannah; Liu, Yongjian

2014-10-01

Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs.Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr04569f

Comparative analysis of detection limits and specificity of molecular diagnostic markers for three pathogens (Microsporidia, Nosema spp.) in the key pollinators Apis mellifera and Bombus terrestris.

PubMed

Erler, Silvio; Lommatzsch, Stefanie; Lattorff, H Michael G

2012-04-01

Global pollinator decline has recently been discussed in the context of honey and bumble bee infections from various pathogens including viruses, bacteria, microsporidia and mites. The microsporidian pathogens Nosema apis, Nosema ceranae and Nosema bombi may in fact be major candidates contributing to this decline. Different molecular and non-molecular detection methods have been developed; however, a comparison, especially of the highly sensitive PCR based methods, is currently lacking. Here, we present the first comparative quantitative real-time PCR study of nine Nosema spp. primers within the framework of primer specificity and sensitivity. With the help of dilution series of defined numbers of spores, we reveal six primer pairs amplifying N. apis, six for N. bombi and four for N. ceranae. All appropriate primer pairs detected an amount of at least 10(4) spores, the majority of which were even as sensitive to detect such low amounts as 10(3) to ten spores. Species specificity of primers was observed for N. apis and N. bombi, but not for N. ceranae. Additionally, we did not find any significant correlation for the amplified fragments with PCR efficiency or the limit of detection. We discuss our findings on the background of false positive and negative results using quantitative real-time PCR. On the basis of these results, future research might be based on appropriate primer selection depending on the experimental needs. Primers may be selected on the basis of specificity or sensitivity. Pathogen species and load may be determined with higher precision enhancing all kinds of diagnostic studies.

Highly sensitive fluorescence detection of metastatic lymph nodes of gastric cancer with photo-oxidation of protoporphyrin IX.

PubMed

Koizumi, N; Harada, Y; Beika, M; Minamikawa, T; Yamaoka, Y; Dai, P; Murayama, Y; Yanagisawa, A; Otsuji, E; Tanaka, H; Takamatsu, T

2016-08-01

The establishment of a precise and rapid method to detect metastatic lymph nodes (LNs) is essential to perform less invasive surgery with reduced gastrectomy along with reduced lymph node dissection. We herein describe a novel imaging strategy to detect 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence in excised LNs specifically with reduced effects of tissue autofluorescence based on photo-oxidation of PpIX. We applied the method in a clinical setting, and evaluated its feasibility. To reduce the unfavorable effect of autofluorescence, we focused on photo-oxidation of PpIX: Following light irradiation, PpIX changes into another substance, photo-protoporphyrin, via an oxidative process, which has a different spectral peak, at 675 nm, whereas PpIX has its spectral peak at 635 nm. Based on the unique spectral alteration, fluorescence spectral imaging before and after light irradiation and subsequent originally-developed image processing was performed. Following in vitro study, we applied this method to a total of 662 excised LNs obtained from 30 gastric cancer patients administered 5-ALA preoperatively. Specific visualization of PpIX was achieved in in vitro study. The method allowed highly sensitive detection of metastatic LNs, with sensitivity of 91.9% and specificity of 90.8% in the in vivo clinical trial. Receiver operating characteristic analysis indicated high diagnostic accuracy, with the area under the curve of 0.926. We established a highly sensitive and specific 5-ALA-induced fluorescence imaging method applicable in clinical settings. The novel method has a potential to become a useful tool for intraoperative rapid diagnosis of LN metastasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interindividual variation in thermal sensitivity of maximal sprint speed, thermal behavior, and resting metabolic rate in a lizard.

PubMed

Artacho, Paulina; Jouanneau, Isabelle; Le Galliard, Jean-François

2013-01-01

Studies of the relationship of performance and behavioral traits with environmental factors have tended to neglect interindividual variation even though quantification of this variation is fundamental to understanding how phenotypic traits can evolve. In ectotherms, functional integration of locomotor performance, thermal behavior, and energy metabolism is of special interest because of the potential for coadaptation among these traits. For this reason, we analyzed interindividual variation, covariation, and repeatability of the thermal sensitivity of maximal sprint speed, preferred body temperature, thermal precision, and resting metabolic rate measured in ca. 200 common lizards (Zootoca vivipara) that varied by sex, age, and body size. We found significant interindividual variation in selected body temperatures and in the thermal performance curve of maximal sprint speed for both the intercept (expected trait value at the average temperature) and the slope (measure of thermal sensitivity). Interindividual differences in maximal sprint speed across temperatures, preferred body temperature, and thermal precision were significantly repeatable. A positive relationship existed between preferred body temperature and thermal precision, implying that individuals selecting higher temperatures were more precise. The resting metabolic rate was highly variable but was not related to thermal sensitivity of maximal sprint speed or thermal behavior. Thus, locomotor performance, thermal behavior, and energy metabolism were not directly functionally linked in the common lizard.

Novel drug and soluble target tolerant antidrug antibody assay for therapeutic antibodies bearing the P329G mutation.

PubMed

Wessels, Uwe; Schick, Eginhard; Ritter, Mirko; Kowalewsky, Frank; Heinrich, Julia; Stubenrauch, Kay

2017-06-01

Bridging immunoassays for detection of antidrug antibodies (ADAs) are typically susceptible to high concentrations of residual drug. Sensitive drug-tolerant assays are, therefore, needed. An immune complex assay to detect ADAs against therapeutic antibodies bearing Pro329Gly mutation was established. The assay uses antibodies specific for the Pro329Gly mutation for capture and human soluble Fcγ receptor for detection. When compared with a bridging assay, the new assay showed similar precision, high sensitivity to IgG1 ADA and dramatically improved drug tolerance. However, it was not able to detect early (IgM-based) immune responses. Applied in combination with a bridging assay, the novel assay serves as orthogonal assay for immunogenicity assessment and allows further characterization of ADA responses.

A Perfect Match Genomic Landscape Provides a Unified Framework for the Precise Detection of Variation in Natural and Synthetic Haploid Genomes

PubMed Central

Palacios-Flores, Kim; García-Sotelo, Jair; Castillo, Alejandra; Uribe, Carina; Aguilar, Luis; Morales, Lucía; Gómez-Romero, Laura; Reyes, José; Garciarubio, Alejandro; Boege, Margareta; Dávila, Guillermo

2018-01-01

We present a conceptually simple, sensitive, precise, and essentially nonstatistical solution for the analysis of genome variation in haploid organisms. The generation of a Perfect Match Genomic Landscape (PMGL), which computes intergenome identity with single nucleotide resolution, reveals signatures of variation wherever a query genome differs from a reference genome. Such signatures encode the precise location of different types of variants, including single nucleotide variants, deletions, insertions, and amplifications, effectively introducing the concept of a general signature of variation. The precise nature of variants is then resolved through the generation of targeted alignments between specific sets of sequence reads and known regions of the reference genome. Thus, the perfect match logic decouples the identification of the location of variants from the characterization of their nature, providing a unified framework for the detection of genome variation. We assessed the performance of the PMGL strategy via simulation experiments. We determined the variation profiles of natural genomes and of a synthetic chromosome, both in the context of haploid yeast strains. Our approach uncovered variants that have previously escaped detection. Moreover, our strategy is ideally suited for further refining high-quality reference genomes. The source codes for the automated PMGL pipeline have been deposited in a public repository. PMID:29367403

[Psychometric properties and diagnostic value of 'lexical screening for aphasias'].

PubMed

Pena-Chavez, R; Martinez-Jimenez, L; Lopez-Espinoza, M

2014-09-16

INTRODUCTION. Language assessment in persons with brain injury makes it possible to know whether they require language rehabilitation or not. Given the importance of a precise evaluation, assessment instruments must be valid and reliable, so as to avoid mistaken and subjective diagnoses. AIM. To validate 'lexical screening for aphasias' in a sample of 58 Chilean individuals. SUBJECTS AND METHODS. A screening-type language test, lasting 20 minutes and based on the lexical processing model devised by Patterson and Shewell (1987), was constructed. The sample was made up of two groups containing 29 aphasic subjects and 29 control subjects from different health centres in the regions of Biobio and Maule, Chile. Their ages ranged between 24 and 79 years and had between 0 and 17 years' schooling. Tests were carried out to determine discriminating validity, concurrent validity with the aphasia disorder assessment battery, reliability, sensitivity and specificity. RESULTS. The statistical analysis showed a high discriminating validity (p < 0.001), an acceptable mean concurrent validity with aphasia disorder assessment battery (rs = 0.65), high mean reliability (alpha = 0.87), moderate mean sensitivity (69%) and high mean specificity (86%). CONCLUSION. 'Lexical screening for aphasias' is valid and reliable for assessing language in persons with aphasias; it is sensitive for detecting aphasic subjects and is specific for precluding language disorders in persons with normal language abilities.

Precision Medicine for Acute Kidney Injury (AKI): Redefining AKI by Agnostic Kidney Tissue Interrogation and Genetics.

PubMed

Kiryluk, Krzysztof; Bomback, Andrew S; Cheng, Yim-Ling; Xu, Katherine; Camara, Pablo G; Rabadan, Raul; Sims, Peter A; Barasch, Jonathan

2018-01-01

Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase. Nonetheless, these biomarkers lack the capacity to subfractionate AKI further (eg, sepsis versus ischemia versus nephrotoxicity from medications, enzymes, or metals) or inform us about the primary and secondary sites of injury. It also is unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single-cell and single-nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification, and staging, and provide the renal community with a significant advance toward precision medicine in the analysis AKI. Copyright © 2017 Elsevier Inc. All rights reserved.

The precision-recall plot is more informative than the ROC plot when evaluating binary classifiers on imbalanced datasets.

PubMed

Saito, Takaya; Rehmsmeier, Marc

2015-01-01

Binary classifiers are routinely evaluated with performance measures such as sensitivity and specificity, and performance is frequently illustrated with Receiver Operating Characteristics (ROC) plots. Alternative measures such as positive predictive value (PPV) and the associated Precision/Recall (PRC) plots are used less frequently. Many bioinformatics studies develop and evaluate classifiers that are to be applied to strongly imbalanced datasets in which the number of negatives outweighs the number of positives significantly. While ROC plots are visually appealing and provide an overview of a classifier's performance across a wide range of specificities, one can ask whether ROC plots could be misleading when applied in imbalanced classification scenarios. We show here that the visual interpretability of ROC plots in the context of imbalanced datasets can be deceptive with respect to conclusions about the reliability of classification performance, owing to an intuitive but wrong interpretation of specificity. PRC plots, on the other hand, can provide the viewer with an accurate prediction of future classification performance due to the fact that they evaluate the fraction of true positives among positive predictions. Our findings have potential implications for the interpretation of a large number of studies that use ROC plots on imbalanced datasets.

Selective Manipulation of Neural Circuits.

PubMed

Park, Hong Geun; Carmel, Jason B

2016-04-01

Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses the genetic identity of a cell, such as a transcription factor unique to a circuit, to drive expression of a molecule that can manipulate cell function. The second uses the spatial connectivity of a circuit to achieve specificity: one genetic element is introduced at the origin of a circuit and the other at its termination. When the two genetic elements combine within a neuron, they can alter its function. These two general approaches can be combined to allow manipulation of neurons with a specific genetic identity by introducing a regulatory gene into the origin or termination of the circuit. We consider the advantages and disadvantages of both these general approaches with regard to specificity and efficacy of the manipulations. We also review the genetic techniques that allow gain- and loss-of-function within specific neural circuits. These approaches introduce light-sensitive channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons that form specific circuits. We compare these tools with others developed for circuit-specific manipulation and describe the advantages of each. Finally, we discuss how these tools might be applied for identification of the neural circuits that mediate behavior and for repair of neural connections.

High precision hyperfine measurements in Bismuth challenge bound-state strong-field QED

NASA Astrophysics Data System (ADS)

Ullmann, Johannes; Andelkovic, Zoran; Brandau, Carsten; Dax, Andreas; Geithner, Wolfgang; Geppert, Christopher; Gorges, Christian; Hammen, Michael; Hannen, Volker; Kaufmann, Simon; König, Kristian; Litvinov, Yuri A.; Lochmann, Matthias; Maaß, Bernhard; Meisner, Johann; Murböck, Tobias; Sánchez, Rodolfo; Schmidt, Matthias; Schmidt, Stefan; Steck, Markus; Stöhlker, Thomas; Thompson, Richard C.; Trageser, Christian; Vollbrecht, Jonas; Weinheimer, Christian; Nörtershäuser, Wilfried

2017-05-01

Electrons bound in highly charged heavy ions such as hydrogen-like bismuth 209Bi82+ experience electromagnetic fields that are a million times stronger than in light atoms. Measuring the wavelength of light emitted and absorbed by these ions is therefore a sensitive testing ground for quantum electrodynamical (QED) effects and especially the electron-nucleus interaction under such extreme conditions. However, insufficient knowledge of the nuclear structure has prevented a rigorous test of strong-field QED. Here we present a measurement of the so-called specific difference between the hyperfine splittings in hydrogen-like and lithium-like bismuth 209Bi82+,80+ with a precision that is improved by more than an order of magnitude. Even though this quantity is believed to be largely insensitive to nuclear structure and therefore the most decisive test of QED in the strong magnetic field regime, we find a 7-σ discrepancy compared with the theoretical prediction.

High precision hyperfine measurements in Bismuth challenge bound-state strong-field QED.

PubMed

Ullmann, Johannes; Andelkovic, Zoran; Brandau, Carsten; Dax, Andreas; Geithner, Wolfgang; Geppert, Christopher; Gorges, Christian; Hammen, Michael; Hannen, Volker; Kaufmann, Simon; König, Kristian; Litvinov, Yuri A; Lochmann, Matthias; Maaß, Bernhard; Meisner, Johann; Murböck, Tobias; Sánchez, Rodolfo; Schmidt, Matthias; Schmidt, Stefan; Steck, Markus; Stöhlker, Thomas; Thompson, Richard C; Trageser, Christian; Vollbrecht, Jonas; Weinheimer, Christian; Nörtershäuser, Wilfried

2017-05-16

Electrons bound in highly charged heavy ions such as hydrogen-like bismuth 209 Bi 82+ experience electromagnetic fields that are a million times stronger than in light atoms. Measuring the wavelength of light emitted and absorbed by these ions is therefore a sensitive testing ground for quantum electrodynamical (QED) effects and especially the electron-nucleus interaction under such extreme conditions. However, insufficient knowledge of the nuclear structure has prevented a rigorous test of strong-field QED. Here we present a measurement of the so-called specific difference between the hyperfine splittings in hydrogen-like and lithium-like bismuth 209 Bi 82+,80+ with a precision that is improved by more than an order of magnitude. Even though this quantity is believed to be largely insensitive to nuclear structure and therefore the most decisive test of QED in the strong magnetic field regime, we find a 7-σ discrepancy compared with the theoretical prediction.

High precision hyperfine measurements in Bismuth challenge bound-state strong-field QED

PubMed Central

Ullmann, Johannes; Andelkovic, Zoran; Brandau, Carsten; Dax, Andreas; Geithner, Wolfgang; Geppert, Christopher; Gorges, Christian; Hammen, Michael; Hannen, Volker; Kaufmann, Simon; König, Kristian; Litvinov, Yuri A.; Lochmann, Matthias; Maaß, Bernhard; Meisner, Johann; Murböck, Tobias; Sánchez, Rodolfo; Schmidt, Matthias; Schmidt, Stefan; Steck, Markus; Stöhlker, Thomas; Thompson, Richard C.; Trageser, Christian; Vollbrecht, Jonas; Weinheimer, Christian; Nörtershäuser, Wilfried

2017-01-01

Electrons bound in highly charged heavy ions such as hydrogen-like bismuth 209Bi82+ experience electromagnetic fields that are a million times stronger than in light atoms. Measuring the wavelength of light emitted and absorbed by these ions is therefore a sensitive testing ground for quantum electrodynamical (QED) effects and especially the electron–nucleus interaction under such extreme conditions. However, insufficient knowledge of the nuclear structure has prevented a rigorous test of strong-field QED. Here we present a measurement of the so-called specific difference between the hyperfine splittings in hydrogen-like and lithium-like bismuth 209Bi82+,80+ with a precision that is improved by more than an order of magnitude. Even though this quantity is believed to be largely insensitive to nuclear structure and therefore the most decisive test of QED in the strong magnetic field regime, we find a 7-σ discrepancy compared with the theoretical prediction. PMID:28508892

Research on H2 speed governor for diesel engine of marine power station

NASA Astrophysics Data System (ADS)

Huang, Man-Lei

2007-09-01

The frequency stability of a marine power system is determined by the dynamic characteristic of the diesel engine speed regulation system in a marine power station. In order to reduce the effect of load disturbances and improve the dynamic precision of a diesel engine speed governor, a controller was designed for a diesel engine speed regulation system using H2 control theory. This transforms the specifications of the system into a standard H2 control problem. Firstly, the mathematical model of a diesel engine speed regulation system using an H2 speed governor is presented. To counter external disturbances and model uncertainty, the design of an H2 speed governor rests on the problem of mixed sensitivity. Computer simulation verified that the H2 speed governor improves the dynamic precision of a system and the ability to adapt to load disturbances, thus enhancing the frequency stability of marine power systems.

Diffractive optics for precision alignment of Euclid space telescope optics (Conference Presentation)

NASA Astrophysics Data System (ADS)

Asfour, Jean-Michel; Weidner, Frank; Bodendorf, Christof; Bode, Andreas; Poleshchuk, Alexander G.; Nasyrov, Ruslan K.; Grupp, Frank; Bender, Ralf

2017-09-01

We present a method for precise alignment of lens elements using specific Computer Generated Hologram (CGH) with an integrated Fizeau reference flat surface and a Fizeau interferometer. The method is used for aligning the so called Camera Lens Assembly for ESAs Euclid telescope. Each lens has a corresponding annular area on the diffractive optics, which is used to control the position of each lens. The lenses are subsequently positioned using individual annular rings of the CGH. The overall alignment accuracy is below 1 µm, the alignment sensitivity is in the range of 0.1 µm. The achieved alignment accuracy of the lenses relative to each other is mainly depending on the stability in time of the alignment tower. Error budgets when using computer generated holograms and physical limitations are explained. Calibration measurements of the alignment system and the typically reached alignment accuracies will be shown and discussed.

Improvements in absolute seismometer sensitivity calibration using local earth gravity measurements

USGS Publications Warehouse

Anthony, Robert E.; Ringler, Adam; Wilson, David

2018-01-01

The ability to determine both absolute and relative seismic amplitudes is fundamentally limited by the accuracy and precision with which scientists are able to calibrate seismometer sensitivities and characterize their response. Currently, across the Global Seismic Network (GSN), errors in midband sensitivity exceed 3% at the 95% confidence interval and are the least‐constrained response parameter in seismic recording systems. We explore a new methodology utilizing precise absolute Earth gravity measurements to determine the midband sensitivity of seismic instruments. We first determine the absolute sensitivity of Kinemetrics EpiSensor accelerometers to 0.06% at the 99% confidence interval by inverting them in a known gravity field at the Albuquerque Seismological Laboratory (ASL). After the accelerometer is calibrated, we install it in its normal configuration next to broadband seismometers and subject the sensors to identical ground motions to perform relative calibrations of the broadband sensors. Using this technique, we are able to determine the absolute midband sensitivity of the vertical components of Nanometrics Trillium Compact seismometers to within 0.11% and Streckeisen STS‐2 seismometers to within 0.14% at the 99% confidence interval. The technique enables absolute calibrations from first principles that are traceable to National Institute of Standards and Technology (NIST) measurements while providing nearly an order of magnitude more precision than step‐table calibrations.

An ATMND/SGI based label-free and fluorescence ratiometric aptasensor for rapid and highly sensitive detection of cocaine in biofluids.

PubMed

Wang, Jiamian; Song, Jie; Wang, Xiuyun; Wu, Shuo; Zhao, Yanqiu; Luo, Pinchen; Meng, Changgong

2016-12-01

A label-free ratiometric fluorescence aptasensor has been developed for the rapid and sensitive detection of cocaine in complex biofluids. The fluorescent aptasensor is composed of a non-labeled GC-38 cocaine aptamer which serves as a basic sensing unit and two fluorophores, 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND) and SYBR Green I (SGI) which serves as a signal reporter and a build-in reference, respectively. The detection principle is based on a specific cocaine mediated ATMND displacement reaction and the corresponding change in the fluorescence ratio of ATMND to SGI. Due to the high affinity of the non-labeled aptamer, the good precision originated from the ratiometric method, and the good fluorescence quantum yield of the fluorophore, the aptasensor shows good analytical performance with respect to cocaine detection. Under optimal conditions, the aptasensor shows a linear range of 0.10-10μM and a low limit of detection of 56nM, with a fast response of 20s. The low limit of detection is comparable to most of the fluorescent aptasensors with signal amplification strategies and much lower than all of the unamplified cocaine aptasensors. Practical sample analysis in a series of complex biofluids, including urine, saliva and serum, also indicates the good precision, stability, and high sensitivity of the aptasensor, which may have great potential for the point-of-care screening of cocaine in complex biofluids. Copyright © 2016 Elsevier B.V. All rights reserved.

Lighting up the brain: genetically encoded fluorescent sensors for imaging neurotransmitters and neuromodulators.

PubMed

Wang, Huan; Jing, Miao; Li, Yulong

2018-06-01

Measuring the precise dynamics of specific neurotransmitters and neuromodulators in the brain is essential for understanding how information is transmitted and processed. Thanks to the development and optimization of various genetically encoded sensors, we are approaching the stage in which a few key neurotransmitters/neuromodulators can be imaged with high cell specificity and good signal-to-noise ratio. Here, we summarize recent progress regarding these sensors, focusing on their design principles, properties, potential applications, and current limitations. We also highlight the G protein-coupled receptor (GPCR) scaffold as a promising platform that may enable the scalable development of the next generation of sensors, enabling the rapid, sensitive, and specific detection of a large repertoire of neurotransmitters/neuromodulators in vivo at cellular or even subcellular resolution. Copyright © 2018 Elsevier Ltd. All rights reserved.

Input-variable sensitivity assessment for sediment transport relations

NASA Astrophysics Data System (ADS)

Fernández, Roberto; Garcia, Marcelo H.

2017-09-01

A methodology to assess input-variable sensitivity for sediment transport relations is presented. The Mean Value First Order Second Moment Method (MVFOSM) is applied to two bed load transport equations showing that it may be used to rank all input variables in terms of how their specific variance affects the overall variance of the sediment transport estimation. In sites where data are scarce or nonexistent, the results obtained may be used to (i) determine what variables would have the largest impact when estimating sediment loads in the absence of field observations and (ii) design field campaigns to specifically measure those variables for which a given transport equation is most sensitive; in sites where data are readily available, the results would allow quantifying the effect that the variance associated with each input variable has on the variance of the sediment transport estimates. An application of the method to two transport relations using data from a tropical mountain river in Costa Rica is implemented to exemplify the potential of the method in places where input data are limited. Results are compared against Monte Carlo simulations to assess the reliability of the method and validate its results. For both of the sediment transport relations used in the sensitivity analysis, accurate knowledge of sediment size was found to have more impact on sediment transport predictions than precise knowledge of other input variables such as channel slope and flow discharge.

Rapid and sensitive gas chromatography ion-trap mass spectrometry method for the determination of tobacco specific N-nitrosamines in secondhand smoke

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

SLEIMAN, Mohamad; MADDALENA, Randy L.; GUNDEL, Lara A.

Tobacco-specific nitrosamines (TSNAs) are some of the most potent carcinogens in tobacco and cigarette smoke. Accurate quantification of these chemicals is needed to help assess public health risks. We developed and validated a specific and sensitive method to measure four TSNAs in both the gas- and particle-phase of secondhand smoke (SHS) using gas chromatography and ion-trap tandem mass spectrometry,. A smoking machine in an 18-m3 room-sized chamber generated relevant concentrations of SHS that were actively sampled on Teflon coated fiber glass (TCFG) filters, and passively sampled on cellulose substrates. A simple solid-liquid extraction protocol using methanol as solvent was successfullymore » applied to both filters with high recoveries ranging from 85 to 115percent. Tandem MS parameters were optimized to obtain the best sensitivity in terms of signal to-noise ratio (S/N) for the target compounds. For each TSNA, the major fragmentation pathways as well as ion structures were elucidated and compared with previously published data. The method showed excellent performances with a linear dynamic range between 2 and 1000 ng mL-1, low detection limits (S/N> 3) of 30-300 pg.ml-1 and precision with experimental errors below 10percent for all compounds. Moreover, no interfering peaks were observed indicating a high selectivity of MS/MS without the need for a sample clean up step. The sampling and analysis method provides a sensitive and accurate tool to detect and quantify traces of TSNA in SHS polluted indoor environments.« less

Optimization of circulating cell-free DNA recovery for KRAS mutation and HPV detection in plasma.

PubMed

Mazurek, Agnieszka M; Fiszer-Kierzkowska, A; Rutkowski, T; Składowski, K; Pierzyna, M; Scieglińska, D; Woźniak, G; Głowacki, G; Kawczyński, R; Małusecka, E

2013-01-01

The precise analysis of tumour markers in blood such as circulating cell-free DNA (cfDNA) could have a significant impact in facilitating monitoring of patients after initial therapy. Although high levels of total cfDNA in plasma of cancer patients are consistently demonstrated, a low sensitivity of DNA alterations is reported. The major question regards the recovery of tumour-specific cfDNA such as KRAS mutated DNA and cancer-associated type 16 of human papillomavirus (HPV16). TaqMan technology was used for detection of KRAS mutation, HPV16 and to quantify cfDNA in blood plasma. Comparison of four different column-based commercial kits shows that the cfDNA purification carried out by the Genomic Mini AX Body Fluids kit and the QIAamp Circulating Nucleic Acid kit gave us the possibility to improve the sensitivity of detection of KRAS mutation and HPV16. The optimized method was used to follow the reduction in cancer-specific cfDNA after therapy. We found that large volume extractions with low volume of DNA eluate enabled trace amounts of tumour-specific cfDNA from cancer patients to be effectively identified. Data presented in this study facilitate detection of tumour-specific cfDNA and improve standards needed for the implementation of cfDNA technology into routine clinical practice.

Detection of VR-2332 strain of porcine reproductive and respiratory syndrome virus type II using an aptamer-based sandwich-type assay.

PubMed

Lee, Su Jin; Kwon, Young Seop; Lee, Ji-eun; Choi, Eun-Jin; Lee, Chang-Hee; Song, Jae-Young; Gu, Man Bock

2013-01-02

Porcine reproductive and respiratory syndrome virus (PRRSV) causes porcine reproductive and respiratory syndrome disease (PRRS), a disease that has a significant and economic impact on the swine industry. In this study, single-stranded DNA (ssDNA) aptamers with high specificity and affinity against VR-2332 strain of PRRSV type II were successfully obtained. Of 19 candidates, the LB32 aptamer was found to be the most specific and sensitive to VR-2332 strain according to an aptamer-based surface plasmon resonance (SPR) analysis. The detection of VR-2332 of PRRSV type II was successfully accomplished using the enzyme-linked antibody-aptamer sandwich (ELAAS) method. The detection limit of ELAAS was 4.8 × 10(0) TCID(50)/mL that is comparable to some of the previous reports of the PCR-based detection but does not require any complicated equipment or extra costs. Moreover, this ELAAS-based PRRSV detection showed similar sensitivity for both the VR-2332 samples spiked in diluted swine serum and in buffer. Therefore, this VR-2332 strain-specific aptamer and its assay method with high specificity can be used as an alternative method for the fast and precise detection of PRRSV.

How Single-site Mutation Affects HP Lattice Proteins

NASA Astrophysics Data System (ADS)

Shi, Guangjie; Landau, David P.; Vogel, Thomas; Wüst, Thomas; Li, Ying Wai

2014-03-01

We developed a heuristic method based on Wang-Landauand multicanonical sampling for determining the ground-state degeneracy of HP lattice proteins . Our algorithm allowed the most precise estimations of the (sometimes substantial) ground-state degeneracies of some widely studied HP sequences. We investigated the effects of single-site mutation on specific long HP lattice proteins comprehensively, including structural changes in ground-states, changes of ground-state degeneracy and thermodynamic properties of the systems. Both extremely sensitive and insensitive cases have been observed; consequently, properties such as specific heat, tortuosities etc. may be either largely unaffected or may change significantly due to mutation. More interestingly, mutation can even induce a lower ground-state energy in a few cases. Supported by NSF.

Development and Validation of Liquid Chromatographic Method for Estimation of Naringin in Nanoformulation

PubMed Central

Musmade, Kranti P.; Trilok, M.; Dengale, Swapnil J.; Bhat, Krishnamurthy; Reddy, M. S.; Musmade, Prashant B.; Udupa, N.

2014-01-01

A simple, precise, accurate, rapid, and sensitive reverse phase high performance liquid chromatography (RP-HPLC) method with UV detection has been developed and validated for quantification of naringin (NAR) in novel pharmaceutical formulation. NAR is a polyphenolic flavonoid present in most of the citrus plants having variety of pharmacological activities. Method optimization was carried out by considering the various parameters such as effect of pH and column. The analyte was separated by employing a C18 (250.0 × 4.6 mm, 5 μm) column at ambient temperature in isocratic conditions using phosphate buffer pH 3.5: acetonitrile (75 : 25% v/v) as mobile phase pumped at a flow rate of 1.0 mL/min. UV detection was carried out at 282 nm. The developed method was validated according to ICH guidelines Q2(R1). The method was found to be precise and accurate on statistical evaluation with a linearity range of 0.1 to 20.0 μg/mL for NAR. The intra- and interday precision studies showed good reproducibility with coefficients of variation (CV) less than 1.0%. The mean recovery of NAR was found to be 99.33 ± 0.16%. The proposed method was found to be highly accurate, sensitive, and robust. The proposed liquid chromatographic method was successfully employed for the routine analysis of said compound in developed novel nanopharmaceuticals. The presence of excipients did not show any interference on the determination of NAR, indicating method specificity. PMID:26556205

Bitwise efficiency in chaotic models

PubMed Central

Düben, Peter; Palmer, Tim

2017-01-01

Motivated by the increasing energy consumption of supercomputing for weather and climate simulations, we introduce a framework for investigating the bit-level information efficiency of chaotic models. In comparison with previous explorations of inexactness in climate modelling, the proposed and tested information metric has three specific advantages: (i) it requires only a single high-precision time series; (ii) information does not grow indefinitely for decreasing time step; and (iii) information is more sensitive to the dynamics and uncertainties of the model rather than to the implementation details. We demonstrate the notion of bit-level information efficiency in two of Edward Lorenz’s prototypical chaotic models: Lorenz 1963 (L63) and Lorenz 1996 (L96). Although L63 is typically integrated in 64-bit ‘double’ floating point precision, we show that only 16 bits have significant information content, given an initial condition uncertainty of approximately 1% of the size of the attractor. This result is sensitive to the size of the uncertainty but not to the time step of the model. We then apply the metric to the L96 model and find that a 16-bit scaled integer model would suffice given the uncertainty of the unresolved sub-grid-scale dynamics. We then show that, by dedicating computational resources to spatial resolution rather than numeric precision in a field programmable gate array (FPGA), we see up to 28.6% improvement in forecast accuracy, an approximately fivefold reduction in the number of logical computing elements required and an approximately 10-fold reduction in energy consumed by the FPGA, for the L96 model. PMID:28989303

Bitwise efficiency in chaotic models

NASA Astrophysics Data System (ADS)

Jeffress, Stephen; Düben, Peter; Palmer, Tim

2017-09-01

Motivated by the increasing energy consumption of supercomputing for weather and climate simulations, we introduce a framework for investigating the bit-level information efficiency of chaotic models. In comparison with previous explorations of inexactness in climate modelling, the proposed and tested information metric has three specific advantages: (i) it requires only a single high-precision time series; (ii) information does not grow indefinitely for decreasing time step; and (iii) information is more sensitive to the dynamics and uncertainties of the model rather than to the implementation details. We demonstrate the notion of bit-level information efficiency in two of Edward Lorenz's prototypical chaotic models: Lorenz 1963 (L63) and Lorenz 1996 (L96). Although L63 is typically integrated in 64-bit `double' floating point precision, we show that only 16 bits have significant information content, given an initial condition uncertainty of approximately 1% of the size of the attractor. This result is sensitive to the size of the uncertainty but not to the time step of the model. We then apply the metric to the L96 model and find that a 16-bit scaled integer model would suffice given the uncertainty of the unresolved sub-grid-scale dynamics. We then show that, by dedicating computational resources to spatial resolution rather than numeric precision in a field programmable gate array (FPGA), we see up to 28.6% improvement in forecast accuracy, an approximately fivefold reduction in the number of logical computing elements required and an approximately 10-fold reduction in energy consumed by the FPGA, for the L96 model.

Reward Pays the Cost of Noise Reduction in Motor and Cognitive Control.

PubMed

Manohar, Sanjay G; Chong, Trevor T-J; Apps, Matthew A J; Batla, Amit; Stamelou, Maria; Jarman, Paul R; Bhatia, Kailash P; Husain, Masud

2015-06-29

Speed-accuracy trade-off is an intensively studied law governing almost all behavioral tasks across species. Here we show that motivation by reward breaks this law, by simultaneously invigorating movement and improving response precision. We devised a model to explain this paradoxical effect of reward by considering a new factor: the cost of control. Exerting control to improve response precision might itself come at a cost--a cost to attenuate a proportion of intrinsic neural noise. Applying a noise-reduction cost to optimal motor control predicted that reward can increase both velocity and accuracy. Similarly, application to decision-making predicted that reward reduces reaction times and errors in cognitive control. We used a novel saccadic distraction task to quantify the speed and accuracy of both movements and decisions under varying reward. Both faster speeds and smaller errors were observed with higher incentives, with the results best fitted by a model including a precision cost. Recent theories consider dopamine to be a key neuromodulator in mediating motivational effects of reward. We therefore examined how Parkinson's disease (PD), a condition associated with dopamine depletion, alters the effects of reward. Individuals with PD showed reduced reward sensitivity in their speed and accuracy, consistent in our model with higher noise-control costs. Including a cost of control over noise explains how reward may allow apparent performance limits to be surpassed. On this view, the pattern of reduced reward sensitivity in PD patients can specifically be accounted for by a higher cost for controlling noise. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

Validation of an Immunodiagnostic Assay for Detection of 13 Streptococcus pneumoniae Serotype-Specific Polysaccharides in Human Urine

PubMed Central

Huijts, Susanne M.; Wu, Kangjian; Souza, Victor; Passador, Sherry; Tinder, Chunyan; Song, Esther; Elfassy, Arik; McNeil, Lisa; Menton, Ronald; French, Roger; Callahan, Janice; Webber, Chris; Gruber, William C.; Bonten, Marc J. M.; Jansen, Kathrin U.

2012-01-01

To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified Streptococcus pneumoniae (13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults. PMID:22675155

Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine.

PubMed

Pride, Michael W; Huijts, Susanne M; Wu, Kangjian; Souza, Victor; Passador, Sherry; Tinder, Chunyan; Song, Esther; Elfassy, Arik; McNeil, Lisa; Menton, Ronald; French, Roger; Callahan, Janice; Webber, Chris; Gruber, William C; Bonten, Marc J M; Jansen, Kathrin U

2012-08-01

To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified Streptococcus pneumoniae (13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults.

High-throughput quantitation of amino acids in rat and mouse biological matrices using stable isotope labeling and UPLC-MS/MS analysis.

PubMed

Takach, Edward; O'Shea, Thomas; Liu, Hanlan

2014-08-01

Quantifying amino acids in biological matrices is typically performed using liquid chromatography (LC) coupled with fluorescent detection (FLD), requiring both derivatization and complete baseline separation of all amino acids. Due to its high specificity and sensitivity, the use of UPLC-MS/MS eliminates the derivatization step and allows for overlapping amino acid retention times thereby shortening the analysis time. Furthermore, combining UPLC-MS/MS with stable isotope labeling (e.g., isobaric tag for relative and absolute quantitation, i.e., iTRAQ) of amino acids enables quantitation while maintaining sensitivity, selectivity and speed of analysis. In this study, we report combining UPLC-MS/MS analysis with iTRAQ labeling of amino acids resulting in the elution and quantitation of 44 amino acids within 5 min demonstrating the speed and convenience of this assay over established approaches. This chromatographic analysis time represented a 5-fold improvement over the conventional HPLC-MS/MS method developed in our laboratory. In addition, the UPLC-MS/MS method demonstrated improvements in both specificity and sensitivity without loss of precision. In comparing UPLC-MS/MS and HPLC-MS/MS results of 32 detected amino acids, only 2 amino acids exhibited imprecision (RSD) >15% using UPLC-MS/MS, while 9 amino acids exhibited RSD >15% using HPLC-MS/MS. Evaluating intra- and inter-assay precision over 3 days, the quantitation range for 32 detected amino acids in rat plasma was 0.90-497 μM, with overall mean intra-day precision of less than 15% and mean inter-day precision of 12%. This UPLC-MS/MS assay was successfully implemented for the quantitative analysis of amino acids in rat and mouse plasma, along with mouse urine and tissue samples, resulting in the following concentration ranges: 0.98-431 μM in mouse plasma for 32 detected amino acids; 0.62-443 μM in rat plasma for 32 detected amino acids; 0.44-8590μM in mouse liver for 33 detected amino acids; 0.61-1241 μM in mouse kidney for 37 detected amino acids; and 1.39-1,681 μM in rat urine for 34 detected amino acids. The utility of the assay was further demonstrated by measuring and comparing plasma amino acid levels between pre-diabetic Zucker diabetic fatty rats (ZDF/Gmi fa/fa) and their lean littermates (ZDF/Gmi fa/?). Significant differences (P<0.001) in 9 amino acid concentrations were observed, with the majority ranging from a 2- to 5-fold increase in pre-diabetic ZDF rats on comparison with ZDF lean rats, consistent with previous literature reports. Copyright © 2014 Elsevier B.V. All rights reserved.

A general study of techniques for ultraviolet astrophysical studies on space vehicles

NASA Technical Reports Server (NTRS)

Moos, H. W.; Fastie, W. G.; Davidsen, A. F.

1977-01-01

Recent accomplishments in three areas of UV instrumentation for space astronomy are discussed. These areas include reliable UV photometry, sensitive photon-detection techniques, and precise telescope pointing. Calibration facilities for spectrometers designed to operate in the spectral regions above 1200 A and down to 400 A are described which employ a series of diodes calibrated against electron synchrotron radiation as well as other radiometric standards. Improvements in photon-detection sensitivity achieved with the aid of pulse-counting electronics and multispectral detectors are reported, and the technique of precise subarcsecond telescope pointing is briefly noted. Some observational results are presented which demonstrate the advantages and precision of the instruments and techniques considered.

BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks.

PubMed

Yan, Winston X; Mirzazadeh, Reza; Garnerone, Silvano; Scott, David; Schneider, Martin W; Kallas, Tomasz; Custodio, Joaquin; Wernersson, Erik; Li, Yinqing; Gao, Linyi; Federova, Yana; Zetsche, Bernd; Zhang, Feng; Bienko, Magda; Crosetto, Nicola

2017-05-12

Precisely measuring the location and frequency of DNA double-strand breaks (DSBs) along the genome is instrumental to understanding genomic fragility, but current methods are limited in versatility, sensitivity or practicality. Here we present Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing. We apply BLISS to profile endogenous and exogenous DSBs in low-input samples of cancer cells, embryonic stem cells and liver tissue. We demonstrate the sensitivity of BLISS by assessing the genome-wide off-target activity of two CRISPR-associated RNA-guided endonucleases, Cas9 and Cpf1, observing that Cpf1 has higher specificity than Cas9. Our results establish BLISS as a versatile, sensitive and efficient method for genome-wide DSB mapping in many applications.

Ultrastructural organisation of HCV from the bloodstream of infected patients revealed by electron microscopy after specific immunocapture.

PubMed

Piver, Eric; Boyer, Audrey; Gaillard, Julien; Bull, Anne; Beaumont, Elodie; Roingeard, Philippe; Meunier, Jean-Christophe

2017-08-01

HCV particles are associated with very low-density lipoprotein components in chronically infected patients. These hybrid particles, or 'lipo-viro particles' (LVPs), are rich in triglycerides, and contain the viral RNA, the capsid protein, E1E2 envelope glycoproteins and apolipoproteins B and E. However, their specific ultrastructural organisation has yet to be determined. We developed a strategy for the preparation of any viral sample that preserves the native structure of the LVPs, facilitating their precise morphological characterisation. Using a strategy based on the direct specific immunocapture of particles on transmission electron microscopy (TEM) grids, we characterised the precise morphology of the viral particle by TEM. The LVP consists of a broad nucleocapsid surrounding an electron-dense centre, presumably containing the HCV genome. The nucleocapsid is surrounded by an irregular, detergent-sensitive crescent probably composed of lipids. Lipid content may determine particle size. These particles carry HCV E1E2, ApoB and ApoE, as shown in our immuno-EM analysis. Our results also suggest that these putative LVPs circulate in the serum of patients as part of a mixed population, including lipoprotein-like particles and complete viral particles. Twenty-five years after the discovery of HCV, this study finally provides information about the precise morphological organisation of viral particles. It is truly remarkable that our TEM images fully confirm the ultrastructure of LVPs predicted by several authors, almost exclusively from the results of molecular biology studies. 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/.

Temperature measurement in the adult emergency department: oral, tympanic membrane and temporal artery temperatures versus rectal temperature.

PubMed

Bijur, Polly E; Shah, Purvi D; Esses, David

2016-12-01

The objective was to compare agreement between three non-invasive measures of temperature and rectal temperatures and to estimate the sensitivity and specificity of these measures to detect a rectal temperature of 38°C or higher. We conducted a study of the diagnostic accuracy of oral, tympanic membrane (TM) and temporal artery (TA) thermometry to measure fever in an urban emergency department (ED). Data were collected from adult patients who received rectal temperature measurement. Bland-Altman analysis was performed; sensitivity, specificity and 95% CIs were calculated. 987 patients were enrolled. 36% of the TM and TA readings differed by 0.5°C or more from rectal temperatures, 50% of oral temperatures. TM measures were most precise-the SD of the difference from rectal was 0.4°C TM, and 0.6°C for oral and TA (p<0.001). The sensitivities of a 38°C cutpoint on oral, TM and TA measures to detect a rectal temperature of 38°C or higher were: 37.0%, 68.3% and 71.1%, respectively (oral vs TM and TA p<0.001). The corresponding specificities were 99.4%, 98.2% and 92.3% (oral, TM and TA) with oral specificity significantly higher than the other two methods (p<0.01). TM and TA cutpoints of 37.5°C provided greater than 90% sensitivity to detect fever with specificity of 90% and 72%, respectively. None of the non-invasive methods met benchmarks for diagnostic accuracy using the criterion of 38°C to detect rectal temperature of 38°C. A TM cutpoint of 37.5°C provides maximum diagnostic accuracy of the three non-invasive measures. 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/.

Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data

NASA Astrophysics Data System (ADS)

Sinha, Subarna; Thomas, Daniel; Chan, Steven; Gao, Yang; Brunen, Diede; Torabi, Damoun; Reinisch, Andreas; Hernandez, David; Chan, Andy; Rankin, Erinn B.; Bernards, Rene; Majeti, Ravindra; Dill, David L.

2017-05-01

Two genes are synthetically lethal (SL) when defects in both are lethal to a cell but a single defect is non-lethal. SL partners of cancer mutations are of great interest as pharmacological targets; however, identifying them by cell line-based methods is challenging. Here we develop MiSL (Mining Synthetic Lethals), an algorithm that mines pan-cancer human primary tumour data to identify mutation-specific SL partners for specific cancers. We apply MiSL to 12 different cancers and predict 145,891 SL partners for 3,120 mutations, including known mutation-specific SL partners. Comparisons with functional screens show that MiSL predictions are enriched for SLs in multiple cancers. We extensively validate a SL interaction identified by MiSL between the IDH1 mutation and ACACA in leukaemia using gene targeting and patient-derived xenografts. Furthermore, we apply MiSL to pinpoint genetic biomarkers for drug sensitivity. These results demonstrate that MiSL can accelerate precision oncology by identifying mutation-specific targets and biomarkers.

Toward microendoscopy-inspired cardiac optogenetics in vivo: technical overview and perspective

NASA Astrophysics Data System (ADS)

Klimas, Aleksandra; Entcheva, Emilia

2014-08-01

The ability to perform precise, spatially localized actuation and measurements of electrical activity in the heart is crucial in understanding cardiac electrophysiology and devising new therapeutic solutions for control of cardiac arrhythmias. Current cardiac imaging techniques (i.e. optical mapping) employ voltage- or calcium-sensitive fluorescent dyes to visualize the electrical signal propagation through cardiac syncytium in vitro or in situ with very high-spatiotemporal resolution. The extension of optogenetics into the cardiac field, where cardiac tissue is genetically altered to express light-sensitive ion channels allowing electrical activity to be elicited or suppressed in a precise cell-specific way, has opened the possibility for all-optical interrogation of cardiac electrophysiology. In vivo application of cardiac optogenetics faces multiple challenges and necessitates suitable optical systems employing fiber optics to actuate and sense electrical signals. In this technical perspective, we present a compendium of clinically relevant access routes to different parts of the cardiac electrical conduction system based on currently employed catheter imaging systems and determine the quantitative size constraints for endoscopic cardiac optogenetics. We discuss the relevant technical advancements in microendoscopy, cardiac imaging, and optogenetics and outline the strategies for combining them to create a portable, miniaturized fiber-based system for all-optical interrogation of cardiac electrophysiology in vivo.

Data integration to prioritize drugs using genomics and curated data.

