Sample records for validating human performance
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2017-01-01
AFRL-SA-WP-SR-2017-0001 Population Spotting Using “ Big Data ”: Validating the Human Performance Concept of Operations Analytic Vision...TITLE AND SUBTITLE Population Spotting Using “ Big Data ”: Validating the Human Performance Concept of Operations Analytic Vision 5a. CONTRACT...STINFO COPY NOTICE AND SIGNATURE PAGE Using Government drawings, specifications, or other data included in this document for any
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Construct Validity of Fresh Frozen Human Cadaver as a Training Model in Minimal Access Surgery
Macafee, David; Pranesh, Nagarajan; Horgan, Alan F.
2012-01-01
Background: The construct validity of fresh human cadaver as a training tool has not been established previously. The aims of this study were to investigate the construct validity of fresh frozen human cadaver as a method of training in minimal access surgery and determine if novices can be rapidly trained using this model to a safe level of performance. Methods: Junior surgical trainees, novices (<3 laparoscopic procedure performed) in laparoscopic surgery, performed 10 repetitions of a set of structured laparoscopic tasks on fresh frozen cadavers. Expert laparoscopists (>100 laparoscopic procedures) performed 3 repetitions of identical tasks. Performances were scored using a validated, objective Global Operative Assessment of Laparoscopic Skills scale. Scores for 3 consecutive repetitions were compared between experts and novices to determine construct validity. Furthermore, to determine if the novices reached a safe level, a trimmed mean of the experts score was used to define a benchmark. Mann-Whitney U test was used for construct validity analysis and 1-sample t test to compare performances of the novice group with the benchmark safe score. Results: Ten novices and 2 experts were recruited. Four out of 5 tasks (nondominant to dominant hand transfer; simulated appendicectomy; intracorporeal and extracorporeal knot tying) showed construct validity. Novices’ scores became comparable to benchmark scores between the eighth and tenth repetition. Conclusion: Minimal access surgical training using fresh frozen human cadavers appears to have construct validity. The laparoscopic skills of novices can be accelerated through to a safe level within 8 to 10 repetitions. PMID:23318058
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NASA Technical Reports Server (NTRS)
Haines, Richard F.
1990-01-01
As telescience systems become more and more complex, autonomous, and opaque to their operators it becomes increasingly difficult to determine whether the total system is performing as it should. Some of the complex and interrelated human performance measurement issues are addressed as they relate to total system validation. The assumption is made that human interaction with the automated system will be required well into the Space Station Freedom era. Candidate human performance measurement-validation techniques are discussed for selected ground-to-space-to-ground and space-to-space situations. Most of these measures may be used in conjunction with an information throughput model presented elsewhere (Haines, 1990). Teleoperations, teleanalysis, teleplanning, teledesign, and teledocumentation are considered, as are selected illustrative examples of space related telescience activities.
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NASA Technical Reports Server (NTRS)
Sebok, Angelia; Wickens, Christopher; Sargent, Robert
2015-01-01
One human factors challenge is predicting operator performance in novel situations. Approaches such as drawing on relevant previous experience, and developing computational models to predict operator performance in complex situations, offer potential methods to address this challenge. A few concerns with modeling operator performance are that models need to realistic, and they need to be tested empirically and validated. In addition, many existing human performance modeling tools are complex and require that an analyst gain significant experience to be able to develop models for meaningful data collection. This paper describes an effort to address these challenges by developing an easy to use model-based tool, using models that were developed from a review of existing human performance literature and targeted experimental studies, and performing an empirical validation of key model predictions.
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An evaluation of NASA's program in human factors research: Aircrew-vehicle system interaction
NASA Technical Reports Server (NTRS)
1982-01-01
Research in human factors in the aircraft cockpit and a proposed program augmentation were reviewed. The dramatic growth of microprocessor technology makes it entirely feasible to automate increasingly more functions in the aircraft cockpit; the promise of improved vehicle performance, efficiency, and safety through automation makes highly automated flight inevitable. An organized data base and validated methodology for predicting the effects of automation on human performance and thus on safety are lacking and without such a data base and validated methodology for analyzing human performance, increased automation may introduce new risks. Efforts should be concentrated on developing methods and techniques for analyzing man machine interactions, including human workload and prediction of performance.
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Validating an artificial intelligence human proximity operations system with test cases
NASA Astrophysics Data System (ADS)
Huber, Justin; Straub, Jeremy
2013-05-01
An artificial intelligence-controlled robot (AICR) operating in close proximity to humans poses risk to these humans. Validating the performance of an AICR is an ill posed problem, due to the complexity introduced by the erratic (noncomputer) actors. In order to prove the AICR's usefulness, test cases must be generated to simulate the actions of these actors. This paper discusses AICR's performance validation in the context of a common human activity, moving through a crowded corridor, using test cases created by an AI use case producer. This test is a two-dimensional simplification relevant to autonomous UAV navigation in the national airspace.
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A Human Proximity Operations System test case validation approach
NASA Astrophysics Data System (ADS)
Huber, Justin; Straub, Jeremy
A Human Proximity Operations System (HPOS) poses numerous risks in a real world environment. These risks range from mundane tasks such as avoiding walls and fixed obstacles to the critical need to keep people and processes safe in the context of the HPOS's situation-specific decision making. Validating the performance of an HPOS, which must operate in a real-world environment, is an ill posed problem due to the complexity that is introduced by erratic (non-computer) actors. In order to prove the HPOS's usefulness, test cases must be generated to simulate possible actions of these actors, so the HPOS can be shown to be able perform safely in environments where it will be operated. The HPOS must demonstrate its ability to be as safe as a human, across a wide range of foreseeable circumstances. This paper evaluates the use of test cases to validate HPOS performance and utility. It considers an HPOS's safe performance in the context of a common human activity, moving through a crowded corridor, and extrapolates (based on this) to the suitability of using test cases for AI validation in other areas of prospective application.
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Human Factors Assessment of Vibration Effects on Visual Performance During Launch
NASA Technical Reports Server (NTRS)
Holden, Kritina
2009-01-01
The Human Factors Assessment of Vibration Effects on Visual Performance During Launch (Visual Performance) investigation will determine visual performance limits during operational vibration and g-loads on the Space Shuttle, specifically through the determination of minimum readable font size during ascent using planned Orion display formats. Research Summary: The aim of the Human Factors Assessment of Vibration Effects on Visual Performance during Launch (Visual Performance) investigation is to provide supplementary data to that collected by the Thrust Oscillation Seat Detailed Technical Objective (DTO) 695 (Crew Seat DTO) which will measure seat acceleration and vibration from one flight deck and two middeck seats during ascent. While the Crew Seat DTO data alone are important in terms of providing a measure of vibration and g-loading, human performance data are required to fully interpret the operational consequences of the vibration values collected during Space Shuttle ascent. During launch, crewmembers will be requested to view placards with varying font sizes and indicate the minimum readable size. In combination with the Crew Seat DTO, the Visual Performance investigation will: Provide flight-validated evidence that will be used to establish vibration limits for visual performance during combined vibration and linear g-loading. o Provide flight data as inputs to ongoing ground-based simulations, which will further validate crew visual performance under vibration loading in a controlled environment. o Provide vibration and performance metrics to help validate procedures for ground tests and analyses of seats, suits, displays and controls, and human-in-the-loop performance.
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Laczó, Jan; Markova, Hana; Lobellova, Veronika; Gazova, Ivana; Parizkova, Martina; Cerman, Jiri; Nekovarova, Tereza; Vales, Karel; Klovrzova, Sylva; Harrison, John; Windisch, Manfred; Vlcek, Kamil; Svoboda, Jan; Hort, Jakub; Stuchlik, Ales
2017-02-01
Development of new drugs for treatment of Alzheimer's disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols. We used scopolamine to model cognitive dysfunction similar to that seen in AD and donepezil, a symptomatic medication for AD, to assess its potential reversible effect on this scopolamine-induced cognitive dysfunction. We tested the effects of scopolamine and the combination of scopolamine and donepezil on place navigation and compared their effects in human and rat versions of the HGT. Place navigation testing consisted of 4 sessions of HGT performed at baseline, 2, 4, and 8 h after dosing in humans or 1, 2.5, and 5 h in rats. Scopolamine worsened performance in both animals and humans. In the animal experiment, co-administration of donepezil alleviated the negative effect of scopolamine. In the human experiment, subjects co-administered with scopolamine and donepezil performed similarly to subjects on placebo and scopolamine, indicating a partial ameliorative effect of donepezil. In the task based on the MWM, scopolamine impaired place navigation, while co-administration of donepezil alleviated this effect in comparable animal and human protocols. Using scopolamine and donepezil to challenge place navigation testing can be studied concurrently in animals and humans and may be a valid and reliable model for translational research, as well as for preclinical and clinical phases of drug trials.
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On the Validity of Beer-Lambert Law and its Significance for Sunscreens.
Herzog, Bernd; Schultheiss, Amélie; Giesinger, Jochen
2018-03-01
The sun protection factor (SPF) is the most important quantity to characterize the performance of sunscreens. As the standard method for its determination is based on clinical trials involving irradiation of human volunteers, calculations of sunscreen performance have become quite popular to reduce the number of in vivo studies. Such simulations imply the calculation of UV transmittance of the sunscreen film using the amounts and spectroscopic properties of the UV absorbers employed, and presuppose the validity of the Beer-Lambert law. As sunscreen films on human skin can contain considerable concentrations of UV absorbers, it is questioned whether the Beer-Lambert law is still valid for these systems. The results of this work show that the validity of the Beer-Lambert law is still given at the high concentrations at which UV absorbers occur in sunscreen films on human skin. © 2017 The American Society of Photobiology.
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The Situation Awareness Weighted Network (SAWN) Model
2014-06-01
Administration Task Load Index (NASA- TLX ), a validated research instrument [Human Performance Research Group 1988]. The participants were asked to rate their...analysis”, Human Factors 40(2): 254–276. 17 Human Performance Research Group (1988) NASA- TLX , NASA Ames Research Center, Moffett Field, CA. Jin, Y. and
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Predicting ionizing radiation exposure using biochemically-inspired genomic machine learning.
Zhao, Jonathan Z L; Mucaki, Eliseos J; Rogan, Peter K
2018-01-01
Background: Gene signatures derived from transcriptomic data using machine learning methods have shown promise for biodosimetry testing. These signatures may not be sufficiently robust for large scale testing, as their performance has not been adequately validated on external, independent datasets. The present study develops human and murine signatures with biochemically-inspired machine learning that are strictly validated using k-fold and traditional approaches. Methods: Gene Expression Omnibus (GEO) datasets of exposed human and murine lymphocytes were preprocessed via nearest neighbor imputation and expression of genes implicated in the literature to be responsive to radiation exposure (n=998) were then ranked by Minimum Redundancy Maximum Relevance (mRMR). Optimal signatures were derived by backward, complete, and forward sequential feature selection using Support Vector Machines (SVM), and validated using k-fold or traditional validation on independent datasets. Results: The best human signatures we derived exhibit k-fold validation accuracies of up to 98% ( DDB2 , PRKDC , TPP2 , PTPRE , and GADD45A ) when validated over 209 samples and traditional validation accuracies of up to 92% ( DDB2 , CD8A , TALDO1 , PCNA , EIF4G2 , LCN2 , CDKN1A , PRKCH , ENO1 , and PPM1D ) when validated over 85 samples. Some human signatures are specific enough to differentiate between chemotherapy and radiotherapy. Certain multi-class murine signatures have sufficient granularity in dose estimation to inform eligibility for cytokine therapy (assuming these signatures could be translated to humans). We compiled a list of the most frequently appearing genes in the top 20 human and mouse signatures. More frequently appearing genes among an ensemble of signatures may indicate greater impact of these genes on the performance of individual signatures. Several genes in the signatures we derived are present in previously proposed signatures. Conclusions: Gene signatures for ionizing radiation exposure derived by machine learning have low error rates in externally validated, independent datasets, and exhibit high specificity and granularity for dose estimation.
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Automated Essay Scoring versus Human Scoring: A Correlational Study
ERIC Educational Resources Information Center
Wang, Jinhao; Brown, Michelle Stallone
2008-01-01
The purpose of the current study was to analyze the relationship between automated essay scoring (AES) and human scoring in order to determine the validity and usefulness of AES for large-scale placement tests. Specifically, a correlational research design was used to examine the correlations between AES performance and human raters' performance.…
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Sebok, Angelia; Wickens, Christopher D
2017-03-01
The objectives were to (a) implement theoretical perspectives regarding human-automation interaction (HAI) into model-based tools to assist designers in developing systems that support effective performance and (b) conduct validations to assess the ability of the models to predict operator performance. Two key concepts in HAI, the lumberjack analogy and black swan events, have been studied extensively. The lumberjack analogy describes the effects of imperfect automation on operator performance. In routine operations, an increased degree of automation supports performance, but in failure conditions, increased automation results in more significantly impaired performance. Black swans are the rare and unexpected failures of imperfect automation. The lumberjack analogy and black swan concepts have been implemented into three model-based tools that predict operator performance in different systems. These tools include a flight management system, a remotely controlled robotic arm, and an environmental process control system. Each modeling effort included a corresponding validation. In one validation, the software tool was used to compare three flight management system designs, which were ranked in the same order as predicted by subject matter experts. The second validation compared model-predicted operator complacency with empirical performance in the same conditions. The third validation compared model-predicted and empirically determined time to detect and repair faults in four automation conditions. The three model-based tools offer useful ways to predict operator performance in complex systems. The three tools offer ways to predict the effects of different automation designs on operator performance.
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NASA Technical Reports Server (NTRS)
Hooey, Becky Lee; Gore, Brian Francis; Mahlstedt, Eric; Foyle, David C.
2013-01-01
The objectives of the current research were to develop valid human performance models (HPMs) of approach and land operations; use these models to evaluate the impact of NextGen Closely Spaced Parallel Operations (CSPO) on pilot performance; and draw conclusions regarding flight deck display design and pilot-ATC roles and responsibilities for NextGen CSPO concepts. This document presents guidelines and implications for flight deck display designs and candidate roles and responsibilities. A companion document (Gore, Hooey, Mahlstedt, & Foyle, 2013) provides complete scenario descriptions and results including predictions of pilot workload, visual attention and time to detect off-nominal events.
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A Perspective on Computational Human Performance Models as Design Tools
NASA Technical Reports Server (NTRS)
Jones, Patricia M.
2010-01-01
The design of interactive systems, including levels of automation, displays, and controls, is usually based on design guidelines and iterative empirical prototyping. A complementary approach is to use computational human performance models to evaluate designs. An integrated strategy of model-based and empirical test and evaluation activities is particularly attractive as a methodology for verification and validation of human-rated systems for commercial space. This talk will review several computational human performance modeling approaches and their applicability to design of display and control requirements.
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ERIC Educational Resources Information Center
Pecorella, Patricia A.; Bowers, David G.
Multiple regression in a double cross-validated design was used to predict two performance measures (total variable expense and absence rate) by multi-month period in five industrial firms. The regressions do cross-validate, and produce multiple coefficients which display both concurrent and predictive effects, peaking 18 months to two years…
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Stress Response as a Function of Task Relevance
2010-12-01
be benchmarked for validity and reliability. The State-Trait Anxiety Index (or STAI; Spielberger and Sydeman, 1994) is a popular self-report...and human performance. In J.E. Driskell & E. Salas (Eds.), Stress and Human Performance Spielberger , C.D. and Sydeman, S.J. (1994). State-Trait
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An Assessment-based Solution to a Human-Service Employee Performance Problem
Wilder, David A.; Majdalany, Lina; Mathisen, David; Strain, Leigh Ann
2013-01-01
The PDC-HS implicated a lack of proper training on participant duties and a lack of performance feedback as contributors to the performance problems. As a result, an intervention targeting training on participant duties and performance feedback was implemented across eight treatment rooms; the intervention increased performance in all rooms. This preliminary validation study suggests the PDC-HS may prove useful in solving performance problems in human-service settings. PMID:25729505
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Jastrzembski, Tiffany S.; Charness, Neil
2009-01-01
The authors estimate weighted mean values for nine information processing parameters for older adults using the Card, Moran, and Newell (1983) Model Human Processor model. The authors validate a subset of these parameters by modeling two mobile phone tasks using two different phones and comparing model predictions to a sample of younger (N = 20; Mage = 20) and older (N = 20; Mage = 69) adults. Older adult models fit keystroke-level performance at the aggregate grain of analysis extremely well (R = 0.99) and produced equivalent fits to previously validated younger adult models. Critical path analyses highlighted points of poor design as a function of cognitive workload, hardware/software design, and user characteristics. The findings demonstrate that estimated older adult information processing parameters are valid for modeling purposes, can help designers understand age-related performance using existing interfaces, and may support the development of age-sensitive technologies. PMID:18194048
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Jastrzembski, Tiffany S; Charness, Neil
2007-12-01
The authors estimate weighted mean values for nine information processing parameters for older adults using the Card, Moran, and Newell (1983) Model Human Processor model. The authors validate a subset of these parameters by modeling two mobile phone tasks using two different phones and comparing model predictions to a sample of younger (N = 20; M-sub(age) = 20) and older (N = 20; M-sub(age) = 69) adults. Older adult models fit keystroke-level performance at the aggregate grain of analysis extremely well (R = 0.99) and produced equivalent fits to previously validated younger adult models. Critical path analyses highlighted points of poor design as a function of cognitive workload, hardware/software design, and user characteristics. The findings demonstrate that estimated older adult information processing parameters are valid for modeling purposes, can help designers understand age-related performance using existing interfaces, and may support the development of age-sensitive technologies.
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Design and Validation of an Infrared Badal Optometer for Laser Speckle (IBOLS)
Teel, Danielle F. W.; Copland, R. James; Jacobs, Robert J.; Wells, Thad; Neal, Daniel R.; Thibos, Larry N.
2009-01-01
Purpose To validate the design of an infrared wavefront aberrometer with a Badal optometer employing the principle of laser speckle generated by a spinning disk and infrared light. The instrument was designed for subjective meridional refraction in infrared light by human patients. Methods Validation employed a model eye with known refractive error determined with an objective infrared wavefront aberrometer. The model eye was used to produce a speckle pattern on an artificial retina with controlled amounts of ametropia introduced with auxiliary ophthalmic lenses. A human observer performed the psychophysical task of observing the speckle pattern (with the aid of a video camera sensitive to infrared radiation) formed on the artificial retina. Refraction was performed by adjusting the vergence of incident light with the Badal optometer to nullify the motion of laser speckle. Validation of the method was performed for different levels of spherical ametropia and for various configurations of an astigmatic model eye. Results Subjective measurements of meridional refractive error over the range −4D to + 4D agreed with astigmatic refractive errors predicted by the power of the model eye in the meridian of motion of the spinning disk. Conclusions Use of a Badal optometer to control laser speckle is a valid method for determining subjective refractive error at infrared wavelengths. Such an instrument will be useful for comparing objective measures of refractive error obtained for the human eye with autorefractors and wavefront aberrometers that employ infrared radiation. PMID:18772719
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The Ethics of PI: A Polemical Overview.
ERIC Educational Resources Information Center
Stewart, Jim
2003-01-01
Suggests that Human Resource Development (HRD) is in and of itself an ethical endeavor. Starts with a brief discussion about human performance improvement, next explores the issue of ethics, and then brings the two together to demonstrate the truth and validity of the argument that performance improvement (PI) is an ethical endeavor. (AEF)
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2015-03-26
Engineering and Management Air Force Institute of Technology Air University Air Education and Training Command In Partial Fulfillment of the...Human Universal Measurement and Assessment Network (HUMAN) Lab human performance experiment trials were used to train , validate and test the...calming music to ease the individual before the start of the study [8]. EEG data contains noise ranging from muscle twitches, blinking and other functions
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Yasukawa, Keiko; Shimosawa, Tatsuo; Okubo, Shigeo; Yatomi, Yutaka
2018-01-01
Background Human mercaptalbumin and human non-mercaptalbumin have been reported as markers for various pathological conditions, such as kidney and liver diseases. These markers play important roles in redox regulations throughout the body. Despite the recognition of these markers in various pathophysiologic conditions, the measurements of human mercaptalbumin and non-mercaptalbumin have not been popular because of the technical complexity and long measurement time of conventional methods. Methods Based on previous reports, we explored the optimal analytical conditions for a high-performance liquid chromatography method using an anion-exchange column packed with a hydrophilic polyvinyl alcohol gel. The method was then validated using performance tests as well as measurements of various patients' serum samples. Results We successfully established a reliable high-performance liquid chromatography method with an analytical time of only 12 min per test. The repeatability (within-day variability) and reproducibility (day-to-day variability) were 0.30% and 0.27% (CV), respectively. A very good correlation was obtained with the results of the conventional method. Conclusions A practical method for the clinical measurement of human mercaptalbumin and non-mercaptalbumin was established. This high-performance liquid chromatography method is expected to be a powerful tool enabling the expansion of clinical usefulness and ensuring the elucidation of the roles of albumin in redox reactions throughout the human body.
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Katoh, Masakazu; Hamajima, Fumiyasu; Ogasawara, Takahiro; Hata, Ken-Ichiro
2009-06-01
A validation study of an in vitro skin irritation testing method using a reconstructed human skin model has been conducted by the European Centre for the Validation of Alternative Methods (ECVAM), and a protocol using EpiSkin (SkinEthic, France) has been approved. The structural and performance criteria of skin models for testing are defined in the ECVAM Performance Standards announced along with the approval. We have performed several evaluations of the new reconstructed human epidermal model LabCyte EPI-MODEL, and confirmed that it is applicable to skin irritation testing as defined in the ECVAM Performance Standards. We selected 19 materials (nine irritants and ten non-irritants) available in Japan as test chemicals among the 20 reference chemicals described in the ECVAM Performance Standard. A test chemical was applied to the surface of the LabCyte EPI-MODEL for 15 min, after which it was completely removed and the model then post-incubated for 42 hr. Cell v iability was measured by MTT assay and skin irritancy of the test chemical evaluated. In addition, interleukin-1 alpha (IL-1alpha) concentration in the culture supernatant after post-incubation was measured to provide a complementary evaluation of skin irritation. Evaluation of the 19 test chemicals resulted in 79% accuracy, 78% sensitivity and 80% specificity, confirming that the in vitro skin irritancy of the LabCyte EPI-MODEL correlates highly with in vivo skin irritation. These results suggest that LabCyte EPI-MODEL is applicable to the skin irritation testing protocol set out in the ECVAM Performance Standards.
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Reverse Engineering Validation using a Benchmark Synthetic Gene Circuit in Human Cells
Kang, Taek; White, Jacob T.; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas
2013-01-01
Multi-component biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network. PMID:23654266
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Reverse engineering validation using a benchmark synthetic gene circuit in human cells.
Kang, Taek; White, Jacob T; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas
2013-05-17
Multicomponent biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network.
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Siva Selva Kumar, M; Ramanathan, M
2016-02-01
A simple and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of olanzapine (OLZ), risperidone (RIS) and 9-hydroxyrisperidone (9-OHRIS) in human plasma in vitro. The sample preparation was performed by simple liquid-liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP18 column maintained at 40°C. Quantification was performed on a photodiode array detector set at 277 nm and clozapine was used as internal standard (IS). OLZ, RIS, 9-OHRIS and IS retention times were found to be 0.9, 1.4, .1.8 and 3.1 min, respectively, and the total run time was 4 min. The method was validated for selectivity, specificity, recovery, linearity, accuracy, precision and sample stability. The calibration curve was linear over the concentration range 1-100 ng/mL for OLZ, RIS and 9-OHRIS. Intra- and inter-day precisions for OLZ, RIS and 9-OHRIS were found to be good with the coefficient of variation <6.96%, and the accuracy ranging from 97.55 to 105.41%, in human plasma. The validated UPLC method was successfully applied to the pharmacokinetic study of RIS and 9-OHRIS in human plasma. Copyright © 2015 John Wiley & Sons, Ltd.
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Validating a Geographical Image Retrieval System.
ERIC Educational Resources Information Center
Zhu, Bin; Chen, Hsinchun
2000-01-01
Summarizes a prototype geographical image retrieval system that demonstrates how to integrate image processing and information analysis techniques to support large-scale content-based image retrieval. Describes an experiment to validate the performance of this image retrieval system against that of human subjects by examining similarity analysis…
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Wang, Zhenlei; Jiang, Ji; Hu, Pei; Zhao, Qian
2017-02-01
Fotagliptin is a novel dipeptidyl peptidase IV inhibitor under clinical development for the treatment of Type II diabetes mellitus. The objective of this study was to develop and validate a specific and sensitive ultra-performance liquid chromatography (UPLC)-MS/MS method for simultaneous determination of fotagliptin and its two major metabolites in human plasma and urine. Methodology & results: After being pretreated using an automatized procedure, the plasma and urine samples were separated and detected using a UPLC-ESI-MS/MS method, which was validated following the international guidelines. A selective and sensitive UPLC-MS/MS method was first developed and validated for quantifying fotagliptin and its metabolite in human plasma and urine. The method was successfully applied to support the clinical study of fotagliptin in Chinese healthy subjects.
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Teijlingen, Raymond van; Meijer, John; Takusagawa, Shin; Gelderen, Marcel van; Beld, Cas van den; Usui, Takashi
2012-03-01
Mirabegron is being developed for the treatment of overactive bladder. To support the development of mirabegron, including pharmacokinetic studies, liquid chromatography/tandem mass spectrometry methods for mirabegron and eight metabolites (M5, M8, M11-M16) were developed and validated for heparinized human plasma containing sodium fluoride. Four separate bioanalytical methods were developed for the analysis of: (1) mirabegron; (2) M5 and M16; (3) M8; and (4) M11-M15. Either solid-phase extraction or liquid-liquid extraction was used to extract the analytes of interest from matrix constituents. For mirabegron, an Inertsil C₈-3 analytical column was used and detection was performed using a triple-quad mass spectrometer equipped with an atmospheric pressure chemical ionization interface. For the metabolite assays, chromatographic separation was performed through a Phenomenex Synergi Fusion-RP C₁₈ analytical column and detection was performed using a triple-quad mass spectrometer equipped with a Heated Electrospray Ionization interface. The validation results demonstrated that the developed liquid chromatography/tandem mass spectrometry methods were precise, accurate, and selective for the determination of mirabegron and its metabolites in human plasma. All methods were successfully applied in evaluating the pharmacokinetic parameters of mirabegron and metabolites in human plasma. Copyright © 2012 Elsevier B.V. All rights reserved.
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Guetterman, Timothy C; Kron, Frederick W; Campbell, Toby C; Scerbo, Mark W; Zelenski, Amy B; Cleary, James F; Fetters, Michael D
2017-01-01
Despite interest in using virtual humans (VHs) for assessing health care communication, evidence of validity is limited. We evaluated the validity of a VH application, MPathic-VR, for assessing performance-based competence in breaking bad news (BBN) to a VH patient. We used a two-group quasi-experimental design, with residents participating in a 3-hour seminar on BBN. Group A (n=15) completed the VH simulation before and after the seminar, and Group B (n=12) completed the VH simulation only after the BBN seminar to avoid the possibility that testing alone affected performance. Pre- and postseminar differences for Group A were analyzed with a paired t -test, and comparisons between Groups A and B were analyzed with an independent t -test. Compared to the preseminar result, Group A's postseminar scores improved significantly, indicating that the VH program was sensitive to differences in assessing performance-based competence in BBN. Postseminar scores of Group A and Group B were not significantly different, indicating that both groups performed similarly on the VH program. Improved pre-post scores demonstrate acquisition of skills in BBN to a VH patient. Pretest sensitization did not appear to influence posttest assessment. These results provide initial construct validity evidence that the VH program is effective for assessing BBN performance-based communication competence.
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Guetterman, Timothy C; Kron, Frederick W; Campbell, Toby C; Scerbo, Mark W; Zelenski, Amy B; Cleary, James F; Fetters, Michael D
2017-01-01
Background Despite interest in using virtual humans (VHs) for assessing health care communication, evidence of validity is limited. We evaluated the validity of a VH application, MPathic-VR, for assessing performance-based competence in breaking bad news (BBN) to a VH patient. Methods We used a two-group quasi-experimental design, with residents participating in a 3-hour seminar on BBN. Group A (n=15) completed the VH simulation before and after the seminar, and Group B (n=12) completed the VH simulation only after the BBN seminar to avoid the possibility that testing alone affected performance. Pre- and postseminar differences for Group A were analyzed with a paired t-test, and comparisons between Groups A and B were analyzed with an independent t-test. Results Compared to the preseminar result, Group A’s postseminar scores improved significantly, indicating that the VH program was sensitive to differences in assessing performance-based competence in BBN. Postseminar scores of Group A and Group B were not significantly different, indicating that both groups performed similarly on the VH program. Conclusion Improved pre–post scores demonstrate acquisition of skills in BBN to a VH patient. Pretest sensitization did not appear to influence posttest assessment. These results provide initial construct validity evidence that the VH program is effective for assessing BBN performance-based communication competence. PMID:28794664
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Jiang, Jian; James, Christopher A; Wong, Philip
2016-09-05
A LC-MS/MS method has been developed and validated for the determination of glycine in human cerebrospinal fluid (CSF). The validated method used artificial cerebrospinal fluid as a surrogate matrix for calibration standards. The calibration curve range for the assay was 100-10,000ng/mL and (13)C2, (15)N-glycine was used as an internal standard (IS). Pre-validation experiments were performed to demonstrate parallelism with surrogate matrix and standard addition methods. The mean endogenous glycine concentration in a pooled human CSF determined on three days by using artificial CSF as a surrogate matrix and the method of standard addition was found to be 748±30.6 and 768±18.1ng/mL, respectively. A percentage difference of -2.6% indicated that artificial CSF could be used as a surrogate calibration matrix for the determination of glycine in human CSF. Quality control (QC) samples, except the lower limit of quantitation (LLOQ) QC and low QC samples, were prepared by spiking glycine into aliquots of pooled human CSF sample. The low QC sample was prepared from a separate pooled human CSF sample containing low endogenous glycine concentrations, while the LLOQ QC sample was prepared in artificial CSF. Standard addition was used extensively to evaluate matrix effects during validation. The validated method was used to determine the endogenous glycine concentrations in human CSF samples. Incurred sample reanalysis demonstrated reproducibility of the method. Copyright © 2016 Elsevier B.V. All rights reserved.
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Baldassano, Steven N; Brinkmann, Benjamin H; Ung, Hoameng; Blevins, Tyler; Conrad, Erin C; Leyde, Kent; Cook, Mark J; Khambhati, Ankit N; Wagenaar, Joost B; Worrell, Gregory A; Litt, Brian
2017-06-01
There exist significant clinical and basic research needs for accurate, automated seizure detection algorithms. These algorithms have translational potential in responsive neurostimulation devices and in automatic parsing of continuous intracranial electroencephalography data. An important barrier to developing accurate, validated algorithms for seizure detection is limited access to high-quality, expertly annotated seizure data from prolonged recordings. To overcome this, we hosted a kaggle.com competition to crowdsource the development of seizure detection algorithms using intracranial electroencephalography from canines and humans with epilepsy. The top three performing algorithms from the contest were then validated on out-of-sample patient data including standard clinical data and continuous ambulatory human data obtained over several years using the implantable NeuroVista seizure advisory system. Two hundred teams of data scientists from all over the world participated in the kaggle.com competition. The top performing teams submitted highly accurate algorithms with consistent performance in the out-of-sample validation study. The performance of these seizure detection algorithms, achieved using freely available code and data, sets a new reproducible benchmark for personalized seizure detection. We have also shared a 'plug and play' pipeline to allow other researchers to easily use these algorithms on their own datasets. The success of this competition demonstrates how sharing code and high quality data results in the creation of powerful translational tools with significant potential to impact patient care. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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ERIC Educational Resources Information Center
Brock, Timothy R.
2009-01-01
Development research methodology (DRM) has been recommended as a viable research approach to expand the practice-to-theory/theory-to-practice literature that human performance technology (HPT) practitioners can integrate into the day-to-day work flow they already use to develop instructional products. However, little has been written about how it…
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NASA Technical Reports Server (NTRS)
Morris, Aaron L.; Olson, Leah M.
2011-01-01
The Crew Exploration Vehicle Parachute Assembly System (CPAS) is engaged in a multi-year design and test campaign aimed at qualifying a parachute recovery system for human use on the Orion Spacecraft. Orion has parachute flight performance requirements that will ultimately be verified through the use of Monte Carlo multi-degree of freedom flight simulations. These simulations will be anchored by real world flight test data and iteratively improved to provide a closer approximation to the real physics observed in the inherently chaotic inflation and steady state flight of the CPAS parachutes. This paper will examine the processes necessary to verify the flight performance requirements of the human rated spacecraft. The focus will be on the requirements verification and model validation planned on CPAS.
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What Do HPT Consultants Do for Performance Analysis?
ERIC Educational Resources Information Center
Kang, Sung
2017-01-01
This study was conducted to contribute to the field of Human Performance Technology (HPT) through the validation of the performance analysis process of the International Society for Performance Improvement (ISPI) HPT model, the most representative and frequently utilized process model in the HPT field. The study was conducted using content…
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Integrating a Motion Base into a CAVE Automatic Virtual Environment: Phase 1
2001-07-01
this, a CAVE system must perform well in the following motion-related areas: visual gaze stability, simulator sickness, realism (or face validity...and performance validity. Visual Gaze Stability Visual gaze stability, the ability to maintain eye fixation on a particular target, depends upon human...reflexes such as the vestibulo-ocular reflex (VOR) and the optokinetic nystagmus (OKN). VOR is a reflex that counter-rotates the eye relative to the
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Active imaging system performance model for target acquisition
NASA Astrophysics Data System (ADS)
Espinola, Richard L.; Teaney, Brian; Nguyen, Quang; Jacobs, Eddie L.; Halford, Carl E.; Tofsted, David H.
2007-04-01
The U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate has developed a laser-range-gated imaging system performance model for the detection, recognition, and identification of vehicle targets. The model is based on the established US Army RDECOM CERDEC NVESD sensor performance models of the human system response through an imaging system. The Java-based model, called NVLRG, accounts for the effect of active illumination, atmospheric attenuation, and turbulence effects relevant to LRG imagers, such as speckle and scintillation, and for the critical sensor and display components. This model can be used to assess the performance of recently proposed active SWIR systems through various trade studies. This paper will describe the NVLRG model in detail, discuss the validation of recent model components, present initial trade study results, and outline plans to validate and calibrate the end-to-end model with field data through human perception testing.
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Investigating human cognitive performance during spaceflight
NASA Astrophysics Data System (ADS)
Pattyn, Nathalie; Migeotte, Pierre-Francois; Demaeseleer, Wim; Kolinsky, Regine; Morais, Jose; Zizi, Martin
2005-08-01
Although astronauts' subjective self-evaluation of cognitive functioning often reports impairments, to date most studies of human higher cognitive functions in space never yielded univocal results. Since no golden standard exists to evaluate the higher cognitive functions, we proposed to assess astronaut's cognitive performance through a novel series of tests combined with the simultaneous recording of physiological parameters. We report here the validation of our methodology and the cognitive results of this testing on the cosmonauts from the 11 days odISSsea mission to the ISS (2002) and on a control group of pilots, carefully matched to the characteristics of the subjects. For the first time, we show a performance decrement in higher cognitive functions during space flight. Our results show a significant performance decrement for inflight measurement, as well as measurable variations in executive control of cognitive functions. Taken together, our data establish the validity of our methodology and the presence of a different information processing in operational conditions.
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Louveau, B; Fernandez, C; Zahr, N; Sauvageon-Martre, H; Maslanka, P; Faure, P; Mourah, S; Goldwirt, L
2016-12-01
A precise and accurate high-performance liquid chromatography (HPLC) quantification method of rifampicin in human plasma was developed and validated using ultraviolet detection after an automatized solid-phase extraction. The method was validated with respect to selectivity, extraction recovery, linearity, intra- and inter-day precision, accuracy, lower limit of quantification and stability. Chromatographic separation was performed on a Chromolith RP 8 column using a mixture of 0.05 m acetate buffer pH 5.7-acetonitrile (35:65, v/v) as mobile phase. The compounds were detected at a wavelength of 335 nm with a lower limit of quantification of 0.05 mg/L in human plasma. Retention times for rifampicin and 6,7-dimethyl-2,3-di(2-pyridyl) quinoxaline used as internal standard were respectively 3.77 and 4.81 min. This robust and exact method was successfully applied in routine for therapeutic drug monitoring in patients treated with rifampicin. Copyright © 2016 John Wiley & Sons, Ltd.
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Police, Anitha; Gurav, Sandip; Dhiman, Vinay; Zainuddin, Mohd; Bhamidipati, Ravi Kanth; Rajagopal, Sriram; Mullangi, Ramesh
2015-11-01
A simple, specific, sensitive and reproducible high-performance liquid chromatography (HPLC) assay method has been developed and validated for the estimation of odanacatib in rat and human plasma. The bioanalytical procedure involves extraction of odanacatib and itraconazole (internal standard, IS) from a 200 μL plasma aliquot with simple liquid-liquid extraction process. Chromatographic separation was achieved on a Symmetry Shield RP18 using an isocratic mobile phase at a flow rate of 0.7 mL/min. The UV detection wave length was 268 nm. Odanacatib and IS eluted at 5.5 and 8.6 min, respectively with a total run time of 10 min. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 50.9-2037 ng/mL (r(2) = 0.994). The intra- and inter-day precisions were in the range of 2.06-5.11 and 5.84-13.1%, respectively, in rat plasma and 2.38-7.90 and 6.39-10.2%, respectively, in human plasma. The validated HPLC method was successfully applied to a pharmacokinetic study in rats. Copyright © 2015 John Wiley & Sons, Ltd.
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Validating Human Performance Models of the Future Orion Crew Exploration Vehicle
NASA Technical Reports Server (NTRS)
Wong, Douglas T.; Walters, Brett; Fairey, Lisa
2010-01-01
NASA's Orion Crew Exploration Vehicle (CEV) will provide transportation for crew and cargo to and from destinations in support of the Constellation Architecture Design Reference Missions. Discrete Event Simulation (DES) is one of the design methods NASA employs for crew performance of the CEV. During the early development of the CEV, NASA and its prime Orion contractor Lockheed Martin (LM) strived to seek an effective low-cost method for developing and validating human performance DES models. This paper focuses on the method developed while creating a DES model for the CEV Rendezvous, Proximity Operations, and Docking (RPOD) task to the International Space Station. Our approach to validation was to attack the problem from several fronts. First, we began the development of the model early in the CEV design stage. Second, we adhered strictly to M&S development standards. Third, we involved the stakeholders, NASA astronauts, subject matter experts, and NASA's modeling and simulation development community throughout. Fourth, we applied standard and easy-to-conduct methods to ensure the model's accuracy. Lastly, we reviewed the data from an earlier human-in-the-loop RPOD simulation that had different objectives, which provided us an additional means to estimate the model's confidence level. The results revealed that a majority of the DES model was a reasonable representation of the current CEV design.
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NASA Technical Reports Server (NTRS)
Pholsiri, Chalongrath; English, James; Seberino, Charles; Lim, Yi-Je
2010-01-01
The Excavator Design Validation tool verifies excavator designs by automatically generating control systems and modeling their performance in an accurate simulation of their expected environment. Part of this software design includes interfacing with human operations that can be included in simulation-based studies and validation. This is essential for assessing productivity, versatility, and reliability. This software combines automatic control system generation from CAD (computer-aided design) models, rapid validation of complex mechanism designs, and detailed models of the environment including soil, dust, temperature, remote supervision, and communication latency to create a system of high value. Unique algorithms have been created for controlling and simulating complex robotic mechanisms automatically from just a CAD description. These algorithms are implemented as a commercial cross-platform C++ software toolkit that is configurable using the Extensible Markup Language (XML). The algorithms work with virtually any mobile robotic mechanisms using module descriptions that adhere to the XML standard. In addition, high-fidelity, real-time physics-based simulation algorithms have also been developed that include models of internal forces and the forces produced when a mechanism interacts with the outside world. This capability is combined with an innovative organization for simulation algorithms, new regolith simulation methods, and a unique control and study architecture to make powerful tools with the potential to transform the way NASA verifies and compares excavator designs. Energid's Actin software has been leveraged for this design validation. The architecture includes parametric and Monte Carlo studies tailored for validation of excavator designs and their control by remote human operators. It also includes the ability to interface with third-party software and human-input devices. Two types of simulation models have been adapted: high-fidelity discrete element models and fast analytical models. By using the first to establish parameters for the second, a system has been created that can be executed in real time, or faster than real time, on a desktop PC. This allows Monte Carlo simulations to be performed on a computer platform available to all researchers, and it allows human interaction to be included in a real-time simulation process. Metrics on excavator performance are established that work with the simulation architecture. Both static and dynamic metrics are included.
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Validating models of target acquisition performance in the dismounted soldier context
NASA Astrophysics Data System (ADS)
Glaholt, Mackenzie G.; Wong, Rachel K.; Hollands, Justin G.
2018-04-01
The problem of predicting real-world operator performance with digital imaging devices is of great interest within the military and commercial domains. There are several approaches to this problem, including: field trials with imaging devices, laboratory experiments using imagery captured from these devices, and models that predict human performance based on imaging device parameters. The modeling approach is desirable, as both field trials and laboratory experiments are costly and time-consuming. However, the data from these experiments is required for model validation. Here we considered this problem in the context of dismounted soldiering, for which detection and identification of human targets are essential tasks. Human performance data were obtained for two-alternative detection and identification decisions in a laboratory experiment in which photographs of human targets were presented on a computer monitor and the images were digitally magnified to simulate range-to-target. We then compared the predictions of different performance models within the NV-IPM software package: Targeting Task Performance (TTP) metric model and the Johnson model. We also introduced a modification to the TTP metric computation that incorporates an additional correction for target angular size. We examined model predictions using NV-IPM default values for a critical model constant, V50, and we also considered predictions when this value was optimized to fit the behavioral data. When using default values, certain model versions produced a reasonably close fit to the human performance data in the detection task, while for the identification task all models substantially overestimated performance. When using fitted V50 values the models produced improved predictions, though the slopes of the performance functions were still shallow compared to the behavioral data. These findings are discussed in relation to the models' designs and parameters, and the characteristics of the behavioral paradigm.
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Reliability of human-supervised formant-trajectory measurement for forensic voice comparison.
Zhang, Cuiling; Morrison, Geoffrey Stewart; Ochoa, Felipe; Enzinger, Ewald
2013-01-01
Acoustic-phonetic approaches to forensic voice comparison often include human-supervised measurement of vowel formants, but the reliability of such measurements is a matter of concern. This study assesses the within- and between-supervisor variability of three sets of formant-trajectory measurements made by each of four human supervisors. It also assesses the validity and reliability of forensic-voice-comparison systems based on these measurements. Each supervisor's formant-trajectory system was fused with a baseline mel-frequency cepstral-coefficient system, and performance was assessed relative to the baseline system. Substantial improvements in validity were found for all supervisors' systems, but some supervisors' systems were more reliable than others.
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Wickens, Christopher D; Sebok, Angelia; Li, Huiyang; Sarter, Nadine; Gacy, Andrew M
2015-09-01
The aim of this study was to develop and validate a computational model of the automation complacency effect, as operators work on a robotic arm task, supported by three different degrees of automation. Some computational models of complacency in human-automation interaction exist, but those are formed and validated within the context of fairly simplified monitoring failures. This research extends model validation to a much more complex task, so that system designers can establish, without need for human-in-the-loop (HITL) experimentation, merits and shortcomings of different automation degrees. We developed a realistic simulation of a space-based robotic arm task that could be carried out with three different levels of trajectory visualization and execution automation support. Using this simulation, we performed HITL testing. Complacency was induced via several trials of correctly performing automation and then was assessed on trials when automation failed. Following a cognitive task analysis of the robotic arm operation, we developed a multicomponent model of the robotic operator and his or her reliance on automation, based in part on visual scanning. The comparison of model predictions with empirical results revealed that the model accurately predicted routine performance and predicted the responses to these failures after complacency developed. However, the scanning models do not account for the entire attention allocation effects of complacency. Complacency modeling can provide a useful tool for predicting the effects of different types of imperfect automation. The results from this research suggest that focus should be given to supporting situation awareness in automation development. © 2015, Human Factors and Ergonomics Society.
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Validation of a multiplex electrochemiluminescent immunoassay platform in human and mouse samples
Bastarache, J.A.; Koyama, T.; Wickersham, N.E; Ware, L.B.
2014-01-01
Despite the widespread use of multiplex immunoassays, there are very few scientific reports that test the accuracy and reliability of a platform prior to publication of experimental data. Our laboratory has previously demonstrated the need for new assay platform validation prior to use of biologic samples from large studies in order to optimize sample handling and assay performance. In this study, our goal was to test the accuracy and reproducibility of an electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD®) and compare this platform to validated, singleplex immunoassays (R&D Systems®) using actual study subject (human plasma and mouse bronchoalveolar lavage fluid (BALF) and plasma) samples. We found that the MSD platform performed well on intra- and inter-assay comparisons, spike and recovery and cross-platform comparisons. The mean intra-assay CV% and range for MSD was 3.49 (0.0-10.4) for IL-6 and 2.04 (0.1-7.9) for IL-8. The correlation between values for identical samples measured on both MSD and R&D was R=0.97 for both analytes. The mouse MSD assay had a broader range of CV% with means ranging from 9.5-28.5 depending on the analyte. The range of mean CV% was similar for single plex ELISAs at 4.3-23.7 depending on the analyte. Regardless of species or sample type, CV% was more variable at lower protein concentrations. In conclusion, we validated a multiplex electrochemiluminscent assay system and found that it has superior test characteristics in human plasma compared to mouse BALF and plasma. Both human and MSD assays compared favorably to well-validated singleplex ELISA's PMID:24768796
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Developing and Validating Practical Eye Metrics for the Sense-Assess-Augment Framework
2015-09-29
Sense-Assess-Augment ( SAA ) Framework. To better close the loop between the human and machine teammates AFRL’s Human Performance Wing and Human...Sense-Assess-Augment ( SAA ) framework, which is designed to sense a suite of physiological signals from the operator, use these signals to assess the...to use psychophysiological measures to improve human-machine teamwork (such as Biocybernetics or Augmented Cognition) the AFRL- SAA research program
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Proceedings of the Human Factors Society 35th annual meeting
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1991-01-01
These volumes cover the proceedings of the 35th annual meeting of the Human Factors Society. Topics include: designing for the future of nuclear power plants international perspectives on advanced control room design; human performance assessment in the nuclear power industry; validity of strength tests for predicting endurance of coal miners, psychosocial issues in hazard management and nuclear power plants; and human factors at the DOE's national laboratories.
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A Study on the Impact of Fatigue on Human Raters When Scoring Speaking Responses
ERIC Educational Resources Information Center
Ling, Guangming; Mollaun, Pamela; Xi, Xiaoming
2014-01-01
The scoring of constructed responses may introduce construct-irrelevant factors to a test score and affect its validity and fairness. Fatigue is one of the factors that could negatively affect human performance in general, yet little is known about its effects on a human rater's scoring quality on constructed responses. In this study, we compared…
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The purpose of this SOP is to define the procedures used for the initial and periodic verification and validation of computer programs used during the Arizona NHEXAS project and the "Border" study. Keywords: Computers; Software; QA/QC.
The National Human Exposure Assessment Sur...
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Korjus, Kristjan; Hebart, Martin N.; Vicente, Raul
2016-01-01
Supervised machine learning methods typically require splitting data into multiple chunks for training, validating, and finally testing classifiers. For finding the best parameters of a classifier, training and validation are usually carried out with cross-validation. This is followed by application of the classifier with optimized parameters to a separate test set for estimating the classifier’s generalization performance. With limited data, this separation of test data creates a difficult trade-off between having more statistical power in estimating generalization performance versus choosing better parameters and fitting a better model. We propose a novel approach that we term “Cross-validation and cross-testing” improving this trade-off by re-using test data without biasing classifier performance. The novel approach is validated using simulated data and electrophysiological recordings in humans and rodents. The results demonstrate that the approach has a higher probability of discovering significant results than the standard approach of cross-validation and testing, while maintaining the nominal alpha level. In contrast to nested cross-validation, which is maximally efficient in re-using data, the proposed approach additionally maintains the interpretability of individual parameters. Taken together, we suggest an addition to currently used machine learning approaches which may be particularly useful in cases where model weights do not require interpretation, but parameters do. PMID:27564393
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Korjus, Kristjan; Hebart, Martin N; Vicente, Raul
2016-01-01
Supervised machine learning methods typically require splitting data into multiple chunks for training, validating, and finally testing classifiers. For finding the best parameters of a classifier, training and validation are usually carried out with cross-validation. This is followed by application of the classifier with optimized parameters to a separate test set for estimating the classifier's generalization performance. With limited data, this separation of test data creates a difficult trade-off between having more statistical power in estimating generalization performance versus choosing better parameters and fitting a better model. We propose a novel approach that we term "Cross-validation and cross-testing" improving this trade-off by re-using test data without biasing classifier performance. The novel approach is validated using simulated data and electrophysiological recordings in humans and rodents. The results demonstrate that the approach has a higher probability of discovering significant results than the standard approach of cross-validation and testing, while maintaining the nominal alpha level. In contrast to nested cross-validation, which is maximally efficient in re-using data, the proposed approach additionally maintains the interpretability of individual parameters. Taken together, we suggest an addition to currently used machine learning approaches which may be particularly useful in cases where model weights do not require interpretation, but parameters do.
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A Resource of Quantitative Functional Annotation for Homo sapiens Genes.
Taşan, Murat; Drabkin, Harold J; Beaver, John E; Chua, Hon Nian; Dunham, Julie; Tian, Weidong; Blake, Judith A; Roth, Frederick P
2012-02-01
The body of human genomic and proteomic evidence continues to grow at ever-increasing rates, while annotation efforts struggle to keep pace. A surprisingly small fraction of human genes have clear, documented associations with specific functions, and new functions continue to be found for characterized genes. Here we assembled an integrated collection of diverse genomic and proteomic data for 21,341 human genes and make quantitative associations of each to 4333 Gene Ontology terms. We combined guilt-by-profiling and guilt-by-association approaches to exploit features unique to the data types. Performance was evaluated by cross-validation, prospective validation, and by manual evaluation with the biological literature. Functional-linkage networks were also constructed, and their utility was demonstrated by identifying candidate genes related to a glioma FLN using a seed network from genome-wide association studies. Our annotations are presented-alongside existing validated annotations-in a publicly accessible and searchable web interface.
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2004-01-01
Cognitive Task Analysis Abstract As Department of Defense (DoD) leaders rely more on modeling and simulation to provide information on which to base...capabilities and intent. Cognitive Task Analysis (CTA) Cognitive Task Analysis (CTA) is an extensive/detailed look at tasks and subtasks performed by a...Domain Analysis and Task Analysis: A Difference That Matters. In Cognitive Task Analysis , edited by J. M. Schraagen, S.
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Schleier, Jerome J.; Peterson, Robert K.D.; Irvine, Kathryn M.; Marshall, Lucy M.; Weaver, David K.; Preftakes, Collin J.
2012-01-01
One of the more effective ways of managing high densities of adult mosquitoes that vector human and animal pathogens is ultra-low-volume (ULV) aerosol applications of insecticides. The U.S. Environmental Protection Agency uses models that are not validated for ULV insecticide applications and exposure assumptions to perform their human and ecological risk assessments. Currently, there is no validated model that can accurately predict deposition of insecticides applied using ULV technology for adult mosquito management. In addition, little is known about the deposition and drift of small droplets like those used under conditions encountered during ULV applications. The objective of this study was to perform field studies to measure environmental concentrations of insecticides and to develop a validated model to predict the deposition of ULV insecticides. The final regression model was selected by minimizing the Bayesian Information Criterion and its prediction performance was evaluated using k-fold cross validation. Density of the formulation and the density and CMD interaction coefficients were the largest in the model. The results showed that as density of the formulation decreases, deposition increases. The interaction of density and CMD showed that higher density formulations and larger droplets resulted in greater deposition. These results are supported by the aerosol physics literature. A k-fold cross validation demonstrated that the mean square error of the selected regression model is not biased, and the mean square error and mean square prediction error indicated good predictive ability.
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NASA Astrophysics Data System (ADS)
Lily; Laila, L.; Prasetyo, B. E.
2018-03-01
A selective, reproducibility, effective, sensitive, simple and fast High-Performance Liquid Chromatography (HPLC) was developed, optimized and validated to analyze 25-Desacetyl Rifampicin (25-DR) in human urine which is from tuberculosis patient. The separation was performed by HPLC Agilent Technologies with column Agilent Eclipse XDB- Ci8 and amobile phase of 65:35 v/v methanol: 0.01 M sodium phosphate buffer pH 5.2, at 254 nm and flow rate of 0.8ml/min. The mean retention time was 3.016minutes. The method was linear from 2–10μg/ml 25-DR with a correlation coefficient of 0.9978. Standard deviation, relative standard deviation and coefficient variation of 2, 6, 10μg/ml 25-DR were 0-0.0829, 03.1752, 0-0.0317%, respectively. The recovery of 5, 7, 9μg/ml25-DR was 80.8661, 91.3480 and 111.1457%, respectively. Limits of detection (LoD) and quantification (LoQ) were 0.51 and 1.7μg/ml, respectively. The method has fulfilled the validity guidelines of the International Conference on Harmonization (ICH) bioanalytical method which includes parameters of specificity, linearity, precision, accuracy, LoD, and LoQ. The developed method is suitable for pharmacokinetic analysis of various concentrations of 25-DR in human urine.
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[Validation of three screening tests used for early detection of cervical cancer].
Rodriguez-Reyes, Esperanza Rosalba; Cerda-Flores, Ricardo M; Quiñones-Pérez, Juan M; Cortés-Gutiérrez, Elva I
2008-01-01
to evaluate the validity (sensitivity, specificity, and accuracy) of three screening methods used in the early detection of the cervical carcinoma versus the histopathology diagnosis. a selected sample of 107 women attended in the Opportune Detection of Cervicouterine Cancer Program in the Hospital de Zona 46, Instituto Mexicano del Seguro Social in Durango, during the 2003 was included. The application of Papa-nicolaou, acetic acid test, and molecular detection of human papillomavirus, and histopatholgy diagnosis were performed in all the patients at the time of the gynecological exam. The detection and tipification of the human papillomavirus was performed by polymerase chain reaction (PCR) and analysis of polymorphisms of length of restriction fragments (RFLP). Histopathology diagnosis was considered the gold standard. The evaluation of the validity was carried out by the Bayesian method for diagnosis test. the positive cases for acetic acid test, Papanicolaou, and PCR were 47, 22, and 19. The accuracy values were 0.70, 0.80 and 0.99, respectively. since the molecular method showed a greater validity in the early detection of the cervical carcinoma we considered of vital importance its implementation in suitable programs of Opportune Detection of Cervicouterino Cancer Program in Mexico. However, in order to validate this conclusion, cross-sectional studies in different region of country must be carried out.
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Motion data classification on the basis of dynamic time warping with a cloud point distance measure
NASA Astrophysics Data System (ADS)
Switonski, Adam; Josinski, Henryk; Zghidi, Hafedh; Wojciechowski, Konrad
2016-06-01
The paper deals with the problem of classification of model free motion data. The nearest neighbors classifier which is based on comparison performed by Dynamic Time Warping transform with cloud point distance measure is proposed. The classification utilizes both specific gait features reflected by a movements of subsequent skeleton joints and anthropometric data. To validate proposed approach human gait identification challenge problem is taken into consideration. The motion capture database containing data of 30 different humans collected in Human Motion Laboratory of Polish-Japanese Academy of Information Technology is used. The achieved results are satisfactory, the obtained accuracy of human recognition exceeds 90%. What is more, the applied cloud point distance measure does not depend on calibration process of motion capture system which results in reliable validation.
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Amarasiri, Mohan; Kitajima, Masaaki; Nguyen, Thanh H; Okabe, Satoshi; Sano, Daisuke
2017-09-15
The multiple-barrier concept is widely employed in international and domestic guidelines for wastewater reclamation and reuse for microbiological risk management, in which a wastewater reclamation system is designed to achieve guideline values of the performance target of microbe reduction. Enteric viruses are one of the pathogens for which the target reduction values are stipulated in guidelines, but frequent monitoring to validate human virus removal efficacy is challenging in a daily operation due to the cumbersome procedures for virus quantification in wastewater. Bacteriophages have been the first choice surrogate for this task, because of the well-characterized nature of strains and the presence of established protocols for quantification. Here, we performed a meta-analysis to calculate the average log 10 reduction values (LRVs) of somatic coliphages, F-specific phages, MS2 coliphage and T4 phage by membrane bioreactor, activated sludge, constructed wetlands, pond systems, microfiltration and ultrafiltration. The calculated LRVs of bacteriophages were then compared with reported human enteric virus LRVs. MS2 coliphage LRVs in MBR processes were shown to be lower than those of norovirus GII and enterovirus, suggesting it as a possible validation and operational monitoring tool. The other bacteriophages provided higher LRVs compared to human viruses. The data sets on LRVs of human viruses and bacteriophages are scarce except for MBR and conventional activated sludge processes, which highlights the necessity of investigating LRVs of human viruses and bacteriophages in multiple treatment unit processes. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Challenges in leveraging existing human performance data for quantifying the IDHEAS HRA method
Liao, Huafei N.; Groth, Katrina; Stevens-Adams, Susan
2015-07-29
Our article documents an exploratory study for collecting and using human performance data to inform human error probability (HEP) estimates for a new human reliability analysis (HRA) method, the IntegrateD Human Event Analysis System (IDHEAS). The method was based on cognitive models and mechanisms underlying human behaviour and employs a framework of 14 crew failure modes (CFMs) to represent human failures typical for human performance in nuclear power plant (NPP) internal, at-power events [1]. A decision tree (DT) was constructed for each CFM to assess the probability of the CFM occurring in different contexts. Data needs for IDHEAS quantification aremore » discussed. Then, the data collection framework and process is described and how the collected data were used to inform HEP estimation is illustrated with two examples. Next, five major technical challenges are identified for leveraging human performance data for IDHEAS quantification. Furthermore, these challenges reflect the data needs specific to IDHEAS. More importantly, they also represent the general issues with current human performance data and can provide insight for a path forward to support HRA data collection, use, and exchange for HRA method development, implementation, and validation.« less
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Computer-Based and Paper-Based Measurement of Recognition Performance
1989-03-01
domains (e.g., ship silhouettes, electronic schemata, human anatomy ) to ascertain the universality of the validity and reliability results...specific graphic 4 database (e.g., ship silhouettes, human anatomy , electronic circuits, topography), con- tributes to its wide applicability. The game, then...seek implementation of FLASH and PICTURE in other content areas or subject-matter domains (e.g., ship silhouettes, electronic schemata, human anatomy ) to
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Zhang, Meng-Qi; Jia, Jing-Ying; Lu, Chuan; Liu, Gang-Yi; Yu, Cheng-Yin; Gui, Yu-Zhou; Liu, Yun; Liu, Yan-Mei; Wang, Wei; Li, Shui-Jun; Yu, Chen
2010-06-01
A simple, reliable and sensitive liquid chromatography-isotope dilution mass spectrometry (LC-ID/MS) was developed and validated for quantification of olanzapine in human plasma. Plasma samples (50 microL) were extracted with tert-butyl methyl ether and isotope-labeled internal standard (olanzapine-D3) was used. The chromatographic separation was performed on XBridge Shield RP 18 (100 mm x 2.1 mm, 3.5 microm, Waters). An isocratic program was used at a flow rate of 0.4 m x min(-1) with mobile phase consisting of acetonitrile and ammonium buffer (pH 8). The protonated ions of analytes were detected in positive ionization by multiple reactions monitoring (MRM) mode. The plasma method, with a lower limit of quantification (LLOQ) of 0.1 ng x mL(-1), demonstrated good linearity over a range of 0.1 - 30 ng x mL(-1) of olanzapine. Specificity, linearity, accuracy, precision, recovery, matrix effect and stability were evaluated during method validation. The validated method was successfully applied to analyzing human plasma samples in bioavailability study.
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New Integrated Modeling Capabilities: MIDAS' Recent Behavioral Enhancements
NASA Technical Reports Server (NTRS)
Gore, Brian F.; Jarvis, Peter A.
2005-01-01
The Man-machine Integration Design and Analysis System (MIDAS) is an integrated human performance modeling software tool that is based on mechanisms that underlie and cause human behavior. A PC-Windows version of MIDAS has been created that integrates the anthropometric character "Jack (TM)" with MIDAS' validated perceptual and attention mechanisms. MIDAS now models multiple simulated humans engaging in goal-related behaviors. New capabilities include the ability to predict situations in which errors and/or performance decrements are likely due to a variety of factors including concurrent workload and performance influencing factors (PIFs). This paper describes a new model that predicts the effects of microgravity on a mission specialist's performance, and its first application to simulating the task of conducting a Life Sciences experiment in space according to a sequential or parallel schedule of performance.