PubMed

Louhimo, Riku; Laakso, Marko; Belitskin, Denis; Klefström, Juha; Lehtonen, Rainer; Hautaniemi, Sampsa

2016-01-01

Genomic alterations affecting drug target proteins occur in several tumor types and are prime candidates for patient-specific tailored treatments. Increasingly, patients likely to benefit from targeted cancer therapy are selected based on molecular alterations. The selection of a precision therapy benefiting most patients is challenging but can be enhanced with integration of multiple types of molecular data. Data integration approaches for drug prioritization have successfully integrated diverse molecular data but do not take full advantage of existing data and literature. We have built a knowledge-base which connects data from public databases with molecular results from over 2200 tumors, signaling pathways and drug-target databases. Moreover, we have developed a data mining algorithm to effectively utilize this heterogeneous knowledge-base. Our algorithm is designed to facilitate retargeting of existing drugs by stratifying samples and prioritizing drug targets. We analyzed 797 primary tumors from The Cancer Genome Atlas breast and ovarian cancer cohorts using our framework. FGFR, CDK and HER2 inhibitors were prioritized in breast and ovarian data sets. Estrogen receptor positive breast tumors showed potential sensitivity to targeted inhibitors of FGFR due to activation of FGFR3. Our results suggest that computational sample stratification selects potentially sensitive samples for targeted therapies and can aid in precision medicine drug repositioning. Source code is available from http://csblcanges.fimm.fi/GOPredict/.

Rapid and sensitive spectrofluorimetric determination of enrofloxacin, levofloxacin and ofloxacin with 2,3,5,6-tetrachloro- p-benzoquinone

NASA Astrophysics Data System (ADS)

Ulu, Sevgi Tatar

2009-06-01

A highly sensitive spectrofluorimetric method was developed for the first time, for the analysis of three fluoroquinolones (FQ) antibacterials, namely enrofloxacin (ENR), levofloxacin (LEV) and ofloxacin (OFL) in pharmaceutical preparations through charge transfer (CT) complex formation with 2,3,5,6-tetrachloro- p-benzoquinone (chloranil,CLA). At the optimum reaction conditions, the FQ-CLA complexes showed excitation maxima ranging from 359 to 363 nm and emission maxima ranging from 442 to 488 nm. Rectilinear calibration graphs were obtained in the concentration range of 50-1000, 50-1000 and 25-500 ng mL -1 for ENR, LEV and OFL, respectively. The detection limit was found to be 17 ng mL -1 for ENR, 17 ng mL -1 for LEV, 8 ng mL -1 for OFL, respectively. Excipients used as additive in commercial formulations did not interfere in the analysis. The method was validated according to the ICH guidelines with respect to specificity, linearity, accuracy, precision and robustness. The proposed method was successfully applied to the analysis of pharmaceutical preparations. The results obtained were in good agreement with those obtained using the official method; no significant difference in the accuracy and precision as revealed by the accepted values of t- and F-tests, respectively.

Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease.

PubMed

Parker, Krystal L; Kim, Youngcho; Alberico, Stephanie L; Emmons, Eric B; Narayanan, Nandakumar S

2016-03-01

Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases.

Optical Materials with a Genome: Nanophotonics with DNA-Stabilized Silver Clusters

NASA Astrophysics Data System (ADS)

Copp, Stacy M.

Fluorescent silver clusters with unique rod-like geometries are stabilized by DNA. The sizes and colors of these clusters, or AgN-DNA, are selected by DNA base sequence, which can tune peak emission from blue-green into the near-infrared. Combined with DNA nanostructures, AgN-DNA promise exciting applications in nanophotonics and sensing. Until recently, however, a lack of understanding of the mechanisms controlling AgN-DNA fluorescence has challenged such applications. This dissertation discusses progress toward understanding the role of DNA as a "genome" for silver clusters and toward using DNA to achieve atomic-scale precision of silver cluster size and nanometer-scale precision of silver cluster position on a DNA breadboard. We also investigate sensitivity of AgN-DNA to local solvent environment, with an eye toward applications in chemical and biochemical sensing. Using robotic techniques to generate large data sets, we show that fluorescent silver clusters are templated by certain DNA base motifs that select "magic-sized" cluster cores of enhanced stabilities. The linear arrangement of bases on the phosphate backbone imposes a unique rod-like geometry on the clusters. Harnessing machine learning and bioinformatics techniques, we also demonstrate that sequences of DNA templates can be selected to stabilize silver clusters with desired optical properties, including high fluorescence intensity and specific fluorescence wavelengths, with much higher rates of success as compared to current strategies. The discovered base motifs can be also used to design modular DNA host strands that enable individual silver clusters with atomically precise sizes to bind at specific programmed locations on a DNA nanostructure. We show that DNA-mediated nanoscale arrangement enables near-field coupling of distinct clusters, demonstrated by dual-color cluster assemblies exhibiting resonant energy transfer. These results demonstrate a new degree of control over the optical properties and relative positions of nanoparticles, selected almost solely by the sequence of DNA. AgN-DNA are promising chemical and biochemical sensors due to the sensitivity of their fluorescence to local environment. However, the mechanisms behind many sensing schemes are not understood, and the nature of the excited state of the silver cluster itself remains unknown. To probe the fluorescence mechanisms of AgN-DNA, we investigate the behavior of purified solutions of these clusters in various solvents. We find that standard models for fluorophore solvatochromism, including the Lippert-Mataga model, do not describe AgN-DNA fluorescence because such models neglect specific interactions between the cluster and surrounding solvent molecules. Fluorescence colors are well-modeled by Mie-Gans theory, suggesting that the local dielectric environment of the cluster does play a role in fluorescence, although additional specific solvent interactions and cluster shape changes may also determine fluorescence color and intensity. These results suggest that AgN-DNA may be sensitive to changes in local dielectric environment on nanometer length scales and may also act as sensors for small molecules with affinity for DNA.

Extended Malus law with terahertz metallic metamaterials for sensitive detection with giant tunable quality factor

NASA Astrophysics Data System (ADS)

Romain, Xavier; Baida, Fadi; Boyer, Philippe

2016-07-01

We study a polarizer-analyzer mounting for the terahertz regime with perfectly conducting metallic polarizers made of a periodic subwavelength pattern. With a renewed Jones formalism, we analytically investigate the influence of the multiple reflections, which occur between the polarizer and the analyzer, on the transmission response. We demonstrate that this interaction leads to a modified transmission response: the extended Malus law. In addition, we show that the transmission response can be controlled by the distance between the polarizer and the analyzer. For particular setups, the mounting exhibits extremely sensitive transmission responses. This interesting feature can be employed for high-precision sensing and characterization applications. We specifically propose a general design for measuring the electro-optical response of materials in the terahertz domain allowing detection of refractive index variations as small as 10-5.

Capture-based next-generation sequencing reveals multiple actionable mutations in cancer patients failed in traditional testing.

PubMed

Xie, Jing; Lu, Xiongxiong; Wu, Xue; Lin, Xiaoyi; Zhang, Chao; Huang, Xiaofang; Chang, Zhili; Wang, Xinjing; Wen, Chenlei; Tang, Xiaomei; Shi, Minmin; Zhan, Qian; Chen, Hao; Deng, Xiaxing; Peng, Chenghong; Li, Hongwei; Fang, Yuan; Shao, Yang; Shen, Baiyong

2016-05-01

Targeted therapies including monoclonal antibodies and small molecule inhibitors have dramatically changed the treatment of cancer over past 10 years. Their therapeutic advantages are more tumor specific and with less side effects. For precisely tailoring available targeted therapies to each individual or a subset of cancer patients, next-generation sequencing (NGS) has been utilized as a promising diagnosis tool with its advantages of accuracy, sensitivity, and high throughput. We developed and validated a NGS-based cancer genomic diagnosis targeting 115 prognosis and therapeutics relevant genes on multiple specimen including blood, tumor tissue, and body fluid from 10 patients with different cancer types. The sequencing data was then analyzed by the clinical-applicable analytical pipelines developed in house. We have assessed analytical sensitivity, specificity, and accuracy of the NGS-based molecular diagnosis. Also, our developed analytical pipelines were capable of detecting base substitutions, indels, and gene copy number variations (CNVs). For instance, several actionable mutations of EGFR,PIK3CA,TP53, and KRAS have been detected for indicating drug susceptibility and resistance in the cases of lung cancer. Our study has shown that NGS-based molecular diagnosis is more sensitive and comprehensive to detect genomic alterations in cancer, and supports a direct clinical use for guiding targeted therapy.

Search strategies to identify information on adverse effects: a systematic review

PubMed Central

Golder, Su; Loke, Yoon

2009-01-01

Objectives: The review evaluated studies of electronic database search strategies designed to retrieve adverse effects data for systematic reviews. Methods: Studies of adverse effects were located in ten databases as well as by checking references, hand-searching, searching citations, and contacting experts. Two reviewers screened the retrieved records for potentially relevant papers. Results: Five thousand three hundred thirteen citations were retrieved, yielding 19 studies designed to develop or evaluate adverse effect filters, of which 3 met the inclusion criteria. All 3 studies identified highly sensitive search strategies capable of retrieving over 95% of relevant records. However, 1 study did not evaluate precision, while the level of precision in the other 2 studies ranged from 0.8% to 2.8%. Methodological issues in these papers included the relatively small number of records, absence of a validation set of records for testing, and limited evaluation of precision. Conclusions: The results indicate the difficulty of achieving highly sensitive searches for information on adverse effects with a reasonable level of precision. Researchers who intend to locate studies on adverse effects should allow for the amount of resources and time required to conduct a highly sensitive search. PMID:19404498

Miniaturized high-precision piezo driven two axes stepper goniometer

NASA Astrophysics Data System (ADS)

Zhong, H.; Schwarz, A.; Wiesendanger, R.

2014-04-01

A miniaturized inertial stepper goniometer with two orthogonal axes (θ and φ axes) has been realized using four shear piezo based actuators arranged in a tetrahedral configuration tangent with a polished sapphire spherical rotor. The measured sensitivity is about 11.5 microdegree (μ°) per Volt. The smallest angular step size, achieved with a minimal peak-to-peak voltage Upp of 200 V is about 0.6 millidegree (m°). The crosstalk between both axes is below 10%. Our specific design is used to accurately position a glass fiber, but the concept can be utilized for many different applications as well.

Validation of an immunoassay for canine thyroid-stimulating hormone and changes in serum concentration following induction of hypothyroidism in dogs.

PubMed

Williams, D A; Scott-Moncrieff, C; Bruner, J; Sustarsic, D; Panosian-Sahakian, N; Unver, E; el Shami, A S

1996-11-15

To validate a new immunoradiometric assay for canine thyroid-stimulating hormone (cTSH) and to document changes in serum cTSH concentration during induction of hypothyroidism in dogs. Six healthy adult male Beagles. Sensitivity, specificity, precision, and accuracy of the cTSH assay were evaluated in vitro. Hypothyroidism was induced in dogs by i.v. administration of sodium iodide I 131 solution. Subsequently, L-thyroxine was administered orally to normalize serum thyroxine concentrations. The cTSH assay appeared to be specific and was sufficiently sensitive to detect cTSH in the serum of these dogs prior to induction of hypothyroidism. There was a 35-fold increase in mean serum cTSH concentration following induction of hypothyroidism, and 35 days after initiation of thyroid replacement therapy, mean serum cTSH concentration was not significantly greater than mean baseline value. Assay of serum cTSH is likely to prove helpful in the differential diagnosis of primary, secondary, and tertiary hypothyroidism in dogs, and in monitoring response to thyroid hormone replacement treatment.

Lab-on-chip systems for integrated bioanalyses

PubMed Central

Madaboosi, Narayanan; Soares, Ruben R.G.; Fernandes, João Tiago S.; Novo, Pedro; Moulas, Geraud; Chu, Virginia

2016-01-01

Biomolecular detection systems based on microfluidics are often called lab-on-chip systems. To fully benefit from the miniaturization resulting from microfluidics, one aims to develop ‘from sample-to-answer’ analytical systems, in which the input is a raw or minimally processed biological, food/feed or environmental sample and the output is a quantitative or qualitative assessment of one or more analytes of interest. In general, such systems will require the integration of several steps or operations to perform their function. This review will discuss these stages of operation, including fluidic handling, which assures that the desired fluid arrives at a specific location at the right time and under the appropriate flow conditions; molecular recognition, which allows the capture of specific analytes at precise locations on the chip; transduction of the molecular recognition event into a measurable signal; sample preparation upstream from analyte capture; and signal amplification procedures to increase sensitivity. Seamless integration of the different stages is required to achieve a point-of-care/point-of-use lab-on-chip device that allows analyte detection at the relevant sensitivity ranges, with a competitive analysis time and cost. PMID:27365042

Determination of glucose in interstitial fluid by surface plasmon resonance biosensor

NASA Astrophysics Data System (ADS)

Huang, Fuxiang; Liu, Jin; Yu, Haixia; Zhang, Zengfu; Li, Dachao; Xu, Kexin

2008-02-01

The concentration of glucose in interstitial fluid determined by using the surface plasmon resonance (SPR) biosensor with chemical bonding D-Galactose/D-Glucose Binding Protein (GGBP) is proposed in this paper. D-Galactose/D-Glucose Binding Protein (GGBP), a kind of protein which has the ability to absorb the glucose specifically, is immobilized on the gold film of the SPR sensor to improve the sensitivity of glucose detecting. The GGBPs mutated at different points have different association abilities with glucose, which bring different measurement range and precision. So the selection of proteins is a critical problem of the determination of glucose by using SPR biosensor. Using different mutated GGBPs, the samples with different concentrations of glucose are measured in the experiment, and the prediction error and precision are discussed. Furthermore, the light intensity of sensor is instable, so the baseline of SPR responses is tracked and adjusted accordingly using the methods - fixing points and fixing areas' ratio. The experiment results show that GGBPs mutated at different points have its corresponding working curves and different measurement precision. In conclusion, the study is significant for the application of SPR biosensor to the minimally invasive diabetes testing and other detection of human body components.

Simultaneous Determination of Ofloxacin and Flavoxate Hydrochloride by Absorption Ratio and Second Derivative UV Spectrophotometry

PubMed Central

Attimarad, Mahesh

2010-01-01

The objective of this study was to develop simple, precise, accurate and sensitive UV spectrophotometric methods for the simultaneous determination of ofloxacin (OFX) and flavoxate HCl (FLX) in pharmaceutical formulations. The first method is based on absorption ratio method, by formation of Q absorbance equation at 289 nm (λmax of OFX) and 322.4 nm (isoabsorptive point). The linearity range was found to be 1 to 30 μg/ml for FLX and OFX. In the method-II second derivative absorption at 311.4 nm for OFX (zero crossing for FLX) and at 246.2 nm for FLX (zero crossing for OFX) was used for the determination of the drugs and the linearity range was found to be 2 to 30 μg/ml for OFX and 2-75 μg /ml for FLX. The accuracy and precision of the methods were determined and validated statistically. Both the methods showed good reproducibility and recovery with % RSD less than 1.5%. Both the methods were found to be rapid, specific, precise and accurate and can be successfully applied for the routine analysis of OFX and FLX in combined dosage form PMID:24826003

Engineering a light-activated caspase-3 for precise ablation of neurons in vivo.

PubMed

Smart, Ashley D; Pache, Roland A; Thomsen, Nathan D; Kortemme, Tanja; Davis, Graeme W; Wells, James A

2017-09-26

The circuitry of the brain is characterized by cell heterogeneity, sprawling cellular anatomy, and astonishingly complex patterns of connectivity. Determining how complex neural circuits control behavior is a major challenge that is often approached using surgical, chemical, or transgenic approaches to ablate neurons. However, all these approaches suffer from a lack of precise spatial and temporal control. This drawback would be overcome if cellular ablation could be controlled with light. Cells are naturally and cleanly ablated through apoptosis due to the terminal activation of caspases. Here, we describe the engineering of a light-activated human caspase-3 (Caspase-LOV) by exploiting its natural spring-loaded activation mechanism through rational insertion of the light-sensitive LOV2 domain that expands upon illumination. We apply the light-activated caspase (Caspase-LOV) to study neurodegeneration in larval and adult Drosophila Using the tissue-specific expression system (UAS)-GAL4, we express Caspase-LOV specifically in three neuronal cell types: retinal, sensory, and motor neurons. Illumination of whole flies or specific tissues containing Caspase-LOV-induced cell death and allowed us to follow the time course and sequence of neurodegenerative events. For example, we find that global synchronous activation of caspase-3 drives degeneration with a different time-course and extent in sensory versus motor neurons. We believe the Caspase-LOV tool we engineered will have many other uses for neurobiologists and others for specific temporal and spatial ablation of cells in complex organisms.

Engineering a light-activated caspase-3 for precise ablation of neurons in vivo

PubMed Central

Smart, Ashley D.; Pache, Roland A.; Thomsen, Nathan D.; Kortemme, Tanja; Davis, Graeme W.; Wells, James A.

2017-01-01

The circuitry of the brain is characterized by cell heterogeneity, sprawling cellular anatomy, and astonishingly complex patterns of connectivity. Determining how complex neural circuits control behavior is a major challenge that is often approached using surgical, chemical, or transgenic approaches to ablate neurons. However, all these approaches suffer from a lack of precise spatial and temporal control. This drawback would be overcome if cellular ablation could be controlled with light. Cells are naturally and cleanly ablated through apoptosis due to the terminal activation of caspases. Here, we describe the engineering of a light-activated human caspase-3 (Caspase-LOV) by exploiting its natural spring-loaded activation mechanism through rational insertion of the light-sensitive LOV2 domain that expands upon illumination. We apply the light-activated caspase (Caspase-LOV) to study neurodegeneration in larval and adult Drosophila. Using the tissue-specific expression system (UAS)-GAL4, we express Caspase-LOV specifically in three neuronal cell types: retinal, sensory, and motor neurons. Illumination of whole flies or specific tissues containing Caspase-LOV–induced cell death and allowed us to follow the time course and sequence of neurodegenerative events. For example, we find that global synchronous activation of caspase-3 drives degeneration with a different time-course and extent in sensory versus motor neurons. We believe the Caspase-LOV tool we engineered will have many other uses for neurobiologists and others for specific temporal and spatial ablation of cells in complex organisms. PMID:28893998

Uranium Measurement Improvements at the Savannah River Technology Center

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

Shick, C. Jr.

Uranium isotope ratio and isotope dilution methods by mass spectrometry are used to achieve sensitivity, precision and accuracy for various applications. This report presents recent progress made at SRTC in the analysis of minor isotopes of uranium. Comparison of routine measurements of NBL certified uranium (U005a) using the SRTC Three Stage Mass Spectrometer (3SMS) and the SRTC Single Stage Mass Spectrometer (SSMS). As expected, the three stage mass spectrometer yielded superior sensitivity, precision, and accuracy for this application.

Molecular diffusion of stable water isotopes in polar firn as a proxy for past temperatures

NASA Astrophysics Data System (ADS)

Holme, Christian; Gkinis, Vasileios; Vinther, Bo M.

2018-03-01

Polar precipitation archived in ice caps contains information on past temperature conditions. Such information can be retrieved by measuring the water isotopic signals of δ18O and δD in ice cores. These signals have been attenuated during densification due to molecular diffusion in the firn column, where the magnitude of the diffusion is isotopologue specific and temperature dependent. By utilizing the differential diffusion signal, dual isotope measurements of δ18O and δD enable multiple temperature reconstruction techniques. This study assesses how well six different methods can be used to reconstruct past surface temperatures from the diffusion-based temperature proxies. Two of the methods are based on the single diffusion lengths of δ18O and δD , three of the methods employ the differential diffusion signal, while the last uses the ratio between the single diffusion lengths. All techniques are tested on synthetic data in order to evaluate their accuracy and precision. We perform a benchmark test to thirteen high resolution Holocene data sets from Greenland and Antarctica, which represent a broad range of mean annual surface temperatures and accumulation rates. Based on the benchmark test, we comment on the accuracy and precision of the methods. Both the benchmark test and the synthetic data test demonstrate that the most precise reconstructions are obtained when using the single isotope diffusion lengths, with precisions of approximately 1.0 °C . In the benchmark test, the single isotope diffusion lengths are also found to reconstruct consistent temperatures with a root-mean-square-deviation of 0.7 °C . The techniques employing the differential diffusion signals are more uncertain, where the most precise method has a precision of 1.9 °C . The diffusion length ratio method is the least precise with a precision of 13.7 °C . The absolute temperature estimates from this method are also shown to be highly sensitive to the choice of fractionation factor parameterization.

A fully integrated distance readout ELISA-Chip for point-of-care testing with sample-in-answer-out capability.

PubMed

Liu, Dan; Li, Xingrui; Zhou, Junkai; Liu, Shibo; Tian, Tian; Song, Yanling; Zhu, Zhi; Zhou, Leiji; Ji, Tianhai; Yang, Chaoyong

2017-10-15

Enzyme-linked immunosorbent assay (ELISA) is a popular laboratory technique for detection of disease-specific protein biomarkers with high specificity and sensitivity. However, ELISA requires labor-intensive and time-consuming procedures with skilled operators and spectroscopic instrumentation. Simplification of the procedures and miniaturization of the devices are crucial for ELISA-based point-of-care (POC) testing in resource-limited settings. Here, we present a fully integrated, instrument-free, low-cost and portable POC platform which integrates the process of ELISA and the distance readout into a single microfluidic chip. Based on manipulation using a permanent magnet, the process is initiated by moving magnetic beads with capture antibody through different aqueous phases containing ELISA reagents to form bead/antibody/antigen/antibody sandwich structure, and finally converts the molecular recognition signal into a highly sensitive distance readout for visual quantitative bioanalysis. Without additional equipment and complicated operations, our integrated ELISA-Chip with distance readout allows ultrasensitive quantitation of disease biomarkers within 2h. The ELISA-Chip method also showed high specificity, good precision and great accuracy. Furthermore, the ELISA-Chip system is highly applicable as a sandwich-based platform for the detection of a variety of protein biomarkers. With the advantages of visual analysis, easy operation, high sensitivity, and low cost, the integrated sample-in-answer-out ELISA-Chip with distance readout shows great potential for quantitative POCT in resource-limited settings. Copyright © 2017. Published by Elsevier B.V.

Development of a genus-specific next generation sequencing approach for sensitive and quantitative determination of the Legionella microbiome in freshwater systems.

PubMed

Pereira, Rui P A; Peplies, Jörg; Brettar, Ingrid; Höfle, Manfred G

2017-03-31

Next Generation Sequencing (NGS) has revolutionized the analysis of natural and man-made microbial communities by using universal primers for bacteria in a PCR based approach targeting the 16S rRNA gene. In our study we narrowed primer specificity to a single, monophyletic genus because for many questions in microbiology only a specific part of the whole microbiome is of interest. We have chosen the genus Legionella, comprising more than 20 pathogenic species, due to its high relevance for water-based respiratory infections. A new NGS-based approach was designed by sequencing 16S rRNA gene amplicons specific for the genus Legionella using the Illumina MiSeq technology. This approach was validated and applied to a set of representative freshwater samples. Our results revealed that the generated libraries presented a low average raw error rate per base (<0.5%); and substantiated the use of high-fidelity enzymes, such as KAPA HiFi, for increased sequence accuracy and quality. The approach also showed high in situ specificity (>95%) and very good repeatability. Only in samples in which the gammabacterial clade SAR86 was present more than 1% non-Legionella sequences were observed. Next-generation sequencing read counts did not reveal considerable amplification/sequencing biases and showed a sensitive as well as precise quantification of L. pneumophila along a dilution range using a spiked-in, certified genome standard. The genome standard and a mock community consisting of six different Legionella species demonstrated that the developed NGS approach was quantitative and specific at the level of individual species, including L. pneumophila. The sensitivity of our genus-specific approach was at least one order of magnitude higher compared to the universal NGS approach. Comparison of quantification by real-time PCR showed consistency with the NGS data. Overall, our NGS approach can determine the quantitative abundances of Legionella species, i. e. the complete Legionella microbiome, without the need for species-specific primers. The developed NGS approach provides a new molecular surveillance tool to monitor all Legionella species in qualitative and quantitative terms if a spiked-in genome standard is used to calibrate the method. Overall, the genus-specific NGS approach opens up a new avenue to massive parallel diagnostics in a quantitative, specific and sensitive way.

Peregrine

PubMed Central

Langevin, Stanley A.; Bent, Zachary W.; Solberg, Owen D.; Curtis, Deanna J.; Lane, Pamela D.; Williams, Kelly P.; Schoeniger, Joseph S.; Sinha, Anupama; Lane, Todd W.; Branda, Steven S.

2013-01-01

Use of second generation sequencing (SGS) technologies for transcriptional profiling (RNA-Seq) has revolutionized transcriptomics, enabling measurement of RNA abundances with unprecedented specificity and sensitivity and the discovery of novel RNA species. Preparation of RNA-Seq libraries requires conversion of the RNA starting material into cDNA flanked by platform-specific adaptor sequences. Each of the published methods and commercial kits currently available for RNA-Seq library preparation suffers from at least one major drawback, including long processing times, large starting material requirements, uneven coverage, loss of strand information and high cost. We report the development of a new RNA-Seq library preparation technique that produces representative, strand-specific RNA-Seq libraries from small amounts of starting material in a fast, simple and cost-effective manner. Additionally, we have developed a new quantitative PCR-based assay for precisely determining the number of PCR cycles to perform for optimal enrichment of the final library, a key step in all SGS library preparation workflows. PMID:23558773

A Perfect Match Genomic Landscape Provides a Unified Framework for the Precise Detection of Variation in Natural and Synthetic Haploid Genomes.

PubMed

Palacios-Flores, Kim; García-Sotelo, Jair; Castillo, Alejandra; Uribe, Carina; Aguilar, Luis; Morales, Lucía; Gómez-Romero, Laura; Reyes, José; Garciarubio, Alejandro; Boege, Margareta; Dávila, Guillermo

2018-04-01

We present a conceptually simple, sensitive, precise, and essentially nonstatistical solution for the analysis of genome variation in haploid organisms. The generation of a Perfect Match Genomic Landscape (PMGL), which computes intergenome identity with single nucleotide resolution, reveals signatures of variation wherever a query genome differs from a reference genome. Such signatures encode the precise location of different types of variants, including single nucleotide variants, deletions, insertions, and amplifications, effectively introducing the concept of a general signature of variation. The precise nature of variants is then resolved through the generation of targeted alignments between specific sets of sequence reads and known regions of the reference genome. Thus, the perfect match logic decouples the identification of the location of variants from the characterization of their nature, providing a unified framework for the detection of genome variation. We assessed the performance of the PMGL strategy via simulation experiments. We determined the variation profiles of natural genomes and of a synthetic chromosome, both in the context of haploid yeast strains. Our approach uncovered variants that have previously escaped detection. Moreover, our strategy is ideally suited for further refining high-quality reference genomes. The source codes for the automated PMGL pipeline have been deposited in a public repository. Copyright © 2018 by the Genetics Society of America.

The bias, accuracy and precision of faecal egg count reduction test results in cattle using McMaster, Cornell-Wisconsin and FLOTAC egg counting methods.

PubMed

Levecke, B; Rinaldi, L; Charlier, J; Maurelli, M P; Bosco, A; Vercruysse, J; Cringoli, G

2012-08-13

The faecal egg count reduction test (FECRT) is the recommended method to monitor anthelmintic drug efficacy in cattle. There is a large variation in faecal egg count (FEC) methods applied to determine FECRT. However, it remains unclear whether FEC methods with an equal analytic sensitivity, but with different methodologies, result in equal FECRT results. We therefore, compared the bias, accuracy and precision of FECRT results for Cornell-Wisconsin (analytic sensitivity = 1 egg per gram faeces (EPG)), FLOTAC (analytic sensitivity = 1 EPG) and McMaster method (analytic sensitivity = 10 EPG) across four levels of egg excretion (1-49 EPG; 50-149 EPG; 150-299 EPG; 300-600 EPG). Finally, we assessed the sensitivity of the FEC methods to detect a truly reduced efficacy. To this end, two different criteria were used to define reduced efficacy based on FECR, including those described in the WAAVP guidelines (FECRT <95% and lower limit of 95%CI <90%) (Coles et al., 1992) and those proposed by El-Abdellati et al. (2010) (upper limit of 95%CI <95%). There was no significant difference in bias and accuracy of FECRT results across the three methods. FLOTAC provided the most precise FECRT results. Cornell-Wisconsin and McMaster gave similar imprecise results. FECRT were significantly underestimated when baseline FEC were low and drugs were more efficacious. For all FEC methods, precision and accuracy of the FECRT improved as egg excretion increased, this effect was greatest for McMaster and least for Cornell-Wisconsin. The sensitivity of the three methods to detect a truly reduced efficacy was high (>90%). Yet, the sensitivity of McMaster and Cornell-Wisconsin may drop when drugs only show sub-optimal efficacy. Overall, the study indicates that the precision of FECRT is affected by the methodology of FEC, and that the level of egg excretion should be considered in the final interpretation of the FECRT. However, more comprehensive studies are required to provide more insights into the complex interplay of factors inherent to study design (sample size and FEC method) and host-parasite interactions (level of egg excretion and aggregation across the host population). Copyright © 2012 Elsevier B.V. All rights reserved.

Context-specific effects of musical expertise on audiovisual integration

PubMed Central

Bishop, Laura; Goebl, Werner

2014-01-01

Ensemble musicians exchange auditory and visual signals that can facilitate interpersonal synchronization. Musical expertise improves how precisely auditory and visual signals are perceptually integrated and increases sensitivity to asynchrony between them. Whether expertise improves sensitivity to audiovisual asynchrony in all instrumental contexts or only in those using sound-producing gestures that are within an observer's own motor repertoire is unclear. This study tested the hypothesis that musicians are more sensitive to audiovisual asynchrony in performances featuring their own instrument than in performances featuring other instruments. Short clips were extracted from audio-video recordings of clarinet, piano, and violin performances and presented to highly-skilled clarinetists, pianists, and violinists. Clips either maintained the audiovisual synchrony present in the original recording or were modified so that the video led or lagged behind the audio. Participants indicated whether the audio and video channels in each clip were synchronized. The range of asynchronies most often endorsed as synchronized was assessed as a measure of participants' sensitivities to audiovisual asynchrony. A positive relationship was observed between musical training and sensitivity, with data pooled across stimuli. While participants across expertise groups detected asynchronies most readily in piano stimuli and least readily in violin stimuli, pianists showed significantly better performance for piano stimuli than for either clarinet or violin. These findings suggest that, to an extent, the effects of expertise on audiovisual integration can be instrument-specific; however, the nature of the sound-producing gestures that are observed has a substantial effect on how readily asynchrony is detected as well. PMID:25324819

Precise SAR measurements in the near-field of RF antenna systems

NASA Astrophysics Data System (ADS)

Hakim, Bandar M.

Wireless devices must meet specific safety radiation limits, and in order to assess the health affects of such devices, standard procedures are used in which standard phantoms, tissue-equivalent liquids, and miniature electric field probes are used. The accuracy of such measurements depend on the precision in measuring the dielectric properties of the tissue-equivalent liquids and the associated calibrations of the electric-field probes. This thesis describes work on the theoretical modeling and experimental measurement of the complex permittivity of tissue-equivalent liquids, and associated calibration of miniature electric-field probes. The measurement method is based on measurements of the field attenuation factor and power reflection coefficient of a tissue-equivalent sample. A novel method, to the best of the authors knowledge, for determining the dielectric properties and probe calibration factors is described and validated. The measurement system is validated using saline at different concentrations, and measurements of complex permittivity and calibration factors have been made on tissue-equivalent liquids at 900MHz and 1800MHz. Uncertainty analysis have been conducted to study the measurement system sensitivity. Using the same waveguide to measure tissue-equivalent permittivity and calibrate e-field probes eliminates a source of uncertainty associated with using two different measurement systems. The measurement system is used to test GSM cell-phones at 900MHz and 1800MHz for Specific Absorption Rate (SAR) compliance using a Specific Anthropomorphic Mannequin phantom (SAM).

Detection methods and performance criteria for genetically modified organisms.

PubMed

Bertheau, Yves; Diolez, Annick; Kobilinsky, André; Magin, Kimberly

2002-01-01

Detection methods for genetically modified organisms (GMOs) are necessary for many applications, from seed purity assessment to compliance of food labeling in several countries. Numerous analytical methods are currently used or under development to support these needs. The currently used methods are bioassays and protein- and DNA-based detection protocols. To avoid discrepancy of results between such largely different methods and, for instance, the potential resulting legal actions, compatibility of the methods is urgently needed. Performance criteria of methods allow evaluation against a common standard. The more-common performance criteria for detection methods are precision, accuracy, sensitivity, and specificity, which together specifically address other terms used to describe the performance of a method, such as applicability, selectivity, calibration, trueness, precision, recovery, operating range, limit of quantitation, limit of detection, and ruggedness. Performance criteria should provide objective tools to accept or reject specific methods, to validate them, to ensure compatibility between validated methods, and be used on a routine basis to reject data outside an acceptable range of variability. When selecting a method of detection, it is also important to consider its applicability, its field of applications, and its limitations, by including factors such as its ability to detect the target analyte in a given matrix, the duration of the analyses, its cost effectiveness, and the necessary sample sizes for testing. Thus, the current GMO detection methods should be evaluated against a common set of performance criteria.

Measuring the bias, precision, accuracy, and validity of self-reported height and weight in assessing overweight and obesity status among adolescents using a surveillance system.

PubMed

Pérez, Adriana; Gabriel, Kelley; Nehme, Eileen K; Mandell, Dorothy J; Hoelscher, Deanna M

2015-07-27

Evidence regarding bias, precision, and accuracy in adolescent self-reported height and weight across demographic subpopulations is lacking. The bias, precision, and accuracy of adolescent self-reported height and weight across subpopulations were examined using a large, diverse and representative sample of adolescents. A second objective was to develop correction equations for self-reported height and weight to provide more accurate estimates of body mass index (BMI) and weight status. A total of 24,221 students from 8th and 11th grade in Texas participated in the School Physical Activity and Nutrition (SPAN) surveillance system in years 2000-2002 and 2004-2005. To assess bias, the differences between the self-reported and objective measures, for height and weight were estimated. To assess precision and accuracy, the Lin's concordance correlation coefficient was used. BMI was estimated for self-reported and objective measures. The prevalence of students' weight status was estimated using self-reported and objective measures; absolute (bias) and relative error (relative bias) were assessed subsequently. Correction equations for sex and race/ethnicity subpopulations were developed to estimate objective measures of height, weight and BMI from self-reported measures using weighted linear regression. Sensitivity, specificity and positive predictive values of weight status classification using self-reported measures and correction equations are assessed by sex and grade. Students in 8th- and 11th-grade overestimated their height from 0.68cm (White girls) to 2.02 cm (African-American boys), and underestimated their weight from 0.4 kg (Hispanic girls) to 0.98 kg (African-American girls). The differences in self-reported versus objectively-measured height and weight resulted in underestimation of BMI ranging from -0.23 kg/m2 (White boys) to -0.7 kg/m2 (African-American girls). The sensitivity of self-reported measures to classify weight status as obese was 70.8% and 81.9% for 8th- and 11th-graders, respectively. These estimates increased when using the correction equations to 77.4% and 84.4% for 8th- and 11th-graders, respectively. When direct measurement is not practical, self-reported measurements provide a reliable proxy measure across grade, sex and race/ethnicity subpopulations of adolescents. Correction equations increase the sensitivity of self-report measures to identify prevalence of overall overweight/obesity status.

Pressure measurements with a precision of 0.001 ppm in magnetic fields at low temperatures

NASA Astrophysics Data System (ADS)

Miura, Y.; Matsushima, N.; Ando, T.; Kuno, S.; Inoue, S.; Ito, K.; Mamiya, T.

1993-11-01

Pressure measurements made by an ac bridge technique with a precision of 0.001 ppm in magnetic fields at low temperatures using a Straty-Adams type gauge are described. In order to improve the sensitivity and the long-term stability of the bridge system, coaxial cables without dielectric insulator were developed, with a small cable capacitance temperature coefficient of the impedance. This pressure measurement system has a sensitivity of dP/P˜5×10-10 and a long-term stability of dP/P˜2.4×10-9 over 18 h. This is especially useful for measurements such as electric and magnetic susceptibility measurements in magnetic fields at low temperatures requiring a high precision.

Comparative Analysis of Automatic Exudate Detection between Machine Learning and Traditional Approaches

NASA Astrophysics Data System (ADS)

Sopharak, Akara; Uyyanonvara, Bunyarit; Barman, Sarah; Williamson, Thomas

To prevent blindness from diabetic retinopathy, periodic screening and early diagnosis are neccessary. Due to lack of expert ophthalmologists in rural area, automated early exudate (one of visible sign of diabetic retinopathy) detection could help to reduce the number of blindness in diabetic patients. Traditional automatic exudate detection methods are based on specific parameter configuration, while the machine learning approaches which seems more flexible may be computationally high cost. A comparative analysis of traditional and machine learning of exudates detection, namely, mathematical morphology, fuzzy c-means clustering, naive Bayesian classifier, Support Vector Machine and Nearest Neighbor classifier are presented. Detected exudates are validated with expert ophthalmologists' hand-drawn ground-truths. The sensitivity, specificity, precision, accuracy and time complexity of each method are also compared.

Aptima HIV-1 Quant Dx--A fully automated assay for both diagnosis and quantification of HIV-1.

PubMed

Nair, Sangeetha Vijaysri; Kim, Hee Cheol; Fortunko, Jacqueline; Foote, Tracy; Peling, Tashi; Tran, Cuong; Nugent, Charles Thomas; Joo, Sunghae; Kang, Youna; Wilkins, Bana; Lednovich, Kristen; Worlock, Andrew

2016-04-01

Separate assays are available for diagnosis and viral load (VL) monitoring of HIV-1. Studies have shown that using a single test for both confirmatory diagnosis and VL increases linkage to care. To validate a single assay for both diagnosis and VL monitoring of HIV-1 on the fully automated Panther platform. Validate the assay by assessing specificity, sensitivity, subtype detection, seroconversion, reproducibility and linearity. Also assess diagnostic agreement with the Procleix(®) Ultrio Elite™ discriminatory assay (Procleix), and agreement of VL results (method comparison) with Ampliprep/COBAS TaqMan HIV-1 version 2.0 (CAP/CTM), using clinical samples. The assay was specific (100%) and sensitive with a 95% limit of detection of 12 copies/mL with the 3rd WHO standards. Aptima detected HIV in seroconversion panels 6 and 11 days before p24 antigen and antibody tests, respectively. Diagnostic agreement with Procleix, was 100%. Regression analysis showed good agreement of VL results between Aptima and CAP/CTM with a slope of 1.02, intercept of 0.07, and correlation coefficient (R(2)) of 0.97. Aptima was more sensitive than CAP/CTM. Equivalent quantification was seen on testing clinical samples and isolates belonging to HIV group M, N, O and P and commercially available subtype panels. Assay results were linear (R(2) 0.9994) with standard deviation of <0.17 log copies across assay range. The good specificity, sensitivity, precision, subtype performance and clinical agreement with other assays demonstrated by Aptima combined with the complete automation provided by the Panther platform makes Aptima a good candidate for both VL monitoring and diagnosis of HIV-1. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

A novel immunoassay using recombinant allergens simplifies peanut allergy diagnosis.

PubMed

Codreanu, F; Collignon, O; Roitel, O; Thouvenot, B; Sauvage, C; Vilain, A-C; Cousin, M-O; Decoster, A; Renaudin, J-M; Astier, C; Monnez, J-M; Vallois, P; Morisset, M; Moneret-Vautrin, D-A; Brulliard, M; Ogier, V; Castelain, M-C; Kanny, G; Bihain, B E; Jacquenet, S

2011-01-01

Double-blind placebo-controlled food challenge (DBPCFC) is currently considered the gold standard for peanut allergy diagnosis. However, this procedure that requires the hospitalization of patients, mostly children, in specialized centers for oral exposure to allergens may cause severe reactions requiring emergency measures. Thus, a simpler and safer diagnosis procedure is needed. The aim of this study was to evaluate the diagnostic performance of a new set of in vitro blood tests for peanut allergy. The levels of IgE directed towards peanut extract and recombinant peanut allergens Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 7, and Ara h 8 were measured in 3 groups of patients enrolled at 2 independent centers: patients with proven peanut allergy (n=166); pollen-sensitized subjects without peanut allergy (n=61), and control subjects without allergic disease (n=10). Seventy-nine percent of the pollen-sensitized patients showed IgE binding to peanut, despite their tolerance to peanut. In contrast, combining the results of specific IgE to peanut extract and to recombinant Ara h 2 and Ara h 6 yielded a peanut allergy diagnosis with a 98% sensitivity and an 85% specificity at a positivity threshold of 0.10 kU/l. Use of a threshold of 0.23 kU/l for recombinant Ara h 2 increased specificity (96%) at the cost of sensitivity (93%). A simple blood test can be used to diagnose peanut allergy with a high level of precision. However, DBPCFC will remain useful for the few cases where immunological and clinical observations yield conflicting results. Copyright © 2010 S. Karger AG, Basel.

Precision muon physics

NASA Astrophysics Data System (ADS)

Gorringe, T. P.; Hertzog, D. W.

2015-09-01

The muon is playing a unique role in sub-atomic physics. Studies of muon decay both determine the overall strength and establish the chiral structure of weak interactions, as well as setting extraordinary limits on charged-lepton-flavor-violating processes. Measurements of the muon's anomalous magnetic moment offer singular sensitivity to the completeness of the standard model and the predictions of many speculative theories. Spectroscopy of muonium and muonic atoms gives unmatched determinations of fundamental quantities including the magnetic moment ratio μμ /μp, lepton mass ratio mμ /me, and proton charge radius rp. Also, muon capture experiments are exploring elusive features of weak interactions involving nucleons and nuclei. We will review the experimental landscape of contemporary high-precision and high-sensitivity experiments with muons. One focus is the novel methods and ingenious techniques that achieve such precision and sensitivity in recent, present, and planned experiments. Another focus is the uncommonly broad and topical range of questions in atomic, nuclear and particle physics that such experiments explore.

The effects of SENSE on PROPELLER imaging.

PubMed

Chang, Yuchou; Pipe, James G; Karis, John P; Gibbs, Wende N; Zwart, Nicholas R; Schär, Michael

2015-12-01

To study how sensitivity encoding (SENSE) impacts periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) image quality, including signal-to-noise ratio (SNR), robustness to motion, precision of motion estimation, and image quality. Five volunteers were imaged by three sets of scans. A rapid method for generating the g-factor map was proposed and validated via Monte Carlo simulations. Sensitivity maps were extrapolated to increase the area over which SENSE can be performed and therefore enhance the robustness to head motion. The precision of motion estimation of PROPELLER blades that are unfolded with these sensitivity maps was investigated. An interleaved R-factor PROPELLER sequence was used to acquire data with similar amounts of motion with and without SENSE acceleration. Two neuroradiologists independently and blindly compared 214 image pairs. The proposed method of g-factor calculation was similar to that provided by the Monte Carlo methods. Extrapolation and rotation of the sensitivity maps allowed for continued robustness of SENSE unfolding in the presence of motion. SENSE-widened blades improved the precision of rotation and translation estimation. PROPELLER images with a SENSE factor of 3 outperformed the traditional PROPELLER images when reconstructing the same number of blades. SENSE not only accelerates PROPELLER but can also improve robustness and precision of head motion correction, which improves overall image quality even when SNR is lost due to acceleration. The reduction of SNR, as a penalty of acceleration, is characterized by the proposed g-factor method. © 2014 Wiley Periodicals, Inc.

Sensitivity study and parameter optimization of OCD tool for 14nm finFET process

NASA Astrophysics Data System (ADS)

Zhang, Zhensheng; Chen, Huiping; Cheng, Shiqiu; Zhan, Yunkun; Huang, Kun; Shi, Yaoming; Xu, Yiping

2016-03-01

Optical critical dimension (OCD) measurement has been widely demonstrated as an essential metrology method for monitoring advanced IC process in the technology node of 90 nm and beyond. However, the rapidly shrunk critical dimensions of the semiconductor devices and the increasing complexity of the manufacturing process bring more challenges to OCD. The measurement precision of OCD technology highly relies on the optical hardware configuration, spectral types, and inherently interactions between the incidence of light and various materials with various topological structures, therefore sensitivity analysis and parameter optimization are very critical in the OCD applications. This paper presents a method for seeking the optimum sensitive measurement configuration to enhance the metrology precision and reduce the noise impact to the greatest extent. In this work, the sensitivity of different types of spectra with a series of hardware configurations of incidence angles and azimuth angles were investigated. The optimum hardware measurement configuration and spectrum parameter can be identified. The FinFET structures in the technology node of 14 nm were constructed to validate the algorithm. This method provides guidance to estimate the measurement precision before measuring actual device features and will be beneficial for OCD hardware configuration.

The Influence of Age and Skull Conductivity on Surface and Subdermal Bipolar EEG Leads

PubMed Central

Wendel, Katrina; Väisänen, Juho; Seemann, Gunnar; Hyttinen, Jari; Malmivuo, Jaakko

2010-01-01

Bioelectric source measurements are influenced by the measurement location as well as the conductive properties of the tissues. Volume conductor effects such as the poorly conducting bones or the moderately conducting skin are known to affect the measurement precision and accuracy of the surface electroencephalography (EEG) measurements. This paper investigates the influence of age via skull conductivity upon surface and subdermal bipolar EEG measurement sensitivity conducted on two realistic head models from the Visible Human Project. Subdermal electrodes (a.k.a. subcutaneous electrodes) are implanted on the skull beneath the skin, fat, and muscles. We studied the effect of age upon these two electrode types according to the scalp-to-skull conductivity ratios of 5, 8, 15, and 30 : 1. The effects on the measurement sensitivity were studied by means of the half-sensitivity volume (HSV) and the region of interest sensitivity ratio (ROISR). The results indicate that the subdermal implantation notably enhances the precision and accuracy of EEG measurements by a factor of eight compared to the scalp surface measurements. In summary, the evidence indicates that both surface and subdermal EEG measurements benefit better recordings in terms of precision and accuracy on younger patients. PMID:20130812

Solar axion search technique with correlated signals from multiple detectors

DOE PAGES

Xu, Wenqin; Elliott, Steven R.

2017-01-25

The coherent Bragg scattering of photons converted from solar axions inside crystals would boost the signal for axion-photon coupling enhancing experimental sensitivity for these hypothetical particles. Knowledge of the scattering angle of solar axions with respect to the crystal lattice is required to make theoretical predications of signal strength. Hence, both the lattice axis angle within a crystal and the absolute angle between the crystal and the Sun must be known. In this paper, we examine how the experimental sensitivity changes with respect to various experimental parameters. We also demonstrate that, in a multiple-crystal setup, knowledge of the relative axismore » orientation between multiple crystals can improve the experimental sensitivity, or equivalently, relax the precision on the absolute solar angle measurement. However, if absolute angles of all crystal axes are measured, we find that a precision of 2°–4° will suffice for an energy resolution of σ E = 0.04E and a flat background. Lastly, we also show that, given a minimum number of detectors, a signal model averaged over angles can substitute for precise crystal angular measurements, with some loss of sensitivity.« less

Development and validation of high-performance liquid chromatography and high-performance thin-layer chromatography methods for the quantification of khellin in Ammi visnaga seed

PubMed Central

Kamal, Abid; Khan, Washim; Ahmad, Sayeed; Ahmad, F. J.; Saleem, Kishwar

2015-01-01

Objective: The present study was used to design simple, accurate and sensitive reversed phase-high-performance liquid chromatography RP-HPLC and high-performance thin-layer chromatography (HPTLC) methods for the development of quantification of khellin present in the seeds of Ammi visnaga. Materials and Methods: RP-HPLC analysis was performed on a C18 column with methanol: Water (75: 25, v/v) as a mobile phase. The HPTLC method involved densitometric evaluation of khellin after resolving it on silica gel plate using ethyl acetate: Toluene: Formic acid (5.5:4.0:0.5, v/v/v) as a mobile phase. Results: The developed HPLC and HPTLC methods were validated for precision (interday, intraday and intersystem), robustness and accuracy, limit of detection and limit of quantification. The relationship between the concentration of standard solutions and the peak response was linear in both HPLC and HPTLC methods with the concentration range of 10–80 μg/mL in HPLC and 25–1,000 ng/spot in HPTLC for khellin. The % relative standard deviation values for method precision was found to be 0.63–1.97%, 0.62–2.05% in HPLC and HPTLC for khellin respectively. Accuracy of the method was checked by recovery studies conducted at three different concentration levels and the average percentage recovery was found to be 100.53% in HPLC and 100.08% in HPTLC for khellin. Conclusions: The developed HPLC and HPTLC methods for the quantification of khellin were found simple, precise, specific, sensitive and accurate which can be used for routine analysis and quality control of A. visnaga and several formulations containing it as an ingredient. PMID:26681890

Interfacial self-assembled functional nanoparticle array: a facile surface-enhanced Raman scattering sensor for specific detection of trace analytes.

PubMed

Zhang, Kun; Ji, Ji; Li, Yixin; Liu, Baohong

2014-07-01

Surface-enhanced Raman scattering (SERS) has proven to be promising for the detection of trace analytes; however, the precise nanofabrication of a specific and sensitive plasmonic SERS-active substrate is still a major challenge that limits the scope of its applications. In this work, gold nanoparticles are self-assembled into densely packed two-dimensional arrays at a liquid/liquid interface between dimethyl carbonate and water in the absence of template controller molecules. Both the simulation and experiment results show that the particles within these film-like arrays exhibit strong electromagnetic coupling and enable large amplification of Raman signals. In order to realize the level of sensing specificity, the surface chemistry of gold nanoparticles (Au NPs) is rationally tailored by incorporating an appropriate chemical moiety that specifically captures molecules of interest. The ease of fabrication and good uniformity make this platform ideal for in situ SERS sensing of trace targets in complex samples.

Peregrine: A rapid and unbiased method to produce strand-specific RNA-Seq libraries from small quantities of starting material.

PubMed

Langevin, Stanley A; Bent, Zachary W; Solberg, Owen D; Curtis, Deanna J; Lane, Pamela D; Williams, Kelly P; Schoeniger, Joseph S; Sinha, Anupama; Lane, Todd W; Branda, Steven S

2013-04-01

Use of second generation sequencing (SGS) technologies for transcriptional profiling (RNA-Seq) has revolutionized transcriptomics, enabling measurement of RNA abundances with unprecedented specificity and sensitivity and the discovery of novel RNA species. Preparation of RNA-Seq libraries requires conversion of the RNA starting material into cDNA flanked by platform-specific adaptor sequences. Each of the published methods and commercial kits currently available for RNA-Seq library preparation suffers from at least one major drawback, including long processing times, large starting material requirements, uneven coverage, loss of strand information and high cost. We report the development of a new RNA-Seq library preparation technique that produces representative, strand-specific RNA-Seq libraries from small amounts of starting material in a fast, simple and cost-effective manner. Additionally, we have developed a new quantitative PCR-based assay for precisely determining the number of PCR cycles to perform for optimal enrichment of the final library, a key step in all SGS library preparation workflows.

Guidance for deriving and presenting percentage study weights in meta-analysis of test accuracy studies.

PubMed

Burke, Danielle L; Ensor, Joie; Snell, Kym I E; van der Windt, Danielle; Riley, Richard D

2018-06-01

Percentage study weights in meta-analysis reveal the contribution of each study toward the overall summary results and are especially important when some studies are considered outliers or at high risk of bias. In meta-analyses of test accuracy reviews, such as a bivariate meta-analysis of sensitivity and specificity, the percentage study weights are not currently derived. Rather, the focus is on representing the precision of study estimates on receiver operating characteristic plots by scaling the points relative to the study sample size or to their standard error. In this article, we recommend that researchers should also provide the percentage study weights directly, and we propose a method to derive them based on a decomposition of Fisher information matrix. This method also generalises to a bivariate meta-regression so that percentage study weights can also be derived for estimates of study-level modifiers of test accuracy. Application is made to two meta-analyses examining test accuracy: one of ear temperature for diagnosis of fever in children and the other of positron emission tomography for diagnosis of Alzheimer's disease. These highlight that the percentage study weights provide important information that is otherwise hidden if the presentation only focuses on precision based on sample size or standard errors. Software code is provided for Stata, and we suggest that our proposed percentage weights should be routinely added on forest and receiver operating characteristic plots for sensitivity and specificity, to provide transparency of the contribution of each study toward the results. This has implications for the PRISMA-diagnostic test accuracy guidelines that are currently being produced. Copyright © 2017 John Wiley & Sons, Ltd.

Innovations in biomedical nanoengineering: nanowell array biosensor.

PubMed

Seo, YoungTae; Jeong, Sunil; Lee, JuKyung; Choi, Hak Soo; Kim, Jonghan; Lee, HeaYeon

2018-01-01

Nanostructured biosensors have pioneered biomedical engineering by providing highly sensitive analyses of biomolecules. The nanowell array (NWA)-based biosensing platform is particularly innovative, where the small size of NWs within the array permits extremely profound sensing of a small quantity of biomolecules. Undoubtedly, the NWA geometry of a gently-sloped vertical wall is critical for selective docking of specific proteins without capillary resistances, and nanoprocessing has contributed to the fabrication of NWA electrodes on gold substrate such as molding process, e-beam lithography, and krypton-fluoride (KrF) stepper semiconductor method. The Lee group at the Mara Nanotech has established this NW-based biosensing technology during the past two decades by engineering highly sensitive electrochemical sensors and providing a broad range of detection methods from large molecules (e.g., cells or proteins) to small molecules (e.g., DNA and RNA). Nanosized gold dots in the NWA enhance the detection of electrochemical biosensing to the range of zeptomoles in precision against the complementary target DNA molecules. In this review, we discuss recent innovations in biomedical nanoengineering with a specific focus on novel NWA-based biosensors. We also describe our continuous efforts in achieving a label-free detection without non-specific binding while maintaining the activity and stability of immobilized biomolecules. This research can lay the foundation of a new platform for biomedical nanoengineering systems.

Innovations in biomedical nanoengineering: nanowell array biosensor

NASA Astrophysics Data System (ADS)

Seo, YoungTae; Jeong, Sunil; Lee, JuKyung; Choi, Hak Soo; Kim, Jonghan; Lee, HeaYeon

2018-04-01

Nanostructured biosensors have pioneered biomedical engineering by providing highly sensitive analyses of biomolecules. The nanowell array (NWA)-based biosensing platform is particularly innovative, where the small size of NWs within the array permits extremely profound sensing of a small quantity of biomolecules. Undoubtedly, the NWA geometry of a gently-sloped vertical wall is critical for selective docking of specific proteins without capillary resistances, and nanoprocessing has contributed to the fabrication of NWA electrodes on gold substrate such as molding process, e-beam lithography, and krypton-fluoride (KrF) stepper semiconductor method. The Lee group at the Mara Nanotech has established this NW-based biosensing technology during the past two decades by engineering highly sensitive electrochemical sensors and providing a broad range of detection methods from large molecules (e.g., cells or proteins) to small molecules (e.g., DNA and RNA). Nanosized gold dots in the NWA enhance the detection of electrochemical biosensing to the range of zeptomoles in precision against the complementary target DNA molecules. In this review, we discuss recent innovations in biomedical nanoengineering with a specific focus on novel NWA-based biosensors. We also describe our continuous efforts in achieving a label-free detection without non-specific binding while maintaining the activity and stability of immobilized biomolecules. This research can lay the foundation of a new platform for biomedical nanoengineering systems.

Spectrophotometric total reducing sugars assay based on cupric reduction.

PubMed

Başkan, Kevser Sözgen; Tütem, Esma; Akyüz, Esin; Özen, Seda; Apak, Reşat

2016-01-15

As the concentration of reducing sugars (RS) is controlled by European legislation for certain specific food and beverages, a simple and sensitive spectrophotometric method for the determination of RS in various food products is proposed. The method is based on the reduction of Cu(II) to Cu(I) with reducing sugars in alkaline medium in the presence of 2,9-dimethyl-1,10-phenanthroline (neocuproine: Nc), followed by the formation of a colored Cu(I)-Nc charge-transfer complex. All simple sugars tested had the linear regression equations with almost equal slope values. The proposed method was successfully applied to fresh apple juice, commercial fruit juices, milk, honey and onion juice. Interference effect of phenolic compounds in plant samples was eliminated by a solid phase extraction (SPE) clean-up process. The method was proven to have higher sensitivity and precision than the widely used dinitrosalicylic acid (DNS) colorimetric method. Copyright © 2015 Elsevier B.V. All rights reserved.

Attomole quantitation of protein separations with accelerator mass spectrometry

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

Vogel, J S; Grant, P G; Buccholz, B A

2000-12-15

Quantification of specific proteins depends on separation by chromatography or electrophoresis followed by chemical detection schemes such as staining and fluorophore adhesion. Chemical exchange of short-lived isotopes, particularly sulfur, is also prevalent despite the inconveniences of counting radioactivity. Physical methods based on isotopic and elemental analyses offer highly sensitive protein quantitation that has linear response over wide dynamic ranges and is independent of protein conformation. Accelerator mass spectrometry quantifies long-lived isotopes such as 14C to sub-attomole sensitivity. We quantified protein interactions with small molecules such as toxins, vitamins, and natural biochemicals at precisions of 1-5% . Micro-proton-induced-xray-emission quantifies elemental abundancesmore » in separated metalloprotein samples to nanogram amounts and is capable of quantifying phosphorylated loci in gels. Accelerator-based quantitation is a possible tool for quantifying the genome translation into proteome.« less

Live-cell thermometry with nitrogen vacancy centers in nanodiamonds

NASA Astrophysics Data System (ADS)

Jayakumar, Harishankar; Fedder, Helmut; Chen, Andrew; Yang, Liudi; Li, Chenghai; Wrachtrup, Joerg; Wang, Sihong; Meriles, Carlos

The ability to measure temperature is typically affected by a tradeoff between sensitivity and spatial resolution. Good thermometers tend to be bulky systems and hence are ill-suited for thermal sensing with high spatial localization. Conversely, the signal resulting from nanoscale temperature probes is often impacted by noise to a level where the measurement precision becomes poor. Adding to the microscopist toolbox, the nitrogen vacancy (NV) center in diamond has recently emerged as a promising platform for high-sensitivity nanoscale thermometry. Of particular interest are applications in living cells because diamond nanocrystals are biocompatible and can be chemically functionalized to target specific organelles. Here we report progress on the ability to probe and compare temperature within and between living cells using nanodiamond-hosted NV thermometry. We focus our study on cancerous cells, where atypical metabolic pathways arguably lead to changes in the way a cell generates heat, and thus on its temperature profile.

A competitive chemiluminescence enzyme immunoassay for rapid and sensitive determination of enrofloxacin

NASA Astrophysics Data System (ADS)

Yu, Fei; Wu, Yongjun; Yu, Songcheng; Zhang, Huili; Zhang, Hongquan; Qu, Lingbo; Harrington, Peter de B.

With alkaline phosphatase (ALP)-adamantane (AMPPD) system as the chemiluminescence (CL) detection system, a highly sensitive, specific and simple competitive chemiluminescence enzyme immunoassay (CLEIA) was developed for the measurement of enrofloxacin (ENR). The physicochemical parameters, such as the chemiluminescent assay mediums, the dilution buffer of ENR-McAb, the volume of dilution buffer, the monoclonal antibody concentration, the incubation time, and other relevant variables of the immunoassay have been optimized. Under the optimal conditions, the detection linear range of 350-1000 pg/mL and the detection limit of 0.24 ng/mL were provided by the proposed method. The relative standard deviations were less than 15% for both intra and inter-assay precision. This method has been successfully applied to determine ENR in spiked samples with the recovery of 103%-96%. It showed that CLEIA was a good potential method in the analysis of residues of veterinary drugs after treatment of related diseases.

Quantification of residual EDU (N-ethyl-N'-(dimethylaminopropyl) carbodiimide (EDC) hydrolyzed urea derivative) and other residual by LC-MS/MS.

PubMed

Lei, Q Paula; Lamb, David H; Shannon, Anthony G; Cai, Xinxing; Heller, Ronald K; Huang, Michael; Zablackis, Earl; Ryall, Robert; Cash, Patricia

2004-12-25

An LC-MS/MS method for determination of the break down product of N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) urea derivative, EDU, has been developed and validated for monitoring the residual coupling reagents. Results indicate that the method exhibits suitable specificity, sensitivity, precision, linearity and accuracy for quantification of residual EDU in the presence of meningococcal polysaccharide-diphtheria toxoid conjugate vaccine and other vaccine matrix compounds. The assay has been validated for a detection range of 10-100 ng/mL and then successfully transferred to quality control (QC) lab. This same method has also been applied to the determination of residual diaminohexane (DAH) in the presence of EDU. LC-MS/MS has proven to be useful as a quick and sensitive approach for simultaneous determination of multiple residual compounds in glycoconjugate vaccine samples.

An efficient deterministic-probabilistic approach to modeling regional groundwater flow: 2. Application to Owens Valley, California

USGS Publications Warehouse

Guymon, Gary L.; Yen, Chung-Cheng

1990-01-01

The applicability of a deterministic-probabilistic model for predicting water tables in southern Owens Valley, California, is evaluated. The model is based on a two-layer deterministic model that is cascaded with a two-point probability model. To reduce the potentially large number of uncertain variables in the deterministic model, lumping of uncertain variables was evaluated by sensitivity analysis to reduce the total number of uncertain variables to three variables: hydraulic conductivity, storage coefficient or specific yield, and source-sink function. Results demonstrate that lumping of uncertain parameters reduces computational effort while providing sufficient precision for the case studied. Simulated spatial coefficients of variation for water table temporal position in most of the basin is small, which suggests that deterministic models can predict water tables in these areas with good precision. However, in several important areas where pumping occurs or the geology is complex, the simulated spatial coefficients of variation are over estimated by the two-point probability method.

An efficient deterministic-probabilistic approach to modeling regional groundwater flow: 2. Application to Owens Valley, California

NASA Astrophysics Data System (ADS)

Guymon, Gary L.; Yen, Chung-Cheng

1990-07-01

The applicability of a deterministic-probabilistic model for predicting water tables in southern Owens Valley, California, is evaluated. The model is based on a two-layer deterministic model that is cascaded with a two-point probability model. To reduce the potentially large number of uncertain variables in the deterministic model, lumping of uncertain variables was evaluated by sensitivity analysis to reduce the total number of uncertain variables to three variables: hydraulic conductivity, storage coefficient or specific yield, and source-sink function. Results demonstrate that lumping of uncertain parameters reduces computational effort while providing sufficient precision for the case studied. Simulated spatial coefficients of variation for water table temporal position in most of the basin is small, which suggests that deterministic models can predict water tables in these areas with good precision. However, in several important areas where pumping occurs or the geology is complex, the simulated spatial coefficients of variation are over estimated by the two-point probability method.

Determination of emamectin benzoate in medicated fish feed: a multisite study.

PubMed

Farer, Leslie J

2005-01-01

A new method was developed for the quantitation of emamectin benzoate in medicated fish feed at levels between 1 and 30 ppm. The new procedure, based on a previously reported assay, consists of a wet methanolic extraction of ground feed, followed by solid-phase extraction and injection onto a gradient liquid chromatographic system. A multisite study involving 3 laboratories (the developing laboratory and 2 independent laboratories) was performed to evaluate precision, recovery, linearity, and sensitivity. Mean recove;ries for triplicate analyses at 3 levels, performed by 2 analysts per laboratory, were between 89 and 97%, with coefficients of variation ranging from 1.6 to 8.6%. Coefficients of determination (r2) obtained from the plotted data were > or =0.993. The precision of the method, determined from 6 replicate preparations from the same batch of medicated feed assayed in 3 separate trials per laboratory, was between 0.6 and 5.8%. The quantitation limit was established at 0.5 ppm. Specificity and robustness studies were performed by the developing laboratory.

Fabry-Perot Interferometer for Column CO2

NASA Technical Reports Server (NTRS)

Heaps, William S.; Kawa, Randolph; Bhartia, P. K. (Technical Monitor)

2002-01-01

Global atmospheric CO2 measurements are essential to resolving significant discrepancies in our understanding of the global carbon budget and, hence, humankind's role in global climate change. The science measurement requirements for CO2 are extremely demanding (precision approx. 0.3%). No atmospheric chemical species has ever been measured from space with this precision. We are developing a novel application of a Fabry-Perot interferometer to detect spectral absorption of reflected sunlight by CO2 and O2 in the atmosphere. Preliminary design studies indicate that the method will be able to achieve the sensitivity and signal-to-noise detection required to measure column CO2 at the target specification. The objective of this program is to construct a prototype instrument for deployment on an aircraft to test the instrument performance and our ability to retrieve the data in the real atmosphere. To date we have assembled a laboratory bench system to begin testing the optical and electronic components. We are also measuring signal and noise levels in actual sunlight to evaluate component performance.

Study of a high-precision SAW-MOEMS strain sensor with laser optics

NASA Astrophysics Data System (ADS)

Liu, Xinwei; Chen, Shufen; Li, Honglang; Zou, Zhengfeng; Fu, Lei; Meng, Yanbin

2015-02-01

A novel structure design of a surface acoustic wave (SAW) micro-optic-electro-mechanical-system (MOEMS) strain sensor with a light readout unit is presented in this paper. By measuring the polarization intensity ratio of the TE/TM mode outputted from the waveguide, the strain produced from an object can be measured precisely. The basic working principle of the SAW MOEMS strain sensor is introduced and the mathematical model of the strain sensor system is established. The SAW characteristics effected by the strain sensor are mathematically deduced. The coupling coefficient between the SAW modes and light modes can be calculated based on the theory of coupling modes. The conversion coefficient of polarized light modes is obtained. Due to the restrictions of the specific parameters of the device, the level of technology and the material characteristics, the sensitivity of the strain sensor system is calculated through simulation as 0.1 μɛ, with a dynamic range of 0 ~ ±50 μɛ.

Development and Validation of RP-LC Method for the Determination of Cinnarizine/Piracetam and Cinnarizine/Heptaminol Acefyllinate in Presence of Cinnarizine Reported Degradation Products

PubMed Central

EL-Houssini, Ola M.; Zawilla, Nagwan H.; Mohammad, Mohammad A.

2013-01-01

Specific stability indicating reverse-phase liquid chromatography (RP-LC) assay method (SIAM) was developed for the determination of cinnarizine (Cinn)/piracetam (Pira) and cinnarizine (Cinn)/heptaminol acefyllinate (Hept) in the presence of the reported degradation products of Cinn. A C18 column and gradient mobile phase was applied for good resolution of all peaks. The detection was achieved at 210 nm and 254 nm for Cinn/Pira and Cinn/Hept, respectively. The responses were linear over concentration ranges of 20–200, 20–1000 and 25–1000 μgmL−1 for Cinn, Pira, and Hept respectively. The proposed method was validated for linearity, accuracy, repeatability, intermediate precision, and robustness via statistical analysis of the data. The method was shown to be precise, accurate, reproducible, sensitive, and selective for the analysis of Cinn/Pira and Cinn/Hept in laboratory prepared mixtures and in pharmaceutical formulations. PMID:24137049

Scientific applications of frequency-stabilized laser technology in space

NASA Technical Reports Server (NTRS)

Schumaker, Bonny L.

1990-01-01

A synoptic investigation of the uses of frequency-stabilized lasers for scientific applications in space is presented. It begins by summarizing properties of lasers, characterizing their frequency stability, and describing limitations and techniques to achieve certain levels of frequency stability. Limits to precision set by laser frequency stability for various kinds of measurements are investigated and compared with other sources of error. These other sources include photon-counting statistics, scattered laser light, fluctuations in laser power, and intensity distribution across the beam, propagation effects, mechanical and thermal noise, and radiation pressure. Methods are explored to improve the sensitivity of laser-based interferometric and range-rate measurements. Several specific types of science experiments that rely on highly precise measurements made with lasers are analyzed, and anticipated errors and overall performance are discussed. Qualitative descriptions are given of a number of other possible science applications involving frequency-stabilized lasers and related laser technology in space. These applications will warrant more careful analysis as technology develops.

A validated high-performance liquid chromatographic method for the determination of glibenclamide in human plasma and its application to pharmacokinetic studies.

PubMed

Niopas, Ioannis; Daftsios, Athanasios C

2002-05-15

Glibenclamide is a potent second generation oral sulfonylurea antidiabetic agent widely used for the treatment of type II diabetes melitus. A rapid, sensitive, precise, accurate and specific HPLC assay for the determination of glibenclamide in human plasma was developed and validated. After addition of flufenamic acid as internal standard, the analytes were isolated from human plasma by liquid-liquid extraction. The method was linear in the 10-400 ng/ml concentration range (r > 0.999). Recovery for glibenclamide was greater than 91.5% and for internal standard was 93.5%. Within-day and between-day precision, expressed as the relative standard deviation (RSD%), ranged from 1.4 to 5.9% and 5.8 to 6.6%, respectively. Assay accuracy was better than 93.4%. The assay was used to estimate the pharmacokinetics of glibenclamide after oral administration of a 5 mg tablet of glibenclamide to 18 healthy volunteers.

A novel spectrofluorimetric method for the assay of pseudoephedrine hydrochloride in pharmaceutical formulations via derivatization with 4-chloro-7-nitrobenzofurazan.

PubMed

El-Didamony, Akram M; Gouda, Ayman A

2011-01-01

A new highly sensitive and specific spectrofluorimetric method has been developed to determine a sympathomimetic drug pseudoephedrine hydrochloride. The present method was based on derivatization with 4-chloro-7-nitrobenzofurazan in phosphate buffer at pH 7.8 to produce a highly fluorescent product which was measured at 532 nm (excitation at 475 nm). Under the optimized conditions a linear relationship and good correlation was found between the fluorescence intensity and pseudoephedrine hydrochloride concentration in the range of 0.5-5 µg mL(-1). The proposed method was successfully applied to the assay of pseudoephedrine hydrochloride in commercial pharmaceutical formulations with good accuracy and precision and without interferences from common additives. Statistical comparison of the results with a well-established method showed excellent agreement and proved that there was no significant difference in the accuracy and precision. The stoichiometry of the reaction was determined and the reaction pathway was postulated. Copyright © 2010 John Wiley & Sons, Ltd.

Precise and accurate assay of pregnenolone and five other neurosteroids in monkey brain tissue by LC-MS/MS.

PubMed

Dury, Alain Y; Ke, Yuyong; Labrie, Fernand

2016-09-01

A series of steroids present in the brain have been named "neurosteroids" following the possibility of their role in the central nervous system impairments such as anxiety disorders, depression, premenstrual dysphoric disorder (PMDD), addiction, or even neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Study of their potential role requires a sensitive and accurate assay of their concentration in the monkey brain, the closest model to the human. We have thus developed a robust, precise and accurate liquid chromatography-tandem mass spectrometry method for the assay of pregnenolone, pregnanolone, epipregnanolone, allopregnanolone, epiallopregnanolone, and androsterone in the cynomolgus monkey brain. The extraction method includes a thorough sample cleanup using protein precipitation and phospholipid removal, followed by hexane liquid-liquid extraction and a Girard T ketone-specific derivatization. This method opens the possibility of investigating the potential implication of these six steroids in the most suitable animal model for neurosteroid-related research. Copyright © 2016 Elsevier Inc. All rights reserved.

Towards Optogenetic Sensory Replacement

PubMed Central

Doroudchi, M. Mehdi; Greenberg, Kenneth P.; Zorzos, Anthony N.; Hauswirth, William W.; Fonstad, Clifton G.; Horsager, Alan; Boyden, Edward S.

2013-01-01

Over the last several years we have developed a rapidly-expanding suite of genetically-encoded reagents (e.g., ChR2, Halo, Arch, Mac, and others) that, when expressed in specific neuron types in the nervous system, enable their activities to be powerfully and precisely activated and silenced in response to light. If the genes that encode for these reagents can be delivered to cells in the body using gene therapy methods, and if the resultant protein payloads operate safely and effectively over therapeutically important periods of time, these molecules could subserve a set of precise prosthetics that use light as the trigger of information entry into the nervous system, e.g. for sensory replacement. Here we discuss the use of ChR2 to make the photoreceptor-deprived retina, as found in diseases such as retinitis pigmentosa, sensitive to light, enabling restoration of functional vision in a mouse model of blindness. We also discuss arrays of light sources that could be useful for delivering patterned sensory information into the nervous system. PMID:22255005

COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples

PubMed Central

Yamagata, Koichi; Yamanishi, Ayako; Kokubu, Chikara; Takeda, Junji; Sese, Jun

2016-01-01

An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis. PMID:26833260

Flight control and landing precision in the nocturnal bee Megalopta is robust to large changes in light intensity.

PubMed

Baird, Emily; Fernandez, Diana C; Wcislo, William T; Warrant, Eric J

2015-01-01

Like their diurnal relatives, Megalopta genalis use visual information to control flight. Unlike their diurnal relatives, however, they do this at extremely low light intensities. Although Megalopta has developed optical specializations to increase visual sensitivity, theoretical studies suggest that this enhanced sensitivity does not enable them to capture enough light to use visual information to reliably control flight in the rainforest at night. It has been proposed that Megalopta gain extra sensitivity by summing visual information over time. While enhancing the reliability of vision, this strategy would decrease the accuracy with which they can detect image motion-a crucial cue for flight control. Here, we test this temporal summation hypothesis by investigating how Megalopta's flight control and landing precision is affected by light intensity and compare our findings with the results of similar experiments performed on the diurnal bumblebee Bombus terrestris, to explore the extent to which Megalopta's adaptations to dim light affect their precision. We find that, unlike Bombus, light intensity does not affect flight and landing precision in Megalopta. Overall, we find little evidence that Megalopta uses a temporal summation strategy in dim light, while we find strong support for the use of this strategy in Bombus.

Flight control and landing precision in the nocturnal bee Megalopta is robust to large changes in light intensity

PubMed Central

Baird, Emily; Fernandez, Diana C.; Wcislo, William T.; Warrant, Eric J.

2015-01-01

Like their diurnal relatives, Megalopta genalis use visual information to control flight. Unlike their diurnal relatives, however, they do this at extremely low light intensities. Although Megalopta has developed optical specializations to increase visual sensitivity, theoretical studies suggest that this enhanced sensitivity does not enable them to capture enough light to use visual information to reliably control flight in the rainforest at night. It has been proposed that Megalopta gain extra sensitivity by summing visual information over time. While enhancing the reliability of vision, this strategy would decrease the accuracy with which they can detect image motion—a crucial cue for flight control. Here, we test this temporal summation hypothesis by investigating how Megalopta's flight control and landing precision is affected by light intensity and compare our findings with the results of similar experiments performed on the diurnal bumblebee Bombus terrestris, to explore the extent to which Megalopta's adaptations to dim light affect their precision. We find that, unlike Bombus, light intensity does not affect flight and landing precision in Megalopta. Overall, we find little evidence that Megalopta uses a temporal summation strategy in dim light, while we find strong support for the use of this strategy in Bombus. PMID:26578977

One novel type of miniaturization FBG rotation angle sensor with high measurement precision and temperature self-compensation

NASA Astrophysics Data System (ADS)

Jiang, Shanchao; Wang, Jing; Sui, Qingmei

2018-03-01

In order to achieve rotation angle measurement, one novel type of miniaturization fiber Bragg grating (FBG) rotation angle sensor with high measurement precision and temperature self-compensation is proposed and studied in this paper. The FBG rotation angle sensor mainly contains two core sensitivity elements (FBG1 and FBG2), triangular cantilever beam, and rotation angle transfer element. In theory, the proposed sensor can achieve temperature self-compensation by complementation of the two core sensitivity elements (FBG1 and FBG2), and it has a boundless angel measurement range with 2π rad period duo to the function of the rotation angle transfer element. Based on introducing the joint working processes, the theory calculation model of the FBG rotation angel sensor is established, and the calibration experiment on one prototype is also carried out to obtain its measurement performance. After experimental data analyses, the measurement precision of the FBG rotation angle sensor prototype is 0.2 ° with excellent linearity, and the temperature sensitivities of FBG1 and FBG2 are 10 pm/° and 10.1 pm/°, correspondingly. All these experimental results confirm that the FBG rotation angle sensor can achieve large-range angle measurement with high precision and temperature self-compensation.

Deep-space navigation with differenced data types. Part 3: An expanded information content and sensitivity analysis

NASA Technical Reports Server (NTRS)

Estefan, J. A.; Thurman, S. W.

1992-01-01

An approximate six-parameter analytic model for Earth-based differential range measurements is presented and is used to derive a representative analytic approximation for differenced Doppler measurements. The analytical models are tasked to investigate the ability of these data types to estimate spacecraft geocentric angular motion, Deep Space Network station oscillator (clock/frequency) offsets, and signal-path calibration errors over a period of a few days, in the presence of systematic station location and transmission media calibration errors. Quantitative results indicate that a few differenced Doppler plus ranging passes yield angular position estimates with a precision on the order of 0.1 to 0.4 micro-rad, and angular rate precision on the order of 10 to 25 x 10(exp -12) rad/sec, assuming no a priori information on the coordinate parameters. Sensitivity analyses suggest that troposphere zenith delay calibration error is the dominant systematic error source in most of the tracking scenarios investigated; as expected, the differenced Doppler data were found to be much more sensitive to troposphere calibration errors than differenced range. By comparison, results computed using wideband and narrowband (delta) VLBI under similar circumstances yielded angular precisions of 0.07 to 0.4 micro-rad, and angular rate precisions of 0.5 to 1.0 x 10(exp -12) rad/sec.

Deep-space navigation with differenced data types. Part 3: An expanded information content and sensitivity analysis

NASA Technical Reports Server (NTRS)

Estefan, J. A.; Thurman, S. W.

1992-01-01

An approximate six-parameter analytic model for Earth-based differenced range measurements is presented and is used to derive a representative analytic approximation for differenced Doppler measurements. The analytical models are tasked to investigate the ability of these data types to estimate spacecraft geocentric angular motion, Deep Space Network station oscillator (clock/frequency) offsets, and signal-path calibration errors over a period of a few days, in the presence of systematic station location and transmission media calibration errors. Quantitative results indicate that a few differenced Doppler plus ranging passes yield angular position estimates with a precision on the order of 0.1 to 0.4 microrad, and angular rate precision on the order of 10 to 25(10)(exp -12) rad/sec, assuming no a priori information on the coordinate parameters. Sensitivity analyses suggest that troposphere zenith delay calibration error is the dominant systematic error source in most of the tracking scenarios investigated; as expected, the differenced Doppler data were found to be much more sensitive to troposphere calibration errors than differenced range. By comparison, results computed using wide band and narrow band (delta)VLBI under similar circumstances yielded angular precisions of 0.07 to 0.4 /microrad, and angular rate precisions of 0.5 to 1.0(10)(exp -12) rad/sec.

[Precision medicine: A major step forward in specific situations, a myth in refractory cancers?

PubMed

Albin, Nicolas; Mc Leer, Anne; Sakhri, Linda

2018-04-01

In recent years, high-throughput sequencing techniques have been developed for cancerology and many clinical trials are currently structured around biomarkers that can guide specific treatment choices. This approach is characteristic of precision medicine, which is actually a concept initiated several decades ago with, for example, retinoic acid in promyelocytic leukemia. This paper will review the different types of molecular alterations and « -omics » biological analyses, bioinformatics tools, coupled drug/biomarkers already validated, the ethical issues of whole genomic sequencing of an individual as part of an inclusion in a clinical trial and finally the first results of precision medicine trials. The AcSé crizotinib program, supported by the Inca (french Cancer National Institute), is emblematic of a success of this personalized medicine illustrated by 4 points: the discovery of a cohort of patients with lung cancer with a ROS1 rearrangement characteristic of a sensitivity to crizotinib, a rapid availability of this innovation through the implementation of a temporary recommendation for use (ANSM), the obtention of a conditional marketing authorization by the pharmaceutical industry and finally, financial assumption of responsibility by French social security (HAS), despite preliminary and non-comparative data. In the case of cancers refractory to standard chemotherapy, and regarding our system of access to drugs illustrated by the PROFILER clinical trial, this approach allows the access to a therapeutic drug targeting specific biomarkers only in 7% of patients included. This does not bode well for efficient treatment and even less for survival. Allowing patients to be included in trials that identify molecular targets by molecular screening, and not being able to propose the drug of interest is a traumatic event for those patients who live in the hope of an immediate future. In refractory disease we must rethink precision medicine in a more humanistic vision for our patients and not only in a dimension of medico-industrial promotion. The implementation of a new multi-drug/multi-molecular target program could address this issue. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Modeling the Relationship between Prosodic Sensitivity and Early Literacy

ERIC Educational Resources Information Center

Holliman, Andrew; Critten, Sarah; Lawrence, Tony; Harrison, Emily; Wood, Clare; Hughes, David

2014-01-01

A growing literature has demonstrated that prosodic sensitivity is related to early literacy development; however, the precise nature of this relationship remains unclear. It has been speculated in recent theoretical models that the observed relationship between prosodic sensitivity and early literacy might be partially mediated by children's…

Precise Temperature Measurement for Increasing the Survival of Newborn Babies in Incubator Environments

PubMed Central

Frischer, Robert; Penhaker, Marek; Krejcar, Ondrej; Kacerovsky, Marian; Selamat, Ali

2014-01-01

Precise temperature measurement is essential in a wide range of applications in the medical environment, however the regarding the problem of temperature measurement inside a simple incubator, neither a simple nor a low cost solution have been proposed yet. Given that standard temperature sensors don't satisfy the necessary expectations, the problem is not measuring temperature, but rather achieving the desired sensitivity. In response, this paper introduces a novel hardware design as well as the implementation that increases measurement sensitivity in defined temperature intervals at low cost. PMID:25494352

A chemical-genetic approach for functional analysis of plant protein kinases

PubMed Central

Salomon, Dor; Bonshtien, Arale

2009-01-01

Plant genomes encode hundreds of protein kinases, yet only for a small fraction of them precise functions and phosphorylation targets have been identified. Recently, we applied a chemical-genetic approach to sensitize the tomato serine/threonine kinase Pto to analogs of PP1, an ATP-competitive and cell-permeable small-molecule inhibitor. The Pto kinase confers resistance to Pst bacteria by activating immune responses upon specific recognition of bacterial effectors. By using PP1 analogs in combination with the analog-sensitive Pto, we shed new light on the role of Pto kinase activity in effector recognition and signal transduction. Here we broaden the use of this chemical-genetic approach to another defense-related plant protein kinase, the MAP kinase LeMPK3. In addition, we show that analog-sensitive but not wild-type kinases are able to use unnatural N6-modified ATP analogs as phosphodonors that can be exploited for tagging direct phosphorylation targets of the kinase of interest. Thus, sensitization of kinases to analogs of the small-molecule inhibitor PP1 and ATP can be an effective tool for the discovery of cellular functions and phosphorylation substrates of plant protein kinases. PMID:19820342

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

PubMed Central

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

2013-01-01

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

Applying under-sampling techniques and cost-sensitive learning methods on risk assessment of breast cancer.

PubMed

Hsu, Jia-Lien; Hung, Ping-Cheng; Lin, Hung-Yen; Hsieh, Chung-Ho

2015-04-01

Breast cancer is one of the most common cause of cancer mortality. Early detection through mammography screening could significantly reduce mortality from breast cancer. However, most of screening methods may consume large amount of resources. We propose a computational model, which is solely based on personal health information, for breast cancer risk assessment. Our model can be served as a pre-screening program in the low-cost setting. In our study, the data set, consisting of 3976 records, is collected from Taipei City Hospital starting from 2008.1.1 to 2008.12.31. Based on the dataset, we first apply the sampling techniques and dimension reduction method to preprocess the testing data. Then, we construct various kinds of classifiers (including basic classifiers, ensemble methods, and cost-sensitive methods) to predict the risk. The cost-sensitive method with random forest classifier is able to achieve recall (or sensitivity) as 100 %. At the recall of 100 %, the precision (positive predictive value, PPV), and specificity of cost-sensitive method with random forest classifier was 2.9 % and 14.87 %, respectively. In our study, we build a breast cancer risk assessment model by using the data mining techniques. Our model has the potential to be served as an assisting tool in the breast cancer screening.

Improving precision of forage yield trials: A case study

USDA-ARS?s Scientific Manuscript database

Field-based agronomic and genetic research relies heavily on the data generated from field evaluations. Therefore, it is imperative to optimize the precision of yield estimates in cultivar evaluation trials to make reliable selections. Experimental error in yield trials is sensitive to several facto...

Technical and clinical performance of a new assay to detect squamous cell carcinoma antigen levels for the differential diagnosis of cervical, lung, and head and neck cancer.

PubMed

Holdenrieder, Stefan; Molina, Rafael; Qiu, Ling; Zhi, Xiuyi; Rutz, Sandra; Engel, Christine; Kasper-Sauer, Pia; Dayyani, Farshid; Korse, Catharina M

2018-04-01

In squamous cell carcinoma, squamous cell carcinoma antigen levels are often elevated. This multi-center study evaluated the technical performance of a new Elecsys ® squamous cell carcinoma assay, which measures serum squamous cell carcinoma antigen 1 and 2 levels in an equimolar manner, and investigated the potential of squamous cell carcinoma antigen for differential diagnosis of cervical, lung, and head and neck squamous cell carcinoma.Assay precision and method comparison experiments were performed across three European sites. Reference ranges for reportedly healthy individuals were determined using samples from banked European and Chinese populations. Differential diagnosis experiments determined whether cervical, lung, or head and neck cancer could be differentiated from apparently healthy, benign, or other malignant cohorts using squamous cell carcinoma antigen levels alone. Squamous cell carcinoma antigen cut-off levels were calculated based on squamous cell carcinoma antigen levels at 95% specificity. Repeatability coefficients of variation across nine analyte concentrations were ≤5.3%, and intermediate precision coefficients of variation were ≤10.3%. Method comparisons showed good correlations with Architect and Kryptor systems (slopes of 1.1 and 1.5, respectively). Reference ranges for 95th percentiles for apparently healthy individuals were 2.3 ng/mL (95% confidence interval: 1.9-3.8; European cohort, n = 153) and 2.7 ng/mL (95% confidence interval: 2.2-3.3; Chinese cohort, n = 146). Strongest differential diagnosis results were observed for cervical squamous cell carcinoma: receiver operating characteristic analysis showed that squamous cell carcinoma antigen levels (2.9 ng/mL cut-off) differentiate cervical squamous cell carcinoma (n = 127) from apparently healthy females (n = 286; area under the curve: 86.2%; 95% confidence interval: 81.8-90.6; sensitivity: 61.4%; specificity: 95.6%), benign diseases (n = 187; area under the curve: 86.3%; 95% confidence interval: 81.2-91.3; sensitivity: 61.4%; specificity: 95.0%), and other cervical cancers (n = 157; area under the curve: 78.9%; 95% confidence interval: 70.8-87.1; sensitivity: 61.4%; specificity: 86.7%). Squamous cell carcinoma may also aid in the differential diagnosis of lung cancer. The Elecsys squamous cell carcinoma assay exhibited good technical performance and is suitable for differential diagnosis of cervical squamous cell carcinoma in clinical practice.

Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of pramipexole in human plasma: application to a clinical pharmacokinetic study.

PubMed

Bharathi, D Vijaya; Hotha, Kishore Kumar; Sagar, P V Vidya; Kumar, S Sirish; Naidu, A; Mullangi, Ramesh

2009-02-01

A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of pramipexole (PPX) with 500 microL human plasma using memantine as an internal standard (IS). The API-4000 was operated under multiple-reaction monitoring mode (MRM) using the electrospray ionization technique. Solid-phase extraction was used to extract PPX and IS from human plasma. The resolution of peaks was achieved with 0.01 m ammonium acetate buffer (pH 4.4):acetonitrile (30:70, v/v) on a Discovery CN column. The total chromatographic run time was 3.0 min and the elution of PPX and IS occurred at approximately 2.32 and 2.52, respectively. The MS/MS ion transitions monitored were 212.10 --> 153.10 for PPX and 180.20 --> 107.30 for IS. The method was proved to be accurate and precise at linearity range of 20-3540 pg/mL with a correlation coefficient (r) of > or =0.999. The intra- and inter-day precision and accuracy values found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of 0.25 mg PPX tablet. Copyright (c) 2008 John Wiley & Sons, Ltd.

A quantitative LC-MS/MS method for simultaneous determination of cocaine and its metabolites in whole blood

PubMed Central

Chen, Xiabin; Zheng, Xirong; Ding, Kai; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

2016-01-01

As new metabolic pathways of cocaine were recently identified, a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine cocaine and nine cocaine-related metabolites in whole blood samples. One-step solid phase extraction was used to extract all of the ten compounds and corresponding internal standards from blood samples. All compounds and internal standards extracted were separated on an Atlantis T3 (100Å, 3 µm, 2.1 mm × 150 mm I.D) column and detected in positive ion and high sensitivity mode with multiple reaction monitoring. This method was validated for its sensitivity, linearity, specificity, accuracy, precision, recovery, and stability. All of the ten compounds were quantifiable ranging from the lower limit of quantification (LLOQs) of ~10 nM (1.9–3.2 ng/ml) to ~1000 nM (190–320 ng/ml) without any interfering substance. Accuracy and precision were determined, and both of them were within the acceptance criteria of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The recovery was above 66.7% for all compounds. Stability tests demonstrated the stability of compounds under different storage conditions in whole blood samples. The method was successfully applied to a pharmacokinetic study with co-administration of cocaine and alcohol in rats. PMID:27923200

Liquid chromatographic determination of oxytetracycline in edible fish fillets from six species of fish

USGS Publications Warehouse

Meinertz, J.R.; Stehly, G.R.; Gingerich, W.H.

1998-01-01

The approved use of oxytetracycline (OTC) in U.S. Aquaculture is limited to specific diseases in salmonids and channel catfish. OTC may also be effective in controlling diseases in other fish species important to public aquaculture, but before approved use of OTC can be augmented, an analytical method for determining OTC in fillet tissue from multiple species of fish will be required to support residue depletion studies. The objective of this study was to develop and validate a liquid chromatographic (LC) method that is accurate, precise, and sensitive for OTC in edible fillets from multiple species of fish. Homogenized fillet tissues from walleye, Atlantic salmon, striped bass, white sturgeon, rainbow trout, and channel catfish were fortified with OTC at nominal concentrations of 10, 20, 100, 1000, and 5000 ng/g. In tissues fortified with OTC at 100, 1000, and 5000 ng/g, mean recoveries ranged from 83 to 90%, and relative standard deviations (RSDs) ranged from 0.9 to 5.8%. In all other tissues, mean recoveries ranged from 59 to 98%, and RSDs ranged from 3.3 to 20%. Method quantitation limits ranged from 6 to 22 ng/g for the 6 species. The LC parameters produced easily integratable OTC peaks without coelution of endogenous compounds. The method is accurate, precise, and sensitive for OTC in fillet tissue from 6 species of fish from 5 phylogenetically diverse groups.

27 CFR 30.25 - Use of precision specific gravity hydrometers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... gravity hydrometers. 30.25 Section 30.25 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... precision specific gravity hydrometers. The provisions of § 30.23 respecting the care, handling, and use of... specific gravity hydrometers. Specific gravity hydrometers shall be read to the nearest subdivision...

27 CFR 30.25 - Use of precision specific gravity hydrometers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... gravity hydrometers. 30.25 Section 30.25 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... precision specific gravity hydrometers. The provisions of § 30.23 respecting the care, handling, and use of... specific gravity hydrometers. Specific gravity hydrometers shall be read to the nearest subdivision...

27 CFR 30.25 - Use of precision specific gravity hydrometers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... gravity hydrometers. 30.25 Section 30.25 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... precision specific gravity hydrometers. The provisions of § 30.23 respecting the care, handling, and use of... specific gravity hydrometers. Specific gravity hydrometers shall be read to the nearest subdivision...

27 CFR 30.25 - Use of precision specific gravity hydrometers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... gravity hydrometers. 30.25 Section 30.25 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... precision specific gravity hydrometers. The provisions of § 30.23 respecting the care, handling, and use of... specific gravity hydrometers. Specific gravity hydrometers shall be read to the nearest subdivision...

27 CFR 30.25 - Use of precision specific gravity hydrometers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... gravity hydrometers. 30.25 Section 30.25 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... precision specific gravity hydrometers. The provisions of § 30.23 respecting the care, handling, and use of... specific gravity hydrometers. Specific gravity hydrometers shall be read to the nearest subdivision...

Otoancorin Knockout Mice Reveal Inertia is the Force for Hearing

NASA Astrophysics Data System (ADS)

Weddell, Thomas; Legan, P. Kevin; Lukashkina, Victoria A.; Goodyear, Richard J.; Welstead, Lindsy; Petit, Chistine; Russell, Ian J.; Lukashkin, Andrei N.; Richardson, Guy P.