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Numerical evaluation of heating in the human head due to magnetic resonance imaging (MRI)
NASA Astrophysics Data System (ADS)
Nguyen, Uyen; Brown, Steve; Chang, Isaac; Krycia, Joe; Mirotznik, Mark S.
2003-06-01
In this paper we present a numerical model for evaluating tissue heating during magnetic resonance imaging (MRI). Our method, which included a detailed anatomical model of a human head, calculated both the electromagnetic power deposition and the associated temperature elevations during a MRI head examination. Numerical studies were conducted using a realistic birdcage coil excited at frequencies ranging from 63 MHz to 500 MHz. The model was validated both experimentally and analytically. The experimental validation was performed at the MR test facility located at the FDA's Center for Devices and Radiological Health (CDRH).
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NASA Technical Reports Server (NTRS)
Wickens, Christopher; Sebok, Angelia; Keller, John; Peters, Steve; Small, Ronald; Hutchins, Shaun; Algarin, Liana; Gore, Brian Francis; Hooey, Becky Lee; Foyle, David C.
2013-01-01
NextGen operations are associated with a variety of changes to the national airspace system (NAS) including changes to the allocation of roles and responsibilities among operators and automation, the use of new technologies and automation, additional information presented on the flight deck, and the entire concept of operations (ConOps). In the transition to NextGen airspace, aviation and air operations designers need to consider the implications of design or system changes on human performance and the potential for error. To ensure continued safety of the NAS, it will be necessary for researchers to evaluate design concepts and potential NextGen scenarios well before implementation. One approach for such evaluations is through human performance modeling. Human performance models (HPMs) provide effective tools for predicting and evaluating operator performance in systems. HPMs offer significant advantages over empirical, human-in-the-loop testing in that (1) they allow detailed analyses of systems that have not yet been built, (2) they offer great flexibility for extensive data collection, (3) they do not require experimental participants, and thus can offer cost and time savings. HPMs differ in their ability to predict performance and safety with NextGen procedures, equipment and ConOps. Models also vary in terms of how they approach human performance (e.g., some focus on cognitive processing, others focus on discrete tasks performed by a human, while others consider perceptual processes), and in terms of their associated validation efforts. The objectives of this research effort were to support the Federal Aviation Administration (FAA) in identifying HPMs that are appropriate for predicting pilot performance in NextGen operations, to provide guidance on how to evaluate the quality of different models, and to identify gaps in pilot performance modeling research, that could guide future research opportunities. This research effort is intended to help the FAA evaluate pilot modeling efforts and select the appropriate tools for future modeling efforts to predict pilot performance in NextGen operations.
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Tabrizi, Jafar Sadegh; Gholipour, Kamal; Iezadi, Shabnam; Farahbakhsh, Mostafa; Ghiasi, Akbar
2018-01-01
The aim was to design a district health management performance framework for Iran's healthcare system. The mixed-method study was conducted between September 2015 and May 2016 in Tabriz, Iran. In this study, the indicators of district health management performance were obtained by analyzing the 45 semi-structured surveys of experts in the public health system. Content validity of performance indicators which were generated in qualitative part were reviewed and confirmed based on content validity index (CVI). Also content validity ratio (CVR) was calculated using data acquired from a survey of 21 experts in quantitative part. The result of this study indicated that, initially, 81 indicators were considered in framework of district health management performance and, at the end, 53 indicators were validated and confirmed. These indicators were classified in 11 categories which include: human resources and organizational creativity, management and leadership, rules and ethics, planning and evaluation, district managing, health resources management and economics, community participation, quality improvement, research in health system, health information management, epidemiology and situation analysis. The designed framework model can be used to assess the district health management and facilitates performance improvement at the district level.
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Ribeiro de Oliveira, Marcelo Magaldi; Nicolato, Arthur; Santos, Marcilea; Godinho, Joao Victor; Brito, Rafael; Alvarenga, Alexandre; Martins, Ana Luiza Valle; Prosdocimi, André; Trivelato, Felipe Padovani; Sabbagh, Abdulrahman J; Reis, Augusto Barbosa; Maestro, Rolando Del
2016-05-01
OBJECT The development of neurointerventional treatments of central nervous system disorders has resulted in the need for adequate training environments for novice interventionalists. Virtual simulators offer anatomical definition but lack adequate tactile feedback. Animal models, which provide more lifelike training, require an appropriate infrastructure base. The authors describe a training model for neurointerventional procedures using the human placenta (HP), which affords haptic training with significantly fewer resource requirements, and discuss its validation. METHODS Twelve HPs were prepared for simulated endovascular procedures. Training exercises performed by interventional neuroradiologists and novice fellows were placental angiography, stent placement, aneurysm coiling, and intravascular liquid embolic agent injection. RESULTS The endovascular training exercises proposed can be easily reproduced in the HP. Face, content, and construct validity were assessed by 6 neurointerventional radiologists and 6 novice fellows in interventional radiology. CONCLUSIONS The use of HP provides an inexpensive training model for the training of neurointerventionalists. Preliminary validation results show that this simulation model has face and content validity and has demonstrated construct validity for the interventions assessed in this study.
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NASA Technical Reports Server (NTRS)
Woodbury, Sarah K.
2008-01-01
The introduction of United Space Alliance's Human Engineering Modeling and Performance Laboratory began in early 2007 in an attempt to address the problematic workspace design issues that the Space Shuttle has imposed on technicians performing maintenance and inspection operations. The Space Shuttle was not expected to require the extensive maintenance it undergoes between flights. As a result, extensive, costly resources have been expended on workarounds and modifications to accommodate ground processing personnel. Consideration of basic human factors principles for design of maintenance is essential during the design phase of future space vehicles, facilities, and equipment. Simulation will be needed to test and validate designs before implementation.
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Optimization of a reversible hood for protecting a pedestrian's head during car collisions.
Huang, Sunan; Yang, Jikuang
2010-07-01
This study evaluated and optimized the performance of a reversible hood (RH) for the prevention of the head injuries of an adult pedestrian from car collisions. The FE model of a production car front was introduced and validated. The baseline RH was developed from the original hood in the validated car front model. In order to evaluate the protective performance of the baseline RH, the FE models of an adult headform and a 50th percentile human head were used in parallel to impact the baseline RH. Based on the evaluation, the response surface method was applied to optimize the RH in terms of the material stiffness, lifting speed, and lifted height. Finally, the headform model and the human head model were again used to evaluate the protective performance of the optimized RH. It was found that the lifted baseline RH can obviously reduce the impact responses of the headform model and the human head model by comparing with the retracted and lifting baseline RH. When the optimized RH was lifted, the HIC values of the headform model and the human head model were further reduced to much lower than 1000. The risk of pedestrian head injuries can be prevented as required by EEVC WG17. Copyright 2009 Elsevier Ltd. All rights reserved.
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A new method to evaluate human-robot system performance
NASA Technical Reports Server (NTRS)
Rodriguez, G.; Weisbin, C. R.
2003-01-01
One of the key issues in space exploration is that of deciding what space tasks are best done with humans, with robots, or a suitable combination of each. In general, human and robot skills are complementary. Humans provide as yet unmatched capabilities to perceive, think, and act when faced with anomalies and unforeseen events, but there can be huge potential risks to human safety in getting these benefits. Robots provide complementary skills in being able to work in extremely risky environments, but their ability to perceive, think, and act by themselves is currently not error-free, although these capabilities are continually improving with the emergence of new technologies. Substantial past experience validates these generally qualitative notions. However, there is a need for more rigorously systematic evaluation of human and robot roles, in order to optimize the design and performance of human-robot system architectures using well-defined performance evaluation metrics. This article summarizes a new analytical method to conduct such quantitative evaluations. While the article focuses on evaluating human-robot systems, the method is generally applicable to a much broader class of systems whose performance needs to be evaluated.
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Uhlig, Johannes; Uhlig, Annemarie; Kunze, Meike; Beissbarth, Tim; Fischer, Uwe; Lotz, Joachim; Wienbeck, Susanne
2018-05-24
The purpose of this study is to evaluate the diagnostic performance of machine learning techniques for malignancy prediction at breast cone-beam CT (CBCT) and to compare them to human readers. Five machine learning techniques, including random forests, back propagation neural networks (BPN), extreme learning machines, support vector machines, and K-nearest neighbors, were used to train diagnostic models on a clinical breast CBCT dataset with internal validation by repeated 10-fold cross-validation. Two independent blinded human readers with profound experience in breast imaging and breast CBCT analyzed the same CBCT dataset. Diagnostic performance was compared using AUC, sensitivity, and specificity. The clinical dataset comprised 35 patients (American College of Radiology density type C and D breasts) with 81 suspicious breast lesions examined with contrast-enhanced breast CBCT. Forty-five lesions were histopathologically proven to be malignant. Among the machine learning techniques, BPNs provided the best diagnostic performance, with AUC of 0.91, sensitivity of 0.85, and specificity of 0.82. The diagnostic performance of the human readers was AUC of 0.84, sensitivity of 0.89, and specificity of 0.72 for reader 1 and AUC of 0.72, sensitivity of 0.71, and specificity of 0.67 for reader 2. AUC was significantly higher for BPN when compared with both reader 1 (p = 0.01) and reader 2 (p < 0.001). Machine learning techniques provide a high and robust diagnostic performance in the prediction of malignancy in breast lesions identified at CBCT. BPNs showed the best diagnostic performance, surpassing human readers in terms of AUC and specificity.
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Geraets, Daan; Cuzick, Jack; Cadman, Louise; Moore, Catherine; Vanden Broeck, Davy; Padalko, Elisaveta; Quint, Wim; Arbyn, Marc
2016-01-01
The Validation of Human Papillomavirus (HPV) Genotyping Tests (VALGENT) studies offer an opportunity to clinically validate HPV assays for use in primary screening for cervical cancer and also provide a framework for the comparison of analytical and type-specific performance. Through VALGENT, we assessed the performance of the cartridge-based Xpert HPV assay (Xpert HPV), which detects 14 high-risk (HR) types and resolves HPV16 and HPV18/45. Samples from women attending the United Kingdom cervical screening program enriched with cytologically abnormal samples were collated. All had been previously tested by a clinically validated standard comparator test (SCT), the GP5+/6+ enzyme immunoassay (EIA). The clinical sensitivity and specificity of the Xpert HPV for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and CIN3+ relative to those of the SCT were assessed as were the inter- and intralaboratory reproducibilities according to international criteria for test validation. Type concordance for HPV16 and HPV18/45 between the Xpert HPV and the SCT was also analyzed. The Xpert HPV detected 94% of CIN2+ and 98% of CIN3+ lesions among all screened women and 90% of CIN2+ and 96% of CIN3+ lesions in women 30 years and older. The specificity for CIN1 or less (≤CIN1) was 83% (95% confidence interval [CI], 80 to 85%) in all women and 88% (95% CI, 86 to 91%) in women 30 years and older. Inter- and intralaboratory agreements for the Xpert HPV were 98% and 97%, respectively. The kappa agreements for HPV16 and HPV18/45 between the clinically validated reference test (GP5+/6+ LMNX) and the Xpert HPV were 0.92 and 0.91, respectively. The clinical performance and reproducibility of the Xpert HPV are comparable to those of well-established HPV assays and fulfill the criteria for use in primary cervical cancer screening. PMID:27385707
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Rezk, Naser L.; White, Nicole; Bridges, Arlene S.; Abdel-Megeed, Mohamed F.; Mohamed, Tarek M.; Moselhy, Said S.; Kashuba, Angela D. M.
2010-01-01
Studying the pharmacokinetics of antiretroviral drugs in breast milk has important implications for the health of both the mother and the infant, particularly in resource-poor countries. Breast milk is a highly complex biological matrix, yet it is necessary to develop and validate methods in this matrix, which simultaneously measure multiple analytes, as women may be taking any number of drug combinations to combat human immunodeficiency virus infection. Here, we report a novel extraction method coupled to high-performance liquid chromatography and tandem mass spectrometry for the accurate, precise, and specific measurement of 7 antiretroviral drugs currently prescribed to infected mothers. Using 200 µL of human breast milk, simultaneous quantification of lamivudine (3TC), stavudine (d4T), zidovudine (ZDV), nevirapine (NVP), nelfinavir (NFV), ritonavir, and lopinavir was validated over the range of 10–10,000 ng/mL. Intraday accuracy and precision for all analytes were 99.3% and 5.0 %, respectively. Interday accuracy and precision were 99.4 % and 7.8%, respectively. Cross-assay validation with UV detection was performed using clinical breast milk samples, and the results of the 2 assays were in good agreement (P = 0.0001, r = 0.97). Breast milk to plasma concentration ratios for the different antiretroviral drugs were determined as follows: 3TC = 2.96, d4T = 1.73, ZDV = 1.17, NVP = 0.82, and NFV = 0.21. PMID:18758393
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Reference Proteome Extracts for Mass Spec Instrument Performance Validation and Method Development
Rosenblatt, Mike; Urh, Marjeta; Saveliev, Sergei
2014-01-01
Biological samples of high complexity are required to test protein mass spec sample preparation procedures and validate mass spec instrument performance. Total cell protein extracts provide the needed sample complexity. However, to be compatible with mass spec applications, such extracts should meet a number of design requirements: compatibility with LC/MS (free of detergents, etc.)high protein integrity (minimal level of protein degradation and non-biological PTMs)compatibility with common sample preparation methods such as proteolysis, PTM enrichment and mass-tag labelingLot-to-lot reproducibility Here we describe total protein extracts from yeast and human cells that meet the above criteria. Two extract formats have been developed: Intact protein extracts with primary use for sample preparation method development and optimizationPre-digested extracts (peptides) with primary use for instrument validation and performance monitoring
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Nijenhuis, C M; Rosing, H; Schellens, J H M; Beijnen, J H
2014-01-01
Vemurafenib is an inhibitor of mutated serine/threonine-protein kinase B-Raf (BRAF) and is registered as Zelboraf(®) for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. To support Therapeutic Drug Monitoring (TDM) and clinical trials, we developed and validated a method for the quantification of vemurafenib in human plasma. Additionally two LC-MS systems with different detectors were tested: the TSQ Quantum Ultra and the API3000. Human plasma samples were collected in the clinic and stored at nominally -20°C. Vemurafenib was isolated from plasma by liquid-liquid extraction, separated on a C18 column with gradient elution, and analysed with triple quadrupole mass spectrometry in positive-ion mode. A stable isotope was used as internal standard for the quantification. Ranging from 1 to 100μg/ml the assay was linear with correlation coefficients (r(2)) of 0.9985 or better. Inter-assay and intra-assay accuracies were within ±7.6% of the nominal concentration; inter-assay and intra-assay precision were within ≤9.3% of the nominal concentration. In addition all results were within the acceptance criteria of the US FDA and the latest EMA guidelines for method validation for both MS detectors. In conclusion, the presented analytical method for vemurafenib in human plasma was successfully validated and the performance of the two LC-MS systems for this assay was comparable. In addition the method was successfully applied to evaluate the pharmacokinetic quantification of vemurafenib in cancer patients treated with vemurafenib. Copyright © 2013 Elsevier B.V. All rights reserved.
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NASA Technical Reports Server (NTRS)
Johannsen, G.; Govindaraj, T.
1980-01-01
The influence of different types of predictor displays in a longitudinal vertical takeoff and landing (VTOL) hover task is analyzed in a theoretical study. Several cases with differing amounts of predictive and rate information are compared. The optimal control model of the human operator is used to estimate human and system performance in terms of root-mean-square (rms) values and to compute optimized attention allocation. The only part of the model which is varied to predict these data is the observation matrix. Typical cases are selected for a subsequent experimental validation. The rms values as well as eye-movement data are recorded. The results agree favorably with those of the theoretical study in terms of relative differences. Better matching is achieved by revised model input data.
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Zachariah, Marianne; Seidling, Hanna M; Neri, Pamela M; Cresswell, Kathrin M; Duke, Jon; Bloomrosen, Meryl; Volk, Lynn A; Bates, David W
2011-01-01
Background Medication-related decision support can reduce the frequency of preventable adverse drug events. However, the design of current medication alerts often results in alert fatigue and high over-ride rates, thus reducing any potential benefits. Methods The authors previously reviewed human-factors principles for relevance to medication-related decision support alerts. In this study, instrument items were developed for assessing the appropriate implementation of these human-factors principles in drug–drug interaction (DDI) alerts. User feedback regarding nine electronic medical records was considered during the development process. Content validity, construct validity through correlation analysis, and inter-rater reliability were assessed. Results The final version of the instrument included 26 items associated with nine human-factors principles. Content validation on three systems resulted in the addition of one principle (Corrective Actions) to the instrument and the elimination of eight items. Additionally, the wording of eight items was altered. Correlation analysis suggests a direct relationship between system age and performance of DDI alerts (p=0.0016). Inter-rater reliability indicated substantial agreement between raters (κ=0.764). Conclusion The authors developed and gathered preliminary evidence for the validity of an instrument that measures the appropriate use of human-factors principles in the design and display of DDI alerts. Designers of DDI alerts may use the instrument to improve usability and increase user acceptance of medication alerts, and organizations selecting an electronic medical record may find the instrument helpful in meeting their clinicians' usability needs. PMID:21946241
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A high-performance spatial database based approach for pathology imaging algorithm evaluation
Wang, Fusheng; Kong, Jun; Gao, Jingjing; Cooper, Lee A.D.; Kurc, Tahsin; Zhou, Zhengwen; Adler, David; Vergara-Niedermayr, Cristobal; Katigbak, Bryan; Brat, Daniel J.; Saltz, Joel H.
2013-01-01
Background: Algorithm evaluation provides a means to characterize variability across image analysis algorithms, validate algorithms by comparison with human annotations, combine results from multiple algorithms for performance improvement, and facilitate algorithm sensitivity studies. The sizes of images and image analysis results in pathology image analysis pose significant challenges in algorithm evaluation. We present an efficient parallel spatial database approach to model, normalize, manage, and query large volumes of analytical image result data. This provides an efficient platform for algorithm evaluation. Our experiments with a set of brain tumor images demonstrate the application, scalability, and effectiveness of the platform. Context: The paper describes an approach and platform for evaluation of pathology image analysis algorithms. The platform facilitates algorithm evaluation through a high-performance database built on the Pathology Analytic Imaging Standards (PAIS) data model. Aims: (1) Develop a framework to support algorithm evaluation by modeling and managing analytical results and human annotations from pathology images; (2) Create a robust data normalization tool for converting, validating, and fixing spatial data from algorithm or human annotations; (3) Develop a set of queries to support data sampling and result comparisons; (4) Achieve high performance computation capacity via a parallel data management infrastructure, parallel data loading and spatial indexing optimizations in this infrastructure. Materials and Methods: We have considered two scenarios for algorithm evaluation: (1) algorithm comparison where multiple result sets from different methods are compared and consolidated; and (2) algorithm validation where algorithm results are compared with human annotations. We have developed a spatial normalization toolkit to validate and normalize spatial boundaries produced by image analysis algorithms or human annotations. The validated data were formatted based on the PAIS data model and loaded into a spatial database. To support efficient data loading, we have implemented a parallel data loading tool that takes advantage of multi-core CPUs to accelerate data injection. The spatial database manages both geometric shapes and image features or classifications, and enables spatial sampling, result comparison, and result aggregation through expressive structured query language (SQL) queries with spatial extensions. To provide scalable and efficient query support, we have employed a shared nothing parallel database architecture, which distributes data homogenously across multiple database partitions to take advantage of parallel computation power and implements spatial indexing to achieve high I/O throughput. Results: Our work proposes a high performance, parallel spatial database platform for algorithm validation and comparison. This platform was evaluated by storing, managing, and comparing analysis results from a set of brain tumor whole slide images. The tools we develop are open source and available to download. Conclusions: Pathology image algorithm validation and comparison are essential to iterative algorithm development and refinement. One critical component is the support for queries involving spatial predicates and comparisons. In our work, we develop an efficient data model and parallel database approach to model, normalize, manage and query large volumes of analytical image result data. Our experiments demonstrate that the data partitioning strategy and the grid-based indexing result in good data distribution across database nodes and reduce I/O overhead in spatial join queries through parallel retrieval of relevant data and quick subsetting of datasets. The set of tools in the framework provide a full pipeline to normalize, load, manage and query analytical results for algorithm evaluation. PMID:23599905
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Lateral specialization in unilateral spatial neglect: a cognitive robotics model.
Conti, Daniela; Di Nuovo, Santo; Cangelosi, Angelo; Di Nuovo, Alessandro
2016-08-01
In this paper, we present the experimental results of an embodied cognitive robotic approach for modelling the human cognitive deficit known as unilateral spatial neglect (USN). To this end, we introduce an artificial neural network architecture designed and trained to control the spatial attentional focus of the iCub robotic platform. Like the human brain, the architecture is divided into two hemispheres and it incorporates bio-inspired plasticity mechanisms, which allow the development of the phenomenon of the specialization of the right hemisphere for spatial attention. In this study, we validate the model by replicating a previous experiment with human patients affected by the USN and numerical results show that the robot mimics the behaviours previously exhibited by humans. We also simulated recovery after the damage to compare the performance of each of the two hemispheres as additional validation of the model. Finally, we highlight some possible advantages of modelling cognitive dysfunctions of the human brain by means of robotic platforms, which can supplement traditional approaches for studying spatial impairments in humans.
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Dong, Ren G; Welcome, Daniel E; McDowell, Thomas W; Wu, John Z
2013-11-25
The relationship between the vibration transmissibility and driving-point response functions (DPRFs) of the human body is important for understanding vibration exposures of the system and for developing valid models. This study identified their theoretical relationship and demonstrated that the sum of the DPRFs can be expressed as a linear combination of the transmissibility functions of the individual mass elements distributed throughout the system. The relationship is verified using several human vibration models. This study also clarified the requirements for reliably quantifying transmissibility values used as references for calibrating the system models. As an example application, this study used the developed theory to perform a preliminary analysis of the method for calibrating models using both vibration transmissibility and DPRFs. The results of the analysis show that the combined method can theoretically result in a unique and valid solution of the model parameters, at least for linear systems. However, the validation of the method itself does not guarantee the validation of the calibrated model, because the validation of the calibration also depends on the model structure and the reliability and appropriate representation of the reference functions. The basic theory developed in this study is also applicable to the vibration analyses of other structures.
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The effect of music on cognitive performance: insight from neurobiological and animal studies.
Rickard, Nikki S; Toukhsati, Samia R; Field, Simone E
2005-12-01
The past 50 years have seen numerous claims that music exposure enhances human cognitive performance. Critical evaluation of studies across a variety of contexts, however, reveals important methodological weaknesses. The current article argues that an interdisciplinary approach is required to advance this research. A case is made for the use of appropriate animal models to avoid many confounds associated with human music research. Although such research has validity limitations for humans, reductionist methodology enables a more controlled exploration of music's elementary effects. This article also explores candidate mechanisms for this putative effect. A review of neurobiological evidence from human and comparative animal studies confirms that musical stimuli modify autonomic and neurochemical arousal indices, and may also modify synaptic plasticity. It is proposed that understanding how music affects animals provides a valuable conjunct to human research and may be vital in uncovering how music might be used to enhance cognitive performance.
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Wahl, Simone; Boulesteix, Anne-Laure; Zierer, Astrid; Thorand, Barbara; van de Wiel, Mark A
2016-10-26
Missing values are a frequent issue in human studies. In many situations, multiple imputation (MI) is an appropriate missing data handling strategy, whereby missing values are imputed multiple times, the analysis is performed in every imputed data set, and the obtained estimates are pooled. If the aim is to estimate (added) predictive performance measures, such as (change in) the area under the receiver-operating characteristic curve (AUC), internal validation strategies become desirable in order to correct for optimism. It is not fully understood how internal validation should be combined with multiple imputation. In a comprehensive simulation study and in a real data set based on blood markers as predictors for mortality, we compare three combination strategies: Val-MI, internal validation followed by MI on the training and test parts separately, MI-Val, MI on the full data set followed by internal validation, and MI(-y)-Val, MI on the full data set omitting the outcome followed by internal validation. Different validation strategies, including bootstrap und cross-validation, different (added) performance measures, and various data characteristics are considered, and the strategies are evaluated with regard to bias and mean squared error of the obtained performance estimates. In addition, we elaborate on the number of resamples and imputations to be used, and adopt a strategy for confidence interval construction to incomplete data. Internal validation is essential in order to avoid optimism, with the bootstrap 0.632+ estimate representing a reliable method to correct for optimism. While estimates obtained by MI-Val are optimistically biased, those obtained by MI(-y)-Val tend to be pessimistic in the presence of a true underlying effect. Val-MI provides largely unbiased estimates, with a slight pessimistic bias with increasing true effect size, number of covariates and decreasing sample size. In Val-MI, accuracy of the estimate is more strongly improved by increasing the number of bootstrap draws rather than the number of imputations. With a simple integrated approach, valid confidence intervals for performance estimates can be obtained. When prognostic models are developed on incomplete data, Val-MI represents a valid strategy to obtain estimates of predictive performance measures.
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DOT National Transportation Integrated Search
2013-01-01
Each railroad covered by 49 CFR 228.407 must perform an analysis of the work schedules of its train employees who are engaged in commuter or intercity rail passenger transportation and identify those schedules that, if worked by such a train employee...
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Xu, Juanjuan; Fang, Rui; Chen, Li; Chen, Daozhen; Xiao, Jian-Ping; Yang, Weimin; Wang, Honghua; Song, Xiaoqing; Ma, Ting; Bo, Shiping; Shi, Chong; Ren, Jun; Huang, Lei; Cai, Li-Yi; Yao, Bing; Xie, X Sunney; Lu, Sijia
2016-10-18
Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.
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A semi-automatic method for left ventricle volume estimate: an in vivo validation study
NASA Technical Reports Server (NTRS)
Corsi, C.; Lamberti, C.; Sarti, A.; Saracino, G.; Shiota, T.; Thomas, J. D.
2001-01-01
This study aims to the validation of the left ventricular (LV) volume estimates obtained by processing volumetric data utilizing a segmentation model based on level set technique. The validation has been performed by comparing real-time volumetric echo data (RT3DE) and magnetic resonance (MRI) data. A validation protocol has been defined. The validation protocol was applied to twenty-four estimates (range 61-467 ml) obtained from normal and pathologic subjects, which underwent both RT3DE and MRI. A statistical analysis was performed on each estimate and on clinical parameters as stroke volume (SV) and ejection fraction (EF). Assuming MRI estimates (x) as a reference, an excellent correlation was found with volume measured by utilizing the segmentation procedure (y) (y=0.89x + 13.78, r=0.98). The mean error on SV was 8 ml and the mean error on EF was 2%. This study demonstrated that the segmentation technique is reliably applicable on human hearts in clinical practice.
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Kabir, Abuzar; Furton, Kenneth G; Tinari, Nicola; Grossi, Laurino; Innosa, Denise; Macerola, Daniela; Tartaglia, Angela; Di Donato, Valentina; D'Ovidio, Cristian; Locatelli, Marcello
2018-05-01
This paper reports a novel fabric phase sorptive extraction-high performance liquid chromatography-photodiode array detection (FPSE-HPLC-PDA) method for the simultaneous extraction and analysis of three drug residues (ciprofloxacin, sulfasalazine, and cortisone) in human whole blood, plasma, and urine samples, generally administered in human patients to treat inflammatory bowel disease (IBD). The drugs of interest were well resolved using a Luna C 18 column (250 mm × 4.6 mm; 5 μm particle size) in gradient elution mode within 20 min. The analytical method was optimized and validated in the range 0.05-10 μg/mL for whole blood, 0.25-10 μg/mL for human plasma, and 0.10-10 μg/mL for human urine. Blank human whole blood, plasma, and urine were used as the sample matrix for the method development and validation; while methyl-p-hydroxybenzoate was used as the internal standard (IS). Weighted-matrix matched standard calibration curves showed a good linearity up to a concentration of 10 μg/mL. The intra- and inter-day accuracy values (precision and trueness) were found in the range from -10.9% to 12.3%, and the performances of the validated FPSE-HPLC-PDA were further tested on real IBD patient samples. This is the first FPSE procedure applied simultaneously to whole blood, plasma, and urine samples for the determination of residual IBD drugs, which possess a wide range of polarity (logP values ranging from 2.30 for Ciprofloxacin, to 1.66 for Cortisone, and 2.92 for Sulfasalazine). The new approach exhibits high potential for immediate adoptation as a rapid, robust and green analytical tool for future clinical and pharmaceutical applications. Copyright © 2018 Elsevier B.V. All rights reserved.
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Johnson, Sheena Joanne; Guediri, Sara M; Kilkenny, Caroline; Clough, Peter J
2011-12-01
This study developed and validated a virtual reality (VR) simulator for use by interventional radiologists. Research in the area of skill acquisition reports practice as essential to become a task expert. Studies on simulation show skills learned in VR can be successfully transferred to a real-world task. Recently, with improvements in technology, VR simulators have been developed to allow complex medical procedures to be practiced without risking the patient. Three studies are reported. In Study I, 35 consultant interventional radiologists took part in a cognitive task analysis to empirically establish the key competencies of the Seldinger procedure. In Study 2, 62 participants performed one simulated procedure, and their performance was compared by expertise. In Study 3, the transferability of simulator training to a real-world procedure was assessed with 14 trainees. Study I produced 23 key competencies that were implemented as performance measures in the simulator. Study 2 showed the simulator had both face and construct validity, although some issues were identified. Study 3 showed the group that had undergone simulator training received significantly higher mean performance ratings on a subsequent patient procedure. The findings of this study support the centrality of validation in the successful design of simulators and show the utility of simulators as a training device. The studies show the key elements of a validation program for a simulator. In addition to task analysis and face and construct validities, the authors highlight the importance of transfer of training in validation studies.
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Computerized Hammer Sounding Interpretation for Concrete Assessment with Online Machine Learning.
Ye, Jiaxing; Kobayashi, Takumi; Iwata, Masaya; Tsuda, Hiroshi; Murakawa, Masahiro
2018-03-09
Developing efficient Artificial Intelligence (AI)-enabled systems to substitute the human role in non-destructive testing is an emerging topic of considerable interest. In this study, we propose a novel hammering response analysis system using online machine learning, which aims at achieving near-human performance in assessment of concrete structures. Current computerized hammer sounding systems commonly employ lab-scale data to validate the models. In practice, however, the response signal patterns can be far more complicated due to varying geometric shapes and materials of structures. To deal with a large variety of unseen data, we propose a sequential treatment for response characterization. More specifically, the proposed system can adaptively update itself to approach human performance in hammering sounding data interpretation. To this end, a two-stage framework has been introduced, including feature extraction and the model updating scheme. Various state-of-the-art online learning algorithms have been reviewed and evaluated for the task. To conduct experimental validation, we collected 10,940 response instances from multiple inspection sites; each sample was annotated by human experts with healthy/defective condition labels. The results demonstrated that the proposed scheme achieved favorable assessment accuracy with high efficiency and low computation load.
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Dubascoux, Stéphane; Andrey, Daniel; Vigo, Mario; Kastenmayer, Peter; Poitevin, Eric
2018-09-01
Nutritional information about human milk is essential as early human growth and development have been closely linked to the status and requirements of several macro- and micro-elements. However, methods addressing whole mineral profiling in human milk have been scarce due in part to their technical complexities to accurately and simultaneously measure the concentration of micro- and macro-trace elements in low volume of human milk. In the present study, a single laboratory validation has been performed using a "dilute and shoot" approach for the quantification of sodium (Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo) and iodine (I), in both human milk and milk preparations. Performances in terms of limits of detection and quantification, of repeatability, reproducibility and trueness have been assessed and verified using various reference or certified materials. For certified human milk sample (NIST 1953), recoveries obtained for reference or spiked values are ranged from 93% to 108% (except for Mn at 151%). This robust method using new technology ICP-MS/MS without high pressure digestion is adapted to both routinely and rapidly analyze human milk micro-sample (i.e. less than 250 μL) in the frame of clinical trials but also to be extended to the mineral profiling of milk preparations like infant formula and adult nutritionals. Copyright © 2018 Elsevier GmbH. All rights reserved.
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Development and validation of the Hospitality Axiological Scale for Humanization of Nursing Care
Galán González-Serna, José María; Ferreras-Mencia, Soledad; Arribas-Marín, Juan Manuel
2017-01-01
ABSTRACT Objective: to develop and validate a scale to evaluate nursing attitudes in relation to hospitality for the humanization of nursing care. Participants: the sample consisted of 499 nursing professionals and undergraduate students of the final two years of the Bachelor of Science in Nursing program. Method: the instrument has been developed and validated to evaluate the ethical values related to hospitality using a methodological approach. Subsequently, a model was developed to measure the dimensions forming the construct hospitality. Results: the Axiological Hospitality Scale showed a high internal consistency, with Cronbach’s Alpha=0.901. The validation of the measuring instrument was performed using factorial, exploratory and confirmatory analysis techniques with high goodness of fit measures. Conclusions: the developed instrument showed an adequate validity and a high internal consistency. Based on the consistency of its psychometric properties, it is possible to affirm that the scale provides a reliable measurement of the hospitality. It was also possible to determine the dimensions or sources that embrace it: respect, responsibility, quality and transpersonal care. PMID:28793127
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Personality and organizational influences on aerospace human performance
NASA Technical Reports Server (NTRS)
Helmreich, Robert L.
1989-01-01
Individual and organizational influences on performance in aerospace environments are discussed. A model of personality with demonstrated validity is described along with reasons why personality's effects on performance have been underestimated. Organizational forces including intergroup conflict and coercive pressures are also described. It is suggested that basic and applied research in analog situations is needed to provide necessary guidance for planning future space missions.
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Mukhopadhyay, Anirban; Maulik, Ujjwal; Bandyopadhyay, Sanghamitra
2012-01-01
Identification of potential viral-host protein interactions is a vital and useful approach towards development of new drugs targeting those interactions. In recent days, computational tools are being utilized for predicting viral-host interactions. Recently a database containing records of experimentally validated interactions between a set of HIV-1 proteins and a set of human proteins has been published. The problem of predicting new interactions based on this database is usually posed as a classification problem. However, posing the problem as a classification one suffers from the lack of biologically validated negative interactions. Therefore it will be beneficial to use the existing database for predicting new viral-host interactions without the need of negative samples. Motivated by this, in this article, the HIV-1–human protein interaction database has been analyzed using association rule mining. The main objective is to identify a set of association rules both among the HIV-1 proteins and among the human proteins, and use these rules for predicting new interactions. In this regard, a novel association rule mining technique based on biclustering has been proposed for discovering frequent closed itemsets followed by the association rules from the adjacency matrix of the HIV-1–human interaction network. Novel HIV-1–human interactions have been predicted based on the discovered association rules and tested for biological significance. For validation of the predicted new interactions, gene ontology-based and pathway-based studies have been performed. These studies show that the human proteins which are predicted to interact with a particular viral protein share many common biological activities. Moreover, literature survey has been used for validation purpose to identify some predicted interactions that are already validated experimentally but not present in the database. Comparison with other prediction methods is also discussed. PMID:22539940
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Ayturk, Ugur M; Puttlitz, Christian M
2011-08-01
The primary objective of this study was to generate a finite element model of the human lumbar spine (L1-L5), verify mesh convergence for each tissue constituent and perform an extensive validation using both kinematic/kinetic and stress/strain data. Mesh refinement was accomplished via convergence of strain energy density (SED) predictions for each spinal tissue. The converged model was validated based on range of motion, intradiscal pressure, facet force transmission, anterolateral cortical bone strain and anterior longitudinal ligament deformation predictions. Changes in mesh resolution had the biggest impact on SED predictions under axial rotation loading. Nonlinearity of the moment-rotation curves was accurately simulated and the model predictions on the aforementioned parameters were in good agreement with experimental data. The validated and converged model will be utilised to study the effects of degeneration on the lumbar spine biomechanics, as well as to investigate the mechanical underpinning of the contemporary treatment strategies.
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Illamola, S M; Labat, L; Benaboud, S; Tubiana, R; Warszawski, J; Tréluyer, J M; Hirt, D
2014-08-15
Lopinavir is an HIV protease inhibitor with high protein binding (98-99%) in human plasma. This study was designed to develop an ultrafiltration method to measure the unbound concentrations of lopinavir overcoming the non-specific binding issue. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of total concentrations of lopinavir in plasma was developed and validated, and an adaptation was also optimized and validated for the determination of unbound concentrations. The chromatographic separation was performed with a C18 column (100 mm × 2.1mm i.d., 5 μm particle size) using a mobile phase containing deionized water with formic acid, and acetonitrile, with gradient elution at a flow-rate of 350 μL min(-1). Identification of the compounds was performed by multiple reaction monitoring, using electrospray ionization in positive ion mode. The method was validated over a clinical range of 0.01-1 μg/mL for human plasma ultrafiltrate and 0.1-15 μg/mL in human plasma. The inter and intra-assay accuracies and precisions were between 0.23% and 11.37% for total lopinavir concentrations, and between 3.50% and 13.30% for plasma ultrafiltrate (unbound concentration). The ultrafiltration method described allows an accurate separation of the unbound fraction of lopinavir, circumscribing the loss of drug by nonspecific binding (NSB), and the validated LC-MS/MS methodology proposed is suitable for the determination of total and unbound concentrations of lopinavir in clinical practice. Copyright © 2014 Elsevier B.V. All rights reserved.
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Thomsson, Ola; Ström-Holst, Bodil; Sjunnesson, Ylva; Bergqvist, Ann-Sofi
2014-09-06
The purpose of this study was to validate a commercially available enzyme-linked immunosorbent assay (ELISA) developed for measuring free cortisol in human saliva and total cortisol concentration in diluted human serum, for its applicability in measuring cortisol concentration in pig saliva. Collection of saliva is less stressful than e.g. blood sampling, and is a non-invasive method. Saliva was collected by allowing sows to chew on cotton swabs held by forceps. Thereafter, the swabs were centrifuged to retrieve the saliva. The ELISA was performed according to instructions provided by the manufacturer. To validate the ELISA, determination of the intra-assay coefficient of variation (CV), inter-assay CV, recovery, linearity and parallelism was performed. The intra-assay CV was below 10% and inter-assay CV below 15% for samples of high, medium and low cortisol concentrations. The mean recovery was 117% and the linearity and parallelism showed an r2-value of 0.994 and 0.993, respectively. For biological assessment of induced social stress, two saliva samples were collected in the morning from 6 primiparous and 21 multiparous sows. One sample was collected when the sows were individually housed in a farrowing pen and a second sample was collected when the sows were group housed. The primiparous sows had a significant higher cortisol concentration compared to the multiparous sows when group housed. The results obtained in this validation study indicate that the ELISA is suitable for measuring cortisol concentration in porcine saliva.
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Methodology, Methods, and Metrics for Testing and Evaluating Augmented Cognition Systems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Greitzer, Frank L.
The augmented cognition research community seeks cognitive neuroscience-based solutions to improve warfighter performance by applying and managing mitigation strategies to reduce workload and improve the throughput and quality of decisions. The focus of augmented cognition mitigation research is to define, demonstrate, and exploit neuroscience and behavioral measures that support inferences about the warfighter’s cognitive state that prescribe the nature and timing of mitigation. A research challenge is to develop valid evaluation methodologies, metrics and measures to assess the impact of augmented cognition mitigations. Two considerations are external validity, which is the extent to which the results apply to operational contexts;more » and internal validity, which reflects the reliability of performance measures and the conclusions based on analysis of results. The scientific rigor of the research methodology employed in conducting empirical investigations largely affects the validity of the findings. External validity requirements also compel us to demonstrate operational significance of mitigations. Thus it is important to demonstrate effectiveness of mitigations under specific conditions. This chapter reviews some cognitive science and methodological considerations in designing augmented cognition research studies and associated human performance metrics and analysis methods to assess the impact of augmented cognition mitigations.« less
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Iwasaki, Motoki; Mukai, Tomomi; Takachi, Ribeka; Ishihara, Junko; Totsuka, Yukari; Tsugane, Shoichiro
2014-08-01
Clarification of the putative etiologic role of heterocyclic aromatic amines (HAAs) in the development of cancer requires a validated assessment tool for dietary HAAs. This study primarily aimed to evaluate the validity of a food frequency questionnaire (FFQ) in estimating HAA intake, using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) level in human hair as the reference method. We first updated analytical methods of PhIP using liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS/MS) and measured 44 fur samples from nine rats from a feeding study as part-verification of the quantitative performance of LC-ESI/MS/MS. We next measured PhIP level in human hair samples from a validation study of the FFQ (n = 65). HAA intake from the FFQ was estimated using information on intake from six fish items and seven meat items and data on HAA content in each food item. Correlation coefficients between PhIP level in human hair and HAA intake from the FFQ were calculated. The animal feeding study of PhIP found a significant dose-response relationship between dosage and PhIP in rat fur. Mean level was 53.8 pg/g hair among subjects with values over the limit of detection (LOD) (n = 57). We found significant positive correlation coefficients between PhIP in human hair and HAA intake from the FFQ, with Spearman rank correlation coefficients of 0.35 for all subjects, 0.21 for subjects with over LOD values, and 0.34 for subjects with over limit of quantification. Findings from the validation study suggest that the FFQ is reasonably valid for the assessment of HAA intake.
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Sala, Federica; Albares, Pablo; Colovic, Milena; Persiani, Stefano; Rovati, Lucio C
2014-01-15
To investigate the pharmacokinetics of silibinin and silibinin hemisuccinate in human plasma, two high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods were developed and validated. The methods require a small volume of sample (100μL), and the recovery of the analytes was complete with a good reproducibility (CV% 1.7-9.5), after a simple protein precipitation. Naringenin was used as internal standard. The chromatographic methods provided a good separation of diastereoisomers A and B of both silibinin and silibinin hemisuccinate onto a Chromolith Performance RP18e 100mm×3mm column, with a resolution of peaks from plasma matrix in less than 6min. The methods precision values expressed as CV% were always ≤6.2% and the accuracy was always well within the acceptable 15% range. Quantification was performed on a triple-quadrupole tandem mass spectrometer by Selected Reaction Monitoring (SRM) mode, in a negative ion mode, via electrospray ionization (ESI). The lower limit of quantitation was set at 5.0ng/mL (silibinin) and 25.0ng/mL (silibinin hemisuccinate), and the linearity was validated up to 1000.0 and 12,500.0ng/mL, for silibinin and silibinin hemisuccinate, respectively, with correlation coefficients (R(2)) of 0.991 or better. The methods were suitable for pharmacokinetic studies and were successfully applied to human plasma samples from subjects treated intravenously with Legalon(®) SIL at the dose of 20mg/kg, expressed as silibinin. Copyright © 2013 Elsevier B.V. All rights reserved.
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Developing an Index to Measure Health System Performance: Measurement for Districts of Nepal.
Kandel, N; Fric, A; Lamichhane, J
2014-01-01
Various frameworks for measuring health system performance have been proposed and discussed. The scope of using performance indicators are broad, ranging from examining national health system to individual patients at various levels of health system. Development of innovative and easy index is essential to measure multidimensionality of health systems. We used indicators, which also serve as proxy to the set of activities, whose primary goal is to maintain and improve health. We used eleven indicators of MDGs, which represent all dimensions of health to develop index. These indicators are computed with similar methodology that of human development index. We used published data of Nepal for computation of the index for districts of Nepal as an illustration. To validate our finding, we compared the indices of these districts with other development indices of Nepal. An index for each district has been computed from eleven indicators. Then indices are compared with that of human development index, socio-economic and infrastructure development indices and findings has shown the similarity on distribution of districts. Categories of low and high performing districts on health system performance are also having low and high human development, socio-economic, and infrastructure indices respectively. This methodology of computing index from various indicators could assist policy makers and program managers to prioritize activities based on their performance. Validation of the findings with that of other development indicators show that this can be one of the tools, which can assist on assessing health system performance for policy makers, program managers and others.
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Human perception testing methodology for evaluating EO/IR imaging systems
NASA Astrophysics Data System (ADS)
Graybeal, John J.; Monfort, Samuel S.; Du Bosq, Todd W.; Familoni, Babajide O.
2018-04-01
The U.S. Army's RDECOM CERDEC Night Vision and Electronic Sensors Directorate (NVESD) Perception Lab is tasked with supporting the development of sensor systems for the U.S. Army by evaluating human performance of emerging technologies. Typical research questions involve detection, recognition and identification as a function of range, blur, noise, spectral band, image processing techniques, image characteristics, and human factors. NVESD's Perception Lab provides an essential bridge between the physics of the imaging systems and the performance of the human operator. In addition to quantifying sensor performance, perception test results can also be used to generate models of human performance and to drive future sensor requirements. The Perception Lab seeks to develop and employ scientifically valid and efficient perception testing procedures within the practical constraints of Army research, including rapid development timelines for critical technologies, unique guidelines for ethical testing of Army personnel, and limited resources. The purpose of this paper is to describe NVESD Perception Lab capabilities, recent methodological improvements designed to align our methodology more closely with scientific best practice, and to discuss goals for future improvements and expanded capabilities. Specifically, we discuss modifying our methodology to improve training, to account for human fatigue, to improve assessments of human performance, and to increase experimental design consultation provided by research psychologists. Ultimately, this paper outlines a template for assessing human perception and overall system performance related to EO/IR imaging systems.
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Predictive performance models and multiple task performance
NASA Technical Reports Server (NTRS)
Wickens, Christopher D.; Larish, Inge; Contorer, Aaron
1989-01-01
Five models that predict how performance of multiple tasks will interact in complex task scenarios are discussed. The models are shown in terms of the assumptions they make about human operator divided attention. The different assumptions about attention are then empirically validated in a multitask helicopter flight simulation. It is concluded from this simulation that the most important assumption relates to the coding of demand level of different component tasks.
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Korzeniowski, Przemyslaw; Brown, Daniel C; Sodergren, Mikael H; Barrow, Alastair; Bello, Fernando
2017-02-01
The goal of this study was to establish face, content, and construct validity of NOViSE-the first force-feedback enabled virtual reality (VR) simulator for natural orifice transluminal endoscopic surgery (NOTES). Fourteen surgeons and surgical trainees performed 3 simulated hybrid transgastric cholecystectomies using a flexible endoscope on NOViSE. Four of them were classified as "NOTES experts" who had independently performed 10 or more simulated or human NOTES procedures. Seven participants were classified as "Novices" and 3 as "Gastroenterologists" with no or minimal NOTES experience. A standardized 5-point Likert-type scale questionnaire was administered to assess the face and content validity. NOViSE showed good overall face and content validity. In 14 out of 15 statements pertaining to face validity (graphical appearance, endoscope and tissue behavior, overall realism), ≥50% of responses were "agree" or "strongly agree." In terms of content validity, 85.7% of participants agreed or strongly agreed that NOViSE is a useful training tool for NOTES and 71.4% that they would recommend it to others. Construct validity was established by comparing a number of performance metrics such as task completion times, path lengths, applied forces, and so on. NOViSE demonstrated early signs of construct validity. Experts were faster and used a shorter endoscopic path length than novices in all but one task. The results indicate that NOViSE authentically recreates a transgastric hybrid cholecystectomy and sets promising foundations for the further development of a VR training curriculum for NOTES without compromising patient safety or requiring expensive animal facilities.
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Time series modeling of human operator dynamics in manual control tasks
NASA Technical Reports Server (NTRS)
Biezad, D. J.; Schmidt, D. K.
1984-01-01
A time-series technique is presented for identifying the dynamic characteristics of the human operator in manual control tasks from relatively short records of experimental data. Control of system excitation signals used in the identification is not required. The approach is a multi-channel identification technique for modeling multi-input/multi-output situations. The method presented includes statistical tests for validity, is designed for digital computation, and yields estimates for the frequency responses of the human operator. A comprehensive relative power analysis may also be performed for validated models. This method is applied to several sets of experimental data; the results are discussed and shown to compare favorably with previous research findings. New results are also presented for a multi-input task that has not been previously modeled to demonstrate the strengths of the method.
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Time Series Modeling of Human Operator Dynamics in Manual Control Tasks
NASA Technical Reports Server (NTRS)
Biezad, D. J.; Schmidt, D. K.
1984-01-01
A time-series technique is presented for identifying the dynamic characteristics of the human operator in manual control tasks from relatively short records of experimental data. Control of system excitation signals used in the identification is not required. The approach is a multi-channel identification technique for modeling multi-input/multi-output situations. The method presented includes statistical tests for validity, is designed for digital computation, and yields estimates for the frequency response of the human operator. A comprehensive relative power analysis may also be performed for validated models. This method is applied to several sets of experimental data; the results are discussed and shown to compare favorably with previous research findings. New results are also presented for a multi-input task that was previously modeled to demonstrate the strengths of the method.
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Immunoassays for the detection of nicergoline and its metabolites in human plasma.
Ezan, E; Delestre, L; Legendre, S; Rivière, R; Doignon, J L; Grognet, J M
2001-04-01
In order to determine nicergoline pharmacokinetics after oral administration to humans, we have developed two radioimmunoassays, one directed against nicergoline and the other directed against known nicergoline metabolites. The assays were validated according to the recommendations of international regulatory agencies and their limits of quantification were 40 and 10 pg/ml, respectively. In order to further validate the methods, a chromatographic separation of immunoreactive entities was performed with samples from healthy volunteers who were given 15 mg of Sermion (nicergoline orally administered). Chromatographic determination of assay specificity showed that the metabolite radioimmunoassay recognised known nicergoline metabolites but also a new metabolite. Using the antibodies directed against nicergoline, we were unable to detect nicergoline in the human plasma. This suggests that nicergoline is absent in the circulation because of complete metabolism through its first-pass effect.
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Real-time remote scientific model validation
NASA Technical Reports Server (NTRS)
Frainier, Richard; Groleau, Nicolas
1994-01-01
This paper describes flight results from the use of a CLIPS-based validation facility to compare analyzed data from a space life sciences (SLS) experiment to an investigator's preflight model. The comparison, performed in real-time, either confirms or refutes the model and its predictions. This result then becomes the basis for continuing or modifying the investigator's experiment protocol. Typically, neither the astronaut crew in Spacelab nor the ground-based investigator team are able to react to their experiment data in real time. This facility, part of a larger science advisor system called Principal Investigator in a Box, was flown on the space shuttle in October, 1993. The software system aided the conduct of a human vestibular physiology experiment and was able to outperform humans in the tasks of data integrity assurance, data analysis, and scientific model validation. Of twelve preflight hypotheses associated with investigator's model, seven were confirmed and five were rejected or compromised.
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He, Gaoli; Guo, Beining; Yu, Jicheng; Zhang, Jing; Wu, Xiaojie; Cao, Guoying; Shi, Yaoguo; Tsai, Cheng-Yuan
2015-05-01
Three methods were developed and validated for determination of nemonoxacin in human feces and its major metabolite, nemonoxacin acyl-β- d-glucuronide, in human urine and feces. Nemonoxacin was extracted by liquid-liquid extraction in feces homogenate samples and nemonoxacin acyl-β- d-glucuronide by a solid-phase extraction procedure for pretreatment of both urine and feces homogenate sample. Separation was performed on a C18 reversed-phase column under isocratic elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. Both analytes were determined by liquid chromatography-tandem mass spectrometry with positive electrospray ionization in selected reaction monitoring mode and gatifloxacin as the internal standard. The lower limit of quantitation (LLOQ) of nemonoxacin in feces was 0.12 µg/g and the calibration curve was linear in the concentration range of 0.12-48.00 µg/g. The LLOQ of the metabolite was 0.0010 µg/mL and 0.03 µg/g in urine and feces matrices, while the linear range was 0.0010-0.2000 µg/mL and 0.03-3.00 µg/g, respectively. Validation included selectivity, accuracy, precision, linearity, recovery, matrix effect, carryover, dilution integrity and stability, indicating that the methods can quantify the corresponding analytes with excellent reliability. The validated methods were successfully applied to an absolute bioavailability clinical study of nemonoxacin malate capsule. Copyright © 2014 John Wiley & Sons, Ltd.
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The use of MR B+1 imaging for validation of FDTD electromagnetic simulations of human anatomies.
Van den Berg, Cornelis A T; Bartels, Lambertus W; van den Bergen, Bob; Kroeze, Hugo; de Leeuw, Astrid A C; Van de Kamer, Jeroen B; Lagendijk, Jan J W
2006-10-07
In this study, MR B(+)(1) imaging is employed to experimentally verify the validity of FDTD simulations of electromagnetic field patterns in human anatomies. Measurements and FDTD simulations of the B(+)(1) field induced by a 3 T MR body coil in a human corpse were performed. It was found that MR B(+)(1) imaging is a sensitive method to measure the radiofrequency (RF) magnetic field inside a human anatomy with a precision of approximately 3.5%. A good correlation was found between the B(+)(1) measurements and FDTD simulations. The measured B(+)(1) pattern for a human pelvis consisted of a global, diagonal modulation pattern plus local B(+)(1) heterogeneties. It is believed that these local B(+)(1) field variations are the result of peaks in the induced electric currents, which could not be resolved by the FDTD simulations on a 5 mm(3) simulation grid. The findings from this study demonstrate that B(+)(1) imaging is a valuable experimental technique to gain more knowledge about the dielectric interaction of RF fields with the human anatomy.
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Foster, J D; Miskovic, D; Allison, A S; Conti, J A; Ockrim, J; Cooper, E J; Hanna, G B; Francis, N K
2016-06-01
Laparoscopic rectal resection is technically challenging, with outcomes dependent upon technical performance. No robust objective assessment tool exists for laparoscopic rectal resection surgery. This study aimed to investigate the application of the objective clinical human reliability analysis (OCHRA) technique for assessing technical performance of laparoscopic rectal surgery and explore the validity and reliability of this technique. Laparoscopic rectal cancer resection operations were described in the format of a hierarchical task analysis. Potential technical errors were defined. The OCHRA technique was used to identify technical errors enacted in videos of twenty consecutive laparoscopic rectal cancer resection operations from a single site. The procedural task, spatial location, and circumstances of all identified errors were logged. Clinical validity was assessed through correlation with clinical outcomes; reliability was assessed by test-retest. A total of 335 execution errors identified, with a median 15 per operation. More errors were observed during pelvic tasks compared with abdominal tasks (p < 0.001). Within the pelvis, more errors were observed during dissection on the right side than the left (p = 0.03). Test-retest confirmed reliability (r = 0.97, p < 0.001). A significant correlation was observed between error frequency and mesorectal specimen quality (r s = 0.52, p = 0.02) and with blood loss (r s = 0.609, p = 0.004). OCHRA offers a valid and reliable method for evaluating technical performance of laparoscopic rectal surgery.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
McClellan, G.E.; Wiker, S.F.
1985-05-31
This report quantifies for the first time the relationship between the signs and symptoms of acute radiation sickness and those of motion sickness. With this relationship, a quantitative comparison is made between data on human performance degradation during motion sickness and estimates of performance degradation during radiation sickness. The comparison validates estimates made by the Intermediate Dose Program on the performance degradation from acute radiation sickness.
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Probabilistic simulation of the human factor in structural reliability
NASA Astrophysics Data System (ADS)
Chamis, Christos C.; Singhal, Surendra N.
1994-09-01
The formal approach described herein computationally simulates the probable ranges of uncertainties for the human factor in probabilistic assessments of structural reliability. Human factors such as marital status, professional status, home life, job satisfaction, work load, and health are studied by using a multifactor interaction equation (MFIE) model to demonstrate the approach. Parametric studies in conjunction with judgment are used to select reasonable values for the participating factors (primitive variables). Subsequently performed probabilistic sensitivity studies assess the suitability of the MFIE as well as the validity of the whole approach. Results show that uncertainties range from 5 to 30 percent for the most optimistic case, assuming 100 percent for no error (perfect performance).
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Probabilistic Simulation of the Human Factor in Structural Reliability
NASA Technical Reports Server (NTRS)
Chamis, Christos C.; Singhal, Surendra N.
1994-01-01
The formal approach described herein computationally simulates the probable ranges of uncertainties for the human factor in probabilistic assessments of structural reliability. Human factors such as marital status, professional status, home life, job satisfaction, work load, and health are studied by using a multifactor interaction equation (MFIE) model to demonstrate the approach. Parametric studies in conjunction with judgment are used to select reasonable values for the participating factors (primitive variables). Subsequently performed probabilistic sensitivity studies assess the suitability of the MFIE as well as the validity of the whole approach. Results show that uncertainties range from 5 to 30 percent for the most optimistic case, assuming 100 percent for no error (perfect performance).
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Translating Fatigue to Human Performance.
Enoka, Roger M; Duchateau, Jacques
2016-11-01
Despite flourishing interest in the topic of fatigue-as indicated by the many presentations on fatigue at the 2015 Annual Meeting of the American College of Sports Medicine-surprisingly little is known about its effect on human performance. There are two main reasons for this dilemma: 1) the inability of current terminology to accommodate the scope of the conditions ascribed to fatigue, and 2) a paucity of validated experimental models. In contrast to current practice, a case is made for a unified definition of fatigue to facilitate its management in health and disease. On the basis of the classic two-domain concept of Mosso, fatigue is defined as a disabling symptom in which physical and cognitive function is limited by interactions between performance fatigability and perceived fatigability. As a symptom, fatigue can only be measured by self-report, quantified as either a trait characteristic or a state variable. One consequence of such a definition is that the word fatigue should not be preceded by an adjective (e.g., central, mental, muscle, peripheral, and supraspinal) to suggest the locus of the changes responsible for an observed level of fatigue. Rather, mechanistic studies should be performed with validated experimental models to identify the changes responsible for the reported fatigue. As indicated by three examples (walking endurance in old adults, time trials by endurance athletes, and fatigue in persons with multiple sclerosis) discussed in the review, however, it has proven challenging to develop valid experimental models of fatigue. The proposed framework provides a foundation to address the many gaps in knowledge of how laboratory measures of fatigue and fatigability affect real-world performance.
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Translating Fatigue to Human Performance
Enoka, Roger M.; Duchateau, Jacques
2016-01-01
Despite flourishing interest in the topic of fatigue—as indicated by the many presentations on fatigue at the 2015 annual meeting of the American College of Sports Medicine—surprisingly little is known about its impact on human performance. There are two main reasons for this dilemma: (1) the inability of current terminology to accommodate the scope of the conditions ascribed to fatigue, and (2) a paucity of validated experimental models. In contrast to current practice, a case is made for a unified definition of fatigue to facilitate its management in health and disease. Based on the classic two-domain concept of Mosso, fatigue is defined as a disabling symptom in which physical and cognitive function is limited by interactions between performance fatigability and perceived fatigability. As a symptom, fatigue can only be measured by self-report, quantified as either a trait characteristic or a state variable. One consequence of such a definition is that the word fatigue should not be preceded by an adjective (e.g., central, mental, muscle, peripheral, and supraspinal) to suggest the locus of the changes responsible for an observed level of fatigue. Rather, mechanistic studies should be performed with validated experimental models to identify the changes responsible for the reported fatigue. As indicated by three examples (walking endurance in old adults, time trials by endurance athletes, and fatigue in persons with multiple sclerosis) discussed in the review, however, it has proven challenging to develop valid experimental models of fatigue. The proposed framework provides a foundation to address the many gaps in knowledge of how laboratory measures of fatigue and fatigability impact real-world performance. PMID:27015386
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de Souza, Vanessa; Zeitoun, Sandra Salloum; Lopes, Camila Takao; de Oliveira, Ana Paula Dias; Lopes, Juliana de Lima; de Barros, Alba Lucia Botura Leite
2014-06-01
To consensually validate the operational definitions of the nursing diagnoses activity intolerance, excessive fluid volume, and decreased cardiac output in patients with decompensated heart failure. Consensual validation was performed in two stages: analogy by similarity of defining characteristics, and development of operational definitions and validation with experts. A total of 38 defining characteristics were found. Operational definitions were developed and content-validated. One hundred percent of agreement was achieved among the seven experts after five rounds. "Ascites" was added in the nursing diagnosis excessive fluid volume. The consensual validation improves interpretation of human response, grounding the selection of nursing interventions and contributing to improved nursing outcomes. Support the assessment of patients with decompensated heart failure. © 2013 NANDA International.