2011-11-01

We demonstrate that in Otoa-/- mice, in which the inner-ear-specific protein otoancorin is absent, excitation of the outer hair cells and cochlear amplification is normal. This finding is remarkable because the tectorial membrane (TM), although remaining functionally attached to the outer hair cell bundles, is completely detached from the spiral limbus. Therefore, as in ancestral vertebrate auditory organs, where inertia provides the excitatory force to the hair cells, it is the inertia of the TM that must be important for exciting the outer hair cells, setting the sensitivity of their transducer conductance, and determining the precise timing of cochlear amplification.

When is it time to get married? Or when should the assay user and the assay developer collaborate?

PubMed Central

Swan, S H; Lasley, B L

1991-01-01

Hormone assays are being developed in the laboratory to detect specific molecular markers in nonclinical populations. Epidemiology is increasingly using these assays to improve the precision with which disease processes and exposures can be defined. This growing body of molecular epidemiology requires a high degree of cooperation between the assay developer and the assay user. We draw on our experience in using a sensitive hormone assay for the detection of early pregnancy via urinary human chorionic gonadotropin to illustrate these points. We conclude that this collaborative effort, in addition to making this study possible, has provided unexpected rewards. PMID:1954925

Cavity enhanced atomic magnetometry

PubMed Central

Crepaz, Herbert; Ley, Li Yuan; Dumke, Rainer

2015-01-01

Atom sensing based on Faraday rotation is an indispensable method for precision measurements, universally suitable for both hot and cold atomic systems. Here we demonstrate an all-optical magnetometer where the optical cell for Faraday rotation spectroscopy is augmented with a low finesse cavity. Unlike in previous experiments, where specifically designed multipass cells had been employed, our scheme allows to use conventional, spherical vapour cells. Spherical shaped cells have the advantage that they can be effectively coated inside with a spin relaxation suppressing layer providing long spin coherence times without addition of a buffer gas. Cavity enhancement shows in an increase in optical polarization rotation and sensitivity compared to single-pass configurations. PMID:26481853

[Chapter 5. Health and Big Data: the emergence of an infrastructure law in the digital space].

PubMed

Devillier, Nathalie

2017-10-27

In the field of health, IoT devices, mobile apps, and online communities generate an enormous amount of data. However, health data benefit from a precise legal definition and protection as sensitive data, whereas well-being data have no specific legal regime. Since those data may contribute to identify individuals' health status, there are potential breaches to confidentiality and privacy. Recent European cases (ECHR and ECJ) reaffirms citizens' fundamental rights to privacy and family life, and to an effective remedy. Such decisions contribute to mitigate the misuse of big data broadly speacking, inclunding in the health sector.

Determination of tylosin residues in different animal tissues by high performance liquid chromatography.

PubMed

Prats, C; Francesch, R; Arboix, M; Pérez, B

2002-01-05

A HPLC method to determine and quantify tylosin residues from calves, pigs and poultry is reported. This procedure permitted tylosin to be separated from muscle, liver, kidney and fat after a simple extraction with chloroform or ethyl acetate under basic conditions. The analytical methodology showed a high specificity and sensitivity and an adequate precision and accuracy with a limit of quantification of 50 microg/kg. Eight calves were administered 20 mg/kg/day of tylosin for 5 days and slaughtered at 7 and 14 days post-administration. Results showed that at the 14th day tylosin levels were lower than the MRL in all target tissues.

[Enzymatic analysis of the quality of foodstuffs].

PubMed

Kolesnov, A Iu

1997-01-01

Enzymatic analysis is an independent and separate branch of enzymology and analytical chemistry. It has become one of the most important methodologies used in food analysis. Enzymatic analysis allows the quick, reliable determination of many food ingredients. Often these contents cannot be determined by conventional methods, or if methods are available, they are determined only with limited accuracy. Today, methods of enzymatic analysis are being increasingly used in the investigation of foodstuffs. Enzymatic measurement techniques are used in industry, scientific and food inspection laboratories for quality analysis. This article describes the requirements of an optimal analytical method: specificity, sample preparation, assay performance, precision, sensitivity, time requirement, analysis cost, safety of reagents.

Field design factors affecting the precision of ryegrass forage yield estimation

USDA-ARS?s Scientific Manuscript database

Field-based agronomic and genetic research relies heavily on the data generated from field evaluations. Therefore, it is imperative to optimize the precision and accuracy of yield estimates in cultivar evaluation trials to make reliable selections. Experimental error in yield trials is sensitive to ...

Sensitivity in error detection of patient specific QA tools for IMRT plans

NASA Astrophysics Data System (ADS)

Lat, S. Z.; Suriyapee, S.; Sanghangthum, T.

2016-03-01

The high complexity of dose calculation in treatment planning and accurate delivery of IMRT plan need high precision of verification method. The purpose of this study is to investigate error detection capability of patient specific QA tools for IMRT plans. The two H&N and two prostate IMRT plans with MapCHECK2 and portal dosimetry QA tools were studied. Measurements were undertaken for original and modified plans with errors introduced. The intentional errors composed of prescribed dose (±2 to ±6%) and position shifting in X-axis and Y-axis (±1 to ±5mm). After measurement, gamma pass between original and modified plans were compared. The average gamma pass for original H&N and prostate plans were 98.3% and 100% for MapCHECK2 and 95.9% and 99.8% for portal dosimetry, respectively. In H&N plan, MapCHECK2 can detect position shift errors starting from 3mm while portal dosimetry can detect errors started from 2mm. Both devices showed similar sensitivity in detection of position shift error in prostate plan. For H&N plan, MapCHECK2 can detect dose errors starting at ±4%, whereas portal dosimetry can detect from ±2%. For prostate plan, both devices can identify dose errors starting from ±4%. Sensitivity of error detection depends on type of errors and plan complexity.

High-Precision Measurement of 13C/12C Isotopic Ratio Using Gas Chromatography-Combustion-Cavity Ring-Down Spectroscopy

NASA Astrophysics Data System (ADS)

Saad, N.; Kuramoto, D. S.; Haase, C.; Crosson, E.; Tan, S.; Zare, R. N.

2009-12-01

Light stable isotope analysis, and in particular, compound specific isotopic analysis (CSIA), is a valuable tool to elucidate pathways and provide a better insight into biological, ecological, and geological systems. We present here the results of compound-specific isotopic carbon analysis of short chain hydrocarbons using the world’s first combination of gas chromatography, combustion interface, and cavity ring-down spectroscopy (GC-C-CRDS). Cavity ring-down spectroscopy (CRDS) is a highly sensitive optical spectroscopy, one application of which is to measure the stable isotopic ratios in small molecules. Because it uses a highly reflective optical cavity with many kilometers effective path length, CRDS provides some of the most sensitive and precise optical absorption measurements. Most optical spectroscopy isotopic analysis measures the quantities of each isotopologue independently using their distinct ro-vibrational spectra. The most common isotopes measured with optical spectroscopy are 13C and 12C in carbon dioxide. However, the isotopes of hydrogen, oxygen, and sulfur have also been measured. Unlike isotope ratio mass spectrometry (IRMS), optical spectroscopy can distinguish among isobars, which have essentially identical m/z ratios. The combination of chemical separation, chemical conversion, and CRDS makes a nearly universal tool for isotopic analysis of mixtures. In addition, CRDS can tolerate a variety of compounds mixed with the target. For example, CRDS can measure carbon dioxide and its isotopic 13C/12C ratio in the presence of oxygen. Using the novel GC-C-CRDS system, we injected a 75-microliter mixture of approximately equal quantities of methane, ethane, and propane into a gas chromatograph using helium as carrier gas. The methane, ethane, and propane were separated in time by 100 to 200 seconds after the chromatograph. Oxygen gas was added, and the hydrocarbons were combusted in a catalytic combustor with platinum and nickel, held at 1150oC. The combusted products were combined with dry nitrogen gas to provide sufficient gas flow for the CRDS analyzer, which measured the 13C/12C isotopic ratio of the separated methane, ethane, and propane, obtaining a precision of 0.95 permil or better. The calibration accuracy was within 3 permil of the values determined using IRMS. The current CRDS-based system is less expensive, does not require highly trained personnel to operate, and is portable, compared with IRMS. We anticipate that advances in spectroscopic analysis will improve the precision and accuracy of the CRDS isotopic measurement, making it comparable with IRMS.

Estimating true human and animal host source contribution in quantitative microbial source tracking using the Monte Carlo method.

PubMed

Wang, Dan; Silkie, Sarah S; Nelson, Kara L; Wuertz, Stefan

2010-09-01

Cultivation- and library-independent, quantitative PCR-based methods have become the method of choice in microbial source tracking. However, these qPCR assays are not 100% specific and sensitive for the target sequence in their respective hosts' genome. The factors that can lead to false positive and false negative information in qPCR results are well defined. It is highly desirable to have a way of removing such false information to estimate the true concentration of host-specific genetic markers and help guide the interpretation of environmental monitoring studies. Here we propose a statistical model based on the Law of Total Probability to predict the true concentration of these markers. The distributions of the probabilities of obtaining false information are estimated from representative fecal samples of known origin. Measurement error is derived from the sample precision error of replicated qPCR reactions. Then, the Monte Carlo method is applied to sample from these distributions of probabilities and measurement error. The set of equations given by the Law of Total Probability allows one to calculate the distribution of true concentrations, from which their expected value, confidence interval and other statistical characteristics can be easily evaluated. The output distributions of predicted true concentrations can then be used as input to watershed-wide total maximum daily load determinations, quantitative microbial risk assessment and other environmental models. This model was validated by both statistical simulations and real world samples. It was able to correct the intrinsic false information associated with qPCR assays and output the distribution of true concentrations of Bacteroidales for each animal host group. Model performance was strongly affected by the precision error. It could perform reliably and precisely when the standard deviation of the precision error was small (≤ 0.1). Further improvement on the precision of sample processing and qPCR reaction would greatly improve the performance of the model. This methodology, built upon Bacteroidales assays, is readily transferable to any other microbial source indicator where a universal assay for fecal sources of that indicator exists. Copyright © 2010 Elsevier Ltd. All rights reserved.

Towards a Uniform Metrological Assessment of Grating-Based Optical Fiber Sensors: From Refractometers to Biosensors

PubMed Central

Chiavaioli, Francesco; Gouveia, Carlos A. J.; Jorge, Pedro A. S.; Baldini, Francesco

2017-01-01

A metrological assessment of grating-based optical fiber sensors is proposed with the aim of providing an objective evaluation of the performance of this sensor category. Attention was focused on the most common parameters, used to describe the performance of both optical refractometers and biosensors, which encompassed sensitivity, with a distinction between volume or bulk sensitivity and surface sensitivity, resolution, response time, limit of detection, specificity (or selectivity), reusability (or regenerability) and some other parameters of generic interest, such as measurement uncertainty, accuracy, precision, stability, drift, repeatability and reproducibility. Clearly, the concepts discussed here can also be applied to any resonance-based sensor, thus providing the basis for an easier and direct performance comparison of a great number of sensors published in the literature up to now. In addition, common mistakes present in the literature made for the evaluation of sensor performance are highlighted, and lastly a uniform performance assessment is discussed and provided. Finally, some design strategies will be proposed to develop a grating-based optical fiber sensing scheme with improved performance. PMID:28635665

Clinical records anonymisation and text extraction (CRATE): an open-source software system.

PubMed

Cardinal, Rudolf N

2017-04-26

Electronic medical records contain information of value for research, but contain identifiable and often highly sensitive confidential information. Patient-identifiable information cannot in general be shared outside clinical care teams without explicit consent, but anonymisation/de-identification allows research uses of clinical data without explicit consent. This article presents CRATE (Clinical Records Anonymisation and Text Extraction), an open-source software system with separable functions: (1) it anonymises or de-identifies arbitrary relational databases, with sensitivity and precision similar to previous comparable systems; (2) it uses public secure cryptographic methods to map patient identifiers to research identifiers (pseudonyms); (3) it connects relational databases to external tools for natural language processing; (4) it provides a web front end for research and administrative functions; and (5) it supports a specific model through which patients may consent to be contacted about research. Creation and management of a research database from sensitive clinical records with secure pseudonym generation, full-text indexing, and a consent-to-contact process is possible and practical using entirely free and open-source software.

Towards a Uniform Metrological Assessment of Grating-Based Optical Fiber Sensors: From Refractometers to Biosensors.

PubMed

Chiavaioli, Francesco; Gouveia, Carlos A J; Jorge, Pedro A S; Baldini, Francesco

2017-06-21

A metrological assessment of grating-based optical fiber sensors is proposed with the aim of providing an objective evaluation of the performance of this sensor category. Attention was focused on the most common parameters, used to describe the performance of both optical refractometers and biosensors, which encompassed sensitivity, with a distinction between volume or bulk sensitivity and surface sensitivity, resolution, response time, limit of detection, specificity (or selectivity), reusability (or regenerability) and some other parameters of generic interest, such as measurement uncertainty, accuracy, precision, stability, drift, repeatability and reproducibility. Clearly, the concepts discussed here can also be applied to any resonance-based sensor, thus providing the basis for an easier and direct performance comparison of a great number of sensors published in the literature up to now. In addition, common mistakes present in the literature made for the evaluation of sensor performance are highlighted, and lastly a uniform performance assessment is discussed and provided. Finally, some design strategies will be proposed to develop a grating-based optical fiber sensing scheme with improved performance.

Performance of Stratified and Subgrouped Disproportionality Analyses in Spontaneous Databases.

PubMed

Seabroke, Suzie; Candore, Gianmario; Juhlin, Kristina; Quarcoo, Naashika; Wisniewski, Antoni; Arani, Ramin; Painter, Jeffery; Tregunno, Philip; Norén, G Niklas; Slattery, Jim

2016-04-01

Disproportionality analyses are used in many organisations to identify adverse drug reactions (ADRs) from spontaneous report data. Reporting patterns vary over time, with patient demographics, and between different geographical regions, and therefore subgroup analyses or adjustment by stratification may be beneficial. The objective of this study was to evaluate the performance of subgroup and stratified disproportionality analyses for a number of key covariates within spontaneous report databases of differing sizes and characteristics. Using a reference set of established ADRs, signal detection performance (sensitivity and precision) was compared for stratified, subgroup and crude (unadjusted) analyses within five spontaneous report databases (two company, one national and two international databases). Analyses were repeated for a range of covariates: age, sex, country/region of origin, calendar time period, event seriousness, vaccine/non-vaccine, reporter qualification and report source. Subgroup analyses consistently performed better than stratified analyses in all databases. Subgroup analyses also showed benefits in both sensitivity and precision over crude analyses for the larger international databases, whilst for the smaller databases a gain in precision tended to result in some loss of sensitivity. Additionally, stratified analyses did not increase sensitivity or precision beyond that associated with analytical artefacts of the analysis. The most promising subgroup covariates were age and region/country of origin, although this varied between databases. Subgroup analyses perform better than stratified analyses and should be considered over the latter in routine first-pass signal detection. Subgroup analyses are also clearly beneficial over crude analyses for larger databases, but further validation is required for smaller databases.

Development of models for classification of action between heat-clearing herbs and blood-activating stasis-resolving herbs based on theory of traditional Chinese medicine.

PubMed

Chen, Zhao; Cao, Yanfeng; He, Shuaibing; Qiao, Yanjiang

2018-01-01

Action (" gongxiao " in Chinese) of traditional Chinese medicine (TCM) is the high recapitulation for therapeutic and health-preserving effects under the guidance of TCM theory. TCM-defined herbal properties (" yaoxing " in Chinese) had been used in this research. TCM herbal property (TCM-HP) is the high generalization and summary for actions, both of which come from long-term effective clinical practice in two thousands of years in China. However, the specific relationship between TCM-HP and action of TCM is complex and unclear from a scientific perspective. The research about this is conducive to expound the connotation of TCM-HP theory and is of important significance for the development of the TCM-HP theory. One hundred and thirty-three herbs including 88 heat-clearing herbs (HCHs) and 45 blood-activating stasis-resolving herbs (BAHRHs) were collected from reputable TCM literatures, and their corresponding TCM-HPs/actions information were collected from Chinese pharmacopoeia (2015 edition). The Kennard-Stone (K-S) algorithm was used to split 133 herbs into 100 calibration samples and 33 validation samples. Then, machine learning methods including supported vector machine (SVM), k-nearest neighbor (kNN) and deep learning methods including deep belief network (DBN), convolutional neutral network (CNN) were adopted to develop action classification models based on TCM-HP theory, respectively. In order to ensure robustness, these four classification methods were evaluated by using the method of tenfold cross validation and 20 external validation samples for prediction. As results, 72.7-100% of 33 validation samples including 17 HCHs and 16 BASRHs were correctly predicted by these four types of methods. Both of the DBN and CNN methods gave out the best results and their sensitivity, specificity, precision, accuracy were all 100.00%. Especially, the predicted results of external validation set showed that the performance of deep learning methods (DBN, CNN) were better than traditional machine learning methods (kNN, SVM) in terms of their sensitivity, specificity, precision, accuracy. Moreover, the distribution patterns of TCM-HPs of HCHs and BASRHs were also analyzed to detect the featured TCM-HPs of these two types of herbs. The result showed that the featured TCM-HPs of HCHs were cold, bitter, liver and stomach meridians entered, while those of BASRHs were warm, bitter and pungent, liver meridian entered. The performance on validation set and external validation set of deep learning methods (DBN, CNN) were better than machine learning models (kNN, SVM) in sensitivity, specificity, precision, accuracy when predicting the actions of heat-clearing and blood-activating stasis-resolving based on TCM-HP theory. The deep learning classification methods owned better generalization ability and accuracy when predicting the actions of heat-clearing and blood-activating stasis-resolving based on TCM-HP theory. Besides, the methods of deep learning would help us to improve our understanding about the relationship between herbal property and action, as well as to enrich and develop the theory of TCM-HP scientifically.

Tactile perception in blind Braille readers: a psychophysical study of acuity and hyperacuity using gratings and dot patterns.

PubMed

Grant, A C; Thiagarajah, M C; Sathian, K

2000-02-01

It is not clear whether the blind are generally superior to the sighted on measures of tactile sensitivity or whether they excel only on certain tests owing to the specifics of their tactile experience. We compared the discrimination performance of blind Braille readers and age-matched sighted subjects on three tactile tasks using precisely specified stimuli. Initially, the blind significantly outperformed the sighted at a hyperacuity task using Braille-like dot patterns, although, with practice, both groups performed equally well. On two other tasks, hyperacute discrimination of gratings that differed in ridge width and spatial-acuity-dependent discrimination of grating orientation, the performance of the blind did not differ significantly from that of sighted subjects. These results probably reflect the specificity of perceptual learning due to Braille-reading experience.

High performance liquid chromatography: Tandem mass spectrometric determination of cisplatin levels in different visceral pleura layers of rats.

PubMed

Xia, Hui; Zhang, Wen; Li, Yingjie; Yu, Changhai

2015-05-01

The aim of the present study was to investigate the concentration of cisplatin in different layers of the visceral pleura in rats, following drug administration. In this study, a sensitive and specific liquid chromatography method coupled with electrospray ionization-tandem mass spectrometry was established to investigate the disposition of cisplatin in different layers of the visceral pleura in rats. Methodological data, including specificity, linearity, accuracy, recovery, precision and lower limits of quantification, confirmed that this novel method may be used to efficiently quantify the cisplatin concentrations in visceral pleura of rats following administration of the drug. Furthermore, the results demonstrated that the desired drug concentration was not achieved in the outer or inner elastic layers of the visceral pleura following injection with cisplatin through various administration methods.

Ultrasensitive Detection of Single-Walled Carbon Nanotubes Using Surface Plasmon Resonance.

PubMed

Jang, Daeho; Na, Wonhwi; Kang, Minwook; Kim, Namjoon; Shin, Sehyun

2016-01-05

Because single-walled carbon nanotubes (SWNTs) are known to be a potentially dangerous material, inducing cancers and other diseases, any possible leakage of SWNTs through an aquatic medium such as drinking water will result in a major public threat. To solve this problem, for the present study, a highly sensitive, quantitative detection method of SWNTs in an aqueous solution was developed using surface plasmon resonance (SPR) spectroscopy. For a highly sensitive and specific detection, a strong affinity conjugation with biotin-streptavidin was adopted on an SPR sensing mechanism. During the pretreatment process, the SWNT surface was functionalized and hydrophilized using a thymine-chain based biotinylated single-strand DNA linker (B-ssDNA) and bovine serum albumin (BSA). The pretreated SWNTs were captured on a sensing film, the surface of which was immobilized with streptavidin on biotinylated gold film. The captured SWNTs were measured in real-time using SPR spectroscopy. Specific binding with SWNTs was verified through several validation experiments. The present method using an SPR sensor is capable of detecting SWNTs of as low as 100 fg/mL, which is the lowest level reported thus far for carbon-nanotube detection. In addition, the SPR sensor showed a linear characteristic within the range of 100 pg/mL to 200 ng/mL. These findings imply that the present SPR sensing method can detect an extremely low level of SWNTs in an aquatic environment with high sensitivity and high specificity, and thus any potential leakage of SWNTs into an aquatic environment can be precisely monitored within a couple of hours.

Retinoid quantification by HPLC/MS(n)

NASA Technical Reports Server (NTRS)

McCaffery, Peter; Evans, James; Koul, Omanand; Volpert, Amy; Reid, Kevin; Ullman, M. David

2002-01-01

Retinoic acid (RA) mediates most of the biological effects of vitamin A that are essential for vertebrate survival. It acts through binding to receptors that belong to the nuclear receptor transcription factor superfamily (Mangelsdorf et al. 1994). It is also a highly potent vertebrate teratogen. To determine the function and effects of endogenous and exogenous RA, it is important to have a highly specific, sensitive, accurate, and precise analytical procedure. Current analyses of RA and other retinoids are labor intensive, of poor sensitivity, have limited specificity, or require compatibility with RA reporter cell lines (Chen et al. 1995. BIOCHEM: Pharmacol. 50: 1257-1264; Creech Kraft et al. 1994. BIOCHEM: J. 301: 111-119; Lanvers et al. 1996. J. Chromatogr. B Biomed. Appl. 685: 233-240; Maden et al. 1998. DEVELOPMENT: 125: 4133-4144; Wagner et al. 1992. DEVELOPMENT: 116: 55-66). This paper describes an HPLC/mass spectrometry/mass spectrometry product ion scan (HPLC/MS(n)) procedure for the analysis of retinoids that employs atmospheric pressure chemical ionization MS. The retinoids are separated by normal-phase column chromatography with a linear hexane-isopropanol-dioxane gradient. Each retinoid is detected by a unique series of MS(n) functions set at optimal collision-induced dissociation energy (30% to 32%) for all MS(n) steps. The scan events are divided into three segments, based on HPLC elution order, to maximize the mass spectrometer duty cycle. The all-trans, 9-cis, and 13-cis RA isomers are separated, if desired, by an isocratic hexane-dioxane-isopropanol mobile phase. This paper describes an HPLC/MS(n) procedure possessing high sensitivity and specificity for retinoids.

Pre- and postoperative evaluation of patients with lumbosacral disc herniation by neurophysiological and clinical assessment.

PubMed

Wojtysiak, Magdalena; Huber, Juliusz; Wiertel-Krawczuk, Agnieszka; Szymankiewicz-Szukała, Agnieszka; Moskal, Jakub; Janicki, Jacek

2014-10-01

The application of complex neurophysiological examination including motor evoked potentials (MEP) for pre- and postoperative evaluation of patients experiencing acute sciatica. The assessment of sensitivity and specificity of needle electromyography, MEP, and H-reflex examinations. The comparative analysis of preoperative and postoperative neurophysiological examination. In spite of the fact that complex neurophysiological diagnostic tools seem to be important for interpretation of incompatible results of neuroimaging and clinical examination, especially in the patients qualified for surgical treatment, their application has never been completely analyzed and documented. Pre- and postoperative electromyography, electroneurography, F-waves, H-reflex, and MEP examination were performed in 23 patients with confirmed disc-root conflict at lumbosacral spine. Clinical evaluation included examination of sensory perception for L5-S1 dermatomes, muscles strength with Lovett's scale, deep tendon reflexes, pain intensity with visual analogue scale, and straight leg raising test. Sensitivity of electromyography at rest and MEP examination for evaluation of L5-S1 roots injury was 22% to 63% and 31% to 56% whereas specificity was 71% to 83% and 57% to 86%, respectively. H-reflex sensitivity and specificity for evaluation of S1 root injury were 56% and 67%, respectively. A significant improvement of root latency parameter in postoperative MEP studies as compared with preoperative was recorded for L5 (P = 0.039) and S1 root's levels (P = 0.05). The analysis of the results from neurophysiological tests together with neuroimaging and clinical examination allow for a precise preoperative indication of the lumbosacral roots injury and accurate postoperative evaluation of patients experiencing sciatica. 3.

Magnetomotive Molecular Nanoprobes

PubMed Central

John, Renu; Boppart, Stephen A.

2012-01-01

Tremendous developments in the field of biomedical imaging in the past two decades have resulted in the transformation of anatomical imaging to molecular-specific imaging. The main approaches towards imaging at a molecular level are the development of high resolution imaging modalities with high penetration depths and increased sensitivity, and the development of molecular probes with high specificity. The development of novel molecular contrast agents and their success in molecular optical imaging modalities have lead to the emergence of molecular optical imaging as a more versatile and capable technique for providing morphological, spatial, and functional information at the molecular level with high sensitivity and precision, compared to other imaging modalities. In this review, we discuss a new class of dynamic contrast agents called magnetomotive molecular nanoprobes for molecular-specific imaging. Magnetomotive agents are superparamagnetic nanoparticles, typically iron-oxide, that are physically displaced by the application of a small modulating external magnetic field. Dynamic phase-sensitive position measurements are performed using any high resolution imaging modality, including optical coherence tomography (OCT), ultrasonography, or magnetic resonance imaging (MRI). The dynamics of the magnetomotive agents can be used to extract the biomechanical tissue properties in which the nanoparticles are bound, and the agents can be used to deliver therapy via magnetomotive displacements to modulate or disrupt cell function, or hyperthermia to kill cells. These agents can be targeted via conjugation to antibodies, and in vivo targeted imaging has been shown in a carcinogen-induced rat mammary tumor model. The iron-oxide nanoparticles also exhibit negative T2 contrast in MRI, and modulations can produce ultrasound imaging contrast for multimodal imaging applications. PMID:21517766

Sensitivity and specificity of the 'knee-up test' for estimation of the American Spinal Injury Association Impairment Scale in patients with acute motor incomplete cervical spinal cord injury.

PubMed

Yugué, Itaru; Okada, Seiji; Maeda, Takeshi; Ueta, Takayoshi; Shiba, Keiichiro

2018-04-01

A retrospective study. Precise classification of the neurological state of patients with acute cervical spinal cord injury (CSCI) can be challenging. This study proposed a useful and simple clinical method to help classify patients with incomplete CSCI. Spinal Injuries Centre, Japan. The sensitivity and specificity of the 'knee-up test' were evaluated in patients with acute CSCI classified as American Spinal Injury Association Impairment Scale (AIS) C or D. The result is positive if the patient can lift the knee in one or both legs to an upright position, whereas the result is negative if the patient is unable to lift the knee in either leg to an upright position. The AIS of these patients was classified according to a strict computerised algorithm designed by Walden et al., and the knee-up test was tested by non-expert examiners. Among the 200 patients, 95 and 105 were classified as AIS C and AIS D, respectively. Overall, 126 and 74 patients demonstrated positive and negative results, respectively, when evaluated using the knee-up test. A total of 104 patients with positive results and 73 patients with negative results were classified as AIS D and AIS C, respectively. The sensitivity, specificity, positive predictive and negative predictive values of this test for all patients were 99.1, 76.8, 82.5 and 98.7, respectively. The knee-up test may allow easy and highly accurate estimation, without the need for special skills, of AIS classification for patients with incomplete CSCI.

Impact of different study populations on reader behavior and performance metrics: initial results

NASA Astrophysics Data System (ADS)

Gallas, Brandon D.; Pisano, Etta; Cole, Elodia; Myers, Kyle

2017-03-01

The FDA recently completed a study on design methodologies surrounding the Validation of Imaging Premarket Evaluation and Regulation called VIPER. VIPER consisted of five large reader sub-studies to compare the impact of different study populations on reader behavior as seen by sensitivity, specificity, and AUC, the area under the ROC curve (receiver operating characteristic curve). The study investigated different prevalence levels and two kinds of sampling of non-cancer patients: a screening population and a challenge population. The VIPER study compared full-field digital mammography (FFDM) to screenfilm mammography (SFM) for women with heterogeneously dense or extremely dense breasts. All cases and corresponding images were sampled from Digital Mammographic Imaging Screening Trial (DMIST) archives. There were 20 readers (American Board Certified radiologists) for each sub-study, and instead of every reader reading every case (fully-crossed study), readers and cases were split into groups to reduce reader workload and the total number of observations (split-plot study). For data collection, readers first decided whether or not they would recall a patient. Following that decision, they provided an ROC score for how close or far that patient was from the recall decision threshold. Performance results for FFDM show that as prevalence increases to 50%, there is a moderate increase in sensitivity and decrease in specificity, whereas AUC is mainly flat. Regarding precision, the statistical efficiency (ratio of variances) of sensitivity and specificity relative to AUC are 0.66 at best and decrease with prevalence. Analyses comparing modalities and the study populations (screening vs. challenge) are still ongoing.

Impact of Different Study Populations on Reader Behavior and Performance Metrics: Initial Results

PubMed Central

Gallas, Brandon D.; Pisano, Etta; Cole, Elodia; Myers, Kyle

2017-01-01

The FDA recently completed a study on design methodologies surrounding the Validation of Imaging Premarket Evaluation and Regulation called VIPER. VIPER consisted of five large reader sub-studies to compare the impact of different study populations on reader behavior as seen by sensitivity, specificity, and AUC, the area under the ROC curve (receiver operating characteristic curve). The study investigated different prevalence levels and two kinds of sampling of non-cancer patients: a screening population and a challenge population. The VIPER study compared full-field digital mammography (FFDM) to screen-film mammography (SFM) for women with heterogeneously dense or extremely dense breasts. All cases and corresponding images were sampled from Digital Mammographic Imaging Screening Trial (DMIST) archives. There were 20 readers (American Board Certified radiologists) for each sub-study, and instead of every reader reading every case (fully-crossed study), readers and cases were split into groups to reduce reader workload and the total number of observations (split-plot study). For data collection, readers first decided whether or not they would recall a patient. Following that decision, they provided an ROC score for how close or far that patient was from the recall decision threshold. Performance results for FFDM show that as prevalence increases to 50%, there is a moderate increase in sensitivity and decrease in specificity, whereas AUC is mainly flat. Regarding precision, the statistical efficiency (ratio of variances) of sensitivity and specificity relative to AUC are 0.66 at best and decrease with prevalence. Analyses comparing modalities and the study populations (screening vs. challenge) are still ongoing. PMID:28845078

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.

A Guide for Collecting Seismic, Acoustic, and Magnetic Data for Multiple Uses

DTIC Science & Technology

1975-01-01

time, simul- (- taneously for the analog technique or sequentially for the digital tech- nique. Both methods require that precision timing networks be...with a precise voltage proportional to the sensitivity of the magnetometer . Whenever any electronic equip- ment affecting cal.bration has to be replaced...described as precisely as possible, including (but not limited to) the following: a. Name of source b. Continuous or transient c. Distance from geophone

Preparation and coherent manipulation of pure quantum states of a single molecular ion

NASA Astrophysics Data System (ADS)

Chou, Chin-Wen; Kurz, Christoph; Hume, David B.; Plessow, Philipp N.; Leibrandt, David R.; Leibfried, Dietrich

2017-05-01

Laser cooling and trapping of atoms and atomic ions has led to advances including the observation of exotic phases of matter, the development of precision sensors and state-of-the-art atomic clocks. The same level of control in molecules could also lead to important developments such as controlled chemical reactions and sensitive probes of fundamental theories, but the vibrational and rotational degrees of freedom in molecules pose a challenge for controlling their quantum mechanical states. Here we use quantum-logic spectroscopy, which maps quantum information between two ion species, to prepare and non-destructively detect quantum mechanical states in molecular ions. We develop a general technique for optical pumping and preparation of the molecule into a pure initial state. This enables us to observe high-resolution spectra in a single ion (CaH+) and coherent phenomena such as Rabi flopping and Ramsey fringes. The protocol requires a single, far-off-resonant laser that is not specific to the molecule, so many other molecular ions, including polyatomic species, could be treated using the same methods in the same apparatus by changing the molecular source. Combined with the long interrogation times afforded by ion traps, a broad range of molecular ions could be studied with unprecedented control and precision. Our technique thus represents a critical step towards applications such as precision molecular spectroscopy, stringent tests of fundamental physics, quantum computing and precision control of molecular dynamics.

Preparation and coherent manipulation of pure quantum states of a single molecular ion.

PubMed

Chou, Chin-Wen; Kurz, Christoph; Hume, David B; Plessow, Philipp N; Leibrandt, David R; Leibfried, Dietrich

2017-05-10

Laser cooling and trapping of atoms and atomic ions has led to advances including the observation of exotic phases of matter, the development of precision sensors and state-of-the-art atomic clocks. The same level of control in molecules could also lead to important developments such as controlled chemical reactions and sensitive probes of fundamental theories, but the vibrational and rotational degrees of freedom in molecules pose a challenge for controlling their quantum mechanical states. Here we use quantum-logic spectroscopy, which maps quantum information between two ion species, to prepare and non-destructively detect quantum mechanical states in molecular ions. We develop a general technique for optical pumping and preparation of the molecule into a pure initial state. This enables us to observe high-resolution spectra in a single ion (CaH + ) and coherent phenomena such as Rabi flopping and Ramsey fringes. The protocol requires a single, far-off-resonant laser that is not specific to the molecule, so many other molecular ions, including polyatomic species, could be treated using the same methods in the same apparatus by changing the molecular source. Combined with the long interrogation times afforded by ion traps, a broad range of molecular ions could be studied with unprecedented control and precision. Our technique thus represents a critical step towards applications such as precision molecular spectroscopy, stringent tests of fundamental physics, quantum computing and precision control of molecular dynamics.

Near-Infrared Light-Sensitive Polyvinyl Alcohol Hydrogel Photoresist for Spatiotemporal Control of Cell-Instructive 3D Microenvironments.

PubMed

Qin, Xiao-Hua; Wang, Xiaopu; Rottmar, Markus; Nelson, Bradley J; Maniura-Weber, Katharina

2018-03-01

Advanced hydrogel systems that allow precise control of cells and their 3D microenvironments are needed in tissue engineering, disease modeling, and drug screening. Multiphoton lithography (MPL) allows true 3D microfabrication of complex objects, but its biological application requires a cell-compatible hydrogel resist that is sufficiently photosensitive, cell-degradable, and permissive to support 3D cell growth. Here, an extremely photosensitive cell-responsive hydrogel composed of peptide-crosslinked polyvinyl alcohol (PVA) is designed to expand the biological applications of MPL. PVA hydrogels are formed rapidly by ultraviolet light within 1 min in the presence of cells, providing fully synthetic matrices that are instructive for cell-matrix remodeling, multicellular morphogenesis, and protease-mediated cell invasion. By focusing a multiphoton laser into a cell-laden PVA hydrogel, cell-instructive extracellular cues are site-specifically attached to the PVA matrix. Cell invasion is thus precisely guided in 3D with micrometer-scale spatial resolution. This robust hydrogel enables, for the first time, ultrafast MPL of cell-responsive synthetic matrices at writing speeds up to 50 mm s -1 . This approach should enable facile photochemical construction and manipulation of 3D cellular microenvironments with unprecedented flexibility and precision. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temporal precision and the capacity of auditory-verbal short-term memory.

PubMed

Gilbert, Rebecca A; Hitch, Graham J; Hartley, Tom

2017-12-01

The capacity of serially ordered auditory-verbal short-term memory (AVSTM) is sensitive to the timing of the material to be stored, and both temporal processing and AVSTM capacity are implicated in the development of language. We developed a novel "rehearsal-probe" task to investigate the relationship between temporal precision and the capacity to remember serial order. Participants listened to a sub-span sequence of spoken digits and silently rehearsed the items and their timing during an unfilled retention interval. After an unpredictable delay, a tone prompted report of the item being rehearsed at that moment. An initial experiment showed cyclic distributions of item responses over time, with peaks preserving serial order and broad, overlapping tails. The spread of the response distributions increased with additional memory load and correlated negatively with participants' auditory digit spans. A second study replicated the negative correlation and demonstrated its specificity to AVSTM by controlling for differences in visuo-spatial STM and nonverbal IQ. The results are consistent with the idea that a common resource underpins both the temporal precision and capacity of AVSTM. The rehearsal-probe task may provide a valuable tool for investigating links between temporal processing and AVSTM capacity in the context of speech and language abilities.

The beam combiners of Gravity VLTI instrument: concept, development, and performance in laboratory

NASA Astrophysics Data System (ADS)

Jocou, L.; Perraut, K.; Moulin, T.; Magnard, Y.; Labeye, P.; Lapras, V.; Nolot, A.; Perrin, G.; Eisenhauer, F.; Holmes, C.; Amorim, A.; Brandner, W.; Straubmeier, C.

2014-07-01

Gravity is one of the second-generation instruments of the Very Large Telescope Interferometer that operates in the near infrared range and that is designed for precision narrow-angle astrometry and interferometric imaging. With its infrared wavefront sensors, pupil stabilization, fringe tracker, and metrology, the instrument is tailored to provide a high sensitivity, imaging with 4-millisecond resolution, and astrometry with a 10μarcsec precision. It will probe physics close to the event horizon of the Galactic Centre black hole, and allow to study mass accretion and jets in young stellar objects and active galactic nuclei, planet formation in circumstellar discs, or detect and measure the masses of black holes in massive star clusters throughout the Milky Way. As the instrument required an outstanding level of precision and stability, integrated optics has been chosen to collect and combine the four VLTI beams in the K band. A dedicated integrated optics chip glued to a fiber array has been developed. Technology breakthroughs have been mandatory to fulfill all the specifications. This paper is focused on the interferometric beam combination system of Gravity. Once the combiner concept described, the paper details the developments that have been led, the integration and the performance of the assemblies.

Progress on Passive Sensor for Ultra-Precise Measurement of Carbon Dioxide from Space

NASA Technical Reports Server (NTRS)

Heaps, William S.; Kawa, S. Randolph

2002-01-01

Global measurements of atmospheric carbon dioxides (CO2) are needed to resolve significant discrepancies that exist in our understanding of the global carbon budget and, therefore, man's role in global climate change. The science measurement requirements for CO2 are extremely demanding (precision c .3%) No atmospheric chemical species has ever been measured from space with this precision. We are developing a novel application of a Fabry-Perot interferometer to detect spectral absorption of reflected sunlight by CO2 and O2 in the atmosphere. Preliminary design studies indicate that the method will be able to achieve the sensitivity and signal-to-noise required to measure column CO2 at the target specification. We are presently engaged in the construction of a prototype instrument for deployment on an aircraft to test the instrument performance and our ability to retrieve the data in the real atmosphere. In the first 6 months we have assembled a laboratory bench system to begin testing the optical and electronic components. We are also undertaking some measurements of signal and noise levels for actual sunlight reflecting from the ground. We shall present results from some of these ground based studies and discuss their implications for a space based system.

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

PubMed

Sung, Nayoung; Kwak-Kim, Joanne; Koo, H S; Yang, K M

2016-09-01

To investigate hCG-β level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-β levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-β levels and the degree of hCG-β increase from POD 12 to 14 were determined for each pregnancy outcome. POD 12 and 14 hCG-β levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-β levels of POD 12 and 14 and the fold increase of hCG-β levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-β had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-β levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-β levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-β for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-β and fold increase of hCG-β improved predictability of pregnancy outcome as compared with that of POD 12 hCG-β alone. The cutoff values of POD 12 and 14 serum hCG-β levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-β level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-β level ≥31.5 mIU/mL, the cutoff value for fold increase of hCG-β was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-β level and fold increase of hCG-β significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of high-risk pregnancies and precise follow-up of abnormal pregnancies.

Drilling Precise Orifices and Slots

NASA Technical Reports Server (NTRS)

Richards, C. W.; Seidler, J. E.

1983-01-01

Reaction control thrustor injector requires precisely machined orifices and slots. Tooling setup consists of rotary table, numerical control system and torque sensitive drill press. Components used to drill oxidizer orifices. Electric discharge machine drills fuel-feed orifices. Device automates production of identical parts so several are completed in less time than previously.

Active remote sensing.

Treesearch

Hans-Erik Andersen; Stephen E. Reutebuch; Robert J. McGaughey

2006-01-01

The development of remote sensing technologies increases the potential to support more precise, efficient, and ecologically-sensitive approaches to forest resource management. One of the primary requirements of precision forest management is accurate and detailed 3D spatial data relating to the type and condition of forest stands and characteristics of the underlying...

Manufacturing plastic injection optical molds

NASA Astrophysics Data System (ADS)

Bourque, David

2008-08-01

ABCO Tool & Die, Inc. is a mold manufacturer specializing in the manufacturing of plastic injection molds for molded optical parts. The purpose of this presentation is to explain the concepts and procedures required to build a mold that produces precision optical parts. Optical molds can produce a variety of molded parts ranging from safety eyewear to sophisticated military lens parts, which must meet precise optical specifications. The manufacturing of these molds begins with the design engineering of precision optical components. The mold design and the related optical inserts are determined based upon the specific optical criteria and optical surface geometry. The mold manufacturing techniques will be based upon the optical surface geometry requirements and specific details. Manufacturing processes used will be specific to prescribed geometrical surface requirements of the molded part. The combined efforts result in a robust optical mold which can produce molded parts that meet the most precise optical specifications.

Improved phase-ellipse method for in-situ geophone calibration.

USGS Publications Warehouse

Liu, Huaibao P.; Peselnick, L.

1986-01-01

For amplitude and phase response calibration of moving-coil electromagnetic geophones 2 parameters are needed, namely the geophone natural frequency, fo, and the geophone upper resonance frequency fu. The phase-ellipse method is commonly used for the in situ determination of these parameters. For a given signal-to-noise ratio, the precision of the measurement of fo and fu depends on the phase sensitivity, f(delta PHI/delta PHIf). For some commercial geophones (f(delta PHI/delta PHI) at fu can be an order of magnitude less than the sensitivity at fo. Presents an improved phase-ellipse method with increased precision. Compared to measurements made with the existing phase-ellipse methods, the method shows a 6- and 3-fold improvement in the precision, respectively, on measurements of fo and fu on a commercial geophone.-from Authors

87Sr/86Sr as a quantitative geochemical proxy for 14C reservoir age in dynamic, brackish waters: assessing applicability and quantifying uncertainties.

NASA Astrophysics Data System (ADS)

Lougheed, Bryan; van der Lubbe, Jeroen; Davies, Gareth

2016-04-01

Accurate geochronologies are crucial for reconstructing the sensitivity of brackish and estuarine environments to rapidly changing past external impacts. A common geochronological method used for such studies is radiocarbon (14C) dating, but its application in brackish environments is severely limited by an inability to quantify spatiotemporal variations in 14C reservoir age, or R(t), due to dynamic interplay between river runoff and marine water. Additionally, old carbon effects and species-specific behavioural processes also influence 14C ages. Using the world's largest brackish water body (the estuarine Baltic Sea) as a test-bed, combined with a comprehensive approach that objectively excludes both old carbon and species-specific effects, we demonstrate that it is possible to use 87Sr/86Sr ratios to quantify R(t) in ubiquitous mollusc shell material, leading to almost one order of magnitude increase in Baltic Sea 14C geochronological precision over the current state-of-the-art. We propose that this novel proxy method can be developed for other brackish water bodies worldwide, thereby improving geochronological control in these climate sensitive, near-coastal environments.

Classification of lung cancer patients and controls by chromatography of modified nucleosides in serum

USGS Publications Warehouse

McEntire, John E.; Kuo, Kenneth C.; Smith, Mark E.; Stalling, David L.; Richens, Jack W.; Zumwalt, Robert W.; Gehrke, Charles W.; Papermaster, Ben W.

1989-01-01

A wide spectrum of modified nucleosides has been quantified by high-performance liquid chromatography in serum of 49 male lung cancer patients, 35 patients with other cancers, and 48 patients hospitalized for nonneoplastic diseases. Data for 29 modified nucleoside peaks were normalized to an internal standard and analyzed by discriminant analysis and stepwise discriminant analysis. A model based on peaks selected by a stepwise discriminant procedure correctly classified 79% of the cancer and 75% of the noncancer subjects. It also demonstrated 84% sensitivity and 79% specificity when comparing lung cancer to noncancer subjects, and 80% sensitivity and 55% specificity in comparing lung cancer to other cancers. The nucleoside peaks having the greatest influence on the models varied dependent on the subgroups compared, confirming the importance of quantifying a wide array of nucleosides. These data support and expand previous studies which reported the utility of measuring modified nucleoside levels in serum and show that precise measurement of an array of 29 modified nucleosides in serum by high-performance liquid chromatography with UV scanning with subsequent data modeling may provide a clinically useful approach to patient classification in diagnosis and subsequent therapeutic monitoring.

Comparison of two immunoradiometric assays for serum thyrotropin

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

Scheinin, B.; Drew, H.; La France, N.

1985-05-01

An ultra-sensitive TSH assay capable of detecting subnormal TSH levels would be useful in confirming suppressed pituitary function as seen in hyperthyroidism. Two sensitive immunoradiometric TSH assays (IRMA's) were studied to determine how well they distinguished thyrotoxic patients from normal subjects. Serono Diagnostics' method employs three monoclonal antibodies specific for different regions of the TSH molecule with a minimum detectable dose (MDD) limit of 0.1 ..mu..IU/ml. Precision studies using a low TSH control in the 1.8 ..mu..IU/ml range gave CV's of 15.0%. Boots-Celltech Diagnostics method is a two site IRMA using two monoclonal antibodies. The MDD limit is 0.05 ..mu..IU/mlmore » with precision CV's of 29.3% at a TSH control range of 0.62 ..mu..IU/ml. In 24 chemically thyrotoxic patients, the mean serum TSH concentration was significantly lower than in the normal control subjects: for Serono, 0.19 ..mu..IU/ml vs. 2.34 ..mu..IU/ml and for Boots Celltech, 0.18 IU/ml vs 2.06 ..mu..IU/ml. The range of TSH was 0 to 0.5 ..mu..IU/ml in thyrotoxic patients using Serono with the exception of one patient having a TSH value of 0.8 ..mu..IU/ml. The normal range was 0.6 to 6.0 ..mu..IU/ml. For Boots Celltech the thyrotoxic range was 0 to 0.2 ..mu..IU/ml with that same thyrotoxic patient giving a TSH value of 0.7 ..mu..IU/ml with a normal range of 0.6 to 5.0 IU/ml. Serum TSH measurements using both procedures are highly sensitive for distinguishing thyrotoxic patients from normal subjects and are useful to confirm suppressed pituitary function.« less

Simultaneous determination of TPN729 and its five metabolites in human plasma and urine by liquid chromatography coupled to tandem mass spectrometry.

PubMed

Liu, Yang; Shao, Shuguang; Song, Hanlin; Yao, Xueting; Liu, Jie; Liu, Hongzhong; Song, Ling; Jiang, Ji; Liu, Dongyang; Hu, Pei

2018-03-20

A specific and sensitive method was firstly developed using high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify TPN729 and its metabolites (TPN729-D1, TPN729-D2, TPN729M15-3 and TPN729M3) in human plasma and (TPN729-D1, TPN729-D2, TPN729M15-3 and TPN729M14) in human urine. Protein precipitation and direct dilution were used to extract TPN729 and its metabolites from plasma and urine, respectively. Ionization of TPN729, TPN729-D1, TPN729-D2, TPN729M15-3, TPN729M3, TPN729M14 and sildenafil (internal standard, IS) was performed using an electrospray ionization (ESI) source in positive mode and detection was carried out with multiple reaction monitoring (MRM) mode. This assay method for TPN729 and its five metabolites has been fully validated in terms of sensitivity, linearity, lower limit of quantification (LLOQ), precision, accuracy, stability, matrix effect and recovery. The LLOQ of TPN729/TPN729-D1/TPN729-D2/TPN729M15-3/TPN729M3 in human plasma and TPN729/TPN729-D1/TPN729-D2/TPN729M15-3/TPN729M14 in human urine were 0.200/0.500/2.00/0.500/1.00 ng/mL and 4.00/2.50/10.0/2.50/1.00 ng/mL, respectively. Inter- and intra-batch precision of TPN729 and its metabolites were less than 15% and the accuracy was within ±15% for both plasma and urine. The extraction recoveries of all analytes at three concentration levels were consistent. In conclusion, the validation results showed that this method was robust, specific, and sensitive and it can successfully fulfill the requirement of clinical pharmacokinetic study of TPN729 in Chinese healthy subjects. Copyright © 2018 Elsevier B.V. All rights reserved.

A sensitive and rapid assay for 4-aminophenol in paracetamol drug and tablet formulation, by flow injection analysis with spectrophotometric detection.

PubMed

Bloomfield, M S

2002-12-06

4-Aminophenol (4AP) is the primary degradation product of paracetamol which is limited at a low level (50 ppm or 0.005% w/w) in the drug substance by the European, United States, British and German Pharmacopoeias, employing a manual colourimetric limit test. The 4AP limit is widened to 1000 ppm or 0.1% w/w for the tablet product monographs, which quote the use of a less sensitive automated HPLC method. The lower drug substance specification limit is applied to our products, (50 ppm, equivalent to 25 mug 4AP in a tablet containing 500-mg paracetamol) and the pharmacopoeial HPLC assay was not suitable at this low level due to matrix interference. For routine analysis a rapid, automated assay was required. This paper presents a highly sensitive, precise and automated method employing the technique of Flow Injection (FI) analysis to quantitatively assay low levels of this degradant. A solution of the drug substance, or an extract of the tablets, containing 4AP and paracetamol is injected into a solvent carrier stream and merged on-line with alkaline sodium nitroprusside reagent, to form a specific blue derivative which is detected spectrophotometrically at 710 nm. Standard HPLC equipment is used throughout. The procedure is fully quantitative and has been optimised for sensitivity and robustness using a multivariate experimental design (multi-level 'Central Composite' response surface) model. The method has been fully validated and is linear down to 0.01 mug ml(-1). The approach should be applicable to a range of paracetamol products.

A parts-per-billion measurement of the antiproton magnetic moment

NASA Astrophysics Data System (ADS)

Smorra, C.; Sellner, S.; Borchert, M. J.; Harrington, J. A.; Higuchi, T.; Nagahama, H.; Tanaka, T.; Mooser, A.; Schneider, G.; Bohman, M.; Blaum, K.; Matsuda, Y.; Ospelkaus, C.; Quint, W.; Walz, J.; Yamazaki, Y.; Ulmer, S.

2017-10-01

Precise comparisons of the fundamental properties of matter-antimatter conjugates provide sensitive tests of charge-parity-time (CPT) invariance, which is an important symmetry that rests on basic assumptions of the standard model of particle physics. Experiments on mesons, leptons and baryons have compared different properties of matter-antimatter conjugates with fractional uncertainties at the parts-per-billion level or better. One specific quantity, however, has so far only been known to a fractional uncertainty at the parts-per-million level: the magnetic moment of the antiproton, . The extraordinary difficulty in measuring with high precision is caused by its intrinsic smallness; for example, it is 660 times smaller than the magnetic moment of the positron. Here we report a high-precision measurement of in units of the nuclear magneton μN with a fractional precision of 1.5 parts per billion (68% confidence level). We use a two-particle spectroscopy method in an advanced cryogenic multi-Penning trap system. Our result  = -2.7928473441(42)μN (where the number in parentheses represents the 68% confidence interval on the last digits of the value) improves the precision of the previous best measurement by a factor of approximately 350. The measured value is consistent with the proton magnetic moment, μp = 2.792847350(9)μN, and is in agreement with CPT invariance. Consequently, this measurement constrains the magnitude of certain CPT-violating effects to below 1.8 × 10-24 gigaelectronvolts, and a possible splitting of the proton-antiproton magnetic moments by CPT-odd dimension-five interactions to below 6 × 10-12 Bohr magnetons.

A parts-per-billion measurement of the antiproton magnetic moment.

PubMed

Smorra, C; Sellner, S; Borchert, M J; Harrington, J A; Higuchi, T; Nagahama, H; Tanaka, T; Mooser, A; Schneider, G; Bohman, M; Blaum, K; Matsuda, Y; Ospelkaus, C; Quint, W; Walz, J; Yamazaki, Y; Ulmer, S

2017-10-18

Precise comparisons of the fundamental properties of matter-antimatter conjugates provide sensitive tests of charge-parity-time (CPT) invariance, which is an important symmetry that rests on basic assumptions of the standard model of particle physics. Experiments on mesons, leptons and baryons have compared different properties of matter-antimatter conjugates with fractional uncertainties at the parts-per-billion level or better. One specific quantity, however, has so far only been known to a fractional uncertainty at the parts-per-million level: the magnetic moment of the antiproton, . The extraordinary difficulty in measuring with high precision is caused by its intrinsic smallness; for example, it is 660 times smaller than the magnetic moment of the positron. Here we report a high-precision measurement of in units of the nuclear magneton μ N with a fractional precision of 1.5 parts per billion (68% confidence level). We use a two-particle spectroscopy method in an advanced cryogenic multi-Penning trap system. Our result  = -2.7928473441(42)μ N (where the number in parentheses represents the 68% confidence interval on the last digits of the value) improves the precision of the previous best measurement by a factor of approximately 350. The measured value is consistent with the proton magnetic moment, μ p  = 2.792847350(9)μ N , and is in agreement with CPT invariance. Consequently, this measurement constrains the magnitude of certain CPT-violating effects to below 1.8 × 10 -24 gigaelectronvolts, and a possible splitting of the proton-antiproton magnetic moments by CPT-odd dimension-five interactions to below 6 × 10 -12 Bohr magnetons.

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).

Precision Pointing Control System (PPCS) star tracker test

NASA Technical Reports Server (NTRS)

1972-01-01

Tests performed on the TRW precision star tracker are described. The unit tested was a two-axis gimballed star tracker designed to provide star LOS data to an accuracy of 1 to 2 sec. The tracker features a unique bearing system and utilizes thermal and mechanical symmetry techniques to achieve high precision which can be demonstrated in a one g environment. The test program included a laboratory evaluation of tracker functional operation, sensitivity, repeatibility, and thermal stability.

A specific and sensitive HPLC-MS/MS micromethod for milrinone plasma levels determination after inhalation in cardiac patients.

PubMed

Gavra, Paul; Nguyen, Anne Q-N; Theoret, Yves; Litalien, Catherine; Denault, André Y; Varin, France

2014-10-01

Milrinone administered through inhalation is an emerging method aimed at specifically reducing pulmonary hypertension without affecting systemic pressures. Its administration has been shown to be useful both in patients undergoing cardiac surgery and for persistent pulmonary hypertension of the newborn. These populations are prone to receive many concomitant medications and/or blood sampling may require a low volume quantification method. To address these issues in view of pharmacokinetic studies, this article aims to develop and validate a specific and sensitive analytical assay using high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) detection for the quantification of milrinone plasma concentrations after inhalation in patients undergoing cardiac surgery. Plasma samples (50 μL) were extracted using ethyl acetate. Milrinone was separated on a C18 analytical column at 50°C. The mobile phase consisted of methanol and 10 mM ammonium acetate (45:55 vol/vol). The electrospray was operated in the negative ionization mode and monitored the following mass transitions: m/z 212.1 → 140.0 at 36 eV for milrinone and m/z 252.1 → 156.1 at 32 eV for olprinone. Calibration curves followed a quadratic regression in the concentration range of 0.3125-640 ng/mL. The lower limit of quantification is 0.3125 ng/mL and is based on a low plasma volume of 50 μL. Mean drug recovery and accuracy were ≥72.3% and 96.0%, respectively. Intraday and interday precision coefficient of variation (%) was ≤7.4% and ≤11.5%, respectively. The specificity allowed milrinone quantification in the multidrug administration conditions of cardiopulmonary bypass. This validated micromethod proved to be highly sensitive and specific while using a low volume of plasma. Its low volume and its lower limit of quantification indicate that this approach is suitable for further characterization of milrinone pharmacokinetics in both adults (inhalation) and neonates.

Incorporating deep learning with convolutional neural networks and position specific scoring matrices for identifying electron transport proteins.

PubMed

Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

2017-09-05

In several years, deep learning is a modern machine learning technique using in a variety of fields with state-of-the-art performance. Therefore, utilization of deep learning to enhance performance is also an important solution for current bioinformatics field. In this study, we try to use deep learning via convolutional neural networks and position specific scoring matrices to identify electron transport proteins, which is an important molecular function in transmembrane proteins. Our deep learning method can approach a precise model for identifying of electron transport proteins with achieved sensitivity of 80.3%, specificity of 94.4%, and accuracy of 92.3%, with MCC of 0.71 for independent dataset. The proposed technique can serve as a powerful tool for identifying electron transport proteins and can help biologists understand the function of the electron transport proteins. Moreover, this study provides a basis for further research that can enrich a field of applying deep learning in bioinformatics. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Case Report: SPECT/CT as the New Diagnostic Tool for Specific Wrist Pathology.

PubMed

Linde, Musters; Ten Broek, M; Kraan, G A

2017-01-01

Single photon emission computed tomography has been introduced as a promising new diagnostic tool in orthopaedic pathology since the early 90'. Computed tomography, the combined with SPECT, gives insight in the specific sight of wrist pathology. Literature already supports introduction of SPECT/CT in wrist pathology, but clinical application is lagging. A 40yr old patient reported first in 2004 with persisting pain after a right distal radius fracture. Several diagnostics and operative interventions were performed, all unsuccessful. Because of the persisting pain a SPECT-CT was performed which showed a cyst in the hamate bone, which was successfully enucleated. The patient was finally pain free at recent follow-up. With a QDash-score of 43 and a PRW (H) E-DLV-score of 58/150. In this case report, SPECT/CT proved a very sensitive diagnostic tool for specific pathology of the wrist. It offered precise localisation and thereby the clinically suspected diagnosis was confirmed and the patient successfully treated.

Quality specification and status of internal quality control of cardiac biomarkers in China from 2011 to 2016.

PubMed

Li, Tingting; Wang, Wei; Zhao, Haijian; He, Falin; Zhong, Kun; Yuan, Shuai; Wang, Zhiguo

2017-09-07

This study aimed to investigate the status of internal quality control (IQC) for cardiac biomarkers from 2011 to 2016 so that we can have overall knowledge of the precision level of measurements in China and set appropriate precision specifications. Internal quality control data of cardiac biomarkers, including creatinine kinase MB (CK-MB) (μg/L), CK-MB(U/L), myoglobin (Mb), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and homocysteines (HCY), were collected by a web-based external quality assessment (EQA) system. Percentages of laboratories meeting five precision quality specifications for current coefficient of variations (CVs) were calculated. Then, appropriate precision specifications were chosen for these six analytes. Finally, the CVs and IQC practice were further analyzed with different grouping methods. The current CVs remained nearly constant for 6 years. cTnT had the highest pass rates every year against five specifications, whereas HCY had the lowest pass rates. Overall, most analytes had a satisfactory performance (pass rates >80%), except for HCY, if one-third TEa or the minimum specification were employed. When the optimal specification was applied, the performance of most analytes was frustrating (pass rates < 60%) except for cTnT. The appropriate precision specifications of Mb, cTnI, cTnT and HCY were set as current CVs less than 9.20%, 9.90%, 7.50%, 10.54%, 7.63%, and 6.67%, respectively. The data of IQC practices indicated wide variation and substantial progress. The precision performance of cTnT was already satisfying, while the other five analytes, especially HCY, were still frustrating; thus, ongoing investigation and continuous improvement for IQC are still needed. © 2017 Wiley Periodicals, Inc.

Ceric and ferrous dosimeters show precision for 50-5000 rad range

NASA Technical Reports Server (NTRS)

Frigerio, N. A.; Henry, V. D.

1968-01-01

Ammonium thiocyanate, added to the usual ferrous sulfate dosimeter solution, yielded a very stable, precise and temperature-independent system eight times as sensitive as the classical Fricke system in the 50 to 5000 rad range. The ceric dosimeters, promising for use in mixed radiation fields, respond nearly independently of LET.

Using High-Precision Specific Gravity Measurements to Study Minerals in Undergraduate Geoscience Courses

ERIC Educational Resources Information Center

Brandriss, Mark E.

2010-01-01

This article describes ways to incorporate high-precision measurements of the specific gravities of minerals into undergraduate courses in mineralogy and physical geology. Most traditional undergraduate laboratory methods of measuring specific gravity are suitable only for unusually large samples, which severely limits their usefulness for student…

SPEER-SERVER: a web server for prediction of protein specificity determining sites

PubMed Central

Chakraborty, Abhijit; Mandloi, Sapan; Lanczycki, Christopher J.; Panchenko, Anna R.; Chakrabarti, Saikat

2012-01-01

Sites that show specific conservation patterns within subsets of proteins in a protein family are likely to be involved in the development of functional specificity. These sites, generally termed specificity determining sites (SDS), might play a crucial role in binding to a specific substrate or proteins. Identification of SDS through experimental techniques is a slow, difficult and tedious job. Hence, it is very important to develop efficient computational methods that can more expediently identify SDS. Herein, we present Specificity prediction using amino acids’ Properties, Entropy and Evolution Rate (SPEER)-SERVER, a web server that predicts SDS by analyzing quantitative measures of the conservation patterns of protein sites based on their physico-chemical properties and the heterogeneity of evolutionary changes between and within the protein subfamilies. This web server provides an improved representation of results, adds useful input and output options and integrates a wide range of analysis and data visualization tools when compared with the original standalone version of the SPEER algorithm. Extensive benchmarking finds that SPEER-SERVER exhibits sensitivity and precision performance that, on average, meets or exceeds that of other currently available methods. SPEER-SERVER is available at http://www.hpppi.iicb.res.in/ss/. PMID:22689646

SPEER-SERVER: a web server for prediction of protein specificity determining sites.

PubMed

Chakraborty, Abhijit; Mandloi, Sapan; Lanczycki, Christopher J; Panchenko, Anna R; Chakrabarti, Saikat

2012-07-01

Sites that show specific conservation patterns within subsets of proteins in a protein family are likely to be involved in the development of functional specificity. These sites, generally termed specificity determining sites (SDS), might play a crucial role in binding to a specific substrate or proteins. Identification of SDS through experimental techniques is a slow, difficult and tedious job. Hence, it is very important to develop efficient computational methods that can more expediently identify SDS. Herein, we present Specificity prediction using amino acids' Properties, Entropy and Evolution Rate (SPEER)-SERVER, a web server that predicts SDS by analyzing quantitative measures of the conservation patterns of protein sites based on their physico-chemical properties and the heterogeneity of evolutionary changes between and within the protein subfamilies. This web server provides an improved representation of results, adds useful input and output options and integrates a wide range of analysis and data visualization tools when compared with the original standalone version of the SPEER algorithm. Extensive benchmarking finds that SPEER-SERVER exhibits sensitivity and precision performance that, on average, meets or exceeds that of other currently available methods. SPEER-SERVER is available at http://www.hpppi.iicb.res.in/ss/.

The clinical relevance of birch pollen profilin cross-reactivity in sensitized patients.

PubMed

Wölbing, F; Kunz, J; Kempf, W E; Grimmel, C; Fischer, J; Biedermann, T

2017-04-01

Overlapping seasons and cross-reactivity, especially to grass pollen profilin, can hamper the diagnosis of birch pollen allergy. To identify the primary sensitizing allergen and the clinical relevance of cross-sensitization, we correlated sensitization profiles with in vitro and in vivo tests, symptom scores, and pollen counts. A total of 433 patients with positive skin prick test (SPT) to birch pollen were analyzed regarding IgE to major birch and grass pollen allergens Bet v 1 and Phl p 1/p 5 and the profilins Bet v 2 and Phl p 12. Subgroups were analyzed by basophil activation test (BAT) and CAP-FEIA-based cross- and self-inhibition tests. A total of 349 patients were sensitized to Bet v 1, 44 patients to both Bet v 1 and Bet v 2, and 15 patients to Bet v 2 only. From Bet v 2-sensitized patients, 40 were also sensitized to Phl p 12. Ex vivo, Bet v 2 and Phl p 12 induced dose-dependent activation in basophils of these patients. Cross- and self-inhibition tests with both allergens confirmed cross-reactivity. However, semiquantitative analysis of SPTs demonstrated markedly increased reactivity to grass compared to birch pollen extract in Bet v 2 only sensitized patients. Accordingly, in most of those patients, clinical symptoms precisely correlated with grass pollen counts. Identification of the clinically relevant and sensitizing allergen needs correlation of actual pollen counts with clinical symptoms and sensitization status to major allergens. Semiquantitative analysis of SPT or BAT and determining profilin-specific IgE can contribute to making the diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Novel glucose fiber sensor combining ThFBG with GOD

NASA Astrophysics Data System (ADS)

Li, Mengmeng; Zhou, Ciming; Fan, Dian; Ou, Yiwen

2016-10-01

We propose a novel glucose fiber optic sensor combining a thinned cladding fiber Bragg grating (ThFBG) with glucose oxidase (GOD). By immobilizing GOD on the surface of a ThFBG, the fabricated sensor can obtain a high specificity to glucose. Because of the evanescent field, the sensor is very sensitive to the ambient refractive index change arising from the catalytic reaction between glucose and GOD. A four-level fiber model was simulated and verified the precision of the sensing principle. Two methods, glutaraldehyde crosslinking method (GCM) and 3-aminopropyl triethoxysilane covalent coupling method (ATCCM), were experimentally utilized to immobilize GOD. And sensor fabricated with the method ATCCM shows a measurement range of 0-0.82 mg/mL which is better than the sensor fabricated with the method GCM with measurement range of 0-0.67 mg/mL under the same condition. By using ATCCM to immobilize GOD with different concentrations, three sensors were fabricated and used for glucose measurement by monitoring the Bragg wavelength (λb) shifts, the results indicate a good linear relationship between wavelength shift and glucose concentration within a specific range, and the measurement range increases as GOD concentration increases. The highest sensitivity of sensor reaches up to 0.0549 nm/(mg.mL-1). The proposed sensor has distinct advantages in sensing structure, cost and specificity.

Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings.

PubMed

Zoeller, R T; Rovet, J

2004-10-01

Abstract The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congenital hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions.

Simultaneous determination of related substances of telmisartan and hydrochlorothiazide in tablet dosage form by using reversed phase high performance liquid chromatographic method

PubMed Central

Mukhopadhyay, Sutirtho; Kadam, Kiran; Sawant, Laxman; Nachane, Dhanashree; Pandita, Nancy

2011-01-01

Objective: Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT1) receptor that is indicated for the treatment of essential hypertension. Hydrochlorothiazide is a widely prescribed diuretic and it is indicated for the treatment of edema, control of essential hypertension and management of diabetes insipidus. In the current article a new, accurate, sensitive, precise, rapid, reversed phase high performance liquid chromatography (RP-HPLC) method was developed for determination of related substances of Telmisartan and Hydrochlorthiazide in tablet dosage form. Materials and Methods: Simultaneous determination of related substances was performed on Kromasil C18 analytical column (250 × 4.6 mm; 5μm pertical size) column at 40°C employing a gradient elution. Mobile phase consisting of solvent A (solution containing 2.0 g of potassium dihydrogen phosphate anhydrous and 1.04 g of Sodium 1- Hexane sulphonic acid monohydrate per liter of water, adjusted to pH 3.0 with orthophosphoric acid) and solvent B (mixture of Acetonitrile: Methanol in the ratio 80:20 v/v) was used at a flow rate of 1.0 ml min–1. UV detection was performed at 270 nm. Results: During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. Conclusions: HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. It may find application for the routine analysis of the related substances of both Telmisartan and Hydrochlorthiazide in this combination tablets. PMID:21966158

Relations between basic and specific motor abilities and player quality of young basketball players.

PubMed

Marić, Kristijan; Katić, Ratko; Jelicić, Mario

2013-05-01

Subjects from 5 first league clubs from Herzegovina were tested with the purpose of determining the relations of basic and specific motor abilities, as well as the effect of specific abilities on player efficiency in young basketball players (cadets). A battery of 12 tests assessing basic motor abilities and 5 specific tests assessing basketball efficiency were used on a sample of 83 basketball players. Two significant canonical correlations, i.e. linear combinations explained the relation between the set of twelve variables of basic motor space and five variables of situational motor abilities. Underlying the first canonical linear combination is the positive effect of the general motor factor, predominantly defined by jumping explosive power, movement speed of the arms, static strength of the arms and coordination, on specific basketball abilities: movement efficiency, the power of the overarm throw, shooting and passing precision, and the skill of handling the ball. The impact of basic motor abilities of precision and balance on specific abilities of passing and shooting precision and ball handling is underlying the second linear combination. The results of regression correlation analysis between the variable set of specific motor abilities and game efficiency have shown that the ability of ball handling has the largest impact on player quality in basketball cadets, followed by shooting precision and passing precision, and the power of the overarm throw.

The system of high accuracy UV spectral radiation system

NASA Astrophysics Data System (ADS)

Lin, Guan-yu; Yu, Lei; Xu, Dian; Cao, Dian-sheng; Yu, Yu-Xiang

2016-10-01

UV spectral radiation detecting and visible observation telescope is designed by the coaxial optical. In order to decrease due to the incident light polarization effect, and improve the detection precision, polarizer need to be used in the light path. Four pieces of quartz of high Precision UV radiation depolarizer retarder stack together is placed in front of Seya namioka dispersion unit. The coherent detection principle of modulation of light signal and the reference signal multiplied processing, increase the phase sensitive detector can be adjustment function, ensure the UV spectral radiation detection stability. A lock-in amplifier is used in the electrical system to advance the accuracy of measurement. To ensure the precision measurement detected, the phase-sensitive detector function can be adjustable. the output value is not more than 10mV before each measurement, so it can be ensured that the stability of the measured radiation spectrum is less than 1 percent.

Research on the high-precision non-contact optical detection technology for banknotes

NASA Astrophysics Data System (ADS)

Jin, Xiaofeng; Liang, Tiancai; Luo, Pengfeng; Sun, Jianfeng

2015-09-01

The technology of high-precision laser interferometry was introduced for optical measurement of the banknotes in this paper. Taking advantage of laser short wavelength and high sensitivity, information of adhesive tape and cavity about the banknotes could be checked efficiently. Compared with current measurement devices, including mechanical wheel measurement device, Infrared measurement device, ultrasonic measurement device, the laser interferometry measurement has higher precision and reliability. This will improve the ability of banknotes feature information in financial electronic equipment.

A printed electronic platform for the specific detection of biomolecules

NASA Astrophysics Data System (ADS)

Doumbia, A.; Webb, M.; Turner, M. L.; Behrendt, J. M.; Wilson, R.

2017-08-01

The rapid detection of disease specific biomarkers in a clinically relevant range using a low-cost sensor can facilitate the development of individual treatment plans for a given patient, known as precision, personalized or genomic medicine. In the recent decade Electrolyte-Gated Organic Field Effect Transistors (EGOFETs), a subtype of OFETs where the dielectric is replaced by an electrolyte, have attracted a great deal of attention for sensing applications. This is due to their capacity to operate at low voltage (< 1 volt) in physiological like media. Although EGOFET based biosensors have been shown to specifically detect biomolecules with high sensitivity and selectivity; the stability, reproducibility, and performance required to reach the desired market are not yet achieved. In this contribution, we describe the development of a stable and reproducible EGOFET sensor that is able to detect biomolecules selectively in real-time. Facile and scalable techniques are used to prepare arrays of these devices. The selectivity of individual EGOFETs is investigated by immobilization of specific ligands to the target molecule of interest on the gate electrode within a microfluidic flow cell.

Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

PubMed Central

Lo, Yuan Hung; Peachey, Tom; Abramson, David; McCulloch, Andrew

2013-01-01

Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004) to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling. PMID:24222910

A comparison of simultaneous plasma, atomic absorption, and iron colorimetric determinations of major and trace constituents in acid mine waters

USGS Publications Warehouse

Ball, J.W.; Nordstrom, D. Kirk

1994-01-01

Sixty-three water samples collected during June to October 1982 from the Leviathan/Bryant Creek drainage basin were originally analyzed by simultaneous multielement direct-current plasma (DCP) atomic-emission spectrometry, flame atomic-absorption spectrometry, graphite-furnace atomic-absorption spectrometry (GFAAS) (thallium only), ultraviolet-visible spectrometry, and hydride-generation atomic-absorption spectrometry.Determinations were made for the following metallic and semi-metallic constituents: AI, As, B, Ba, Be, Bi, Cd, Ca, Cr, Co, Cu, Fe(11), Fe(total), Li, Pb, Mg, Mn, Mo, Ni, K, Sb, Se, Si, Na, Sr, TI, V, and Zn. These samples were re-analyzed later by simultaneous multielement inductively coupled plasma (ICP) atomic-emission spectrometry and Zeeman-corrected GFAAS to determine the concentrations of many of the same constituents with improved accuracy, precision, and sensitivity. The result of this analysis has been the generation of comparative concentration values for a significant subset of the solute constituents. Many of the more recently determined values replace less-than-detection values for the trace metals; others constitute duplicate analyses for the major constituents. The multiple determinations have yielded a more complete, accurate, and precise set of analytical data. They also have resulted in an opportunity to compare the performance of the plasma-emission instruments operated in their respective simultaneous multielement modes. Flame atomic-absorption spectrometry was judged best for Na and K and hydride-generation atomic-absorption spectrometry was judged best for As because of their lower detection limit and relative freedom from interelement spectral effects. Colorimetric determination using ferrozine as the color agent was judged most accurate, precise, and sensitive for Fe. Cadmium, lead, and vanadium concentrations were too low in this set of samples to enable a determination of whether ICP or DCP is a more suitable technique. Of the remaining elements, Ba, Be, Ca, Cr, Mg, Mn, Sr, and Zn have roughly equivalent accuracy, precision, and detection limit by ICP and DCP. Cobalt and Ni were determined to be better analyzed by ICP, because of lower detection limits; B, Cu, Mo, and Si were determined to be better analyzed by DCP, because of relative freedom from interferences. The determination oral by DCP was far more sensitive, owing to the use of a more sensitive wavelength, compared with the ICP. However, there is a very serious potential interference from a strong Ca emission line near the 396.15 nanometer DCP wavelength. Thus, there is no clear choice between the plasma techniques tested, for the determination oral. The ICP and DCP detection limits are typically between 0.001 and 0.5 milligrams per liter in acid mine waters. For those metals best analyzed by ICP and/or DCP, but below these limits, GFAAS is the method of choice because of its relatively greater sensitivity and specificity. Six of the elements were not determined by DCP, ICP or Zeeman-corrected GFAAS, and are not discussed in this report. These elements are: Bi, Fe(11), Li, Sb, Se, and TI.

Bragg gravity-gradiometer using the 1S0–3P1 intercombination transition of 88Sr

NASA Astrophysics Data System (ADS)

del Aguila, R. P.; Mazzoni, T.; Hu, L.; Salvi, L.; Tino, G. M.; Poli, N.

2018-04-01

We present a gradiometer based on matter-wave interference of alkaline-earth-metal atoms, namely 88Sr. The coherent manipulation of the atomic external degrees of freedom is obtained by large-momentum-transfer Bragg diffraction, driven by laser fields detuned away from the narrow 1S0–3P1 intercombination transition. We use a well-controlled artificial gradient, realized by changing the relative frequencies of the Bragg pulses during the interferometer sequence, in order to characterize the sensitivity of the gradiometer. The sensitivity reaches 1.5 × 10‑5 s‑2 for an interferometer time of 20 ms, limited only by geometrical constraints. We observed extremely low sensitivity of the gradiometric phase to magnetic field gradients, approaching a value 104 times lower than the sensitivity of alkali-atom based gradiometers, limited by the interferometer sensitivity. An efficient double-launch technique employing accelerated red vertical lattices from a single magneto-optical trap cloud is also demonstrated. These results highlight strontium as an ideal candidate for precision measurements of gravity gradients, with potential application in future precision tests of fundamental physics.

Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson’s disease

NASA Astrophysics Data System (ADS)

Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R.

2016-09-01

Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson’s disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson’s Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought.

Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson’s disease

PubMed Central

Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R.

2016-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson’s disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson’s Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought. PMID:27624437

Validation of the LacTek test applied to spiked extracts of tissue samples: determination of performance characteristics.

PubMed

Mitchell, J M; Yee, A J; McNab, W B; Griffiths, M W; McEwen, S A

1999-01-01

LacTek tests are competitive enzyme-linked immunosorbent assays intended for rapid detection of antimicrobial residues in bovine milk. In this study, the LacTek test protocol was modified for use with extracts of bovine tissue to detect beta-lactam, tetracycline, and sulfamethazine residues. Test performance characteristics--precision, accuracy, ruggedness, practicability, and analytical specificity and sensitivity--were investigated. Results suggest that LacTek tests can be easily adapted to detect antimicrobial residues in extracts of lean ground beef. However, positive samples may not contain residues at violative concentrations (i.e., Canadian maximum residue limits), and therefore, additional analysis would be required for final confirmation and quantitation (e.g., chromatography).

Bacterial chemoreceptors: high-performance signaling in networked arrays.

PubMed

Hazelbauer, Gerald L; Falke, Joseph J; Parkinson, John S

2008-01-01

Chemoreceptors are crucial components in the bacterial sensory systems that mediate chemotaxis. Chemotactic responses exhibit exquisite sensitivity, extensive dynamic range and precise adaptation. The mechanisms that mediate these high-performance functions involve not only actions of individual proteins but also interactions among clusters of components, localized in extensive patches of thousands of molecules. Recently, these patches have been imaged in native cells, important features of chemoreceptor structure and on-off switching have been identified, and new insights have been gained into the structural basis and functional consequences of higher order interactions among sensory components. These new data suggest multiple levels of molecular interactions, each of which contribute specific functional features and together create a sophisticated signaling device.

Bacterial chemoreceptors: high-performance signaling in networked arrays

PubMed Central

Hazelbauer, Gerald L.; Falke, Joseph J.; Parkinson, John S.

2010-01-01

Chemoreceptors are crucial components in the bacterial sensory systems that mediate chemotaxis. Chemotactic responses exhibit exquisite sensitivity, extensive dynamic range and precise adaptation. The mechanisms that mediate these high-performance functions involve not only actions of individual proteins but also interactions among clusters of components, localized in extensive patches of thousands of molecules. Recently, these patches have been imaged in native cells, important features of chemoreceptor structure and on–off switching have been identified, and new insights have been gained into the structural basis and functional consequences of higher order interactions among sensory components. These new data suggest multiple levels of molecular interactions, each of which contribute specific functional features and together create a sophisticated signaling device. PMID:18165013

Posttreatment Lyme disease syndrome.

PubMed

Aucott, John N

2015-06-01

The prognosis following appropriate antibiotic treatment of early or late Lyme disease is favorable but can be complicated by persistent symptoms of unknown cause termed posttreatment Lyme disease syndrome (PTLDS), characterized by fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months or longer after completion of antibiotic therapy. Risk factors include delayed diagnosis, increased severity of symptoms, and presence of neurologic symptoms at time of initial treatment. Two-tier serologic testing is neither sensitive nor specific for diagnosis of PTLDS because of variability in convalescent serologic responses after treatment of early Lyme disease. Optimal treatment of PTLDS awaits more precise understanding of the pathophysiologic mechanisms involved in this illness and future treatment trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Intravesical dosimetry applied to laser positioning in photodynamic therapy

NASA Astrophysics Data System (ADS)

Beslon, Guillaume; Ambroise, Philippe; Heit, Bernard; Bremont, Jacques; Guillemin, Francois H.

1996-12-01

Superficial bladder tumor is a challenging indication for photodynamic therapy. Due to lack of specificity of the sensitizers, the light has to be precisely monitored over the bladder surface, illuminated by an isotropic source, to restrict the cytotoxic effect to the tumor without affecting the normal epithelium. In order to assist the surgeon while processing the therapy, an urothelium illumination model is proposed. It is computed through a spline interpolation, on the basis of 12 intravesical sensors. This paper presents the overall system architecture and details the modelization and visualization processes. With this model, the surgeon is able to master the source displacement inside the bladder and to homogenize the tissue exposure.

Amorphous silicon radiation detectors

DOEpatents

Street, Robert A.; Perez-Mendez, Victor; Kaplan, Selig N.

1992-01-01

Hydrogenated amorphous silicon radiation detector devices having enhanced signal are disclosed. Specifically provided are transversely oriented electrode layers and layered detector configurations of amorphous silicon, the structure of which allow high electric fields upon application of a bias thereby beneficially resulting in a reduction in noise from contact injection and an increase in signal including avalanche multiplication and gain of the signal produced by incoming high energy radiation. These enhanced radiation sensitive devices can be used as measuring and detection means for visible light, low energy photons and high energy ionizing particles such as electrons, x-rays, alpha particles, beta particles and gamma radiation. Particular utility of the device is disclosed for precision powder crystallography and biological identification.

Amorphous silicon radiation detectors

DOEpatents

Street, R.A.; Perez-Mendez, V.; Kaplan, S.N.

1992-11-17

Hydrogenated amorphous silicon radiation detector devices having enhanced signal are disclosed. Specifically provided are transversely oriented electrode layers and layered detector configurations of amorphous silicon, the structure of which allow high electric fields upon application of a bias thereby beneficially resulting in a reduction in noise from contact injection and an increase in signal including avalanche multiplication and gain of the signal produced by incoming high energy radiation. These enhanced radiation sensitive devices can be used as measuring and detection means for visible light, low energy photons and high energy ionizing particles such as electrons, x-rays, alpha particles, beta particles and gamma radiation. Particular utility of the device is disclosed for precision powder crystallography and biological identification. 13 figs.

Optimal Measurements for Simultaneous Quantum Estimation of Multiple Phases

NASA Astrophysics Data System (ADS)

Pezzè, Luca; Ciampini, Mario A.; Spagnolo, Nicolò; Humphreys, Peter C.; Datta, Animesh; Walmsley, Ian A.; Barbieri, Marco; Sciarrino, Fabio; Smerzi, Augusto

2017-09-01

A quantum theory of multiphase estimation is crucial for quantum-enhanced sensing and imaging and may link quantum metrology to more complex quantum computation and communication protocols. In this Letter, we tackle one of the key difficulties of multiphase estimation: obtaining a measurement which saturates the fundamental sensitivity bounds. We derive necessary and sufficient conditions for projective measurements acting on pure states to saturate the ultimate theoretical bound on precision given by the quantum Fisher information matrix. We apply our theory to the specific example of interferometric phase estimation using photon number measurements, a convenient choice in the laboratory. Our results thus introduce concepts and methods relevant to the future theoretical and experimental development of multiparameter estimation.

Enumeration of Vibrio cholerae O1 in Bangladesh waters by fluorescent-antibody direct viable count.

PubMed Central

Brayton, P R; Tamplin, M L; Huq, A; Colwell, R R

1987-01-01

A field trial to enumerate Vibrio cholerae O1 in aquatic environments in Bangladesh was conducted, comparing fluorescent-antibody direct viable count with culture detection by the most-probable-number index. Specificity of a monoclonal antibody prepared against the O1 antigen was assessed and incorporated into the fluorescence staining method. All pond and water samples yielded higher counts of viable V. cholerae O1 by fluorescent-antibody direct viable count than by the most-probable-number index. Fluorescence microscopy is a more sensitive detection system than culture methods because it allows the enumeration of both culturable and nonculturable cells and therefore provides more precise monitoring of microbiological water quality. PMID:3324967

A compact, large-range interferometer for precision measurement and inertial sensing

NASA Astrophysics Data System (ADS)

Cooper, S. J.; Collins, C. J.; Green, A. C.; Hoyland, D.; Speake, C. C.; Freise, A.; Mow-Lowry, C. M.

2018-05-01

We present a compact, fibre-coupled interferometer with high sensitivity and a large working range. We propose to use this interferometer as a readout mechanism for future inertial sensors, removing a major limiting noise source, and in precision positioning systems. The interferometer’s peak sensitivity is 2 × 10-{14} m \\sqrt{Hz-1} at 70 Hz and 7 × 10-{11} m \\sqrt{Hz-1} at 10 mHz. If deployed on a GS-13 geophone, the resulting inertial sensing output will be limited by the suspension thermal noise of the reference mass from 10 mHz to 2 Hz.

Variations in the electrical short-circuit current decay for recombination lifetime and velocity measurements

NASA Technical Reports Server (NTRS)

Jung, Tae-Won; Lindholm, Fredrik A.; Neugroschel, Arnost

1987-01-01

An improved measurement system for electrical short-circuit current decay is presented that extends applicability of the method to silicon solar cells having an effective lifetime as low as 1 microsec. The system uses metal/oxide/semiconductor transistors as voltage-controlled switches. Advances in theory developed here increase precision and sensitivity in the determination of the minority-carrier recombination lifetime and recombination velocity. A variation of the method, which exploits measurements made on related back-surface field and back-ohmic contact devices, further improves precision and sensitivity. The improvements are illustrated by application to 15 different silicon solar cells.

Precisely Controlled Ultrathin Conjugated Polymer Films for Large Area Transparent Transistors and Highly Sensitive Chemical Sensors.

PubMed

Khim, Dongyoon; Ryu, Gi-Seong; Park, Won-Tae; Kim, Hyunchul; Lee, Myungwon; Noh, Yong-Young

2016-04-13

A uniform ultrathin polymer film is deposited over a large area with molecularlevel precision by the simple wire-wound bar-coating method. The bar-coated ultrathin films not only exhibit high transparency of up to 90% in the visible wavelength range but also high charge carrier mobility with a high degree of percolation through the uniformly covered polymer nanofibrils. They are capable of realizing highly sensitive multigas sensors and represent the first successful report of ethylene detection using a sensor based on organic field-effect transistors. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

A comparison of analysis methods to estimate contingency strength.

PubMed

Lloyd, Blair P; Staubitz, Johanna L; Tapp, Jon T

2018-05-09

To date, several data analysis methods have been used to estimate contingency strength, yet few studies have compared these methods directly. To compare the relative precision and sensitivity of four analysis methods (i.e., exhaustive event-based, nonexhaustive event-based, concurrent interval, concurrent+lag interval), we applied all methods to a simulated data set in which several response-dependent and response-independent schedules of reinforcement were programmed. We evaluated the degree to which contingency strength estimates produced from each method (a) corresponded with expected values for response-dependent schedules and (b) showed sensitivity to parametric manipulations of response-independent reinforcement. Results indicated both event-based methods produced contingency strength estimates that aligned with expected values for response-dependent schedules, but differed in sensitivity to response-independent reinforcement. The precision of interval-based methods varied by analysis method (concurrent vs. concurrent+lag) and schedule type (continuous vs. partial), and showed similar sensitivities to response-independent reinforcement. Recommendations and considerations for measuring contingencies are identified. © 2018 Society for the Experimental Analysis of Behavior.

Lowering the quantification limit of the QubitTM RNA HS assay using RNA spike-in.

PubMed

Li, Xin; Ben-Dov, Iddo Z; Mauro, Maurizio; Williams, Zev

2015-05-06

RNA quantification is often a prerequisite for most RNA analyses such as RNA sequencing. However, the relatively low sensitivity and large sample consumption of traditional RNA quantification methods such as UV spectrophotometry and even the much more sensitive fluorescence-based RNA quantification assays, such as the Qubit™ RNA HS Assay, are often inadequate for measuring minute levels of RNA isolated from limited cell and tissue samples and biofluids. Thus, there is a pressing need for a more sensitive method to reliably and robustly detect trace levels of RNA without interference from DNA. To improve the quantification limit of the Qubit™ RNA HS Assay, we spiked-in a known quantity of RNA to achieve the minimum reading required by the assay. Samples containing trace amounts of RNA were then added to the spike-in and measured as a reading increase over RNA spike-in baseline. We determined the accuracy and precision of reading increases between 1 and 20 pg/μL as well as RNA-specificity in this range, and compared to those of RiboGreen(®), another sensitive fluorescence-based RNA quantification assay. We then applied Qubit™ Assay with RNA spike-in to quantify plasma RNA samples. RNA spike-in improved the quantification limit of the Qubit™ RNA HS Assay 5-fold, from 25 pg/μL down to 5 pg/μL while maintaining high specificity to RNA. This enabled quantification of RNA with original concentration as low as 55.6 pg/μL compared to 250 pg/μL for the standard assay and decreased sample consumption from 5 to 1 ng. Plasma RNA samples that were not measurable by the Qubit™ RNA HS Assay were measurable by our modified method. The Qubit™ RNA HS Assay with RNA spike-in is able to quantify RNA with high specificity at 5-fold lower concentration and uses 5-fold less sample quantity than the standard Qubit™ Assay.

Utility of 99mTc-Hynic-TOC in 131I Whole-Body Scan Negative Thyroid Cancer Patients with Elevated Serum Thyroglobulin Levels

PubMed Central

Shinto, Ajit S.; Kamaleshwaran, K. K.; Mallia, Madhav; Korde, Aruna; Samuel, Grace; Banerjee, Sharmila; Velayutham, Pavanasam; Damodharan, Suresh; Sairam, Madhu

2015-01-01

Several studies have reported on the expression of somatostatin receptors (SSTRs) in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed Technetium-99m labeled somatostatin analog, 99mTc-Hynic-TOC, in terms of precise localization of the disease. The study population consisted of 28 patients (16 men, 12 women; age range: 39-72 years) with histologically confirmed DTC, who presented with recurrent or persistent disease as indicated by elevated serum thyroglobulin (Tg) levels after initial treatment (serum Tg > 10 ng/ml off T4 suppression for 4-6 weeks). All patients were negative on the Iodine-131 posttherapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed in all patients. SSTR scintigraphy was true positive in 23 cases (82.1%), true negative in two cases (7.1%) and false negative in three cases (10.7%) which resulted in a sensitivity of 88.46%, specificity of 100% and an accuracy of 89.2%. Sensitivity of 99mTc-Hynic-TOC scan was higher (93.7%) for patients with advanced stages, that is stages III and IV. 18F-FDG showed a sensitivity of 93.7%, a specificity of 50% and an accuracy of 89.3%. 18F-FDG PET was found to be more sensitive, with lower specificity due to false positive results in 2 patients. Analysis on a lesion basis demonstrated substantial agreement between the two imaging techniques with a Cohen's kappa of 0.66. Scintigraphy with 99mTc-Hynic-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localization diagnostics in thyroid cancer patients with recurrent or metastatic disease. PMID:26097420

Utility of (99m)Tc-Hynic-TOC in 131I Whole-Body Scan Negative Thyroid Cancer Patients with Elevated Serum Thyroglobulin Levels.

PubMed

Shinto, Ajit S; Kamaleshwaran, K K; Mallia, Madhav; Korde, Aruna; Samuel, Grace; Banerjee, Sharmila; Velayutham, Pavanasam; Damodharan, Suresh; Sairam, Madhu

2015-01-01

Several studies have reported on the expression of somatostatin receptors (SSTRs) in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed Technetium-99m labeled somatostatin analog, (99m)Tc-Hynic-TOC, in terms of precise localization of the disease. The study population consisted of 28 patients (16 men, 12 women; age range: 39-72 years) with histologically confirmed DTC, who presented with recurrent or persistent disease as indicated by elevated serum thyroglobulin (Tg) levels after initial treatment (serum Tg > 10 ng/ml off T4 suppression for 4-6 weeks). All patients were negative on the Iodine-131 posttherapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was performed in all patients. SSTR scintigraphy was true positive in 23 cases (82.1%), true negative in two cases (7.1%) and false negative in three cases (10.7%) which resulted in a sensitivity of 88.46%, specificity of 100% and an accuracy of 89.2%. Sensitivity of (99m)Tc-Hynic-TOC scan was higher (93.7%) for patients with advanced stages, that is stages III and IV. (18)F-FDG showed a sensitivity of 93.7%, a specificity of 50% and an accuracy of 89.3%. (18)F-FDG PET was found to be more sensitive, with lower specificity due to false positive results in 2 patients. Analysis on a lesion basis demonstrated substantial agreement between the two imaging techniques with a Cohen's kappa of 0.66. Scintigraphy with (99m)Tc-Hynic-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localization diagnostics in thyroid cancer patients with recurrent or metastatic disease.