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Fachi, Mariana Millan; Leonart, Letícia Paula; Cerqueira, Letícia Bonancio; Pontes, Flavia Lada Degaut; de Campos, Michel Leandro; Pontarolo, Roberto
2017-06-15
A systematic and critical review was conducted on bioanalytical methods validated to quantify combinations of antidiabetic agents in human blood. The aim of this article was to verify how the validation process of bioanalytical methods is performed and the quality of the published records. The validation assays were evaluated according to international guidelines. The main problems in the validation process are pointed out and discussed to help researchers to choose methods that are truly reliable and can be successfully applied for their intended use. The combination of oral antidiabetic agents was chosen as these are some of the most studied drugs and several methods are present in the literature. Moreover, this article may be applied to the validation process of all bioanalytical. Copyright © 2017 Elsevier B.V. All rights reserved.
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Furlong, Michael T; Savant, Ishani; Yuan, Moucun; Scott, Laura; Mylott, William; Mariannino, Thomas; Kadiyala, Pathanjali; Roongta, Vikram; Arnold, Mark E
2013-05-01
Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent myocardial infarction, recent stroke, or established peripheral arterial disease. A sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable quantification of four diastereomeric and chemically reactive thiol metabolites, two of which are pharmacologically active, in human plasma. The metabolites were stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'-methoxyacetophenone (MPB). Following organic solvent mediated-protein precipitation in a 96-well plate format, chromatographic separation was achieved by gradient elution on an Ascentis Express RP-amide column. Chromatographic conditions were optimized to ensure separation of the four derivatized active metabolites. Derivatized metabolites and stable isotope-labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay precision values for replicate quality control samples were within 14.3% for all analytes during the assay validation. Mean quality control accuracy values were within ±6.3% of nominal values for all analytes. Assay recoveries were high (>79%). The four derivatized analytes were stable in human blood for at least 2 h at room temperature and on ice. The analytes were also stable in human plasma for at least 25 h at room temperature, 372 days at -20 °C and -70 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of all four thiol metabolites in human plasma in support of a human pharmacokinetic study. Copyright © 2013 Elsevier B.V. All rights reserved.
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NASA Technical Reports Server (NTRS)
Kennedy, Robert S.; Lane, Norman E.; Kuntz, Lois A.
1987-01-01
Surrogate measures are proposed as an alternative to direct assessment of operational performance for purposes of screening agents who may have to work under unusual stresses or in exotic environments. Such measures are particularly proposed when the surrogate can be empirically validated against the operational criterion. The focus is on cognitive (or throughput) performances in humans as opposed to sensory (input) or motor (output) measures, but the methods should be applicable for development of batteries which will tap input/output functions. A menu of performance tasks is under development for implementation on a battery-operated portable microcomputer, with 21 tests currently available. The tasks are reliable and become stable in minimum amounts of time; appear sensitive to some agents; comprise constructs related to actual job tasks; and are easily administered in most environments. Implications for human factors engineering studies in environmental stress are discussed.
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Radiation Measurements Performed with Active Detectors Relevant for Human Space Exploration
Narici, Livio; Berger, Thomas; Matthiä, Daniel; Reitz, Günther
2015-01-01
A reliable radiation risk assessment in space is a mandatory step for the development of countermeasures and long-duration mission planning in human spaceflight. Research in radiobiology provides information about possible risks linked to radiation. In addition, for a meaningful risk evaluation, the radiation exposure has to be assessed to a sufficient level of accuracy. Consequently, both the radiation models predicting the risks and the measurements used to validate such models must have an equivalent precision. Corresponding measurements can be performed both with passive and active devices. The former is easier to handle, cheaper, lighter, and smaller but they measure neither the time dependence of the radiation environment nor some of the details useful for a comprehensive radiation risk assessment. Active detectors provide most of these details and have been extensively used in the International Space Station. To easily access such an amount of data, a single point access is becoming essential. This review presents an ongoing work on the development of a tool that allows obtaining information about all relevant measurements performed with active detectors providing reliable inputs for radiation model validation. PMID:26697408
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Radiation Measurements Performed with Active Detectors Relevant for Human Space Exploration.
Narici, Livio; Berger, Thomas; Matthiä, Daniel; Reitz, Günther
2015-01-01
A reliable radiation risk assessment in space is a mandatory step for the development of countermeasures and long-duration mission planning in human spaceflight. Research in radiobiology provides information about possible risks linked to radiation. In addition, for a meaningful risk evaluation, the radiation exposure has to be assessed to a sufficient level of accuracy. Consequently, both the radiation models predicting the risks and the measurements used to validate such models must have an equivalent precision. Corresponding measurements can be performed both with passive and active devices. The former is easier to handle, cheaper, lighter, and smaller but they measure neither the time dependence of the radiation environment nor some of the details useful for a comprehensive radiation risk assessment. Active detectors provide most of these details and have been extensively used in the International Space Station. To easily access such an amount of data, a single point access is becoming essential. This review presents an ongoing work on the development of a tool that allows obtaining information about all relevant measurements performed with active detectors providing reliable inputs for radiation model validation.
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Liu, Yanhong; Zhang, Weihua; Yang, Yuhui
2008-10-19
A hydrophilic interaction high performance liquid chromatography-tandem mass spectrometric method has been developed and validated for simultaneous quantification of dacarbazine (DTIC) and its terminal metabolite, 5-amino-4-imidazole-carboxamide (AIC) in human plasma. The plasma samples are first extracted by a C8+SCX mixed-mode 96-well plate to extend the extraction stability of DTIC and AIC. The extracted residues are further cleaned by a primary and secondary amine (PSA) adsorbent for minimization of matrix effect. Analyses are done on an Amide-80 HPLC column coupled to a tandem mass spectrometer fitted with an atmospheric pressure turbo ion spray ionization interface in the positive-ion mode. Both DTIC and AIC have reproducible retention times on the Amide-80 HPLC column. This type of column not only has an excellent column life (over 4000 injections), but also has zero carryover effect. The injection volume should be limited at 10 microL or less to avoid the peak splitting. The validated concentration ranges are from 0.5 to 500 ng/mL for DTIC and from 2.0 to 500 ng/mL for AIC. The validated method has been successfully applied to determine the pharmacokinetic profiles for human patients receiving DTIC infusions.
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Validating a biometric authentication system: sample size requirements.
Dass, Sarat C; Zhu, Yongfang; Jain, Anil K
2006-12-01
Authentication systems based on biometric features (e.g., fingerprint impressions, iris scans, human face images, etc.) are increasingly gaining widespread use and popularity. Often, vendors and owners of these commercial biometric systems claim impressive performance that is estimated based on some proprietary data. In such situations, there is a need to independently validate the claimed performance levels. System performance is typically evaluated by collecting biometric templates from n different subjects, and for convenience, acquiring multiple instances of the biometric for each of the n subjects. Very little work has been done in 1) constructing confidence regions based on the ROC curve for validating the claimed performance levels and 2) determining the required number of biometric samples needed to establish confidence regions of prespecified width for the ROC curve. To simplify the analysis that address these two problems, several previous studies have assumed that multiple acquisitions of the biometric entity are statistically independent. This assumption is too restrictive and is generally not valid. We have developed a validation technique based on multivariate copula models for correlated biometric acquisitions. Based on the same model, we also determine the minimum number of samples required to achieve confidence bands of desired width for the ROC curve. We illustrate the estimation of the confidence bands as well as the required number of biometric samples using a fingerprint matching system that is applied on samples collected from a small population.
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2014-12-31
collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1...24 3. Posttest Questionnaires .................................................................................. 26 4. Work...abnormal behavior for humans. Many human physiological functions are controlled by the circadian clock; for example, sleep and its associated functions
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Can visual arts training improve physician performance?
Katz, Joel T; Khoshbin, Shahram
2014-01-01
Clinical educators use medical humanities as a means to improve patient care by training more self-aware, thoughtful, and collaborative physicians. We present three examples of integrating fine arts - a subset of medical humanities - into the preclinical and clinical training as models that can be adapted to other medical environments to address a wide variety of perceived deficiencies. This novel teaching method has promise to improve physician skills, but requires further validation.
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A system performance throughput model applicable to advanced manned telescience systems
NASA Technical Reports Server (NTRS)
Haines, Richard F.
1990-01-01
As automated space systems become more complex, autonomous, and opaque to the flight crew, it becomes increasingly difficult to determine whether the total system is performing as it should. Some of the complex and interrelated human performance measurement issues are addressed that are related to total system validation. An evaluative throughput model is presented which can be used to generate a human operator-related benchmark or figure of merit for a given system which involves humans at the input and output ends as well as other automated intelligent agents. The concept of sustained and accurate command/control data information transfer is introduced. The first two input parameters of the model involve nominal and off-nominal predicted events. The first of these calls for a detailed task analysis while the second is for a contingency event assessment. The last two required input parameters involving actual (measured) events, namely human performance and continuous semi-automated system performance. An expression combining these four parameters was found using digital simulations and identical, representative, random data to yield the smallest variance.
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Haram, Kerstyn M; Peltier, Heidi J; Lu, Bin; Bhasin, Manoj; Otu, Hasan H; Choy, Bob; Regan, Meredith; Libermann, Towia A; Latham, Gary J; Sanda, Martin G; Arredouani, Mohamed S
2008-10-01
Translation of preclinical studies into effective human cancer therapy is hampered by the lack of defined molecular expression patterns in mouse models that correspond to the human counterpart. We sought to generate an open source TRAMP mouse microarray dataset and to use this array to identify differentially expressed genes from human prostate cancer (PCa) that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. We performed microarrays on total RNA extracted and amplified from eight TRAMP tumors and nine normal prostates. A subset of differentially expressed genes was validated by QRT-PCR. Differentially expressed TRAMP genes were analyzed for concordant expression in publicly available human prostate array datasets and a subset of resulting genes was analyzed by QRT-PCR. Cross-referencing differentially expressed TRAMP genes to public human prostate array datasets revealed 66 genes with concordant expression in mouse and human PCa; 56 between metastases and normal and 10 between primary tumor and normal tissues. Of these 10 genes, two, Sox4 and Tubb2a, were validated by QRT-PCR. Our analysis also revealed various dysregulations in major biologic pathways in the TRAMP prostates. We report a TRAMP microarray dataset of which a gene subset was validated by QRT-PCR with expression patterns consistent with previous gene-specific TRAMP studies. Concordance analysis between TRAMP and human PCa associated genes supports the utility of the model and suggests several novel molecular targets for preclinical therapy.
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NASA Technical Reports Server (NTRS)
Gore, Brian F.
2011-01-01
As automation and advanced technologies are introduced into transport systems ranging from the Next Generation Air Transportation System termed NextGen, to the advanced surface transportation systems as exemplified by the Intelligent Transportations Systems, to future systems designed for space exploration, there is an increased need to validly predict how the future systems will be vulnerable to error given the demands imposed by the assistive technologies. One formalized approach to study the impact of assistive technologies on the human operator in a safe and non-obtrusive manner is through the use of human performance models (HPMs). HPMs play an integral role when complex human-system designs are proposed, developed, and tested. One HPM tool termed the Man-machine Integration Design and Analysis System (MIDAS) is a NASA Ames Research Center HPM software tool that has been applied to predict human-system performance in various domains since 1986. MIDAS is a dynamic, integrated HPM and simulation environment that facilitates the design, visualization, and computational evaluation of complex man-machine system concepts in simulated operational environments. The paper will discuss a range of aviation specific applications including an approach used to model human error for NASA s Aviation Safety Program, and what-if analyses to evaluate flight deck technologies for NextGen operations. This chapter will culminate by raising two challenges for the field of predictive HPMs for complex human-system designs that evaluate assistive technologies: that of (1) model transparency and (2) model validation.
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Kang, Homan; Jeong, Sinyoung; Jo, Ahla; Chang, Hyejin; Yang, Jin-Kyoung; Jeong, Cheolhwan; Kyeong, San; Lee, Youn Woo; Samanta, Animesh; Maiti, Kaustabh Kumar; Cha, Myeong Geun; Kim, Taek-Keun; Lee, Sukmook; Jun, Bong-Hyun; Chang, Young-Tae; Chung, Junho; Lee, Ho-Young; Jeong, Dae Hong; Lee, Yoon-Sik
2018-02-01
Immunotargeting ability of antibodies may show significant difference between in vitro and in vivo. To select antibody leads with high affinity and specificity, it is necessary to perform in vivo validation of antibody candidates following in vitro antibody screening. Herein, a robust in vivo validation of anti-tetraspanin-8 antibody candidates against human colon cancer using ratiometric quantification method is reported. The validation is performed on a single mouse and analyzed by multiplexed surface-enhanced Raman scattering using ultrasensitive and near infrared (NIR)-active surface-enhanced resonance Raman scattering nanoprobes (NIR-SERRS dots). The NIR-SERRS dots are composed of NIR-active labels and Au/Ag hollow-shell assembled silica nanospheres. A 93% of NIR-SERRS dots is detectable at a single-particle level and signal intensity is 100-fold stronger than that from nonresonant molecule-labeled spherical Au NPs (80 nm). The result of SERRS-based antibody validation is comparable to that of the conventional method using single-photon-emission computed tomography. The NIR-SERRS-based strategy is an alternate validation method which provides cost-effective and accurate multiplexing measurements for antibody-based drug development. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Scaling effects in a non-linear electromagnetic energy harvester for wearable sensors
NASA Astrophysics Data System (ADS)
Geisler, M.; Boisseau, S.; Perez, M.; Ait-Ali, I.; Perraud, S.
2016-11-01
In the field of inertial energy harvesters targeting human mechanical energy, the ergonomics of the solutions impose to find the best compromise between dimensions reduction and electrical performance. In this paper, we study the properties of a non-linear electromagnetic generator at different scales, by performing simulations based on an experimentally validated model and real human acceleration recordings. The results display that the output power of the structure is roughly proportional to its scaling factor raised to the power of five, which indicates that this system is more relevant at lengths over a few centimetres.
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NASA Astrophysics Data System (ADS)
Veldkamp, Ted; Ward, Philip; de Moel, Hans; Aerts, Jeroen; Muller Schmied, Hannes; Portmann, Felix; Zhao, Fang; Gerten, Dieter; Masaki, Yoshimitsu; Pokhrel, Yadu; Satoh, Yusuke; Gosling, Simon; Zaherpour, Jamal; Wada, Yoshihide
2017-04-01
Human impacts on freshwater resources and hydrological features form the core of present-day water related hazards, like flooding, droughts, water scarcity, and water quality issues. Driven by the societal and scientific needs to correctly model such water related hazards a fair amount of resources has been invested over the past decades to represent human activities and their interactions with the hydrological cycle in global hydrological models (GHMs). Use of these GHMs - including the human dimension - is widespread, especially in water resources research. Evaluation or comparative assessments of the ability of such GHMs to represent real-world hydrological conditions are, unfortunately, however often limited to (near-)natural river basins. Such studies are, therefore, not able to test the model representation of human activities and its associated impact on estimates of freshwater resources or assessments of hydrological extremes. Studies that did perform a validation exercise - including the human dimension and looking into managed catchments - either focused only on one hydrological model, and/or incorporated only a few data points (i.e. river basins) for validation. To date, a comprehensive comparative analysis that evaluates whether and where incorporating the human dimension actually improves the performance of different GHMs with respect to their representation of real-world hydrological conditions and extremes is missing. The absence of such study limits the potential benchmarking of GHMs and their outcomes in hydrological hazard and risk assessments significantly, potentially hampering incorporation of GHMs and their modelling results in actual policy making and decision support with respect to water resources management. To address this issue, we evaluate in this study the performance of five state-of-the-art GHMs that include anthropogenic activities in their modelling scheme, with respect to their representation of monthly discharges and hydrological extremes. To this end, we compared their monthly discharge simulations under a naturalized and a time-dependent human impact simulation, with monthly GRDC river discharge observations of 2,412 stations over the period 1971-2010. Evaluation metrics that were used to assess the performance of the GHMs included the modified Kling-Gupta Efficiency index, and its individual parameters describing the linear correlation coefficient, the bias ratio, and the variability ratio, as well as indicators for hydrological extremes (Q90, Q10). Our results show that inclusion of anthropogenic activities in the modelling framework generally enhances the overall performance of the GHMs studied, mainly driven by bias-improvements, and to a lesser extent due to changes in modelled hydrological variability. Whilst the inclusion of anthropogenic activities takes mainly effect in the managed catchments, a significant share of the (near-)natural catchments is influenced as well. To get estimates of hydrological extremes right, especially when looking at low-flows, inclusion of human activities is paramount. Whilst high-flow estimates are mainly decreased, impact of human activities on low-flows is ambiguous, i.e. due to the relative importance of the timing of return flows and reservoir operations. Even with inclusion of the human dimension we find, nevertheless, a persistent overestimation of hydrological extremes across all models, which should be accounted for in future assessments.
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Zhou, Xiaobo; Qiu, Weiliang; Sathirapongsasuti, J. Fah.; Cho, Michael H.; Mancini, John D.; Lao, Taotao; Thibault, Derek M.; Litonjua, Gus; Bakke, Per S.; Gulsvik, Amund; Lomas, David A.; Beaty, Terri H.; Hersh, Craig P.; Anderson, Christopher; Geigenmuller, Ute; Raby, Benjamin A.; Rennard, Stephen I.; Perrella, Mark A.; Choi, Augustine M.K.; Quackenbush, John; Silverman, Edwin K.
2013-01-01
Hedgehog Interacting Protein (HHIP) was implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS). However, it remains unclear how HHIP contributes to COPD pathogenesis. To identify genes regulated by HHIP, we performed gene expression microarray analysis in a human bronchial epithelial cell line (Beas-2B) stably infected with HHIP shRNAs. HHIP silencing led to differential expression of 296 genes; enrichment for variants nominally associated with COPD was found. Eighteen of the differentially expressed genes were validated by real-time PCR in Beas-2B cells. Seven of 11 validated genes tested in human COPD and control lung tissues demonstrated significant gene expression differences. Functional annotation indicated enrichment for extracellular matrix and cell growth genes. Network modeling demonstrated that the extracellular matrix and cell proliferation genes influenced by HHIP tended to be interconnected. Thus, we identified potential HHIP targets in human bronchial epithelial cells that may contribute to COPD pathogenesis. PMID:23459001
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Discomfort Evaluation of Truck Ingress/Egress Motions Based on Biomechanical Analysis
Choi, Nam-Chul; Lee, Sang Hun
2015-01-01
This paper presents a quantitative discomfort evaluation method based on biomechanical analysis results for human body movement, as well as its application to an assessment of the discomfort for truck ingress and egress. In this study, the motions of a human subject entering and exiting truck cabins with different types, numbers, and heights of footsteps were first measured using an optical motion capture system and load sensors. Next, the maximum voluntary contraction (MVC) ratios of the muscles were calculated through a biomechanical analysis of the musculoskeletal human model for the captured motion. Finally, the objective discomfort was evaluated using the proposed discomfort model based on the MVC ratios. To validate this new discomfort assessment method, human subject experiments were performed to investigate the subjective discomfort levels through a questionnaire for comparison with the objective discomfort levels. The validation results showed that the correlation between the objective and subjective discomforts was significant and could be described by a linear regression model. PMID:26067194
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A validation framework for brain tumor segmentation.
Archip, Neculai; Jolesz, Ferenc A; Warfield, Simon K
2007-10-01
We introduce a validation framework for the segmentation of brain tumors from magnetic resonance (MR) images. A novel unsupervised semiautomatic brain tumor segmentation algorithm is also presented. The proposed framework consists of 1) T1-weighted MR images of patients with brain tumors, 2) segmentation of brain tumors performed by four independent experts, 3) segmentation of brain tumors generated by a semiautomatic algorithm, and 4) a software tool that estimates the performance of segmentation algorithms. We demonstrate the validation of the novel segmentation algorithm within the proposed framework. We show its performance and compare it with existent segmentation. The image datasets and software are available at http://www.brain-tumor-repository.org/. We present an Internet resource that provides access to MR brain tumor image data and segmentation that can be openly used by the research community. Its purpose is to encourage the development and evaluation of segmentation methods by providing raw test and image data, human expert segmentation results, and methods for comparing segmentation results.
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Human Perception of Ambiguous Inertial Motion Cues
NASA Technical Reports Server (NTRS)
Zhang, Guan-Lu
2010-01-01
Human daily activities on Earth involve motions that elicit both tilt and translation components of the head (i.e. gazing and locomotion). With otolith cues alone, tilt and translation can be ambiguous since both motions can potentially displace the otolithic membrane by the same magnitude and direction. Transitions between gravity environments (i.e. Earth, microgravity and lunar) have demonstrated to alter the functions of the vestibular system and exacerbate the ambiguity between tilt and translational motion cues. Symptoms of motion sickness and spatial disorientation can impair human performances during critical mission phases. Specifically, Space Shuttle landing records show that particular cases of tilt-translation illusions have impaired the performance of seasoned commanders. This sensorimotor condition is one of many operational risks that may have dire implications on future human space exploration missions. The neural strategy with which the human central nervous system distinguishes ambiguous inertial motion cues remains the subject of intense research. A prevailing theory in the neuroscience field proposes that the human brain is able to formulate a neural internal model of ambiguous motion cues such that tilt and translation components can be perceptually decomposed in order to elicit the appropriate bodily response. The present work uses this theory, known as the GIF resolution hypothesis, as the framework for experimental hypothesis. Specifically, two novel motion paradigms are employed to validate the neural capacity of ambiguous inertial motion decomposition in ground-based human subjects. The experimental setup involves the Tilt-Translation Sled at Neuroscience Laboratory of NASA JSC. This two degree-of-freedom motion system is able to tilt subjects in the pitch plane and translate the subject along the fore-aft axis. Perception data will be gathered through subject verbal reports. Preliminary analysis of perceptual data does not indicate that the GIF resolution hypothesis is completely valid for non-rotational periodic motions. Additionally, human perception of translation is impaired without visual or spatial reference. The performance of ground-base subjects in estimating tilt after brief training is comparable with that of crewmembers without training.
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Hoffman, Justin T; Rossi, Steven S; Espina-Quinto, Rowena; Letendre, Scott; Capparelli, Edmund V
2013-04-01
Previously published methods for determination of efavirenz (EFV) in human dried blood spots (DBS) use costly and complex liquid chromatography/mass spectrometry. We describe the validation and evaluation of a simple and inexpensive high-performance liquid chromatography method for EFV quantification in human DBS and dried plasma spots (DPS), using ultraviolet detection appropriate for resource-limited settings. One hundred microliters of heparinized whole blood or plasma were spotted onto blood collection cards, dried, punched, and eluted. Eluates are injected onto a C-18 reversed phase high-performance liquid chromatography column. EFV is separated isocratically using a potassium phosphate and acetonitrile mobile phase. Ultraviolet detection is at 245 nm. Quantitation is by use of external calibration standards. Following validation, the method was evaluated using whole blood and plasma from HIV-positive patients undergoing EFV therapy. Mean recovery of drug from DBS is 91.5%. The method is linear over the validated concentration range of 0.3125-20.0 μg/mL. A good correlation (Spearman r = 0.96) between paired plasma and DBS EFV concentrations from the clinical samples was observed, and hematocrit level was not found to be a significant determinant of the EFV DBS level. The mean observed C DBS/C plasma ratio was 0.68. A good correlation (Spearman r = 0.96) between paired plasma and DPS EFV concentrations from the clinical samples was observed. The mean percent deviation of DPS samples from plasma samples is 1.68%. Dried whole blood spot or dried plasma spot sampling is well suited for monitoring EFV therapy in resource-limited settings, particularly when high sensitivity is not essential.
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Wearable carbon nanotube-based fabric sensors for monitoring human physiological performance
NASA Astrophysics Data System (ADS)
Wang, Long; Loh, Kenneth J.
2017-05-01
A target application of wearable sensors is to detect human motion and to monitor physical activity for improving athletic performance and for delivering better physical therapy. In addition, measuring human vital signals (e.g., respiration rate and body temperature) provides rich information that can be used to assess a subject’s physiological or psychological condition. This study aims to design a multifunctional, wearable, fabric-based sensing system. First, carbon nanotube (CNT)-based thin films were fabricated by spraying. Second, the thin films were integrated with stretchable fabrics to form the fabric sensors. Third, the strain and temperature sensing properties of sensors fabricated using different CNT concentrations were characterized. Furthermore, the sensors were demonstrated to detect human finger bending motions, so as to validate their practical strain sensing performance. Finally, to monitor human respiration, the fabric sensors were integrated with a chest band, which was directly worn by a human subject. Quantification of respiration rates were successfully achieved. Overall, the fabric sensors were characterized by advantages such as flexibility, ease of fabrication, lightweight, low-cost, noninvasiveness, and user comfort.
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Robotics-based synthesis of human motion.
Khatib, O; Demircan, E; De Sapio, V; Sentis, L; Besier, T; Delp, S
2009-01-01
The synthesis of human motion is a complex procedure that involves accurate reconstruction of movement sequences, modeling of musculoskeletal kinematics, dynamics and actuation, and characterization of reliable performance criteria. Many of these processes have much in common with the problems found in robotics research. Task-based methods used in robotics may be leveraged to provide novel musculoskeletal modeling methods and physiologically accurate performance predictions. In this paper, we present (i) a new method for the real-time reconstruction of human motion trajectories using direct marker tracking, (ii) a task-driven muscular effort minimization criterion and (iii) new human performance metrics for dynamic characterization of athletic skills. Dynamic motion reconstruction is achieved through the control of a simulated human model to follow the captured marker trajectories in real-time. The operational space control and real-time simulation provide human dynamics at any configuration of the performance. A new criteria of muscular effort minimization has been introduced to analyze human static postures. Extensive motion capture experiments were conducted to validate the new minimization criterion. Finally, new human performance metrics were introduced to study in details an athletic skill. These metrics include the effort expenditure and the feasible set of operational space accelerations during the performance of the skill. The dynamic characterization takes into account skeletal kinematics as well as muscle routing kinematics and force generating capacities. The developments draw upon an advanced musculoskeletal modeling platform and a task-oriented framework for the effective integration of biomechanics and robotics methods.
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Sharma, Niraj K; Pedreira, Carlos; Centeno, Maria; Chaudhary, Umair J; Wehner, Tim; França, Lucas G S; Yadee, Tinonkorn; Murta, Teresa; Leite, Marco; Vos, Sjoerd B; Ourselin, Sebastien; Diehl, Beate; Lemieux, Louis
2017-07-01
To validate the application of an automated neuronal spike classification algorithm, Wave_clus (WC), on interictal epileptiform discharges (IED) obtained from human intracranial EEG (icEEG) data. Five 10-min segments of icEEG recorded in 5 patients were used. WC and three expert EEG reviewers independently classified one hundred IED events into IED classes or non-IEDs. First, we determined whether WC-human agreement variability falls within inter-reviewer agreement variability by calculating the variation of information for each classifier pair and quantifying the overlap between all WC-reviewer and all reviewer-reviewer pairs. Second, we compared WC and EEG reviewers' spike identification and individual spike class labels visually and quantitatively. The overlap between all WC-human pairs and all human pairs was >80% for 3/5 patients and >58% for the other 2 patients demonstrating WC falling within inter-human variation. The average sensitivity of spike marking for WC was 91% and >87% for all three EEG reviewers. Finally, there was a strong visual and quantitative similarity between WC and EEG reviewers. WC performance is indistinguishable to that of EEG reviewers' suggesting it could be a valid clinical tool for the assessment of IEDs. WC can be used to provide quantitative analysis of epileptic spikes. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
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Domańska, Barbara; Stumpp, Oliver; Poon, Steven; Oray, Serkan; Mountian, Irina; Pichon, Clovis
2018-01-01
We incorporated patient feedback from human factors studies (HFS) in the patient-centric design and validation of ava ® , an electromechanical device (e-Device) for self-injecting the anti-tumor necrosis factor certolizumab pegol (CZP). Healthcare professionals, caregivers, healthy volunteers, and patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or Crohn's disease participated in 11 formative HFS to optimize the e-Device design through intended user feedback; nine studies involved simulated injections. Formative participant questionnaire feedback was collected following e-Device prototype handling. Validation HFS (one EU study and one US study) assessed the safe and effective setup and use of the e-Device using 22 predefined critical tasks. Task outcomes were categorized as "failures" if participants did not succeed within three attempts. Two hundred eighty-three participants entered formative (163) and validation (120) HFS; 260 participants performed one or more simulated e-Device self-injections. Design changes following formative HFS included alterations to buttons and the graphical user interface screen. All validation HFS participants completed critical tasks necessary for CZP dose delivery, with minimal critical task failures (12 of 572 critical tasks, 2.1%, in the EU study, and 2 of 5310 critical tasks, less than 0.1%, in the US study). CZP e-Device development was guided by intended user feedback through HFS, ensuring the final design addressed patients' needs. In both validation studies, participants successfully performed all critical tasks, demonstrating safe and effective e-Device self-injections. UCB Pharma. Plain language summary available on the journal website.
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Mental State Assessment and Validation Using Personalized Physiological Biometrics
Patel, Aashish N.; Howard, Michael D.; Roach, Shane M.; Jones, Aaron P.; Bryant, Natalie B.; Robinson, Charles S. H.; Clark, Vincent P.; Pilly, Praveen K.
2018-01-01
Mental state monitoring is a critical component of current and future human-machine interfaces, including semi-autonomous driving and flying, air traffic control, decision aids, training systems, and will soon be integrated into ubiquitous products like cell phones and laptops. Current mental state assessment approaches supply quantitative measures, but their only frame of reference is generic population-level ranges. What is needed are physiological biometrics that are validated in the context of task performance of individuals. Using curated intake experiments, we are able to generate personalized models of three key biometrics as useful indicators of mental state; namely, mental fatigue, stress, and attention. We demonstrate improvements to existing approaches through the introduction of new features. Furthermore, addressing the current limitations in assessing the efficacy of biometrics for individual subjects, we propose and employ a multi-level validation scheme for the biometric models by means of k-fold cross-validation for discrete classification and regression testing for continuous prediction. The paper not only provides a unified pipeline for extracting a comprehensive mental state evaluation from a parsimonious set of sensors (only EEG and ECG), but also demonstrates the use of validation techniques in the absence of empirical data. Furthermore, as an example of the application of these models to novel situations, we evaluate the significance of correlations of personalized biometrics to the dynamic fluctuations of accuracy and reaction time on an unrelated threat detection task using a permutation test. Our results provide a path toward integrating biometrics into augmented human-machine interfaces in a judicious way that can help to maximize task performance.
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Theilmann, Wiebke; Löscher, Wolfgang; Socala, Katarzyna; Frieling, Helge; Bleich, Stefan; Brandt, Claudia
2014-06-01
Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Mental State Assessment and Validation Using Personalized Physiological Biometrics.
Patel, Aashish N; Howard, Michael D; Roach, Shane M; Jones, Aaron P; Bryant, Natalie B; Robinson, Charles S H; Clark, Vincent P; Pilly, Praveen K
2018-01-01
Mental state monitoring is a critical component of current and future human-machine interfaces, including semi-autonomous driving and flying, air traffic control, decision aids, training systems, and will soon be integrated into ubiquitous products like cell phones and laptops. Current mental state assessment approaches supply quantitative measures, but their only frame of reference is generic population-level ranges. What is needed are physiological biometrics that are validated in the context of task performance of individuals. Using curated intake experiments, we are able to generate personalized models of three key biometrics as useful indicators of mental state; namely, mental fatigue, stress, and attention. We demonstrate improvements to existing approaches through the introduction of new features. Furthermore, addressing the current limitations in assessing the efficacy of biometrics for individual subjects, we propose and employ a multi-level validation scheme for the biometric models by means of k -fold cross-validation for discrete classification and regression testing for continuous prediction. The paper not only provides a unified pipeline for extracting a comprehensive mental state evaluation from a parsimonious set of sensors (only EEG and ECG), but also demonstrates the use of validation techniques in the absence of empirical data. Furthermore, as an example of the application of these models to novel situations, we evaluate the significance of correlations of personalized biometrics to the dynamic fluctuations of accuracy and reaction time on an unrelated threat detection task using a permutation test. Our results provide a path toward integrating biometrics into augmented human-machine interfaces in a judicious way that can help to maximize task performance.
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Lee, Kang Choon; Chun, Young Goo; Kim, Insoo; Shin, Beom Soo; Park, Eun-Seok; Yoo, Sun Dong; Youn, Yu Seok
2009-07-15
A simple, specific and sensitive derivatization with monobromobimane (mBrB) and the corresponding HPLC-fluorescence quantitation method for the analysis of bucillamine in human plasma was developed and validated. The analytical procedure involves a simple protein precipitation, pre-column fluorescence derivatization, and separation by reversed-phase high performance liquid chromatography (RP-HPLC). The calibration curve showed good linearity over a wide concentration range (50 ng/mL to 10 microg/mL) in human plasma (r(2)=0.9998). The lower limit of quantitation (LLOQ) was 50 ng/mL. The average precision and accuracy at LLOQ were within 6.3% and 107.6%, respectively. This method was successfully applied to a pharmacokinetic study after oral administration of a dose (300 mg) of bucillamine to 20 healthy Korean volunteers.
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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
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Royo Sánchez, Ana Cristina; Aguilar Martín, Juan José; Santolaria Mazo, Jorge
2014-12-01
Motion capture systems are often used for checking and analyzing human motion in biomechanical applications. It is important, in this context, that the systems provide the best possible accuracy. Among existing capture systems, optical systems are those with the highest accuracy. In this paper, the development of a new calibration procedure for optical human motion capture systems is presented. The performance and effectiveness of that new calibration procedure are also checked by experimental validation. The new calibration procedure consists of two stages. In the first stage, initial estimators of intrinsic and extrinsic parameters are sought. The camera calibration method used in this stage is the one proposed by Tsai. These parameters are determined from the camera characteristics, the spatial position of the camera, and the center of the capture volume. In the second stage, a simultaneous nonlinear optimization of all parameters is performed to identify the optimal values, which minimize the objective function. The objective function, in this case, minimizes two errors. The first error is the distance error between two markers placed in a wand. The second error is the error of position and orientation of the retroreflective markers of a static calibration object. The real co-ordinates of the two objects are calibrated in a co-ordinate measuring machine (CMM). The OrthoBio system is used to validate the new calibration procedure. Results are 90% lower than those from the previous calibration software and broadly comparable with results from a similarly configured Vicon system.
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Chen, Xinhui; Bushman, Lane R; McAllister, Kevin J; Anderson, Peter L; Kiser, Jennifer J
2014-12-01
The purpose of this study was to validate a reversed-phase high-performance liquid chromatographic (HPLC), tandem mass spectrometry (MS/MS) assay for the determination of telaprevir and its R-diastereomer (VRT-127394) in acidified and nonacidified human plasma. The chromatographic baseline separation of telaprevir and telaprevir-R was performed on a Waters XBridge(TM) BEH Shield C18 , 2.1 × 75 mm column with a 2.5 µm particle size, under isocratic conditions consisting of a mobile phase of 50:45:5 water-acetonitrile-isopropanol with 1% ammonia at 0.2 mL/min. This method utilized a stable isotope internal standard with 11 deuterium atoms on the structure of the telaprevir molecule (telaprevir-d11). An internal standard for the telaprevir-R (telaprevir-R-d11) was also prepared by incubating telaprevir-d11 in basic solution, which facilitated isomer inter-conversion. The detection and quantitation of telaprevir, telaprevir-R, telaprevir-IS and telaprevir-R-IS was achieved by positive ion electrospray (ESI+) MS/MS detection. The assay quantifiable limit was 5.0 ng/mL when 0.100 mL of acidified human plasma was extracted. Accuracy and precision were validated over the calibration range of 5.0-5000 ng/mL. It was demonstrated using patient samples that, contrary to previous recommendations, quantitation of telaprevir does not require acidified plasma. Copyright © 2014 John Wiley & Sons, Ltd.
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Agnihotri, Samira; Sundeep, P. V. D. S.; Seelamantula, Chandra Sekhar; Balakrishnan, Rohini
2014-01-01
Objective identification and description of mimicked calls is a primary component of any study on avian vocal mimicry but few studies have adopted a quantitative approach. We used spectral feature representations commonly used in human speech analysis in combination with various distance metrics to distinguish between mimicked and non-mimicked calls of the greater racket-tailed drongo, Dicrurus paradiseus and cross-validated the results with human assessment of spectral similarity. We found that the automated method and human subjects performed similarly in terms of the overall number of correct matches of mimicked calls to putative model calls. However, the two methods also misclassified different subsets of calls and we achieved a maximum accuracy of ninety five per cent only when we combined the results of both the methods. This study is the first to use Mel-frequency Cepstral Coefficients and Relative Spectral Amplitude - filtered Linear Predictive Coding coefficients to quantify vocal mimicry. Our findings also suggest that in spite of several advances in automated methods of song analysis, corresponding cross-validation by humans remains essential. PMID:24603717
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Andersen, Michael P; Nielsen, Karin K
2003-05-05
A sensitive and specific LC/MS/MS method has been developed and validated for determination of ragaglitazar (NNC 61-0029 or DRF 2725) in human plasma. After solid-phase extraction (SPEC((R)) PLUS C(8)) of plasma, separation was performed on a Symmetry Shield RP8 column (mobile phase: acetonitrile: 10 mM ammonium acetate, pH 5.6 (40:60 v/v)). Two ranges were validated having LLOQs of either 0.500 or 100 ng/ml and linearity up to either 500 or 50000 ng/ml. The intra-assay precision and accuracy were 1.1% to 15.7% and 85.8% to 118.2% (range 0.500-500 ng/ml) and 2.0% to 8.8% and 92.9% to 104.8% (range 100-50000 ng/ml). The method was applied for determination of ragaglitazar in plasma from phase 1 and 2 clinical studies.
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Wearable ECG Based on Impulse-Radio-Type Human Body Communication.
Wang, Jianqing; Fujiwara, Takuya; Kato, Taku; Anzai, Daisuke
2016-09-01
Human body communication (HBC) provides a promising physical layer for wireless body area networks (BANs) in healthcare and medical applications, because of its low propagation loss and high security characteristics. In this study, we have developed a wearable electrocardiogram (ECG) which employs impulse radio (IR)-type HBC technology for transmitting vital signals on the human body in a wearable BAN scenario. The HBC-based wearable ECG has two excellent features. First, the wideband performance of the IR scheme contributed to very low radiation power so that the transceiver is easy to satisfy the extremely weak radio laws, which does not need a license. This feature can provide big convenience in the use and spread of the wearable ECG. Second, the realization of common use of sensing and transmitting electrodes based on time sharing and capacitive coupling largely simplified the HBC-based ECG structure and contributed to its miniaturization. To verify the validity of the HBC-based ECG, we evaluated its communication performance and ECG acquisition performance. The measured bit error rate, smaller than 10 -3 at 1.25 Mb/s, showed a good physical layer communication performance, and the acquired ECG waveform and various heart-rate variability parameters in time and frequency domains exhibited good agreement with a commercially available radio-frequency ECG and a Holter ECG. These results sufficiently showed the validity and feasibility of the HBC-based ECG for healthcare applications. This should be the first time to have realized a real-time ECG transmission by using the HBC technology.
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HFE safety reviews of advanced nuclear power plant control rooms
NASA Technical Reports Server (NTRS)
Ohara, John
1994-01-01
Advanced control rooms (ACR's) will utilize human-system interface (HSI) technologies that may have significant implications for plant safety in that they will affect the operator's overall role and means of interacting with the system. The Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) aspects of HSI's to ensure that they are designed to good HFE principles and support performance and reliability in order to protect public health and safety. However, the only available NRC guidance was developed more than ten years ago, and does not adequately address the human performance issues and technology changes associated with ACR's. Accordingly, a new approach to ACR safety reviews was developed based upon the concept of 'convergent validity'. This approach to ACR safety reviews is described.
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Human Health Countermeasures (HHC) Element Management Plan: Human Research Program. Revision B
NASA Technical Reports Server (NTRS)
Norsk, Peter; Baumann, David
2012-01-01
NASA s Human Research Program (HRP) is an applied research and technology program within the Human Exploration and Operations Mission Directorate (HEOMD) that addresses human health and performance risk mitigation strategies in support of exploration missions. The HRP research and technology development is focused on the highest priority risks to crew health and safety with the goal of ensuring mission success and maintaining long-term crew health. Crew health and performance standards, defined by the NASA Chief Health and Medical Officer (CHMO), set the acceptable risk level for exploration missions. The HRP conducts research to inform these standards as well as provide deliverables, such as countermeasures, that ensure standards can be met to maximize human performance and mission success. The Human Health Countermeasures (HHC) Element was formed as part of the HRP to develop a scientifically-based, integrated approach to understanding and mitigating the health risks associated with human spaceflight. These health risks have been organized into four research portfolios that group similar or related risks. A fifth portfolio exists for managing technology developments and infrastructure projects. The HHC Element portfolios consist of: a) Vision and Cardiovascular; b) Exercise and Performance; c) Multisystem; d) Bone; and e) Technology and Infrastructure. The HHC identifies gaps associated with the health risks and plans human physiology research that will result in knowledge required to more fully understand risks and will result in validated countermeasures to mitigate risks.
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Hogan, Michael P; Pace, David E; Hapgood, Joanne; Boone, Darrell C
2006-11-01
Situation awareness (SA) is defined as the perception of elements in the environment within a volume of time and space, the comprehension of their meaning, and the projection of their status in the near future. This construct is vital to decision making in intense, dynamic environments. It has been used in aviation as it relates to pilot performance, but has not been applied to medical education. The most widely used objective tool for measuring trainee SA is the Situation Awareness Global Assessment Technique (SAGAT). The purpose of this study was to design and validate SAGAT for assessment of practical trauma skills, and to compare SAGAT results to traditional checklist style scoring. Using the Human Patient Simulator, we designed SAGAT for practical trauma skills assessment based on Advanced Trauma Life Support objectives. Sixteen subjects (four staff surgeons, four senior residents, four junior residents, and four medical students) participated in three scenarios each. They were assessed using SAGAT and traditional checklist assessment. A questionnaire was used to assess possible confounding factors in attaining SA and overall trainee satisfaction. SAGAT was found to show significant difference (analysis of variance; p < 0.001) in scores based on level of training lending statistical support to construct validity. SAGAT was likewise found to display reliability (Cronbach's alpha 0.767), and significant scoring correlation with traditional checklist performance measures (Pearson's coefficient 0.806). The questionnaire revealed no confounding factors and universal satisfaction with the human patient simulator and SAGAT. SAGAT is a valid, reliable assessment tool for trauma trainees in the dynamic clinical environment created by human patient simulation. Information provided by SAGAT could provide specific feedback, direct individualized teaching, and support curriculum change. Introduction of SAGAT could improve the current assessment model for practical trauma education.
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Can Visual Arts Training Improve Physician Performance?
Katz, Joel T.; Khoshbin, Shahram
2014-01-01
Clinical educators use medical humanities as a means to improve patient care by training more self-aware, thoughtful, and collaborative physicians. We present three examples of integrating fine arts — a subset of medical humanities — into the preclinical and clinical training as models that can be adapted to other medical environments to address a wide variety of perceived deficiencies. This novel teaching method has promise to improve physician skills, but requires further validation. PMID:25125749
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Modeling Visual, Vestibular and Oculomotor Interactions in Self-Motion Estimation
NASA Technical Reports Server (NTRS)
Perrone, John
1997-01-01
A computational model of human self-motion perception has been developed in collaboration with Dr. Leland S. Stone at NASA Ames Research Center. The research included in the grant proposal sought to extend the utility of this model so that it could be used for explaining and predicting human performance in a greater variety of aerospace applications. This extension has been achieved along with physiological validation of the basic operation of the model.
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Digital Systems Validation Handbook. Volume 2
1992-07-01
imitate human intelligence functions. ASSURANCE ASSESSMENT. (4) Procedures whose purpose is to ensure that a proposed system functions according to...The spectrum (20 to 20,000 Hz) of human hearing, often defined as extending from approximately 20 Hz to 50 kHz and sometimes to 150 kHz. Audio noise...contained body of code which can be called by other routines to perform a function. SUPER-DIAGNOSTIC FILTER. (7) An algorithm which provides all the
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1987-10-01
PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT, TASK Human Resources Research Organization 2 P 3 QA2 79 9"INiTNUMBERS 1100...classification tests which will validly predict carefully developed measures of job performance . The project addresses the 675,000-person enlisted personnel...are to include both Army-wide job performance measures based on newly developed rating scales, and direct hands-on measures of MOS-specific task
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Hubert, C; Houari, S; Rozet, E; Lebrun, P; Hubert, Ph
2015-05-22
When using an analytical method, defining an analytical target profile (ATP) focused on quantitative performance represents a key input, and this will drive the method development process. In this context, two case studies were selected in order to demonstrate the potential of a quality-by-design (QbD) strategy when applied to two specific phases of the method lifecycle: the pre-validation study and the validation step. The first case study focused on the improvement of a liquid chromatography (LC) coupled to mass spectrometry (MS) stability-indicating method by the means of the QbD concept. The design of experiments (DoE) conducted during the optimization step (i.e. determination of the qualitative design space (DS)) was performed a posteriori. Additional experiments were performed in order to simultaneously conduct the pre-validation study to assist in defining the DoE to be conducted during the formal validation step. This predicted protocol was compared to the one used during the formal validation. A second case study based on the LC/MS-MS determination of glucosamine and galactosamine in human plasma was considered in order to illustrate an innovative strategy allowing the QbD methodology to be incorporated during the validation phase. An operational space, defined by the qualitative DS, was considered during the validation process rather than a specific set of working conditions as conventionally performed. Results of all the validation parameters conventionally studied were compared to those obtained with this innovative approach for glucosamine and galactosamine. Using this strategy, qualitative and quantitative information were obtained. Consequently, an analyst using this approach would be able to select with great confidence several working conditions within the operational space rather than a given condition for the routine use of the method. This innovative strategy combines both a learning process and a thorough assessment of the risk involved. Copyright © 2015 Elsevier B.V. All rights reserved.
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Integrated Testing Approaches for the NASA Ares I Crew Launch Vehicle
NASA Technical Reports Server (NTRS)
Taylor, James L.; Cockrell, Charles E.; Tuma, Margaret L.; Askins, Bruce R.; Bland, Jeff D.; Davis, Stephan R.; Patterson, Alan F.; Taylor, Terry L.; Robinson, Kimberly L.
2008-01-01
The Ares I crew launch vehicle is being developed by the U.S. National Aeronautics and Space Administration (NASA) to provide crew and cargo access to the International Space Station (ISS) and, together with the Ares V cargo launch vehicle, serves as a critical component of NASA's future human exploration of the Moon. During the preliminary design phase, NASA defined and began implementing plans for integrated ground and flight testing necessary to achieve the first human launch of Ares I. The individual Ares I flight hardware elements - including the first stage five segment booster (FSB), upper stage, and J-2X upper stage engine - will undergo extensive development, qualification, and certification testing prior to flight. Key integrated system tests include the upper stage Main Propulsion Test Article (MPTA), acceptance tests of the integrated upper stage and upper stage engine assembly, a full-scale integrated vehicle ground vibration test (IVGVT), aerodynamic testing to characterize vehicle performance, and integrated testing of the avionics and software components. The Ares I-X development flight test will provide flight data to validate engineering models for aerodynamic performance, stage separation, structural dynamic performance, and control system functionality. The Ares I-Y flight test will validate ascent performance of the first stage, stage separation functionality, validate the ability of the upper stage to manage cryogenic propellants to achieve upper stage engine start conditions, and a high-altitude demonstration of the launch abort system (LAS) following stage separation. The Orion 1 flight test will be conducted as a full, un-crewed, operational flight test through the entire ascent flight profile prior to the first crewed launch.
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Lin, Yuanjie; Feng, Chao; Xu, Qian; Lu, Dasheng; Qiu, Xinlei; Jin, Yu'e; Wang, Guoquan; Wang, Dongli; She, Jianwen; Zhou, Zhijun
2016-07-01
An improved method based on tandem solid phase extraction (SPE) cleanup and gas chromatography-high resolution mass spectrometry (GC-HRMS) has been validated for a rapid determination of dibenzo-p-dioxins/furans (PCDD/Fs), dioxin-like polychlorinated biphenyls (PCBs), marker polychlorinated biphenyls (M-PCBs), and polybrominated diphenyl ethers (PBDEs) using a large volume (50 mL) of human milk. This method was well validated for the measurement of these analytes in human milk from the general population with low limits of detection (LODs, 0.004-0.12 ng/g lipid), satisfactory accuracy (75-120 % of recoveries), and precision [less than 10 % of relative standard deviations (RSDs)]. To comprehensively evaluate the performance of this method, a good, presently validated and routinely used method based on an automated sample clean-up system (ASCS, based on the commercial acid multilayer silica, basic alumina, and carbon columns) was used in parallel for comparison. Compared with the ASCS method, this method presented comparable specificity. Additionally, this method, in contrast to ASCS method, highly reduced consumption of solvents (40 mL versus 500 mL), which results in much lower background in the procedural blank, reduced time, and enhanced sample pretreatment throughput. This method was also applied in a pilot study to measure a batch of human milk samples with satisfactory results. Graphical Abstract Characteristics of the application of tandem SPE cleanup for determination of PCDD/Fs, DL-PCBs,M-PCBs and PBDEs in human milk.
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Comfort, Shaun; Perera, Sujan; Hudson, Zoe; Dorrell, Darren; Meireis, Shawman; Nagarajan, Meenakshi; Ramakrishnan, Cartic; Fine, Jennifer
2018-06-01
There is increasing interest in social digital media (SDM) as a data source for pharmacovigilance activities; however, SDM is considered a low information content data source for safety data. Given that pharmacovigilance itself operates in a high-noise, lower-validity environment without objective 'gold standards' beyond process definitions, the introduction of large volumes of SDM into the pharmacovigilance workflow has the potential to exacerbate issues with limited manual resources to perform adverse event identification and processing. Recent advances in medical informatics have resulted in methods for developing programs which can assist human experts in the detection of valid individual case safety reports (ICSRs) within SDM. In this study, we developed rule-based and machine learning (ML) models for classifying ICSRs from SDM and compared their performance with that of human pharmacovigilance experts. We used a random sampling from a collection of 311,189 SDM posts that mentioned Roche products and brands in combination with common medical and scientific terms sourced from Twitter, Tumblr, Facebook, and a spectrum of news media blogs to develop and evaluate three iterations of an automated ICSR classifier. The ICSR classifier models consisted of sub-components to annotate the relevant ICSR elements and a component to make the final decision on the validity of the ICSR. Agreement with human pharmacovigilance experts was chosen as the preferred performance metric and was evaluated by calculating the Gwet AC1 statistic (gKappa). The best performing model was tested against the Roche global pharmacovigilance expert using a blind dataset and put through a time test of the full 311,189-post dataset. During this effort, the initial strict rule-based approach to ICSR classification resulted in a model with an accuracy of 65% and a gKappa of 46%. Adding an ML-based adverse event annotator improved the accuracy to 74% and gKappa to 60%. This was further improved by the addition of an additional ML ICSR detector. On a blind test set of 2500 posts, the final model demonstrated a gKappa of 78% and an accuracy of 83%. In the time test, it took the final model 48 h to complete a task that would have taken an estimated 44,000 h for human experts to perform. The results of this study indicate that an effective and scalable solution to the challenge of ICSR detection in SDM includes a workflow using an automated ML classifier to identify likely ICSRs for further human SME review.
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Freyberger, Alexius; Wilson, Vickie; Weimer, Marc; Tan, Shirlee; Tran, Hoai-Son; Ahr, Hans-Jürgen
2010-08-01
Despite about two decades of research in the field of endocrine active compounds, still no validated human recombinant (hr) estrogen receptor-alpha (ERalpha) binding assay is available, although hr-ERalpha is available from several sources. In a joint effort, US EPA and Bayer Schering Pharma with funding from the EU-sponsored 6th framework project, ReProTect, developed a model protocol for such a binding assay. Important features of this assay are the use of a full length hr-ERalpha and performance in a 96-well plate format. A full length hr-ERalpha was chosen, as it was considered to provide the most accurate and human-relevant results, whereas truncated receptors could perform differently. Besides three reference compounds [17beta-estradiol, norethynodrel, dibutylphthalate] nine test compounds with different affinities for the ERalpha [diethylstilbestrol (DES), ethynylestradiol, meso-hexestrol, equol, genistein, o,p'-DDT, nonylphenol, n-butylparaben, and corticosterone] were used to explore the performance of the assay. Three independent experiments per compound were performed on different days, and dilutions of test compounds from deep-frozen stocks, solutions of radiolabeled ligand and receptor preparation were freshly prepared for each experiment. The ERalpha binding properties of reference and test compounds were well detected. As expected dibutylphthalate and corticosterone were non-binders in this assay. In terms of the relative ranking of binding affinities, there was good agreement with published data obtained from experiments using a human recombinant ERalpha ligand binding domain. Irrespective of the chemical nature of the compound, individual IC(50)-values for a given compound varied by not more than a factor of 2.5. Our data demonstrate that the assay was robust and reliably ranked compounds with strong, weak, and no affinity for the ERalpha with high accuracy. It avoids the manipulation and use of animals, i.e., the preparation of uterine cytosol as receptor source from ovariectomized rats, as a recombinant protein is used and thus contributes to the 3R concept (reduce, replace, and refine). Furthermore, in contrast to other assays, this assay could be adjusted to an intermediate/high throughput format. On the whole, this assay is a promising candidate for further validation. Copyright 2010 Elsevier Inc. All rights reserved.
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First validation of the PASSPORT training environment for arthroscopic skills.
Tuijthof, Gabriëlle J M; van Sterkenburg, Maayke N; Sierevelt, Inger N; van Oldenrijk, Jakob; Van Dijk, C Niek; Kerkhoffs, Gino M M J
2010-02-01
The demand for high quality care is in contrast to reduced training time for residents to develop arthroscopic skills. Thereto, simulators are introduced to train skills away from the operating room. In our clinic, a physical simulation environment to Practice Arthroscopic Surgical Skills for Perfect Operative Real-life Treatment (PASSPORT) is being developed. The PASSPORT concept consists of maintaining the normal arthroscopic equipment, replacing the human knee joint by a phantom, and integrating registration devices to provide performance feedback. The first prototype of the knee phantom allows inspection, treatment of menisci, irrigation, and limb stressing. PASSPORT was evaluated for face and construct validity. Construct validity was assessed by measuring the performance of two groups with different levels of arthroscopic experience (20 surgeons and 8 residents). Participants performed a navigation task five times on PASSPORT. Task times were recorded. Face validity was assessed by completion of a short questionnaire on the participants' impressions and comments for improvements. Construct validity was demonstrated as the surgeons (median task time 19.7 s [8.0-37.6]) were more efficient than the residents (55.2 s [27.9-96.6]) in task completion for each repetition (Mann-Whitney U test, P < 0.05). The prototype of the knee phantom sufficiently imitated limb outer appearance (79%), portal resistance (82%), and arthroscopic view (81%). Improvements are required for the stressing device and the material of cruciate ligaments. Our physical simulation environment (PASSPORT) demonstrates its potential to evolve as a training modality. In future, automated performance feedback is aimed for.
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False-positive pregnancy test after transfusion of solvent/detergent-treated plasma.
Jilma-Stohlawetz, Petra; Wreford-Bush, Tim; Mills, Francesca; Davidson, Fiona; Kursten, Friedrich W; Jilma, Bernd; Birchall, Janet
2017-12-01
The transmission of pathogens, antibodies, and proteins is a possible consequence of blood product transfusion. A female patient had an unexpected positive serum β-human chorionic gonadotropin result, indicative of pregnancy, after she had received a transfusion with 1 unit of platelet concentrate, 4 units of red blood cells, and 4 units of pooled solvent/detergent-treated plasma (Octaplas). To investigate the possibility of passive transfusion of β-human chorionic gonadotropin from the plasma transfusion, one additional unit from the same batch was thawed and analyzed. To validate the β-human chorionic gonadotropin assay for use in solvent/detergent-treated plasma and to investigate any interference in the assay, dilution experiments were performed using the implicated plasma batch diluted with male and non-pregnant female sera. Also, plasma from a known pregnant woman was diluted with Octaplas (tested negative for β-human chorionic gonadotropin) and with a male serum to validate the assay for use in solvent/detergent-treated plasma. The implicated solvent/detergent-treated plasma had a mean β-human chorionic gonadotropin level of 91.5 mIU/mL. Results from the dilution experiments revealed an excellent correlation (r > 0.99) between β-human chorionic gonadotropin measurement in solvent/detergent-treated plasma and male serum and no over or under recovery of the expected results. Further measurements of β-human chorionic gonadotropin levels in the female recipient revealed an estimated half-life of 6 hours. This case demonstrates the importance of considering the possibility of passive transmission of analytes to a patient from the transfusion of blood products. Furthermore, the measurement of β-human chorionic gonadotropin is valid in solvent/detergent-treated plasma using a Roche Cobas analyzer. © 2017 AABB.
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Zhou, Ying; Jiang, Ji; Hu, Pei; Wang, Hongyun
2014-12-01
A rapid, simple and validated method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has been developed for the determination of granisetron in human plasma. Plasma samples were pre-purified by protein precipitation procedure. The chromatographic separation was achieved with Synergi Polar-RP (75 × 2 mm, 4 µm) column using a mixture of 5 mm pH4.0 ammonium formate and methanol (300:316, v/v) under isocratic conditions at a flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. The analysis time was about 2.5 min. The method was fully validated over the concentration range 0.1-10 ng/mL. The lower limit of quantification was 0.1 ng/mL. Inter- and intra-batch precision was <6.1% and the accuracy was within 95.6-100.0%. The mean extraction recovery was 96.3%. Selectivity, matrix effect and stability were also validated. The method was applied to the comparative pharmacokinetic study of granisetron in Chinese healthy subjects. Copyright © 2014 John Wiley & Sons, Ltd.
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Towards natural language question generation for the validation of ontologies and mappings.
Ben Abacha, Asma; Dos Reis, Julio Cesar; Mrabet, Yassine; Pruski, Cédric; Da Silveira, Marcos
2016-08-08
The increasing number of open-access ontologies and their key role in several applications such as decision-support systems highlight the importance of their validation. Human expertise is crucial for the validation of ontologies from a domain point-of-view. However, the growing number of ontologies and their fast evolution over time make manual validation challenging. We propose a novel semi-automatic approach based on the generation of natural language (NL) questions to support the validation of ontologies and their evolution. The proposed approach includes the automatic generation, factorization and ordering of NL questions from medical ontologies. The final validation and correction is performed by submitting these questions to domain experts and automatically analyzing their feedback. We also propose a second approach for the validation of mappings impacted by ontology changes. The method exploits the context of the changes to propose correction alternatives presented as Multiple Choice Questions. This research provides a question optimization strategy to maximize the validation of ontology entities with a reduced number of questions. We evaluate our approach for the validation of three medical ontologies. We also evaluate the feasibility and efficiency of our mappings validation approach in the context of ontology evolution. These experiments are performed with different versions of SNOMED-CT and ICD9. The obtained experimental results suggest the feasibility and adequacy of our approach to support the validation of interconnected and evolving ontologies. Results also suggest that taking into account RDFS and OWL entailment helps reducing the number of questions and validation time. The application of our approach to validate mapping evolution also shows the difficulty of adapting mapping evolution over time and highlights the importance of semi-automatic validation.
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Kruse, Niels; Mollenhauer, Brit
2015-11-01
The quantification of α-Synuclein in cerebrospinal fluid (CSF) as a biomarker has gained tremendous interest in the last years. Several commercially available immunoassays are emerging. We here describe the full validation of one commercially available ELISA assay for the quantification of α-Synuclein in human CSF (Covance alpha-Synuclein ELISA kit). The study was conducted within the BIOMARKAPD project in the European initiative Joint Program for Neurodegenerative Diseases (JPND). We investigated the effect of several pre-analytical and analytical confounders: i.e. (1) need for centrifugation of freshly drawn CSF, (2) sample stability, (3) delay of freezing, (4) volume of storage aliquots, (5) freeze/thaw cycles, (6) thawing conditions, (7) dilution linearity, (8) parallelism, (9) spike recovery, and (10) precision. None of these confounders influenced the levels of α-Synuclein in CSF significantly. We found a very high intra-assay precision. The inter-assay precision was lower than expected due to different performances of kit lots used. Overall the validated immunoassay is useful for the quantification of α-Synuclein in human CSF. Copyright © 2015 Elsevier B.V. All rights reserved.