Component resolution reveals additional major allergens in patients with honeybee venom allergy.

PubMed

Köhler, Julian; Blank, Simon; Müller, Sabine; Bantleon, Frank; Frick, Marcel; Huss-Marp, Johannes; Lidholm, Jonas; Spillner, Edzard; Jakob, Thilo

2014-05-01

Detection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of sensitization to the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance. We performed an analysis of sensitization profiles of patients with HBV allergy to a panel of HBV allergens. Diagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP. IgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen-specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3- and Api m 10-specific IgG4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations. Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Determination of molindone enantiomers in human plasma by high-performance liquid chromatography-tandem mass spectrometry using macrocyclic antibiotic chiral stationary phases.

PubMed

Jiang, Hongliang; Li, Yinghe; Pelzer, Mary; Cannon, Michelle J; Randlett, Christopher; Junga, Heiko; Jiang, Xiangyu; Ji, Qin C

2008-05-30

A sensitive and selective bioanalytical assay was developed and validated for the determination of enantiomeric molindone in human plasma using high-performance liquid chromatography-tandem mass spectrometry along with supported liquid extraction procedures. The chiral separation was evaluated and optimized on macrocyclic antibiotic type chiral stationary phases (CSPs) based on teicoplanin aglycone (Chirobiotic TAG) in polar organic, polar ionic, and reversed-phase mode chromatography, respectively. Complete baseline separation was achieved on a Chirobiotic TAG column under isocratic condition in reversed-phase chromatography. The method validation was conducted using a Chirobiotic TAG column (100 mm x 2.1 mm) over the curve range 0.100-100 ng/ml for each molindone enantiomer using 0.0500 ml of plasma sample. The flow rate was 0.8 ml/min and the total run time was 9 min. Supported liquid extraction in a 96-well plate format was used for sample preparation. Parameters including recovery, matrix effect, linearity, sensitivity, specificity, carryover, precision, accuracy, dilution integrity, and stability were evaluated. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels were RSD

Modified automatic R-peak detection algorithm for patients with epilepsy using a portable electrocardiogram recorder.

PubMed

Jeppesen, J; Beniczky, S; Fuglsang Frederiksen, A; Sidenius, P; Johansen, P

2017-07-01

Earlier studies have shown that short term heart rate variability (HRV) analysis of ECG seems promising for detection of epileptic seizures. A precise and accurate automatic R-peak detection algorithm is a necessity in a real-time, continuous measurement of HRV, in a portable ECG device. We used the portable CE marked ePatch® heart monitor to record the ECG of 14 patients, who were enrolled in the videoEEG long term monitoring unit for clinical workup of epilepsy. Recordings of the first 7 patients were used as training set of data for the R-peak detection algorithm and the recordings of the last 7 patients (467.6 recording hours) were used to test the performance of the algorithm. We aimed to modify an existing QRS-detection algorithm to a more precise R-peak detection algorithm to avoid the possible jitter Qand S-peaks can create in the tachogram, which causes error in short-term HRVanalysis. The proposed R-peak detection algorithm showed a high sensitivity (Se = 99.979%) and positive predictive value (P+ = 99.976%), which was comparable with a previously published QRS-detection algorithm for the ePatch® ECG device, when testing the same dataset. The novel R-peak detection algorithm designed to avoid jitter has very high sensitivity and specificity and thus is a suitable tool for a robust, fast, real-time HRV-analysis in patients with epilepsy, creating the possibility for real-time seizure detection for these patients.

A UPLC-MS/MS method for simultaneous determination of five flavonoids from Stellera chamaejasme L. in rat plasma and its application to a pharmacokinetic study.

PubMed

Li, Yun-Qing; Li, Cheng-Jian; Lv, Lei; Cao, Qing-Qing; Qian, Xian; Li, Si Wei; Wang, Hui; Zhao, Liang

2018-06-01

Stellera chamaejasme L. has been used as a traditional Chinese medicine for the treatment of scabies, tinea, stubborn skin ulcers, chronic tracheitis, cancer and tuberculosis. A sensitive and selective ultra-high liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of five flavonoids (stelleranol, chamaechromone, neochamaejasmin A, chamaejasmine and isochamaejasmin) of S. chamaejasme L. in rat plasma. Chromatographic separation was accomplished on an Agilent Poroshell 120 EC-C 18 column (2.1 × 100 mm, 2.7 μm) with gradient elution at a flow rate of 0.4 mL/min and the total analysis time was 7 min. The analytes were detected using multiple reaction monitoring in positive ionization mode. The samples were prepared by liquid-liquid extraction with ethyl acetate. The UPLC-MS/MS method was validated for specificity, linearity, sensitivity, accuracy and precision, recovery, matrix effect and stability. The validated method exhibited good linearity (r ≥ 0.9956), and the lower limits of quantification ranged from 0.51 to 0.64 ng/mL for five flavonoids. The intra- and inter-day precision were both <10.2%, and the accuracy ranged from -11.79 to 9.21%. This method was successfully applied to a pharmacokinetic study of five flavonoids in rats after oral administration of ethyl acetate extract of S. chamaejasme L. Copyright © 2018 John Wiley & Sons, Ltd.

QbD-Based Development and Validation of a Stability-Indicating HPLC Method for Estimating Ketoprofen in Bulk Drug and Proniosomal Vesicular System.

PubMed

Yadav, Nand K; Raghuvanshi, Ashish; Sharma, Gajanand; Beg, Sarwar; Katare, Om P; Nanda, Sanju

2016-03-01

The current studies entail systematic quality by design (QbD)-based development of simple, precise, cost-effective and stability-indicating high-performance liquid chromatography method for estimation of ketoprofen. Analytical target profile was defined and critical analytical attributes (CAAs) were selected. Chromatographic separation was accomplished with an isocratic, reversed-phase chromatography using C-18 column, pH 6.8, phosphate buffer-methanol (50 : 50v/v) as a mobile phase at a flow rate of 1.0 mL/min and UV detection at 258 nm. Systematic optimization of chromatographic method was performed using central composite design by evaluating theoretical plates and peak tailing as the CAAs. The method was validated as per International Conference on Harmonization guidelines with parameters such as high sensitivity, specificity of the method with linearity ranging between 0.05 and 250 µg/mL, detection limit of 0.025 µg/mL and quantification limit of 0.05 µg/mL. Precision was demonstrated using relative standard deviation of 1.21%. Stress degradation studies performed using acid, base, peroxide, thermal and photolytic methods helped in identifying the degradation products in the proniosome delivery systems. The results successfully demonstrated the utility of QbD for optimizing the chromatographic conditions for developing highly sensitive liquid chromatographic method for ketoprofen. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Diagnostic accuracy of contrast-enhanced ultrasound in assessing the therapeutic response to radio frequency ablation for liver tumors: systematic review and meta-analysis.

PubMed

Xuan, Min; Zhou, Fengsheng; Ding, Yan; Zhu, Qiaoying; Dong, Ji; Zhou, Hao; Cheng, Jun; Jiang, Xiao; Wu, Pengxi

2018-04-01

To review the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) used to detect residual or recurrent liver tumors after radiofrequency ablation (RFA). This technique uses contrast-enhanced computer tomography or/and contrast-enhanced magnetic resonance imaging as the gold standard of investigation. MEDLINE, EMBASE, and COCHRANE were systematically searched for all potentially eligible studies comparing CEUS with the reference standard that follows RFA. Risk of bias and applicability concerns were addressed by adopting the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled point estimates for sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios (DOR) with 95% CI were computed before plotting the sROC (summary receiver operating characteristic) curve. Meta-regression and subgroup analysis were used to identify the source of the heterogeneity that was detected. Publication bias was evaluated using Deeks' funnel plot asymmetry test. Ten eligible studies on 1162 lesions that occurred between 2001 and 2016 were included in the final analysis. The quality of the included studies assessed by the QUADAS-2 tool was considered reasonable. The pooled sensitivity and specificity of CEUS in detecting residual or recurrent liver tumors had the following values: 0.90 (95% CI 0.85-0.94) and 1.00 (95% CI 0.99-1.00), respectively. Overall DOR was 420.10 (95% CI 142.30-1240.20). The sources of heterogeneity could not be precisely identified by meta-regression or subgroup analysis. No evidence of publication bias was found. This study confirmed that CEUS exhibits high sensitivity and specificity in assessing therapeutic responses to RFA for liver tumors.

Validation of Rules to Predict Emergent Surgical Intervention in Pediatric Trauma Patients

PubMed Central

Boatright, Dowin H; Byyny, Richard L; Hopkins, Emily; Bakes, Katherine; Hissett, Jennifer; Tunson, Java; Easter, Joshua S; Vogel, Jody A; Bensard, Denis; Haukoos, Jason S

2014-01-01

Background Trauma centers use guidelines to determine when a trauma surgeon is needed in the emergency department (ED) on patient arrival. A decision rule from Loma Linda University identified patients with penetrating injury and tachycardia as requiring emergent surgical intervention. Our goal was to validate this rule and to compare it to the American College of Surgeons’ Major Resuscitation Criteria (MRC). Study Design We used data from 1993 through 2010 from two Level 1 trauma centers in Denver, Colorado. Patient demographics, injury severity, times of ED arrival and surgical intervention, and all variables of the Loma Linda Rule and the MRC were obtained. The outcome, emergent intervention (defined as requiring operative intervention by a trauma surgeon within one hour of arrival to the ED or performance of cricothyroidotomy or thoracotomy in the ED) was confirmed using standardized abstraction. Sensitivities, specificities, and 95% confidence intervals (CIs) were calculated. Results 8,078 patients were included and 47 (0.6%) required emergent intervention. Of the 47 patients, the median age was 11 years (IQR: 7–14), 70% were male, 30% had penetrating mechanisms, and the median ISS was 25 (IQR: 9–41). At the two institutions, the Loma Linda Rule had a sensitivity and specificity of 69% (95% CI: 45%–94%) and 76% (95% CI: 69%–83%), respectively, and the MRC had a sensitivity and specificity of 80% (95% CI: 70%–92%) and 81% (95% CI: 77%–85%), respectively. Conclusions Emergent surgical intervention is rare in the pediatric trauma population. Although precision of predictive accuracies of the Loma Linda Rule and MRC were limited by small numbers of outcomes, neither set of criteria appears to be sufficiently accurate to recommend their routine use. PMID:23623222

New design, development, and optimization of an in-house quantitative TaqMan Real-time PCR assay for HIV-1 viral load measurement.

PubMed

Noorbazargan, Hassan; Nadji, Seyed Alireza; Samiee, Siamak Mirab; Paryan, Mahdi; Mohammadi-Yeganeh, Samira

2018-04-01

Background Viral load measurement is commonly applicable to monitor HIV infection in patients to determine the number of HIV-RNA in serum samples of individuals. The aim of the present study was to set up a highly specific, sensitive, and reproducible home-brewed Real-time PCR assay based on TaqMan chemistry to quantify HIV-1 RNA genome. Methods In this study, three sets of primer pairs and a TaqMan probe were designed for HIV subtypes conserved sequences. An internal control was included in this assay to evaluate the presence of inhibition. Standard curve and threshold cycle values were determined using in vitro transcribed RNA from int region of HIV-1. A serial dilution of RNA standards was generated by in vitro transcription, from 10 to 10 9 copies/ml to find the sensitivity and the limit of detection (LOD) of the assay and to evaluate its performance in a quantitative RT-PCR assay. Results The assay has a low LOD equivalent to 33.13 copies/ml of HIV-1 RNA and a linear range of detection from 10 to 10 9 copies/ml. The coefficient of variation (CV) for Inter and Intra-assay precision of this in-house HIV Real-time RT-PCR ranged from 0.28 to 2.49% and 0.72 to 4.47%, respectively. The analytical and clinical specificity was 100%. Conclusions The results indicate that the developed method has a suitable specificity and sensitivity and is highly reproducible and cost-benefit. Therefore, it will be useful to monitor HIV infection in plasma samples of individuals.

A technique to improve diagnostic information from fine-needle aspirations: immunohistochemistry on cytoscrape.

PubMed

Skov, Birgit Guldhammer; Kiss, Katalin; Ramsted, Julie; Linnemann, Dorte

2009-04-25

Cytologic examination of fine-needle aspiration (FNA) material is being used increasingly for the diagnosis of pulmonary lesions. Accurate distinction between nonsmall cell lung cancer (NSCLC), including subgroups, and small cell lung cancer and between primary lung cancer and metastases has therapeutic impact. However, the distinction between these groups may be difficult on smears. In this report, the authors describe a simple method, called cytoscrape (CS), which can be used on virtually any smear to produce material useful for ancillary methods, including immunohistochemistry. Aspirates from 47 patients who had possible malignant infiltrates identified on computed tomography scans of the chest were included. Smears were stained by May-Grunwald-Giemsa and Diff-Quick for diagnostic purposes. CS material was obtained by gently scraping cells off the slides. Clots were made, and the sections were stained for thyroid transcription factor-1 (TTF-1) and mucin. The utility of the CS technique was evaluated by assessing the sensitivity and specificity of the method and by quantifying the extra diagnostic information obtained by the method relative to smears alone. Malignant tumor cells in the CS material were identified in 43 aspirates (91%). Both the sensitivity and the specificity for TTF-1 were 100%. The sensitivity for mucin was 60%, and the specificity for mucin was 100%. The diagnoses made on smears were improved by CS in 31 patients (72%), in that more precise separation of subgroups of NSCLC was possible or information on primary tumors was obtained. The CS technique improved the diagnostic information from FNA in a clinically relevant way. The method is simple, quick, and inexpensive. (c) 2009 American Cancer Society.

Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

PubMed

Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

2017-03-09

It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

Psychoacoustic Assessment to Improve Tinnitus Diagnosis

PubMed Central

Hutchins, Sean; Hébert, Sylvie

2013-01-01

The diagnosis of tinnitus relies on self-report. Psychoacoustic measurements of tinnitus pitch and loudness are essential for assessing claims and discriminating true from false ones. For this reason, the quantification of tinnitus remains a challenging research goal. We aimed to: (1) assess the precision of a new tinnitus likeness rating procedure with a continuous-pitch presentation method, controlling for music training, and (2) test whether tinnitus psychoacoustic measurements have the sensitivity and specificity required to detect people faking tinnitus. Musicians and non-musicians with tinnitus, as well as simulated malingerers without tinnitus, were tested. Most were retested several weeks later. Tinnitus pitch matching was first assessed using the likeness rating method: pure tones from 0.25 to 16 kHz were presented randomly to participants, who had to rate the likeness of each tone to their tinnitus, and to adjust its level from 0 to 100 dB SPL. Tinnitus pitch matching was then assessed with a continuous-pitch method: participants had to match the pitch of their tinnitus to an external tone by moving their finger across a touch-sensitive strip, which generated a continuous pure tone from 0.5 to 20 kHz in 1-Hz steps. The predominant tinnitus pitch was consistent across both methods for both musicians and non-musicians, although musicians displayed better external tone pitch matching abilities. Simulated malingerers rated loudness much higher than did the other groups with a high degree of specificity (94.4%) and were unreliable in loudness (not pitch) matching from one session to the other. Retest data showed similar pitch matching responses for both methods for all participants. In conclusion, tinnitus pitch and loudness reliably correspond to the tinnitus percept, and psychoacoustic loudness matches are sensitive and specific to the presence of tinnitus. PMID:24349414

A survey on sleep assessment methods

PubMed Central

Silva, Josep; Cauli, Omar

2018-01-01

Purpose A literature review is presented that aims to summarize and compare current methods to evaluate sleep. Methods Current sleep assessment methods have been classified according to different criteria; e.g., objective (polysomnography, actigraphy…) vs. subjective (sleep questionnaires, diaries…), contact vs. contactless devices, and need for medical assistance vs. self-assessment. A comparison of validation studies is carried out for each method, identifying their sensitivity and specificity reported in the literature. Finally, the state of the market has also been reviewed with respect to customers’ opinions about current sleep apps. Results A taxonomy that classifies the sleep detection methods. A description of each method that includes the tendencies of their underlying technologies analyzed in accordance with the literature. A comparison in terms of precision of existing validation studies and reports. Discussion In order of accuracy, sleep detection methods may be arranged as follows: Questionnaire < Sleep diary < Contactless devices < Contact devices < Polysomnography A literature review suggests that current subjective methods present a sensitivity between 73% and 97.7%, while their specificity ranges in the interval 50%–96%. Objective methods such as actigraphy present a sensibility higher than 90%. However, their specificity is low compared to their sensitivity, being one of the limitations of such technology. Moreover, there are other factors, such as the patient’s perception of her or his sleep, that can be provided only by subjective methods. Therefore, sleep detection methods should be combined to produce a synergy between objective and subjective methods. The review of the market indicates the most valued sleep apps, but it also identifies problems and gaps, e.g., many hardware devices have not been validated and (especially software apps) should be studied before their clinical use. PMID:29844990

Detection of the KIT D816V mutation in peripheral blood of systemic mastocytosis: diagnostic implications.

PubMed

Jara-Acevedo, Maria; Teodosio, Cristina; Sanchez-Muñoz, Laura; Álvarez-Twose, Ivan; Mayado, Andrea; Caldas, Carolina; Matito, Almudena; Morgado, José M; Muñoz-González, Javier I; Escribano, Luis; Garcia-Montero, Andrés C; Orfao, Alberto

2015-08-01

Recent studies have found the KIT D816V mutation in peripheral blood of virtually all adult systemic mastocytosis patients once highly sensitive PCR techniques were used; thus, detection of the KIT D816V mutation in peripheral blood has been proposed to be included in the diagnostic work-up of systemic mastocytosis algorithms. However, the precise frequency of the mutation, the biological significance of peripheral blood-mutated cells and their potential association with involvement of bone marrow hematopoietic cells other than mast cells still remain to be investigated. Here, we determined the frequency of peripheral blood involvement by the KIT D816V mutation, as assessed by two highly sensitive PCR methods, and investigated its relationship with multilineage involvement of bone marrow hematopoiesis. Overall, our results confirmed the presence of the KIT D816V mutation in peripheral blood of most systemic mastocytosis cases (161/190; 85%)--with an increasing frequency from indolent systemic mastocytosis without skin lesions (29/44; 66%) to indolent systemic mastocytosis with skin involvement (124/135; 92%), and more aggressive disease subtypes (11/11; 100%)--as assessed by the allele-specific oligonucleotide-qPCR method, which was more sensitive (P<.0001) than the peptide nucleic acid-mediated PCR approach (84/190; 44%). Although the presence of the KIT mutation in peripheral blood, as assessed by the allele-specific oligonucleotide-qPCR technique, did not accurately predict for multilineage bone marrow involvement of hematopoiesis, the allele-specific oligonucleotide-qPCR allele burden and the peptide nucleic acid-mediated-PCR approach did. These results suggest that both methods provide clinically useful and complementary information through the identification and/or quantification of the KIT D816V mutation in peripheral blood of patients suspected of systemic mastocytosis.

Passive language mapping combining real-time oscillation analysis with cortico-cortical evoked potentials for awake craniotomy.

PubMed

Tamura, Yukie; Ogawa, Hiroshi; Kapeller, Christoph; Prueckl, Robert; Takeuchi, Fumiya; Anei, Ryogo; Ritaccio, Anthony; Guger, Christoph; Kamada, Kyousuke

2016-12-01

OBJECTIVE Electrocortical stimulation (ECS) is the gold standard for functional brain mapping; however, precise functional mapping is still difficult in patients with language deficits. High gamma activity (HGA) between 80 and 140 Hz on electrocorticography is assumed to reflect localized cortical processing, whereas the cortico-cortical evoked potential (CCEP) can reflect bidirectional responses evoked by monophasic pulse stimuli to the language cortices when there is no patient cooperation. The authors propose the use of "passive" mapping by combining HGA mapping and CCEP recording without active tasks during conscious resections of brain tumors. METHODS Five patients, each with an intraaxial tumor in their dominant hemisphere, underwent conscious resection of their lesion with passive mapping. The authors performed functional localization for the receptive language area, using real-time HGA mapping, by listening passively to linguistic sounds. Furthermore, single electrical pulses were delivered to the identified receptive temporal language area to detect CCEPs in the frontal lobe. All mapping results were validated by ECS, and the sensitivity and specificity were evaluated. RESULTS Linguistic HGA mapping quickly identified the language area in the temporal lobe. Electrical stimulation by linguistic HGA mapping to the identified temporal receptive language area evoked CCEPs on the frontal lobe. The combination of linguistic HGA and frontal CCEPs needed no patient cooperation or effort. In this small case series, the sensitivity and specificity were 93.8% and 89%, respectively. CONCLUSIONS The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain.

How does the Distress Thermometer compare to the Hospital Anxiety and Depression Scale for detecting possible cases of psychological morbidity among cancer survivors?

PubMed

Boyes, Allison; D'Este, Catherine; Carey, Mariko; Lecathelinais, Christophe; Girgis, Afaf

2013-01-01

Use of the Distress Thermometer (DT) as a screening tool is increasing across the cancer trajectory. This study examined the accuracy and optimal cut-off score of the DT compared to the Hospital Anxiety and Depression Scale (HADS) for detecting possible cases of psychological morbidity among adults in early survivorship. This study is a cross-sectional survey of 1,323 adult cancer survivors recruited from two state-based cancer registries in Australia. Participants completed the DT and the HADS at 6 months post-diagnosis. Compared to the HADS subscale threshold ≥8, the DT performed well in discriminating between cases and non-cases of anxiety, depression and comorbid anxiety-depression with an area under the curve of 0.85, 0.84 and 0.87, respectively. A DT cut-off score of ≥2 was best for clinical use (sensitivity, 87-95 %; specificity, 60-68 %), ≥4 was best for research use (sensitivity, 67-82 %; specificity, 81-88 %) and ≥3 was the best balance between sensitivity (77-88 %) and specificity (72-79 %) for detecting cases of anxiety, depression and comorbid anxiety-depression. The DT demonstrated a high level of precision in identifying non-cases of psychological morbidity at all possible thresholds (negative predictive value, 77-99 %). The recommended DT cut-off score of ≥4 was not supported for universal use among recent cancer survivors. The optimal DT threshold depends upon whether the tool is being used in the clinical or research setting. The DT may best serve to initially identify non-cases as part of a two-stage screening process. The performance of the DT against 'gold standard' clinical interview should be evaluated with cancer survivors.

Troponin T and Heart Type Fatty Acid Binding Protein (h-Fabp) as Biomarkers in Patients Presenting with Chest Pain.

PubMed

Reddy, Lakshmi Lavanya; Shah, Swarup A V; Dherai, Alpa J; Ponde, Chandrashekhar K; Ashavaid, Tester F

2016-03-01

Acute coronary syndrome (ACS) is a term for a range of clinical signs and symptoms suggestive of myocardial ischemia. It results in functional and structural changes and ultimately releasing protein from injured cardiomyocytes. These cardiac markers play a major role in diagnosis and prognosis of ACS. This study aims to assess the efficacy of heart type fatty acid binding protein (h-FABP) as a marker for ACS along with the routinely used hs-TropT. In our observational study, plasma h-FABP (cut-off 6.32 ng/ml) and routinely done hs-Trop T (cutoff 0.1 and 0.014 ng/ml) were estimated by immunometric laboratory assays in 88 patients with acute chest pain. Based on the clinical and laboratory test findings the patients were grouped into ACS (n = 41) and non-ACS (n = 47). The diagnostic sensitivity, specificity, NPV, PPV and ROC curve at 95 % CI were determined. Sensitivity of hs-TropT (0.1 ng/ml), hs-TropT (0.014 ng/ml) and h-FABP were 53, 86 and 78 % respectively and specificity for the same were 98, 73 and 70 % respectively. Sensitivity, specificity and NPV calculated for a cut-off combination of hs-TropT 0.014 ng/ml and h-FABP was 100, 51 and 100 % respectively. These results were substantiated by ROC analysis. Measurement of plasma h-FABP and hs-TropT together on admission appears to be more precise predictor of ACS rather than either hs-Trop T or h-FABP.

B-type natriuretic peptides help in cardioembolic stroke diagnosis: pooled data meta-analysis.

PubMed

Llombart, Víctor; Antolin-Fontes, Albert; Bustamante, Alejandro; Giralt, Dolors; Rost, Natalia S; Furie, Karen; Shibazaki, Kensaku; Biteker, Murat; Castillo, José; Rodríguez-Yáñez, Manuel; Fonseca, Ana Catarina; Watanabe, Tetsu; Purroy, Francisco; Zhixin, Wu; Etgen, Thorleif; Hosomi, Naohisa; Jafarian Kerman, Scott Reza; Sharma, Jagdish C; Knauer, Carolin; Santamarina, Estevo; Giannakoulas, George; García-Berrocoso, Teresa; Montaner, Joan

2015-05-01

Determining the underlying cause of stroke is important to optimize secondary prevention treatment. Increased blood levels of natriuretic peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have been repeatedly associated with cardioembolic stroke. Here, we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants' data meta-analysis. We searched publications in PubMed database until November 2013 that compared BNP and NT-proBNP circulating levels among stroke causes. Standardized individual participants' data were collected to estimate predictive values of BNP/NT-proBNP for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in logistic regression models together with clinical variables to assess the sensitivity and specificity to identify cardioembolic strokes and the additional value of biomarkers using area under the curve and integrated discrimination improvement index. From 23 selected articles, we collected information of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were added considering the lowest and the highest quartile, respectively. Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models. Sensitivity, specificity, and precision of the models were validated in 197 patients with initially undetermined stroke with final pathogenic diagnosis after ancillary follow-up. Natriuretic peptides are strongly increased in cardioembolic strokes. Future multicentre prospective studies comparing BNP and NT-proBNP might aid in finding the optimal biomarker, the best time point, and the optimal cutoff points for cardioembolic stroke identification. © 2015 American Heart Association, Inc.

Modeling and Positioning of a PZT Precision Drive System.

PubMed

Liu, Che; Guo, Yanling

2017-11-08

The fact that piezoelectric ceramic transducer (PZT) precision drive systems in 3D printing are faced with nonlinear problems with respect to positioning, such as hysteresis and creep, has had an extremely negative impact on the precision of laser focusing systems. To eliminate the impact of PZT nonlinearity during precision drive movement, mathematical modeling and theoretical analyses of each module comprising the system were carried out in this study, a micro-displacement measurement circuit based on Position Sensitive Detector (PSD) is constructed, followed by the establishment of system closed-loop control and creep control models. An XL-80 laser interferometer (Renishaw, Wotton-under-Edge, UK) was used to measure the performance of the precision drive system, showing that system modeling and control algorithms were correct, with the requirements for precision positioning of the drive system satisfied.

Modeling and Positioning of a PZT Precision Drive System

PubMed Central

Liu, Che; Guo, Yanling

2017-01-01

The fact that piezoelectric ceramic transducer (PZT) precision drive systems in 3D printing are faced with nonlinear problems with respect to positioning, such as hysteresis and creep, has had an extremely negative impact on the precision of laser focusing systems. To eliminate the impact of PZT nonlinearity during precision drive movement, mathematical modeling and theoretical analyses of each module comprising the system were carried out in this study, a micro-displacement measurement circuit based on Position Sensitive Detector (PSD) is constructed, followed by the establishment of system closed-loop control and creep control models. An XL-80 laser interferometer (Renishaw, Wotton-under-Edge, UK) was used to measure the performance of the precision drive system, showing that system modeling and control algorithms were correct, with the requirements for precision positioning of the drive system satisfied. PMID:29117140

Validation of HPLC and UV spectrophotometric methods for the determination of meropenem in pharmaceutical dosage form.

PubMed

Mendez, Andreas S L; Steppe, Martin; Schapoval, Elfrides E S

2003-12-04

A high-performance liquid chromatographic method and a UV spectrophotometric method for the quantitative determination of meropenem, a highly active carbapenem antibiotic, in powder for injection were developed in present work. The parameters linearity, precision, accuracy, specificity, robustness, limit of detection and limit of quantitation were studied according to International Conference on Harmonization guidelines. Chromatography was carried out by reversed-phase technique on an RP-18 column with a mobile phase composed of 30 mM monobasic phosphate buffer and acetonitrile (90:10; v/v), adjusted to pH 3.0 with orthophosphoric acid. The UV spectrophotometric method was performed at 298 nm. The samples were prepared in water and the stability of meropenem in aqueous solution at 4 and 25 degrees C was studied. The results were satisfactory with good stability after 24 h at 4 degrees C. Statistical analysis by Student's t-test showed no significant difference between the results obtained by the two methods. The proposed methods are highly sensitive, precise and accurate and can be used for the reliable quantitation of meropenem in pharmaceutical dosage form.

Development and validation of liquid chromatographic and UV derivative spectrophotometric methods for the determination of famciclovir in pharmaceutical dosage forms.

PubMed

Srinubabu, Gedela; Sudharani, Batchu; Sridhar, Lade; Rao, Jvln Seshagiri

2006-06-01

A high-performance liquid chromatographic method and a UV derivative spectrophotometric method for the determination of famciclovir, a highly active antiviral agent, in tablets were developed in the present work. The various parameters, such as linearity, precision, accuracy, specificity, robustness, limit of detection and limit of quantitation were studied according to International Conference on Harmonization guidelines. HPLC was carried out by using the reversed-phase technique on an RP-18 column with a mobile phase composed of 50 mM monobasic phosphate buffer and methanol (50 : 50; v/v), adjusted to pH 3.05 with orthophosphoric acid. The mobile phase was pumped at a flow rate of 1 ml/min and detection was made at 242 nm with UV dual absorbance detector. The first derivative UV spectrophotometric method was performed at 226.5 nm. Statistical analysis was done by Student's t-test and F-test, which showed no significant difference between the results obtained by the two methods. The proposed methods are highly sensitive, precise and accurate and therefore can be used for its Intended purpose.

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

Kalaydzhyan, Tigran

Within the general theory of relativity, the curvature of spacetime is related to the energy and momentum of the present matter and radiation. One of the more specific predictions of general relativity is the deflection of light and particle trajectories in the gravitational field of massive objects. Bending angles for electromagnetic waves and light in particular were measured with a high precision. However, the effect of gravity on relativistic massive particles was never studied experimentally. Here we propose and analyze experiments devoted to that purpose. We demonstrate a high sensitivity of the laser Compton scattering at high energy accelerators tomore » the effects of gravity. The main observable – maximal energy of the scattered photons – would experience a significant shift in the ambient gravitational field even for otherwise negligible violation of the equivalence principle. In conclusion, we confirm predictions of general relativity for ultrarelativistic electrons of energy of tens of GeV at a current level of resolution and expect our work to be a starting point of further high-precision studies on current and future accelerators, such as PETRA, European XFEL and ILC.« less

Testing general relativity on accelerators

DOE PAGES

Kalaydzhyan, Tigran

2015-09-07

Within the general theory of relativity, the curvature of spacetime is related to the energy and momentum of the present matter and radiation. One of the more specific predictions of general relativity is the deflection of light and particle trajectories in the gravitational field of massive objects. Bending angles for electromagnetic waves and light in particular were measured with a high precision. However, the effect of gravity on relativistic massive particles was never studied experimentally. Here we propose and analyze experiments devoted to that purpose. We demonstrate a high sensitivity of the laser Compton scattering at high energy accelerators tomore » the effects of gravity. The main observable – maximal energy of the scattered photons – would experience a significant shift in the ambient gravitational field even for otherwise negligible violation of the equivalence principle. In conclusion, we confirm predictions of general relativity for ultrarelativistic electrons of energy of tens of GeV at a current level of resolution and expect our work to be a starting point of further high-precision studies on current and future accelerators, such as PETRA, European XFEL and ILC.« less

Selectively Sized Graphene-Based Nanopores for in Situ Single Molecule Sensing

PubMed Central

2015-01-01

The use of nanopore biosensors is set to be extremely important in developing precise single molecule detectors and providing highly sensitive advanced analysis of biological molecules. The precise tailoring of nanopore size is a significant step toward achieving this, as it would allow for a nanopore to be tuned to a corresponding analyte. The work presented here details a methodology for selectively opening nanopores in real-time. The tunable nanopores on a quartz nanopipette platform are fabricated using the electroetching of a graphene-based membrane constructed from individual graphene nanoflakes (ø ∼30 nm). The device design allows for in situ opening of the graphene membrane, from fully closed to fully opened (ø ∼25 nm), a feature that has yet to be reported in the literature. The translocation of DNA is studied as the pore size is varied, allowing for subfeatures of DNA to be detected with slower DNA translocations at smaller pore sizes, and the ability to observe trends as the pore is opened. This approach opens the door to creating a device that can be target to detect specific analytes. PMID:26204996

[Assessment of lymph node metastasis in gastric cancer: status quo, recent advances and new perspectives].

PubMed

Tu, Min; Zhu, Zhen-shu; Shi, Lin-sen; Jiang, Xi-qun; Wang, Hao; Guan, Wen-xian

2012-02-01

The precondition of accurate gastric cancer surgery is precise assessment of lymph node metastasis. To date, no imaging modality achieves both high sensitivity and high specificity in detecting lymph node metastasis in gastric cancer. Intraoperative sentinel node tracing and biopsy are the most popular method to identify the localization of tumor cell, but is limited to early gastric cancer. Nano-composite materials, designed for tumor imaging and tracing, show us a newly emerging domain for tumor detection in gastric cancer. The function of these nano-composite materials to detect lymph node metastasis in gastric cancer relies on the effective backflow of lymph system. However, the lymph vessels can be obstructed by tumor cells in advanced gastric cancer, which may restrain the application of these nanoparticles. Therefore, more methods to detect lymph node metastasis in gastric cancer should be explored. This review summarizes the characteristic of the targeted nanosphere. Based on the reported studies, a novel idea is conceived that targeted multifunctional nanosphere may be a potential method to achieve precise assessment of lymph node metastasis in gastric cancer.

Validated modified Lycopodium spore method development for standardisation of ingredients of an ayurvedic powdered formulation Shatavaryadi churna.

PubMed

Kumar, Puspendra; Jha, Shivesh; Naved, Tanveer

2013-01-01

Validated modified lycopodium spore method has been developed for simple and rapid quantification of herbal powdered drugs. Lycopodium spore method was performed on ingredients of Shatavaryadi churna, an ayurvedic formulation used as immunomodulator, galactagogue, aphrodisiac and rejuvenator. Estimation of diagnostic characters of each ingredient of Shatavaryadi churna individually was carried out. Microscopic determination, counting of identifying number, measurement of area, length and breadth of identifying characters were performed using Leica DMLS-2 microscope. The method was validated for intraday precision, linearity, specificity, repeatability, accuracy and system suitability, respectively. The method is simple, precise, sensitive, and accurate, and can be used for routine standardisation of raw materials of herbal drugs. This method gives the ratio of individual ingredients in the powdered drug so that any adulteration of genuine drug with its adulterant can be found out. The method shows very good linearity value between 0.988-0.999 for number of identifying character and area of identifying character. Percentage purity of the sample drug can be determined by using the linear equation of standard genuine drug.

System-state and operating condition sensitive control method and apparatus for electric power delivery systems

NASA Technical Reports Server (NTRS)

Burns, III, William Wesley (Inventor); Wilson, Thomas George (Inventor)

1978-01-01

This invention provides a method and apparatus for determining a precise switching sequence for the power switching elements of electric power delivery systems of the on-off switching type and which enables extremely fast transient response, precise regulation and highly stable operation. The control utilizes the values of the power delivery system power handling network components, a desired output characteristic, a system timing parameter, and the externally imposed operating conditions to determine where steady state operations should be in order to yield desired output characteristics for the given system specifications. The actual state of the power delivery system is continuously monitored and compared to a state-space boundary which is derived from the desired equilibrium condition, and from the information obtained from this comparison, the system is moved to the desired equilibrium condition in one cycle of switching control. Since the controller continuously monitors the power delivery system's externally imposed operating conditions, a change in the conditions is immediately sensed and a new equilibrium condition is determined and achieved, again in a single cycle of switching control.

A real-time compliance mapping system using standard endoscopic surgical forceps.

PubMed

Fakhry, Morkos; Bello, Fernando; Hanna, George B

2009-04-01

In endoscopic surgery, the use of long surgical instruments through access ports diminishes tactile feedback and degrades the surgeon's ability to identify hidden tissue abnormalities. To overcome this constraint, we developed a real-time compliance mapping system that is composed of: 1) a standard surgical instrument with a high-precision sensor configuration design; 2) real-time objective interpretation of the output signals for tissue identification; and 3) a novel human-computer interaction technique using interactive voice and handle force monitoring techniques to suit operating theater working environment. The system was calibrated and used in clinical practice in four routine endoscopic human procedures. In a laboratory-based experiment to compare the tissue discriminatory power of the system with that of surgeons' hands, the system's tissue discriminatory power was three times more sensitive and 10% less specific. The data acquisition precision was tested using principal component analysis (R(2)X = 0.975, Q2 [cumulative (cum)] = 0.808 ) and partial least square discriminate analysis (R(2)X = 0.903, R(2)Y = 0.729, Q2 (cum) = 0.572).

Possibility for precise Weinberg-angle measurement in centrosymmetric crystals with axis

NASA Astrophysics Data System (ADS)

Mukhamedjanov, T. N.; Sushkov, O. P.

2006-03-01

We demonstrate that parity-nonconserving interaction due to the nuclear weak charge QW leads to a nonlinear magnetoelectric effect in centrosymmetric paramagnetic crystals. It is shown that the effect exists only in crystals with special symmetry axis k . Kinematically, the correlation (correction to energy) has the form HPNC∝QWE•[B×k](B•k) , where B and E are external magnetic and electric fields. This gives rise to the magnetic induction MPNC∝QW{k(B•[k×E])+[k×E](B•k)} . To be specific, we consider rare-earth-metal trifluorides and, in particular, dysprosium trifluoride which looks the most suitable for experiment. We estimate the optimal temperature for the experiment to be of a few kelvin. For the magnetic field B=1T and the electric field E=10kV/cm , the expected magnetic induction is 4πMPNC˜0.5×10-11G , six orders of magnitude larger than the best sensitivity currently under discussion. Dysprosium has several stable isotopes, and so comparison of the effects for different isotopes provides the possibility for precise measurement of the Weinberg angle.

COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples.

PubMed

Yamagata, Koichi; Yamanishi, Ayako; Kokubu, Chikara; Takeda, Junji; Sese, Jun

2016-05-05

An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

More noise does not mean more precision: A review of Aldenberg and Rorije (2013).

PubMed

Fox, David R

2015-09-01

This paper provides a critical review of recently published work that suggests that the precision of hazardous concentration estimates from Species Sensitivity Distributions (SSDs) is improved when the uncertainty in the input data is taken into account. Our review confirms that this counter-intuitive result is indeed incorrect. 2015 FRAME.

MultiMiTar: a novel multi objective optimization based miRNA-target prediction method.

PubMed

Mitra, Ramkrishna; Bandyopadhyay, Sanghamitra

2011-01-01

Machine learning based miRNA-target prediction algorithms often fail to obtain a balanced prediction accuracy in terms of both sensitivity and specificity due to lack of the gold standard of negative examples, miRNA-targeting site context specific relevant features and efficient feature selection process. Moreover, all the sequence, structure and machine learning based algorithms are unable to distribute the true positive predictions preferentially at the top of the ranked list; hence the algorithms become unreliable to the biologists. In addition, these algorithms fail to obtain considerable combination of precision and recall for the target transcripts that are translationally repressed at protein level. In the proposed article, we introduce an efficient miRNA-target prediction system MultiMiTar, a Support Vector Machine (SVM) based classifier integrated with a multiobjective metaheuristic based feature selection technique. The robust performance of the proposed method is mainly the result of using high quality negative examples and selection of biologically relevant miRNA-targeting site context specific features. The features are selected by using a novel feature selection technique AMOSA-SVM, that integrates the multi objective optimization technique Archived Multi-Objective Simulated Annealing (AMOSA) and SVM. MultiMiTar is found to achieve much higher Matthew's correlation coefficient (MCC) of 0.583 and average class-wise accuracy (ACA) of 0.8 compared to the others target prediction methods for a completely independent test data set. The obtained MCC and ACA values of these algorithms range from -0.269 to 0.155 and 0.321 to 0.582, respectively. Moreover, it shows a more balanced result in terms of precision and sensitivity (recall) for the translationally repressed data set as compared to all the other existing methods. An important aspect is that the true positive predictions are distributed preferentially at the top of the ranked list that makes MultiMiTar reliable for the biologists. MultiMiTar is now available as an online tool at www.isical.ac.in/~bioinfo_miu/multimitar.htm. MultiMiTar software can be downloaded from www.isical.ac.in/~bioinfo_miu/multimitar-download.htm.

The Next Generation Transit Survey (NGTS)

NASA Astrophysics Data System (ADS)

Wheatley, Peter J.; West, Richard G.; Goad, Michael R.; Jenkins, James S.; Pollacco, Don L.; Queloz, Didier; Rauer, Heike; Udry, Stéphane; Watson, Christopher A.; Chazelas, Bruno; Eigmüller, Philipp; Lambert, Gregory; Genolet, Ludovic; McCormac, James; Walker, Simon; Armstrong, David J.; Bayliss, Daniel; Bento, Joao; Bouchy, François; Burleigh, Matthew R.; Cabrera, Juan; Casewell, Sarah L.; Chaushev, Alexander; Chote, Paul; Csizmadia, Szilárd; Erikson, Anders; Faedi, Francesca; Foxell, Emma; Gänsicke, Boris T.; Gillen, Edward; Grange, Andrew; Günther, Maximilian N.; Hodgkin, Simon T.; Jackman, James; Jordán, Andrés; Louden, Tom; Metrailler, Lionel; Moyano, Maximiliano; Nielsen, Louise D.; Osborn, Hugh P.; Poppenhaeger, Katja; Raddi, Roberto; Raynard, Liam; Smith, Alexis M. S.; Soto, Maritza; Titz-Weider, Ruth

2018-04-01

We describe the Next Generation Transit Survey (NGTS), which is a ground-based project searching for transiting exoplanets orbiting bright stars. NGTS builds on the legacy of previous surveys, most notably WASP, and is designed to achieve higher photometric precision and hence find smaller planets than have previously been detected from the ground. It also operates in red light, maximizing sensitivity to late K and early M dwarf stars. The survey specifications call for photometric precision of 0.1 per cent in red light over an instantaneous field of view of 100 deg2, enabling the detection of Neptune-sized exoplanets around Sun-like stars and super-Earths around M dwarfs. The survey is carried out with a purpose-built facility at Cerro Paranal, Chile, which is the premier site of the European Southern Observatory (ESO). An array of twelve 20 cm f/2.8 telescopes fitted with back-illuminated deep-depletion CCD cameras is used to survey fields intensively at intermediate Galactic latitudes. The instrument is also ideally suited to ground-based photometric follow-up of exoplanet candidates from space telescopes such as TESS, Gaia and PLATO. We present observations that combine precise autoguiding and the superb observing conditions at Paranal to provide routine photometric precision of 0.1 per cent in 1 h for stars with I-band magnitudes brighter than 13. We describe the instrument and data analysis methods as well as the status of the survey, which achieved first light in 2015 and began full-survey operations in 2016. NGTS data will be made publicly available through the ESO archive.

Fluorescence confocal mosaicing microscopy of basal cell carcinomas ex vivo: demonstration of rapid surgical pathology with high sensitivity and specificity

NASA Astrophysics Data System (ADS)

Gareau, Daniel S.; Karen, Julie K.; Dusza, Stephen W.; Tudisco, Marie; Nehal, Kishwer S.; Rajadhyaksha, Milind

2009-02-01

Mohs surgery, for the precise removal of basal cell carcinomas (BCCs), consists of a series of excisions guided by the surgeon's examination of the frozen histology of the previous excision. The histology reveals atypical nuclear morphology, identifying cancer. The preparation of frozen histology is accurate but labor-intensive and slow. Nuclear pathology can be achieved by staining with acridine orange (1 mM, 20 s) BCCs in Mohs surgical skin excisions within 5-9 minutes, compared to 20-45 for frozen histology. For clinical utility, images must have high contrast and high resolution. We report tumor contrast of 10-100 fold over the background dermis and submicron (diffraction limited) resolution over a cm field of view. BCCs were detected with an overall sensitivity of 96.6%, specificity of 89.2%, positive predictive value of 93.0% and negative predictive value of 94.7%. The technique was therefore accurate for normal tissue as well as tumor. We conclude that fluorescence confocal mosaicing serves as a sensitive and rapid pathological tool. Beyond Mohs surgery, this technology may be extended to suit other pathological needs with the development of new contrast agents. The technique reported here accurately detects all subtypes of BCC in skin excisions, including the large nodular, small micronodular, and tiny sclerodermaform tumors. However, this technique may be applicable to imaging tissue that is larger, more irregular and of various mechanical compliances with further engineering of the tissue mounting and staging mechanisms.

Influence of speckle image reconstruction on photometric precision for large solar telescopes

NASA Astrophysics Data System (ADS)

Peck, C. L.; Wöger, F.; Marino, J.

2017-11-01

Context. High-resolution observations from large solar telescopes require adaptive optics (AO) systems to overcome image degradation caused by Earth's turbulent atmosphere. AO corrections are, however, only partial. Achieving near-diffraction limited resolution over a large field of view typically requires post-facto image reconstruction techniques to reconstruct the source image. Aims: This study aims to examine the expected photometric precision of amplitude reconstructed solar images calibrated using models for the on-axis speckle transfer functions and input parameters derived from AO control data. We perform a sensitivity analysis of the photometric precision under variations in the model input parameters for high-resolution solar images consistent with four-meter class solar telescopes. Methods: Using simulations of both atmospheric turbulence and partial compensation by an AO system, we computed the speckle transfer function under variations in the input parameters. We then convolved high-resolution numerical simulations of the solar photosphere with the simulated atmospheric transfer function, and subsequently deconvolved them with the model speckle transfer function to obtain a reconstructed image. To compute the resulting photometric precision, we compared the intensity of the original image with the reconstructed image. Results: The analysis demonstrates that high photometric precision can be obtained for speckle amplitude reconstruction using speckle transfer function models combined with AO-derived input parameters. Additionally, it shows that the reconstruction is most sensitive to the input parameter that characterizes the atmospheric distortion, and sub-2% photometric precision is readily obtained when it is well estimated.

Dynamic Response of a Planetary Gear System Using a Finite Element/Contact Mechanics Model

NASA Technical Reports Server (NTRS)

Parker, Robert G.; Agashe, Vinayak; Vijayakar, Sandeep M.

2000-01-01

The dynamic response of a helicopter planetary gear system is examined over a wide range of operating speeds and torques. The analysis tool is a unique, semianalytical finite element formulation that admits precise representation of the tooth geometry and contact forces that are crucial in gear dynamics. Importantly, no a priori specification of static transmission error excitation or mesh frequency variation is required; the dynamic contact forces are evaluated internally at each time step. The calculated response shows classical resonances when a harmonic of mesh frequency coincides with a natural frequency. However, peculiar behavior occurs where resonances expected to be excited at a given speed are absent. This absence of particular modes is explained by analytical relationships that depend on the planetary configuration and mesh frequency harmonic. The torque sensitivity of the dynamic response is examined and compared to static analyses. Rotation mode response is shown to be more sensitive to input torque than translational mode response.

Finding Qualitative Research Evidence for Health Technology Assessment.

PubMed

DeJean, Deirdre; Giacomini, Mita; Simeonov, Dorina; Smith, Andrea

2016-08-01

Health technology assessment (HTA) agencies increasingly use reviews of qualitative research as evidence for evaluating social, experiential, and ethical aspects of health technologies. We systematically searched three bibliographic databases (MEDLINE, CINAHL, and Social Science Citation Index [SSCI]) using published search filters or "hedges" and our hybrid filter to identify qualitative research studies pertaining to chronic obstructive pulmonary disease and early breast cancer. The search filters were compared in terms of sensitivity, specificity, and precision. Our screening by title and abstract revealed that qualitative research constituted only slightly more than 1% of all published research on each health topic. The performance of the published search filters varied greatly across topics and databases. Compared with existing search filters, our hybrid filter demonstrated a consistently high sensitivity across databases and topics, and minimized the resource-intensive process of sifting through false positives. We identify opportunities for qualitative health researchers to improve the uptake of qualitative research into evidence-informed policy making. © The Author(s) 2016.

Analysis of beryllium and depleted uranium: An overview of detection methods in aerosols and soils

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

Camins, I.; Shinn, J.H.

We conducted a survey of commercially available methods for analysis of beryllium and depleted uranium in aerosols and soils to find a reliable, cost-effective, and sufficiently precise method for researchers involved in environmental testing at the Yuma Proving Ground, Yuma, Arizona. Criteria used for evaluation include cost, method of analysis, specificity, sensitivity, reproducibility, applicability, and commercial availability. We found that atomic absorption spectrometry with graphite furnace meets these criteria for testing samples for beryllium. We found that this method can also be used to test samples for depleted uranium. However, atomic absorption with graphite furnace is not as sensitive amore » measurement method for depleted uranium as it is for beryllium, so we recommend that quality control of depleted uranium analysis be maintained by testing 10 of every 1000 samples by neutron activation analysis. We also evaluated 45 companies and institutions that provide analyses of beryllium and depleted uranium. 5 refs., 1 tab.« less

A double-fibre Fabry-Perot sensor based on modified fringe counting and direct phase demodulation

NASA Astrophysics Data System (ADS)

Li, M.; Tong, B.; Arsad, N.; Guo, J. J.

2013-09-01

A modified double-fibre Fabry-Perot cavity is developed for determination of the fringe moving direction and higher sensitivity in applications of liquid level and displacement sensors. Two fibres are integrated into a silica ferrule where the ends of the two fibres in the ferrule serve as the front surfaces of the Fabry-Perot cavities, and a diaphragm, which is replaced by a moving mirror for measurement of displacement, serves as the rear surface for both cavities in liquid level sensing. Our design has no strict requirements for a specific phase difference between the two optical paths, just a constant difference resulting from the processing error between the two fibre end positions rather than a precise optical path difference of λ/8 to judge the pattern shift direction. Experimental results demonstrate the feasibility of this approach to determining the fringe moving direction, a displacement sensitivity of 3 µm and good linearity for both applications.

A Novel Immunoreagent for the Specific and Sensitive Detection of the Explosive Triacetone Triperoxide (TATP).

PubMed

Walter, Maria Astrid; Panne, Ulrich; Weller, Michael G

2011-07-07

Triacetone triperoxide (TATP) is a primary explosive, which was used in various terrorist attacks in the past. For the development of biosensors, immunochemical µ-TAS, electronic noses, immunological test kits, or test strips, the availability of antibodies of high quality is crucial. Recently, we presented the successful immunization of mice, based on the design, synthesis, and conjugation of a novel TATP derivative. Here, the long-term immunization of rabbits is shown, which resulted in antibodies of extreme selectivity and more than 1,000 times better affinity in relation to the antibodies from mice. Detection limits below 10 ng L-1 (water) were achieved. The working range covers more than four decades, calculated from a precision profile. The cross-reactivity tests revealed an extraordinary selectivity of the antibodies-not a single compound could be identified as a relevant cross-reactant. The presented immunoreagent might be a major step for the development of highly sensitive and selective TATP detectors particularly for security applications.

All-Optical Electrophysiology for Disease Modeling and Pharmacological Characterization of Neurons.

PubMed

Werley, Christopher A; Brookings, Ted; Upadhyay, Hansini; Williams, Luis A; McManus, Owen B; Dempsey, Graham T

2017-09-11

A key challenge for establishing a phenotypic screen for neuronal excitability is measurement of membrane potential changes with high throughput and accuracy. Most approaches for probing excitability rely on low-throughput, invasive methods or lack cell-specific information. These limitations stimulated the development of novel strategies for characterizing the electrical properties of cultured neurons. Among these was the development of optogenetic technologies (Optopatch) that allow for stimulation and recording of membrane voltage signals from cultured neurons with single-cell sensitivity and millisecond temporal resolution. Neuronal activity is elicited using blue light activation of the channelrhodopsin variant 'CheRiff'. Action potentials and synaptic signals are measured with 'QuasAr', a rapid and sensitive voltage-indicating protein with near-infrared fluorescence that scales proportionately with transmembrane potential. This integrated technology of optical stimulation and recording of electrical signals enables investigation of neuronal electrical function with unprecedented scale and precision. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

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

Christy, Brian; Anella, Ryan; Lommen, Andrea

Pulsar timing arrays (PTAs) are a collection of precisely timed millisecond pulsars (MSPs) that can search for gravitational waves (GWs) in the nanohertz frequency range by observing characteristic signatures in the timing residuals. The sensitivity of a PTA depends on the direction of the propagating GW source, the timing accuracy of the pulsars, and the allocation of the available observing time. The goal of this paper is to determine the optimal time allocation strategy among the MSPs in the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) for a single source of GW under a particular set of assumptions. Wemore » consider both an isotropic distribution of sources across the sky and a specific source in the Virgo cluster. This work improves on previous efforts by modeling the effect of intrinsic spin noise for each pulsar. We find that, in general, the array is optimized by maximizing time spent on the best-timed pulsars, with sensitivity improvements typically ranging from a factor of 1.5 to 4.« less

A Novel Immunoreagent for the Specific and Sensitive Detection of the Explosive Triacetone Triperoxide (TATP)

PubMed Central

Walter, Maria Astrid; Panne, Ulrich; Weller, Michael G.

2011-01-01

Triacetone triperoxide (TATP) is a primary explosive, which was used in various terrorist attacks in the past. For the development of biosensors, immunochemical µ-TAS, electronic noses, immunological test kits, or test strips, the availability of antibodies of high quality is crucial. Recently, we presented the successful immunization of mice, based on the design, synthesis, and conjugation of a novel TATP derivative. Here, the long-term immunization of rabbits is shown, which resulted in antibodies of extreme selectivity and more than 1,000 times better affinity in relation to the antibodies from mice. Detection limits below 10 ng L−1 (water) were achieved. The working range covers more than four decades, calculated from a precision profile. The cross-reactivity tests revealed an extraordinary selectivity of the antibodies—not a single compound could be identified as a relevant cross-reactant. The presented immunoreagent might be a major step for the development of highly sensitive and selective TATP detectors particularly for security applications. PMID:25586922

Optimized efficient liver T1ρ mapping using limited spin lock times

NASA Astrophysics Data System (ADS)

Yuan, Jing; Zhao, Feng; Griffith, James F.; Chan, Queenie; Wang, Yi-Xiang J.

2012-03-01

T1ρ relaxation has recently been found to be sensitive to liver fibrosis and has potential to be used for early detection of liver fibrosis and grading. Liver T1ρ imaging and accurate mapping are challenging because of the long scan time, respiration motion and high specific absorption rate. Reduction and optimization of spin lock times (TSLs) are an efficient way to reduce scan time and radiofrequency energy deposition of T1ρ imaging, but maintain the near-optimal precision of T1ρ mapping. This work analyzes the precision in T1ρ estimation with limited, in particular two, spin lock times, and explores the feasibility of using two specific operator-selected TSLs for efficient and accurate liver T1ρ mapping. Two optimized TSLs were derived by theoretical analysis and numerical simulations first, and tested experimentally by in vivo rat liver T1ρ imaging at 3 T. The simulation showed that the TSLs of 1 and 50 ms gave optimal T1ρ estimation in a range of 10-100 ms. In the experiment, no significant statistical difference was found between the T1ρ maps generated using the optimized two-TSL combination and the maps generated using the six TSLs of [1, 10, 20, 30, 40, 50] ms according to one-way ANOVA analysis (p = 0.1364 for liver and p = 0.8708 for muscle).

Modeling and experimental design for metabolic flux analysis of lysine-producing Corynebacteria by mass spectrometry.

PubMed

Wittmann, C; Heinzle, E

2001-04-01

Experimental design of (13)C-tracer studies for metabolic flux analysis with mass spectrometric determination of labeling patterns was performed for the central metabolism of Corynebacterium glutamicum comprising various flux scenarios. Ratio measurement of mass isotopomer pools of Corynebacterium products lysine, alanine, and trehalose is sufficient to quantify the flux partitioning ratios (i) between glycolysis and pentose phosphate pathways (Phi(PPP)), (ii) between the split pathways in the lysine biosynthesis (Phi(DH)), (iii) at the pyruvate node (Phi(PC)), and reversibilities of (iv) glucose 6-phosphate isomerase (zeta(PGI)), (v) at the pyruvate node (zeta(PC/PEPCK)), and (vi) of transaldolase and transketolases in the PPP. Weighted sensitivities for flux parameters were derived from partial derivatives to quantitatively evaluate experimental approaches and predict precision for estimated flux parameters. Deviation of intensity ratios from ideal values of 1 was used as weighting function. Weighted flux sensitivities can be used to identify optimal type and degree of tracer labeling or potential intensity ratios to be measured. Experimental design for lysine-producing strain C. glutamicum MH 20-22B (Marx et al., Biotechnol. Bioeng. 49, 111-129, 1996) and various potential mutants with different alterations in the flux pattern showed that specific tracer labelings are optimal to quantify a certain flux parameter uninfluenced by the overall flux situation. Identified substrates of choice are [1-(13)C]glucose for the estimation of Phi(PPP) and zeta(PGI) and a 1 : 1 mixture of [U-(12)C/U-(13)C]glucose for the determination of zeta(PC/PEPCK). Phi(PC) can be quantified by feeding [4-(13)C]glucose or [U-(12)C/U-(13)C]glucose (1 : 1), whereas Phi(DH) is accessible via [4-(13)C]glucose. The sensitivity for the quantification of a certain flux parameter can be influenced by superposition through other flux parameters in the network, but substrate and measured mass isotopomers of choice remain the same. In special cases, reduced labeling degree of the tracer substrate can increase the precision of flux analysis. Enhanced precision and flux information can be achieved via multiply labeled substrates. The presented approach can be applied for effective experimental design of (13)C tracer studies for metabolic flux analysis. Intensity ratios of other products such as glutamate, valine, phenylalanine, and riboflavin also sensitively reflect flux parameters, which underlines the great potential of mass spectrometry for flux analysis. Copyright 2001 Academic Press.

Experimentally induced central sensitization in the cervical spine evokes postural stiffening strategies in healthy young adults.

PubMed

Huntley, Andrew H; Srbely, John Z; Zettel, John L

2015-02-01

Dysequilibrium of cervicogenic origin can result from pain and injury to cervical paraspinal tissues post-whiplash; however, the specific physiological mechanisms still remain unclear. Central sensitization is a neuradaptive process which has been clinically associated with conditions of chronic pain and hypersensitivity. Strong links have been demonstrated between pain hypersensitivity and postural deficits post-whiplash; however, the precise mechanisms are still poorly understood. The purpose of this study was to explore the mechanisms of cervicogenic disequilibrium by investigating the effect of experimentally induced central sensitization in the cervical spine on postural stability in young healthy adults. Sixteen healthy young adults (7 males (22.6±1.13 years) and 9 females (22±2.69 years)) performed 30-s full-tandem stance trials on an AMTI force plate under normal and centrally sensitized conditions. The primary outcome variables included the standard deviation of the center of pressure (COP) position in medio-lateral (M-L) and antero-posterior (A-P) directions; sway range of the COP in M-L and A-P directions and the mean power frequency (MPF) of the COP and horizontal ground shear forces. Variability and sway range of the COP decreased with experimental induction of central sensitization, accompanied by an increase in MPF of COP displacement in both M-L and A-P directions, suggesting an increase in postural stiffening post-sensitization versus non-sensitized controls. Future studies need to further explore this relationship in clinical (whiplash, chronic pain) populations. Copyright © 2015 Elsevier B.V. All rights reserved.

Engineering and agronomy aspects of a long-term precision agriculture field experiment

USDA-ARS?s Scientific Manuscript database

Much research has been conducted on specific precision agriculture tools and implementation strategies, but little has been reported on long-term evaluation of integrated precision agriculture field experiments. In 2004 our research team developed and initiated a multi-faceted “precision agriculture...

New Chromogenic Agar Medium for the Identification of Candida spp.

PubMed Central

Cooke, Venitia M.; Miles, R. J.; Price, R. G.; Midgley, G.; Khamri, W.; Richardson, A. C.

2002-01-01

A new chromogenic agar medium (Candida diagnostic agar [CDA]) for differentiation of Candida spp. is described. This medium is based on Sabouraud dextrose agar (Oxoid CM41) and contains (per liter) 40.0 g of glucose, 10.0 g of mycological peptone, and 15.0 g of agar along with a novel chromogenic glucosaminidase substrate, ammonium 4-{2-[4-(2-acetamido-2-deoxy-β-d-glucopyranosyloxy)-3-methoxyphenyl]-vinyl}-1-(propan-3-yl-oate)-quinolium bromide (0.32 g liter−1). The glucosaminidase substrate in CDA was hydrolyzed by Candida albicans and Candida dubliniensis, yielding white colonies with deep-red spots on a yellow transparent background after 24 to 48 h of incubation at 37°C. Colonies of Candida tropicalis and Candida kefyr were uniformly pink, and colonies of other Candida spp., including Candida glabrata and Candida parapsilosis, were white. CDA was evaluated by using 115 test strains of Candida spp. and other clinically important yeasts and was compared with two commercially available chromogenic agars (Candida ID agar [bioMerieux] and CHROMagar Candida [CHROMagar Company Ltd.]). On all three agars, colonies of C. albicans were not distinguished from colonies of C. dubliniensis. However, for the group containing C. albicans plus C. dubliniensis, both the sensitivity and the specificity of detection when CDA was used were 100%, compared with values of 97.6 and 100%, respectively, with CHROMagar Candida and 100 and 96.8%, respectively, with Candida ID agar. In addition, for the group containing C. tropicalis plus C. kefyr, the sensitivity and specificity of detection when CDA was used were also 100%, compared with 72.7 and 98.1%, respectively, with CHROMagar Candida. Candida ID agar did not differentiate C. tropicalis and C. kefyr strains but did differentiate members of a broader group (C. tropicalis, C. kefyr, Candida lusitaniae plus Candida guilliermondii); the sensitivity and specificity of detection for members of this group were 94.7 and 93.8%, respectively. In addition to the increased sensitivity and/or specificity of Candida detection when CDA was used, differentiation of colony types on CDA (red spotted, pink, or no color) was unambiguous and did not require precise assessment of colony color. PMID:12089051

High precision during food recruitment of experienced (reactivated) foragers in the stingless bee Scaptotrigona mexicana (Apidae, Meliponini)

NASA Astrophysics Data System (ADS)

Sánchez, Daniel; Nieh, James C.; Hénaut, Yann; Cruz, Leopoldo; Vandame, Rémy

Several studies have examined the existence of recruitment communication mechanisms in stingless bees. However, the spatial accuracy of location-specific recruitment has not been examined. Moreover, the location-specific recruitment of reactivated foragers, i.e., foragers that have previously experienced the same food source at a different location and time, has not been explicitly examined. However, such foragers may also play a significant role in colony foraging, particularly in small colonies. Here we report that reactivated Scaptotrigona mexicana foragers can recruit with high precision to a specific food location. The recruitment precision of reactivated foragers was evaluated by placing control feeders to the left and the right of the training feeder (direction-precision tests) and between the nest and the training feeder and beyond it (distance-precision tests). Reactivated foragers arrived at the correct location with high precision: 98.44% arrived at the training feeder in the direction trials (five-feeder fan-shaped array, accuracy of at least +/-6° of azimuth at 50 m from the nest), and 88.62% arrived at the training feeder in the distance trials (five-feeder linear array, accuracy of at least +/-5 m or +/-10% at 50 m from the nest). Thus, S. mexicana reactivated foragers can find the indicated food source at a specific distance and direction with high precision, higher than that shown by honeybees, Apis mellifera, which do not communicate food location at such close distances to the nest.

Prostate cancer marker panel with single cell sensitivity in urine.

PubMed

Nickens, Kristen P; Ali, Amina; Scoggin, Tatiana; Tan, Shyh-Han; Ravindranath, Lakshmi; McLeod, David G; Dobi, Albert; Tacha, David; Sesterhenn, Isabell A; Srivastava, Shiv; Petrovics, Gyorgy

2015-06-15

Over one million men undergo prostate biopsies annually in the United States, a majority of whom due to elevated serum PSA. More than half of the biopsies turn out to be negative for prostate cancer (CaP). The limitations of both the PSA test and the biopsy procedure have led to the development for more precise CaP detection assays in urine (e.g., PCA3, TMPRSS2-ERG) or blood (e.g., PHI, 4K). Here, we describe the development and evaluation of the Urine CaP Marker Panel (UCMP) assay for sensitive and reproducible detection of CaP cells in post-digital rectal examination (post-DRE) urine. The cellular content of the post-DRE urine was captured on a translucent filter membrane, which is placed on Cytoclear slides for direct evaluation by microscopy and immuno-cytochemistry (ICC). Cells captured on the membrane were assayed for PSA and Prostein expression to identify prostate epithelial cells, and for ERG and AMACR to identify prostate tumor cells. Immunostained cells were analyzed for quantitative and qualitative features and correlated with biopsy positive and negative status for malignancy. The assay was optimized for single cell capture sensitivity and downstream evaluations by spiking a known number of cells from established CaP cell lines, LNCaP and VCaP, into pre-cleared control urine. The cells captured from the post-DRE urine of subjects, obtained prior to biopsy procedure, were co-stained for ERG, AMACR (CaP specific), and Prostein or PSA (prostate epithelium specific) rendering a whole cell based analysis and characterization. A feasibility cohort of 63 post-DRE urine specimens was assessed. Comparison of the UCMP results with blinded biopsy results showed an assay sensitivity of 64% (16 of 25) and a specificity of 68.8% (22 of 32) for CaP detection by biopsy. This pilot study assessing a minimally invasive CaP detection assay with single cell sensitivity cell-capture and characterization from the post-DRE urine holds promise for further development of this novel assay platform. Prostate 75: 969-975, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

Deficits in Coordinative Bimanual Timing Precision in Children with Specific Language Impairment

ERIC Educational Resources Information Center

Vuolo, Janet; Goffman, Lisa; Zelaznik, Howard N.

2017-01-01

Purpose: Our objective was to delineate components of motor performance in specific language impairment (SLI); specifically, whether deficits in timing precision in one effector (unimanual tapping) and in two effectors (bimanual clapping) are observed in young children with SLI. Method: Twenty-seven 4- to 5-year-old children with SLI and 21…

Recombinant antibody mediated delivery of organelle-specific DNA pH sensors along endocytic pathways

NASA Astrophysics Data System (ADS)

Modi, Souvik; Halder, Saheli; Nizak, Clément; Krishnan, Yamuna

2013-12-01

DNA has been used to build nanomachines with potential in cellulo and in vivo applications. However their different in cellulo applications are limited by the lack of generalizable strategies to deliver them to precise intracellular locations. Here we describe a new molecular design of DNA pH sensors with response times that are nearly 20 fold faster. Further, by changing the sequence of the pH sensitive domain of the DNA sensor, we have been able to tune their pH sensitive regimes and create a family of DNA sensors spanning ranges from pH 4 to 7.6. To enable a generalizable targeting methodology, this new sensor design also incorporates a `handle' domain. We have identified, using a phage display screen, a set of three recombinant antibodies (scFv) that bind sequence specifically to the handle domain. Sequence analysis of these antibodies revealed several conserved residues that mediate specific interactions with the cognate DNA duplex. We also found that all three scFvs clustered into different branches indicating that their specificity arises from mutations in key residues. When one of these scFvs is fused to a membrane protein (furin) that traffics via the cell surface, the scFv-furin chimera binds the `handle' and ferries a family of DNA pH sensors along the furin endocytic pathway. Post endocytosis, all DNA nanodevices retain their functionality in cellulo and provide spatiotemporal pH maps of retrogradely trafficking furin inside living cells. This new molecular technology of DNA-scFv-protein chimeras can be used to site-specifically complex DNA nanostructures for bioanalytical applications.DNA has been used to build nanomachines with potential in cellulo and in vivo applications. However their different in cellulo applications are limited by the lack of generalizable strategies to deliver them to precise intracellular locations. Here we describe a new molecular design of DNA pH sensors with response times that are nearly 20 fold faster. Further, by changing the sequence of the pH sensitive domain of the DNA sensor, we have been able to tune their pH sensitive regimes and create a family of DNA sensors spanning ranges from pH 4 to 7.6. To enable a generalizable targeting methodology, this new sensor design also incorporates a `handle' domain. We have identified, using a phage display screen, a set of three recombinant antibodies (scFv) that bind sequence specifically to the handle domain. Sequence analysis of these antibodies revealed several conserved residues that mediate specific interactions with the cognate DNA duplex. We also found that all three scFvs clustered into different branches indicating that their specificity arises from mutations in key residues. When one of these scFvs is fused to a membrane protein (furin) that traffics via the cell surface, the scFv-furin chimera binds the `handle' and ferries a family of DNA pH sensors along the furin endocytic pathway. Post endocytosis, all DNA nanodevices retain their functionality in cellulo and provide spatiotemporal pH maps of retrogradely trafficking furin inside living cells. This new molecular technology of DNA-scFv-protein chimeras can be used to site-specifically complex DNA nanostructures for bioanalytical applications. Electronic supplementary information (ESI) available: Detailed description of all oligonucleotide sequences used in this study; list of figures that support claims from the main text. Mainly these show sensor sequences, phage display results, scFv purification and binding data, cell images clamped at different pH and co-localization studies with endocytic tracers. See DOI: 10.1039/c3nr03769j

Influence of parameter values on the oscillation sensitivities of two p53-Mdm2 models.

PubMed

Cuba, Christian E; Valle, Alexander R; Ayala-Charca, Giancarlo; Villota, Elizabeth R; Coronado, Alberto M

2015-09-01

Biomolecular networks that present oscillatory behavior are ubiquitous in nature. While some design principles for robust oscillations have been identified, it is not well understood how these oscillations are affected when the kinetic parameters are constantly changing or are not precisely known, as often occurs in cellular environments. Many models of diverse complexity level, for systems such as circadian rhythms, cell cycle or the p53 network, have been proposed. Here we assess the influence of hundreds of different parameter sets on the sensitivities of two configurations of a well-known oscillatory system, the p53 core network. We show that, for both models and all parameter sets, the parameter related to the p53 positive feedback, i.e. self-promotion, is the only one that presents sizeable sensitivities on extrema, periods and delay. Moreover, varying the parameter set values to change the dynamical characteristics of the response is more restricted in the simple model, whereas the complex model shows greater tunability. These results highlight the importance of the presence of specific network patterns, in addition to the role of parameter values, when we want to characterize oscillatory biochemical systems.

Sensing Using Rare-Earth-Doped Upconversion Nanoparticles

PubMed Central

Hao, Shuwei; Chen, Guanying; Yang, Chunhui

2013-01-01

Optical sensing plays an important role in theranostics due to its capability to detect hint biochemical entities or molecular targets as well as to precisely monitor specific fundamental psychological processes. Rare-earth (RE) doped upconversion nanoparticles (UCNPs) are promising for these endeavors due to their unique frequency converting capability; they emit efficient and sharp visible or ultraviolet (UV) luminescence via use of ladder-like energy levels of RE ions when excited at near infrared (NIR) light that are silent to tissues. These features allow not only a high penetration depth in biological tissues but also a high detection sensitivity. Indeed, the energy transfer between UCNPs and biomolecular or chemical indicators provide opportunities for high-sensitive bio- and chemical-sensing. A temperature-sensitive change of the intensity ratio between two close UC bands promises them for use in temperature mapping of a single living cell. In this work, we review recent investigations on using UCNPs for the detection of biomolecules (avidin, ATP, etc.), ions (cyanide, mecury, etc.), small gas molecules (oxygen, carbon dioxide, ammonia, etc.), as well as for in vitro temperature sensing. We also briefly summarize chemical methods in synthesizing UCNPs of high efficiency that are important for the detection limit. PMID:23650480

Single crystal CVD diamond membranes as Position Sensitive X-ray Detector

NASA Astrophysics Data System (ADS)

Desjardins, K.; Menneglier, C.; Pomorski, M.

2017-12-01

Transparent X-ray Beam Position Monitor (XBPM) has been specifically developed for low energy X-ray beamlines (1.4 keV < E < 5 keV) allowing to transmit more than 80% of 2 keV energy beam. The detector is based on a free-standing single crystal CVD diamond membrane of 4 μm thickness with position-sensitive DLC (Diamond-Like Carbon) resistive electrodes in duo-lateral configuration. The measured X-ray beam induced current (XBIC) due to the interaction of X-rays with diamond membrane allows precise monitoring of the absolute beam flux and the beam position (by the reconstruction of its center-of-gravity) at beam transmissions reaching 95%. This detector has been installed at SOLEIL synchrotron on the SIRIUS beamline monochromator output and it has shown charge collection efficiency (CCE) reaching 100% with no lag-effects and excellent beam intensity sensitivity monitoring. X-ray beam mapping of the detector showed an XBIC response inhomogeneity of less than 10% across the membrane, corresponding mainly to the measured variation of the diamond plate thickness. The measured beam position resolution is at sub-micron level depending on the beam flux and the readout electronics bandwidth.

A sensitive analysis method for 7 diterpenoids in rat plasma by liquid chromatography-electrospray ionization mass spectrometry and its application to pharmacokinetic study of Isodon serra extract.

PubMed

Du, Yingfeng; Liu, Pengwei; Zhu, Hong; Shi, Xiaowei; Zhao, Chengcheng; Wang, Na; Zhang, Lantong

2011-10-28

A simple and sensitive LC-MS/MS method has been developed and validated for the identification and quantification of epinodosin, epinodosinol, nodosin, oridonin, lasiokariurinol, lasiokaurin and rabdoternin A in rat plasma using sulfamethoxazole as the internal standard. The plasma sample pre-treatment consisted of a liquid-liquid extraction. Chromatographic separation was achieved on a C18 column with linear gradient elution using water and methanol, which were both acidified with 0.1% formic acid, at a flow rate of 0.7 mL/min. A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source. A novel multi-determination-periods program was executed to achieve a higher sensitivity by setting five scanning periods. The method presented here utilizes a novel determination strategy, enabling the application of positive and negative ESI-MS in a single run. The optimized mass transition ion-pairs (m/z) for quantitation were 361.2/287.1 for epinodosin, 382.3/347.3 for epinodosinol, 363.3/281.2 for nodosin, 365.3/347.3 for oridonin, 407.3/329.1 for lasiokariurinol, 405.2/59.0 for lasiokaurin, 363.2/283.1 for rabdoternin A and 254.1/156.0 for IS. The total run time was 20.50 min (including 5 min equilibration time) between injections. The specificity, linearity, accuracy, precision, recovery, matrix effect and several validation results demonstrate that this method is sensitive, specific and reliable. The proposed method was further applied to investigate the pharmacokinetics of all analytes after a single oral administration of Isodon serra extract to rats. Copyright © 2011 Elsevier B.V. All rights reserved.

HIV-1 viral load measurement in venous blood and fingerprick blood using Abbott RealTime HIV-1 DBS assay.

PubMed

Tang, Ning; Pahalawatta, Vihanga; Frank, Andrea; Bagley, Zowie; Viana, Raquel; Lampinen, John; Leckie, Gregor; Huang, Shihai; Abravaya, Klara; Wallis, Carole L

2017-07-01

HIV RNA suppression is a key indicator for monitoring success of antiretroviral therapy. From a logistical perspective, viral load (VL) testing using Dried Blood Spots (DBS) is a promising alternative to plasma based VL testing in resource-limited settings. To evaluate the analytical and clinical performance of the Abbott RealTime HIV-1 assay using a fully automated one-spot DBS sample protocol. Limit of detection (LOD), linearity, lower limit of quantitation (LLQ), upper limit of quantitation (ULQ), and precision were determined using serial dilutions of HIV-1 Virology Quality Assurance stock (VQA Rush University), or HIV-1-containing armored RNA, made in venous blood. To evaluate correlation, bias, and agreement, 497 HIV-1 positive adult clinical samples were collected from Ivory Coast, Uganda and South Africa. For each HIV-1 participant, DBS-fingerprick, DBS-venous and plasma sample results were compared. Correlation and bias values were obtained. The sensitivity and specificity were analyzed at a threshold of 1000 HIV-1 copies/mL generated using the standard plasma protocol. The Abbott HIV-1 DBS protocol had an LOD of 839 copies/mL, a linear range from 500 to 1×10 7 copies/mL, an LLQ of 839 copies/mL, a ULQ of 1×10 7 copies/mL, and an inter-assay SD of ≤0.30 log copies/mL for all tested levels within this range. With clinical samples, the correlation coefficient (r value) was 0.896 between DBS-fingerprick and plasma and 0.901 between DBS-venous and plasma, and the bias was -0.07 log copies/mL between DBS-fingerprick and plasma and -0.02 log copies/mL between DBS-venous and plasma. The sensitivity of DBS-fingerprick and DBS-venous was 93%, while the specificity of both DBS methods was 95%. The results demonstrated that the Abbott RealTime HIV-1 assay with DBS sample protocol is highly sensitive, specific and precise across a wide dynamic range and correlates well with plasma values. The Abbott RealTime HIV-1 assay with DBS sample protocol provides an alternative sample collection and transfer option in resource-limited settings and expands the utility of a viral load test to monitor HIV-1 ART treatment for infected patients. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Accuracy of clinical techniques for evaluating lower limb sensorimotor functions associated with increased fall risk

PubMed Central

Donaghy, Alex; DeMott, Trina; Allet, Lara; Kim, Hogene; Ashton-Miller, James; Richardson, James K.

2015-01-01

Background In prior work laboratory-based measures of hip motor function and ankle proprioceptive precision were critical to maintaining unipedal stance and fall/fall-related injury risk. However, the optimal clinical evaluation techniques for predicting these measures are unknown. Objective To evaluate the diagnostic accuracy of common clinical maneuvers in predicting laboratory-based measures of frontal plane hip rate of torque development (HipRTD) and ankle proprioceptive thresholds (AnkPRO) associated with increased fall risk. Design Prospective, observational study. Setting Biomechanical research laboratory. Participants Forty-one older subjects (age 69.1 ± 8.3 years), 25 with varying degrees of diabetic distal symmetric polyneuropathy and 16 without. Assessments Clinical hip strength was evaluated by manual muscle testing (MMT) and lateral plank time (LPT), defined as the number seconds the laterally lying subject could lift hips from the support surface. Foot/ankle evaluation included Achilles reflex, and vibratory, proprioceptive, monofilament, and pinprick sensations at the great toe. Main Outcome Measures HipRTD, abduction and adduction, using a custom whole-body dynamometer. AnkPRO determined with subjects standing using a foot cradle system and a staircase series of 100 frontal plane rotational stimuli. Results Pearson correlation coefficients (r) and receiver operator characteristic (ROC) curves revealed that LPT correlated more strongly with HipRTD (r/p = .61/<.001 and .67/<.001, for abductor/adductor, respectively) than did hip abductor MMT (r/p = .31/.044). Subjects with greater vibratory and proprioceptive sensation, and intact Achilles reflexes, monofilament, and pin sensation had more precise AnkPRO. LPT of < 12 seconds yielded a sensitivity/specificity of 91%/80% for identifying HipRTD < .25 (body size in Newton-meters), and vibratory perception of < 8 seconds yielded a sensitivity/specificity of 94%/80% for the identification of AnkPRO > 1.0 degree. Conclusions LPT is a more effective measure of HipRTD than MMT. Similarly, clinical vibratory sense and monofilament testing are effective measures of AnkPRO, whereas clinical proprioceptive sense is not. PMID:26409195

Exploring cosmic origins with CORE: Cosmological parameters

NASA Astrophysics Data System (ADS)

Di Valentino, E.; Brinckmann, T.; Gerbino, M.; Poulin, V.; Bouchet, F. R.; Lesgourgues, J.; Melchiorri, A.; Chluba, J.; Clesse, S.; Delabrouille, J.; Dvorkin, C.; Forastieri, F.; Galli, S.; Hooper, D. C.; Lattanzi, M.; Martins, C. J. A. P.; Salvati, L.; Cabass, G.; Caputo, A.; Giusarma, E.; Hivon, E.; Natoli, P.; Pagano, L.; Paradiso, S.; Rubiño-Martin, J. A.; Achúcarro, A.; Ade, P.; Allison, R.; Arroja, F.; Ashdown, M.; Ballardini, M.; Banday, A. J.; Banerji, R.; Bartolo, N.; Bartlett, J. G.; Basak, S.; Baumann, D.; de Bernardis, P.; Bersanelli, M.; Bonaldi, A.; Bonato, M.; Borrill, J.; Boulanger, F.; Bucher, M.; Burigana, C.; Buzzelli, A.; Cai, Z.-Y.; Calvo, M.; Carvalho, C. S.; Castellano, G.; Challinor, A.; Charles, I.; Colantoni, I.; Coppolecchia, A.; Crook, M.; D'Alessandro, G.; De Petris, M.; De Zotti, G.; Diego, J. M.; Errard, J.; Feeney, S.; Fernandez-Cobos, R.; Ferraro, S.; Finelli, F.; de Gasperis, G.; Génova-Santos, R. T.; González-Nuevo, J.; Grandis, S.; Greenslade, J.; Hagstotz, S.; Hanany, S.; Handley, W.; Hazra, D. K.; Hernández-Monteagudo, C.; Hervias-Caimapo, C.; Hills, M.; Kiiveri, K.; Kisner, T.; Kitching, T.; Kunz, M.; Kurki-Suonio, H.; Lamagna, L.; Lasenby, A.; Lewis, A.; Liguori, M.; Lindholm, V.; Lopez-Caniego, M.; Luzzi, G.; Maffei, B.; Martin, S.; Martinez-Gonzalez, E.; Masi, S.; Matarrese, S.; McCarthy, D.; Melin, J.-B.; Mohr, J. J.; Molinari, D.; Monfardini, A.; Negrello, M.; Notari, A.; Paiella, A.; Paoletti, D.; Patanchon, G.; Piacentini, F.; Piat, M.; Pisano, G.; Polastri, L.; Polenta, G.; Pollo, A.; Quartin, M.; Remazeilles, M.; Roman, M.; Ringeval, C.; Tartari, A.; Tomasi, M.; Tramonte, D.; Trappe, N.; Trombetti, T.; Tucker, C.; Väliviita, J.; van de Weygaert, R.; Van Tent, B.; Vennin, V.; Vermeulen, G.; Vielva, P.; Vittorio, N.; Young, K.; Zannoni, M.

2018-04-01

We forecast the main cosmological parameter constraints achievable with the CORE space mission which is dedicated to mapping the polarisation of the Cosmic Microwave Background (CMB). CORE was recently submitted in response to ESA's fifth call for medium-sized mission proposals (M5). Here we report the results from our pre-submission study of the impact of various instrumental options, in particular the telescope size and sensitivity level, and review the great, transformative potential of the mission as proposed. Specifically, we assess the impact on a broad range of fundamental parameters of our Universe as a function of the expected CMB characteristics, with other papers in the series focusing on controlling astrophysical and instrumental residual systematics. In this paper, we assume that only a few central CORE frequency channels are usable for our purpose, all others being devoted to the cleaning of astrophysical contaminants. On the theoretical side, we assume ΛCDM as our general framework and quantify the improvement provided by CORE over the current constraints from the Planck 2015 release. We also study the joint sensitivity of CORE and of future Baryon Acoustic Oscillation and Large Scale Structure experiments like DESI and Euclid. Specific constraints on the physics of inflation are presented in another paper of the series. In addition to the six parameters of the base ΛCDM, which describe the matter content of a spatially flat universe with adiabatic and scalar primordial fluctuations from inflation, we derive the precision achievable on parameters like those describing curvature, neutrino physics, extra light relics, primordial helium abundance, dark matter annihilation, recombination physics, variation of fundamental constants, dark energy, modified gravity, reionization and cosmic birefringence. In addition to assessing the improvement on the precision of individual parameters, we also forecast the post-CORE overall reduction of the allowed parameter space with figures of merit for various models increasing by as much as ~ 107 as compared to Planck 2015, and 105 with respect to Planck 2015 + future BAO measurements.

Porous organic polymers with different pore structures for sensitive solid-phase microextraction of environmental organic pollutants.

PubMed

Huang, Zhoubing; Liu, Shuqin; Xu, Jianqiao; Yin, Li; Zheng, Juan; Zhou, Ningbo; Ouyang, Gangfeng

2017-10-09

Adsorption capacity is the major sensitivity-limited factor in solid-phase microextraction. Due to its light-weight properties, large specific surface area and high porosity, especially tunable pore structures, the utilization of porous organic polymers as solid-phase microextraction adsorbents has attracting researchers' attentions. However, these works mostly concentrated on the utilization of specific porous organic polymers for preparing high-performance solid-phase microextraction coatings. The relationship between pore structures and adsorption performance of the porous organic polymers still remain unclear. Herein, three porous organic polymers with similar properties but different pore distributions were prepared by condensation polymerization reaction of phloroglucinol and terephthalaldehyde, which were fabricated as solid-phase microextraction coatings subsequently. The adsorption capacity of the porous organic polymers-coated fibers were evaluated by using benzene and its derivatives (i.e.,benzene, toluene, ethylbenzene and m-xylene) and polycyclic aromatic hydrocarbons as the target analytes. The results showed that the different adsorption performance of these porous organic polymers was mainly caused by their different pore volumes instead of their surface areas or pore sizes. Finally, the proposed method by using the mesoporous organic polymer coating was successfully applied to the determination of benzene and its derivatives in environmental water samples. As for analytical performance, high pre-concentration factors (74-2984), satisfactory relative recoveries (94.5 ± 18.5-116.9 ± 12.5%), intraday precision (2.44-5.34%), inter-day precision (4.62-7.02%), low limit of detections (LODs, 0.10-0.29 ng L -1 ) and limit of quantifications (LOQs, 0.33-0.96 ng L -1 ) were achieved under the optimal conditions. This study provides an important idea in the rational design of porous organic polymers for solid-phase microextraction or other adsorption applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and Development of a Quantitative TaqMan Real-Time PCR Assay for Evaluation of HIV-1 (group M) Viral Load in Plasma Using Armored RNA Standard.

PubMed

Gholami, Mohammad; Baesi, Kazem; Rouzbahani, Negin H; Mohraz, Minoo

2018-06-01

Human immunodeficiency virus-1 (HIV-1) is a viral infectious agent that gradually extinguishes the immune system, resulting in the acquired immune deficiency syndrome (AIDS). The aim of this study was to develop a TaqMan based detection assay to evaluate HIV-1 plasma viral load and to construct a stable internal positive control (IPC) and external positive control (EPC) RNA based on Armored RNA (AR) technology. The MS2 maturase, coat protein gene and HIV-1 pol gene were cloned in pET-32a plasmid. The recently fabricated recombinant plasmid was transformed into Escherichia coli strain BL2 (DE3) and protein expression and Armored RNA was fabricated in presence of isopropyl-L-thio-D-galactopyranoside (IPTG). The Armored RNA was precipitated and purified by polyethylene glycol (PEG) and sephacryl S-200 chromatography. The stability of Armored RNA was evaluated by treatment with DNase I and RNase A and confirmed by transmission electron microscopy (TEM) and gel agarose electrophoresis. The specificity, sensitivity, inter- and intra-day precision, and the dynamic range of the assay were experimentally determined. The AR was stable in presence of ribonuclease, and the assay had a dynamic detection range from 101 to 105 copies of AR. The coefficient of variation (CV) was 4.8% for intra-assay and 5.8% for inter-assay precision. Clinical specificity and sensitivity of the assay were assessed at 100% and 96.66%, respectively. The linear regression analysis confirmed a high correlation between the in-house and the commercial assay, Real Star HIV-1-qRTPCR, respectively (R2 = 0.888). The AR standard is non-infectious and highly resistant in the presence of ribonuclease. The TaqMan assay developed is able to quantify HIV viral load based on a novel conserved region of HIV-1 pol gene which has minimal sequence inconsistency.

Contourlet textual features: improving the diagnosis of solitary pulmonary nodules in two dimensional CT images.

PubMed

Wang, Jingjing; Sun, Tao; Gao, Ni; Menon, Desmond Dev; Luo, Yanxia; Gao, Qi; Li, Xia; Wang, Wei; Zhu, Huiping; Lv, Pingxin; Liang, Zhigang; Tao, Lixin; Liu, Xiangtong; Guo, Xiuhua

2014-01-01

To determine the value of contourlet textural features obtained from solitary pulmonary nodules in two dimensional CT images used in diagnoses of lung cancer. A total of 6,299 CT images were acquired from 336 patients, with 1,454 benign pulmonary nodule images from 84 patients (50 male, 34 female) and 4,845 malignant from 252 patients (150 male, 102 female). Further to this, nineteen patient information categories, which included seven demographic parameters and twelve morphological features, were also collected. A contourlet was used to extract fourteen types of textural features. These were then used to establish three support vector machine models. One comprised a database constructed of nineteen collected patient information categories, another included contourlet textural features and the third one contained both sets of information. Ten-fold cross-validation was used to evaluate the diagnosis results for the three databases, with sensitivity, specificity, accuracy, the area under the curve (AUC), precision, Youden index, and F-measure were used as the assessment criteria. In addition, the synthetic minority over-sampling technique (SMOTE) was used to preprocess the unbalanced data. Using a database containing textural features and patient information, sensitivity, specificity, accuracy, AUC, precision, Youden index, and F-measure were: 0.95, 0.71, 0.89, 0.89, 0.92, 0.66, and 0.93 respectively. These results were higher than results derived using the database without textural features (0.82, 0.47, 0.74, 0.67, 0.84, 0.29, and 0.83 respectively) as well as the database comprising only textural features (0.81, 0.64, 0.67, 0.72, 0.88, 0.44, and 0.85 respectively). Using the SMOTE as a pre-processing procedure, new balanced database generated, including observations of 5,816 benign ROIs and 5,815 malignant ROIs, and accuracy was 0.93. Our results indicate that the combined contourlet textural features of solitary pulmonary nodules in CT images with patient profile information could potentially improve the diagnosis of lung cancer.

An in-house assay for BK polyomavirus quantification using the Abbott m2000 RealTime system.

PubMed

Muldrew, Kenneth L; Lovett, Jennie L

2013-11-01

BK polyomavirus (BKPyV) quantification is useful for monitoring renal transplant patient response to therapy. The Abbott m2000 RealTime System employed by some clinical laboratories to perform US Food and Drug Administration-approved assays can also be used to develop in-house assays such as the one presented here. This study aimed to validate an in-house quantitative real-time PCR assay targeting the BKPyV major capsid VP1 gene for assessment of viral load using the Abbott m2000 RealTime System. BKPyV load was measured in 95 urine and plasma samples previously tested for BKPyV by one of three laboratories (46 BKPyV-positive samples consisting of 35 plasma and 11 urine samples; 49 samples negative for BKPyV consisting of 47 plasma and two urine samples). Two additional plasma specimens from the College of American Pathologists proficiency testing survey were also analysed. Precision studies were performed by diluting a high-viral-titre patient sample into BKPyV-negative pooled plasma to create high-positive (6.16 log10 copies ml(-1)) and low-positive (3.16 log10 copies ml(-1)) samples. For precision studies of inter-assay variability, a high-positive (7.0 log10 copies ml(-1)) and a low-positive (3.0 log10 copies ml(-1)) sample were measured in 20 separate runs. The assay's limit of quantification and limit of detection were 2.70 and 2.25 log10 copies ml(-1), respectively. The assay was linear from 2.70 to 9.26 log10 copies ml(-1). Of the 48 known positives, 43 were detected as positive, with three reported by the reference laboratory as values lower than the limit of detection. Two known positives at 3.27 and 3.80 log10 copies ml(-1) tested negative by the m2000 BKPyV assay. Of the 49 known negative samples, 48 were negative by the m2000 BKPyV load assay, with one sample confirmed positive by a reference laboratory. Qualitative analysis prior to discrepancy testing demonstrated a sensitivity of 89.58 % and a specificity of 97.96 %. Precision studies demonstrated inter-assay coefficients of variation of 0.63 % (high positive) and 4.38 % (low positive). Genotyping was performed on 22 patient samples, of which 21 (95.45 %) were type I and one (4.55 %) was type II. In conclusion, the m2000 BKPyV viral load assay sensitivity, specificity, linear range, precision and cost effectiveness make it an attractive methodology for clinical laboratories using the Abbott m2000 RealTime System.

Precise and accurate isotope ratio measurements by ICP-MS.