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A Unified Model of Performance: Validation of its Predictions across Different Sleep/Wake Schedules
Ramakrishnan, Sridhar; Wesensten, Nancy J.; Balkin, Thomas J.; Reifman, Jaques
2016-01-01
Study Objectives: Historically, mathematical models of human neurobehavioral performance developed on data from one sleep study were limited to predicting performance in similar studies, restricting their practical utility. We recently developed a unified model of performance (UMP) to predict the effects of the continuum of sleep loss—from chronic sleep restriction (CSR) to total sleep deprivation (TSD) challenges—and validated it using data from two studies of one laboratory. Here, we significantly extended this effort by validating the UMP predictions across a wide range of sleep/wake schedules from different studies and laboratories. Methods: We developed the UMP on psychomotor vigilance task (PVT) lapse data from one study encompassing four different CSR conditions (7 d of 3, 5, 7, and 9 h of sleep/night), and predicted performance in five other studies (from four laboratories), including different combinations of TSD (40 to 88 h), CSR (2 to 6 h of sleep/night), control (8 to 10 h of sleep/night), and nap (nocturnal and diurnal) schedules. Results: The UMP accurately predicted PVT performance trends across 14 different sleep/wake conditions, yielding average prediction errors between 7% and 36%, with the predictions lying within 2 standard errors of the measured data 87% of the time. In addition, the UMP accurately predicted performance impairment (average error of 15%) for schedules (TSD and naps) not used in model development. Conclusions: The unified model of performance can be used as a tool to help design sleep/wake schedules to optimize the extent and duration of neurobehavioral performance and to accelerate recovery after sleep loss. Citation: Ramakrishnan S, Wesensten NJ, Balkin TJ, Reifman J. A unified model of performance: validation of its predictions across different sleep/wake schedules. SLEEP 2016;39(1):249–262. PMID:26518594
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Human Research Program Requirements Document (Revision C)
NASA Technical Reports Server (NTRS)
Vargas, Paul R.
2009-01-01
The purpose of this document is to define, document, and allocate the Human Research Program (HRP) requirements to the HRP Program Elements. It establishes the flow-down of requirements from Exploration Systems Mission Directorate (ESMD) and Office of the Chief Health and Medical Officer (OCHMO) to the various Program Elements of the HRP to ensure that human research and technology countermeasure investments are made to insure the delivery of countermeasures and technologies that satisfy ESMD's and OCHMO's exploration mission requirements. Requirements driving the HRP work and deliverables are derived from the exploration architecture, as well as Agency standards regarding the maintenance of human health and performance. Agency human health and performance standards will define acceptable risk for each type and duration of exploration mission. It is critical to have the best available scientific and clinical evidence in setting and validating these standards. In addition, it is imperative that the best available evidence on preventing and mitigating human health and performance risks is incorporated into exploration mission and vehicle designs. These elements form the basis of the HRP research and technology development requirements and highlight the importance of HRP investments in enabling NASA's exploration missions. This PRD defines the requirements of the HRP which is comprised of the following major Program Elements: Behavioral Health and Performance (BHP), Exploration Medical Capability (ExMC), Human Health Countermeasures (HHC), ISS Medical Project (ISSMP), Space Human Factors and Habitability (SHFH), and Space Radiation (SR).
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Tabacu, Stefan
2015-01-01
In this paper, a methodology for the development and validation of a numerical model of the human head using generic procedures is presented. All steps required, starting with the model generation, model validation and applications will be discussed. The proposed model may be considered as a dual one due to its capabilities to switch from deformable to a rigid body according to the application's requirements. The first step is to generate the numerical model of the human head using geometry files or medical images. The required stiffness and damping for the elastic connection used for the rigid body model are identified by performing a natural frequency analysis. The presented applications for model validation are related to impact analysis. The first case is related to Nahum's (Nahum and Smith 1970) experiments pressure data being evaluated and a pressure map generated using the results from discrete elements. For the second case, the relative displacement between the brain and the skull is evaluated according to Hardy's (Hardy WH, Foster CD, Mason, MJ, Yang KH, King A, Tashman S. 2001.Investigation of head injury mechanisms using neutral density technology and high-speed biplanar X-ray. Stapp Car Crash J. 45:337-368, SAE Paper 2001-22-0016) experiments. The main objective is to validate the rigid model as a quick and versatile tool for acquiring the input data for specific brain analyses.
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Haraksingh, Rajini R.; Abyzov, Alexej; Gerstein, Mark; Urban, Alexander E.; Snyder, Michael
2011-01-01
Accurate and efficient genome-wide detection of copy number variants (CNVs) is essential for understanding human genomic variation, genome-wide CNV association type studies, cytogenetics research and diagnostics, and independent validation of CNVs identified from sequencing based technologies. Numerous, array-based platforms for CNV detection exist utilizing array Comparative Genome Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) genotyping or both. We have quantitatively assessed the abilities of twelve leading genome-wide CNV detection platforms to accurately detect Gold Standard sets of CNVs in the genome of HapMap CEU sample NA12878, and found significant differences in performance. The technologies analyzed were the NimbleGen 4.2 M, 2.1 M and 3×720 K Whole Genome and CNV focused arrays, the Agilent 1×1 M CGH and High Resolution and 2×400 K CNV and SNP+CGH arrays, the Illumina Human Omni1Quad array and the Affymetrix SNP 6.0 array. The Gold Standards used were a 1000 Genomes Project sequencing-based set of 3997 validated CNVs and an ultra high-resolution aCGH-based set of 756 validated CNVs. We found that sensitivity, total number, size range and breakpoint resolution of CNV calls were highest for CNV focused arrays. Our results are important for cost effective CNV detection and validation for both basic and clinical applications. PMID:22140474
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Takamura, Ayari; Watanabe, Ken; Akutsu, Tomoko
2017-07-01
Identification of human semen is indispensable for the investigation of sexual assaults. Fluorescence staining methods using commercial kits, such as the series of SPERM HY-LITER™ kits, have been useful to detect human sperm via strong fluorescence. These kits have been examined from various forensic aspects. However, because of a lack of evaluation methods, these studies did not provide objective, or quantitative, descriptions of the results nor clear criteria for the decisions reached. In addition, the variety of validations was considerably limited. In this study, we conducted more advanced validations of SPERM HY-LITER™ Express using our established image analysis method. Use of this method enabled objective and specific identification of fluorescent sperm's spots and quantitative comparisons of the sperm detection performance under complex experimental conditions. For body fluid mixtures, we examined interference with the fluorescence staining from other body fluid components. Effects of sample decomposition were simulated in high humidity and high temperature conditions. Semen with quite low sperm concentrations, such as azoospermia and oligospermia samples, represented the most challenging cases in application of the kit. Finally, the tolerance of the kit against various acidic and basic environments was analyzed. The validations herein provide useful information for the practical applications of the SPERM HY-LITER™ Express kit, which were previously unobtainable. Moreover, the versatility of our image analysis method toward various complex cases was demonstrated.
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Boutet, Isabelle; Collin, Charles A; MacLeod, Lindsey S; Messier, Claude; Holahan, Matthew R; Berry-Kravis, Elizabeth; Gandhi, Reno M; Kogan, Cary S
2018-01-01
To generate meaningful information, translational research must employ paradigms that allow extrapolation from animal models to humans. However, few studies have evaluated translational paradigms on the basis of defined validation criteria. We outline three criteria for validating translational paradigms. We then evaluate the Hebb-Williams maze paradigm (Hebb and Williams, 1946; Rabinovitch and Rosvold, 1951) on the basis of these criteria using Fragile X syndrome (FXS) as model disease. We focused on this paradigm because it allows direct comparison of humans and animals on tasks that are behaviorally equivalent (criterion #1) and because it measures spatial information processing, a cognitive domain for which FXS individuals and mice show impairments as compared to controls (criterion #2). We directly compared the performance of affected humans and mice across different experimental conditions and measures of behavior to identify which conditions produce comparable patterns of results in both species. Species differences were negligible for Mazes 2, 4, and 5 irrespective of the presence of visual cues, suggesting that these mazes could be used to measure spatial learning in both species. With regards to performance on the first trial, which reflects visuo-spatial problem solving, Mazes 5 and 9 without visual cues produced the most consistent results. We conclude that the Hebb-Williams mazes paradigm has the potential to be utilized in translational research to measure comparable cognitive functions in FXS humans and animals (criterion #3).
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Predictive models of safety based on audit findings: Part 1: Model development and reliability.
Hsiao, Yu-Lin; Drury, Colin; Wu, Changxu; Paquet, Victor
2013-03-01
This consecutive study was aimed at the quantitative validation of safety audit tools as predictors of safety performance, as we were unable to find prior studies that tested audit validity against safety outcomes. An aviation maintenance domain was chosen for this work as both audits and safety outcomes are currently prescribed and regulated. In Part 1, we developed a Human Factors/Ergonomics classification framework based on HFACS model (Shappell and Wiegmann, 2001a,b), for the human errors detected by audits, because merely counting audit findings did not predict future safety. The framework was tested for measurement reliability using four participants, two of whom classified errors on 1238 audit reports. Kappa values leveled out after about 200 audits at between 0.5 and 0.8 for different tiers of errors categories. This showed sufficient reliability to proceed with prediction validity testing in Part 2. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.
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Multivariate Modelling of the Career Intent of Air Force Personnel.
1980-09-01
index (HOPP) was used as a measure of current job satisfaction . As with the Vroom and Fishbein/Graen models, two separate validations were accom...34 Organizational Behavior and Human Performance , 23: 251-267, 1979. Lewis, Logan M. "Expectancy Theory as a Predictive Model of Career Intent, Job Satisfaction ...W. Albright. "Expectancy Theory Predictions of the Satisfaction , Effort, Performance , and Retention of Naval Aviation Officers," Organizational
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Rood, Johannes J M; van Bussel, Mark T J; Schellens, Jan H M; Beijnen, Jos H; Sparidans, Rolf W
2016-09-15
A method for the quantitative analysis by ultra-performance liquid chromatography-tandem mass spectrometry of the highly selective irreversible covalent inhibitor of EGFR-TK, osimertinib in human plasma was developed and validated, using pazopanib as an internal standard. The validation was performed in a range from 1 to 1000ng/ml, with the lowest level corresponding to the lower limit of quantitation. Gradient elution was performed on a 1.8μm particle trifunctional bonded C18 column by 1% (v/v) formic acid in water, and acetonitrile as mobile phase. The analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer after positive ionization with the heated electrospray interface. Within-day precisions ranged from 3.4 to 10.3%, and between-day precisions from 3.8 to 10.4%, accuracies were 95.5-102.8%. Plasma (either lithium heparin or sodium EDTA) pretreatment was performed by salting-out assisted liquid-liquid extraction using acetonitrile and magnesium sulfate. This method was used to analyze the osimertinib blood plasma levels of five adult patients with metastatic T790M mutated non-small cellular lung carcinoma for therapeutic drug monitoring purposes. Copyright © 2016 Elsevier B.V. All rights reserved.
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Validation of a Cost-Efficient Multi-Purpose SNP Panel for Disease Based Research
Hou, Liping; Phillips, Christopher; Azaro, Marco; Brzustowicz, Linda M.; Bartlett, Christopher W.
2011-01-01
Background Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA “barcoding” to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies. Principal Findings Empirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the “barcode.” Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel. Conclusion The panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping our specific assay contained herein, this panel represents a useful and economical panel for human geneticists. PMID:21611176
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Thomas, Emily; Murphy, Mary; Pitt, Rebecca; Rivers, Angela; Leavens, David A
2008-11-01
Povinelli, Bierschwale, and Cech (1999) reported that when tested on a visual attention task, the behavior of juvenile chimpanzees did not support a high-level understanding of visual attention. This study replicates their research using adult humans and aims to investigate the validity of their experimental design. Participants were trained to respond to pointing cues given by an experimenter, and then tested on their ability to locate hidden objects from visual cues. Povinelli et al.'s assertion that the generalization of pointing to gaze is indicative of a high-level framework was not supported by our findings: Training improved performance only on initial probe trials when the experimenter's gaze was not directed at the baited cup. Furthermore, participants performed above chance on such trials, the same result exhibited by chimpanzees and used as evidence by Povinelli et al. to support a low-level framework. These findings, together with the high performance of participants in an incongruent condition, in which the experimenter pointed to or gazed at an unbaited container, challenge the validity of their experimental design. (PsycINFO Database Record (c) 2008 APA, all rights reserved).
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Human Factors Research Under Ground-Based and Space Conditions. Part 2
NASA Technical Reports Server (NTRS)
1997-01-01
In this session, Session WP2, the discussion focuses on the following topics: Training Astronauts Using Three-Dimensional Visualizations of the International Space Station; Measurement and Validation of Bidirectional Reflectance of Shuttle and Space Station Materials for Computerized Lighting Models; Effects of Environmental Color on Mood and Performance of Astronauts in ISS; Psychophysical Measures of Motion and Orientation, Implications for Human Interface Design; and the Sopite Syndrome Revisited, Drowsiness and Mood Changes in Student Aviators.
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Recent technology products from Space Human Factors research
NASA Technical Reports Server (NTRS)
Jenkins, James P.
1991-01-01
The goals of the NASA Space Human Factors program and the research carried out concerning human factors are discussed with emphasis given to the development of human performance models, data, and tools. The major products from this program are described, which include the Laser Anthropometric Mapping System; a model of the human body for evaluating the kinematics and dynamics of human motion and strength in microgravity environment; an operational experience data base for verifying and validating the data repository of manned space flights; the Operational Experience Database Taxonomy; and a human-computer interaction laboratory whose products are the display softaware and requirements and the guideline documents and standards for applications on human-computer interaction. Special attention is given to the 'Convoltron', a prototype version of a signal processor for synthesizing the head-related transfer functions.
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Qiu, Xiangjun; Lou, Dan; Su, Ding; Liu, Zebin; Gao, Pengtao; Zhang, Nan-sheng
2015-06-15
An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine acetaminophen (AAP) and dihydrocodeine (DHC) in human plasma simultaneously. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard midazolam were separated on an Acquity UPLC BEH C18 column and mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 151.2→110.0 and m/z 302.3→199.2 were used to quantify for AAP and DHC, respectively. The linearity of this method was found to be within the concentration range of 50-10000ng/mL for AAP, and 1-100ng/mL for DHC in human plasma, respectively. The lower limit of quantification (LLOQ) was 50ng/mL and 1ng/mL for AAP and DHC in human plasma, respectively. The relative standard deviations (RSD) of intra and inter precision were less than 10% for both AAP and DHC. The analysis time of per sample was 1.0min. The developed and validated method was successfully applied to a pharmacokinetic study of AAP (500mg) with DHC (20mg) capsule in Chinese healthy volunteers (N=20). Copyright © 2015 Elsevier B.V. All rights reserved.
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Tomková, Jana; Ondra, Peter; Válka, Ivo
2015-06-01
This paper presents a method for the simultaneous determination of α-amanitin, β-amanitin and muscarine in human urine by solid-phase extraction (SPE) and ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry. The method can be used for a diagnostics of mushroom poisonings. Different SPE cartridges were tested for sample preparation, namely hydrophilic modified reversed-phase (Oasis HLB) and polymeric weak cation phase (Strata X-CW). The latter gave better results and therefore it was chosen for the subsequent method optimization and partial validation. In the course of validation, limits of detection, linearity, intraday and interday precisions and recoveries were evaluated. The obtained LOD values of α-amanitin and β-amanitin were 1ng/mL and of muscarine 0.09ng/mL. The intraday and interday precisions of human urine spiked with α-amanitin (10ng/mL), β-amanitin (10ng/mL) and muscarine (1ng/mL) ranged from 6% to 10% and from 7% to 13%, respectively. The developed method was proved to be a relevant tool for the simultaneous determination of the studied mushroom toxins in human urine after mushroom poisoning. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Todd, Christopher A.; Greene, Kelli M.; Montefiori, David C.; Sarzotti-Kelsoe, Marcella
2012-01-01
The Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody – Vaccine Immune Monitoring Consortium (CAVD/CA-VIMC) assisted an international network of laboratories in transferring a validated assay used to judge HIV-1 vaccine immunogenicity in compliance with Good Clinical Laboratory Practice (GCLP) with the goal of adding quality to the conduct of endpoint assays for Human Immunodeficiency Virus I (HIV-1) vaccine human clinical trials. Eight Regional Laboratories in the international setting (Regional Laboratories), many located in regions where the HIV-1 epidemic is most prominent, were selected to implement the standardized, GCLP-compliant Neutralizing Antibody Assay for HIV-1 in TZM-bl Cells (TZM-bl NAb Assay). Each laboratory was required to undergo initial training and implementation of the immunologic assay on-site and then perform partial assay re-validation, competency testing, and undergo formal external audits for GCLP compliance. Furthermore, using a newly established external proficiency testing program for the TZM-bl NAb Assay has allowed the Regional Laboratories to assess the comparability of assay results at their site with the results of neutralizing antibody assays performed around the world. As a result, several of the CAVD/CA-VIMC Regional Laboratories are now in the process of conducting or planning to conduct the GCLP-compliant TZM-bl NAb Assay as an indicator of vaccine immunogenicity for ongoing human clinical trials. PMID:22303476
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Ozaki, Daniel A; Gao, Hongmei; Todd, Christopher A; Greene, Kelli M; Montefiori, David C; Sarzotti-Kelsoe, Marcella
2012-01-01
The Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody-Vaccine Immune Monitoring Consortium (CAVD/CA-VIMC) assisted an international network of laboratories in transferring a validated assay used to judge HIV-1 vaccine immunogenicity in compliance with Good Clinical Laboratory Practice (GCLP) with the goal of adding quality to the conduct of endpoint assays for Human Immunodeficiency Virus I (HIV-1) vaccine human clinical trials. Eight Regional Laboratories in the international setting (Regional Laboratories), many located in regions where the HIV-1 epidemic is most prominent, were selected to implement the standardized, GCLP-compliant Neutralizing Antibody Assay for HIV-1 in TZM-bl Cells (TZM-bl NAb Assay). Each laboratory was required to undergo initial training and implementation of the immunologic assay on-site and then perform partial assay re-validation, competency testing, and undergo formal external audits for GCLP compliance. Furthermore, using a newly established external proficiency testing program for the TZM-bl NAb Assay has allowed the Regional Laboratories to assess the comparability of assay results at their site with the results of neutralizing antibody assays performed around the world. As a result, several of the CAVD/CA-VIMC Regional Laboratories are now in the process of conducting or planning to conduct the GCLP-compliant TZM-bl NAb Assay as an indicator of vaccine immunogenicity for ongoing human clinical trials.
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Meyer, Markus R; Caspar, Achim; Brandt, Simon D; Maurer, Hans H
2014-01-01
The first synthetic tryptamines have entered the designer drug market in the late 1990s and were distributed as psychedelic recreational drugs. In the meantime, several analogs have been brought onto the market indicating a growing interest in this drug class. So far, only scarce analytical data were available on the detectability of tryptamines in human biosamples. Therefore, the aim of the presented study was the development and full validation of a method for their detection in human urine and plasma and their quantification in human plasma. The liquid chromatography-linear ion trap mass spectrometry method presented covered 37 tryptamines as well as five β-carbolines, ibogaine, and yohimbine. Compounds were analyzed after protein precipitation of urine or fast liquid-liquid extraction of plasma using an LXQ linear ion trap coupled to an Accela ultra ultra high-performance liquid chromatography system. Data mining was performed via information-dependent acquisition or targeted product ion scan mode with positive electrospray ionization. The assay was selective for all tested substances with limits of detection in urine between 10 and 100 ng/mL and in plasma between 1 and 100 ng/mL. A validated quantification in plasma according to international recommendation could be demonstrated for 33 out of 44 analytes.
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Validation of a Task Network Human Performance Model of Driving
2007-04-01
34 Table 23. NASA - TLX scores for study conditions...35 Table 24. ANOVA for NASA - TLX scores for study conditions (α = 0.05)...............................35 Table 25...Significant difference between conditions for NASA - TLX in the simulator study.....36 Table 26. ANOVA table for mental demand subscale of NASA - TLX
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Evaluation of Complex Human Performance: The Promise of Computer-Based Simulation
ERIC Educational Resources Information Center
Newsom, Robert S.; And Others
1978-01-01
For the training and placement of professional workers, multiple-choice instruments are the norm for wide-scale measurement and evaluation efforts. These instruments contain fundamental problems. Computer-based management simulations may provide solutions to these problems, appear scoreable and reliable, offer increased validity, and are better…
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DOT National Transportation Integrated Search
2008-11-01
Although the current crew rest and duty restrictions for commercial space transportation remain in place, the Federal Aviation Administration (FAA) continues to review the regulation on a regular basis for validity and efficacy based on input from sc...
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Techniques for obtaining subjective response to vertical vibration
NASA Technical Reports Server (NTRS)
Clarke, M. J.; Oborne, D. J.
1975-01-01
Laboratory experiments were performed to validate the techniques used for obtaining ratings in the field surveys carried out by the University College of Swansea. In addition, attempts were made to evaluate the basic form of the human response to vibration. Some of the results obtained by different methods are described.
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Mahony, Mary C; Patterson, Patricia; Hayward, Brooke; North, Robert; Green, Dawne
2015-05-01
To demonstrate, using human factors engineering (HFE), that a redesigned, pre-filled, ready-to-use, pre-asembled follitropin alfa pen can be used to administer prescribed follitropin alfa doses safely and accurately. A failure modes and effects analysis identified hazards and harms potentially caused by use errors; risk-control measures were implemented to ensure acceptable device use risk management. Participants were women with infertility, their significant others, and fertility nurse (FN) professionals. Preliminary testing included 'Instructions for Use' (IFU) and pre-validation studies. Validation studies used simulated injections in a representative use environment; participants received prior training on pen use. User performance in preliminary testing led to IFU revisions and a change to outer needle cap design to mitigate needle stick potential. In the first validation study (49 users, 343 simulated injections), in the FN group, one observed critical use error resulted in a device design modification and another in an IFU change. A second validation study tested the mitigation strategies; previously reported use errors were not repeated. Through an iterative process involving a series of studies, modifications were made to the pen design and IFU. Simulated-use testing demonstrated that the redesigned pen can be used to administer follitropin alfa effectively and safely.
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New methodology to reconstruct in 2-D the cuspal enamel of modern human lower molars.
Modesto-Mata, Mario; García-Campos, Cecilia; Martín-Francés, Laura; Martínez de Pinillos, Marina; García-González, Rebeca; Quintino, Yuliet; Canals, Antoni; Lozano, Marina; Dean, M Christopher; Martinón-Torres, María; Bermúdez de Castro, José María
2017-08-01
In the last years different methodologies have been developed to reconstruct worn teeth. In this article, we propose a new 2-D methodology to reconstruct the worn enamel of lower molars. Our main goals are to reconstruct molars with a high level of accuracy when measuring relevant histological variables and to validate the methodology calculating the errors associated with the measurements. This methodology is based on polynomial regression equations, and has been validated using two different dental variables: cuspal enamel thickness and crown height of the protoconid. In order to perform the validation process, simulated worn modern human molars were employed. The associated errors of the measurements were also estimated applying methodologies previously proposed by other authors. The mean percentage error estimated in reconstructed molars for these two variables in comparison with their own real values is -2.17% for the cuspal enamel thickness of the protoconid and -3.18% for the crown height of the protoconid. This error significantly improves the results of other methodologies, both in the interobserver error and in the accuracy of the measurements. The new methodology based on polynomial regressions can be confidently applied to the reconstruction of cuspal enamel of lower molars, as it improves the accuracy of the measurements and reduces the interobserver error. The present study shows that it is important to validate all methodologies in order to know the associated errors. This new methodology can be easily exportable to other modern human populations, the human fossil record and forensic sciences. © 2017 Wiley Periodicals, Inc.
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Kaluzhny, Yulia; Kandárová, Helena; Handa, Yuki; DeLuca, Jane; Truong, Thoa; Hunter, Amy; Kearney, Paul; d'Argembeau-Thornton, Laurence; Klausner, Mitchell
2015-05-01
The 7th Amendment to the EU Cosmetics Directive and the EU REACH Regulation have reinforced the need for in vitro ocular test methods. Validated in vitro ocular toxicity tests that can predict the human response to chemicals, cosmetics and other consumer products are required for the safety assessment of materials that intentionally, or inadvertently, come into contact with the eye. The EpiOcular Eye Irritation Test (EIT), which uses the normal human cell-based EpiOcular™ tissue model, was developed to address this need. The EpiOcular-EIT is able to discriminate, with high sensitivity and accuracy, between ocular irritant/corrosive materials and those that require no labelling. Although the original EpiOcular-EIT protocol was successfully pre-validated in an international, multicentre study sponsored by COLIPA (the predecessor to Cosmetics Europe), data from two larger studies (the EURL ECVAM-COLIPA validation study and an independent in-house validation at BASF SE) resulted in a sensitivity for the protocol for solids that was below the acceptance criteria set by the Validation Management Group (VMG) for eye irritation, and indicated the need for improvement of the assay's sensitivity for solids. By increasing the exposure time for solid materials from 90 minutes to 6 hours, the optimised EpiOcular-EIT protocol achieved 100% sensitivity, 68.4% specificity and 84.6% accuracy, thereby meeting all the acceptance criteria set by the VMG. In addition, to satisfy the needs of Japan and the Pacific region, the EpiOcular-EIT method was evaluated for its performance after extended shipment and storage of the tissues (4-5 days), and it was confirmed that the assay performs with similar levels of sensitivity, specificity and reproducibility in these circumstances. 2015 FRAME.
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Brady, Karen; Cracknell, Nina; Zulch, Helen; Mills, Daniel Simon
2018-01-01
Working dogs are selected based on predictions from tests that they will be able to perform specific tasks in often challenging environments. However, withdrawal from service in working dogs is still a big problem, bringing into question the reliability of the selection tests used to make these predictions. A systematic review was undertaken aimed at bringing together available information on the reliability and predictive validity of the assessment of behavioural characteristics used with working dogs to establish the quality of selection tests currently available for use to predict success in working dogs. The search procedures resulted in 16 papers meeting the criteria for inclusion. A large range of behaviour tests and parameters were used in the identified papers, and so behaviour tests and their underpinning constructs were grouped on the basis of their relationship with positive core affect (willingness to work, human-directed social behaviour, object-directed play tendencies) and negative core affect (human-directed aggression, approach withdrawal tendencies, sensitivity to aversives). We then examined the papers for reports of inter-rater reliability, within-session intra-rater reliability, test-retest validity and predictive validity. The review revealed a widespread lack of information relating to the reliability and validity of measures to assess behaviour and inconsistencies in terminologies, study parameters and indices of success. There is a need to standardise the reporting of these aspects of behavioural tests in order to improve the knowledge base of what characteristics are predictive of optimal performance in working dog roles, improving selection processes and reducing working dog redundancy. We suggest the use of a framework based on explaining the direct or indirect relationship of the test with core affect.
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Locatelli, Marcello; Kabir, Abuzar; Innosa, Denise; Lopatriello, Teresa; Furton, Kenneth G
2017-01-01
This paper reports a novel fabric phase sorptive extraction-high performance liquid chromatography-photodiode array detection (FPSE-HPLC-PDA) method for the simultaneous extraction and analysis of twelve azole antimicrobial drug residues that include ketoconazole, terconazole, voriconazole, bifonazole, clotrimazole, tioconazole, econazole, butoconazole, miconazole, posaconazole, ravuconazole, and itraconazole in human plasma and urine samples. The selected azole antimicrobial drugs were well resolved by using a Luna C 18 column (250mm×4.6mm; 5μm particle size) in gradient elution mode within 36min. The analytical method was calibrated and validated in the range from 0.1 to 8μg/mL for all the drug compounds. Blank human plasma and urine were used as the sample matrix for the analysis; while benzyl-4-hydroxybenzoate was used as the internal standard (IS). The limit of quantification of the FPSE-HPLC-PDA method was found as 0.1μg/mL and the weighted-matrix matched standard calibration curves of the drugs showed a good linearity upto a concentration of 8μg/mL. The parallelism tests were also performed to evaluate whether overrange sample can be analyzed after dilution, without compromising the analytical performances of the validated method. The intra- and inter-day precision (RSD%) values were found ≤13.1% and ≤13.9%, respectively. The intra- and inter-day trueness (bias%) values were found in the range from -12.1% to 10.5%. The performances of the validated FPSE-HPLC-PDA were further tested on real samples collected from healthy volunteers after a single dose administration of itraconazole and miconazole. To the best of our knowledge, this is the first FPSE extraction procedure applied on plasma and urine samples for the simultaneous determination of twelve azole drugs possessing a wide range of logK ow values (extending from 0.4 for fluconazole to 6.70 of butoconazole) and could be adopted as a rapid and robust green analytical tool for clinical and pharmaceutical applications. Copyright © 2016 Elsevier B.V. All rights reserved.
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Blessy, S A Praylin Selva; Sulochana, C Helen
2015-01-01
Segmentation of brain tumor from Magnetic Resonance Imaging (MRI) becomes very complicated due to the structural complexities of human brain and the presence of intensity inhomogeneities. To propose a method that effectively segments brain tumor from MR images and to evaluate the performance of unsupervised optimal fuzzy clustering (UOFC) algorithm for segmentation of brain tumor from MR images. Segmentation is done by preprocessing the MR image to standardize intensity inhomogeneities followed by feature extraction, feature fusion and clustering. Different validation measures are used to evaluate the performance of the proposed method using different clustering algorithms. The proposed method using UOFC algorithm produces high sensitivity (96%) and low specificity (4%) compared to other clustering methods. Validation results clearly show that the proposed method with UOFC algorithm effectively segments brain tumor from MR images.
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Bae, Jung-Woo; Choi, Chang-Ik; Jang, Choon-Gon; Lee, Seok-Yong
2011-11-01
A simple and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) technique was developed and validated for the determination of sibutramine and its N-desmethyl metabolites (M1 and M2) in human plasma. After extraction with methyl t-butyl ether, chromatographic separation of analytes in human plasma was performed using a reverse-phase Luna C18 column with a mobile phase of acetonitrile-10 mm ammonium formate buffer (50:50, v/v) and quantified by ESI-MS/MS detection in positive ion mode. The flow rate of the mobile phase was 200 μL/min and the retention times of sibutramine, M1, M2 and internal standard (chlorpheniramine) were 1.5, 1.4, 1.3 and 0.9 min, respectively. The calibration curves were linear over the range 0.05-20 ng/mL, for sibutramine, M1 and M2. The lower limit of quantification was 0.05 ng/mL using 500 μL of human plasma. The mean accuracy and the precision in the intra- and inter-day validation for sibutramine, M1 and M2 were acceptable. This LC-MS/MS method showed improved sensitivity and a short run time for the quantification of sibutramine and its two active metabolites in plasma. The validated method was successfully applied to a pharmacokinetic study in human. Copyright © 2011 John Wiley & Sons, Ltd.
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Selective Attention to Auditory Memory Neurally Enhances Perceptual Precision.
Lim, Sung-Joo; Wöstmann, Malte; Obleser, Jonas
2015-12-09
Selective attention to a task-relevant stimulus facilitates encoding of that stimulus into a working memory representation. It is less clear whether selective attention also improves the precision of a stimulus already represented in memory. Here, we investigate the behavioral and neural dynamics of selective attention to representations in auditory working memory (i.e., auditory objects) using psychophysical modeling and model-based analysis of electroencephalographic signals. Human listeners performed a syllable pitch discrimination task where two syllables served as to-be-encoded auditory objects. Valid (vs neutral) retroactive cues were presented during retention to allow listeners to selectively attend to the to-be-probed auditory object in memory. Behaviorally, listeners represented auditory objects in memory more precisely (expressed by steeper slopes of a psychometric curve) and made faster perceptual decisions when valid compared to neutral retrocues were presented. Neurally, valid compared to neutral retrocues elicited a larger frontocentral sustained negativity in the evoked potential as well as enhanced parietal alpha/low-beta oscillatory power (9-18 Hz) during memory retention. Critically, individual magnitudes of alpha oscillatory power (7-11 Hz) modulation predicted the degree to which valid retrocues benefitted individuals' behavior. Our results indicate that selective attention to a specific object in auditory memory does benefit human performance not by simply reducing memory load, but by actively engaging complementary neural resources to sharpen the precision of the task-relevant object in memory. Can selective attention improve the representational precision with which objects are held in memory? And if so, what are the neural mechanisms that support such improvement? These issues have been rarely examined within the auditory modality, in which acoustic signals change and vanish on a milliseconds time scale. Introducing a new auditory memory paradigm and using model-based electroencephalography analyses in humans, we thus bridge this gap and reveal behavioral and neural signatures of increased, attention-mediated working memory precision. We further show that the extent of alpha power modulation predicts the degree to which individuals' memory performance benefits from selective attention. Copyright © 2015 the authors 0270-6474/15/3516094-11$15.00/0.
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Shewale, Jaiprakash G; Schneida, Elaine; Wilson, Jonathan; Walker, Jerilyn A; Batzer, Mark A; Sinha, Sudhir K
2007-03-01
The human DNA quantification (H-Quant) system, developed for use in human identification, enables quantitation of human genomic DNA in biological samples. The assay is based on real-time amplification of AluYb8 insertions in hominoid primates. The relatively high copy number of subfamily-specific Alu repeats in the human genome enables quantification of very small amounts of human DNA. The oligonucleotide primers present in H-Quant are specific for human DNA and closely related great apes. During the real-time PCR, the SYBR Green I dye binds to the DNA that is synthesized by the human-specific AluYb8 oligonucleotide primers. The fluorescence of the bound SYBR Green I dye is measured at the end of each PCR cycle. The cycle at which the fluorescence crosses the chosen threshold correlates to the quantity of amplifiable DNA in that sample. The minimal sensitivity of the H-Quant system is 7.6 pg/microL of human DNA. The amplicon generated in the H-Quant assay is 216 bp, which is within the same range of the common amplifiable short tandem repeat (STR) amplicons. This size amplicon enables quantitation of amplifiable DNA as opposed to a quantitation of degraded or nonamplifiable DNA of smaller sizes. Development and validation studies were performed on the 7500 real-time PCR system following the Quality Assurance Standards for Forensic DNA Testing Laboratories.
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NASA Astrophysics Data System (ADS)
Santiago-Alvarado, A.; Cruz-Félix, A.; Hernández Méndez, A.; Pérez-Maldonado, Y.; Domínguez-Osante, C.
2015-05-01
Tunable lenses have attracted much attention due to their potential applications in such areas like machine vision, laser projection, ophthalmology, etc. In this work we present the design of a tunable opto-mechatronic system capable of focusing and to regulate the entrance illumination that mimics the performance made by the iris and the crystalline lens of the human eye. A solid elastic lens made of PDMS has been used in order to mimic the crystalline lens and an automatic diaphragm has been used to mimic the iris of the human eye. Also, a characterization of such system has been performed with standard values of luminosity for the human eye have been taken into account to calibrate and to validate the entrance illumination levels to the overall optical system.
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Predicting detection performance with model observers: Fourier domain or spatial domain?
Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia
2016-02-27
The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.
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Predicting detection performance with model observers: Fourier domain or spatial domain?
Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia
2016-01-01
The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images. PMID:27239086
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Lee, Ciaran M; Zhu, Haibao; Davis, Timothy H; Deshmukh, Harshahardhan; Bao, Gang
2017-01-01
The CRISPR/Cas9 system is a powerful tool for precision genome editing. The ability to accurately modify genomic DNA in situ with single nucleotide precision opens up new possibilities for not only basic research but also biotechnology applications and clinical translation. In this chapter, we outline the procedures for design, screening, and validation of CRISPR/Cas9 systems for targeted modification of coding sequences in the human genome and how to perform genome editing in induced pluripotent stem cells with high efficiency and specificity.
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A Bacterial Glycoengineered Antigen for Improved Serodiagnosis of Porcine Brucellosis
Cortina, María E.; Balzano, Rodrigo E.; Rey Serantes, Diego A.; Caillava, Ana J.; Elena, Sebastián; Ferreira, A. C.; Nicola, Ana M.; Ugalde, Juan E.
2016-01-01
Brucellosis is a highly zoonotic disease that affects animals and human beings. Brucella suis is the etiological agent of porcine brucellosis and one of the major human brucellosis pathogens. Laboratory diagnosis of porcine brucellosis mainly relies on serological tests, and it has been widely demonstrated that serological assays based on the detection of anti O-polysaccharide antibodies are the most sensitive tests. Here, we validate a recombinant glycoprotein antigen, an N-formylperosamine O-polysaccharide–protein conjugate (OAg-AcrA), for diagnosis of porcine brucellosis. An indirect immunoassay based on the detection of anti-O-polysaccharide IgG antibodies was developed coupling OAg-AcrA to enzyme-linked immunosorbent assay plates (glyco-iELISA). To validate the assay, 563 serum samples obtained from experimentally infected and immunized pigs, as well as animals naturally infected with B. suis biovar 1 or 2, were tested. A receiver operating characteristic (ROC) analysis was performed, and based on this analysis, the optimum cutoff value was 0.56 (relative reactivity), which resulted in a diagnostic sensitivity and specificity of 100% and 99.7%, respectively. A cutoff value of 0.78 resulted in a test sensitivity of 98.4% and a test specificity of 100%. Overall, our results demonstrate that the glyco-iELISA is highly accurate for diagnosis of porcine brucellosis, improving the diagnostic performance of current serological tests. The recombinant glycoprotein OAg-AcrA can be produced in large homogeneous batches in a standardized way, making it an ideal candidate for further validation as a universal antigen for diagnosis of “smooth” brucellosis in animals and humans. PMID:26984975
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Fernandez-Miranda, Juan C; Pathak, Sudhir; Engh, Johnathan; Jarbo, Kevin; Verstynen, Timothy; Yeh, Fang-Cheng; Wang, Yibao; Mintz, Arlan; Boada, Fernando; Schneider, Walter; Friedlander, Robert
2012-08-01
High-definition fiber tracking (HDFT) is a novel combination of processing, reconstruction, and tractography methods that can track white matter fibers from cortex, through complex fiber crossings, to cortical and subcortical targets with subvoxel resolution. To perform neuroanatomical validation of HDFT and to investigate its neurosurgical applications. Six neurologically healthy adults and 36 patients with brain lesions were studied. Diffusion spectrum imaging data were reconstructed with a Generalized Q-Ball Imaging approach. Fiber dissection studies were performed in 20 human brains, and selected dissection results were compared with tractography. HDFT provides accurate replication of known neuroanatomical features such as the gyral and sulcal folding patterns, the characteristic shape of the claustrum, the segmentation of the thalamic nuclei, the decussation of the superior cerebellar peduncle, the multiple fiber crossing at the centrum semiovale, the complex angulation of the optic radiations, the terminal arborization of the arcuate tract, and the cortical segmentation of the dorsal Broca area. From a clinical perspective, we show that HDFT provides accurate structural connectivity studies in patients with intracerebral lesions, allowing qualitative and quantitative white matter damage assessment, aiding in understanding lesional patterns of white matter structural injury, and facilitating innovative neurosurgical applications. High-grade gliomas produce significant disruption of fibers, and low-grade gliomas cause fiber displacement. Cavernomas cause both displacement and disruption of fibers. Our HDFT approach provides an accurate reconstruction of white matter fiber tracts with unprecedented detail in both the normal and pathological human brain. Further studies to validate the clinical findings are needed.
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Sreenivasulu, Vudagandla; Ramesh, Mullangi; Kumar, Inamadugu Jaswanth; Babu, Ravi Vasu; Pilli, Nageswara Rao; Krishnaiah, Abburi
2013-02-01
A simple, sensitive and rapid LC-MS/MS-ESI method has been developed and validated for simultaneous quantification of the carisoprodol and aspirin in human plasma. Carisoprodol was detected in positive ion mode, whereas aspirin was detected in negative ion mode. Carbamazepine and furosemide were used as internal standards (IS) for quantification of carisoprodol and aspirin, respectively. The extraction procedure involves a liquid-liquid extraction method with ter-butyl methyl ether. Chromatographic separation was achieved on a Zorbax XDB-Phenyl (4.6 × 75 mm, 3.5 µm) column using an isocratic mobile phase (5 mm ammonium acetate:methanol, 20:80, v/v) at a flow rate of 0.8 mL/min with a total run time of 2.2 min. A detailed method validation was performed as per the FDA guidelines. The standard curves found to be linear in the range of 25.5-4900 and 15.3-3000 ng/mL for carisoprodol and aspirin, respectively. The results met the acceptance criteria. Carisoprodol and aspirin were found to be stable in various stability studies. The validated method was successfully applied to a pharmacokinetic study following co-administration of carisoprodol (250 mg) and aspirin (75 mg) tablets by oral route to human volunteers. Copyright © 2012 John Wiley & Sons, Ltd.
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Kimiskidis, Vasilios; Spanakis, Marios; Niopas, Ioannis; Kazis, Dimitrios; Gabrieli, Chrysi; Kanaze, Feras Imad; Divanoglou, Daniil
2007-01-17
An isocratic reversed-phase HPLC-UV procedure for the determination of oxcarbazepine and its main metabolites 10-hydroxy-10,11-dihydrocarbamazepine and 10,11-dihydroxy-trans-10,11-dihydrocarbamazepine in human plasma and cerebrospinal fluid has been developed and validated. After addition of bromazepam as internal standard, the analytes were isolated from plasma and cerebrospinal fluid by liquid-liquid extraction. Separation was achieved on a X-TERRA C18 column using a mobile phase composed of 20 mM KH(2)PO(4), acetonitrile, and n-octylamine (76:24:0.05, v/v/v) at 40 degrees C and detected at 237 nm. The described assay was validated in terms of linearity, accuracy, precision, recovery and lower limit of quantification according to the FDA validation guidelines. Calibration curves were linear with a coefficient of variation (r) greater than 0.998. Accuracy ranged from 92.3% to 106.0% and precision was between 2.3% and 8.2%. The method has been applied to plasma and cerebrospinal fluid samples obtained from patients treated with oxcarbazepine, both in monotherapy and adjunctive therapy.
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Konda, Ravi Kumar; Chandu, Babu Rao; Challa, B.R.; Kothapalli, Chandrasekhar B.
2012-01-01
The most suitable bio-analytical method based on liquid–liquid extraction has been developed and validated for quantification of Rasagiline in human plasma. Rasagiline-13C3 mesylate was used as an internal standard for Rasagiline. Zorbax Eclipse Plus C18 (2.1 mm×50 mm, 3.5 μm) column provided chromatographic separation of analyte followed by detection with mass spectrometry. The method involved simple isocratic chromatographic condition and mass spectrometric detection in the positive ionization mode using an API-4000 system. The total run time was 3.0 min. The proposed method has been validated with the linear range of 5–12000 pg/mL for Rasagiline. The intra-run and inter-run precision values were within 1.3%–2.9% and 1.6%–2.2% respectively for Rasagiline. The overall recovery for Rasagiline and Rasagiline-13C3 mesylate analog was 96.9% and 96.7% respectively. This validated method was successfully applied to the bioequivalence and pharmacokinetic study of human volunteers under fasting condition. PMID:29403764
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Zhou, Ting; Tan, Lei; Cederquist, Gustav Y; Fan, Yujie; Hartley, Brigham J; Mukherjee, Suranjit; Tomishima, Mark; Brennand, Kristen J; Zhang, Qisheng; Schwartz, Robert E; Evans, Todd; Studer, Lorenz; Chen, Shuibing
2017-08-03
Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients. Copyright © 2017 Elsevier Inc. All rights reserved.
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Optimal Modality Selection for Cooperative Human-Robot Task Completion.
Jacob, Mithun George; Wachs, Juan P
2016-12-01
Human-robot cooperation in complex environments must be fast, accurate, and resilient. This requires efficient communication channels where robots need to assimilate information using a plethora of verbal and nonverbal modalities such as hand gestures, speech, and gaze. However, even though hybrid human-robot communication frameworks and multimodal communication have been studied, a systematic methodology for designing multimodal interfaces does not exist. This paper addresses the gap by proposing a novel methodology to generate multimodal lexicons which maximizes multiple performance metrics over a wide range of communication modalities (i.e., lexicons). The metrics are obtained through a mixture of simulation and real-world experiments. The methodology is tested in a surgical setting where a robot cooperates with a surgeon to complete a mock abdominal incision and closure task by delivering surgical instruments. Experimental results show that predicted optimal lexicons significantly outperform predicted suboptimal lexicons (p <; 0.05) in all metrics validating the predictability of the methodology. The methodology is validated in two scenarios (with and without modeling the risk of a human-robot collision) and the differences in the lexicons are analyzed.
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Transcriptome Profiling of Human FoxP3+ Regulatory T Cells
Bhairavabhotla, Ravikiran; Kim, Yong C.; Glass, Deborah D.; Escobar, Thelma M.; Patel, Mira C.; Zahr, Rami; Nguyen, Cuong K.; Kilaru, Gokhul K.; Muljo, Stefan A.; Shevach, Ethan M.
2015-01-01
The major goal of this study was to perform an in depth characterization of the “gene signature” of human FoxP3+ T regulatory cells (Tregs). Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro, were analyzed via RNA sequencing (RNA-seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3, IKZF2, and CTLA4 in Tregs. Notably, a number of yet uncharacterized genes (RTKN2, LAYN, UTS2, CSF2RB, TRIB1, F5, CECAM4, CD70, ENC1 and NKG7) were identified and validated as being differentially expressed in human Tregs. We further characterize the functional roles of RTKN2 and LAYN by analyzing their roles in vitro human Treg suppression assays by knocking them down in Tregs and overexpressing them in Tconvs. In order to facilitate a better understanding of the human Treg gene expression signature, we have generated from our results a hypothetical interactome of genes and miRNAs in Tregs and Tconvs, PMID:26686412
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Kim, Da-Hye; Oh, Jeong-Eun
2017-05-01
Human hair has many advantages as a non-invasive sample; however, analytical methods for detecting perfluoroalkyl substances (PFASs) in human hair are still in the development stage. Therefore, the aim of this study was to develop and validate a method for monitoring 11 PFASs in human hair. Solid-phase extraction (SPE), ion-pairing extraction (IPE), a combined method (SPE+IPE) and solvent extraction with ENVI-carb clean-up were compared to develop an optimal extraction method using two types of hair sample (powder and piece forms). Analysis of PFASs was performed using liquid chromatography and tandem mass spectrometry. Among the four different extraction procedures, the SPE method using powdered hair showed the best extraction efficiency and recoveries ranged from 85.8 to 102%. The method detection limits for the SPE method were 0.114-0.796 ng/g and good precision (below 10%) and accuracy (66.4-110%) were obtained. In light of these results, SPE is considered the optimal method for PFAS extraction from hair. It was also successfully used to detect PFASs in human hair samples. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Integrated Human-in-the-Loop Ground Testing - Value, History, and the Future
NASA Technical Reports Server (NTRS)
Henninger, Donald L.
2016-01-01
Systems for very long-duration human missions to Mars will be designed to operate reliably for many years and many of these systems will never be returned to Earth. The need for high reliability is driven by the requirement for safe functioning of remote, long-duration crewed systems and also by unsympathetic abort scenarios. Abort from a Mars mission could be as long as 450 days to return to Earth. The key to developing a human-in-the-loop architecture is a development process that allows for a logical sequence of validating successful development in a stepwise manner, with assessment of key performance parameters (KPPs) at each step; especially important are KPPs for technologies evaluated in a full systems context with human crews on Earth and on space platforms such as the ISS. This presentation will explore the implications of such an approach to technology development and validation including the roles of ground and space-based testing necessary to develop a highly reliable system for long duration human exploration missions. Historical development and systems testing from Mercury to the International Space Station (ISS) to ground testing will be reviewed. Current work as well as recommendations for future work will be described.
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NASA Astrophysics Data System (ADS)
Li, Bin
Spatial control behaviors account for a large proportion of human everyday activities from normal daily tasks, such as reaching for objects, to specialized tasks, such as driving, surgery, or operating equipment. These behaviors involve intensive interactions within internal processes (i.e. cognitive, perceptual, and motor control) and with the physical world. This dissertation builds on a concept of interaction pattern and a hierarchical functional model. Interaction pattern represents a type of behavior synergy that humans coordinates cognitive, perceptual, and motor control processes. It contributes to the construction of the hierarchical functional model that delineates humans spatial control behaviors as the coordination of three functional subsystems: planning, guidance, and tracking/pursuit. This dissertation formalizes and validates these two theories and extends them for the investigation of human spatial control skills encompassing development and assessment. Specifically, this dissertation first presents an overview of studies in human spatial control skills encompassing definition, characteristic, development, and assessment, to provide theoretical evidence for the concept of interaction pattern and the hierarchical functional model. The following, the human experiments for collecting motion and gaze data and techniques to register and classify gaze data, are described. This dissertation then elaborates and mathematically formalizes the hierarchical functional model and the concept of interaction pattern. These theories then enables the construction of a succinct simulation model that can reproduce a variety of human performance with a minimal set of hypotheses. This validates the hierarchical functional model as a normative framework for interpreting human spatial control behaviors. The dissertation then investigates human skill development and captures the emergence of interaction pattern. The final part of the dissertation applies the hierarchical functional model for skill assessment and introduces techniques to capture interaction patterns both from the top down using their geometric features and from the bottom up using their dynamical characteristics. The validity and generality of the skill assessment is illustrated using two the remote-control flight and laparoscopic surgical training experiments.
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Matsunami, Risë K; Angelides, Kimon; Engler, David A
2015-05-18
There is currently considerable discussion about the accuracy of blood glucose concentrations determined by personal blood glucose monitoring systems (BGMS). To date, the FDA has allowed new BGMS to demonstrate accuracy in reference to other glucose measurement systems that use the same or similar enzymatic-based methods to determine glucose concentration. These types of reference measurement procedures are only comparative in nature and are subject to the same potential sources of error in measurement and system perturbations as the device under evaluation. It would be ideal to have a completely orthogonal primary method that could serve as a true standard reference measurement procedure for establishing the accuracy of new BGMS. An isotope-dilution liquid chromatography/mass spectrometry (ID-UPLC-MRM) assay was developed using (13)C6-glucose as a stable isotope analogue to specifically measure glucose concentration in human plasma, and validated for use against NIST standard reference materials, and against fresh isolates of whole blood and plasma into which exogenous glucose had been spiked. Assay performance was quantified to NIST-traceable dry weight measures for both glucose and (13)C6-glucose. The newly developed assay method was shown to be rapid, highly specific, sensitive, accurate, and precise for measuring plasma glucose levels. The assay displayed sufficient dynamic range and linearity to measure across the range of both normal and diabetic blood glucose levels. Assay performance was measured to within the same uncertainty levels (<1%) as the NIST definitive method for glucose measurement in human serum. The newly developed ID UPLC-MRM assay can serve as a validated reference measurement procedure to which new BGMS can be assessed for glucose measurement performance. © 2015 Diabetes Technology Society.
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Matsunami, Risë K.; Angelides, Kimon; Engler, David A.
2015-01-01
Background: There is currently considerable discussion about the accuracy of blood glucose concentrations determined by personal blood glucose monitoring systems (BGMS). To date, the FDA has allowed new BGMS to demonstrate accuracy in reference to other glucose measurement systems that use the same or similar enzymatic-based methods to determine glucose concentration. These types of reference measurement procedures are only comparative in nature and are subject to the same potential sources of error in measurement and system perturbations as the device under evaluation. It would be ideal to have a completely orthogonal primary method that could serve as a true standard reference measurement procedure for establishing the accuracy of new BGMS. Methods: An isotope-dilution liquid chromatography/mass spectrometry (ID-UPLC-MRM) assay was developed using 13C6-glucose as a stable isotope analogue to specifically measure glucose concentration in human plasma, and validated for use against NIST standard reference materials, and against fresh isolates of whole blood and plasma into which exogenous glucose had been spiked. Assay performance was quantified to NIST-traceable dry weight measures for both glucose and 13C6-glucose. Results: The newly developed assay method was shown to be rapid, highly specific, sensitive, accurate, and precise for measuring plasma glucose levels. The assay displayed sufficient dynamic range and linearity to measure across the range of both normal and diabetic blood glucose levels. Assay performance was measured to within the same uncertainty levels (<1%) as the NIST definitive method for glucose measurement in human serum. Conclusions: The newly developed ID UPLC-MRM assay can serve as a validated reference measurement procedure to which new BGMS can be assessed for glucose measurement performance. PMID:25986627
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Sensor Applications and Data Validation
NASA Technical Reports Server (NTRS)
Wiley, John
2008-01-01
The mechanical configuration of automobiles have changed marginally while improvements in sensors and control have dramatically improved engine efficiency, reliability and useful life. The aviation industry has also taken advantage of sensors and control systems to reduce operational costs. Sensors and high fidelity control systems fly planes at levels of performance beyond human capability. Sophisticated environmental controls allow a greater level of comfort and efficiency in our homes. Sensors have given the medical field a better understanding of the human body and the environment in which we live.
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Segmentation of human upper body movement using multiple IMU sensors.
Aoki, Takashi; Lin, Jonathan Feng-Shun; Kulic, Dana; Venture, Gentiane
2016-08-01
This paper proposes an approach for the segmentation of human body movements measured by inertial measurement unit sensors. Using the angular velocity and linear acceleration measurements directly, without converting to joint angles, we perform segmentation by formulating the problem as a classification problem, and training a classifier to differentiate between motion end-point and within-motion points. The proposed approach is validated with experiments measuring the upper body movement during reaching tasks, demonstrating classification accuracy of over 85.8%.
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Snodgrass, Ryan; Gardner, Andrea; Jiang, Li; Fu, Cheng; Cesarman, Ethel; Erickson, David
2016-01-01
Resource-limited settings present unique engineering challenges for medical diagnostics. Diagnosis is often needed for those unable to reach central healthcare systems, making portability and independence from traditional energy infrastructure essential device parameters. In 2014, our group presented a microfluidic device that performed a solar-powered variant of the polymerase chain reaction, which we called solar thermal PCR. In this work, we expand on our previous effort by presenting an integrated, portable, solar thermal PCR system targeted towards the diagnosis of Kaposi’s sarcoma. We call this system KS-Detect, and we now report the system’s performance as a diagnostic tool using pseudo-biopsy samples made from varying concentrations of human lymphoma cell lines positive for the KS herpesvirus (KSHV). KS-Detect achieved 83% sensitivity and 70% specificity at high (≥10%) KSHV+ cell concentrations when diagnosing pseudo-biopsy samples by smartphone image. Using histology, we confirm that our prepared pseudo-biopsies contain similar KSHV+ cell concentrations as human biopsies positive for KS. Through our testing of samples derived from human cell lines, we validate KS-Detect as a viable, portable KS diagnostic tool, and we identify critical engineering considerations for future solar-thermal PCR devices. PMID:26799834
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Taneja, Isha; Raju, Kanumuri Siva Rama; Singh, Sheelendra Pratap; Wahajuddin, Muhammad
2015-11-25
The pharmacokinetic compatibility of short-acting CDRI candidate antimalarial trioxane derivative, 99-411, was tested with long-acting prescription antimalarials, lumefantrine and piperaquine. LC-ESI-MS/MS methods were validated for simultaneous bioanalysis of lumefantrine and 99-411 and of piperaquine and 99-411 combinations. The interaction studies were performed in rats using these validated methods. The total systemic exposure of 99-411 increased when administered with either lumefantrine or piperaquine. However, co-administration of 99-411 significantly decreased the systemic exposure of piperaquine by half-fold while it had no effect on the kinetics of lumefantrine. 99-411, thus, seemed to be a good alternative to artemisinin derivatives for combination treatment with lumefantrine. To explore the reason for increased plasma levels of 99-411, an in situ permeability study was performed by co-perfusing lumefantrine and 99-411. In presence of lumefantrine, the absorption of 99-411 was significantly increased by 1.37 times than when given alone. Lumefantrine did not affect the metabolism of 99-411 when tested in vitro in human liver microsomes. Additionally, ATPase assay suggest that 99-411 was a substrate of human P-gp, thus, indicating the probability of interaction at the absorption level in humans as well.
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Slip resistance of winter footwear on snow and ice measured using maximum achievable incline.
Hsu, Jennifer; Shaw, Robert; Novak, Alison; Li, Yue; Ormerod, Marcus; Newton, Rita; Dutta, Tilak; Fernie, Geoff
2016-05-01
Protective footwear is necessary for preventing injurious slips and falls in winter conditions. Valid methods for assessing footwear slip resistance on winter surfaces are needed in order to evaluate footwear and outsole designs. The purpose of this study was to utilise a method of testing winter footwear that was ecologically valid in terms of involving actual human testers walking on realistic winter surfaces to produce objective measures of slip resistance. During the experiment, eight participants tested six styles of footwear on wet ice, on dry ice, and on dry ice after walking over soft snow. Slip resistance was measured by determining the maximum incline angles participants were able to walk up and down in each footwear-surface combination. The results indicated that testing on a variety of surfaces is necessary for establishing winter footwear performance and that standard mechanical bench tests for footwear slip resistance do not adequately reflect actual performance. Practitioner Summary: Existing standardised methods for measuring footwear slip resistance lack validation on winter surfaces. By determining the maximum inclines participants could walk up and down slopes of wet ice, dry ice, and ice with snow, in a range of footwear, an ecologically valid test for measuring winter footwear performance was established.
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Slip resistance of winter footwear on snow and ice measured using maximum achievable incline
Hsu, Jennifer; Shaw, Robert; Novak, Alison; Li, Yue; Ormerod, Marcus; Newton, Rita; Dutta, Tilak; Fernie, Geoff
2016-01-01
Abstract Protective footwear is necessary for preventing injurious slips and falls in winter conditions. Valid methods for assessing footwear slip resistance on winter surfaces are needed in order to evaluate footwear and outsole designs. The purpose of this study was to utilise a method of testing winter footwear that was ecologically valid in terms of involving actual human testers walking on realistic winter surfaces to produce objective measures of slip resistance. During the experiment, eight participants tested six styles of footwear on wet ice, on dry ice, and on dry ice after walking over soft snow. Slip resistance was measured by determining the maximum incline angles participants were able to walk up and down in each footwear–surface combination. The results indicated that testing on a variety of surfaces is necessary for establishing winter footwear performance and that standard mechanical bench tests for footwear slip resistance do not adequately reflect actual performance. Practitioner Summary: Existing standardised methods for measuring footwear slip resistance lack validation on winter surfaces. By determining the maximum inclines participants could walk up and down slopes of wet ice, dry ice, and ice with snow, in a range of footwear, an ecologically valid test for measuring winter footwear performance was established. PMID:26555738
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Rapid and sensitive method for determination of withaferin-A in human plasma by HPLC.
Patial, Pankaj; Gota, Vikram
2011-02-01
To develop and validate a rapid and sensitive high-performance liquid chromatographic method for determination of withaferin-A in human plasma. Withaferin-A, the active molecule of a traditional Indian herb, has demonstrated several biological activities in preclinical models. A validated bioassay is not available for its pharmacokinetic evaluation. The chromatographic system used a reverse-phase C18 column with UV-visible detection at 225 nm. The mobile phase consisted of water and acetonitrile applied in a gradient flow. Withaferin-A was extracted by simple protein-precipitation technique. The calibration curve was linear in the concentration range of 0.05-1.6 µg/ml. The method has the desired sensitivity to detect the plasma concentration range of withaferin-A that is likely to show biological activity based on in vitro data. This is the first HPLC method ever described for the estimation of withaferin-A in human plasma which could be applied for pharmacokinetic studies.
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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.
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Kinoshita, Angela; Sullasi, Henry L; Asfora, Viviane K; Azevedo, Renata L; Guzzo, Pedro; Guidon, Niede; Figueiredo, Ana Maria G; Khoury, Helen; Pessis, Anne-Marie; Baffa, Oswaldo
2016-06-07
This work reports the dating of a fossil human tooth and shell found at the archaeological site Toca do Enoque located in Serra das Confusões National Park (Piauí, Brazil). Many prehistoric paintings have been found at this site. An archaeological excavation unearthed three sepulchers with human skeletons and some shells. Two Brazilian laboratories, in Ribeirão Preto (USP) and Recife (UFPE), independently performed Electron Spin Resonance (ESR) measurements to date the tooth and the shell and obtain the equivalent dose received by each sample. The laboratories determined similar ages for the tooth and the shell (~4.8 kyBP). The results agreed with C-14 dating of the shell and other samples (charcoal) collected in the same sepulcher. Therefore, this work provides a valid inter-comparison of results by two independent ESR-dating laboratories and between two dating methods; i.e., C-14 and ESR, showing the validity of ESR dating for this range of ages.