PubMed

Becker, J S; Dietze, H J

2000-09-01

The precise and accurate determination of isotope ratios by inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) is important for quite different application fields (e.g. for isotope ratio measurements of stable isotopes in nature, especially for the investigation of isotope variation in nature or age dating, for determining isotope ratios of radiogenic elements in the nuclear industry, quality assurance of fuel material, for reprocessing plants, nuclear material accounting and radioactive waste control, for tracer experiments using stable isotopes or long-lived radionuclides in biological or medical studies). Thermal ionization mass spectrometry (TIMS), which used to be the dominant analytical technique for precise isotope ratio measurements, is being increasingly replaced for isotope ratio measurements by ICP-MS due to its excellent sensitivity, precision and good accuracy. Instrumental progress in ICP-MS was achieved by the introduction of the collision cell interface in order to dissociate many disturbing argon-based molecular ions, thermalize the ions and neutralize the disturbing argon ions of plasma gas (Ar+). The application of the collision cell in ICP-QMS results in a higher ion transmission, improved sensitivity and better precision of isotope ratio measurements compared to quadrupole ICP-MS without the collision cell [e.g., for 235U/238U approximately 1 (10 microg x L(-1) uranium) 0.07% relative standard deviation (RSD) vs. 0.2% RSD in short-term measurements (n = 5)]. A significant instrumental improvement for ICP-MS is the multicollector device (MC-ICP-MS) in order to obtain a better precision of isotope ratio measurements (with a precision of up to 0.002%, RSD). CE- and HPLC-ICP-MS are used for the separation of isobaric interferences of long-lived radionuclides and stable isotopes by determination of spallation nuclide abundances in an irradiated tantalum target.

Age estimation of burbot using pectoral fin rays, brachiostegal rays, and otoliths

USGS Publications Warehouse

Klein, Zachary B.; Terrazas, Marc M.; Quist, Michael C.

2014-01-01

Throughout much of its native distribution, burbot (Lota lota) is a species of conservation concern. Understanding dynamic rate functions is critical for the effective management of sensitive burbot populations, which necessitates accurate and precise age estimates. Managing sensitive burbot populations requires an accurate and precise non-lethal alternative. In an effort to identify a non-lethal ageing structure, we compared the precision of age estimates obtained from otoliths, pectoral fin rays, dorsal fin rays and branchiostegal rays from 208 burbot collected from the Green River drainage, Wyoming. Additionally, we compared the accuracy of age estimates from pectoral fin rays, dorsal fin rays and branchiostegal rays to those of otoliths. Dorsal fin rays were immediately deemed a poor ageing structure and removed from further analysis. Age-bias plots of consensus ages derived from branchiostegal rays and pectoral fin rays were appreciably different from those obtained from otoliths. Exact agreement between readers and reader confidence was highest for otoliths and lowest for branchiostegal rays. Age-bias plots indicated that age estimates obtained from branchiostegal rays and pectoral fin rays were substantially different from age estimates obtained from otoliths. Our results indicate that otoliths provide the most precise age estimates for burbot.

The MOLLER Experiment: ``An Ultra-precise Measurement of the Weak Charge of the Electron using moller Scattering''

NASA Astrophysics Data System (ADS)

Beminiwattha, Rakitha; Moller Collaboration

2017-09-01

Parity Violating Electron Scattering (PVES) is an extremely successful precision frontier tool that has been used for testing the Standard Model (SM) and understanding nucleon structure. Several generations of highly successful PVES programs at SLAC, MIT-Bates, MAMI-Mainz, and Jefferson Lab have contributed to the understanding of nucleon structure and testing the SM. But missing phenomena like matter-antimatter asymmetry, neutrino flavor oscillations, and dark matter and energy suggest that the SM is only a `low energy' effective theory. The MOLLER experiment at Jefferson Lab will measure the weak charge of the electron, QWe = 1 - 4sin2θW , with a precision of 2.4 % by measuring the parity violating asymmetry in electron-electron () scattering and will be sensitive to subtle but measurable deviations from precisely calculable predictions from the SM. The MOLLER experiment will provide the best contact interaction search for leptons at low OR high energy makes it a probe of physics beyond the Standard Model with sensitivities to mass-scales of new PV physics up to 7.5 TeV. Overview of the experiment and recent pre-R&D progress will be reported.

Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

PubMed

Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

2016-01-01

Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

Analysis of image formation in optical coherence elastography using a multiphysics approach

PubMed Central

Chin, Lixin; Curatolo, Andrea; Kennedy, Brendan F.; Doyle, Barry J.; Munro, Peter R. T.; McLaughlin, Robert A.; Sampson, David D.

2014-01-01

Image formation in optical coherence elastography (OCE) results from a combination of two processes: the mechanical deformation imparted to the sample and the detection of the resulting displacement using optical coherence tomography (OCT). We present a multiphysics model of these processes, validated by simulating strain elastograms acquired using phase-sensitive compression OCE, and demonstrating close correspondence with experimental results. Using the model, we present evidence that the approximation commonly used to infer sample displacement in phase-sensitive OCE is invalidated for smaller deformations than has been previously considered, significantly affecting the measurement precision, as quantified by the displacement sensitivity and the elastogram signal-to-noise ratio. We show how the precision of OCE is affected not only by OCT shot-noise, as is usually considered, but additionally by phase decorrelation due to the sample deformation. This multiphysics model provides a general framework that could be used to compare and contrast different OCE techniques. PMID:25401007

FiGHTS: a preliminary screening tool for adolescent firearms-carrying.

PubMed

Hayes, D Neil; Sege, Robert

2003-12-01

Adolescent firearms-carrying is a risk factor for serious injury and death. Clinical screening tools for firearms-carrying have not yet been developed. We present the development of a preliminary screening test for adolescent firearms-carrying based on the growing body of knowledge of firearms-related risk factors. A convenience sample of 15,000 high school students from the 1999 National Youth Risk Behavior Survey was analyzed for the purpose of model building. Known risk factors for firearms-carrying were candidates for 2 models predicting recent firearms-carrying. The "brief FiGHTS score" screening tool excluded terms related to sexual behavior, significant substance abuse, or criminal behavior (Fi=fighting, G=gender, H=hurt while fighting, T=threatened, S=smoker). An "extended FiGHTS score," which included 13 items, was developed for more precise estimates. The brief FiGHTS score had a sensitivity of 82%, a specificity of 71%, and an area under the receiver operating characteristic (ROC) curve of 0.84. The extended FiGHTS score had an area under the ROC curve of 0.90. Both models performed well in a validation data set of 55,000 students. The brief and extended FiGHTS scores have high sensitivity and specificity for predicting firearms-carrying and may be appropriate for clinical testing.

A semi-nested real-time PCR method to detect low chimerism percentage in small quantity of hematopoietic stem cell transplant DNA samples.

PubMed

Aloisio, Michelangelo; Bortot, Barbara; Gandin, Ilaria; Severini, Giovanni Maria; Athanasakis, Emmanouil

2017-02-01

Chimerism status evaluation of post-allogeneic hematopoietic stem cell transplantation samples is essential to predict post-transplant relapse. The most commonly used technique capable of detecting small increments of chimerism is quantitative real-time PCR. Although this method is already used in several laboratories, previously described protocols often lack sensitivity and the amount of the DNA required for each chimerism analysis is too high. In the present study, we compared a novel semi-nested allele-specific real-time PCR (sNAS-qPCR) protocol with our in-house standard allele-specific real-time PCR (gAS-qPCR) protocol. We selected two genetic markers and analyzed technical parameters (slope, y-intercept, R2, and standard deviation) useful to determine the performances of the two protocols. The sNAS-qPCR protocol showed better sensitivity and precision. Moreover, the sNAS-qPCR protocol requires, as input, only 10 ng of DNA, which is at least 10-fold less than the gAS-qPCR protocols described in the literature. Finally, the proposed sNAS-qPCR protocol could prove very useful for performing chimerism analysis with a small amount of DNA, as in the case of blood cell subsets.

Diffuse reflectance spectroscopy for optical nerve identification. Preliminary ex vivo results for feedback controlled oral and maxillofacial laser surgery

NASA Astrophysics Data System (ADS)

Stelzle, Florian; Zam, Azhar; Adler, Werner; Douplik, Alexandre; Tangermann-Gerk, Katja; Nkenke, Emeka; Neukam, Friedrich Wilhelm; Schmidt, Michael

Objective: Laser surgery has many advantages. However, due to a lack of haptic feedback it is accompanied by the risk of iatrogenic nerve damage. The aim of this study was to evaluate the possibilities of optical nerve identification by diffuse reflectance spectroscopy to set the base for a feedback control system to enhance nerve preservation in oral and maxillofacial laser surgery. Materials and Methods: Diffuse reflectance spectra of nerve tissue, skin, mucosa, fat tissue, muscle, cartilage and bone (15120 spectra) of ex vivo pig heads were acquired in the wavelength range of 350-650 nm. Tissue differentiation was performed by principal components analysis (PCA) followed by linear discriminant analysis (LDA). Specificity and sensitivity were calculated by receiver operating characteristic (ROC) analysis and the area under curve (AUC). Results: Nerve tissue could correctly be identified and differed from skin, mucosa, fat tissue, muscle, cartilage and bone in more than 90% of the cases (AUC results) with a specificity of over 78% and a sensitivity of more than 86%. Conclusion: Nerve tissue can be identified by diffuse reflectance spectroscopy with high precision and reliability. The results may set the base for a feedback system to prevent iatrogenic nerve damage performing oral and maxillofacial laser surgery.

Simultaneous determination of sixteen metabolites related to neural tube defects in maternal serum by liquid chromatography coupling with electrospray tandem mass spectrometry.

PubMed

Liang, Xiao-Ping; Liang, Qiong-Lin; Xia, Jian-Fei; Wang, Yong; Hu, Ping; Wang, Yi-Ming; Zheng, Xiao-Ying; Zhang, Ting; Luo, Guo-An

2009-06-15

Disturbances in maternal folate, homocysteine, and glutathione metabolism have been reported to be associated with neural tube defects (NTDs). However, the role played by specific components in the metabolic pathways leading to NTDs remains unclear. Thus an analytical method for simultaneous measurement of sixteen compounds involved in such three metabolic pathways by high performance liquid chromatography-tandem mass spectrometry was developed. The use of hydrophilic chromatography column improved the separation of polar analytes and the detection mode of multiple-reaction monitoring (MRM) enhanced the specificity and sensitivity so as to achieve simultaneous determination of three class of metabolites which have much variance in polarity and contents. The influence of parameters such as temperature, pH, flow rate on the performance of the analytes were studied to get an optimal condition. The method was validated for its linearity, accuracy, and precision, and also used for the analysis of serum samples of NTDs-affected pregnancies and normal women. The result showed that the present method is sensitive and reliable for simultaneous determination of as many as sixteen interesting metabolites which may provide a new means to study the underlying mechanism of NTDs as well as to discover new potential biomarkers.

A Digital PCR-Based Method for Efficient and Highly Specific Screening of Genome Edited Cells

PubMed Central

Berman, Jennifer R.; Postovit, Lynne-Marie

2016-01-01

The rapid adoption of gene editing tools such as CRISPRs and TALENs for research and eventually therapeutics necessitates assays that can rapidly detect and quantitate the desired alterations. Currently, the most commonly used assay employs “mismatch nucleases” T7E1 or “Surveyor” that recognize and cleave heteroduplexed DNA amplicons containing mismatched base-pairs. However, this assay is prone to false positives due to cancer-associated mutations and/or SNPs and requires large amounts of starting material. Here we describe a powerful alternative wherein droplet digital PCR (ddPCR) can be used to decipher homozygous from heterozygous mutations with superior levels of both precision and sensitivity. We use this assay to detect knockout inducing alterations to stem cell associated proteins, NODAL and SFRP1, generated using either TALENs or an “all-in-one” CRISPR/Cas plasmid that we have modified for one-step cloning and blue/white screening of transformants. Moreover, we highlight how ddPCR can be used to assess the efficiency of varying TALEN-based strategies. Collectively, this work highlights how ddPCR-based screening can be paired with CRISPR and TALEN technologies to enable sensitive, specific, and streamlined approaches to gene editing and validation. PMID:27089539

Sensitivity, specificity, and reproducibility of four measures of laboratory turnaround time.

PubMed

Valenstein, P N; Emancipator, K

1989-04-01

The authors studied the performance of four measures of laboratory turnaround time: the mean, median, 90th percentile, and proportion of tests reported within a predetermined cut-off interval (proportion of acceptable tests [PAT]). Measures were examined with the use of turnaround time data from 11,070 stat partial thromboplastin times, 16,761 urine cultures, and 28,055 stat electrolyte panels performed by a single laboratory. For laboratories with long turnaround times, the most important quality of a turnaround time measure is high reproducibility, so that improvement in reporting speed can be distinguished from random variation resulting from sampling. The mean was found to be the most reproducible of the four measures, followed by the median. The mean achieved acceptable precision with sample sizes of 100-500 tests. For laboratories with normally rapid turnaround times, the most important quality of a measure is high sensitivity and specificity for detecting whether turnaround time has dropped below standards. The PAT was found to be the best measure of turnaround time in this setting but required sample sizes of at least 500 tests to achieve acceptable accuracy. Laboratory turnaround time may be measured for different reasons. The method of measurement should be chosen with an eye toward its intended application.

Immunodiagnostic monoclonal antibody-based sandwich ELISA of fasciolosis by detection of Fasciola gigantica circulating fatty acid binding protein.

PubMed

Anuracpreeda, Panat; Chawengkirttikul, Runglawan; Sobhon, Prasert

2016-09-01

Up to now, parasitological diagnosis of fasciolosis is often unreliable and possesses low sensitivity. Hence, the detection of circulating parasite antigens is thought to be a better alternative for diagnosis of fasciolosis, as it reflects the real parasite burden. In the present study, a monoclonal antibody (MoAb) against recombinant Fasciola gigantica fatty acid binding protein (rFgFABP) has been produced. As well, a reliable sandwich enzyme-linked immunosorbent assay (sandwich ELISA) has been developed for the detection of circulating FABP in the sera of mice experimentally and cattle naturally infected with F. gigantica. MoAb 3A3 and biotinylated rabbit anti-recombinant FABP antibody were selected due to their high reactivities and specificities. The lower detection limit of sandwich ELISA was 5 pg mL-1, and no cross-reaction with other parasite antigens was observed. This assay could detect F. gigantica infection from day 1 post infection. In experimental mice, the sensitivity, specificity and accuracy of this assay were 93·3, 100 and 98·2%, while in natural cattle they were 96·7, 100 and 99·1%. Hence, this sandwich ELISA method showed high efficiencies and precisions for diagnosis of fasciolosis by F. gigantica.

The systemic inflammatory response syndrome (SIRS) to identify infected patients in the emergency room.

PubMed

Jaimes, Fabián; Garcés, Jenny; Cuervo, Jorge; Ramírez, Federico; Ramírez, Jorge; Vargas, Andrea; Quintero, Claudia; Ochoa, Jorge; Tandioy, Fabio; Zapata, Láder; Estrada, Juan; Yepes, Maria; Leal, Hiulber

2003-08-01

Evaluation of the usefulness of criteria for systemic inflammatory response syndrome (SIRS) compared with the final diagnosis of infection in patients admitted to the emergency room of two university-based hospitals. Longitudinal cohort study. Hospital Universitario San Vicente de Paul and Hospital General de Medellín, Medellín, Colombia. PATIENTS. Seven hundred thirty-four patients with suspected infection as main diagnosis for admittance into the emergency room. Sensitivity, specificity, predictive values and likelihood ratios (LR) of SIRS criteria at admission were determined using, as gold standards, the diagnosis at the time of discharge based on clinical history and evolution, and microbiological confirmation of infection. SIRS criteria were met by 503 patients (68.5%); the discharge diagnosis of infection was found in 657 (89.4%) and 276 (37%) had microbiological confirmation. SIRS criteria exhibited a sensitivity of 69%, specificity of 35%, positive predictive value (PPV) of 90%, negative predictive value (NPV) of 12% and positive LR of 1.06. There were no differences between the two gold standards. The finding of two or more SIRS criteria was of little usefulness for diagnosis of infection. It is necessary to work with new criteria and probably with biological markers, in order to obtain a simple, precise and operative definition of the sepsis phenomenon.

Upper-limb sensory impairments after stroke: Self-reported experiences of daily life and rehabilitation.

PubMed

Carlsson, Håkan; Gard, Gunvor; Brogårdh, Christina

2018-01-10

To describe stroke survivors' experiences of sensory impairment in the upper limb, the influence of such impairment on daily life, coping strategies used, and sensory training for the affected hand. A qualitative study with a content analysis approach. Fifteen post-stroke patients interviewed individually. Five categories emerged from the data: "Changed and varied perception of the sensation"; "Affected movement control"; "Problems using the hand in daily life"; "Various strategies to cope with upper limb disability"; and "Lack of sensory training". Numbness and tingling, changes in temperature sensitivity, and increased sensitivity to touch and pain were reported. Many subjects had difficulty adjusting their grip force and performing movements with precision. It was problematic and mentally fatiguing managing personal care and carrying out household and leisure activities. Practical adaptations, compensation with vision, increased concentration, and use of the less affected hand were strategies used to overcome difficulties. Despite their problems very few subjects had received any specific sensory training for the hand. Stroke survivors perceive that sensory impairment of the upper limb has a highly negative impact on daily life, but specific rehabilitation for the upper limb is lacking. These findings imply that the clinical management of upper limb sensory impairment after stroke requires more attention.

Quantitative detection of the potato cyst nematode, Globodera pallida, and the beet cyst nematode, Heterodera schachtii, using Real-Time PCR with SYBR green I dye.

PubMed

Madani, Mehrdad; Subbotin, Sergei A; Moens, Maurice

2005-04-01

The potato cyst nematode Globodera pallida and the beet cyst nematode Heterodera schachtii are major nematode pests in world agriculture. Precise identification and knowledge about the number of nematodes in field soil are necessary to develop effective integrated pest control. Here we report the results of the Real-Time PCR assay for the rapid detection and quantification of G. pallida and H. schachtii. Using species specific primers and SYBR green I dye, we were able to detect a single second stage juvenile of cyst forming nematodes in samples. The specificity of the reaction was confirmed by the lack of amplification of DNAs from other Heterodera or Globodera species. Validation tests showed a rather high correlation between real numbers of second stage juveniles in a sample and expected numbers detected by Real-Time PCR. Reasons for observed differences in sensitivity and reliability of quantification detection for two species as well as other problems of Real-Time PCR are discussed. The Real-Time PCR assay with SYBR green I dye targeting fragments of the ITS-rDNA provided a sensitive means for the rapid and simultaneous detection and quantification of juveniles of these pests.

In vivo bioelectronic nose using transgenic mice for specific odor detection.

PubMed

Gao, Keqiang; Li, Songmin; Zhuang, Liujing; Qin, Zhen; Zhang, Bin; Huang, Liquan; Wang, Ping

2018-04-15

The olfactory system is a natural biosensor since its peripheral olfactory sensory neurons (OSNs) respond to the external stimuli and transmit the signals to the olfactory bulb (OB) where they are integrated and processed. The axonal connections from the OSNs expressing about 1000 different types of odorant receptors are precisely organized and sorted out onto 1800 glomeruli in the OB, from which the olfactory information is delivered to and perceived by the central nervous system. This process is carried out with particularly high sensitivity, specificity and rapidity, which can be used for explosive detection. Biomimetic olfactory biosensors use various biological components from the olfactory system as sensing elements, possessing great commercial prospects. In this study, we utilized the genetically labeled murine M72 olfactory sensory neurons with the green fluorescent protein (GFP) as sensing components and obtained long-term in vivo electrophysiological recordings from the M72 OSNs by implanting the microelectrode arrays (MEAs) into the behaving mouse's OB. The electrophysiological responses showed high reliability, reproducibility and specificity for odor detection, and particularly, the high sensitivity for the detection of odorants that contain benzene rings. Furthermore, our results indicated that it can detect trinitrotoluene (TNT) in liquid at a concentration as low as 10 -5 M and can distinguish TNT from other chemicals with a similar structure. Thus our study demonstrated that the in vivo biomimetic olfactory system could provide novel approaches to enhancing the specificity and increasing working lifespan of olfactory biosensors capable of detecting explosives. Copyright © 2017 Elsevier B.V. All rights reserved.

High precision spectroscopy and imaging in THz frequency range

NASA Astrophysics Data System (ADS)

Vaks, Vladimir L.

2014-03-01

Application of microwave methods for development of the THz frequency range has resulted in elaboration of high precision THz spectrometers based on nonstationary effects. The spectrometers characteristics (spectral resolution and sensitivity) meet the requirements for high precision analysis. The gas analyzers, based on the high precision spectrometers, have been successfully applied for analytical investigations of gas impurities in high pure substances. These investigations can be carried out both in absorption cell and in reactor. The devices can be used for ecological monitoring, detecting the components of chemical weapons and explosive in the atmosphere. The great field of THz investigations is the medicine application. Using the THz spectrometers developed one can detect markers for some diseases in exhaled air.

Alignment of a vector magnetometer to an optical prism

NASA Astrophysics Data System (ADS)

Dietrich, M. R.; Bailey, K. G.; O'Connor, T. P.

2017-05-01

A method for alignment of a vector magnetometer to a rigidly attached prism is presented. This enables optical comparison of the magnetometer axes to physical surfaces in the apparatus, and thus an absolute determination of the magnetic field direction in space. This is in contrast with more common techniques, which focus on precise determination of the relative angles between magnetometer axes, and so are more suited to measuring differences in the direction of magnetic fields. Here we demonstrate precision better than 500 μrad on a fluxgate magnetometer, which also gives the coil orthogonality errors to a similar precision. The relative sensitivity of the three axes is also determined, with a precision of about 5 ×10 -4 .

Shape optimization using a NURBS-based interface-enriched generalized FEM

DOE PAGES

Najafi, Ahmad R.; Safdari, Masoud; Tortorelli, Daniel A.; ...

2016-11-26

This study presents a gradient-based shape optimization over a fixed mesh using a non-uniform rational B-splines-based interface-enriched generalized finite element method, applicable to multi-material structures. In the proposed method, non-uniform rational B-splines are used to parameterize the design geometry precisely and compactly by a small number of design variables. An analytical shape sensitivity analysis is developed to compute derivatives of the objective and constraint functions with respect to the design variables. Subtle but important new terms involve the sensitivity of shape functions and their spatial derivatives. As a result, verification and illustrative problems are solved to demonstrate the precision andmore » capability of the method.« less

Aspects of Particle Physics Beyond the Standard Model

NASA Astrophysics Data System (ADS)

Lu, Xiaochuan

This dissertation describes a few aspects of particles beyond the Standard Model, with a focus on the remaining questions after the discovery of a Standard Model-like Higgs boson. In specific, three topics are discussed in sequence: neutrino mass and baryon asymmetry, naturalness problem of Higgs mass, and placing constraints on theoretical models from precision measurements. First, the consequence of the neutrino mass anarchy on cosmology is studied. Attentions are paid in particular to the total mass of neutrinos and baryon asymmetry through leptogenesis. With the assumption of independence among mass matrix entries in addition to the basis independence, Gaussian measure is the only choice. On top of Gaussian measure, a simple approximate U(1) flavor symmetry makes leptogenesis highly successful. Correlations between the baryon asymmetry and the light-neutrino quantities are investigated. Also discussed are possible implications of recently suggested large total mass of neutrinos by the SDSS/BOSS data. Second, the Higgs mass implies fine-tuning for minimal theories of weak-scale supersymmetry (SUSY). Non-decoupling effects can boost the Higgs mass when new states interact with the Higgs, but new sources of SUSY breaking that accompany such extensions threaten naturalness. I will show that two singlets with a Dirac mass can increase the Higgs mass while maintaining naturalness in the presence of large SUSY breaking in the singlet sector. The modified Higgs phenomenology of this scenario, termed "Dirac NMSSM", is also studied. Finally, the sensitivities of future precision measurements in probing physics beyond the Standard Model are studied. A practical three-step procedure is presented for using the Standard Model effective field theory (SM EFT) to connect ultraviolet (UV) models of new physics with weak scale precision observables. With this procedure, one can interpret precision measurements as constraints on the UV model concerned. A detailed explanation is given for calculating the effective action up to one-loop order in a manifestly gauge covariant fashion. This covariant derivative expansion method dramatically simplifies the process of matching a UV model with the SM EFT, and also makes available a universal formalism that is easy to use for a variety of UV models. A few general aspects of RG running effects and choosing operator bases are discussed. Mapping results are provided between the bosonic sector of the SM EFT and a complete set of precision electroweak and Higgs observables to which present and near future experiments are sensitive. Many results and tools which should prove useful to those wishing to use the SM EFT are detailed in several appendices.

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.

Statistical precision of the intensities retrieved from constrained fitting of overlapping peaks in high-resolution mass spectra

DOE PAGES

Cubison, M. J.; Jimenez, J. L.

2015-06-05

Least-squares fitting of overlapping peaks is often needed to separately quantify ions in high-resolution mass spectrometer data. A statistical simulation approach is used to assess the statistical precision of the retrieved peak intensities. The sensitivity of the fitted peak intensities to statistical noise due to ion counting is probed for synthetic data systems consisting of two overlapping ion peaks whose positions are pre-defined and fixed in the fitting procedure. The fitted intensities are sensitive to imperfections in the m/Q calibration. These propagate as a limiting precision in the fitted intensities that may greatly exceed the precision arising from counting statistics.more » The precision on the fitted peak intensity falls into one of three regimes. In the "counting-limited regime" (regime I), above a peak separation χ ~ 2 to 3 half-widths at half-maximum (HWHM), the intensity precision is similar to that due to counting error for an isolated ion. For smaller χ and higher ion counts (~ 1000 and higher), the intensity precision rapidly degrades as the peak separation is reduced ("calibration-limited regime", regime II). Alternatively for χ < 1.6 but lower ion counts (e.g. 10–100) the intensity precision is dominated by the additional ion count noise from the overlapping ion and is not affected by the imprecision in the m/Q calibration ("overlapping-limited regime", regime III). The transition between the counting and m/Q calibration-limited regimes is shown to be weakly dependent on resolving power and data spacing and can thus be approximated by a simple parameterisation based only on peak intensity ratios and separation. A simple equation can be used to find potentially problematic ion pairs when evaluating results from fitted spectra containing many ions. Longer integration times can improve the precision in regimes I and III, but a given ion pair can only be moved out of regime II through increased spectrometer resolving power. As a result, studies presenting data obtained from least-squares fitting procedures applied to mass spectral peaks should explicitly consider these limits on statistical precision.« less

Lessons learned from the use of HRP-2 based rapid diagnostic test in community-wide screening and treatment of asymptomatic carriers of Plasmodium falciparum in Burkina Faso.

PubMed

Tiono, Alfred B; Ouédraogo, Alphonse; Diarra, Amidou; Coulibaly, Sam; Soulama, Issiaka; Konaté, Amadou T; Barry, Aïssata; Mukhopadhyay, Amitava; Sirima, Sodiomon B; Hamed, Kamal

2014-01-27

Rapid diagnostic tests (RDTs) are immune chromatographic tests targeting antigens of one or more Plasmodium species and offer the potential to extend accurate malaria diagnosis in endemic areas. In this study, the performance of Plasmodium falciparum-specific histidine-rich protein-2 (PfHRP-2) RDT in the detection of asymptomatic carriers from a hyperendemic region of Burkina Faso was compared with microscopy to gain further insight on its relevance in community-based interventions. The performance of HRP-2 test was evaluated in terms of sensitivity, specificity, positive and negative predictive values, discordant values, likelihood ratios, accuracy, and precision using microscopy as the 'gold standard'. This analysis was carried out in a controlled, parallel, cluster-randomized (18 clusters; 1:1) study in children and adults. The effect of systematic treatment of P. falciparum asymptomatic carriers during three consecutive monthly community screening campaigns on the incidence of symptomatic malaria episodes over a 12-month period was compared with no treatment of asymptomatic carriers. Sensitivity of HRP-2 test in asymptomatic carriers was higher in campaign 1 (92.4%) when compared to campaign 2 (84.0%) and campaign 3 (77.8%). The sensitivity of HRP-2 test increased as parasite density increased across all the age groups. Highest sensitivity (≥97.0%) was recorded at parasite densities of 1,000-4,999/μl, except for children aged 10 to 14 years. The specificity of HRP-2 test was comparable across age groups and highest in campaign 3 (95.9%). The negative predictive values were high across the three campaigns (≥92.7%) while the positive predictive values ranged from 23.2 to 73.8%. False-positive and false-negative rates were high in campaign 1 and campaign 3, respectively. The performance of HRP-2 test in detecting asymptomatic carriers of P. falciparum varied by age and parasite density. Although the use of HRP-2 test is beneficial for the diagnosis of acute malaria, its low sensitivity in screening asymptomatic carriers may limit its utility in pre-elimination interventional settings. The use of a practical and more sensitive test such as loop-mediated isothermal amplification in combination with a cost effective HRP-2 test may be worth exploring in such settings.

TU-H-CAMPUS-TeP2-03: High Sensitivity and High Resolution Fiber Based Micro-Detector for Sub-Millimeter Preclinical Dosimetry

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

Izaguirre, E; Pokhrel, S; Knewtson, T

2016-06-15

Purpose: Current precision of small animal and cell micro-irradiators has continuously increased during the past years. Currently, preclinical irradiators can deliver sub-millimeter fields with micrometric precision but there are no water equivalent dosimeters to determine small field profiles and dose in the orthovoltage range of energies with micrometric resolution and precision. We have developed a fiber based micro-dosimeter with the resolution and dosimetric accuracy required for radiobiological research. Methods: We constructed two prototypes of micro-dosimeters based on different compositions of fiber scintillators to study the spatial resolution and dosimetric precision of small animal and cell micro-irradiators. The first has greenmore » output and the second has blue output. The blue output dosimeter has the highest sensitivity because it matches the spectral sensitivity of silicon photomultipliers. A blue detector with 500um cross section was built and tested respect to a CC01 ion chamber, film, and the 1500um green output detector. Orthovoltage fields from 1×1mm2 to 5×5mm2 were used for detector characteristics comparison. Results: The blue fiber dosimeter shows great agreement with films and matches dose measurements with the gold-standard ion chamber for 5×5mm2 fields. The detector has the appropriate sensitivity to measure fields from 1×1mm2 to larger sizes with a 1% dosimetric accuracy. The spatial resolution is in the sub-millimeter range and the spectral matching with the photomultiplier allows reducing the sensor cross section even further than the presented prototype. These results suggest that scintillating fibers combined with silicon photomultipliers is the appropriate technology to pursue micro-dosimetry for small animals and disperse cell samples. Conclusion: The constructed detectors establish a new landmark for the resolution and sensitivity of fiber based microdetectors. The validation of the detector in our small animal and cell irradiator shows that they are appropriate for preclinical and micro single cell irradiation quality assurance and dosimetry.« less

Future DUNE constraints on EFT

NASA Astrophysics Data System (ADS)

Falkowski, Adam; Grilli di Cortona, Giovanni; Tabrizi, Zahra

2018-04-01

In the near future, fundamental interactions at high-energy scales may be most efficiently studied via precision measurements at low energies. A universal language to assemble and interpret precision measurements is the so-called SMEFT, which is an effective field theory (EFT) where the Standard Model (SM) Lagrangian is extended by higher-dimensional operators. In this paper we investigate the possible impact of the DUNE neutrino experiment on constraining the SMEFT. The unprecedented neutrino flux offers an opportunity to greatly improve the current limits via precision measurements of the trident production and neutrino scattering off electrons and nuclei in the DUNE near detector. We quantify the DUNE sensitivity to dimension-6 operators in the SMEFT Lagrangian, and find that in some cases operators suppressed by an O(30) TeV scale can be probed. We also compare the DUNE reach to that of future experiments involving atomic parity violation and polarization asymmetry in electron scattering, which are sensitive to an overlapping set of SMEFT parameters.

qCSF in Clinical Application: Efficient Characterization and Classification of Contrast Sensitivity Functions in Amblyopia

PubMed Central

Hou, Fang; Huang, Chang-Bing; Lesmes, Luis; Feng, Li-Xia; Tao, Liming; Zhou, Yi-Feng; Lu, Zhong-Lin

2010-01-01

Purpose. The qCSF method is a novel procedure for rapid measurement of spatial contrast sensitivity functions (CSFs). It combines Bayesian adaptive inference with a trial-to-trial information gain strategy, to directly estimate four parameters defining the observer's CSF. In the present study, the suitability of the qCSF method for clinical application was examined. Methods. The qCSF method was applied to rapidly assess spatial CSFs in 10 normal and 8 amblyopic participants. The qCSF was evaluated for accuracy, precision, test–retest reliability, suitability of CSF model assumptions, and accuracy of amblyopia screening. Results. qCSF estimates obtained with as few as 50 trials matched those obtained with 300 Ψ trials. The precision of qCSF estimates obtained with 120 and 130 trials, in normal subjects and amblyopes, matched the precision of 300 Ψ trials. For both groups and both methods, test–retest sensitivity estimates were well matched (all R > 0.94). The qCSF model assumptions were valid for 8 of 10 normal participants and all amblyopic participants. Measures of the area under log CSF (AULCSF) and the cutoff spatial frequency (cutSF) were lower in the amblyopia group; these differences were captured within 50 qCSF trials. Amblyopia was detected at an approximately 80% correct rate in 50 trials, when a logistic regression model was used with AULCSF and cutSF as predictors. Conclusions. The qCSF method is sufficiently rapid, accurate, and precise in measuring CSFs in normal and amblyopic persons. It has great potential for clinical practice. PMID:20484592

Development of a liquid chromatography-mass spectrometry based enzyme activity assay for phosphatidylcholine-specific phospholipase C.

PubMed

Murakami, Chiaki; Mizuno, Satoru; Kado, Sayaka; Sakane, Fumio

2017-06-01

Phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) hydrolyzes PC to generate the second messenger 1,2-diacylglycerol (DG) and phosphocholine. PC-PLC plays pivotal roles in inflammation, carcinogenesis, tumor progression, atherogenesis, and subarachnoid hemorrhage. Although the activity of PC-PLC in mammalian tissues was discovered approximately 40 years ago, neither the protein nor its gene has been identified. In the present study, we developed a non-radioactive enzyme activity assay for PC-PLC based on mass spectrometric detection of DG following HPLC separation. This new liquid chromatography-mass spectrometry (LC-MS) assay directly determines a specific reaction product, 1-palmitoyl-2-oleoyl-DG, that is generated from 1-palmitoyl-2-oleoyl-PC by purified Bacillus cereus PC-PLC. The LC-MS assay offers several advantages including a lower background (0.02% versus 91%), higher signal background ratio (4242 versus 1.06)/signal noise ratio (7494 versus 4.4), higher sensitivity (≥32-fold), and lower limit of quantitation (0.04 pmol versus 0.69 pmol of PC-PLC), than a conventional fluorometric assay, which indirectly detects phosphocholine produced in the reaction. In addition to Bacillus cereus PC-PLC, the LC-MS assay was applicable to the measurement of mammalian PC-PLC prepared from the mouse brain. The radioisotope-free, highly sensitive and precise LC-MS assay for PC-PLC would be useful for the purification and identification of PC-PLC protein. Copyright © 2017 Elsevier Inc. All rights reserved.

Selection of the internal control gene for real-time quantitative rt-PCR assays in temperature treated Leptospira.

PubMed

Carrillo-Casas, Erika Margarita; Hernández-Castro, Rigoberto; Suárez-Güemes, Francisco; de la Peña-Moctezuma, Alejandro

2008-06-01

Analysis of gene expression requires sensitive, precise, and reproducible measurements for specific mRNA sequences. To avoid bias, real-time RT-PCR is referred to one or several internal control genes. Here, we sought to identify a gene to be used as normalizer by analyzing three functional distinct housekeeping genes (lipL41, flaB, and 16S rRNA) for their expression level and stability in temperature treated Leptospira cultures. Leptospira interrogans serovar Hardjo subtype Hardjoprajitno was cultured at 30 degrees C for 7 days until a density of 10(6) cells/ml was reached and then shifted to physiological temperatures (37 degrees C and 42 degrees C) and to environmental temperatures (25 degrees C and 30 degrees C) during a 24 h period. cDNA was amplified by quantitative PCR using SYBR Green I technology and gene-specific primers for lipL41, flaB, and 16S rRNA. Expression stability (M) was assessed by geNorm and Normfinder v.18. 16S rRNA registered an average expression stability of M = 1.1816, followed by flaB (M = 1.682) and lipL41 (M = 1.763). 16S rRNA was identified as the most stable gene and can be used as a normalizer, as it showed greater expression stability than lipL41 and flaB in the four temperature treatments. Hence, comparisons of gene expression will have a higher sensitivity and specificity.

Multiple Reaction Monitoring for Direct Quantitation of Intact Proteins Using a Triple Quadrupole Mass Spectrometer

NASA Astrophysics Data System (ADS)

Wang, Evelyn H.; Combe, Peter C.; Schug, Kevin A.

2016-05-01

Methods that can efficiently and effectively quantify proteins are needed to support increasing demand in many bioanalytical fields. Triple quadrupole mass spectrometry (QQQ-MS) is sensitive and specific, and it is routinely used to quantify small molecules. However, low resolution fragmentation-dependent MS detection can pose inherent difficulties for intact proteins. In this research, we investigated variables that affect protein and fragment ion signals to enable protein quantitation using QQQ-MS. Collision induced dissociation gas pressure and collision energy were found to be the most crucial variables for optimization. Multiple reaction monitoring (MRM) transitions for seven standard proteins, including lysozyme, ubiquitin, cytochrome c from both equine and bovine, lactalbumin, myoglobin, and prostate-specific antigen (PSA) were determined. Assuming the eventual goal of applying such methodology is to analyze protein in biological fluids, a liquid chromatography method was developed. Calibration curves of six standard proteins (excluding PSA) were obtained to show the feasibility of intact protein quantification using QQQ-MS. Linearity (2-3 orders), limits of detection (0.5-50 μg/mL), accuracy (<5% error), and precision (1%-12% CV) were determined for each model protein. Sensitivities for different proteins varied considerably. Biological fluids, including human urine, equine plasma, and bovine plasma were used to demonstrate the specificity of the approach. The purpose of this model study was to identify, study, and demonstrate the advantages and challenges for QQQ-MS-based intact protein quantitation, a largely underutilized approach to date.

High-sensitivity MALDI-TOF MS quantification of anthrax lethal toxin for diagnostics and evaluation of medical countermeasures.

PubMed

Boyer, Anne E; Gallegos-Candela, Maribel; Quinn, Conrad P; Woolfitt, Adrian R; Brumlow, Judith O; Isbell, Katherine; Hoffmaster, Alex R; Lins, Renato C; Barr, John R

2015-04-01

Inhalation anthrax has a rapid progression and high fatality rate. Pathology and death from inhalation of Bacillus anthracis spores are attributed to the actions of secreted protein toxins. Protective antigen (PA) binds and imports the catalytic component lethal factor (LF), a zinc endoprotease, and edema factor (EF), an adenylyl cyclase, into susceptible cells. PA-LF is termed lethal toxin (LTx) and PA-EF, edema toxin. As the universal transporter for both toxins, PA is an important target for vaccination and immunotherapeutic intervention. However, its quantification has been limited to methods of relatively low analytic sensitivity. Quantification of LTx may be more clinically relevant than LF or PA alone because LTx is the toxic form that acts on cells. A method was developed for LTx-specific quantification in plasma using anti-PA IgG magnetic immunoprecipitation of PA and quantification of LF activity that co-purified with PA. The method was fast (<4 h total time to detection), sensitive at 0.033 ng/mL LTx in plasma for the fast analysis (0.0075 ng/mL LTx in plasma for an 18 h reaction), precise (6.3-9.9% coefficient of variation), and accurate (0.1-12.7%error; n ≥ 25). Diagnostic sensitivity was 100% (n = 27 animal/clinical cases). Diagnostic specificity was 100% (n = 141). LTx was detected post-antibiotic treatment in 6/6 treated rhesus macaques and 3/3 clinical cases of inhalation anthrax and as long as 8 days post-treatment. Over the course of infection in two rhesus macaques, LTx was first detected at 0.101 and 0.237 ng/mL at 36 h post-exposure and increased to 1147 and 12,107 ng/mL in late-stage anthrax. This demonstrated the importance of LTx as a diagnostic and therapeutic target. This method provides a sensitive, accurate tool for anthrax toxin detection and evaluation of PA-directed therapeutics.

Specific contributions of basal ganglia and cerebellum to the neural tracking of rhythm.

PubMed

Nozaradan, Sylvie; Schwartze, Michael; Obermeier, Christian; Kotz, Sonja A

2017-10-01

How specific brain networks track rhythmic sensory input over time remains a challenge in neuroimaging work. Here we show that subcortical areas, namely the basal ganglia and the cerebellum, specifically contribute to the neural tracking of rhythm. We tested patients with focal lesions in either of these areas and healthy controls by means of electroencephalography (EEG) while they listened to rhythmic sequences known to induce selective neural tracking at a frequency corresponding to the most-often perceived pulse-like beat. Both patients and controls displayed neural responses to the rhythmic sequences. However, these response patterns were different across groups, with patients showing reduced tracking at beat frequency, especially for the more challenging rhythms. In the cerebellar patients, this effect was specific to the rhythm played at a fast tempo, which places high demands on the temporally precise encoding of events. In contrast, basal ganglia patients showed more heterogeneous responses at beat frequency specifically for the most complex rhythm, which requires more internal generation of the beat. These findings provide electrophysiological evidence that these subcortical structures selectively shape the neural representation of rhythm. Moreover, they suggest that the processing of rhythmic auditory input relies on an extended cortico-subcortico-cortical functional network providing specific timing and entrainment sensitivities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Super-sensitive time-resolved fluoroimmunoassay for thyroid-stimulating hormone utilizing europium(III) nanoparticle labels achieved by protein corona stabilization, short binding time, and serum preprocessing.

PubMed

Näreoja, Tuomas; Rosenholm, Jessica M; Lamminmäki, Urpo; Hänninen, Pekka E

2017-05-01

Thyrotropin or thyroid-stimulating hormone (TSH) is used as a marker for thyroid function. More precise and more sensitive immunoassays are needed to facilitate continuous monitoring of thyroid dysfunctions and to assess the efficacy of the selected therapy and dosage of medication. Moreover, most thyroid diseases are autoimmune diseases making TSH assays very prone to immunoassay interferences due to autoantibodies in the sample matrix. We have developed a super-sensitive TSH immunoassay utilizing nanoparticle labels with a detection limit of 60 nU L -1 in preprocessed serum samples by reducing nonspecific binding. The developed preprocessing step by affinity purification removed interfering compounds and improved the recovery of spiked TSH from serum. The sensitivity enhancement was achieved by stabilization of the protein corona of the nanoparticle bioconjugates and a spot-coated configuration of the active solid-phase that reduced sedimentation of the nanoparticle bioconjugates and their contact time with antibody-coated solid phase, thus making use of the higher association rate of specific binding due to high avidity nanoparticle bioconjugates. Graphical Abstract We were able to decrease the lowest limit of detection and increase sensitivity of TSH immunoassay using Eu(III)-nanoparticles. The improvement was achieved by decreasing binding time of nanoparticle bioconjugates by small capture area and fast circular rotation. Also, we applied a step to stabilize protein corona of the nanoparticles and a serum-preprocessing step with a structurally related antibody.

Integration of spectral domain optical coherence tomography with microperimetry generates unique datasets for the simultaneous identification of visual function and retinal structure in ophthalmological applications

NASA Astrophysics Data System (ADS)

Koulen, Peter; Gallimore, Gary; Vincent, Ryan D.; Sabates, Nelson R.; Sabates, Felix N.

2011-06-01

Conventional perimeters are used routinely in various eye disease states to evaluate the central visual field and to quantitatively map sensitivity. However, standard automated perimetry proves difficult for retina and specifically macular disease due to the need for central and steady fixation. Advances in instrumentation have led to microperimetry, which incorporates eye tracking for placement of macular sensitivity values onto an image of the macular fundus thus enabling a precise functional and anatomical mapping of the central visual field. Functional sensitivity of the retina can be compared with the observed structural parameters that are acquired with high-resolution spectral domain optical coherence tomography and by integration of scanning laser ophthalmoscope-driven imaging. Findings of the present study generate a basis for age-matched comparison of sensitivity values in patients with macular pathology. Microperimetry registered with detailed structural data performed before and after intervention treatments provides valuable information about macular function, disease progression and treatment success. This approach also allows for the detection of disease or treatment related changes in retinal sensitivity when visual acuity is not affected and can drive the decision making process in choosing different treatment regimens and guiding visual rehabilitation. This has immediate relevance for applications in central retinal vein occlusion, central serous choroidopathy, age-related macular degeneration, familial macular dystrophy and several other forms of retina related visual disability.

Future projects in asteroseismology: the unique role of Antarctica

NASA Astrophysics Data System (ADS)

Mosser, B.; Siamois Team

Asteroseismology requires observables registered in stringent conditions: very high sensitivity, uninterrupted time series, long duration. These specifications then allow to study the details of the stellar interior structure. Space-borne and ground-based asteroseismic projects are presented and compared. With CoRoT as a precursor, then Kepler and maybe Plato, the roadmap in space appears to be precisely designed. In parallel, ground-based projects are necessary to provide different and unique information on bright stars with Doppler measurements. Dome C appears to be the ideal place for ground-based asteroseismic observations. The unequalled weather conditions yield a duty cycle comparable to space. Long time series (up to 3 months) will be possible, thanks to the long duration of the polar night.

Limitations on analysis of small particles with an electron probe: pollution studies

USGS Publications Warehouse

Heidel, R.H.; Desborough, G.A.

1975-01-01

Recent literature concerning the size and composition of airborne lead particles in automobile exhaust emissions determined by electron microprobe analysis reports 14 distinct lead compounds. Particle sizes reported were from 0.2 ??m to 2 ??m in the diameter. The determination of chemical formulae for compounds requires quantitative elemental data for individual particles. It was also assumed that the lead bearing particles analysed were solid (specifically non porous or non fluffy) compounds which occurred as discrete (non aggregate) particles. Intensity data obtained in the laboratory from the excited volume in a 1 ??m diameter sphere of solid lead chloride indicate insufficient precision and sensitivity to obtain chemical formulae as reported in the literature for exhaust emission products.