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NASA Occupant Protection Standards Development
NASA Technical Reports Server (NTRS)
Somers, Jeffrey T.; Gernhardt, Michael A.; Lawrence, Charles
2011-01-01
Current National Aeronautics and Space Administration (NASA) occupant protection standards and requirements are based on extrapolations of biodynamic models, which were based on human tests performed under pre-Space Shuttle human flight programs where the occupants were in different suit and seat configurations than is expected for the Multi Purpose Crew Vehicle (MPCV) and Commercial Crew programs. As a result, there is limited statistical validity to the occupant protection standards. Furthermore, the current standards and requirements have not been validated in relevant spaceflight suit, seat configurations or loading conditions. The objectives of this study were to develop new standards and requirements for occupant protection and rigorously validate these new standards with sub-injurious human testing. To accomplish these objectives we began by determining which critical injuries NASA would like to protect for. We then defined the anthropomorphic test device (ATD) and the associated injury metrics of interest. Finally, we conducted a literature review of available data for the Test Device for Human Occupant Restraint New Technology (THOR-NT) ATD to determine injury assessment reference values (IARV) to serve as a baseline for further development. To better understand NASA s environment, we propose conducting sub-injurious human testing in spaceflight seat and suit configurations with spaceflight dynamic loads, with a sufficiently high number of subjects to validate no injury during nominal landing loads. In addition to validate nominal loads, the THOR-NT ATD will be tested in the same conditions as the human volunteers, allowing correlation between human and ATD responses covering the Orion nominal landing environment and commercial vehicle expected nominal environments. All testing will be conducted without the suit and with the suit to ascertain the contribution of the suit to human and ATD responses. In addition to the testing campaign proposed, additional data analysis is proposed to mine existing human injury and response data from other sources, including military volunteer testing, automotive Crash Injury Research Engineering Network (CIREN), and IndyCar impact and injury data. These data sources can allow a better extrapolation of the ATD responses to off-nominal conditions above the nominal range that can safely be tested. These elements will be used to develop injury risk functions for each of the injury metrics measured from the ATD. These risk functions would serve as the basis for the NASA standards. Finally, we propose defining standard test methodology for evaluating future spacecraft designs against the IARVs, including developing a star-rating system to allow crew safety comparisons between vehicles.
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Top DoD Management Challenges, Fiscal Year 2018
2018-01-01
Afghan Human Resource Information Management System to validate ANDSF personnel numbers and salaries; • Afghan Personnel Pay System to facilitate...unit strength accountability and personnel verification; and • Core Information Management System to improve accountability of equipment inventories...ACQUISITION AND CONTRACT MANAGEMENT Federal Acquisition Regulation requires contractor performance information be collected in the Contractor
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ERIC Educational Resources Information Center
Scheuer, Claude; Bund, Andreas; Becker, Werner; Herrmann, Christian
2017-01-01
Basic motor competencies (in German: Motorische Basiskompetenzen; MOBAK) are motor performance dispositions formulated as minimum standards that empower children to participate in the culture of human movement. In opposition to movement-specific and process-oriented fundamental movement skills assessing the quality of movement execution, basic…
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Validation of an ergonomic method to withdraw [99mTc] radiopharmaceuticals.
Blondeel-Gomes, Sandy; Marie, Solène; Fouque, Julien; Loyeau, Sabrina; Madar, Olivier; Lokiec, François
2017-11-10
The main objective of the present work was to ensure quality of radiopharmaceuticals syringes withdrawn with a "Spinal needle/obturator In-Stopper" system. Methods: Visual examinations and physicochemical tests are performed at T0 and T+4h for [ 99m Tc]albumin nanocolloid and T+7h for [ 99m Tc]eluate, [ 99m Tc] HydroxyMethylene DiPhosphonate and [ 99m Tc]Human Serum Albumin. Microbiological validation was performed according to European pharmacopoeia. Fingertip radiation exposure was evaluated to confirm the safety of the system. Results: Results show stable visual and physicochemical properties. The integrity of the connector was not affected after 30 punctures (no cores). No microbiological contamination was found on tested syringes. Conclusion: The system could be used 30 times. The stability of syringes drawing with this method is guaranteed up to 4 hours for [ 99m Tc]albumin nanocolloid and 7 hours for [ 99m Tc]eluate, [ 99m Tc]HydroxyMethylene DisPhosphonate and [ 99m Tc]Human serum albumin. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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NASA Astrophysics Data System (ADS)
Piechna, A.; Cieślicki, K.; Lombarski, L.; Ciszek, B.
2015-02-01
Arterial walls are a multilayer structures with nonlinear material characteristics. Furthermore, residual stresses exist in unloaded state (zero-pressure condition) and they affect arterial behavior. To investigate these phenomena a number of theoretical and numerical studies were performed, however no experimental validation was proposed and realized yet. We cannot get rid of residual stresses without damaging the arterial segment. In this paper we propose a novel experiment to validate a numerical model of artery with residual stresses. The inspiration for our study originates from experiments made by Dobrin on dogs' arteries (1999). We applied the idea of turning the artery inside out. After such an operation the sequence of layer is reversed and the residual stresses are re-ordered. We performed several pressure-inflation tests on human Common Carotid Arteries (CCA) in normal and inverted configurations. The nonlinear responses of arterial behavior were obtained and compared to the numerical model. Computer simulations were carried out using the commercial software which applied the finite element method (FEM). Then, these results were discussed.
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SDBI 1904: Human Factors Assessment of Vibration Effects on Visual Performance during Launch
NASA Technical Reports Server (NTRS)
Thompson, Shelby G.; Holden, Kritina; Root, Phillip; Ebert, Douglas; Jones, Jeffery; Adelstein, Bernard
2009-01-01
The primary objective of the of Human Factors Short Duration Bioastronautics Investigation (SDBI) 1904 is to determine visual performance limits during operational vibration and g-loads, specifically through the determination of minimal usable font sized using Orion-type display formats. Currently there is little to no data available to quantify human visual performance under these extreme conditions. Existing data on shuttle vibration magnitude and frequency is incomplete, does not address sear and crew vibration in the current configuration, and does not address human visual performance. There have been anecdotal reports of performance decrements from shuttle crews, but no structured data has been collected. The SDBI is a companion effort to the Detailed Test Objective (DTO) 695, which will measure shuttle seat accelerations (vibration) during ascent. Data fro the SDBI will serve an important role in interpreting the DTO vibration data. This data will be collected during the ascent phase of three shuttle missions (STS-119, 127, and 128). Both SDBI1904 and DTO 695 are low impact with respect to flight resources, and combined they represent an efficient and focused problem solving approach. The SDBI and DTO data will be correlated to determine the nature of perceived visual performance under varying vibrations and g-loads. This project will provide: 1) Immediate data for developing preliminary human performance vibration requirements; 2) Flight validated inputs for ongoing and future ground-based research; and 3) Information of functional needs that will drive Orion display format design decisions.
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Hernando, Barbara; Ibañez, Maria Victoria; Deserio-Cuesta, Julio Alberto; Soria-Navarro, Raquel; Vilar-Sastre, Inca; Martinez-Cadenas, Conrado
2018-03-01
Prediction of human pigmentation traits, one of the most differentiable externally visible characteristics among individuals, from biological samples represents a useful tool in the field of forensic DNA phenotyping. In spite of freckling being a relatively common pigmentation characteristic in Europeans, little is known about the genetic basis of this largely genetically determined phenotype in southern European populations. In this work, we explored the predictive capacity of eight freckle and sunlight sensitivity-related genes in 458 individuals (266 non-freckled controls and 192 freckled cases) from Spain. Four loci were associated with freckling (MC1R, IRF4, ASIP and BNC2), and female sex was also found to be a predictive factor for having a freckling phenotype in our population. After identifying the most informative genetic variants responsible for human ephelides occurrence in our sample set, we developed a DNA-based freckle prediction model using a multivariate regression approach. Once developed, the capabilities of the prediction model were tested by a repeated 10-fold cross-validation approach. The proportion of correctly predicted individuals using the DNA-based freckle prediction model was 74.13%. The implementation of sex into the DNA-based freckle prediction model slightly improved the overall prediction accuracy by 2.19% (76.32%). Further evaluation of the newly-generated prediction model was performed by assessing the model's performance in a new cohort of 212 Spanish individuals, reaching a classification success rate of 74.61%. Validation of this prediction model may be carried out in larger populations, including samples from different European populations. Further research to validate and improve this newly-generated freckle prediction model will be needed before its forensic application. Together with DNA tests already validated for eye and hair colour prediction, this freckle prediction model may lead to a substantially more detailed physical description of unknown individuals from DNA found at the crime scene. Copyright © 2017 Elsevier B.V. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Sanchez, A; Little, K; Chung, J
Purpose: To validate the use of a Channelized Hotelling Observer (CHO) model for guiding image processing parameter selection and enable improved nodule detection in digital chest radiography. Methods: In a previous study, an anthropomorphic chest phantom was imaged with and without PMMA simulated nodules using a GE Discovery XR656 digital radiography system. The impact of image processing parameters was then explored using a CHO with 10 Laguerre-Gauss channels. In this work, we validate the CHO’s trend in nodule detectability as a function of two processing parameters by conducting a signal-known-exactly, multi-reader-multi-case (MRMC) ROC observer study. Five naive readers scored confidencemore » of nodule visualization in 384 images with 50% nodule prevalence. The image backgrounds were regions-of-interest extracted from 6 normal patient scans, and the digitally inserted simulated nodules were obtained from phantom data in previous work. Each patient image was processed with both a near-optimal and a worst-case parameter combination, as determined by the CHO for nodule detection. The same 192 ROIs were used for each image processing method, with 32 randomly selected lung ROIs per patient image. Finally, the MRMC data was analyzed using the freely available iMRMC software of Gallas et al. Results: The image processing parameters which were optimized for the CHO led to a statistically significant improvement (p=0.049) in human observer AUC from 0.78 to 0.86, relative to the image processing implementation which produced the lowest CHO performance. Conclusion: Differences in user-selectable image processing methods on a commercially available digital radiography system were shown to have a marked impact on performance of human observers in the task of lung nodule detection. Further, the effect of processing on humans was similar to the effect on CHO performance. Future work will expand this study to include a wider range of detection/classification tasks and more observers, including experienced chest radiologists.« less
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Kant and the development of the human and cultural sciences.
Makkreel, Rudolf A
2008-12-01
Starting with Kant's doubts about psychology as a natural science capable of explaining human behavior, several alternative attempts to conceive of human life, culture and history are examined. Kant proposes an anthropology that will be a commonly useful human science rather than a universally valid natural science. This anthropology relates to philosophy as a mode of world-cognition. Special attention is given to how Kant's theory of right can help define our appropriate place in a communal world. The different ways in which Wilhelm Dilthey and Hermann Cohen respond to Kant's idea of legitimate appropriation are also considered. The various tasks that descriptive elucidation, explanation, reflective understanding, characterization and interpretation can perform for the human and cultural sciences are examined throughout the essay.
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Chen, Xing; Huang, Yu-An; You, Zhu-Hong; Yan, Gui-Ying; Wang, Xue-Song
2017-03-01
Accumulating clinical observations have indicated that microbes living in the human body are closely associated with a wide range of human noninfectious diseases, which provides promising insights into the complex disease mechanism understanding. Predicting microbe-disease associations could not only boost human disease diagnostic and prognostic, but also improve the new drug development. However, little efforts have been attempted to understand and predict human microbe-disease associations on a large scale until now. In this work, we constructed a microbe-human disease association network and further developed a novel computational model of KATZ measure for Human Microbe-Disease Association prediction (KATZHMDA) based on the assumption that functionally similar microbes tend to have similar interaction and non-interaction patterns with noninfectious diseases, and vice versa. To our knowledge, KATZHMDA is the first tool for microbe-disease association prediction. The reliable prediction performance could be attributed to the use of KATZ measurement, and the introduction of Gaussian interaction profile kernel similarity for microbes and diseases. LOOCV and k-fold cross validation were implemented to evaluate the effectiveness of this novel computational model based on known microbe-disease associations obtained from HMDAD database. As a result, KATZHMDA achieved reliable performance with average AUCs of 0.8130 ± 0.0054, 0.8301 ± 0.0033 and 0.8382 in 2-fold and 5-fold cross validation and LOOCV framework, respectively. It is anticipated that KATZHMDA could be used to obtain more novel microbes associated with important noninfectious human diseases and therefore benefit drug discovery and human medical improvement. Matlab codes and dataset explored in this work are available at http://dwz.cn/4oX5mS . xingchen@amss.ac.cn or zhuhongyou@gmail.com or wangxuesongcumt@163.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
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Validation of the human odor span task: effects of nicotine.
MacQueen, David A; Drobes, David J
2017-10-01
Amongst non-smokers, nicotine generally enhances performance on tasks of attention, with limited effect on working memory. In contrast, nicotine has been shown to produce robust enhancements of working memory in non-humans. To address this gap, the present study investigated the effects of nicotine on the performance of non-smokers on a cognitive battery which included a working memory task reverse-translated from use with rodents (the odor span task, OST). Nicotine has been reported to enhance OST performance in rats and the present study assessed whether this effect generalizes to human performance. Thirty non-smokers were tested on three occasions after consuming either placebo, 2 mg, or 4 mg nicotine gum. On each occasion, participants completed a battery of clinical and experimental tasks of working memory and attention. Nicotine was associated with dose-dependent enhancements in sustained attention, as evidenced by increased hit accuracy on the rapid visual information processing (RVIP) task. However, nicotine failed to produce main effects on OST performance or on alternative measures of working memory (digit span, spatial span, letter-number sequencing, 2-back) or attention (digits forward, 0-back). Interestingly, enhancement of RVIP performance occurred concomitant to significant reductions in self-reported attention/concentration. Human OST performance was significantly related to N-back performance, and as in rodents, OST accuracy declined with increasing memory load. Given the similarity of human and rodent OST performance under baseline conditions and the strong association between OST and visual 0-back accuracy, the OST may be particular useful in the study of conditions characterized by inattention.
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An Integrated Framework for Human-Robot Collaborative Manipulation.
Sheng, Weihua; Thobbi, Anand; Gu, Ye
2015-10-01
This paper presents an integrated learning framework that enables humanoid robots to perform human-robot collaborative manipulation tasks. Specifically, a table-lifting task performed jointly by a human and a humanoid robot is chosen for validation purpose. The proposed framework is split into two phases: 1) phase I-learning to grasp the table and 2) phase II-learning to perform the manipulation task. An imitation learning approach is proposed for phase I. In phase II, the behavior of the robot is controlled by a combination of two types of controllers: 1) reactive and 2) proactive. The reactive controller lets the robot take a reactive control action to make the table horizontal. The proactive controller lets the robot take proactive actions based on human motion prediction. A measure of confidence of the prediction is also generated by the motion predictor. This confidence measure determines the leader/follower behavior of the robot. Hence, the robot can autonomously switch between the behaviors during the task. Finally, the performance of the human-robot team carrying out the collaborative manipulation task is experimentally evaluated on a platform consisting of a Nao humanoid robot and a Vicon motion capture system. Results show that the proposed framework can enable the robot to carry out the collaborative manipulation task successfully.
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de Souza Baptista, Roberto; Bo, Antonio P L; Hayashibe, Mitsuhiro
2017-06-01
Performance assessment of human movement is critical in diagnosis and motor-control rehabilitation. Recent developments in portable sensor technology enable clinicians to measure spatiotemporal aspects to aid in the neurological assessment. However, the extraction of quantitative information from such measurements is usually done manually through visual inspection. This paper presents a novel framework for automatic human movement assessment that executes segmentation and motor performance parameter extraction in time-series of measurements from a sequence of human movements. We use the elements of a Switching Linear Dynamic System model as building blocks to translate formal definitions and procedures from human movement analysis. Our approach provides a method for users with no expertise in signal processing to create models for movements using labeled dataset and later use it for automatic assessment. We validated our framework on preliminary tests involving six healthy adult subjects that executed common movements in functional tests and rehabilitation exercise sessions, such as sit-to-stand and lateral elevation of the arms and five elderly subjects, two of which with limited mobility, that executed the sit-to-stand movement. The proposed method worked on random motion sequences for the dual purpose of movement segmentation (accuracy of 72%-100%) and motor performance assessment (mean error of 0%-12%).
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NASA-STD-7009 Guidance Document for Human Health and Performance Models and Simulations
NASA Technical Reports Server (NTRS)
Walton, Marlei; Mulugeta, Lealem; Nelson, Emily S.; Myers, Jerry G.
2014-01-01
Rigorous verification, validation, and credibility (VVC) processes are imperative to ensure that models and simulations (MS) are sufficiently reliable to address issues within their intended scope. The NASA standard for MS, NASA-STD-7009 (7009) [1] was a resultant outcome of the Columbia Accident Investigation Board (CAIB) to ensure MS are developed, applied, and interpreted appropriately for making decisions that may impact crew or mission safety. Because the 7009 focus is engineering systems, a NASA-STD-7009 Guidance Document is being developed to augment the 7009 and provide information, tools, and techniques applicable to the probabilistic and deterministic biological MS more prevalent in human health and performance (HHP) and space biomedical research and operations.
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Zhou, Ying; Liu, Ming; Jiang, Ji; Wang, Hongyun; Hu, Pei
2013-11-15
A sensitive and rapid method based on ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the simultaneous determination of blonanserin, its major active metabolite (N-deethyl form) and other three metabolites (N-oxide form, Ethylenediamine form and Carboxylate form) in human plasma. Plasma samples were pre-purified by solid-phase extraction (SPE) and analyzed using a gradient chromatographic separation over an Acquity UPLC CSH C18 column. The mobile phase consisted of acetonitrile-water containing 5mM ammonium formate and 0.1% formic acid at a flow rate of 0.5mL/min. Positive electrospray ionization was employed as the ionization source in the multiple reaction monitoring (MRM) mode. The analysis time was about 3.5min. The method was fully validated over the concentration range of 0.01-1ng/mL for all analytes. The lower limit of quantification (LLOQ) was 0.01ng/mL. Inter- and intra-batch precision was less than 15% and the accuracy was within 85-115%. The mean extraction recoveries of all analytes at two concentration levels were consistent. Selectivity, matrix effect and stability were also validated. The method was applied to the pharmacokinetic study of blonanserin in Chinese healthy subjects. Copyright © 2013 Elsevier B.V. All rights reserved.
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Issues in benchmarking human reliability analysis methods : a literature review.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lois, Erasmia; Forester, John Alan; Tran, Tuan Q.
There is a diversity of human reliability analysis (HRA) methods available for use in assessing human performance within probabilistic risk assessment (PRA). Due to the significant differences in the methods, including the scope, approach, and underlying models, there is a need for an empirical comparison investigating the validity and reliability of the methods. To accomplish this empirical comparison, a benchmarking study is currently underway that compares HRA methods with each other and against operator performance in simulator studies. In order to account for as many effects as possible in the construction of this benchmarking study, a literature review was conducted,more » reviewing past benchmarking studies in the areas of psychology and risk assessment. A number of lessons learned through these studies are presented in order to aid in the design of future HRA benchmarking endeavors.« less
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Issues in Benchmarking Human Reliability Analysis Methods: A Literature Review
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ronald L. Boring; Stacey M. L. Hendrickson; John A. Forester
There is a diversity of human reliability analysis (HRA) methods available for use in assessing human performance within probabilistic risk assessments (PRA). Due to the significant differences in the methods, including the scope, approach, and underlying models, there is a need for an empirical comparison investigating the validity and reliability of the methods. To accomplish this empirical comparison, a benchmarking study comparing and evaluating HRA methods in assessing operator performance in simulator experiments is currently underway. In order to account for as many effects as possible in the construction of this benchmarking study, a literature review was conducted, reviewing pastmore » benchmarking studies in the areas of psychology and risk assessment. A number of lessons learned through these studies are presented in order to aid in the design of future HRA benchmarking endeavors.« less
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Borovcová, Lucie; Pauk, Volodymyr; Lemr, Karel
2018-05-01
New psychoactive substances represent serious social and health problem as tens of new compounds are detected in Europe annually. They often show structural proximity or even isomerism, which complicates their analysis. Two methods based on ultra high performance supercritical fluid chromatography and ultra high performance liquid chromatography with mass spectrometric detection were validated and compared. A simple dilute-filter-and-shoot protocol utilizing propan-2-ol or methanol for supercritical fluid or liquid chromatography, respectively, was proposed to detect and quantify 15 cathinones and phenethylamines in human urine. Both methods offered fast separation (<3 min) and short total analysis time. Precision was well <15% with a few exceptions in liquid chromatography. Limits of detection in urine ranged from 0.01 to 2.3 ng/mL, except for cathinone (5 ng/mL) in supercritical fluid chromatography. Nevertheless, this technique distinguished all analytes including four pairs of isomers, while liquid chromatography was unable to resolve fluoromethcathinone regioisomers. Concerning matrix effects and recoveries, supercritical fluid chromatography produced more uniform results for different compounds and at different concentration levels. This work demonstrates the performance and reliability of supercritical fluid chromatography and corroborates its applicability as an alternative tool for analysis of new psychoactive substances in biological matrixes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Pharmacodynamics of Promethazine in Human Subjects
NASA Technical Reports Server (NTRS)
Gatlin, K. T.; Boyd, J. L.; Wang, Z.; Das, H.; Putcha, L.
2005-01-01
Promethazine (PMZ) is the drug of choice for the treatment of symptoms associated with space motion sickness in astronauts. Side effects of PMZ include sedation, dizziness and cognitive performance impairment. In this study, we examined pharmacodynamics (PD) in human subjects and validated methods for evaluating cognitive performance effects of medications in space. METHODS: PMZ (12.5,25, and 50 mg) or placebo was administered by IM injection to human subjects in a randomized double-blind treatment design. Samples and data were collected for 72 h post dose. PD evaluation was performed using a battery of performance tests administered using WinSCAT (Windows based Space Cognitive Assessment Test) on a laptop computer, and ARES (ANAM Readiness Evaluation System) on a PDA, plasma concentrations of PMZ were measured using a LC-MS method. RESULTS: Results indicate a linear correlation between PMZ concentration and cognitive performance parameters (p<0.01). Test accuracy decreased and test completion time and response time increased significantly with increasing plasma PMZ concentration. CONCLUSIONS: These results suggest a concentration dependent decrement in cognitive performance associated with PMZ. WinSCAT and ARES are sensitive tools for the assessment PMZ PD and may be applicable for such evaluations with other neurocognitive drugs.
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Rodríguez-Gómez, R; Martín, J; Zafra-Gómez, A; Alonso, E; Vílchez, J L; Navalón, A
2017-02-01
Rapid industrial growth has increased human exposure to a large variety of chemicals with adverse health effects. These industrial chemicals are usually present in the environment, foods, beverages, clothes and personal care products. Among these compounds, endocrine disrupting chemicals (EDCs) have raised concern over the last years. In the present work, the determination of 21 EDCs in human hair samples is proposed. An analytical method based on the digestion of the samples with a mixture of acetic acid/methanol (20:80, v/v) followed by a solid-liquid microextraction and analysis by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated. The most influential parameters affecting the extraction method were optimized. The method was validated using matrix-matched calibration and recovery assays. Limits of detection ranged from 0.2 to 4 ng g -1 , limits of quantification from 0.5 to 12 ng g -1 , and inter- and intra-day variability was under 15% in all cases. Recovery rates for spiked samples ranged from 92.1 to 113.8%. The method was applied for the determination of the selected compounds in human hair. Samples were collected weekly from six randomly selected volunteers (three men and three women) over a three-month period. All the analyzed samples tested positive for at least one of the analyzed compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Astvad, Karen Marie Thyssen; Meletiadis, Joseph; Whalley, Sarah
2017-01-01
ABSTRACT The invertebrate model organism Galleria mellonella can be used to assess the efficacy of treatment of fungal infection. The fluconazole dose best mimicking human exposure during licensed dosing is unknown. We validated a bioassay for fluconazole detection in hemolymph and determined the fluconazole pharmacokinetics and pharmacodynamics in larval hemolymph in order to estimate a humanized dose for future experiments. A bioassay using 4-mm agar wells, 20 μl hemolymph, and the hypersusceptible Candida albicans DSY2621 was established and compared to a validated liquid chromatography-tandem mass spectrometry (LC–MS-MS) method. G. mellonella larvae were injected with fluconazole (5, 10, and 20 mg/kg of larval weight), and hemolymph was harvested for 24 h for pharmacokinetics calculations. The exposure was compared to the human exposure during standard licensed dosing. The bioassay had a linear standard curve between 1 and 20 mg/liter. Accuracy and coefficients of variation (percent) values were below 10%. The Spearman coefficient between assays was 0.94. Fluconazole larval pharmacokinetics followed one-compartment linear kinetics, with the 24-h area under the hemolymph concentration-time curve (AUC24 h) being 93, 173, and 406 mg · h/liter for the three doses compared to 400 mg · h/liter in humans under licensed treatment. In conclusion, a bioassay was validated for fluconazole determination in hemolymph. The pharmacokinetics was linear. An exposure comparable to the human exposure during standard licensed dosing was obtained with 20 mg/kg. PMID:28760893
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De La Vega, Francisco M; Dailey, David; Ziegle, Janet; Williams, Julie; Madden, Dawn; Gilbert, Dennis A
2002-06-01
Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies--specifically for candidate-gene, candidate-region, and whole-genome association studies--will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics' human genome assembly and enormous resource ofphysically mapped SNPs (approximately 4,000,000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency ofthe polymorphisms. We also discuss an advanced, high-performance SNP assay chemisty--a new generation of the TaqMan probe-based, 5' nuclease assay-and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.
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NASA Astrophysics Data System (ADS)
Straub, Jeremy
2014-06-01
Resident space objects (RSOs) pose a significant threat to orbital assets. Due to high relative velocities, even a small RSO can cause significant damage to an object that it strikes. Worse, in many cases a collision may create numerous additional RSOs, if the impacted object shatters apart. These new RSOs will have heterogeneous mass, size and orbital characteristics. Collision avoidance systems (CASs) are used to maneuver spacecraft out of the path of RSOs to prevent these impacts. A RSO CAS must be validated to ensure that it is able to perform effectively given a virtually unlimited number of strike scenarios. This paper presents work on the creation of a testing environment and AI testing routine that can be utilized to perform verification and validation activities for cyber-physical systems. It reviews prior work on automated and autonomous testing. Comparative performance (relative to the performance of a human tester) is discussed.
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Objective measures of situation awareness in a simulated medical environment
Wright, M; Taekman, J; Endsley, M
2004-01-01
One major limitation in the use of human patient simulators is a lack of objective, validated measures of human performance. Objective measures are necessary if simulators are to be used to evaluate the skills and training of medical practitioners and teams or to evaluate the impact of new processes or equipment design on overall system performance. Situation awareness (SA) refers to a person's perception and understanding of their dynamic environment. This awareness and comprehension is critical in making correct decisions that ultimately lead to correct actions in medical care settings. An objective measure of SA may be more sensitive and diagnostic than traditional performance measures. This paper reviews a theory of SA and discusses the methods required for developing an objective measure of SA within the context of a simulated medical environment. Analysis and interpretation of SA data for both individual and team performance in health care are also presented. PMID:15465958
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Matuszak, Małgorzata; Minorczyk, Maria; Góralczyk, Katarzyna; Hernik, Agnieszka; Struciński, Paweł; Liszewska, Monika; Czaja, Katarzyna; Korcz, Wojciech; Łyczewska, Monika; Ludwicki, Jan K
2016-01-01
Polybrominated diphenyl ethers (PBDEs) as other persistent organic pollutants like polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) pose a significant hazard to human health, mainly due to interference with the endocrine system and carcinogenetic effects. Humans are exposed to these substances mainly through a food of animal origin. These pollutants are globally detected in human matrices which requires to dispose reliable and simple analytical method that would enable further studies to assess the exposure of specific human populations to these compounds. The purpose of this study was to modify and validate of the analytical procedure for the simultaneous determination of selected PBDEs, PCBs and OCPs in human blood serum samples. The analytical measurement was performed by GC-µECD following preparation of serum samples (denaturation, multiple extraction, lipid removal). Identity of the compounds was confirmed by GC-MS. The method was characterised by the appropriate linearity, good repeatability (CV below 20%). The recoveries ranged from 52.9 to 125.0% depending on compound and level of fortification. The limit of quantification was set at 0.03 ng mL(-1) of serum. The modified analytical method proved to be suitable for the simultaneous determination of selected PBDEs, PCBs and OCPs in human blood serum by GC-µECD with good precision.
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NASA Technical Reports Server (NTRS)
Arneson, Heather; Evans, Antony D.; Li, Jinhua; Wei, Mei Yueh
2017-01-01
Integrated Demand Management (IDM) is a near- to mid-term NASA concept that proposes to address mismatches in air traffic system demand and capacity by using strategic flow management capabilities to pre-condition demand into the more tactical Time-Based Flow Management System (TBFM). This paper describes an automated simulation capability to support IDM concept development. The capability closely mimics existing human-in-the-loop (HITL) capabilities, automating both the human components and collaboration between operational systems, and speeding up the real-time aircraft simulations. Such a capability allows for parametric studies that will inform the HITL simulations, identifying breaking points and parameter values at which significant changes in system behavior occur. This paper also describes the initial validation of individual components of the automated simulation capability, and an example application comparing the performance of the IDM concept under two TBFM scheduling paradigms. The results and conclusions from this simulation compare closely to those from previous HITL simulations using similar scenarios, providing an initial validation of the automated simulation capability.
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Vitali, Rachel V.; Cain, Stephen M.; Zaferiou, Antonia M.; Ojeda, Lauro V.; Perkins, Noel C.
2017-01-01
Three-dimensional rotations across the human knee serve as important markers of knee health and performance in multiple contexts including human mobility, worker safety and health, athletic performance, and warfighter performance. While knee rotations can be estimated using optical motion capture, that method is largely limited to the laboratory and small capture volumes. These limitations may be overcome by deploying wearable inertial measurement units (IMUs). The objective of this study is to present a new IMU-based method for estimating 3D knee rotations and to benchmark the accuracy of the results using an instrumented mechanical linkage. The method employs data from shank- and thigh-mounted IMUs and a vector constraint for the medial-lateral axis of the knee during periods when the knee joint functions predominantly as a hinge. The method is carefully validated using data from high precision optical encoders in a mechanism that replicates 3D knee rotations spanning (1) pure flexion/extension, (2) pure internal/external rotation, (3) pure abduction/adduction, and (4) combinations of all three rotations. Regardless of the movement type, the IMU-derived estimates of 3D knee rotations replicate the truth data with high confidence (RMS error < 4° and correlation coefficient r≥0.94). PMID:28846613
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Hand gesture recognition in confined spaces with partial observability and occultation constraints
NASA Astrophysics Data System (ADS)
Shirkhodaie, Amir; Chan, Alex; Hu, Shuowen
2016-05-01
Human activity detection and recognition capabilities have broad applications for military and homeland security. These tasks are very complicated, however, especially when multiple persons are performing concurrent activities in confined spaces that impose significant obstruction, occultation, and observability uncertainty. In this paper, our primary contribution is to present a dedicated taxonomy and kinematic ontology that are developed for in-vehicle group human activities (IVGA). Secondly, we describe a set of hand-observable patterns that represents certain IVGA examples. Thirdly, we propose two classifiers for hand gesture recognition and compare their performance individually and jointly. Finally, we present a variant of Hidden Markov Model for Bayesian tracking, recognition, and annotation of hand motions, which enables spatiotemporal inference to human group activity perception and understanding. To validate our approach, synthetic (graphical data from virtual environment) and real physical environment video imagery are employed to verify the performance of these hand gesture classifiers, while measuring their efficiency and effectiveness based on the proposed Hidden Markov Model for tracking and interpreting dynamic spatiotemporal IVGA scenarios.
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Cook, Sarah F; King, Amber D; van den Anker, John N; Wilkins, Diana G
2015-12-15
Drug metabolism plays a key role in acetaminophen (paracetamol)-induced hepatotoxicity, and quantification of acetaminophen metabolites provides critical information about factors influencing susceptibility to acetaminophen-induced hepatotoxicity in clinical and experimental settings. The aims of this study were to develop, validate, and apply high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) methods for simultaneous quantification of acetaminophen, acetaminophen-glucuronide, acetaminophen-sulfate, acetaminophen-glutathione, acetaminophen-cysteine, and acetaminophen-N-acetylcysteine in small volumes of human plasma and urine. In the reported procedures, acetaminophen-d4 and acetaminophen-d3-sulfate were utilized as internal standards (IS). Analytes and IS were recovered from human plasma (10μL) by protein precipitation with acetonitrile. Human urine (10μL) was prepared by fortification with IS followed only by sample dilution. Calibration concentration ranges were tailored to literature values for each analyte in each biological matrix. Prepared samples from plasma and urine were analyzed under the same HPLC-ESI-MS/MS conditions, and chromatographic separation was achieved through use of an Agilent Poroshell 120 EC-C18 column with a 20-min run time per injected sample. The analytes could be accurately and precisely quantified over 2.0-3.5 orders of magnitude. Across both matrices, mean intra- and inter-assay accuracies ranged from 85% to 112%, and intra- and inter-assay imprecision did not exceed 15%. Validation experiments included tests for specificity, recovery and ionization efficiency, inter-individual variability in matrix effects, stock solution stability, and sample stability under a variety of storage and handling conditions (room temperature, freezer, freeze-thaw, and post-preparative). The utility and suitability of the reported procedures were illustrated by analysis of pharmacokinetic samples collected from neonates receiving intravenous acetaminophen. Copyright © 2015 Elsevier B.V. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Rainina, Evguenia I.; McCune, D. E.; Luna, Maria L.
2012-05-31
The goal of this study was to validate the previously observed high biological kill performance of PAEROSOL, a semi-dry, micro-aerosol decontamination technology, against common HAI in a non-human subject trial within a hospital setting of Madigan Army Medical Center (MAMC) on Joint Base Lewis-McChord in Tacoma, Washington. In addition to validating the disinfecting efficacy of PAEROSOL, the objectives of the trial included a demonstration of PAEROSOL environmental safety, (i.e., impact to hospital interior materials and electronic equipment exposed during testing) and PAEROSOL parameters optimization for future deployment.
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Using stroboscopic flow imaging to validate large-scale computational fluid dynamics simulations
NASA Astrophysics Data System (ADS)
Laurence, Ted A.; Ly, Sonny; Fong, Erika; Shusteff, Maxim; Randles, Amanda; Gounley, John; Draeger, Erik
2017-02-01
The utility and accuracy of computational modeling often requires direct validation against experimental measurements. The work presented here is motivated by taking a combined experimental and computational approach to determine the ability of large-scale computational fluid dynamics (CFD) simulations to understand and predict the dynamics of circulating tumor cells in clinically relevant environments. We use stroboscopic light sheet fluorescence imaging to track the paths and measure the velocities of fluorescent microspheres throughout a human aorta model. Performed over complex physiologicallyrealistic 3D geometries, large data sets are acquired with microscopic resolution over macroscopic distances.
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Hoffman, Justin T; Rossi, Steven S; Espina-Quinto, Rowena; Letendre, Scott; Capparelli, Edmund V
2013-01-01
Background Previously published methods for determination of efavirenz (EFV) in human dried blood spots (DBS) employ costly and complex liquid chromatography/mass spectrometry. We describe the validation and evaluation of a simple and inexpensive high-performance liquid chromatography (HPLC) method for EFV quantification in human DBS and dried plasma spots (DPS), using ultraviolet (UV) detection appropriate for resource-limited settings. Methods 100μl of heparinized whole blood or plasma were spotted onto blood collection cards, dried, punched, and eluted. Eluates are injected onto a C-18 reversed phase HPLC column. EFV is separated isocratically using a potassium phosphate and ACN mobile phase. UV detection is at 245nm. Quantitation is by use of external calibration standards. Following validation, the method was evaluated using whole blood and plasma from HIV-positive patients undergoing EFV therapy. Results Mean recovery of drug from dried blood spots is 91.5%. The method is linear over the validated concentration range of 0.3125 – 20.0μg/mL. A good correlation (Spearman r=0.96) between paired plasma and DBS EFV concentrations from the clinical samples was observed, and hematocrit level was not found to be a significant determinant of the EFV DBS level. The mean observed CDBS/Cplasma ratio was 0.68. A good correlation (Spearman r=0.96) between paired plasma and DPS EFV concentrations from the clinical samples was observed. The mean percent deviation of DPS samples from plasma samples is 1.68%. Conclusions Dried whole blood spot or dried plasma spot sampling is well suited for monitoring EFV therapy in resource limited settings, particularly when high sensitivity is not essential. PMID:23503446
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Natarajan, Arutselvan; Arksey, Natasha; Iagaru, Andrei; Chin, Frederick T; Gambhir, Sanjiv Sam
2015-01-01
Manufacturing of 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-rituximab injection under good manufacturing practices (GMP) was validated for imaging of patients with CD20+ B-cell non-Hodgkin lymphoma. Rituximab was purified by size exclusion high performance liquid chromatography (HPLC) and conjugated to DOTA-mono-(N-hydroxysuccinimidyl) ester. 64CuCl2, buffers, reagents, and other raw materials were obtained as high-grade quality. Following a semi-automated synthesis of 64Cu-DOTA-rituximab, a series of quality control tests was performed. The product was further tested in vivo using micro-positron emission tomography/computed tomography (PET/CT) to assess targeting ability towards human CD20 in transgenic mice. Three batches of 64Cu-DOTA-rituximab final product were prepared as per GMP specifications. The radiolabeling yield from these batches was 93.1 ± 5.8%; these provided final product with radiopharmaceutical yield, purity, and specific activity of 59.2 ± 5.1% (0.9 ± 0.1 GBq of 64Cu), > 95% (by HPLC and radio-thin layer chromatography), and 229.4 ± 43.3 GBq/µmol (or 1.5 ± 0.3 MBq/µg), respectively. The doses passed apyrogenicity and human serum stability specifications, were sterile up to 14 days, and retained > 60% immunoreactivity. In vivo micro-PET/CT mouse images at 24 hours postinjection showed that the tracer targeted the intended sites of human CD20 expression. Thus, we have validated the manufacturing of GMP grade 64Cu-DOTA-rituximab for injection in the clinical setting.
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Development and validation of Aviation Causal Contributors for Error Reporting Systems (ACCERS).
Baker, David P; Krokos, Kelley J
2007-04-01
This investigation sought to develop a reliable and valid classification system for identifying and classifying the underlying causes of pilot errors reported under the Aviation Safety Action Program (ASAP). ASAP is a voluntary safety program that air carriers may establish to study pilot and crew performance on the line. In ASAP programs, similar to the Aviation Safety Reporting System, pilots self-report incidents by filing a short text description of the event. The identification of contributors to errors is critical if organizations are to improve human performance, yet it is difficult for analysts to extract this information from text narratives. A taxonomy was needed that could be used by pilots to classify the causes of errors. After completing a thorough literature review, pilot interviews and a card-sorting task were conducted in Studies 1 and 2 to develop the initial structure of the Aviation Causal Contributors for Event Reporting Systems (ACCERS) taxonomy. The reliability and utility of ACCERS was then tested in studies 3a and 3b by having pilots independently classify the primary and secondary causes of ASAP reports. The results provided initial evidence for the internal and external validity of ACCERS. Pilots were found to demonstrate adequate levels of agreement with respect to their category classifications. ACCERS appears to be a useful system for studying human error captured under pilot ASAP reports. Future work should focus on how ACCERS is organized and whether it can be used or modified to classify human error in ASAP programs for other aviation-related job categories such as dispatchers. Potential applications of this research include systems in which individuals self-report errors and that attempt to extract and classify the causes of those events.
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A Bacterial Glycoengineered Antigen for Improved Serodiagnosis of Porcine Brucellosis.
Cortina, María E; Balzano, Rodrigo E; Rey Serantes, Diego A; Caillava, Ana J; Elena, Sebastián; Ferreira, A C; Nicola, Ana M; Ugalde, Juan E; Comerci, Diego J; Ciocchini, Andrés E
2016-06-01
Brucellosis is a highly zoonotic disease that affects animals and human beings. Brucella suis is the etiological agent of porcine brucellosis and one of the major human brucellosis pathogens. Laboratory diagnosis of porcine brucellosis mainly relies on serological tests, and it has been widely demonstrated that serological assays based on the detection of anti O-polysaccharide antibodies are the most sensitive tests. Here, we validate a recombinant glycoprotein antigen, an N-formylperosamine O-polysaccharide-protein conjugate (OAg-AcrA), for diagnosis of porcine brucellosis. An indirect immunoassay based on the detection of anti-O-polysaccharide IgG antibodies was developed coupling OAg-AcrA to enzyme-linked immunosorbent assay plates (glyco-iELISA). To validate the assay, 563 serum samples obtained from experimentally infected and immunized pigs, as well as animals naturally infected with B. suis biovar 1 or 2, were tested. A receiver operating characteristic (ROC) analysis was performed, and based on this analysis, the optimum cutoff value was 0.56 (relative reactivity), which resulted in a diagnostic sensitivity and specificity of 100% and 99.7%, respectively. A cutoff value of 0.78 resulted in a test sensitivity of 98.4% and a test specificity of 100%. Overall, our results demonstrate that the glyco-iELISA is highly accurate for diagnosis of porcine brucellosis, improving the diagnostic performance of current serological tests. The recombinant glycoprotein OAg-AcrA can be produced in large homogeneous batches in a standardized way, making it an ideal candidate for further validation as a universal antigen for diagnosis of "smooth" brucellosis in animals and humans. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Direct quantification of fatty acids in human milk by gas chromatography.
Cruz-Hernandez, Cristina; Goeuriot, Sebastien; Giuffrida, Francesca; Thakkar, Sagar K; Destaillats, Frédéric
2013-04-05
Human milk provides the key nutrients necessary for the infants' growth and development. The fatty acid composition of human milk has been extensively studied over the last 20 years and the results obtained by analyzing the fatty acid profile followed by lipid extraction and expressing data as g per 100g of fatty acids. The main drawback is that normalizing data set does not give any information on the amount of fatty acid mother's milk and therefore the level of intake by the infant. The objective of the present study was to develop and validate a direct method to analyze the fatty acid content in liquid human milk samples. Hydrochloric acid in a solution of methanol was selected as the catalyst and methyl undecanoate (11:0) as the internal standard together with tritridecanoin (13:0 TAG) to monitor transesterification performance. The separation of fatty acid methyl esters (FAME) was performed using a 100 m highly polar capillary column and a certified calibration mixture used to calculate experimental response factors. The method is suitable to quantify fatty acids in human milk from a 250 μL sample and allow expression of the data in mg of fatty acids per deciliter of human milk as well as weight % of fatty acids. The method has been validated and show a good repeatability [CV(r)<15% and CV(r)<20% for the concentrations close to the LOQ] and a good intermediate reproducibility [CV(iR)<15% and CV(iR)<20% for the concentrations close to the LOQ]. The method was applied to analyze human milk samples obtained from 50 mothers 4 weeks post partum and the data are provided in absolute and relative quantity. These results show that the inter-individual variability of the fatty acid content in human milk is of prime importance and such information cannot be captured with normalized data sets. Copyright © 2013 Elsevier B.V. All rights reserved.
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Validity and reliability of a health care service evaluation instrument for tuberculosis
Scatena, Lucia Marina; Wysocki, Anneliese Domingues; Beraldo, Aline Ale; Magnabosco, Gabriela Tavares; Brunello, Maria Eugênia Firmino; Netto, Antonio Ruffino; Nogueira, Jordana de Almeida; Silva, Reinaldo Antonio; Brito, Ewerton William Gomes; Alexandre, Patricia Borges Dias; Monroe, Aline Aparecida; Villa, Tereza Cristina Scatena
2015-01-01
OBJECTIVE To evaluate the validity and reliability of an instrument that evaluates the structure of primary health care units for the treatment of tuberculosis. METHODS This cross-sectional study used simple random sampling and evaluated 1,037 health care professionals from five Brazilian municipalities (Natal, state of Rio Grande do Norte; Cabedelo, state of Paraíba; Foz do Iguaçu, state of Parana; Sao José do Rio Preto, state of Sao Paulo, and Uberaba, state of Minas Gerais) in 2011. Structural indicators were identified and validated, considering different methods of organization of the health care system in the municipalities of different population sizes. Each structure represented the organization of health care services and contained the resources available for the execution of health care services: physical resources (equipment, consumables, and facilities); human resources (number and qualification); and resources for maintenance of the existing infrastructure and technology (deemed as the organization of health care services). The statistical analyses used in the validation process included reliability analysis, exploratory factor analysis, and confirmatory factor analysis. RESULTS The validation process indicated the retention of five factors, with 85.9% of the total variance explained, internal consistency between 0.6460 and 0.7802, and quality of fit of the confirmatory factor analysis of 0.995 using the goodness-of-fit index. The retained factors comprised five structural indicators: professionals involved in the care of tuberculosis patients, training, access to recording instruments, availability of supplies, and coordination of health care services with other levels of care. Availability of supplies had the best performance and the lowest coefficient of variation among the services evaluated. The indicators of assessment of human resources and coordination with other levels of care had satisfactory performance, but the latter showed the highest coefficient of variation. The performance of the indicators “training” and “access to recording instruments” was inferior to that of other indicators. CONCLUSIONS The instrument showed feasibility of application and potential to assess the structure of primary health care units for the treatment of tuberculosis. PMID:25741651
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Mitter, Christian; Jakab, András; Brugger, Peter C.; Ricken, Gerda; Gruber, Gerlinde M.; Bettelheim, Dieter; Scharrer, Anke; Langs, Georg; Hainfellner, Johannes A.; Prayer, Daniela; Kasprian, Gregor
2015-01-01
Diffusion tensor imaging (DTI) and tractography offer the unique possibility to visualize the developing white matter macroanatomy of the human fetal brain in vivo and in utero and are currently under investigation for their potential use in the diagnosis of developmental pathologies of the human central nervous system. However, in order to establish in utero DTI as a clinical imaging tool, an independent comparison between macroscopic imaging and microscopic histology data in the same subject is needed. The present study aimed to cross-validate normal as well as abnormal in utero tractography results of commissural and internal capsule fibers in human fetal brains using postmortem histological structure tensor (ST) analysis. In utero tractography findings from two structurally unremarkable and five abnormal fetal brains were compared to the results of postmortem ST analysis applied to digitalized whole hemisphere sections of the same subjects. An approach to perform ST-based deterministic tractography in histological sections was implemented to overcome limitations in correlating in utero tractography to postmortem histology data. ST analysis and histology-based tractography of fetal brain sections enabled the direct assessment of the anisotropic organization and main fiber orientation of fetal telencephalic layers on a micro- and macroscopic scale, and validated in utero tractography results of corpus callosum and internal capsule fiber tracts. Cross-validation of abnormal in utero tractography results could be achieved in four subjects with agenesis of the corpus callosum (ACC) and in two cases with malformations of internal capsule fibers. In addition, potential limitations of current DTI-based in utero tractography could be demonstrated in several brain regions. Combining the three-dimensional nature of DTI-based in utero tractography with the microscopic resolution provided by histological ST analysis may ultimately facilitate a more complete morphologic characterization of axon guidance disorders at prenatal stages of human brain development. PMID:26732460
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2009-09-01
Legionella Pneumophila (ATCC 33152) were acquired from the American Type Culture Collection (ATCC; Manassas, VA, USA). Conventional PCR testing The primers... Legionella Pneumophila – One nanogram of genomic DNA was used as a DNA template in each assay. Assays were performed in triplicate. Samples were negative at
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-16
..., entitled Protection of Children from Environmental Health Risks and Safety Risks (62 FR 19885, April 23... toxicity.'' EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide... considered its validity, completeness, and reliability and the relationship of this information to human risk...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-01-25
... elements of process validation for the manufacture of human and animal drug and biological products... process validation for the manufacture of human and animal drug and biological products, including APIs. This guidance describes process validation activities in three stages: In Stage 1, Process Design, the...
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Nucleic acid tests for the detection of alpha human papillomaviruses.
Poljak, Mario; Cuzick, Jack; Kocjan, Boštjan J; Iftner, Thomas; Dillner, Joakim; Arbyn, Marc
2012-11-20
Testing for high-risk types of alpha human papillomaviruses (HPV) is an invaluable part of clinical guidelines for cervical carcinoma screening, management and treatment. In this comprehensive inventory of commercial tests for detection of alpha-HPV, we identified at least 125 distinct HPV tests and at least 84 variants of the original tests. However, only a small subset of HPV tests has documented clinical performance for any of the standard HPV testing indications. For more than 75% of HPV tests currently on the market, no single publication in peer-reviewed literature can be identified. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated in the lab, it is essential that the whole procedure of HPV testing is subject to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Manufacturers of HPV tests are urged to put more effort into evaluating their current and future products analytically, using international standards, and for clinical applications, using clinically validated endpoints. To assist with analytical validation, the World Health Organization is developing international standards for HPV types other than HPV16 and HPV18 and is planning development of external quality control panels specifically designed to be used for performance evaluation of current and future HPV tests. There is a need for more competitively priced HPV tests, especially for resource-poor countries, and uniform test validation criteria based on international standards should enable issuing more competitive and fair tender notices for purchasing. Automation systems allowing large-scale testing, as well as further increases in clinical performance, are the main needs in the further improvement of HPV tests. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Development and Initial Validation of an Instrument for Human Capital Planning
ERIC Educational Resources Information Center
Zula, Kenneth J.; Chermack, Thomas J.
2008-01-01
This article reports on development and validation of an instrument for use in human capital approaches for organizational planning. The article describes use of a team of subject matter experts in developing a measure of human capital planning, and use of exploratory factor analysis techniques to validate the resulting instrument. These data were…
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aMAP is a validated pipeline for registration and segmentation of high-resolution mouse brain data
Niedworok, Christian J.; Brown, Alexander P. Y.; Jorge Cardoso, M.; Osten, Pavel; Ourselin, Sebastien; Modat, Marc; Margrie, Troy W.
2016-01-01
The validation of automated image registration and segmentation is crucial for accurate and reliable mapping of brain connectivity and function in three-dimensional (3D) data sets. While validation standards are necessarily high and routinely met in the clinical arena, they have to date been lacking for high-resolution microscopy data sets obtained from the rodent brain. Here we present a tool for optimized automated mouse atlas propagation (aMAP) based on clinical registration software (NiftyReg) for anatomical segmentation of high-resolution 3D fluorescence images of the adult mouse brain. We empirically evaluate aMAP as a method for registration and subsequent segmentation by validating it against the performance of expert human raters. This study therefore establishes a benchmark standard for mapping the molecular function and cellular connectivity of the rodent brain. PMID:27384127
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An Evaluation of the Performance Diagnostic Checklist-Human Services (PDC-HS) Across Domains.
Wilder, David A; Lipschultz, Joshua; Gehrman, Chana
2018-06-01
The Performance Diagnostic Checklist-Human Services (PDC-HS) is an informant-based tool designed to assess the environmental variables that contribute to poor employee performance in human service settings. Although the PDC-HS has been shown to effectively identify variables contributing to problematic performance, interventions based on only two of the four PDC-HS domains have been evaluated to date. In addition, the extent to which PDC-HS-indicated interventions are more effective than nonindicated interventions for two domains remains unclear. In the current study, we administered the PDC-HS to supervisors to assess the variables contributing to infrequent teaching of verbal operants and use of a timer by therapists at a center-based autism treatment program. Each of the four PDC-HS domains was identified as contributing to poor performance for at least one therapist. We then evaluated PDC-HS-indicated interventions for each domain. In addition, to assess the predictive validity of the tool, we evaluated various nonindicated interventions prior to implementing a PDC-HS-indicated intervention for two of the four domains. Results suggest that the PDC-HS-indicated interventions were effective across all four domains and were more effective than the nonindicated interventions for the two domains for which they were evaluated. Results are discussed in terms of the utility of the PDC-HS to identify appropriate interventions to manage therapist performance in human service settings.
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Enhanced Oceanic Operations Human-In-The-Loop In-Trail Procedure Validation Simulation Study
NASA Technical Reports Server (NTRS)
Murdoch, Jennifer L.; Bussink, Frank J. L.; Chamberlain, James P.; Chartrand, Ryan C.; Palmer, Michael T.; Palmer, Susan O.
2008-01-01
The Enhanced Oceanic Operations Human-In-The-Loop In-Trail Procedure (ITP) Validation Simulation Study investigated the viability of an ITP designed to enable oceanic flight level changes that would not otherwise be possible. Twelve commercial airline pilots with current oceanic experience flew a series of simulated scenarios involving either standard or ITP flight level change maneuvers and provided subjective workload ratings, assessments of ITP validity and acceptability, and objective performance measures associated with the appropriate selection, request, and execution of ITP flight level change maneuvers. In the majority of scenarios, subject pilots correctly assessed the traffic situation, selected an appropriate response (i.e., either a standard flight level change request, an ITP request, or no request), and executed their selected flight level change procedure, if any, without error. Workload ratings for ITP maneuvers were acceptable and not substantially higher than for standard flight level change maneuvers, and, for the majority of scenarios and subject pilots, subjective acceptability ratings and comments for ITP were generally high and positive. Qualitatively, the ITP was found to be valid and acceptable. However, the error rates for ITP maneuvers were higher than for standard flight level changes, and these errors may have design implications for both the ITP and the study's prototype traffic display. These errors and their implications are discussed.
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Assessment of mass detection performance in contrast enhanced digital mammography
NASA Astrophysics Data System (ADS)
Carton, Ann-Katherine; de Carvalho, Pablo M.; Li, Zhijin; Dromain, Clarisse; Muller, Serge
2015-03-01
We address the detectability of contrast-agent enhancing masses for contrast-agent enhanced spectral mammography (CESM), a dual-energy technique providing functional projection images of breast tissue perfusion and vascularity using simulated CESM images. First, the realism of simulated CESM images from anthropomorphic breast software phantoms generated with a software X-ray imaging platform was validated. Breast texture was characterized by power-law coefficients calculated in data sets of real clinical and simulated images. We also performed a 2-alternative forced choice (2-AFC) psychophysical experiment whereby simulated and real images were presented side-by-side to an experienced radiologist to test if real images could be distinguished from the simulated images. It was found that texture in our simulated CESM images has a fairly realistic appearance. Next, the relative performance of human readers and previously developed mathematical observers was assessed for the detection of iodine-enhancing mass lesions containing different contrast agent concentrations. A four alternative-forced-choice (4 AFC) task was designed; the task for the model and human observer was to detect which one of the four simulated DE recombined images contained an iodineenhancing mass. Our results showed that the NPW and NPWE models largely outperform human performance. After introduction of an internal noise component, both observers approached human performance. The CHO observer performs slightly worse than the average human observer. There is still work to be done in improving model observers as predictors of human-observer performance. Larger trials could also improve our test statistics. We hope that in the future, this framework of software breast phantoms, virtual image acquisition and processing, and mathematical observers can be beneficial to optimize CESM imaging techniques.
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Validation of the process criteria for assessment of a hospital nursing service.
Feldman, Liliane Bauer; Cunha, Isabel Cristina Kowal Olm; D'Innocenzo, Maria
2013-01-01
to validate an instrument containing process criteria for assessment of a hospital nursing service based on the National Accreditation Organization program. a descriptive, quantitative methodological study performed in stages. An instrument constructed with 69 process criteria was assessed by 49 nurses from accredited hospitals in 2009, according to a Likert scale, and validated by 16 judges through Delphi rounds in 2010. the original instrument assessed by nurses with 69 process criteria was judged by the degree of importance, and changed to 39 criteria. In the first Delphi round, the 39 criteria reached consensus among the 19 judges, with a medium reliability by Cronbach's alpha. In the second round, 40 converging criteria were validated by 16 judges, with high reliability. The criteria addressed management, costs, teaching, education, indicators, protocols, human resources, communication, among others. the 40 process criteria formed a validated instrument to assess the hospital nursing service which, when measured, can better direct interventions by nurses in reaching and strengthening outcomes.
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Behavioral Health and Performance Element: Tools and Technologies
NASA Technical Reports Server (NTRS)
Leveton, Lauren B.
2009-01-01
This slide presentation reviews the research into the Behavioral Health and Performance (BHP) of the Human Research Program. The program element goal is to identify, characterize and prevent or reduce behavioral health and performance risks associated with space travel, exploration, and return to terrestrial life. To accomplish this goal the program focuses on applied research that is designed to yield deliverables that reduce risk. There are several different elements that are of particular interest: Behavioral Medicine, Sleep, and team composition, and team work. In order to assure success for NASA missions the Human Research Program develops and validate the standards for each of the areas of interest. There is discussion of the impact on BHP while astronauts are on Long Duration Missions. The effort in this research is to create tools to meet the BHP concerns, these prospective tools are reviewed.
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EVALUATING ROBOT TECHNOLOGIES AS TOOLS TO EXPLORE RADIOLOGICAL AND OTHER HAZARDOUS ENVIRONMENTS
DOE Office of Scientific and Technical Information (OSTI.GOV)
Curtis W. Nielsen; David I. Gertman; David J. Bruemmer
2008-03-01
There is a general consensus that robots could be beneficial in performing tasks within hazardous radiological environments. Most control of robots in hazardous environments involves master-slave or teleoperation relationships between the human and the robot. While teleoperation-based solutions keep humans out of harms way, they also change the training requirements to accomplish a task. In this paper we present a research methodology that allowed scientists at Idaho National Laboratory to identify, develop, and prove a semi-autonomous robot solution for search and characterization tasks within a hazardous environment. Two experiments are summarized that validated the use of semi-autonomy and show thatmore » robot autonomy can help mitigate some of the performance differences between operators who have different levels of robot experience, and can improve performance over teleoperated systems.« less
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Marshall Space Flight Center's Virtual Reality Applications Program 1993
NASA Technical Reports Server (NTRS)
Hale, Joseph P., II
1993-01-01
A Virtual Reality (VR) applications program has been under development at the Marshall Space Flight Center (MSFC) since 1989. Other NASA Centers, most notably Ames Research Center (ARC), have contributed to the development of the VR enabling technologies and VR systems. This VR technology development has now reached a level of maturity where specific applications of VR as a tool can be considered. The objectives of the MSFC VR Applications Program are to develop, validate, and utilize VR as a Human Factors design and operations analysis tool and to assess and evaluate VR as a tool in other applications (e.g., training, operations development, mission support, teleoperations planning, etc.). The long-term goals of this technology program is to enable specialized Human Factors analyses earlier in the hardware and operations development process and develop more effective training and mission support systems. The capability to perform specialized Human Factors analyses earlier in the hardware and operations development process is required to better refine and validate requirements during the requirements definition phase. This leads to a more efficient design process where perturbations caused by late-occurring requirements changes are minimized. A validated set of VR analytical tools must be developed to enable a more efficient process for the design and development of space systems and operations. Similarly, training and mission support systems must exploit state-of-the-art computer-based technologies to maximize training effectiveness and enhance mission support. The approach of the VR Applications Program is to develop and validate appropriate virtual environments and associated object kinematic and behavior attributes for specific classes of applications. These application-specific environments and associated simulations will be validated, where possible, through empirical comparisons with existing, accepted tools and methodologies. These validated VR analytical tools will then be available for use in the design and development of space systems and operations and in training and mission support systems.
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Min, Hophil; Kim, Sang Jin; Oh, Sohee; Kim, Kyunggon; Yu, Hyeong Gon; Park, Taesung; Kim, Youngsoo
2016-01-01
Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR. PMID:26665153
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HuMOVE: a low-invasive wearable monitoring platform in sexual medicine.
Ciuti, Gastone; Nardi, Matteo; Valdastri, Pietro; Menciassi, Arianna; Basile Fasolo, Ciro; Dario, Paolo
2014-10-01
To investigate an accelerometer-based wearable system, named Human Movement (HuMOVE) platform, designed to enable quantitative and continuous measurement of sexual performance with minimal invasiveness and inconvenience for users. Design, implementation, and development of HuMOVE, a wearable platform equipped with an accelerometer sensor for monitoring inertial parameters for sexual performance assessment and diagnosis, were performed. The system enables quantitative measurement of movement parameters during sexual intercourse, meeting the requirements of wearability, data storage, sampling rate, and interfacing methods, which are fundamental for human sexual intercourse performance analysis. HuMOVE was validated through characterization using a controlled experimental test bench and evaluated in a human model during simulated sexual intercourse conditions. HuMOVE demonstrated to be a robust and quantitative monitoring platform and a reliable candidate for sexual performance evaluation and diagnosis. Characterization analysis on the controlled experimental test bench demonstrated an accurate correlation between the HuMOVE system and data from a reference displacement sensor. Experimental tests in the human model during simulated intercourse conditions confirmed the accuracy of the sexual performance evaluation platform and the effectiveness of the selected and derived parameters. The obtained outcomes also established the project expectations in terms of usability and comfort, evidenced by the questionnaires that highlighted the low invasiveness and acceptance of the device. To the best of our knowledge, HuMOVE platform is the first device for human sexual performance analysis compatible with sexual intercourse; the system has the potential to be a helpful tool for physicians to accurately classify sexual disorders, such as premature or delayed ejaculation. Copyright © 2014 Elsevier Inc. All rights reserved.
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A Unified Model of Performance: Validation of its Predictions across Different Sleep/Wake Schedules.
Ramakrishnan, Sridhar; Wesensten, Nancy J; Balkin, Thomas J; Reifman, Jaques
2016-01-01
Historically, mathematical models of human neurobehavioral performance developed on data from one sleep study were limited to predicting performance in similar studies, restricting their practical utility. We recently developed a unified model of performance (UMP) to predict the effects of the continuum of sleep loss-from chronic sleep restriction (CSR) to total sleep deprivation (TSD) challenges-and validated it using data from two studies of one laboratory. Here, we significantly extended this effort by validating the UMP predictions across a wide range of sleep/wake schedules from different studies and laboratories. We developed the UMP on psychomotor vigilance task (PVT) lapse data from one study encompassing four different CSR conditions (7 d of 3, 5, 7, and 9 h of sleep/night), and predicted performance in five other studies (from four laboratories), including different combinations of TSD (40 to 88 h), CSR (2 to 6 h of sleep/night), control (8 to 10 h of sleep/night), and nap (nocturnal and diurnal) schedules. The UMP accurately predicted PVT performance trends across 14 different sleep/wake conditions, yielding average prediction errors between 7% and 36%, with the predictions lying within 2 standard errors of the measured data 87% of the time. In addition, the UMP accurately predicted performance impairment (average error of 15%) for schedules (TSD and naps) not used in model development. The unified model of performance can be used as a tool to help design sleep/wake schedules to optimize the extent and duration of neurobehavioral performance and to accelerate recovery after sleep loss. © 2016 Associated Professional Sleep Societies, LLC.
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Carnahan, Brian; Meyer, Gérard; Kuntz, Lois-Ann
2003-01-01
Multivariate classification models play an increasingly important role in human factors research. In the past, these models have been based primarily on discriminant analysis and logistic regression. Models developed from machine learning research offer the human factors professional a viable alternative to these traditional statistical classification methods. To illustrate this point, two machine learning approaches--genetic programming and decision tree induction--were used to construct classification models designed to predict whether or not a student truck driver would pass his or her commercial driver license (CDL) examination. The models were developed and validated using the curriculum scores and CDL exam performances of 37 student truck drivers who had completed a 320-hr driver training course. Results indicated that the machine learning classification models were superior to discriminant analysis and logistic regression in terms of predictive accuracy. Actual or potential applications of this research include the creation of models that more accurately predict human performance outcomes.
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Tandem internal models execute motor learning in the cerebellum.
Honda, Takeru; Nagao, Soichi; Hashimoto, Yuji; Ishikawa, Kinya; Yokota, Takanori; Mizusawa, Hidehiro; Ito, Masao
2018-06-25
In performing skillful movement, humans use predictions from internal models formed by repetition learning. However, the computational organization of internal models in the brain remains unknown. Here, we demonstrate that a computational architecture employing a tandem configuration of forward and inverse internal models enables efficient motor learning in the cerebellum. The model predicted learning adaptations observed in hand-reaching experiments in humans wearing a prism lens and explained the kinetic components of these behavioral adaptations. The tandem system also predicted a form of subliminal motor learning that was experimentally validated after training intentional misses of hand targets. Patients with cerebellar degeneration disease showed behavioral impairments consistent with tandemly arranged internal models. These findings validate computational tandemization of internal models in motor control and its potential uses in more complex forms of learning and cognition. Copyright © 2018 the Author(s). Published by PNAS.
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Frey, Alexander J; Wang, Qingqing; Busch, Christine; Feldman, Daniel; Bottalico, Lisa; Mesaros, Clementina A; Blair, Ian A; Vachani, Anil; Snyder, Nathaniel W
2016-12-01
A multiplexed quantitative method for the analysis of three major unconjugated steroids in human serum by stable isotope dilution liquid chromatography-high resolution mass spectrometry (LC-HRMS) was developed and validated on a Q Exactive Plus hybrid quadrupole/Orbitrap mass spectrometer. This quantification utilized isotope dilution and Girard P derivatization on the keto-groups of testosterone (T), androstenedione (AD) and dehydroepiandrosterone (DHEA) to improve ionization efficiency using electrospray ionization. Major isomeric compounds to T and DHEA; the inactive epimer of testosterone (epiT), and the metabolite of AD, 5α-androstanedione (5α-AD) were completely resolved on a biphenyl column within an 18min method. Inter- and intra-day method validation using LC-HRMS with qualifying product ions was performed and acceptable analytical performance was achieved. The method was further validated by comparing steroid levels from 100μL of serum from young vs older subjects. Since this approach provides high-dimensional HRMS data, untargeted analysis by age group was performed. DHEA and T were detected among the top analytes most significantly different across the two groups after untargeted LC-HRMS analysis, as well as a number of other still unknown metabolites, indicating the potential for combined targeted/untargeted analysis in steroid analysis. Copyright © 2016 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Leksono, EB; Suparno; Vanany, I.
2018-04-01
Service only supply chain (SOSC) concept is service supply chain (SSC) implementation on pure services. The globalization and stakeholder pressure makes operation of SSC should give the attention to the environment effect, community, economic and intangibility assets. SOSC performance measurement (SOSCPM) may be developed for measuring of performance for sustainability aspects and intangibility assets to meet customer satisfaction. This article discusses sustainable SOSCPM based on balanced scorecard (BSC), include sustainability aspects, intangibility and relations between perspectives and indicators. From literature review, it is found 34 performance indicators that must be confirm to expert and SC actors by survey. From survey validation using weighted average and level of consensus, it is found 29 valid indicators for processed by DEMATEL. From DEMATEL, it is found 26 indicators can be used on sustainable SOSCPM. Furthermore, innovation and growth perspective most influence to other, and customer perspective most important. Intangibility indicators incorporated on innovation and growth perspective very related with human resources. Finally, relations between perspectives and indicator used to design of BSC strategy maps.
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NASA Technical Reports Server (NTRS)
Carr, James L.; Madani, Houria
2007-01-01
Geostationary Operational Environmental Satellite (GOES) Image Navigation and Registration (INR) performance is specified at the 3- level, meaning that 99.7% of a collection of individual measurements must comply with specification thresholds. Landmarks are measured by the Replacement Product Monitor (RPM), part of the operational GOES ground system, to assess INR performance and to close the INR loop. The RPM automatically discriminates between valid and invalid measurements enabling it to run without human supervision. In general, this screening is reliable, but a small population of invalid measurements will be falsely identified as valid. Even a small population of invalid measurements can create problems when assessing performance at the 3-sigma level. This paper describes an additional layer of quality control whereby landmarks of the highest quality ("platinum") are identified by their self-consistency. The platinum screening criteria are not simple statistical outlier tests against sigma values in populations of INR errors. In-orbit INR performance metrics for GOES-12 and GOES-13 are presented using the platinum landmark methodology.
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Concept Design of Cryogenic Propellant Storage and Transfer for Space Exploration
NASA Technical Reports Server (NTRS)
Free, James M.; Motil, Susan M.; Kortes, Trudy F.; Meyer, Michael L.; taylor, William J.
2012-01-01
NASA is in the planning and investigation process of developing innovative paths for human space exploration that strengthen the capability to extend human and robotic presence beyond low Earth orbit and throughout the solar system. NASA is establishing the foundations to enable humans to safely reach multiple potential destinations, including the Moon, asteroids, Lagrange points, and Mars and its environs through technology and capability development. To achieve access to these destinations within a reasonable flight time will require the use of high performance cryogenic propulsion systems. Therefore NASA is examining mission concepts for a Cryogenic Propellant Storage and Transfer (CPST) Flight Demonstration which will test and validate key capabilities and technologies required for future exploration elements such as large cryogenic propulsion stages and propellant depots. The CPST project will perform key ground testing in fiscal year 2012 and execute project formulation and implementation leading to a flight demonstration in 2017.
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Liu, Xuemei; Chen, Rui; Zeng, Guanghuai; Gao, Ying; Liu, Xiuping; Zhang, Donglei; Hu, Pei; Wang, Hongyun; Jiang, Ji
2018-06-04
Hemay005 is a novel small-molecule inhibitor of phosphodiesterase-4 developed for the treatment of psoriasis. Measurement of Hemay005 in biological samples is critical for evaluation of its pharmacokinetics in clinical studies. Methodology & results: Plasma and urine samples were extracted and then chromatographed on an Acquity UPLC HSS T3 column with a gradient elution. Detection was performed on a Xevo TQ-S tandem mass spectrometer using negative ESI. For the first time, a sensitive and robust ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the quantitative determination of Hemay005 in human plasma and urine, and it was successfully applied to evaluate the pharmacokinetics of Hemay005 in healthy subjects in a first-in-human study.
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Adaptive Shape Kernel-Based Mean Shift Tracker in Robot Vision System
2016-01-01
This paper proposes an adaptive shape kernel-based mean shift tracker using a single static camera for the robot vision system. The question that we address in this paper is how to construct such a kernel shape that is adaptive to the object shape. We perform nonlinear manifold learning technique to obtain the low-dimensional shape space which is trained by training data with the same view as the tracking video. The proposed kernel searches the shape in the low-dimensional shape space obtained by nonlinear manifold learning technique and constructs the adaptive kernel shape in the high-dimensional shape space. It can improve mean shift tracker performance to track object position and object contour and avoid the background clutter. In the experimental part, we take the walking human as example to validate that our method is accurate and robust to track human position and describe human contour. PMID:27379165
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Hughes, Charmayne M L; Baber, Chris; Bienkiewicz, Marta; Worthington, Andrew; Hazell, Alexa; Hermsdörfer, Joachim
2015-01-01
Approximately 33% of stroke patients have difficulty performing activities of daily living, often committing errors during the planning and execution of such activities. The objective of this study was to evaluate the ability of the human error identification (HEI) technique SHERPA (Systematic Human Error Reduction and Prediction Approach) to predict errors during the performance of daily activities in stroke patients with left and right hemisphere lesions. Using SHERPA we successfully predicted 36 of the 38 observed errors, with analysis indicating that the proportion of predicted and observed errors was similar for all sub-tasks and severity levels. HEI results were used to develop compensatory cognitive strategies that clinicians could employ to reduce or prevent errors from occurring. This study provides evidence for the reliability and validity of SHERPA in the design of cognitive rehabilitation strategies in stroke populations.
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Kopf, Thomas; Schmitz, Gerd
2013-11-01
The determination of the fatty acid (FA) profile of lipid classes is essential for lipidomic analysis. We recently developed a GC/MS-method for the analysis of the FA profile of total FAs, i.e. the totality of bound and unbound FAs, in any given biological sample (TOFAs). Here, we present a method for the analysis of non-esterified fatty acids (NEFAs) in biological samples, i.e. the fraction that is present as extractable free fatty acids. Lipid extraction is performed according to Dole using 80/20 2-propanol/n-hexane (v/v), with 0.1% H2SO4. The fatty acid-species composition of this NEFA-fraction is determined as FAME after derivatization with our GC/MS-method on a BPX column (Shimadzu). Validation of the NEFA-method presented was performed in human plasma samples. The validated method has been used with human plasma, cells and tissues, as well as mammalian body fluids and tissue samples. The newly developed solid-phase-extraction (SPE)-GC-MS method allows the rapid separation of the NEFA-fraction from a neutral lipid extract of plasma samples. As a major advantage compared to G-FID-methods, GC-MS allows the use of stable isotope labeled fatty acid precursors to monitor fatty acid metabolism. Copyright © 2013 Elsevier B.V. All rights reserved.
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Gong, Zhilong; Chandler, Kiresha; Webster, Stephen; Kerley, Remy; Buist, Susan; McCort-Tipton, Melanie
2012-03-15
We report for the first time an ultra performance liquid chromatographic method with tandem mass spectrometric detection (UPLC/MS/MS) for the determination of norethindrone alone in human plasma over the concentration range of 50.0-25000 pg mL(-1) using a sample volume of 0.250 mL. Norethindrone and its internal standard (ISTD), norethindrone-(13)C(2), were extracted from human plasma by supported liquid extraction (SLE). After evaporation of the organic solvent, samples were reconstituted and analyzed on an UPLC/MS/MS system. The UPLC system used a Waters BEH C18 (100 mm × 2.1mm, 1.7 μm) column with mobile phase A of 0.05% formic acid in water:acetonitrile (65:35, v/v) and mobile phase B of 0.05% formic acid in methanol:acetonitrile (50:50, v/v). The flow rate was 0.500 mL min(-1). The method was fully validated. The inter-run accuracy and precision at the lower limit of quantitation (LLOQ), low, mid and high quality control (QC) concentration levels were 99.2-108.4% with a <8.1% CV (coefficient of variation), respectively. The validated method has been successfully applied to analysis of thousands of pharmacokinetic samples. Copyright © 2012 Elsevier B.V. All rights reserved.
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Liu, Xiaoying; Liu, Qian; Wang, Dongmei; Wang, Xueya; Zhang, Peng; Xu, Haiyan; Zhao, Hui; Zhao, Huaiqing
2010-05-01
A highly sensitive and selective LC-MS/MS method was developed and validated for the determination of dauricine in human plasma, using protopine as internal standard (IS). The analyte and IS were extracted by liquid-liquid extraction and analyzed by LC-MS/MS. Chromatographic separation was performed on Agilent TC-C(18) column with a mobile phase of methanol-water-glacial acetic acid (60:40:0.8, v/v/v) at a flow rate of 0.7 mL/min. Detection was performed on a triple quadrupole tandem mass spectrum by multiple reaction monitoring (MRM) mode using the electrospray ionization technique in positive mode. The method was linear over the concentration range of 1-200 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL in human plasma with acceptable precision and accuracy. The intra- and inter-day precision was less than 5.9% determined from quality control (QC) samples at concentrations of 2.0, 20.0 and 160 ng/mL, and the accuracy was within +/-9.9%. This method was successfully applied for the evaluation of pharmacokinetics of dauricine after oral doses of 100, 300 and 600 mg phenolic alkaloids of menispermum dauricum tablet (PAMDT) to 12 Chinese healthy volunteers. 2010 Elsevier B.V. All rights reserved.
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Taneja, Isha; Raju, Kanumuri Siva Rama; Singh, Sheelendra Pratap; Wahajuddin, Muhammad
2015-01-01
The pharmacokinetic compatibility of short-acting CDRI candidate antimalarial trioxane derivative, 99–411, was tested with long-acting prescription antimalarials, lumefantrine and piperaquine. LC-ESI-MS/MS methods were validated for simultaneous bioanalysis of lumefantrine and 99–411 and of piperaquine and 99–411 combinations. The interaction studies were performed in rats using these validated methods. The total systemic exposure of 99–411 increased when administered with either lumefantrine or piperaquine. However, co-administration of 99–411 significantly decreased the systemic exposure of piperaquine by half-fold while it had no effect on the kinetics of lumefantrine. 99–411, thus, seemed to be a good alternative to artemisinin derivatives for combination treatment with lumefantrine. To explore the reason for increased plasma levels of 99–411, an in situ permeability study was performed by co-perfusing lumefantrine and 99–411. In presence of lumefantrine, the absorption of 99–411 was significantly increased by 1.37 times than when given alone. Lumefantrine did not affect the metabolism of 99–411 when tested in vitro in human liver microsomes. Additionally, ATPase assay suggest that 99–411 was a substrate of human P-gp, thus, indicating the probability of interaction at the absorption level in humans as well. PMID:26602250
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Validation of Bioreactor and Human-on-a-Chip Devices for Chemical Safety Assessment.
Rebelo, Sofia P; Dehne, Eva-Maria; Brito, Catarina; Horland, Reyk; Alves, Paula M; Marx, Uwe
2016-01-01
Equipment and device qualification and test assay validation in the field of tissue engineered human organs for substance assessment remain formidable tasks with only a few successful examples so far. The hurdles seem to increase with the growing complexity of the biological systems, emulated by the respective models. Controlled single tissue or organ culture in bioreactors improves the organ-specific functions and maintains their phenotypic stability for longer periods of time. The reproducibility attained with bioreactor operations is, per se, an advantage for the validation of safety assessment. Regulatory agencies have gradually altered the validation concept from exhaustive "product" to rigorous and detailed process characterization, valuing reproducibility as a standard for validation. "Human-on-a-chip" technologies applying micro-physiological systems to the in vitro combination of miniaturized human organ equivalents into functional human micro-organisms are nowadays thought to be the most elaborate solution created to date. They target the replacement of the current most complex models-laboratory animals. Therefore, we provide here a road map towards the validation of such "human-on-a-chip" models and qualification of their respective bioreactor and microchip equipment along a path currently used for the respective animal models.
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Cacho, J; Sevillano, J; de Castro, J; Herrera, E; Ramos, M P
2008-11-01
Insulin resistance plays a role in the pathogenesis of diabetes, including gestational diabetes. The glucose clamp is considered the gold standard for determining in vivo insulin sensitivity, both in human and in animal models. However, the clamp is laborious, time consuming and, in animals, requires anesthesia and collection of multiple blood samples. In human studies, a number of simple indexes, derived from fasting glucose and insulin levels, have been obtained and validated against the glucose clamp. However, these indexes have not been validated in rats and their accuracy in predicting altered insulin sensitivity remains to be established. In the present study, we have evaluated whether indirect estimates based on fasting glucose and insulin levels are valid predictors of insulin sensitivity in nonpregnant and 20-day-pregnant Wistar and Sprague-Dawley rats. We have analyzed the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), and the fasting glucose-to-insulin ratio (FGIR) by comparing them with the insulin sensitivity (SI(Clamp)) values obtained during the hyperinsulinemic-isoglycemic clamp. We have performed a calibration analysis to evaluate the ability of these indexes to accurately predict insulin sensitivity as determined by the reference glucose clamp. Finally, to assess the reliability of these indexes for the identification of animals with impaired insulin sensitivity, performance of the indexes was analyzed by receiver operating characteristic (ROC) curves in Wistar and Sprague-Dawley rats. We found that HOMA-IR, QUICKI, and FGIR correlated significantly with SI(Clamp), exhibited good sensitivity and specificity, accurately predicted SI(Clamp), and yielded lower insulin sensitivity in pregnant than in nonpregnant rats. Together, our data demonstrate that these indexes provide an easy and accurate measure of insulin sensitivity during pregnancy in the rat.
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Dunmire, Barbrina; Cunitz, Bryan W.; He, Xuemei; Sorensen, Mathew D.; Harper, Jonathan D.; Bailey, Michael R.; Lendvay, Thomas S.
2014-01-01
Abstract Purpose: Ultrasonic propulsion to reposition urinary tract calculi requires knowledge about ultrasound image capture, device manipulation, and interpretation. The purpose of this study was to validate a cognitive and technical skills curriculum to teach urologists ultrasonic propulsion to reposition kidney stones in tissue phantoms. Materials and Methods: Ten board-certified urologists recruited from a single institution underwent a didactic session on renal ultrasound imaging. Subjects completed technical skills modules in tissue phantoms, including kidney imaging, pushing a stone through a translucent maze, and repositioning a lower pole calyceal stone. Objective cognitive and technical performance metrics were recorded. Subjects completed a questionnaire to ascertain face and content validity on a five-point Likert scale. Results: Eight urologists (80%) had never attended a previous ultrasound course, and nine (90%) performed renal ultrasounds less frequently than every 6 months. Mean cognitive skills scores improved from 55% to 91% (p<0.0001) on pre- and post-didactic tests. In the kidney phantom, 10 subjects (100%) repositioned the lower pole calyceal stone to at least the lower pole infundibulum, while 9 (90%) successfully repositioned the stone to the renal pelvis. A mean±SD (15.7±13.3) pushes were required to complete the task over an average of 4.6±2.2 minutes. Urologists rated the curriculum's effectiveness and realism as a training tool at a mean score of 4.6/5.0 and 4.1/5.0, respectively. Conclusions: The curriculum for ultrasonic propulsion is effective and useful for training urologists with limited ultrasound proficiency in stone repositioning technique. Further studies in animate and human models will be required to assess predictive validity. PMID:24228719
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Hsi, Ryan S; Dunmire, Barbrina; Cunitz, Bryan W; He, Xuemei; Sorensen, Mathew D; Harper, Jonathan D; Bailey, Michael R; Lendvay, Thomas S
2014-04-01
Ultrasonic propulsion to reposition urinary tract calculi requires knowledge about ultrasound image capture, device manipulation, and interpretation. The purpose of this study was to validate a cognitive and technical skills curriculum to teach urologists ultrasonic propulsion to reposition kidney stones in tissue phantoms. Ten board-certified urologists recruited from a single institution underwent a didactic session on renal ultrasound imaging. Subjects completed technical skills modules in tissue phantoms, including kidney imaging, pushing a stone through a translucent maze, and repositioning a lower pole calyceal stone. Objective cognitive and technical performance metrics were recorded. Subjects completed a questionnaire to ascertain face and content validity on a five-point Likert scale. Eight urologists (80%) had never attended a previous ultrasound course, and nine (90%) performed renal ultrasounds less frequently than every 6 months. Mean cognitive skills scores improved from 55% to 91% (p<0.0001) on pre- and post-didactic tests. In the kidney phantom, 10 subjects (100%) repositioned the lower pole calyceal stone to at least the lower pole infundibulum, while 9 (90%) successfully repositioned the stone to the renal pelvis. A mean±SD (15.7±13.3) pushes were required to complete the task over an average of 4.6±2.2 minutes. Urologists rated the curriculum's effectiveness and realism as a training tool at a mean score of 4.6/5.0 and 4.1/5.0, respectively. The curriculum for ultrasonic propulsion is effective and useful for training urologists with limited ultrasound proficiency in stone repositioning technique. Further studies in animate and human models will be required to assess predictive validity.
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NASA Technical Reports Server (NTRS)
Ullman, Richard; Bane, Bob; Yang, Jingli
2008-01-01
A computer program partly automates the task of determining whether an HDF-EOS 5 file is valid in that it conforms to specifications for such characteristics as attribute names, dimensionality of data products, and ranges of legal data values. ["HDF-EOS" and variants thereof are defined in "Converting EOS Data From HDF-EOS to netCDF" (GSC-15007-1), which is the first of several preceding articles in this issue of NASA Tech Briefs.] Previously, validity of a file was determined in a tedious and error-prone process in which a person examined human-readable dumps of data-file-format information. The present software helps a user to encode the specifications for an HDFEOS 5 file, and then inspects the file for conformity with the specifications: First, the user writes the specifications in Extensible Markup Language (XML) by use of a document type definition (DTD) that is part of the program. Next, the portion of the program (denoted the validator) that performs the inspection is executed, using, as inputs, the specifications in XML and the HDF-EOS 5 file to be validated. Finally, the user examines the output of the validator.
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NASA Technical Reports Server (NTRS)
Corker, Kevin M.; Labacqz, J. Victor (Technical Monitor)
1997-01-01
The Man-Machine Interaction Design and Analysis System (MIDAS) under joint U.S. Army and NASA cooperative is intended to assist designers of complex human/automation systems in successfully incorporating human performance capabilities and limitations into decision and action support systems. MIDAS is a computational representation of multiple human operators, selected perceptual, cognitive, and physical functions of those operators, and the physical/functional representation of the equipment with which they operate. MIDAS has been used as an integrated predictive framework for the investigation of human/machine systems, particularly in situations with high demands on the operators. We have extended the human performance models to include representation of both human operators and intelligent aiding systems in flight management, and air traffic service. The focus of this development is to predict human performance in response to aiding system developed to identify aircraft conflict and to assist in the shared authority for resolution. The demands of this application requires representation of many intelligent agents sharing world-models, coordinating action/intention, and cooperative scheduling of goals and action in an somewhat unpredictable world of operations. In recent applications to airborne systems development, MIDAS has demonstrated an ability to predict flight crew decision-making and procedural behavior when interacting with automated flight management systems and Air Traffic Control. In this paper, we describe two enhancements to MIDAS. The first involves the addition of working memory in the form of an articulatory buffer for verbal communication protocols and a visuo-spatial buffer for communications via digital datalink. The second enhancement is a representation of multiple operators working as a team. This enhanced model was used to predict the performance of human flight crews and their level of compliance with commercial aviation communication procedures. We show how the data produced by MIDAS compares with flight crew performance data from full mission simulations. Finally, we discuss the use of these features to study communication issues connected with aircraft-based separation assurance.
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Identification of Suitable Areas for West Nile Virus Circulation in Tunisia.
Ben Hassine, T; Conte, A; Calistri, P; Candeloro, L; Ippoliti, C; De Massis, F; Danzetta, M L; Bejaoui, M; Hammami, S
2017-04-01
West Nile virus (WNV) is a mosquito-transmitted Flavivirus belonging to the Japanese encephalitis antigenic complex of the Flaviviridae family. It is transmitted primarily by the bite of infected mosquitoes, particularly Culex spp. and Aedes/Ochlerotatus spp., which acquire the virus by feeding on viraemic birds. Humans, horses and other mammals are regarded as incidental or dead-end hosts. In the last decades, an increasing number of cases of WNV infection in horses and humans have been notified in the Mediterranean basin. In Tunisia, human cases of WNV-related meningoencephalitis were detected in 1997, 2003, 2007, 2010, 2011 and 2012. Based on the analysis of climatic and environmental conditions found in the locations where human cases have been reported in 2012, the aim of this study was to identify similar areas in Tunisia potentially at risk of disease occurrence. Data related to 85 neuroinvasive West Nile fever (WNF) human cases were georeferenced and a set of environmental and climatic variables (wetlands and humid areas, normalized difference vegetation index (NDVI), temperatures and elevation, migratory bird settlements) were used in the analysis. Areas, ecologically similar to those where human cases were detected, were identified using the Mahalanobis distance statistic. A leave-one-out cross-validation was performed to validate the sensitivity of the model, and 78 of 85 points were correctly classified. © 2015 Blackwell Verlag GmbH.
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Human Factors Validation of the AeroForm Tissue Expander System for Breast Reconstruction.
Kelley, Kathy; Kim, Jennie
The tissue expansion process using traditional saline expanders is lengthy and uncomfortable. A new technology has been developed, providing a needle-free option implanted after a mastectomy, and is activated by a handheld remote control releasing small amounts (10 cc) of carbon dioxide from an internal reservoir. The expander is gradually filled with CO2 resulting in mechanical stretching of the overlying tissue. The AeroForm System has been evaluated in a series of clinical trials including a randomized, controlled U.S. study comparing the AeroForm System with saline expanders. Results demonstrated patients can safely and reliably dose and complete their expansions in half the time compared to saline expanders. A human factors validation study was conducted in 8 patients to evaluate whether patients could correctly use the device to complete their expansion at home. The sessions were recorded and data on performance, behavioral, and subjective measures were collected and analyzed and submitted to the FDA as part of the U.S. marketing approval. All 8 participants were successful in using the controller to deliver a simulated dose. Participants found the device easy to use and the training material provided adequate to understand use of the controller. For women who choose 2-stage breast reconstruction, a new safe and effective option is available for tissue expansion, offering a convenient and empowering alternative. The human factors validation study conducted confirmed the simplicity of the device and further validated that the device can be used safely and effectively for breast tissue expansion.
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McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D
2014-01-01
Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. PMID:24811361
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Kismödi, Eszter; Kiragu, Karusa; Sawicki, Olga; Smith, Sally; Brion, Sophie; Sharma, Aditi; Mworeko, Lilian; Iovita, Alexandrina
2017-12-01
In 2014, the World Health Organization (WHO) initiated a process for validation of the elimination of mother-to-child transmission (EMTCT) of HIV and syphilis by countries. For the first time in such a process for the validation of disease elimination, WHO introduced norms and approaches that are grounded in human rights, gender equality, and community engagement. This human rights-based validation process can serve as a key opportunity to enhance accountability for human rights protection by evaluating EMTCT programs against human rights norms and standards, including in relation to gender equality and by ensuring the provision of discrimination-free quality services. The rights-based validation process also involves the assessment of participation of affected communities in EMTCT program development, implementation, and monitoring and evaluation. It brings awareness to the types of human rights abuses and inequalities faced by women living with, at risk of, or affected by HIV and syphilis, and commits governments to eliminate those barriers. This process demonstrates the importance and feasibility of integrating human rights, gender, and community into key public health interventions in a manner that improves health outcomes, legitimizes the participation of affected communities, and advances the human rights of women living with HIV.
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Design of a Virtual Player for Joint Improvisation with Humans in the Mirror Game
Zhai, Chao; Alderisio, Francesco; Tsaneva-Atanasova, Krasimira; di Bernardo, Mario
2016-01-01
Joint improvisation is often observed among humans performing joint action tasks. Exploring the underlying cognitive and neural mechanisms behind the emergence of joint improvisation is an open research challenge. This paper investigates jointly improvised movements between two participants in the mirror game, a paradigmatic joint task example. First, experiments involving movement coordination of different dyads of human players are performed in order to build a human benchmark. No designation of leader and follower is given beforehand. We find that joint improvisation is characterized by the lack of a leader and high levels of movement synchronization. Then, a theoretical model is proposed to capture some features of their interaction, and a set of experiments is carried out to test and validate the model ability to reproduce the experimental observations. Furthermore, the model is used to drive a computer avatar able to successfully improvise joint motion with a human participant in real time. Finally, a convergence analysis of the proposed model is carried out to confirm its ability to reproduce joint movements between the participants. PMID:27123927
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Design of a Virtual Player for Joint Improvisation with Humans in the Mirror Game.
Zhai, Chao; Alderisio, Francesco; Słowiński, Piotr; Tsaneva-Atanasova, Krasimira; di Bernardo, Mario
2016-01-01
Joint improvisation is often observed among humans performing joint action tasks. Exploring the underlying cognitive and neural mechanisms behind the emergence of joint improvisation is an open research challenge. This paper investigates jointly improvised movements between two participants in the mirror game, a paradigmatic joint task example. First, experiments involving movement coordination of different dyads of human players are performed in order to build a human benchmark. No designation of leader and follower is given beforehand. We find that joint improvisation is characterized by the lack of a leader and high levels of movement synchronization. Then, a theoretical model is proposed to capture some features of their interaction, and a set of experiments is carried out to test and validate the model ability to reproduce the experimental observations. Furthermore, the model is used to drive a computer avatar able to successfully improvise joint motion with a human participant in real time. Finally, a convergence analysis of the proposed model is carried out to confirm its ability to reproduce joint movements between the participants.
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The Multifactor Measure of Performance: Its Development, Norming, and Validation.
Bar-On, Reuven
2018-01-01
This article describes the development as well as the initial norming and validation of the Multifactor Measure of Performance™ (MMP™), which is a psychometric instrument that is designed to study, assess and enhance key predictors of human performance to help individuals perform at a higher level. It was created by the author, for the purpose of going beyond existing conceptual and psychometric models that often focus on relatively few factors that are purported to assess performance at school, in the workplace and elsewhere. The relative sparsity of multifactorial pre-employment assessment instruments exemplifies, for the author, one of the important reasons for developing the MMP™, which attempts to comprehensively evaluate a wider array of factors that are thought to contribute to performance. In that this situation creates a need in the area of test-construction that should be addressed, the author sought to develop a multifactorial assessment and development instrument that could concomitantly evaluate a combination of physical, cognitive, intra-personal, inter-personal, and motivational factors that significantly contribute to performance. The specific aim of this article is to show why, how and if this could be done as well as to present and discuss the potential importance of the results obtained to date. The findings presented here will hopefully add to what is known about human performance and thus contribute to the professional literature, in addition to contribute to the continued development of the MMP™. The impetus for developing the MMP™ is first explained below, followed by a detailed description of the process involved and the findings obtained; and their potential application is then discussed as well as the possible limitations of the present research and the need for future studies to address them.
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The Multifactor Measure of Performance: Its Development, Norming, and Validation
Bar-On, Reuven
2018-01-01
This article describes the development as well as the initial norming and validation of the Multifactor Measure of Performance™ (MMP™)1, which is a psychometric instrument that is designed to study, assess and enhance key predictors of human performance to help individuals perform at a higher level. It was created by the author, for the purpose of going beyond existing conceptual and psychometric models that often focus on relatively few factors that are purported to assess performance at school, in the workplace and elsewhere. The relative sparsity of multifactorial pre-employment assessment instruments exemplifies, for the author, one of the important reasons for developing the MMP™, which attempts to comprehensively evaluate a wider array of factors that are thought to contribute to performance. In that this situation creates a need in the area of test-construction that should be addressed, the author sought to develop a multifactorial assessment and development instrument that could concomitantly evaluate a combination of physical, cognitive, intra-personal, inter-personal, and motivational factors that significantly contribute to performance. The specific aim of this article is to show why, how and if this could be done as well as to present and discuss the potential importance of the results obtained to date. The findings presented here will hopefully add to what is known about human performance and thus contribute to the professional literature, in addition to contribute to the continued development of the MMP™. The impetus for developing the MMP™ is first explained below, followed by a detailed description of the process involved and the findings obtained; and their potential application is then discussed as well as the possible limitations of the present research and the need for future studies to address them. PMID:29515479
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UAS-NAS Integrated Human in the Loop: Test Environment Report
NASA Technical Reports Server (NTRS)
Murphy, Jim; Otto, Neil; Jovic, Srba
2015-01-01
The desire and ability to fly Unmanned Aircraft Systems (UAS) in the National Airspace System (NAS) is of increasing urgency. The application of unmanned aircraft to perform national security, defense, scientific, and emergency management are driving the critical need for less restrictive access by UAS to the NAS. UAS represent a new capability that will provide a variety of services in the government (public) and commercial (civil) aviation sectors. The growth of this potential industry has not yet been realized due to the lack of a common understanding of what is required to safely operate UAS in the NAS. NASA's UAS Integration in the NAS Project is conducting research in the areas of Separation Assurance/Sense and Avoid Interoperability (SSI), Human Systems Integration (HSI), and Communication to support reducing the barriers of UAS access to the NAS. This research was broken into two research themes namely, UAS Integration and Test Infrastructure. UAS Integration focuses on airspace integration procedures and performance standards to enable UAS integration in the air transportation system, covering Sense and Avoid (SAA) performance standards, command and control performance standards, and human systems integration. The focus of the Test Infrastructure theme was to enable development and validation of airspace integration procedures and performance standards, including the execution of integrated test and evaluation. In support of the integrated test and evaluation efforts, the Project developed an adaptable, scalable, and schedulable relevant test environment incorporating live, virtual, and constructive elements capable of validating concepts and technologies for unmanned aircraft systems to safely operate in the NAS. To accomplish this task, the Project planned to conduct three integrated events: a Human-in-the-Loop simulation and two Flight Test series that integrated key concepts, technologies and/or procedures in a relevant air traffic environment. Each of the integrated events were built on the technical achievements, fidelity and complexity of previous simulations and tests, resulting in research findings that support the development of regulations governing the access of UAS into the NAS. The purpose of this document is to describe how well the system under test was representative
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Final Report 2007: DOE-FG02-87ER60561
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kilbourn, Michael R
2007-04-26
This project involved a multi-faceted approach to the improvement of techniques used in Positron Emission Tomography (PET), from radiochemistry to image processing and data analysis. New methods for radiochemical syntheses were examined, new radiochemicals prepared for evaluation and eventual use in human PET studies, and new pre-clinical methods examined for validation of biochemical parameters in animal studies. The value of small animal PET imaging in measuring small changes of in vivo biochemistry was examined and directly compared to traditional tissue sampling techniques. In human imaging studies, the ability to perform single experimental sessions utilizing two overlapping injections of radiopharmaceuticals wasmore » tested, and it was shown that valid biochemical measures for both radiotracers can be obtained through careful pharmacokinetic modeling of the PET emission data. Finally, improvements in reconstruction algorithms for PET data from small animal PET scanners was realized and these have been implemented in commercial releases. Together, the project represented an integrated effort to improve and extend all basic science aspects of PET imaging at both the animal and human level.« less
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Genome-Wide Identification of CBX2 Targets: Insights in the Human Sex Development Network
Eid, Wassim; Opitz, Lennart
2015-01-01
Chromobox homolog 2 (CBX2) is a chromatin modifier that plays an important role in sexual development and its disorders (disorders of sex development [DSD]), yet the exact rank and function of human CBX2 in this pathway remains unclear. Here, we performed large-scale mapping and analysis of in vivo target loci of the protein CBX2 in Sertoli-like NT-2D1 cells, using the DNA adenine methyltransferase identification technique. We identified close to 1600 direct targets for CBX2. Intriguingly, validation of selected candidate genes using qRT-PCR in cells overexpressing CBX2 or in which CBX2 has been knocked down indicated that several CBX2-responsive genes encode proteins that are involved in DSD. We further validated these effects on the candidate genes using a mutated CBX2 causing DSD in human patient. Overall, our findings suggest that CBX2 role in the sex development cascade is to stimulate the male pathway and concurrently inhibit the female pathway. These data provide fundamental insights into potential etiology of DSD. PMID:25569159
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Gandhi, Abhishek; Guttikar, Swati; Trivedi, Priti
2015-10-01
A sensitive and simultaneous liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-butyl ether: n-hexane (50:50, v/v) solvent mixture, followed by dansyl derivatization. The chromatographic separation was performed on a Kinetex C 18 (50 mm×4.6 mm, 2.6 µm) column with a mobile phase of 0.1% (v/v) formic acid in water and acetonitrile in gradient composition. The mass transitions were monitored in electrospray positive ionization mode. The assay exhibited a linear range of 0.100-20.0 ng/mL for levonorgestrel and 4.00-500 pg/mL for ethinyl estradiol in human plasma. A run time of 9.0 min for each sample made it possible to analyze a throughput of more than 100 samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic and bioequivalence studies.
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NASA Technical Reports Server (NTRS)
Ghatas, Rania W.; Jack, Devin P.; Tsakpinis, Dimitrios; Sturdy, James L.; Vincent, Michael J.; Hoffler, Keith D.; Myer, Robert R.; DeHaven, Anna M.
2017-01-01
As Unmanned Aircraft Systems (UAS) make their way to mainstream aviation operations within the National Airspace System (NAS), research efforts are underway to develop a safe and effective environment for their integration into the NAS. Detect and Avoid (DAA) systems are required to account for the lack of "eyes in the sky" due to having no human on-board the aircraft. The technique, results, and lessons learned from a detailed End-to-End Verification and Validation (E2-V2) simulation study of a DAA system representative of RTCA SC-228's proposed Phase I DAA Minimum Operational Performance Standards (MOPS), based on specific test vectors and encounter cases, will be presented in this paper.
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A Qualitative Analysis of Rater Behavior on an L2 Speaking Assessment
ERIC Educational Resources Information Center
Kim, Hyun Jung
2015-01-01
Human raters are normally involved in L2 performance assessment; as a result, rater behavior has been widely investigated to reduce rater effects on test scores and to provide validity arguments. Yet raters' cognition and use of rubrics in their actual rating have rarely been explored qualitatively in L2 speaking assessments. In this study three…
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Predictive models of safety based on audit findings: Part 2: Measurement of model validity.
Hsiao, Yu-Lin; Drury, Colin; Wu, Changxu; Paquet, Victor
2013-07-01
Part 1 of this study sequence developed a human factors/ergonomics (HF/E) based classification system (termed HFACS-MA) for safety audit findings and proved its measurement reliability. In Part 2, we used the human error categories of HFACS-MA as predictors of future safety performance. Audit records and monthly safety incident reports from two airlines submitted to their regulatory authority were available for analysis, covering over 6.5 years. Two participants derived consensus results of HF/E errors from the audit reports using HFACS-MA. We adopted Neural Network and Poisson regression methods to establish nonlinear and linear prediction models respectively. These models were tested for the validity of prediction of the safety data, and only Neural Network method resulted in substantially significant predictive ability for each airline. Alternative predictions from counting of audit findings and from time sequence of safety data produced some significant results, but of much smaller magnitude than HFACS-MA. The use of HF/E analysis of audit findings provided proactive predictors of future safety performance in the aviation maintenance field. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.
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Kuze, Yoji; Kogame, Akifumi; Jinno, Fumihiro; Kondo, Takahiro; Asahi, Satoru
2015-09-15
Azilsartan medoxomil potassium salt (TAK-491) is an orally administered angiotensin II type 1 receptor blocker for the treatment of hypertension and is an ester-based prodrug that is rapidly hydrolyzed to the pharmacologically active moiety, azilsartan (TAK-536), during absorption. TAK-536 is biotransformed to the 2 metabolites M-I by decarboxylation and M-II by dealkylation. In this study, we developed and validated a LC/MS/MS method which can simultaneously determine 4 analytes, TAK-491, TAK-536, M-I and M-II. The bioanalytical method can be outlined as follows: two structural analogues are used as the internal standards. The analytes and the IS are extracted from human plasma using solid phase extraction. After evaporating, the residue is reconstituted and injected into a LC/MS/MS system with an ESI probe and analyzed in the positive ion mode. Separation is performed through a conventional reversed-phase column with a mobile phase of water/acetonitrile/acetic acid (40:60:0.05, v/v/v) mixture at a flow rate of 0.2mL/min. The total run time is 8.5min. The calibration range is 1-2500ng/mL in human plasma for all the analytes. Instability issues of the prodrug, TAK-491, were overcome and all the validation results met the acceptance criteria in accordance with the regulatory guideline/guidance. As a result of the clinical study, the human PK profiles of TAK-536, M-I and M-II were successfully obtained and also it was confirmed that TAK-491 was below the LLOQ (1ng/mL) in the human plasma samples. Copyright © 2015 Elsevier B.V. All rights reserved.
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Cuesta-Gragera, Ana; Navarro-Fontestad, Carmen; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; García-Arieta, Alfredo; Trocóniz, Iñaki F; Casabó, Vicente G; Bermejo, Marival
2015-07-10
The objective of this paper is to apply a previously developed semi-physiologic pharmacokinetic model implemented in NONMEM to simulate bioequivalence trials (BE) of acetyl salicylic acid (ASA) in order to validate the model performance against ASA human experimental data. ASA is a drug with first-pass hepatic and intestinal metabolism following Michaelis-Menten kinetics that leads to the formation of two main metabolites in two generations (first and second generation metabolites). The first aim was to adapt the semi-physiological model for ASA in NOMMEN using ASA pharmacokinetic parameters from literature, showing its sequential metabolism. The second aim was to validate this model by comparing the results obtained in NONMEM simulations with published experimental data at a dose of 1000 mg. The validated model was used to simulate bioequivalence trials at 3 dose schemes (100, 1000 and 3000 mg) and with 6 test formulations with decreasing in vivo dissolution rate constants versus the reference formulation (kD 8-0.25 h (-1)). Finally, the third aim was to determine which analyte (parent drug, first generation or second generation metabolite) was more sensitive to changes in formulation performance. The validation results showed that the concentration-time curves obtained with the simulations reproduced closely the published experimental data, confirming model performance. The parent drug (ASA) was the analyte that showed to be more sensitive to the decrease in pharmaceutical quality, with the highest decrease in Cmax and AUC ratio between test and reference formulations. Copyright © 2015 Elsevier B.V. All rights reserved.
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A Planet Hunters Search of the Kepler TCE Inventory
NASA Astrophysics Data System (ADS)
Schwamb, Meg; Lintott, Chris; Fischer, Debra; Smith, Arfon; Boyajian, Tabetha; Brewer, John; Giguere, Matt; Lynn, Stuart; Schawinski, Kevin; Simpson, Rob; Wang, Ji
2013-07-01
NASA's Kepler spacecraft has spent the past 4 years monitoring ~160,000 stars for the signatures of transiting exoplanets. Planet Hunters (http://www.planethunters.org), part of the Zooniverse (http://www.zooniverse.org) collection of citizen science projects, uses the power of human pattern recognition via the World Wide Web to identify transits in the Kepler public data. We have demonstrated the success of a citizen science approach with the project's discoveries including PH1 b, a transiting circumbinary planet in a four star system., and over 20 previously unknown planet candidates. The Kepler team has released the list of 18,406 potential transit signals or threshold-crossing events (TCEs) identified in Quarters 1-12 (~1000 days) by their automated Transit Planet Search (TPS) algorithm. The majority of these detections found by TPS are triggered by transient events and are not valid planet candidates. To identify planetary candidates from the detected TCEs, a human review of the validation reports, generated by the Kepler pipeline for each TCE, is performed by several Kepler team members. We have undertaken an independent crowd-sourced effort to perform a systematic search of the Kepler Q1-12 TCE list. With the Internet we can obtain multiple assessments of each TCE's data validation report. Planet Hunters volunteers evaluate whether a transit is visible in the Kepler light curve folded on the expected period identified by TPS. We present the first results of this analysis.
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NASA Astrophysics Data System (ADS)
Zaychik, Kirill B.
Acceptable results have been obtained using conventional techniques to model the generic human operator's control behavior. However, little research has been done in an attempt to identify an individual based on his/her control behavior. The main hypothesis investigated in this dissertation is that different operators exhibit different control behavior when performing a given control task. Furthermore, inter-person differences are manifested in the amplitude and frequency content of the non-linear component of the control behavior. Two enhancements to the existing models of the human operator, which allow personalization of the modeled control behavior, are presented in this dissertation. One of the proposed enhancements accounts for the "testing" control signals, which are introduced by an operator for more accurate control of the system and/or to adjust his/her control strategy. Such enhancement uses the Artificial Neural Network (ANN), which can be fine-tuned to model the "testing" control behavior of a given individual. The other model enhancement took the form of an equiripple filter (EF), which conditions the power spectrum of the control signal before it is passed through the plant dynamics block. The filter design technique uses Parks-McClellan algorithm, which allows parameterization of the desired levels of power at certain frequencies. A novel automated parameter identification technique (APID) was developed to facilitate the identification process of the parameters of the selected models of the human operator. APID utilizes a Genetic Algorithm (GA) based optimization engine called the Bit-climbing Algorithm (BCA). Proposed model enhancements were validated using the experimental data obtained at three different sources: the Manual Control Laboratory software experiments, Unmanned Aerial Vehicle simulation, and NASA Langley Research Center Visual Motion Simulator studies. Validation analysis involves comparison of the actual and simulated control activity signals. Validation criteria used in this dissertation is based on comparing Power Spectral Densities of the control signals against that of the Precision model of the human operator. This dissertation also addresses the issue of applying the proposed human operator model augmentation to evaluate the effectiveness of the motion feedback when simulating the actual pilot control behavior in a flight simulator. The proposed modeling methodology allows for quantitative assessments and prediction of the need for platform motion, while performing aircraft/pilot simulation studies.
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Song, Ta-Shu; Hsieh, Yow-Wen; Peng, Ching-Tien; Liu, Cheng-Hsiung; Chen, Tai-Lin; Hour, Mann-Jen
2012-12-01
A fast and accurate liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay was first developed and validated for the determination of deferiprone in human plasma. The analytes were extracted with acetonitrile from only 50 μL aliquots of human plasma to achieve the protein precipitation. After extraction, chromatographic separation of analytes in human plasma was performed using a Synergi Fusion-RP 80A column at 30 °C. The mobile phase consisted of methanol and 0.2% formic acid containing 0.2 mM EDTA (60:40, v/v). The flow rate of the mobile phase was 0.8 mL/min. The total run time for each sample analysis was 4 min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the precursor-to-parent ion transitions m/z 140.1 → 53.1 for deferiprone and m/z 143.1 → 98.1 for internal standard. A linear range was established from 0.1 to 20 µg/mL. The limit of detection was determined as 0.05 µg/mL. The validated method was estimated for linearity, recovery, stability, precision and accuracy. Intraday and interday precisions were 4.3-5.5 and 4.6-7.3%, respectively. The recovery of deferiprone was in the range of 80.1-86.8%. The method was successfully applied to a pharmacokinetic study of deferiprone in six thalassemia patients. Copyright © 2012 John Wiley & Sons, Ltd.
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Simulation-based training for prostate surgery.
Khan, Raheej; Aydin, Abdullatif; Khan, Muhammad Shamim; Dasgupta, Prokar; Ahmed, Kamran
2015-10-01
To identify and review the currently available simulators for prostate surgery and to explore the evidence supporting their validity for training purposes. A review of the literature between 1999 and 2014 was performed. The search terms included a combination of urology, prostate surgery, robotic prostatectomy, laparoscopic prostatectomy, transurethral resection of the prostate (TURP), simulation, virtual reality, animal model, human cadavers, training, assessment, technical skills, validation and learning curves. Furthermore, relevant abstracts from the American Urological Association, European Association of Urology, British Association of Urological Surgeons and World Congress of Endourology meetings, between 1999 and 2013, were included. Only studies related to prostate surgery simulators were included; studies regarding other urological simulators were excluded. A total of 22 studies that carried out a validation study were identified. Five validated models and/or simulators were identified for TURP, one for photoselective vaporisation of the prostate, two for holmium enucleation of the prostate, three for laparoscopic radical prostatectomy (LRP) and four for robot-assisted surgery. Of the TURP simulators, all five have demonstrated content validity, three face validity and four construct validity. The GreenLight laser simulator has demonstrated face, content and construct validities. The Kansai HoLEP Simulator has demonstrated face and content validity whilst the UroSim HoLEP Simulator has demonstrated face, content and construct validity. All three animal models for LRP have been shown to have construct validity whilst the chicken skin model was also content valid. Only two robotic simulators were identified with relevance to robot-assisted laparoscopic prostatectomy, both of which demonstrated construct validity. A wide range of different simulators are available for prostate surgery, including synthetic bench models, virtual-reality platforms, animal models, human cadavers, distributed simulation and advanced training programmes and modules. The currently validated simulators can be used by healthcare organisations to provide supplementary training sessions for trainee surgeons. Further research should be conducted to validate simulated environments, to determine which simulators have greater efficacy than others and to assess the cost-effectiveness of the simulators and the transferability of skills learnt. With surgeons investigating new possibilities for easily reproducible and valid methods of training, simulation offers great scope for implementation alongside traditional methods of training. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.
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Plenis, Alina; Chmielewska, Aleksandra; Konieczna, Lucyna; Lamparczyk, Henryk
2007-09-01
A rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC) with ultraviolet detection has been developed for the determination of moclobemide and its metabolites, p-chloro-N-(-2-morpholinoethyl)benzamide N'-oxide (Ro 12-5637) and p-chloro-N-[2-(3-oxomorpholino)ethyl]-benzamide (Ro 12-8095), in human plasma. The assay was performed after single liquid-liquid extraction with dichloromethane at alkaline pH using phenacetin as the internal standard. Chromatographic separation was performed on a C(18) column using a mixture of acetonitrile and water (25:75, v/v), adjusted to pH 2.7 with ortho-phosphoric acid, as mobile phase. Spectrophotometric detection was performed at 239 nm. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The quantification limit for moclobemide and Ro 12-8095 was 10 ng/mL, and for Ro 12-5637 was 30 ng/mL. Linearity of the method was confirmed for the range 20-2500 ng/mL for moclobemide (r = 0.9998), 20-1750 ng/mL for Ro 12-8095 (r = 0.9996) and 30-350 ng/mL for Ro 12-5637 (r = 0.9991). Moreover, within-day and between-day precisions and accuracies of the method were established. The described method was successfully applied in pharmacokinetic studies of parent drug and its two metabolites after a single oral administration of 150 mg of moclobemide to 20 healthy volunteers. Copyright (c) 2007 John Wiley & Sons, Ltd.
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Low cost, patterning of human hNT brain cells on parylene-C with UV & IR laser machining.
Raos, Brad J; Unsworth, C P; Costa, J L; Rohde, C A; Doyle, C S; Delivopoulos, E; Murray, A F; Dickinson, M E; Simpson, M C; Graham, E S; Bunting, A S
2013-01-01
This paper describes the use of 800nm femtosecond infrared (IR) and 248nm nanosecond ultraviolet (UV) laser radiation in performing ablative micromachining of parylene-C on SiO2 substrates for the patterning of human hNT astrocytes. Results are presented that support the validity of using IR laser ablative micromachining for patterning human hNT astrocytes cells while UV laser radiation produces photo-oxidation of the parylene-C and destroys cell patterning. The findings demonstrate how IR laser ablative micromachining of parylene-C on SiO2 substrates can offer a low cost, accessible alternative for rapid prototyping, high yield cell patterning.
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Probabilistic simulation of the human factor in structural reliability
NASA Technical Reports Server (NTRS)
Chamis, C. C.
1993-01-01
A formal approach is described in an attempt to computationally simulate the probable ranges of uncertainties of the human factor in structural probabilistic assessments. A multi-factor interaction equation (MFIE) model has been adopted for this purpose. Human factors such as marital status, professional status, home life, job satisfaction, work load and health, are considered to demonstrate the concept. Parametric studies in conjunction with judgment are used to select reasonable values for the participating factors (primitive variables). Suitability of the MFIE in the subsequently probabilistic sensitivity studies are performed to assess the validity of the whole approach. Results obtained show that the uncertainties for no error range from five to thirty percent for the most optimistic case.
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An evaluative model of system performance in manned teleoperational systems
NASA Technical Reports Server (NTRS)
Haines, Richard F.
1989-01-01
Manned teleoperational systems are used in aerospace operations in which humans must interact with machines remotely. Manual guidance of remotely piloted vehicles, controling a wind tunnel, carrying out a scientific procedure remotely are examples of teleoperations. A four input parameter throughput (Tp) model is presented which can be used to evaluate complex, manned, teleoperations-based systems and make critical comparisons among candidate control systems. The first two parameters of this model deal with nominal (A) and off-nominal (B) predicted events while the last two focus on measured events of two types, human performance (C) and system performance (D). Digital simulations showed that the expression A(1-B)/C+D) produced the greatest homogeneity of variance and distribution symmetry. Results from a recently completed manned life science telescience experiment will be used to further validate the model. Complex, interacting teleoperational systems may be systematically evaluated using this expression much like a computer benchmark is used.
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Development of microcomputer-based mental acuity tests.
Turnage, J J; Kennedy, R S; Smith, M G; Baltzley, D R; Lane, N E
1992-10-01
Recent disasters have focused attention on performance problems due to the use of alcohol and controlled substances in the workplace. Environmental stressors such as thermal extremes, mixed gases, noise, motion, and vibration also have adverse effects on human performance and operator efficiency. However, the lack of a standardized, sensitive, human performance assessment battery has probably delayed the systematic study of the deleterious effects of various toxic chemicals and drugs at home and in the workplace. The collective goal of the research reported here is the development of a menu of tests embedded in a coherent package of hardware and software that may be useful in repeated-measures studies of a broad range of agents that can degrade human performance. A menu of 40 tests from the Automated Performance Test System (APTS) is described, and the series of interlocking studies supporting its development is reviewed. The APTS tests, which run on several versions of laptop portables and desktop personal computers, have been shown to be stable, reliable, and factorially rich, and to have predictive validities with holistic measures of intelligence and simulator performances. In addition, sensitivity studies have been conducted in which performance changes due to stressors, agents, and treatments were demonstrated. We believe that tests like those described here have prospective use as an adjunct to urine testing for the screening for performance loss of individuals who are granted access to workplaces and stations that impact public safety.
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Development of microcomputer-based mental acuity tests
NASA Technical Reports Server (NTRS)
Turnage, J. J.; Kennedy, R. S.; Smith, M. G.; Baltzley, D. R.; Lane, N. E.
1992-01-01
Recent disasters have focused attention on performance problems due to the use of alcohol and controlled substances in the workplace. Environmental stressors such as thermal extremes, mixed gases, noise, motion, and vibration also have adverse effects on human performance and operator efficiency. However, the lack of a standardized, sensitive, human performance assessment battery has probably delayed the systematic study of the deleterious effects of various toxic chemicals and drugs at home and in the workplace. The collective goal of the research reported here is the development of a menu of tests embedded in a coherent package of hardware and software that may be useful in repeated-measures studies of a broad range of agents that can degrade human performance. A menu of 40 tests from the Automated Performance Test System (APTS) is described, and the series of interlocking studies supporting its development is reviewed. The APTS tests, which run on several versions of laptop portables and desktop personal computers, have been shown to be stable, reliable, and factorially rich, and to have predictive validities with holistic measures of intelligence and simulator performances. In addition, sensitivity studies have been conducted in which performance changes due to stressors, agents, and treatments were demonstrated. We believe that tests like those described here have prospective use as an adjunct to urine testing for the screening for performance loss of individuals who are granted access to workplaces and stations that impact public safety.
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[Scientific ethics of human cloning].
Valenzuela, Carlos Y
2005-01-01
True cloning is fission, budding or other types of asexual reproduction. In humans it occurs in monozygote twinning. This type of cloning is ethically and religiously good. Human cloning can be performed by twinning (TWClo) or nuclear transfer (NTClo). Both methods need a zygote or a nuclear transferred cell, obtained in vitro (IVTec). They are under the IVTec ethics. IVTecs use humans (zygotes, embryos) as drugs or things; increase the risk of malformations; increase development and size of abnormalities and may cause long-term changes. Cloning for preserving extinct (or almost extinct) animals or humans when sexual reproduction is not possible is ethically valid. The previous selection of a phenotype in human cloning violates some ethical principles. NTClo for reproductive or therapeutic purposes is dangerous since it increases the risk for nucleotide or chromosome mutations, de-programming or re-programming errors, aging or malignancy of the embryo cells thus obtained.
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Pilot In-Trail Procedure Validation Simulation Study
NASA Technical Reports Server (NTRS)
Bussink, Frank J. L.; Murdoch, Jennifer L.; Chamberlain, James P.; Chartrand, Ryan; Jones, Kenneth M.
2008-01-01
A Human-In-The-Loop experiment was conducted at the National Aeronautics and Space Administration (NASA) Langley Research Center (LaRC) to investigate the viability of the In-Trail Procedure (ITP) concept from a flight crew perspective, by placing participating airline pilots in a simulated oceanic flight environment. The test subject pilots used new onboard avionics equipment that provided improved information about nearby traffic and enabled them, when specific criteria were met, to request an ITP flight level change referencing one or two nearby aircraft that might otherwise block the flight level change. The subject pilots subjective assessments of ITP validity and acceptability were measured via questionnaires and discussions, and their objective performance in appropriately selecting, requesting, and performing ITP flight level changes was evaluated for each simulated flight scenario. Objective performance and subjective workload assessment data from the experiment s test conditions were analyzed for statistical and operational significance and are reported in the paper. Based on these results, suggestions are made to further improve the ITP.
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In Vitro Simulation and Validation of the Circulation with Congenital Heart Defects
Figliola, Richard S.; Giardini, Alessandro; Conover, Tim; Camp, Tiffany A.; Biglino, Giovanni; Chiulli, John; Hsia, Tain-Yen
2010-01-01
Despite the recent advances in computational modeling, experimental simulation of the circulation with congenital heart defect using mock flow circuits remains an important tool for device testing, and for detailing the probable flow consequences resulting from surgical and interventional corrections. Validated mock circuits can be applied to qualify the results from novel computational models. New mathematical tools, coupled with advanced clinical imaging methods, allow for improved assessment of experimental circuit performance relative to human function, as well as the potential for patient-specific adaptation. In this review, we address the development of three in vitro mock circuits specific for studies of congenital heart defects. Performance of an in vitro right heart circulation circuit through a series of verification and validation exercises is described, including correlations with animal studies, and quantifying the effects of circuit inertiance on test results. We present our experience in the design of mock circuits suitable for investigations of the characteristics of the Fontan circulation. We use one such mock circuit to evaluate the accuracy of Doppler predictions in the presence of aortic coarctation. PMID:21218147
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Blast effect on the lower extremities and its mitigation: a computational study.
Dong, Liqiang; Zhu, Feng; Jin, Xin; Suresh, Mahi; Jiang, Binhui; Sevagan, Gopinath; Cai, Yun; Li, Guangyao; Yang, King H
2013-12-01
A series of computational studies were performed to investigate the response of the lower extremities of mounted soldiers under landmine detonation. A numerical human body model newly developed at Wayne State University was used to simulate two types of experimental studies and the model predictions were validated against test data in terms of the tibia axial force as well as bone fracture pattern. Based on the validated model, the minimum axial force causing tibia facture was found. Then a series of parametric studies was conducted to determine the critical velocity (peak velocity of the floor plate) causing tibia fracture at different upper/lower leg angles. In addition, to limit the load transmission through the vehicular floor, two types of energy absorbing materials, namely IMPAXX(®) foam and aluminum alloy honeycomb, were selected for floor matting. Their performances in terms of blast effect mitigation were compared using the validated numerical model, and it has been found that honeycomb is a more efficient material for blast injury prevention under the loading conditions studied. © 2013 Elsevier Ltd. All rights reserved.
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Zhao, Yang; Chen, Hui-Jun; Caritis, Steve; Venkataramanan, Raman
2016-02-01
A liquid chromatography-tandem mass spectrometric method for the quantification of granisetron and its major metabolite, 7-hydroxy granisetron in human plasma and urine samples was developed and validated. Respective stable isotopically labeled granisetron and 7-hydroxy granisetron were used as internal standards (IS). Chromatography was performed using an Xselect HSS T3 analytical column with a mobile phase of 20% acetonitrile in water (containing 0.2 mM ammonium formate and 0.14% formic acid, pH 4) delivered in an isocratic mode. Tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring was used for quantification. The standard curves were linear in the concentration ranges of 0.5-100 ng/mL for granisetron and 0.1-100 ng/mL for 7-hydroxy granisetron in human plasma samples, and 2-2000 ng/mL for granisetron and 2-1000 ng/mL for 7-hydroxy granisetron in human urine samples, respectively. The accuracies were >85% and the precision as determined by the coefficient of variations was <10%. No significant matrix effects were observed for granisetron or 7-hydroxy granisetron in either plasma or urine samples. Granisetron was stable under various storage and experimental conditions. This validated method was successfully applied to a pharmacokinetic study after intravenous administration of 1 mg granisetron to a pregnant subject. Copyright © 2015 John Wiley & Sons, Ltd.
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NASA Astrophysics Data System (ADS)
Anghel, D.-C.; Ene, A.; Ştirbu, C.; Sicoe, G.
2017-10-01
This paper presents a study about the factors that influence the working performances of workers in the automotive industry. These factors regard mainly the transportations conditions, taking into account the fact that a large number of workers live in places that are far away of the enterprise. The quantitative data obtained from this study will be generalized by using a neural network, software simulated. The neural network is able to estimate the performance of workers even for the combinations of input factors that had been not recorded by the study. The experimental data obtained from the study will be divided in two classes. The first class that contains approximately 80% of data will be used by the Java software for the training of the neural network. The weights resulted from the training process will be saved in a text file. The other class that contains the rest of the 20% of experimental data will be used to validate the neural network. The training and the validation of the networks are performed in a Java software (TrainAndValidate java class). We designed another java class, Test.java that will be used with new input data, for new situations. The experimental data collected from the study. The software that simulated the neural network. The software that estimates the working performance, when new situations are met. This application is useful for human resources department of an enterprise. The output results are not quantitative. They are qualitative (from low performance to high performance, divided in five classes).
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Enhanced Missing Proteins Detection in NCI60 Cell Lines Using an Integrative Search Engine Approach.
Guruceaga, Elizabeth; Garin-Muga, Alba; Prieto, Gorka; Bejarano, Bartolomé; Marcilla, Miguel; Marín-Vicente, Consuelo; Perez-Riverol, Yasset; Casal, J Ignacio; Vizcaíno, Juan Antonio; Corrales, Fernando J; Segura, Victor
2017-12-01
The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this endeavor, an in depth analysis of shotgun experiments might represent a valuable resource to select a biological matrix in design validation experiments. In this work, we used all the proteomic experiments from the NCI60 cell lines and applied an integrative approach based on the results obtained from Comet, Mascot, OMSSA, and X!Tandem. This workflow benefits from the complementarity of these search engines to increase the proteome coverage. Five missing proteins C-HPP guidelines compliant were identified, although further validation is needed. Moreover, 165 missing proteins were detected with only one unique peptide, and their functional analysis supported their participation in cellular pathways as was also proposed in other studies. Finally, we performed a combined analysis of the gene expression levels and the proteomic identifications from the common cell lines between the NCI60 and the CCLE project to suggest alternatives for further validation of missing protein observations.
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Enhanced Missing Proteins Detection in NCI60 Cell Lines Using an Integrative Search Engine Approach
2017-01-01
The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this endeavor, an in depth analysis of shotgun experiments might represent a valuable resource to select a biological matrix in design validation experiments. In this work, we used all the proteomic experiments from the NCI60 cell lines and applied an integrative approach based on the results obtained from Comet, Mascot, OMSSA, and X!Tandem. This workflow benefits from the complementarity of these search engines to increase the proteome coverage. Five missing proteins C-HPP guidelines compliant were identified, although further validation is needed. Moreover, 165 missing proteins were detected with only one unique peptide, and their functional analysis supported their participation in cellular pathways as was also proposed in other studies. Finally, we performed a combined analysis of the gene expression levels and the proteomic identifications from the common cell lines between the NCI60 and the CCLE project to suggest alternatives for further validation of missing protein observations. PMID:28960077
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Vikingsson, Svante; Strömqvist, Malin; Svedberg, Anna; Hansson, Johan; Höiom, Veronica; Gréen, Henrik
2016-08-01
A novel, rapid and sensitive liquid chromatography tandem-mass spectrometry method for quantification of vemurafenib in human plasma, that also for the first time allows for metabolite semi-quantification, was developed and validated to support clinical trials and therapeutic drug monitoring. Vemurafenib was analysed by precipitation with methanol followed by a 1.9 min isocratic liquid chromatography tandem masspectrometry analysis using an Acquity BEH C18 column with methanol and formic acid using isotope labelled internal standards. Analytes were detected in multireaction monitoring mode on a Xevo TQ. Semi-quantification of vemurafenib metabolites was performed using the same analytical system and sample preparation with gradient elution. The vemurafenib method was successfully validated in the range 0.5-100 μg/mL according to international guidelines. The metabolite method was partially validated owing to the lack of commercially available reference materials. For the first time concentration levels at steady state for melanoma patients treated with vemurafenib is presented. The low abundance of vemurafenib metabolites suggests that they lack clinical significance. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
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Validation of biological activity testing procedure of recombinant human interleukin-7.
Lutsenko, T N; Kovalenko, M V; Galkin, O Yu
2017-01-01
Validation procedure for method of monitoring the biological activity of reсombinant human interleukin-7 has been developed and conducted according to the requirements of national and international recommendations. This method is based on the ability of recombinant human interleukin-7 to induce proliferation of T lymphocytes. It has been shown that to control the biological activity of recombinant human interleukin-7 peripheral blood mononuclear cells (PBMCs) derived from blood or cell lines can be used. Validation characteristics that should be determined depend on the method, type of product or object test/measurement and biological test systems used in research. The validation procedure for the method of control of biological activity of recombinant human interleukin-7 in peripheral blood mononuclear cells showed satisfactory results on all parameters tested such as specificity, accuracy, precision and linearity.
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MetaMap: An atlas of metatranscriptomic reads in human disease-related RNA-seq data.
Simon, L M; Karg, S; Westermann, A J; Engel, M; Elbehery, A H A; Hense, B; Heinig, M; Deng, L; Theis, F J
2018-06-12
With the advent of the age of big data in bioinformatics, large volumes of data and high performance computing power enable researchers to perform re-analyses of publicly available datasets at an unprecedented scale. Ever more studies imply the microbiome in both normal human physiology and a wide range of diseases. RNA sequencing technology (RNA-seq) is commonly used to infer global eukaryotic gene expression patterns under defined conditions, including human disease-related contexts, but its generic nature also enables the detection of microbial and viral transcripts. We developed a bioinformatic pipeline to screen existing human RNA-seq datasets for the presence of microbial and viral reads by re-inspecting the non-human-mapping read fraction. We validated this approach by recapitulating outcomes from 6 independent controlled infection experiments of cell line models and comparison with an alternative metatranscriptomic mapping strategy. We then applied the pipeline to close to 150 terabytes of publicly available raw RNA-seq data from >17,000 samples from >400 studies relevant to human disease using state-of-the-art high performance computing systems. The resulting data of this large-scale re-analysis are made available in the presented MetaMap resource. Our results demonstrate that common human RNA-seq data, including those archived in public repositories, might contain valuable information to correlate microbial and viral detection patterns with diverse diseases. The presented MetaMap database thus provides a rich resource for hypothesis generation towards the role of the microbiome in human disease. Additionally, codes to process new datasets and perform statistical analyses are made available at https://github.com/theislab/MetaMap.
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Sell, Timothy C; Abt, John P; Crawford, Kim; Lovalekar, Mita; Nagai, Takashi; Deluzio, Jennifer B; Smalley, Brain W; McGrail, Mark A; Rowe, Russell S; Cardin, Sylvain; Lephart, Scott M
2010-01-01
Physical training for United States military personnel requires a combination of injury prevention and performance optimization to counter unintentional musculoskeletal injuries and maximize warrior capabilities. Determining the most effective activities and tasks to meet these goals requires a systematic, research-based approach that is population specific based on the tasks and demands of the Warrior. The authors have modified the traditional approach to injury prevention to implement a comprehensive injury prevention and performance optimization research program with the 101st Airborne Division (Air Assault) at Fort Campbell, KY. This is second of two companion papers and presents the last three steps of the research model and includes Design and Validation of the Interventions, Program Integration and Implementation, and Monitor and Determine the Effectiveness of the Program. An 8-week trial was performed to validate the Eagle Tactical Athlete Program (ETAP) to improve modifiable suboptimal characteristics identified in Part I. The experimental group participated in ETAP under the direction of a ETAP Strength and Conditioning Specialist while the control group performed the current physical training at Fort Campbell under the direction of a Physical Training Leader and as governed by FM 21-20 for the 8-week study period. Soldiers performing ETAP demonstrated improvements in several tests for strength, flexibility, performance, physiology, and the APFT compared to current physical training performed at Fort Campbell. ETAP was proven valid to improve certain suboptimal characteristics within the 8-week trial as compared to the current training performed at Fort Campbell. ETAP has long-term implications and with expected greater improvements when implemented into a Division pre-deployment cycle of 10-12 months which will result in further systemic adaptations for each variable.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jeffrey C. JOe; Ronald L. Boring
Probabilistic Risk Assessment (PRA) and Human Reliability Assessment (HRA) are important technical contributors to the United States (U.S.) Nuclear Regulatory Commission’s (NRC) risk-informed and performance based approach to regulating U.S. commercial nuclear activities. Furthermore, all currently operating commercial NPPs in the U.S. are required by federal regulation to be staffed with crews of operators. Yet, aspects of team performance are underspecified in most HRA methods that are widely used in the nuclear industry. There are a variety of "emergent" team cognition and teamwork errors (e.g., communication errors) that are 1) distinct from individual human errors, and 2) important to understandmore » from a PRA perspective. The lack of robust models or quantification of team performance is an issue that affects the accuracy and validity of HRA methods and models, leading to significant uncertainty in estimating HEPs. This paper describes research that has the objective to model and quantify team dynamics and teamwork within NPP control room crews for risk informed applications, thereby improving the technical basis of HRA, which improves the risk-informed approach the NRC uses to regulate the U.S. commercial nuclear industry.« less
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Baseline experiments in teleoperator control
NASA Technical Reports Server (NTRS)
Hankins, W. W., III; Mixon, R. W.
1986-01-01
Studies have been conducted at the NASA Langley Research Center (LaRC) to establish baseline human teleoperator interface data and to assess the influence of some of the interface parameters on human performance in teleoperation. As baseline data, the results will be used to assess future interface improvements resulting from this research in basic teleoperator human factors. In addition, the data have been used to validate LaRC's basic teleoperator hardware setup and to compare initial teleoperator study results. Four subjects controlled a modified industrial manipulator to perform a simple task involving both high and low precision. Two different schemes for controlling the manipulator were studied along with both direct and indirect viewing of the task. Performance of the task was measured as the length of time required to complete the task along with the number of errors made in the process. Analyses of variance were computed to determine the significance of the influences of each of the independent variables. Comparisons were also made between the LaRC data and data taken earlier by Grumman Aerospace Corp. at their facilities.
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Crazy like a fox. Validity and ethics of animal models of human psychiatric disease.
Rollin, Michael D H; Rollin, Bernard E
2014-04-01
Animal models of human disease play a central role in modern biomedical science. Developing animal models for human mental illness presents unique practical and philosophical challenges. In this article we argue that (1) existing animal models of psychiatric disease are not valid, (2) attempts to model syndromes are undermined by current nosology, (3) models of symptoms are rife with circular logic and anthropomorphism, (4) any model must make unjustified assumptions about subjective experience, and (5) any model deemed valid would be inherently unethical, for if an animal adequately models human subjective experience, then there is no morally relevant difference between that animal and a human.
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THE VALIDITY OF HUMAN AND COMPUTERIZED WRITING ASSESSMENT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ronald L. Boring
2005-09-01
This paper summarizes an experiment designed to assess the validity of essay grading between holistic and analytic human graders and a computerized grader based on latent semantic analysis. The validity of the grade was gauged by the extent to which the student’s knowledge of the topic correlated with the grader’s expert knowledge. To assess knowledge, Pathfinder networks were generated by the student essay writers, the holistic and analytic graders, and the computerized grader. It was found that the computer generated grades more closely matched the definition of valid grading than did human generated grades.
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Carlucci, Giuseppe; Selvaggi, Federico; Sulpizio, Sara; Bassi, Claudio; Carlucci, Maura; Cotellese, Roberto; Ferrone, Vincenzo; Innocenti, Paolo; Locatelli, Marcello
2015-06-01
A simple and sensitive method based on the combination of derivatization and high-performance liquid chromatography with ultraviolet and fluorimetric detection was developed for the simultaneous determination of octreotide and gabexate mesylate metabolite in human pancreatic juice samples. Parameters of the derivatization procedure affecting extraction efficiency were optimized. The developed method was validated according to the International Conference on Harmonization guidelines. The calibration curves were linear over a range of 0.1-15 µg/mL for octreotide and 0.20-15 µg/mL for gabexate mesylate metabolite. Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The limits of detection were 0.025 and 0.05, respectively, for octreotide and gabexate mesylate metabolite. This paper reports the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-FL) method for the simultaneous analysis of octreotide and gabexate mesylate metabolite in pancreatic juice by protein precipitation using zinc sulfate-methanol-acetonitrile containing the derivatizing reagent, 4-fluoro-7-nitro-[2,1,3]-benzoxadiazole (NBD-F). Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The method was validated over the concentration ranges 0.1-15 and 0.2-15 µg/mL for octreotide and gabexate mesylate metabolite, respectively, in human pancreatic juice. Biphalin and methyl-p-hydroxybenzoate were used as the internal standards. This method was successfully utilized to support clinical studies in humans. The results from assay validations show that the method is selective, sensitive and robust. The limit of quantification of the method was 0.1 µg/mL for octreotide and 0.2 µg/mL for gabexate mesylate metabolite, and matrix matched standard curves showed a good linearity up to 15 µg/mL. In the entire analytical range the intra- and inter-day precision (RSD%) values were respectively ≤5.9% and ≤3.1% for octreotide and ≤2.0% and ≤3.9% for gabexate mesylate metabolite. For both analytes the intra- and inter-day accuracy (bias) values ranged respectively from -6.8 to -2.5% and from -4.6 to -5.7%. This method utilizes derivatization with NBD-F and provides adequate sensitivity for both drugs. Copyright © 2014 John Wiley & Sons, Ltd.
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MicroRNA therapeutics in cardiovascular medicine
Thum, Thomas
2012-01-01
Cardiovascular diseases are the most common causes of human morbidity and mortality despite significant therapeutic improvements by surgical, interventional and pharmacological approaches in the last decade. MicroRNAs (miRNAs) are important and powerful mediators in a wide range of diseases and thus emerged as interesting new drug targets. An array of animal and even human miRNA-based therapeutic studies has been performed, which validate miRNAs as being successfully targetable to treat a wide range of diseases. Here, the current knowledge about miRNAs therapeutics in cardiovascular diseases on their way to clinical use are reviewed and discussed. PMID:22162462
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NASA Astrophysics Data System (ADS)
Ibrahim, Omar A.; Elwi, Taha A.; Islam, Naz E.
2012-11-01
A miniaturized microstrip antenna is analyzed for implantable biomedical applications. The antenna is designed using two different commercial software packages, CST Microwave Studio and HFSS, to validate the results. The proposed design operates in the WMTS frequency band. The antenna performance is tested inside the human body, Hugo model. The antenna design is readjusted to get the desired resonant frequency. The resonant frequency, bandwidth, gain, and radiation pattern of the proposed antenna are provided in this paper. Furthermore, the effect of losses inside human body due to the fat layer is recognized.
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Comparison of two weighted integration models for the cueing task: linear and likelihood
NASA Technical Reports Server (NTRS)
Shimozaki, Steven S.; Eckstein, Miguel P.; Abbey, Craig K.
2003-01-01
In a task in which the observer must detect a signal at two locations, presenting a precue that predicts the location of a signal leads to improved performance with a valid cue (signal location matches the cue), compared to an invalid cue (signal location does not match the cue). The cue validity effect has often been explained with a limited capacity attentional mechanism improving the perceptual quality at the cued location. Alternatively, the cueing effect can also be explained by unlimited capacity models that assume a weighted combination of noisy responses across the two locations. We compare two weighted integration models, a linear model and a sum of weighted likelihoods model based on a Bayesian observer. While qualitatively these models are similar, quantitatively they predict different cue validity effects as the signal-to-noise ratios (SNR) increase. To test these models, 3 observers performed in a cued discrimination task of Gaussian targets with an 80% valid precue across a broad range of SNR's. Analysis of a limited capacity attentional switching model was also included and rejected. The sum of weighted likelihoods model best described the psychophysical results, suggesting that human observers approximate a weighted combination of likelihoods, and not a weighted linear combination.
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International Validation of Two Human Recombinant Estrogen Receptor (ERa) Binding Assays
An international validation study has been successfully completed for 2 competitive binding assays using human recombinant ERa. Assays evaluated included the Freyberger-Wilson (FW) assay using a full length human ER, and the Chemical Evaluation and Research Institute (CERI) assay...
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Virtual temporal bone dissection system: OSU virtual temporal bone system: development and testing.
Wiet, Gregory J; Stredney, Don; Kerwin, Thomas; Hittle, Bradley; Fernandez, Soledad A; Abdel-Rasoul, Mahmoud; Welling, D Bradley
2012-03-01
The objective of this project was to develop a virtual temporal bone dissection system that would provide an enhanced educational experience for the training of otologic surgeons. A randomized, controlled, multi-institutional, single-blinded validation study. The project encompassed four areas of emphasis: structural data acquisition, integration of the system, dissemination of the system, and validation. Structural acquisition was performed on multiple imaging platforms. Integration achieved a cost-effective system. Dissemination was achieved on different levels including casual interest, downloading of software, and full involvement in development and validation studies. A validation study was performed at eight different training institutions across the country using a two-arm randomized trial where study subjects were randomized to a 2-week practice session using either the virtual temporal bone or standard cadaveric temporal bones. Eighty subjects were enrolled and randomized to one of the two treatment arms; 65 completed the study. There was no difference between the two groups using a blinded rating tool to assess performance after training. A virtual temporal bone dissection system has been developed and compared to cadaveric temporal bones for practice using a multicenter trial. There was no statistical difference between practice on the current simulator compared to practice on human cadaveric temporal bones. Further refinements in structural acquisition and interface design have been identified, which can be implemented prior to full incorporation into training programs and used for objective skills assessment. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
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Dynamic gene expression response to altered gravity in human T cells.
Thiel, Cora S; Hauschild, Swantje; Huge, Andreas; Tauber, Svantje; Lauber, Beatrice A; Polzer, Jennifer; Paulsen, Katrin; Lier, Hartwin; Engelmann, Frank; Schmitz, Burkhard; Schütte, Andreas; Layer, Liliana E; Ullrich, Oliver
2017-07-12
We investigated the dynamics of immediate and initial gene expression response to different gravitational environments in human Jurkat T lymphocytic cells and compared expression profiles to identify potential gravity-regulated genes and adaptation processes. We used the Affymetrix GeneChip® Human Transcriptome Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding genes and performed the experiments during a parabolic flight and a suborbital ballistic rocket mission to cross-validate gravity-regulated gene expression through independent research platforms and different sets of control experiments to exclude other factors than alteration of gravity. We found that gene expression in human T cells rapidly responded to altered gravity in the time frame of 20 s and 5 min. The initial response to microgravity involved mostly regulatory RNAs. We identified three gravity-regulated genes which could be cross-validated in both completely independent experiment missions: ATP6V1A/D, a vacuolar H + -ATPase (V-ATPase) responsible for acidification during bone resorption, IGHD3-3/IGHD3-10, diversity genes of the immunoglobulin heavy-chain locus participating in V(D)J recombination, and LINC00837, a long intergenic non-protein coding RNA. Due to the extensive and rapid alteration of gene expression associated with regulatory RNAs, we conclude that human cells are equipped with a robust and efficient adaptation potential when challenged with altered gravitational environments.
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Kojima, Hajime; Katoh, Masakazu; Shinoda, Shinsuke; Hagiwara, Saori; Suzuki, Tamie; Izumi, Runa; Yamaguchi, Yoshihiro; Nakamura, Maki; Kasahawa, Toshihiko; Shibai, Aya
2014-07-01
Three validation studies were conducted by the Japanese Society for Alternatives to Animal Experiments in order to assess the performance of a skin irritation assay using reconstructed human epidermis (RhE) LabCyte EPI-MODEL24 (LabCyte EPI-MODEL24 SIT) developed by the Japan Tissue Engineering Co., Ltd. (J-TEC), and the results of these studies were submitted to the Organisation for Economic Co-operation and Development (OECD) for the creation of a Test Guideline (TG). In the summary review report from the OECD, the peer review panel indicated the need to resolve an issue regarding the misclassification of 1-bromohexane. To this end, a rinsing operation intended to remove exposed chemicals was reviewed and the standard operating procedure (SOP) revised by J-TEC. Thereafter, in order to confirm general versatility of the revised SOP, a new validation management team was organized by the Japanese Center for the Validation of Alternative Methods (JaCVAM) to undertake a catch-up validation study that would compare the revised assay with similar in vitro skin irritation assays, per OECD TG No. 439 (2010). The catch-up validation and supplementary studies for LabCyte EPI-MODEL24 SIT using the revised SOPs were conducted at three laboratories. These results showed that the revised SOP of LabCyte EPI-MODEL24 SIT conformed more accurately to the classifications for skin irritation under the United Nations Globally Harmonised System of Classification and Labelling of Chemicals (UN GHS), thereby highlighting the importance of an optimized rinsing operation for the removal of exposed chemicals in obtaining consistent results from in vitro skin irritation assays. Copyright © 2013 John Wiley & Sons, Ltd.
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Urrutia, María Teresa; Gajardo, Macarena; Padilla, Oslando
2017-05-22
Despite a clear association between human papillomavirus and cervical cancer, knowledge in adolescent populations regarding the disease and methods for its detection and prevention is deficient. The aim of this study was to develop and test a new questionnaire concerning knowledge on cervical cancer. An instrument was developed and validated to measure knowledge in 226 Chilean adolescents between April and June 2011. Content validity, construct validity, and reliability analysis of the instrument were performed. The new, validated instrument, called CEC-61 (Conocimientos en Cancer Cérvicouterino-61 items/Knowledge in Cervical Cancer-61 items), contains nine factors and 61 items. The new questionnaire explained 81% of the variance with a reliability of 0.96. The assessment of knowledge with a valid and reliable instrument is the first step in creating interventions for a population and to encourage appropriate preventive behavior. CEC-61 is highly reliable and has a clear factorial structure to evaluate knowledge in nine domains related to cervical cancer disease, cervical cancer risk, papilloma virus infection, the Papanicolaou test, and the papilloma virus vaccine.
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Mitra, Amitava; Kim, Nanhye; Spark, Darren; Toner, Frank; Craig, Susan; Roper, Clive; Meyer, Thomas A
2016-12-01
The primary objective of this work was to investigate, using an in vitro human skin permeation study, whether changes in the excipients of butenafine hydrochloride cream would have any effect on bioperformance of the formulation. Such in vitro data would be a surrogate for any requirement of a bioequivalence (BE) study to demonstrate formulation similarity. A LC-MS/MS method for quantitation of butenafine in various matrices was developed and validated. A pilot study was performed to validate the in vitro skin permeation methodology using three cream formulations containing butenafine hydrochloride at concentrations of 0.5, 1.0 and 1.5% (w/w). Finally, a definitive in vitro human skin permeation study was conducted, comparing the extent of butenafine hydrochloride permeation from the new formulation to that from the current formulation. The results of the study comparing the two formulations showed that there was no statistically significant difference in the extent of butenafine permeation into human skin. In conclusion, these in vitro data demonstrated that the formulation change is likely to have no significant impact on the bioperformance of 1% (w/w) butenafine hydrochloride cream. Copyright © 2016 Elsevier Inc. All rights reserved.
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A contaminant-free assessment of Endogenous Retroviral RNA in human plasma
Karamitros, Timokratis; Paraskevis, Dimitrios; Hatzakis, Angelos; Psichogiou, Mina; Elefsiniotis, Ioannis; Hurst, Tara; Geretti, Anna-Maria; Beloukas, Apostolos; Frater, John; Klenerman, Paul; Katzourakis, Aris; Magiorkinis, Gkikas
2016-01-01
Endogenous retroviruses (ERVs) comprise 6–8% of the human genome. HERVs are silenced in most normal tissues, up-regulated in stem cells and in placenta but also in cancer and HIV-1 infection. Crucially, there are conflicting reports on detecting HERV RNA in non-cellular clinical samples such as plasma that suggest the study of HERV RNA can be daunting. Indeed, we find that the use of real-time PCR in a quality assured clinical laboratory setting can be sensitive to low-level proviral contamination. We developed a mathematical model for low-level contamination that allowed us to design a laboratory protocol and standard operating procedures for robust measurement of HERV RNA. We focus on one family, HERV-K HML-2 (HK2) that has been most recently active even though they invaded our ancestral genomes almost 30 millions ago. We extensively validated our experimental design on a model cell culture system showing high sensitivity and specificity, totally eliminating the proviral contamination. We then tested 236 plasma samples from patients infected with HIV-1, HCV or HBV and found them to be negative. The study of HERV RNA for human translational studies should be performed with extensively validated protocols and standard operating procedures to control the widespread low-level human DNA contamination. PMID:27640347
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Analytical validation of viral CNS Flow Chip kit for detection of acute meningitis and encephalitis.
Pérez-Ruiz, Mercedes; Pedrosa-Corral, Irene; Sanbonmatsu-Gámez, Sara; Gómez-Camarasa, Cristina; Navarro-Marí, José María
2018-06-12
A new molecular assay (Viral CNS Flow Chip kit, Master Diagnóstica, Spain) has been developed for the detection of eight viruses causing acute meningitis and encephalitis, i.e. herpes simplex viruses 1-2, varicella zoster virus, human enterovirus, human parechovirus, Toscana virus, human cytomegalovirus and Epstein Barr virus. The new assay is a multiplex one-step RT-PCR followed by automatic flow-through hybridization, colorimetric detection and image analysis. The limit of detection was 50 copies/reaction, and 10 copies/reaction for human enterovirus and the other seven viruses, respectively. The analytical validation was performed with nucleic acids extracted from 268 cerebrospinal fluid samples and the results were compared with routine molecular assays. An excellent coefficient of agreement was observed between V-CNS and routine assays [kappa index: 0.948 (95%CI: 0.928-0.968)]. The overall sensitivity and specificity was 95.9% (95%CI: 91.2-98.3%) and 99.9% (95%CI: 99.6-100%), respectively. Viral CNS Flow Chip kit is an efficient multiplex platform for the detection of the main viruses involved in acute meningitis and encephalitis. The inclusion of a TOSV genome target may improve the laboratory diagnosis of viral neurological infections in endemic areas. Copyright © 2018 Elsevier B.V. All rights reserved.
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Determination of personal care products -benzophenones and parabens- in human menstrual blood.
Jiménez-Díaz, I; Iribarne-Durán, L M; Ocón, O; Salamanca, E; Fernández, M F; Olea, N; Barranco, E
2016-11-01
Benzophenones and parabens are synthetic chemicals used in many personal care products, foods and pharmaceuticals. Benzophenones are used to protect the skin and materials from the adverse effects of UV-radiation, and parabens are used as preservatives. Despite their widespread occurrence and proven endocrine disrupting activity, relatively little is known about human exposure to these compounds. In the present work, an analytical method based on sample treatment using dispersive liquid-liquid microextraction (DLLME) for the extraction of six benzophenones (benzophenone-1, -2, -3, -6, -8 and 4-hydroxybenzophenone) and four parabens (methyl-, ethyl-, propyl- and butyl- paraben) from human menstrual blood samples, followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is proposed and validated. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. The limits of detection ranged from 0.1 to 0.3ngmL -1 , with recoveries of 93.8% to 108.9%, and precision (evaluated as relative standard deviation) lower than 14% for all selected compounds. This method was successfully applied for the determination of the target compounds in 25 samples of human menstrual blood. Methylparaben and benzophenone-3 were the most frequently detected compounds (96%). Copyright © 2016 Elsevier B.V. All rights reserved.
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Desmedt, Bart; Ates, Gamze; Courselle, Patricia; De Beer, Jacques O; Rogiers, Vera; Hendrickx, Benoit; Deconinck, Eric; De Paepe, Kristien
2016-01-01
In Europe, hydroquinone is a forbidden cosmetic ingredient. It is, however, still abundantly used because of its effective skin-whitening properties. The question arises as to whether the quantities of hydroquinone used become systemically available and may cause damage to human health. Dermal absorption studies can provide this information. In the EU, dermal absorption has to be assessed in vitro since the Cosmetic Regulation 1223/2009/EC forbids the use of animals. To obtain human-relevant data, a Franz diffusion cell protocol was validated using human skin. The results obtained were comparable to those from a multicentre validation study. The protocol was applied to hydroquinone and the dermal absorption ranged between 31 and 44%, which is within the range of published in vivo human values. This shows that a well-validated in vitro dermal absorption study using human skin provides relevant human data. The validated protocol was used to determine the dermal absorption of illegal skin-whitening cosmetics containing hydroquinone. All samples gave high dermal absorption values, rendering them all unsafe for human health. These results add to our knowledge of illegal cosmetics on the EU market, namely that they exhibit a negative toxicological profile and are likely to induce health problems. © 2017 S. Karger AG, Basel.
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Ioannidis, J P; McQueen, P G; Goedert, J J; Kaslow, R A
1998-03-01
Complex immunogenetic associations of disease involving a large number of gene products are difficult to evaluate with traditional statistical methods and may require complex modeling. The authors evaluated the performance of feed-forward backpropagation neural networks in predicting rapid progression to acquired immunodeficiency syndrome (AIDS) for patients with human immunodeficiency virus (HIV) infection on the basis of major histocompatibility complex variables. Networks were trained on data from patients from the Multicenter AIDS Cohort Study (n = 139) and then validated on patients from the DC Gay cohort (n = 102). The outcome of interest was rapid disease progression, defined as progression to AIDS in <6 years from seroconversion. Human leukocyte antigen (HLA) variables were selected as network inputs with multivariate regression and a previously described algorithm selecting markers with extreme point estimates for progression risk. Network performance was compared with that of logistic regression. Networks with 15 HLA inputs and a single hidden layer of five nodes achieved a sensitivity of 87.5% and specificity of 95.6% in the training set, vs. 77.0% and 76.9%, respectively, achieved by logistic regression. When validated on the DC Gay cohort, networks averaged a sensitivity of 59.1% and specificity of 74.3%, vs. 53.1% and 61.4%, respectively, for logistic regression. Neural networks offer further support to the notion that HIV disease progression may be dependent on complex interactions between different class I and class II alleles and transporters associated with antigen processing variants. The effect in the current models is of moderate magnitude, and more data as well as other host and pathogen variables may need to be considered to improve the performance of the models. Artificial intelligence methods may complement linear statistical methods for evaluating immunogenetic associations of disease.
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McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D
2014-07-01
Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. © 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.
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Development and Fit-for-Purpose Validation of a Soluble Human Programmed Death-1 Protein Assay.
Ni, Yan G; Yuan, Xiling; Newitt, John A; Peterson, Jon E; Gleason, Carol R; Haulenbeek, Jonathan; Santockyte, Rasa; Lafont, Virginie; Marsilio, Frank; Neely, Robert J; DeSilva, Binodh; Piccoli, Steven P
2015-07-01
Programmed death-1 (PD-1) protein is a co-inhibitory receptor which negatively regulates immune cell activation and permits tumors to evade normal immune defense. Anti-PD-1 antibodies have been shown to restore immune cell activation and effector function-an exciting breakthrough in cancer immunotherapy. Recent reports have documented a soluble form of PD-1 (sPD-1) in the circulation of normal and disease state individuals. A clinical assay to quantify sPD-1 would contribute to the understanding of sPD-1-function and facilitate the development of anti-PD-1 drugs. Here, we report the development and validation of a sPD-1 protein assay. The assay validation followed the framework for full validation of a biotherapeutic pharmacokinetic assay. A purified recombinant human PD-1 protein was characterized extensively and was identified as the assay reference material which mimics the endogenous analyte in structure and function. The lower limit of quantitation (LLOQ) was determined to be 100 pg/mL, with a dynamic range spanning three logs to 10,000 pg/mL. The intra- and inter-assay imprecision were ≤15%, and the assay bias (percent deviation) was ≤10%. Potential matrix effects were investigated in sera from both normal healthy volunteers and selected cancer patients. Bulk-prepared frozen standards and pre-coated Streptavidin plates were used in the assay to ensure consistency in assay performance over time. This assay appears to specifically measure total sPD-1 protein since the human anti-PD-1 antibody, nivolumab, and the endogenous ligands of PD-1 protein, PDL-1 and PDL-2, do not interfere with the assay.
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Liu, Liling; Cui, Zhiyi; Deng, Yuzhong; Dean, Brian; Hop, Cornelis E C A; Liang, Xiaorong
2016-02-01
A high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for the quantitative determination of NAD(+) in human whole blood using a surrogate analyte approach was developed and validated. Human whole blood was acidified using 0.5N perchloric acid at a ratio of 1:3 (v:v, blood:perchloric acid) during sample collection. 25μL of acidified blood was extracted using a protein precipitation method and the resulting extracts were analyzed using reverse-phase chromatography and positive electrospray ionization mass spectrometry. (13)C5-NAD(+) was used as the surrogate analyte for authentic analyte, NAD(+). The standard curve ranging from 0.250 to 25.0μg/mL in acidified human blood for (13)C5-NAD(+) was fitted to a 1/x(2) weighted linear regression model. The LC-MS/MS response between surrogate analyte and authentic analyte at the same concentration was obtained before and after the batch run. This response factor was not applied when determining the NAD(+) concentration from the (13)C5-NAD(+) standard curve since the percent difference was less than 5%. The precision and accuracy of the LC-MS/MS assay based on the five analytical QC levels were well within the acceptance criteria from both FDA and EMA guidance for bioanalytical method validation. Average extraction recovery of (13)C5-NAD(+) was 94.6% across the curve range. Matrix factor was 0.99 for both high and low QC indicating minimal ion suppression or enhancement. The validated assay was used to measure the baseline level of NAD(+) in 29 male and 21 female human subjects. This assay was also used to study the circadian effect of endogenous level of NAD(+) in 10 human subjects. Copyright © 2015 Elsevier B.V. All rights reserved.
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NASA Technical Reports Server (NTRS)
Putnam, J. B.; Unataroiu, C. D.; Somers, J. T.
2014-01-01
The THOR anthropomorphic test device (ATD) has been developed and continuously improved by the National Highway Traffic Safety Administration to provide automotive manufacturers an advanced tool that can be used to assess the injury risk of vehicle occupants in crash tests. Recently, a series of modifications were completed to improve the biofidelity of THOR ATD [1]. The updated THOR Modification Kit (THOR-K) ATD was employed at Wright-Patterson Air Base in 22 impact tests in three configurations: vertical, lateral, and spinal [2]. Although a computational finite element (FE) model of the THOR had been previously developed [3], updates to the model were needed to incorporate the recent changes in the modification kit. The main goal of this study was to develop and validate a FE model of the THOR-K ATD. The CAD drawings of the THOR-K ATD were reviewed and FE models were developed for the updated parts. For example, the head-skin geometry was found to change significantly, so its model was re-meshed (Fig. 1a). A protocol was developed to calibrate each component identified as key to the kinematic and kinetic response of the THOR-K head/neck ATD FE model (Fig. 1b). The available ATD tests were divided in two groups: a) calibration tests where the unknown material parameters of deformable parts (e.g., head skin, pelvis foam) were optimized to match the data and b) validation tests where the model response was only compared with test data by calculating their score using CORrelation and Analysis (CORA) rating system. Finally, the whole ATD model was validated under horizontal-, vertical-, and lateral-loading conditions against data recorded in the Wright Patterson tests [2]. Overall, the final THOR-K ATD model developed in this study is shown to respond similarly to the ATD in all validation tests. This good performance indicates that the optimization performed during calibration by using the CORA score as objective function is not test specific. Therefore confidence is provided in the ATD model for uses in predicting response in test conditions not performed in this study such those observed in the spacecraft landing. Comparison studies with ATD and human models may also be performed to contribute to future changes in THOR ATD design in an effort to improve its biofidelity, which has been traditionally based on post-mortem human subject testing and designer experience.
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On-Orbit Prospective Echocardiography on International Space Station
NASA Technical Reports Server (NTRS)
Hamilton, Douglas R.; Sargsyan, Ashot E.; Martin, David; Garcia, Kathleen M.; Melton, Shannon; Feiverson, Alan; Dulchavsky, Scott A.
2010-01-01
A number of echocardiographic research projects and experiments have been flown on almost every space vehicle since 1970, but validation of standard methods and the determination of Space Normal cardiac function has not been reported to date. Advanced Diagnostics in Microgravity (ADUM) -remote guided echocardiographic technique provides a novel and effective approach to on-board assessment of cardiac physiology and structure using a just-in-time training algorithm and real-time remote guidance aboard the International Space Station (ISS). The validation of remotely guided echocardiographic techniques provides the procedures and protocols to perform scientific and clinical echocardiography on the ISS and the Moon. The objectives of this study were: 1.To confirm the ability of non-physician astronaut/cosmonaut crewmembers to perform clinically relevant remotely guided echocardiography using the Human Research Facility on board the ISS. 2.To compare the preflight, postflight and in-flight echocardiographic parameters commonly used in clinical medicine.
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Leston, Sara; Freitas, Andreia; Rosa, João; Barbosa, Jorge; Lemos, Marco F L; Pardal, Miguel Ângelo; Ramos, Fernando
2016-10-15
Together with fish, algae reared in aquaculture systems have gained importance in the last years, for many purposes. Besides their use as biofilters of effluents, macroalgae's rich nutritional profiles have increased their inclusion in human diets but also in animal feeds as sources of fatty acids, especially important for the fish industry. Nonetheless, algae are continuously exposed to environmental contaminants including antibiotics and possess the ability for bioaccumulation of such compounds. Therefore, the present paper describes the development and validation of an ultra-high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of antibiotics in the green macroalgae Ulva lactuca. This multi-residue method enables the determination of 38 compounds distributed between seven classes and was fully validated according to EU Decision 2002/657/EC. Copyright © 2016 Elsevier B.V. All rights reserved.
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A single-islet microplate assay to measure mouse and human islet insulin secretion.
Truchan, Nathan A; Brar, Harpreet K; Gallagher, Shannon J; Neuman, Joshua C; Kimple, Michelle E
2015-01-01
One complication to comparing β-cell function among islet preparations, whether from genetically identical or diverse animals or human organ donors, is the number of islets required per assay. Islet numbers can be limiting, meaning that fewer conditions can be tested; other islet measurements must be excluded; or islets must be pooled from multiple animals/donors for each experiment. Furthermore, pooling islets negates the possibility of performing single-islet comparisons. Our aim was to validate a 96-well plate-based single islet insulin secretion assay that would be as robust as previously published methods to quantify glucose-stimulated insulin secretion from mouse and human islets. First, we tested our new assay using mouse islets, showing robust stimulation of insulin secretion 24 or 48 h after islet isolation. Next, we utilized the assay to quantify mouse islet function on an individual islet basis, measurements that would not be possible with the standard pooled islet assay methods. Next, we validated our new assay using human islets obtained from the Integrated Islet Distribution Program (IIDP). Human islets are known to have widely varying insulin secretion capacity, and using our new assay we reveal biologically relevant factors that are significantly correlated with human islet function, whether displayed as maximal insulin secretion response or fold-stimulation of insulin secretion. Overall, our results suggest this new microplate assay will be a useful tool for many laboratories, expert or not in islet techniques, to be able to precisely quantify islet insulin secretion from their models of interest.
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Meursinge Reynders, Reint
2016-01-01
The validity of studies that assess the effectiveness of an intervention (EoI) depends on variables such as the type of study design, the quality of their methodology, and the participants enrolled. Five leading veterinary journals and 5 leading human medical journals were hand-searched for EoI studies for the year 2013. We assessed (1) the prevalence of randomized controlled trials (RCTs) among EoI studies, (2) the type of participants enrolled, and (3) the methodological quality of the selected studies. Of 1707 eligible articles, 590 were EoI articles and 435 RCTs. Random allocation to the intervention was performed in 52% (114/219; 95%CI:45.2–58.8%) of veterinary EoI articles, against 87% (321/371; 82.5–89.7%) of human EoI articles (adjusted OR:9.2; 3.4–24.8). Veterinary RCTs were smaller (median: 26 animals versus 465 humans) and less likely to enroll real patients, compared with human RCTs (OR:331; 45–2441). Only 2% of the veterinary RCTs, versus 77% of the human RCTs, reported power calculations, primary outcomes, random sequence generation, allocation concealment and estimation methods. Currently, internal and external validity of veterinary EoI studies is limited compared to human medical ones. To address these issues, veterinary interventional research needs to improve its methodology, increase the number of published RCTs and enroll real clinical patients. PMID:26835187
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HLPI-Ensemble: Prediction of human lncRNA-protein interactions based on ensemble strategy.
Hu, Huan; Zhang, Li; Ai, Haixin; Zhang, Hui; Fan, Yetian; Zhao, Qi; Liu, Hongsheng
2018-03-27
LncRNA plays an important role in many biological and disease progression by binding to related proteins. However, the experimental methods for studying lncRNA-protein interactions are time-consuming and expensive. Although there are a few models designed to predict the interactions of ncRNA-protein, they all have some common drawbacks that limit their predictive performance. In this study, we present a model called HLPI-Ensemble designed specifically for human lncRNA-protein interactions. HLPI-Ensemble adopts the ensemble strategy based on three mainstream machine learning algorithms of Support Vector Machines (SVM), Random Forests (RF) and Extreme Gradient Boosting (XGB) to generate HLPI-SVM Ensemble, HLPI-RF Ensemble and HLPI-XGB Ensemble, respectively. The results of 10-fold cross-validation show that HLPI-SVM Ensemble, HLPI-RF Ensemble and HLPI-XGB Ensemble achieved AUCs of 0.95, 0.96 and 0.96, respectively, in the test dataset. Furthermore, we compared the performance of the HLPI-Ensemble models with the previous models through external validation dataset. The results show that the false positives (FPs) of HLPI-Ensemble models are much lower than that of the previous models, and other evaluation indicators of HLPI-Ensemble models are also higher than those of the previous models. It is further showed that HLPI-Ensemble models are superior in predicting human lncRNA-protein interaction compared with previous models. The HLPI-Ensemble is publicly available at: http://ccsipb.lnu.edu.cn/hlpiensemble/ .
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Leonelli, Sabina; Ankeny, Rachel A.; Nelson, Nicole C.; Ramsden, Edmund
2014-01-01
Argument We examine the criteria used to validate the use of nonhuman organisms in North-American alcohol addiction research from the 1950s to the present day. We argue that this field, where the similarities between behaviors in humans and non-humans are particularly difficult to assess, has addressed questions of model validity by transforming the situatedness of non-human organisms into an experimental tool. We demonstrate that model validity does not hinge on the standardization of one type of organism in isolation, as often the case with genetic model organisms. Rather, organisms are viewed as necessarily situated: they cannot be understood as a model for human behavior in isolation from their environmental conditions. Hence the environment itself is standardized as part of the modeling process; and model validity is assessed with reference to the environmental conditions under which organisms are studied. PMID:25233743
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Quantitative bioanalysis of strontium in human serum by inductively coupled plasma-mass spectrometry
Somarouthu, Srikanth; Ohh, Jayoung; Shaked, Jonathan; Cunico, Robert L; Yakatan, Gerald; Corritori, Suzana; Tami, Joe; Foehr, Erik D
2015-01-01
Aim: A bioanalytical method using inductively-coupled plasma-mass spectrometry to measure endogenous levels of strontium in human serum was developed and validated. Results & methodology: This article details the experimental procedures used for the method development and validation thus demonstrating the application of the inductively-coupled plasma-mass spectrometry method for quantification of strontium in human serum samples. The assay was validated for specificity, linearity, accuracy, precision, recovery and stability. Significant endogenous levels of strontium are present in human serum samples ranging from 19 to 96 ng/ml with a mean of 34.6 ± 15.2 ng/ml (SD). Discussion & conclusion: Calibration procedures and sample pretreatment were simplified for high throughput analysis. The validation demonstrates that the method was sensitive, selective for quantification of strontium (88Sr) and is suitable for routine clinical testing of strontium in human serum samples. PMID:28031925
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Jensen, Greg; Terrace, Herbert
2017-01-01
Humans are highly adept at categorizing visual stimuli, but studies of human categorization are typically validated by verbal reports. This makes it difficult to perform comparative studies of categorization using non-human animals. Interpretation of comparative studies is further complicated by the possibility that animal performance may merely reflect reinforcement learning, whereby discrete features act as discriminative cues for categorization. To assess and compare how humans and monkeys classified visual stimuli, we trained 7 rhesus macaques and 41 human volunteers to respond, in a specific order, to four simultaneously presented stimuli at a time, each belonging to a different perceptual category. These exemplars were drawn at random from large banks of images, such that the stimuli presented changed on every trial. Subjects nevertheless identified and ordered these changing stimuli correctly. Three monkeys learned to order naturalistic photographs; four others, close-up sections of paintings with distinctive styles. Humans learned to order both types of stimuli. All subjects classified stimuli at levels substantially greater than that predicted by chance or by feature-driven learning alone, even when stimuli changed on every trial. However, humans more closely resembled monkeys when classifying the more abstract painting stimuli than the photographic stimuli. This points to a common classification strategy in both species, one that humans can rely on in the absence of linguistic labels for categories. PMID:28961270
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kovesdi, C.; Spielman, Z.; LeBlanc, K.
An important element of human factors engineering (HFE) pertains to measurement and evaluation (M&E). The role of HFE-M&E should be integrated throughout the entire control room modernization (CRM) process and be used for human-system performance evaluation and diagnostic purposes with resolving potential human engineering deficiencies (HEDs) and other human machine interface (HMI) design issues. NUREG-0711 describes how HFE in CRM should employ a hierarchical set of measures, particularly during integrated system validation (ISV), including plant performance, personnel task performance, situation awareness, cognitive workload, and anthropometric/ physiological factors. Historically, subjective measures have been primarily used since they are easier to collectmore » and do not require specialized equipment. However, there are pitfalls with relying solely on subjective measures in M&E such that negatively impact reliability, sensitivity, and objectivity. As part of comprehensively capturing a diverse set of measures that strengthen findings and inferences made of the benefits from emerging technologies like advanced displays, this paper discusses the value of using eye tracking as an objective method that can be used in M&E. A brief description of eye tracking technology and relevant eye tracking measures is provided. Additionally, technical considerations and the unique challenges with using eye tracking in full-scaled simulations are addressed. Finally, this paper shares preliminary findings regarding the use of a wearable eye tracking system in a full-scale simulator study. These findings should help guide future full-scale simulator studies using eye tracking as a methodology to evaluate human-system performance.« less
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NASA Astrophysics Data System (ADS)
Widodo, W.; Sudibyo, E.; Sari, D. A. P.
2018-04-01
This study aims to develop student worksheets for higher education that apply integrated science learning in discussing issues about motion in humans. These worksheets will guide students to solve the problem about human movement. They must integrate their knowledge about biology, physics, and chemistry to solve the problem. The worksheet was validated by three experts in Natural Science Integrated Science, especially in Human Movement topic. The aspects of the validation were feasibility of the content, the construction, and the language. This research used the Likert scale to measure the validity of each aspect, which is 4.00 for very good validity criteria, 3.00 for good validity criteria, 2.00 for more or less validity criteria, and 1.00 for not good validity criteria. Data showed that the validity for each aspect were in the range of good validity and very good validity criteria (3.33 to 3.67 for the content aspect, 2.33 to 4.00 for the construction aspect, and 3.33 to 4.00 for language aspect). However, there was a part of construction aspect that needed to improve. Overall, this students’ worksheet can be applied in classroom after some revisions based on suggestions from the validators.
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Bowen, Raffick A R; Adcock, Dorothy M
2016-12-01
Blood collection tubes (BCTs) are an often under-recognized variable in the preanalytical phase of clinical laboratory testing. Unfortunately, even the best-designed and manufactured BCTs may not work well in all clinical settings. Clinical laboratories, in collaboration with healthcare providers, should carefully evaluate BCTs prior to putting them into clinical use to determine their limitations and ensure that patients are not placed at risk because of inaccuracies due to poor tube performance. Selection of the best BCTs can be achieved through comparing advertising materials, reviewing the literature, observing the device at a scientific meeting, receiving a demonstration, evaluating the device under simulated conditions, or testing the device with patient samples. Although many publications have discussed method validations, few detail how to perform experiments for tube verification and validation. This article highlights the most common and impactful variables related to BCTs and discusses the validation studies that a typical clinical laboratory should perform when selecting BCTs. We also present a brief review of how in vitro diagnostic devices, particularly BCTs, are regulated in the United States, the European Union, and Canada. The verification and validation of BCTs will help to avoid the economic and human costs associated with incorrect test results, including poor patient care, unnecessary testing, and delays in test results. We urge laboratorians, tube manufacturers, diagnostic companies, and other researchers to take all the necessary steps to protect against the adverse effects of BCT components and their additives on clinical assays. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
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On the performance of piezoelectric harvesters loaded by finite width impulses
NASA Astrophysics Data System (ADS)
Doria, A.; Medè, C.; Desideri, D.; Maschio, A.; Codecasa, L.; Moro, F.
2018-02-01
The response of cantilevered piezoelectric harvesters loaded by finite width impulses of base acceleration is studied analytically in the frequency domain in order to identify the parameters that influence the generated voltage. Experimental tests are then performed on harvesters loaded by hammer impacts. The latter are used to confirm analytical results and to validate a linear finite element (FE) model of a unimorph harvester. The FE model is, in turn, used to extend analytical results to more general harvesters (tapered, inverse tapered, triangular) and to more general impulses (heel strike in human gait). From analytical and numerical results design criteria for improving harvester performance are obtained.
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Assessment of mechanical properties of human head tissues for trauma modelling.
Lozano-Mínguez, Estívaliz; Palomar, Marta; Infante-García, Diego; Rupérez, María José; Giner, Eugenio
2018-05-01
Many discrepancies are found in the literature regarding the damage and constitutive models for head tissues as well as the values of the constants involved in the constitutive equations. Their proper definition is required for consistent numerical model performance when predicting human head behaviour, and hence skull fracture and brain damage. The objective of this research is to perform a critical review of constitutive models and damage indicators describing human head tissue response under impact loading. A 3D finite element human head model has been generated by using computed tomography images, which has been validated through the comparison to experimental data in the literature. The threshold values of the skull and the scalp that lead to fracture have been analysed. We conclude that (1) compact bone properties are critical in skull fracture, (2) the elastic constants of the cerebrospinal fluid affect the intracranial pressure distribution, and (3) the consideration of brain tissue as a nearly incompressible solid with a high (but not complete) water content offers pressure responses consistent with the experimental data. Copyright © 2018 John Wiley & Sons, Ltd.
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The history behind successful uterine transplantation in humans
Castellón, Luis Arturo Ruvalcaba; Amador, Martha Isolina García; González, Roberto Enrique Díaz; Eduardo, Montoya Sarmiento Jorge; Díaz-García, César; Kvarnström, Niclas; Bränström, Mats
2017-01-01
This paper aimed to describe the basic aspects of uterine transplant (UTx) research in humans, including preliminary experiences in rodents and domestic species. Studies in rats, domestic species, and non-human primates validated and optimized the UTx procedure in terms of its surgical aspects, immunosuppression, rejection diagnosis, peculiarities of pregnancy in immunosuppressed patients, and patients with special uterine conditions. In animal species, the first live birth from UTx was achieved in a syngeneic mouse model in 2003. Twenty-five UTx procedures have been performed in humans. The first two cases were unsuccessful, but established the need for rigorous research to improve success rates. As a result of a controlled clinical study under a strictly designed research protocol, nine subsequent UTx procedures have resulted in six healthy live births, the first of them in 2014. Further failed UTx procedures have been performed in China, Czech Republic, Brazil, Germany, and the United States, most of which using living donors. Albeit still an experimental procedure in, UTx is the first potential alternative for the treatment of absolute uterine factor infertility (AUFI). PMID:28609280
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Model-based metrics of human-automation function allocation in complex work environments
NASA Astrophysics Data System (ADS)
Kim, So Young
Function allocation is the design decision which assigns work functions to all agents in a team, both human and automated. Efforts to guide function allocation systematically has been studied in many fields such as engineering, human factors, team and organization design, management science, and cognitive systems engineering. Each field focuses on certain aspects of function allocation, but not all; thus, an independent discussion of each does not address all necessary issues with function allocation. Four distinctive perspectives emerged from a review of these fields: technology-centered, human-centered, team-oriented, and work-oriented. Each perspective focuses on different aspects of function allocation: capabilities and characteristics of agents (automation or human), team structure and processes, and work structure and the work environment. Together, these perspectives identify the following eight issues with function allocation: 1) Workload, 2) Incoherency in function allocations, 3) Mismatches between responsibility and authority, 4) Interruptive automation, 5) Automation boundary conditions, 6) Function allocation preventing human adaptation to context, 7) Function allocation destabilizing the humans' work environment, and 8) Mission Performance. Addressing these issues systematically requires formal models and simulations that include all necessary aspects of human-automation function allocation: the work environment, the dynamics inherent to the work, agents, and relationships among them. Also, addressing these issues requires not only a (static) model, but also a (dynamic) simulation that captures temporal aspects of work such as the timing of actions and their impact on the agent's work. Therefore, with properly modeled work as described by the work environment, the dynamics inherent to the work, agents, and relationships among them, a modeling framework developed by this thesis, which includes static work models and dynamic simulation, can capture the issues with function allocation. Then, based on the eight issues, eight types of metrics are established. The purpose of these metrics is to assess the extent to which each issue exists with a given function allocation. Specifically, the eight types of metrics assess workload, coherency of a function allocation, mismatches between responsibility and authority, interruptive automation, automation boundary conditions, human adaptation to context, stability of the human's work environment, and mission performance. Finally, to validate the modeling framework and the metrics, a case study was conducted modeling four different function allocations between a pilot and flight deck automation during the arrival and approach phases of flight. A range of pilot cognitive control modes and maximum human taskload limits were also included in the model. The metrics were assessed for these four function allocations and analyzed to validate capability of the metrics to identify important issues in given function allocations. In addition, the design insights provided by the metrics are highlighted. This thesis concludes with a discussion of mechanisms for further validating the modeling framework and function allocation metrics developed here, and highlights where these developments can be applied in research and in the design of function allocations in complex work environments such as aviation operations.
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Casiraghi, Francesca; Lertwattanarak, Raweewan; Luzi, Livio; Chavez, Alberto O; Davalli, Alberto M; Naegelin, Terry; Comuzzie, Anthony G; Frost, Patricia; Musi, Nicolas; Folli, Franco
2013-01-01
The purpose of this study was to compare and validate the use of SenseWear Armband (SWA) placed on the arm (SWA ARM) and on the back (SWA BACK) in healthy humans during resting and a cycle-ergometer exercise and to evaluate the SWA to estimate Resting Energy Expenditure (REE) and Total Energy Expenditure (TEE) in healthy baboons. We studied 26 (15F/11M) human subjects wearing SWA in two different anatomical sites (arm and back) during resting and a cycle-ergometer test and directly compared these results with indirect calorimetry evaluation (IC), performed at the same time. We then inserted the SWA in a metabolic jacket for baboons and evaluated the TEE and REE in free living condition for 6 days in 21 (8F/13M) non-human primates. In humans we found a good correlation between SWA place on the ARM and on the BACK with IC during the resting experiment (1.1±0.3 SWAs, 1±0.2 IC kcal/min) and a slight underestimation in the SWAs data compared with IC during the cycle-ergometer exercise (5±1.9 SWA ARM, 4.5±1.5 SWA BACK and 5.4±2.1 IC kcal/min). In the non-human primate (baboons) experiment SWA estimated a TEE of 0.54±0.009 kcal/min during free living and a REE of 0.82±0.06 kcal/min. SWA, an extremely simple and inexpensive apparatus, provides quite accurate measurements of energy expenditure in humans and in baboons. Energy expenditure data obtained with SWA are highly correlated with the data obtained with "gold standard", IC, in humans.
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Feuk, Lars; MacDonald, Jeffrey R; Tang, Terence; Carson, Andrew R; Li, Martin; Rao, Girish; Khaja, Razi; Scherer, Stephen W
2005-10-01
With a draft genome-sequence assembly for the chimpanzee available, it is now possible to perform genome-wide analyses to identify, at a submicroscopic level, structural rearrangements that have occurred between chimpanzees and humans. The goal of this study was to investigate chromosomal regions that are inverted between the chimpanzee and human genomes. Using the net alignments for the builds of the human and chimpanzee genome assemblies, we identified a total of 1,576 putative regions of inverted orientation, covering more than 154 mega-bases of DNA. The DNA segments are distributed throughout the genome and range from 23 base pairs to 62 mega-bases in length. For the 66 inversions more than 25 kilobases (kb) in length, 75% were flanked on one or both sides by (often unrelated) segmental duplications. Using PCR and fluorescence in situ hybridization we experimentally validated 23 of 27 (85%) semi-randomly chosen regions; the largest novel inversion confirmed was 4.3 mega-bases at human Chromosome 7p14. Gorilla was used as an out-group to assign ancestral status to the variants. All experimentally validated inversion regions were then assayed against a panel of human samples and three of the 23 (13%) regions were found to be polymorphic in the human genome. These polymorphic inversions include 730 kb (at 7p22), 13 kb (at 7q11), and 1 kb (at 16q24) fragments with a 5%, 30%, and 48% minor allele frequency, respectively. Our results suggest that inversions are an important source of variation in primate genome evolution. The finding of at least three novel inversion polymorphisms in humans indicates this type of structural variation may be a more common feature of our genome than previously realized.
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Rikli, Roberta E; Jones, C Jessie
2013-04-01
To develop and validate criterion-referenced fitness standards for older adults that predict the level of capacity needed for maintaining physical independence into later life. The proposed standards were developed for use with a previously validated test battery for older adults-the Senior Fitness Test (Rikli, R. E., & Jones, C. J. (2001). Development and validation of a functional fitness test for community--residing older adults. Journal of Aging and Physical Activity, 6, 127-159; Rikli, R. E., & Jones, C. J. (1999a). Senior fitness test manual. Champaign, IL: Human Kinetics.). A criterion measure to assess physical independence was identified. Next, scores from a subset of 2,140 "moderate-functioning" older adults from a larger cross-sectional database, together with findings from longitudinal research on physical capacity and aging, were used as the basis for proposing fitness standards (performance cut points) associated with having the ability to function independently. Validity and reliability analyses were conducted to test the standards for their accuracy and consistency as predictors of physical independence. Performance standards are presented for men and women ages 60-94 indicating the level of fitness associated with remaining physically independent until late in life. Reliability and validity indicators for the standards ranged between .79 and .97. The proposed standards provide easy-to-use, previously unavailable methods for evaluating physical capacity in older adults relative to that associated with physical independence. Most importantly, the standards can be used in planning interventions that target specific areas of weakness, thus reducing risk for premature loss of mobility and independence.
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Cheng, Ching-Min; Hwang, Sheue-Ling
2015-03-01
This paper outlines the human error identification (HEI) techniques that currently exist to assess latent human errors. Many formal error identification techniques have existed for years, but few have been validated to cover latent human error analysis in different domains. This study considers many possible error modes and influential factors, including external error modes, internal error modes, psychological error mechanisms, and performance shaping factors, and integrates several execution procedures and frameworks of HEI techniques. The case study in this research was the operational process of changing chemical cylinders in a factory. In addition, the integrated HEI method was used to assess the operational processes and the system's reliability. It was concluded that the integrated method is a valuable aid to develop much safer operational processes and can be used to predict human error rates on critical tasks in the plant. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.
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Dweep, Harsh; Sticht, Carsten; Pandey, Priyanka; Gretz, Norbert
2011-10-01
MicroRNAs are small, non-coding RNA molecules that can complementarily bind to the mRNA 3'-UTR region to regulate the gene expression by transcriptional repression or induction of mRNA degradation. Increasing evidence suggests a new mechanism by which miRNAs may regulate target gene expression by binding in promoter and amino acid coding regions. Most of the existing databases on miRNAs are restricted to mRNA 3'-UTR region. To address this issue, we present miRWalk, a comprehensive database on miRNAs, which hosts predicted as well as validated miRNA binding sites, information on all known genes of human, mouse and rat. All mRNAs, mitochondrial genes and 10 kb upstream flanking regions of all known genes of human, mouse and rat were analyzed by using a newly developed algorithm named 'miRWalk' as well as with eight already established programs for putative miRNA binding sites. An automated and extensive text-mining search was performed on PubMed database to extract validated information on miRNAs. Combined information was put into a MySQL database. miRWalk presents predicted and validated information on miRNA-target interaction. Such a resource enables researchers to validate new targets of miRNA not only on 3'-UTR, but also on the other regions of all known genes. The 'Validated Target module' is updated every month and the 'Predicted Target module' is updated every 6 months. miRWalk is freely available at http://mirwalk.uni-hd.de/. Copyright © 2011 Elsevier Inc. All rights reserved.
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EGFR Overexpressed in Colonic Neoplasia Can be Detected on Wide-Field Endoscopic Imaging.
Zhou, Juan; Joshi, Bishnu P; Duan, Xiyu; Pant, Asha; Qiu, Zhen; Kuick, Rork; Owens, Scott R; Wang, Thomas D
2015-07-16
Colorectal cancer initially lies dormant as dysplasia, a premalignant state that provides an opportunity for early cancer detection. Dysplasia can be flat in morphology, focal in size, and patchy in distribution, and thus it appears "invisible" on conventional wide-field endoscopy. We aim to develop and validate a peptide that is specific for epidermal growth factor receptor (EGFR), a cell surface target that is overexpressed in colonic adenomas and is readily accessible for imaging. We expressed and purified the extracellular domain of EGFR for use with phage display to identify a peptide QRHKPRE that binds to domain 2 of this target. A near-infrared fluorescence endoscope was used to perform in vivo imaging to validate specific peptide binding to spontaneous colonic adenomas in a mouse model with topical administration. We also validated specific peptide binding to human colonic adenomas on immunohistochemistry and immunofluorescence. After labeling with Cy5.5, we validated specific peptide binding to EGFR on knockdown and competition studies. Peptide binding to cells occurred within 2.46 min and had an affinity of 50 nm. No downstream signaling was observed. We measured a target-to-background ratio of 4.0±1.7 and 2.7±0.7, for polyps and flat lesions, respectively. On immunofluorescence of human colonic specimens, greater intensity from peptide binding to dysplasia than normal was found with a 19.4-fold difference. We have selected and validated a peptide that can be used as a specific contrast agent to identify colonic adenomas that overexpress EGFR in vivo on fluorescence endoscopy.
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Human factors engineering verification and validation for APR1400 computerized control room
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shin, Y. C.; Moon, H. K.; Kim, J. H.
2006-07-01
This paper introduces the Advanced Power Reactor 1400 (APR1400) HFE V and V activities the Korea Hydro Nuclear Plant Co. LTD. (KHNP) has performed for the last 10 years and some of the lessons learned through these activities. The features of APR1400 main control room include large display panel, redundant compact workstations, computer-based procedure, and safety console. Several iterations of human factors evaluations have been performed from small scale proof of concept tests to large scale integrated system tests for identifying human engineering deficiencies in the human system interface design. Evaluations in the proof of concept test were focused onmore » checking the presence of any show stopper problems in the design concept. Later evaluations were mostly for finding design problems and for assuring the resolution of human factors issues of advanced control room. The results of design evaluations were useful not only for refining the control room design, but also for licensing the standard design. Several versions of APR1400 mock-ups with dynamic simulation models of currently operating Korea Standard Nuclear Plant (KSNP) have been used for the evaluations with the participation of operators from KSNP plants. (authors)« less
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SAR in human head model due to resonant wireless power transfer system.
Zhang, Chao; Liu, Guoqiang; Li, Yanhong; Song, Xianjin
2016-04-29
Efficient mid-range wireless power transfer between transmitter and the receiver has been achieved based on the magnetic resonant coupling method. The influence of electromagnetic field on the human body due to resonant wireless power transfer system (RWPT) should be taken into account during the design process of the system. To analyze the transfer performance of the RWPT system and the change rules of the specific absorption rate (SAR) in the human head model due to the RWPT system. The circuit-field coupling method for a RWPT system with consideration of the displacement current was presented. The relationship between the spiral coil parameters and transfer performance was studied. The SAR in the human head model was calculated under two different exposure conditions. A system with output power higher than 10 W at 0.2 m distance operating at a frequency of approximately 1 MHz was designed. The FEM simulation results show the peak SAR value is below the safety limit which appeared when the human head model is in front of the transmitter. The simulation results agreed well with the experimental results, which verified the validity of the analysis and design.
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Nakhleh, Raouf E; Grimm, Erin E; Idowu, Michael O; Souers, Rhona J; Fitzgibbons, Patrick L
2010-05-01
To ensure quality human epidermal growth receptor 2 (HER2) testing in breast cancer, the American Society of Clinical Oncology/College of American Pathologists guidelines were introduced with expected compliance by 2008. To assess the effect these guidelines have had on pathology laboratories and their ability to address key components. In late 2008, a survey was distributed with the HER2 immunohistochemistry (IHC) proficiency testing program. It included questions regarding pathology practice characteristics and assay validation using fluorescence in situ hybridization or another IHC laboratory assay and assessed pathologist HER2 scoring competency. Of the 907 surveys sent, 757 (83.5%) were returned. The median laboratory accessioned 15 000 cases and performed 190 HER2 tests annually. Quantitative computer image analysis was used by 33% of laboratories. In-house fluorescence in situ hybridization was performed in 23% of laboratories, and 60% of laboratories addressed the 6- to 48-hour tissue fixation requirement by embedding tissue on the weekend. HER2 testing was performed on the initial biopsy in 40%, on the resection specimen in 6%, and on either in 56% of laboratories. Testing was validated with only fluorescence in situ hybridization in 47% of laboratories, whereas 10% of laboratories used another IHC assay only; 13% used both assays, and 12% and 15% of laboratories had not validated their assays or chose "not applicable" on the survey question, respectively. The 90% concordance rate with fluorescence in situ hybridization results was achieved by 88% of laboratories for IHC-negative findings and by 81% of laboratories for IHC-positive cases. The 90% concordance rate for laboratories using another IHC assay was achieved by 80% for negative findings and 75% for positive cases. About 91% of laboratories had a pathologist competency assessment program. This survey demonstrates the extent and characteristics of HER2 testing. Although some American Society of Clinical Oncology/College of American Pathologists guidelines have been implemented, gaps remain in validation of HER2 IHC testing.
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Automation and robotics human performance
NASA Technical Reports Server (NTRS)
Mah, Robert W.
1990-01-01
The scope of this report is limited to the following: (1) assessing the feasibility of the assumptions for crew productivity during the intra-vehicular activities and extra-vehicular activities; (2) estimating the appropriate level of automation and robotics to accomplish balanced man-machine, cost-effective operations in space; (3) identifying areas where conceptually different approaches to the use of people and machines can leverage the benefits of the scenarios; and (4) recommending modifications to scenarios or developing new scenarios that will improve the expected benefits. The FY89 special assessments are grouped into the five categories shown in the report. The high level system analyses for Automation & Robotics (A&R) and Human Performance (HP) were performed under the Case Studies Technology Assessment category, whereas the detailed analyses for the critical systems and high leverage development areas were performed under the appropriate operations categories (In-Space Vehicle Operations or Planetary Surface Operations). The analysis activities planned for the Science Operations technology areas were deferred to FY90 studies. The remaining activities such as analytic tool development, graphics/video demonstrations and intelligent communicating systems software architecture were performed under the Simulation & Validations category.
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Pizzo, Fabiola; Lombardo, Anna; Manganaro, Alberto; Benfenati, Emilio
2016-01-01
The prompt identification of chemical molecules with potential effects on liver may help in drug discovery and in raising the levels of protection for human health. Besides in vitro approaches, computational methods in toxicology are drawing attention. We built a structure-activity relationship (SAR) model for evaluating hepatotoxicity. After compiling a data set of 950 compounds using data from the literature, we randomly split it into training (80%) and test sets (20%). We also compiled an external validation set (101 compounds) for evaluating the performance of the model. To extract structural alerts (SAs) related to hepatotoxicity and non-hepatotoxicity we used SARpy, a statistical application that automatically identifies and extracts chemical fragments related to a specific activity. We also applied the chemical grouping approach for manually identifying other SAs. We calculated accuracy, specificity, sensitivity and Matthews correlation coefficient (MCC) on the training, test and external validation sets. Considering the complexity of the endpoint, the model performed well. In the training, test and external validation sets the accuracy was respectively 81, 63, and 68%, specificity 89, 33, and 33%, sensitivity 93, 88, and 80% and MCC 0.63, 0.27, and 0.13. Since it is preferable to overestimate hepatotoxicity rather than not to recognize unsafe compounds, the model's architecture followed a conservative approach. As it was built using human data, it might be applied without any need for extrapolation from other species. This model will be freely available in the VEGA platform. PMID:27920722
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Xu, Nan; Spreng, R Nathan; Doerschuk, Peter C
2017-01-01
Resting-state functional MRI (rs-fMRI) is widely used to noninvasively study human brain networks. Network functional connectivity is often estimated by calculating the timeseries correlation between blood-oxygen-level dependent (BOLD) signal from different regions of interest (ROIs). However, standard correlation cannot characterize the direction of information flow between regions. In this paper, we introduce and test a new concept, prediction correlation, to estimate effective connectivity in functional brain networks from rs-fMRI. In this approach, the correlation between two BOLD signals is replaced by a correlation between one BOLD signal and a prediction of this signal via a causal system driven by another BOLD signal. Three validations are described: (1) Prediction correlation performed well on simulated data where the ground truth was known, and outperformed four other methods. (2) On simulated data designed to display the "common driver" problem, prediction correlation did not introduce false connections between non-interacting driven ROIs. (3) On experimental data, prediction correlation recovered the previously identified network organization of human brain. Prediction correlation scales well to work with hundreds of ROIs, enabling it to assess whole brain interregional connectivity at the single subject level. These results provide an initial validation that prediction correlation can capture the direction of information flow and estimate the duration of extended temporal delays in information flow between regions of interest ROIs based on BOLD signal. This approach not only maintains the high sensitivity to network connectivity provided by the correlation analysis, but also performs well in the estimation of causal information flow in the brain.
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Thomas, Reuben; Thomas, Russell S.; Auerbach, Scott S.; Portier, Christopher J.
2013-01-01
Background Several groups have employed genomic data from subchronic chemical toxicity studies in rodents (90 days) to derive gene-centric predictors of chronic toxicity and carcinogenicity. Genes are annotated to belong to biological processes or molecular pathways that are mechanistically well understood and are described in public databases. Objectives To develop a molecular pathway-based prediction model of long term hepatocarcinogenicity using 90-day gene expression data and to evaluate the performance of this model with respect to both intra-species, dose-dependent and cross-species predictions. Methods Genome-wide hepatic mRNA expression was retrospectively measured in B6C3F1 mice following subchronic exposure to twenty-six (26) chemicals (10 were positive, 2 equivocal and 14 negative for liver tumors) previously studied by the US National Toxicology Program. Using these data, a pathway-based predictor model for long-term liver cancer risk was derived using random forests. The prediction model was independently validated on test sets associated with liver cancer risk obtained from mice, rats and humans. Results Using 5-fold cross validation, the developed prediction model had reasonable predictive performance with the area under receiver-operator curve (AUC) equal to 0.66. The developed prediction model was then used to extrapolate the results to data associated with rat and human liver cancer. The extrapolated model worked well for both extrapolated species (AUC value of 0.74 for rats and 0.91 for humans). The prediction models implied a balanced interplay between all pathway responses leading to carcinogenicity predictions. Conclusions Pathway-based prediction models estimated from sub-chronic data hold promise for predicting long-term carcinogenicity and also for its ability to extrapolate results across multiple species. PMID:23737943
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Thomas, Reuben; Thomas, Russell S; Auerbach, Scott S; Portier, Christopher J
2013-01-01
Several groups have employed genomic data from subchronic chemical toxicity studies in rodents (90 days) to derive gene-centric predictors of chronic toxicity and carcinogenicity. Genes are annotated to belong to biological processes or molecular pathways that are mechanistically well understood and are described in public databases. To develop a molecular pathway-based prediction model of long term hepatocarcinogenicity using 90-day gene expression data and to evaluate the performance of this model with respect to both intra-species, dose-dependent and cross-species predictions. Genome-wide hepatic mRNA expression was retrospectively measured in B6C3F1 mice following subchronic exposure to twenty-six (26) chemicals (10 were positive, 2 equivocal and 14 negative for liver tumors) previously studied by the US National Toxicology Program. Using these data, a pathway-based predictor model for long-term liver cancer risk was derived using random forests. The prediction model was independently validated on test sets associated with liver cancer risk obtained from mice, rats and humans. Using 5-fold cross validation, the developed prediction model had reasonable predictive performance with the area under receiver-operator curve (AUC) equal to 0.66. The developed prediction model was then used to extrapolate the results to data associated with rat and human liver cancer. The extrapolated model worked well for both extrapolated species (AUC value of 0.74 for rats and 0.91 for humans). The prediction models implied a balanced interplay between all pathway responses leading to carcinogenicity predictions. Pathway-based prediction models estimated from sub-chronic data hold promise for predicting long-term carcinogenicity and also for its ability to extrapolate results across multiple species.
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Roberts, Kirsty; Hemmings, Andrew J; McBride, Sebastian D; Parker, Matthew O
2017-12-01
Large animal models of human neurological disorders are advantageous compared to rodent models due to their neuroanatomical complexity, longevity and their ability to be maintained in naturalised environments. Some large animal models spontaneously develop behaviours that closely resemble the symptoms of neural and psychiatric disorders. The horse is an example of this; the domestic form of this species consistently develops spontaneous stereotypic behaviours akin to the compulsive and impulsive behaviours observed in human neurological disorders such as Tourette's syndrome. The ability to non-invasively probe normal and abnormal equine brain function through cognitive testing may provide an extremely useful methodological tool to assess brain changes associated with certain human neurological and psychiatric conditions. An automated operant system with the ability to present visual and auditory stimuli as well as dispense salient food reward was developed. To validate the system, ten horses were trained and tested using a standard cognitive task (three choice serial reaction time task (3-CSRTT)). All animals achieved total learning criterion and performed six probe sessions. Learning criterion was met within 16.30±0.79 sessions over a three day period. During six probe sessions, level of performance was maintained at 80.67±0.57% (mean±SEM) accuracy. This is the first mobile fully automated system developed to examine cognitive function in the horse. A fully-automated operant system for mobile cognitive function of a large animal model has been designed and validated. Horses pose an interesting complementary model to rodents for the examination of human neurological dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.
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Nascimento, Marilia B.; Santos, Wagner J. T.; Medeiros, Zulma M.; Lima Neto, Adelino S.; Costa, Dorcas L.; Costa, Carlos H. N.; dos Santos, Washington L. C.; Pontes de Carvalho, Lain C.; Oliveira, Geraldo G. S.
2017-01-01
Current strategies for the control of zoonotic visceral leishmaniasis (VL) rely on its efficient diagnosis in both human and canine hosts. The most promising and cost effective approach is based on serologic assays with recombinant proteins. However, no single antigen has been found so far which can be effectively used to detect the disease in both dogs and humans. In previous works, we identified Leishmania infantum antigens with potential for the serodiagnosis of VL. Here, we aimed to expand the panel of the available antigens for VL diagnosis through another screening of a genomic expression library. Seven different protein-coding gene fragments were identified, five of which encoding proteins which have not been previously studied in Leishmania and rich in repetitive motifs. Poly-histidine tagged polypeptides were generated from six genes and evaluated for their potential for diagnosis of VL by ELISA (Enzyme Linked ImmunoSorbent Assay) with sera from infected humans and dogs. None of those was valid for the detection of human VL (26–52% sensitivity) although their performance was increased in the canine sera (48–91% sensitivity), with one polypeptide useful for the diagnosis of canine leishmaniasis. Next, we assayed a mixture of three antigens, found to be best for human or canine VL, among 13 identified through different screenings. This “Mix” resulted in similar levels of sensitivity for both human (84%) and canine (88%) sera. With improvements, this validates the use of multiple proteins, including antigens identified here, as components of a single system for the diagnosis of both forms of leishmaniasis. PMID:28957332
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Magalhães, Franklin B; Castro Neto, Artur L; Nascimento, Marilia B; Santos, Wagner J T; Medeiros, Zulma M; Lima Neto, Adelino S; Costa, Dorcas L; Costa, Carlos H N; Dos Santos, Washington L C; Pontes de Carvalho, Lain C; Oliveira, Geraldo G S; de Melo Neto, Osvaldo P
2017-01-01
Current strategies for the control of zoonotic visceral leishmaniasis (VL) rely on its efficient diagnosis in both human and canine hosts. The most promising and cost effective approach is based on serologic assays with recombinant proteins. However, no single antigen has been found so far which can be effectively used to detect the disease in both dogs and humans. In previous works, we identified Leishmania infantum antigens with potential for the serodiagnosis of VL. Here, we aimed to expand the panel of the available antigens for VL diagnosis through another screening of a genomic expression library. Seven different protein-coding gene fragments were identified, five of which encoding proteins which have not been previously studied in Leishmania and rich in repetitive motifs. Poly-histidine tagged polypeptides were generated from six genes and evaluated for their potential for diagnosis of VL by ELISA (Enzyme Linked ImmunoSorbent Assay) with sera from infected humans and dogs. None of those was valid for the detection of human VL (26-52% sensitivity) although their performance was increased in the canine sera (48-91% sensitivity), with one polypeptide useful for the diagnosis of canine leishmaniasis. Next, we assayed a mixture of three antigens, found to be best for human or canine VL, among 13 identified through different screenings. This "Mix" resulted in similar levels of sensitivity for both human (84%) and canine (88%) sera. With improvements, this validates the use of multiple proteins, including antigens identified here, as components of a single system for the diagnosis of both forms of leishmaniasis.
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Robotic Billiards: Understanding Humans in Order to Counter Them.
Nierhoff, Thomas; Leibrandt, Konrad; Lorenz, Tamara; Hirche, Sandra
2016-08-01
Ongoing technological advances in the areas of computation, sensing, and mechatronics enable robotic-based systems to interact with humans in the real world. To succeed against a human in a competitive scenario, a robot must anticipate the human behavior and include it in its own planning framework. Then it can predict the next human move and counter it accordingly, thus not only achieving overall better performance but also systematically exploiting the opponent's weak spots. Pool is used as a representative scenario to derive a model-based planning and control framework where not only the physics of the environment but also a model of the opponent is considered. By representing the game of pool as a Markov decision process and incorporating a model of the human decision-making based on studies, an optimized policy is derived. This enables the robot to include the opponent's typical game style into its tactical considerations when planning a stroke. The results are validated in simulations and real-life experiments with an anthropomorphic robot playing pool against a human.
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A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors.
Venkataraman, Anand; Yang, Kun; Irizarry, Jose; Mackiewicz, Mark; Mita, Paolo; Kuang, Zheng; Xue, Lin; Ghosh, Devlina; Liu, Shuang; Ramos, Pedro; Hu, Shaohui; Bayron Kain, Diane; Keegan, Sarah; Saul, Richard; Colantonio, Simona; Zhang, Hongyan; Behn, Florencia Pauli; Song, Guang; Albino, Edisa; Asencio, Lillyann; Ramos, Leonardo; Lugo, Luvir; Morell, Gloriner; Rivera, Javier; Ruiz, Kimberly; Almodovar, Ruth; Nazario, Luis; Murphy, Keven; Vargas, Ivan; Rivera-Pacheco, Zully Ann; Rosa, Christian; Vargas, Moises; McDade, Jessica; Clark, Brian S; Yoo, Sooyeon; Khambadkone, Seva G; de Melo, Jimmy; Stevanovic, Milanka; Jiang, Lizhi; Li, Yana; Yap, Wendy Y; Jones, Brittany; Tandon, Atul; Campbell, Elliot; Montelione, Gaetano T; Anderson, Stephen; Myers, Richard M; Boeke, Jef D; Fenyö, David; Whiteley, Gordon; Bader, Joel S; Pino, Ignacio; Eichinger, Daniel J; Zhu, Heng; Blackshaw, Seth
2018-03-19
A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.
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sNebula, a network-based algorithm to predict binding between human leukocyte antigens and peptides
DOE Office of Scientific and Technical Information (OSTI.GOV)
Luo, Heng; Ye, Hao; Ng, Hui Wen
Understanding the binding between human leukocyte antigens (HLAs) and peptides is important to understand the functioning of the immune system. Since it is time-consuming and costly to measure the binding between large numbers of HLAs and peptides, computational methods including machine learning models and network approaches have been developed to predict HLA-peptide binding. However, there are several limitations for the existing methods. We developed a network-based algorithm called sNebula to address these limitations. We curated qualitative Class I HLA-peptide binding data and demonstrated the prediction performance of sNebula on this dataset using leave-one-out cross-validation and five-fold cross-validations. Furthermore, this algorithmmore » can predict not only peptides of different lengths and different types of HLAs, but also the peptides or HLAs that have no existing binding data. We believe sNebula is an effective method to predict HLA-peptide binding and thus improve our understanding of the immune system.« less
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sNebula, a network-based algorithm to predict binding between human leukocyte antigens and peptides
Luo, Heng; Ye, Hao; Ng, Hui Wen; Sakkiah, Sugunadevi; Mendrick, Donna L.; Hong, Huixiao
2016-01-01
Understanding the binding between human leukocyte antigens (HLAs) and peptides is important to understand the functioning of the immune system. Since it is time-consuming and costly to measure the binding between large numbers of HLAs and peptides, computational methods including machine learning models and network approaches have been developed to predict HLA-peptide binding. However, there are several limitations for the existing methods. We developed a network-based algorithm called sNebula to address these limitations. We curated qualitative Class I HLA-peptide binding data and demonstrated the prediction performance of sNebula on this dataset using leave-one-out cross-validation and five-fold cross-validations. This algorithm can predict not only peptides of different lengths and different types of HLAs, but also the peptides or HLAs that have no existing binding data. We believe sNebula is an effective method to predict HLA-peptide binding and thus improve our understanding of the immune system. PMID:27558848
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sNebula, a network-based algorithm to predict binding between human leukocyte antigens and peptides
Luo, Heng; Ye, Hao; Ng, Hui Wen; ...
2016-08-25
Understanding the binding between human leukocyte antigens (HLAs) and peptides is important to understand the functioning of the immune system. Since it is time-consuming and costly to measure the binding between large numbers of HLAs and peptides, computational methods including machine learning models and network approaches have been developed to predict HLA-peptide binding. However, there are several limitations for the existing methods. We developed a network-based algorithm called sNebula to address these limitations. We curated qualitative Class I HLA-peptide binding data and demonstrated the prediction performance of sNebula on this dataset using leave-one-out cross-validation and five-fold cross-validations. Furthermore, this algorithmmore » can predict not only peptides of different lengths and different types of HLAs, but also the peptides or HLAs that have no existing binding data. We believe sNebula is an effective method to predict HLA-peptide binding and thus improve our understanding of the immune system.« less
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An IMU-to-Body Alignment Method Applied to Human Gait Analysis.
Vargas-Valencia, Laura Susana; Elias, Arlindo; Rocon, Eduardo; Bastos-Filho, Teodiano; Frizera, Anselmo
2016-12-10
This paper presents a novel calibration procedure as a simple, yet powerful, method to place and align inertial sensors with body segments. The calibration can be easily replicated without the need of any additional tools. The proposed method is validated in three different applications: a computer mathematical simulation; a simplified joint composed of two semi-spheres interconnected by a universal goniometer; and a real gait test with five able-bodied subjects. Simulation results demonstrate that, after the calibration method is applied, the joint angles are correctly measured independently of previous sensor placement on the joint, thus validating the proposed procedure. In the cases of a simplified joint and a real gait test with human volunteers, the method also performs correctly, although secondary plane errors appear when compared with the simulation results. We believe that such errors are caused by limitations of the current inertial measurement unit (IMU) technology and fusion algorithms. In conclusion, the presented calibration procedure is an interesting option to solve the alignment problem when using IMUs for gait analysis.
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Zeric Stosic, Marina Z; Jaksic, Sandra M; Stojanov, Igor M; Apic, Jelena B; Ratajac, Radomir D
2016-11-01
High-performance liquid chromatography (HPLC) method with diode array detection (DAD) were optimized and validated for separation and determination of tetramethrin in an antiparasitic human shampoo. In order to optimize separation conditions, two different columns, different column oven temperatures, as well as mobile phase composition and ratio, were tested. Best separation was achieved on the Supelcosil TM LC-18- DB column (4.6 x 250 mm), particle size 5 jim, with mobile phase methanol : water (78 : 22, v/v) at a flow rate of 0.8 mL/min and at temperature of 30⁰C. The detection wavelength of the detector was set at 220 nm. Under the optimum chromatographic conditions, standard calibration curve was measured with good linearity [r2 = 0.9997]. Accuracy of the method defined as a mean recovery of tetramethrin from shampoo matrix was 100.09%. The advantages of this method are that it can easily be used for the routine analysis of drug tetramethrin in pharmaceutical formulas and in all pharmaceutical researches involving tetramethrin.
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NASA Technical Reports Server (NTRS)
Arneson, Heather; Evans, Antony D.; Li, Jinhua; Wei, Mei Yueh
2017-01-01
Integrated Demand Management (IDM) is a near- to mid-term NASA concept that proposes to address mismatches in air traffic system demand and capacity by using strategic flow management capabilities to pre-condition demand into the more tactical Time-Based Flow Management System (TBFM). This paper describes an automated simulation capability to support IDM concept development. The capability closely mimics existing human-in-the-loop (HITL) capabilities, while automating both the human components and collaboration between operational systems, and speeding up the real-time aircraft simulations. Such a capability allows for parametric studies to be carried out that can inform the HITL simulations, identifying breaking points and parameter values at which significant changes in system behavior occur. The paper describes the initial validation of the automated simulation capability against results from previous IDM HITL experiments, quantifying the differences. The simulator is then used to explore the performance of the IDM concept under the simple scenario of a capacity constrained airport under a wide range of wind conditions.
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Local figure-ground cues are valid for natural images.
Fowlkes, Charless C; Martin, David R; Malik, Jitendra
2007-06-08
Figure-ground organization refers to the visual perception that a contour separating two regions belongs to one of the regions. Recent studies have found neural correlates of figure-ground assignment in V2 as early as 10-25 ms after response onset, providing strong support for the role of local bottom-up processing. How much information about figure-ground assignment is available from locally computed cues? Using a large collection of natural images, in which neighboring regions were assigned a figure-ground relation by human observers, we quantified the extent to which figural regions locally tend to be smaller, more convex, and lie below ground regions. Our results suggest that these Gestalt cues are ecologically valid, and we quantify their relative power. We have also developed a simple bottom-up computational model of figure-ground assignment that takes image contours as input. Using parameters fit to natural image statistics, the model is capable of matching human-level performance when scene context limited.
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Where Public Health Meets Human Rights
Kiragu, Karusa; Sawicki, Olga; Smith, Sally; Brion, Sophie; Sharma, Aditi; Mworeko, Lilian; Iovita, Alexandrina
2017-01-01
Abstract In 2014, the World Health Organization (WHO) initiated a process for validation of the elimination of mother-to-child transmission (EMTCT) of HIV and syphilis by countries. For the first time in such a process for the validation of disease elimination, WHO introduced norms and approaches that are grounded in human rights, gender equality, and community engagement. This human rights-based validation process can serve as a key opportunity to enhance accountability for human rights protection by evaluating EMTCT programs against human rights norms and standards, including in relation to gender equality and by ensuring the provision of discrimination-free quality services. The rights-based validation process also involves the assessment of participation of affected communities in EMTCT program development, implementation, and monitoring and evaluation. It brings awareness to the types of human rights abuses and inequalities faced by women living with, at risk of, or affected by HIV and syphilis, and commits governments to eliminate those barriers. This process demonstrates the importance and feasibility of integrating human rights, gender, and community into key public health interventions in a manner that improves health outcomes, legitimizes the participation of affected communities, and advances the human rights of women living with HIV. PMID:29302179
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Jiang, Hui; Sidhu, Rohini; Fujiwara, Hideji; De Meulder, Marc; de Vries, Ronald; Gong, Yong; Kao, Mark; Porter, Forbes D.; Yanjanin, Nicole M.; Carillo-Carasco, Nuria; Xu, Xin; Ottinger, Elizabeth; Woolery, Myra; Ory, Daniel S.; Jiang, Xuntian
2014-01-01
2-Hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used excipient for drug formulation, has emerged as an investigational new drug for the treatment of Niemann-Pick type C1 (NPC1) disease, a neurodegenerative cholesterol storage disorder. Development of a sensitive quantitative LC-MS/MS assay to monitor the pharmacokinetics (PKs) of HP-β-CD required for clinical trials has been challenging owing to the dispersity of the HP-β-CD. To support a phase 1 clinical trial for ICV delivery of HP-β-CD in NPC1 patients, novel methods for quantification of HP-β-CD in human plasma and cerebrospinal fluid (CSF) using LC-MS/MS were developed and validated: a 2D-LC-in-source fragmentation-MS/MS (2D-LC-IF-MS/MS) assay and a reversed phase ultra performance LC-MS/MS (RP-UPLC-MS/MS) assay. In both assays, protein precipitation and “dilute and shoot” procedures were used to process plasma and CSF, respectively. The assays were fully validated and in close agreement, and allowed determination of PK parameters for HP-β-CD. The LC-MS/MS methods are ∼100-fold more sensitive than the current HPLC assay, and were successfully employed to analyze HP-β-CD in human plasma and CSF samples to support the phase 1 clinical trial of HP-β-CD in NPC1 patients. PMID:24868096
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Jiang, Hui; Sidhu, Rohini; Fujiwara, Hideji; De Meulder, Marc; de Vries, Ronald; Gong, Yong; Kao, Mark; Porter, Forbes D; Yanjanin, Nicole M; Carillo-Carasco, Nuria; Xu, Xin; Ottinger, Elizabeth; Woolery, Myra; Ory, Daniel S; Jiang, Xuntian
2014-07-01
2-Hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used excipient for drug formulation, has emerged as an investigational new drug for the treatment of Niemann-Pick type C1 (NPC1) disease, a neurodegenerative cholesterol storage disorder. Development of a sensitive quantitative LC-MS/MS assay to monitor the pharmacokinetics (PKs) of HP-β-CD required for clinical trials has been challenging owing to the dispersity of the HP-β-CD. To support a phase 1 clinical trial for ICV delivery of HP-β-CD in NPC1 patients, novel methods for quantification of HP-β-CD in human plasma and cerebrospinal fluid (CSF) using LC-MS/MS were developed and validated: a 2D-LC-in-source fragmentation-MS/MS (2D-LC-IF-MS/MS) assay and a reversed phase ultra performance LC-MS/MS (RP-UPLC-MS/MS) assay. In both assays, protein precipitation and "dilute and shoot" procedures were used to process plasma and CSF, respectively. The assays were fully validated and in close agreement, and allowed determination of PK parameters for HP-β-CD. The LC-MS/MS methods are ∼100-fold more sensitive than the current HPLC assay, and were successfully employed to analyze HP-β-CD in human plasma and CSF samples to support the phase 1 clinical trial of HP-β-CD in NPC1 patients. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
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Eichhold, Thomas H; McCauley-Myers, David L; Khambe, Deepa A; Thompson, Gary A; Hoke, Steven H
2007-01-17
A method for the simultaneous determination of dextromethorphan (DEX), dextrorphan (DET), and guaifenesin (GG) in human plasma was developed, validated, and applied to determine plasma concentrations of these compounds in samples from six clinical pharmacokinetic (PK) studies. Semi-automated liquid handling systems were used to perform the majority of the sample manipulation including liquid/liquid extraction (LLE) of the analytes from human plasma. Stable-isotope-labeled analogues were utilized as internal standards (ISTDs) for each analyte to facilitate accurate and precise quantification. Extracts were analyzed using gradient liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Use of semi-automated LLE with LC-MS/MS proved to be a very rugged and reliable approach for analysis of more than 6200 clinical study samples. The lower limit of quantification was validated at 0.010, 0.010, and 1.0 ng/mL of plasma for DEX, DET, and GG, respectively. Accuracy and precision of quality control (QC) samples for all three analytes met FDA Guidance criteria of +/-15% for average QC accuracy with coefficients of variation less than 15%. Data from the thorough evaluation of the method during development, validation, and application are presented to characterize selectivity, linearity, over-range sample analysis, accuracy, precision, autosampler carry-over, ruggedness, extraction efficiency, ionization suppression, and stability. Pharmacokinetic data are also provided to illustrate improvements in systemic drug and metabolite concentration-time profiles that were achieved by formulation optimization.
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Chang, Jae-Ho; Lee, Kyu-Jae; Kim, Soo-Ki; Yoo, Dae-Hyun; Kang, Tae-Young
2014-01-01
Background & objectives: To study effects of drugs against rheumatoid arthritis (RA) synoviocytes or fibroblast like synoviocytes (FLS) are used. To overcome the drawbacks of using FLS, this study was conducted to show the validity of SW982 synovial cell line in RA study. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V propidium iodide (PI) staining, mitochondrial membrane potential assay, Triton X-114 Phase partitioning, and immunolot for apoptosis signaling in SW982 human synovial cell line were performed. Results: Fluvastatin induced apoptosis in a dose- and time-dependent manner in TNFα -stimulated SW982 human synovial cells. A geranylgeranylpyrophosphate (GGPP) inhibitor, but not a farnesylpyrophosphate (FPP) inhibitor, induced apoptosis, and fluvastatin-induced apoptosis was associated with the translocation of isoprenylated RhoA and Rac1 proteins from the cell membrane to the cytosol. Fluvastatin-induced downstream apoptotic signals were associated with inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Accordingly, 89 kDa apoptotic cleavage fragment of poly (ADP-ribose) polymerase (PARP) was detected. Interpretation & conclusions: Collectively, our data indicate that fluvastatin induces apoptotic cell death in TNFα-stimulated SW982 human synovial cells through the inactivation of the geranylgerenylated membrane fraction of RhoA and Rac1 proteins and the subsequent inhibition of the PI3K/Akt signaling pathway. This finding shows the validity of SW982 cell line for RA study. PMID:24604047
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An integrated physiology model to study regional lung damage effects and the physiologic response
2014-01-01
Background This work expands upon a previously developed exercise dynamic physiology model (DPM) with the addition of an anatomic pulmonary system in order to quantify the impact of lung damage on oxygen transport and physical performance decrement. Methods A pulmonary model is derived with an anatomic structure based on morphometric measurements, accounting for heterogeneous ventilation and perfusion observed experimentally. The model is incorporated into an existing exercise physiology model; the combined system is validated using human exercise data. Pulmonary damage from blast, blunt trauma, and chemical injury is quantified in the model based on lung fluid infiltration (edema) which reduces oxygen delivery to the blood. The pulmonary damage component is derived and calibrated based on published animal experiments; scaling laws are used to predict the human response to lung injury in terms of physical performance decrement. Results The augmented dynamic physiology model (DPM) accurately predicted the human response to hypoxia, altitude, and exercise observed experimentally. The pulmonary damage parameters (shunt and diffusing capacity reduction) were fit to experimental animal data obtained in blast, blunt trauma, and chemical damage studies which link lung damage to lung weight change; the model is able to predict the reduced oxygen delivery in damage conditions. The model accurately estimates physical performance reduction with pulmonary damage. Conclusions We have developed a physiologically-based mathematical model to predict performance decrement endpoints in the presence of thoracic damage; simulations can be extended to estimate human performance and escape in extreme situations. PMID:25044032
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Sen, Indranil; Zou, Wei; Alvaran, Josephine; Nguyen, Linda; Gajek, Ryszard; She, Jianwen
2015-01-01
In order to better distinguish the different toxic inorganic and organic forms of arsenic (As) exposure in individuals, we have developed and validated a simple and robust analytical method for determining the following six As species in human urine: arsenous (III) acid (As-III), As (V) acid, monomethylarsonic acid, dimethylarsinic acid, arsenobetaine (AsB), and arsenocholine. In this method, human urine is diluted using a pH 5.8 buffer, separation is performed using an anion exchange column with isocratic HPLC, and detection is achieved using inductively coupled plasma-MS. The method uses a single mobile phase consisting of low concentrations of both phosphate buffer (5 mM) and ammonium nitrate salt (5 mM) at pH 9.0; this minimizes the column equilibration time and overcomes challenges with separation between AsB and As-III. In addition, As-III oxidation is prevented by degassing the sample preparation buffer at pH 5.8, degassing the mobile phase online at pH 9.0, and by the use of low temperature (-70 °C) and flip-cap airtight tubes for long term storage of samples. The method was validated using externally provided reference samples. Results were in agreement with target values at varying concentrations and successfully passed external performance test criteria. Internal QC samples were prepared and repeatedly analyzed to assess the method's long-term precision, and further analyses were completed on anonymous donor urine to assess the quality of the method's baseline separation. Results from analyses of external reference samples agreed with target values at varying concentrations, and results from precision studies yielded absolute CV values of 3-14% and recovery from 82 to 115% for the six As species. Analysis of anonymous donor urine confirmed the well-resolved baseline separation capabilities of the method for real participant samples.
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Purcell, Maureen K.; Getchell, Rodman G.; McClure, Carol A.; Weber, S.E.; Garver, Kyle A.
2011-01-01
Real-time, or quantitative, polymerase chain reaction (qPCR) is quickly supplanting other molecular methods for detecting the nucleic acids of human and other animal pathogens owing to the speed and robustness of the technology. As the aquatic animal health community moves toward implementing national diagnostic testing schemes, it will need to evaluate how qPCR technology should be employed. This review outlines the basic principles of qPCR technology, considerations for assay development, standards and controls, assay performance, diagnostic validation, implementation in the diagnostic laboratory, and quality assurance and control measures. These factors are fundamental for ensuring the validity of qPCR assay results obtained in the diagnostic laboratory setting.
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Evaluation of the Clinical Performance of the HPV-Risk Assay Using the VALGENT-3 Panel.
Polman, N J; Oštrbenk, A; Xu, L; Snijders, P J F; Meijer, C J L M; Poljak, M; Heideman, D A M; Arbyn, M
2017-12-01
Human papillomavirus (HPV) testing is increasingly being incorporated into cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a framework designed to evaluate the clinical performance of various HPV tests relative to that of the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay with samples from the VALGENT-3 panel and to compare its performance to that of the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in routine cervical cancer screening and is enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV-Risk assay by investigators blind to the clinical data. HPV prevalence was analyzed, and the clinical performance of the HPV-Risk assay for the detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05; P = 1.000), but the specificity of the HPV-Risk assay was significantly higher than that of HC2 (relative specificity, 1.02; 95% CI, 1.01 to 1.04; P < 0.001). For the detection of CIN2+, similar results were obtained, with the relative sensitivity being 0.98 (95% CI, 0.93 to 1.02; P = 0.257) and the relative specificity being 1.02 (95% CI, 1.01 to 1.03; P < 0.001). The performance of the HPV-Risk assay for the detection of CIN3+ and CIN2+ was noninferior to that of HC2, with all P values being ≤0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to the clinically validated HC2 by the use of samples from the VALGENT-3 panel for test validation and comparison. Copyright © 2017 Polman et al.
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A cross-validated cytoarchitectonic atlas of the human ventral visual stream.
Rosenke, Mona; Weiner, Kevin S; Barnett, Michael A; Zilles, Karl; Amunts, Katrin; Goebel, Rainer; Grill-Spector, Kalanit
2018-04-15
The human ventral visual stream consists of several areas that are considered processing stages essential for perception and recognition. A fundamental microanatomical feature differentiating areas is cytoarchitecture, which refers to the distribution, size, and density of cells across cortical layers. Because cytoarchitectonic structure is measured in 20-micron-thick histological slices of postmortem tissue, it is difficult to assess (a) how anatomically consistent these areas are across brains and (b) how they relate to brain parcellations obtained with prevalent neuroimaging methods, acquired at the millimeter and centimeter scale. Therefore, the goal of this study was to (a) generate a cross-validated cytoarchitectonic atlas of the human ventral visual stream on a whole brain template that is commonly used in neuroimaging studies and (b) to compare this atlas to a recently published retinotopic parcellation of visual cortex (Wang et al., 2014). To achieve this goal, we generated an atlas of eight cytoarchitectonic areas: four areas in the occipital lobe (hOc1-hOc4v) and four in the fusiform gyrus (FG1-FG4), then we tested how the different alignment techniques affect the accuracy of the resulting atlas. Results show that both cortex-based alignment (CBA) and nonlinear volumetric alignment (NVA) generate an atlas with better cross-validation performance than affine volumetric alignment (AVA). Additionally, CBA outperformed NVA in 6/8 of the cytoarchitectonic areas. Finally, the comparison of the cytoarchitectonic atlas to a retinotopic atlas shows a clear correspondence between cytoarchitectonic and retinotopic areas in the ventral visual stream. The successful performance of CBA suggests a coupling between cytoarchitectonic areas and macroanatomical landmarks in the human ventral visual stream, and furthermore, that this coupling can be utilized for generating an accurate group atlas. In addition, the coupling between cytoarchitecture and retinotopy highlights the potential use of this atlas in understanding how anatomical features contribute to brain function. We make this cytoarchitectonic atlas freely available in both BrainVoyager and FreeSurfer formats (http://vpnl.stanford.edu/vcAtlas). The availability of this atlas will enable future studies to link cytoarchitectonic organization to other parcellations of the human ventral visual stream with potential to advance the understanding of this pathway in typical and atypical populations. Copyright © 2017 Elsevier Inc. All rights reserved.
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Audiovisual integration facilitates monkeys' short-term memory.
Bigelow, James; Poremba, Amy
2016-07-01
Many human behaviors are known to benefit from audiovisual integration, including language and communication, recognizing individuals, social decision making, and memory. Exceptionally little is known about the contributions of audiovisual integration to behavior in other primates. The current experiment investigated whether short-term memory in nonhuman primates is facilitated by the audiovisual presentation format. Three macaque monkeys that had previously learned an auditory delayed matching-to-sample (DMS) task were trained to perform a similar visual task, after which they were tested with a concurrent audiovisual DMS task with equal proportions of auditory, visual, and audiovisual trials. Parallel to outcomes in human studies, accuracy was higher and response times were faster on audiovisual trials than either unisensory trial type. Unexpectedly, two subjects exhibited superior unimodal performance on auditory trials, a finding that contrasts with previous studies, but likely reflects their training history. Our results provide the first demonstration of a bimodal memory advantage in nonhuman primates, lending further validation to their use as a model for understanding audiovisual integration and memory processing in humans.
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Integrated System Test Approaches for the NASA Ares I Crew Launch Vehicle
NASA Technical Reports Server (NTRS)
Cockrell, Charles E., Jr.; Askins, Bruce R.; Bland, Jeffrey; Davis, Stephan; Holladay, Jon B.; Taylor, James L.; Taylor, Terry L.; Robinson, Kimberly F.; Roberts, Ryan E.; Tuma, Margaret
2007-01-01
The Ares I Crew Launch Vehicle (CLV) is being developed by the U.S. National Aeronautics and Space Administration (NASA) to provide crew access to the International Space Station (ISS) and, together with the Ares V Cargo Launch Vehicle (CaLV), serves as one component of a future launch capability for human exploration of the Moon. During the system requirements definition process and early design cycles, NASA defined and began implementing plans for integrated ground and flight testing necessary to achieve the first human launch of Ares I. The individual Ares I flight hardware elements: the first stage five segment booster (FSB), upper stage, and J-2X upper stage engine, will undergo extensive development, qualification, and certification testing prior to flight. Key integrated system tests include the Main Propulsion Test Article (MPTA), acceptance tests of the integrated upper stage and upper stage engine assembly, a full-scale integrated vehicle dynamic test (IVDT), aerodynamic testing to characterize vehicle performance, and integrated testing of the avionics and software components. The Ares I-X development flight test will provide flight data to validate engineering models for aerodynamic performance, stage separation, structural dynamic performance, and control system functionality. The Ares I-Y flight test will validate ascent performance of the first stage, stage separation functionality, and a highaltitude actuation of the launch abort system (LAS) following separation. The Orion-1 flight test will be conducted as a full, un-crewed, operational flight test through the entire ascent flight profile prior to the first crewed launch.
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Time Sharing Between Robotics and Process Control: Validating a Model of Attention Switching.
Wickens, Christopher Dow; Gutzwiller, Robert S; Vieane, Alex; Clegg, Benjamin A; Sebok, Angelia; Janes, Jess
2016-03-01
The aim of this study was to validate the strategic task overload management (STOM) model that predicts task switching when concurrence is impossible. The STOM model predicts that in overload, tasks will be switched to, to the extent that they are attractive on task attributes of high priority, interest, and salience and low difficulty. But more-difficult tasks are less likely to be switched away from once they are being performed. In Experiment 1, participants performed four tasks of the Multi-Attribute Task Battery and provided task-switching data to inform the role of difficulty and priority. In Experiment 2, participants concurrently performed an environmental control task and a robotic arm simulation. Workload was varied by automation of arm movement and both the phases of environmental control and existence of decision support for fault management. Attention to the two tasks was measured using a head tracker. Experiment 1 revealed the lack of influence of task priority and confirmed the differing roles of task difficulty. In Experiment 2, the percentage attention allocation across the eight conditions was predicted by the STOM model when participants rated the four attributes. Model predictions were compared against empirical data and accounted for over 95% of variance in task allocation. More-difficult tasks were performed longer than easier tasks. Task priority does not influence allocation. The multiattribute decision model provided a good fit to the data. The STOM model is useful for predicting cognitive tunneling given that human-in-the-loop simulation is time-consuming and expensive. © 2016, Human Factors and Ergonomics Society.
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Automatically rating trainee skill at a pediatric laparoscopic suturing task.
Oquendo, Yousi A; Riddle, Elijah W; Hiller, Dennis; Blinman, Thane A; Kuchenbecker, Katherine J
2018-04-01
Minimally invasive surgeons must acquire complex technical skills while minimizing patient risk, a challenge that is magnified in pediatric surgery. Trainees need realistic practice with frequent detailed feedback, but human grading is tedious and subjective. We aim to validate a novel motion-tracking system and algorithms that automatically evaluate trainee performance of a pediatric laparoscopic suturing task. Subjects (n = 32) ranging from medical students to fellows performed two trials of intracorporeal suturing in a custom pediatric laparoscopic box trainer after watching a video of ideal performance. The motions of the tools and endoscope were recorded over time using a magnetic sensing system, and both tool grip angles were recorded using handle-mounted flex sensors. An expert rated the 63 trial videos on five domains from the Objective Structured Assessment of Technical Skill (OSATS), yielding summed scores from 5 to 20. Motion data from each trial were processed to calculate 280 features. We used regularized least squares regression to identify the most predictive features from different subsets of the motion data and then built six regression tree models that predict summed OSATS score. Model accuracy was evaluated via leave-one-subject-out cross-validation. The model that used all sensor data streams performed best, achieving 71% accuracy at predicting summed scores within 2 points, 89% accuracy within 4, and a correlation of 0.85 with human ratings. 59% of the rounded average OSATS score predictions were perfect, and 100% were within 1 point. This model employed 87 features, including none based on completion time, 77 from tool tip motion, 3 from tool tip visibility, and 7 from grip angle. Our novel hardware and software automatically rated previously unseen trials with summed OSATS scores that closely match human expert ratings. Such a system facilitates more feedback-intensive surgical training and may yield insights into the fundamental components of surgical skill.
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Cavnar, Peter; Inman, Kristina
2015-01-01
HS1-associated protein X-1 (Hax1) is a 35 kDa protein that is ubiquitously expressed. Hax1 is an anti-apoptotic protein with additional roles in cell motility, and autosomal recessive loss of Hax1 results in Kostmann syndrome, a form of severe congenital neutropenia. Because of the important role of Hax1 in neutrophils we demonstrate here validation of two commercially available research antibodies directed against human Hax1 in the human myeloid leukemia cell line PLB-985 cells. We show that both the mouse anti-Hax1 monoclonal IgG directed against amino acids 10-148 of Hax1 and a rabbit anti-Hax1 polyclonal IgG antibody directed against full-length Hax1 reliably and consistently detect Hax1 during immunoblotting of three different PLB-985 cell densities. Using shRNA mediated Hax1 knockdown, we demonstrate the specificity of both Hax1 antibodies. In addition, our results suggest that the rabbit anti-Hax1 polyclonal antibody provides a stronger intensity in detecting Hax1 protein, with detection in as few as 0.1 x 10 (6) cells in 6 total replicates we have performed.
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Lefranc, Sandrine; Roca, Pauline; Perrot, Matthieu; Poupon, Cyril; Le Bihan, Denis; Mangin, Jean-François; Rivière, Denis
2016-05-01
Segregating the human cortex into distinct areas based on structural connectivity criteria is of widespread interest in neuroscience. This paper presents a groupwise connectivity-based parcellation framework for the whole cortical surface using a new high quality diffusion dataset of 79 healthy subjects. Our approach performs gyrus by gyrus to parcellate the whole human cortex. The main originality of the method is to compress for each gyrus the connectivity profiles used for the clustering without any anatomical prior information. This step takes into account the interindividual cortical and connectivity variability. To this end, we consider intersubject high density connectivity areas extracted using a surface-based watershed algorithm. A wide validation study has led to a fully automatic pipeline which is robust to variations in data preprocessing (tracking type, cortical mesh characteristics and boundaries of initial gyri), data characteristics (including number of subjects), and the main algorithmic parameters. A remarkable reproducibility is achieved in parcellation results for the whole cortex, leading to clear and stable cortical patterns. This reproducibility has been tested across non-overlapping subgroups and the validation is presented mainly on the pre- and postcentral gyri. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
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Using the GPS to Collect Trajectory Data for Ejection Seat Design, Validation, and Testing
2002-03-01
Performing Organization Report Number AFIT/GE/ENG/02M-27 Sponsoring/Monitoring Agency Name(s) and Address(es) AFRL/HEPA ATT: Mr. John Plaga Q...APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED. i Acknowledgments I would like to start by thanking Mr. John Plaga from the Air...Human Effectiveness division, especially Mr. John Plaga for his contributions during the hardware acquisition and configuration. In addition the
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Information Search in Judgment Tasks: The Effects of Unequal Cue Validity and Cost.
1984-05-01
bookbag before betting on the contents of the bag being sampled ( Edwards , 1965). They proposed an alternative model for the regression (or continuous...ly displaced vertically for clarity.) The analogous relationship for the Bayesian model is developed by Edwards (1965). Snapper and Peterson (1971...A re- gression model and some preliminary findings." Organizational Behavior and Human Performance, 1982, 30, 330-350. Edwards , W.: "Optimal
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NASA Technical Reports Server (NTRS)
Thompson, Shelby; Holden, Kritina; Ebert, Douglas; Root, Phillip; Adelstein, Bernard; Jones, Jeffery
2009-01-01
The primary objective of the Short Duration Bioastronautics Investigation (SDBI) 1904 was to determine visual performance limits during Shuttle operational vibration and g-loads, specifically through the determination of minimal usable font sizes using Orion-type display formats. Currently there is little to no data available to quantify human visual performance under the extreme g- and vibration conditions of launch. Existing data on shuttle vibration magnitude and frequency is incomplete and does not address human visual performance. There have been anecdotal reports of performance decrements from shuttle crews, but no structured data have been collected. Previous work by NASA on the effects of vibration and linear g-loads on human performance was conducted during the Gemini era, but these experiments were performed using displays and controls that are dramatically different than current concepts being considered by the Constellation Program. Recently, three investigations of visual performance under vibration have been completed at NASA Ames Research Center: the first examining whole-body vibration, the second employing whole-body vibration coupled with a sustained g-load, and a third examining the effects of peak versus extended duration vibration. However, all of these studies were conducted using only a single x-axis direction (eyeballs in/out). Estimates of thrust oscillations from the Constellation Ares-I first stage are driving the need for realistic human performance requirements. SDBI 1904 was an opportunity to address the need for requirements by conducting a highly focused and applied evaluation in a relevant spaceflight environment. The SDBI was a companion effort to Detailed Test Objective (DTO) 695, which measured shuttle seat accelerations (vibration) during ascent. Data from the SDBI will serve an important role in interpreting the DTO vibration data. Both SDBI 1904 and DTO 695 were low impact with respect to flight resources, and combined, they represent an efficient and focused problem solving approach. This project provided (a) immediate data for developing preliminary human performance vibration requirements; (b) flight validated inputs for ongoing and future ground-based research; and (c) preliminary information related to Orion display format design.
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Serrano, Ana Belén; Capriotti, Anna Laura; Cavaliere, Chiara; Piovesana, Susy; Samperi, Roberto; Ventura, Salvatore; Laganà, Aldo
2015-01-01
A novel method for the simultaneous determination of enniatins A, A1, B and B1 and beauvericin, both in human urine and plasma samples, was developed and validated. The method consisted of a simple and easy pretreatment, specific for each matrix, followed by solid phase extraction (SPE) and detection by high performance liquid chromatography-tandem mass spectrometry with an electrospray ion source. The optimized SPE method was performed on graphitized carbon black cartridges after suitable dilution of the extracts, which allowed high mycotoxin absolute recoveries (76%–103%) and the removal of the major interferences from the matrix. The method was extensively evaluated for plasma and urine samples separately, providing satisfactory results in terms of linearity (R2 of 0.991–0.999), process efficiency (>81%), trueness (recoveries between 85% and 120%), intra-day precision (relative standard deviation, RSD < 18%), inter-day precision (RSD < 21%) and method quantification limits (ranging between 20 ng·L−1 and 40 ng·L−1 in plasma and between 5 ng·L−1 and 20 ng·L−1 in urine). Finally, the highly sensitive validated method was applied to some urine and plasma samples from different donors. PMID:26371043
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Chhun, Stéphanie; Rey, Elisabeth; Tran, Agnes; Lortholary, Olivier; Pons, Gérard; Jullien, Vincent
2007-06-01
A sensitive and selective high-performance liquid chromatographic (HPLC) method with ultra-violet detection has been developed and validated for the simultaneous determination of posaconazole and voriconazole, two systemic anti-fungal agents. An internal standard diazepam was added to 100 microL of human plasma followed by 3 mL of hexane-methylene chloride (70:30, v/v). The organic layer was evaporated to dryness and the residue was reconstituted with 100 microL of mobile phase before being injected in the chromatographic system. The compounds were separated on a C8 column using sodium potassium phosphate buffer (0.04 M, pH 6.0): acetonitrile:ultrapure water (45:52.5:2.5, v/v/v) as mobile phase. All compounds were detected at a wavelength of 255 nm. The assay was linear and validated over the range 0.2-10.0 mg/L for voriconazole and 0.05-10.0 mg/L for posaconazole. The biases were comprised between -3 and 5% for voriconazole and -2 and 8% for posaconazole. The intra- and inter-day precisions of the method were lower than 8% for the routine quality control (QC). The mean recovery was 98% for voriconazole and 108% for posaconazole. This method provides a useful tool for therapeutic drug monitoring.
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Salehi, Simin; Rasoul-Amini, Sara; Adib, Noushin; Shekarchi, Maryam
2016-08-01
In this study a novel method is described for selective quantization of domperidone in biological matrices applying molecular imprinted polymers (MIPs) as a sample clean up procedure using high performance liquid chromatography coupled with a fluorescence detector. MIPs were synthesized with chloroform as the porogen, ethylene glycol dimethacrylate as the crosslinker, methacrylic acid as the monomer, and domperidone as the template molecule. The new imprinted polymer was used as a molecular sorbent for separation of domperidone from serum. Molecular recognition properties, binding capacity and selectivity of MIPs were determined. The results demonstrated exceptional affinity for domperidone in biological fluids. The domperidone analytical method using MIPs was verified according to validation parameters, such as selectivity, linearity (5-80ng/mL, r(2)=0.9977), precision and accuracy (10-40ng/mL, intra-day=1.7-5.1%, inter-day=4.5-5.9%, and accuracy 89.07-98.9%).The limit of detection (LOD) and quantization (LOQ) of domperidone was 0.0279 and 0.092ng/mL, respectively. The simplicity and suitable validation parameters makes this a highly valuable selective bioequivalence method for domperidone analysis in human serum. Copyright © 2016 Elsevier B.V. All rights reserved.
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Man in space: The use of animal models
NASA Astrophysics Data System (ADS)
Ballard, Rodney W.; Souza, Kenneth A.
Animals have traditionally preceded man into space. During animal and human travels in space over the past almost 30 years, numerous anatomical, physiological, and biochemical changes have been observed. In order to safely qualify humans for extended duration space missions, scientific research needs to be performed. It may be possible to achieve many of these research goals with flight crews serving as experimental subjects; however, to do this with human subjects alone is impractical. Therefore, the use of animal surrogates as experimental subjects is essential to provide the missing information on the effects of spaceflights, to validate countermeasures, and to test medical treatment techniques which will be necessary for long duration missions. This research to assure human health, safety, and productivity in future extended duration space flights will include flights on NASA's Space Shuttle, unmanned biosatellites, and the Space Station Freedom.
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Micro-patterned graphene-based sensing skins for human physiological monitoring
NASA Astrophysics Data System (ADS)
Wang, Long; Loh, Kenneth J.; Chiang, Wei-Hung; Manna, Kausik
2018-03-01
Ultrathin, flexible, conformal, and skin-like electronic transducers are emerging as promising candidates for noninvasive and nonintrusive human health monitoring. In this work, a wearable sensing membrane is developed by patterning a graphene-based solution onto ultrathin medical tape, which can then be attached to the skin for monitoring human physiological parameters and physical activity. Here, the sensor is validated for monitoring finger bending/movements and for recognizing hand motion patterns, thereby demonstrating its future potential for evaluating athletic performance, physical therapy, and designing next-generation human-machine interfaces. Furthermore, this study also quantifies the sensor’s ability to monitor eye blinking and radial pulse in real-time, which can find broader applications for the healthcare sector. Overall, the printed graphene-based sensing skin is highly conformable, flexible, lightweight, nonintrusive, mechanically robust, and is characterized by high strain sensitivity.
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Man in space: the use of animal models.
Ballard, R W; Souza, K A
1991-01-01
Animals have traditionally preceded man into space. During animal and human travels in space over the past almost 30 years, numerous anatomical, physiological, and biochemical changes have been observed. In order to safely qualify humans for extended duration space missions, scientific research needs to be performed. It may be possible to achieve many of these research goals with flight crews serving as experimental subjects; however, to do this with human subjects alone is impractical. Therefore, the use of animal surrogates as experimental subjects is essential to provide the missing information on the effects of spaceflights, to validate countermeasures, and to test medical treatment techniques which will be necessary for long duration missions. This research to assure human health, safety, and productivity in future extended duration space flights will include flights on NASA's Space Shuttle, unmanned biosatellites, and the Space Station Freedom.
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Human neuron-astrocyte 3D co-culture-based assay for evaluation of neuroprotective compounds.
Terrasso, Ana Paula; Silva, Ana Carina; Filipe, Augusto; Pedroso, Pedro; Ferreira, Ana Lúcia; Alves, Paula Marques; Brito, Catarina
Central nervous system drug development has registered high attrition rates, mainly due to the lack of efficacy of drug candidates, highlighting the low reliability of the models used in early-stage drug development and the need for new in vitro human cell-based models and assays to accurately identify and validate drug candidates. 3D human cell models can include different tissue cell types and represent the spatiotemporal context of the original tissue (co-cultures), allowing the establishment of biologically-relevant cell-cell and cell-extracellular matrix interactions. Nevertheless, exploitation of these 3D models for neuroprotection assessment has been limited due to the lack of data to validate such 3D co-culture approaches. In this work we combined a 3D human neuron-astrocyte co-culture with a cell viability endpoint for the implementation of a novel in vitro neuroprotection assay, over an oxidative insult. Neuroprotection assay robustness and specificity, and the applicability of Presto Blue, MTT and CytoTox-Glo viability assays to the 3D co-culture were evaluated. Presto Blue was the adequate endpoint as it is non-destructive and is a simpler and reliable assay. Semi-automation of the cell viability endpoint was performed, indicating that the assay setup is amenable to be transferred to automated screening platforms. Finally, the neuroprotection assay setup was applied to a series of 36 test compounds and several candidates with higher neuroprotective effect than the positive control, Idebenone, were identified. The robustness and simplicity of the implemented neuroprotection assay with the cell viability endpoint enables the use of more complex and reliable 3D in vitro cell models to identify and validate drug candidates. Copyright © 2016 Elsevier Inc. All rights reserved.
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Rodríguez-Gómez, R; Jiménez-Díaz, I; Zafra-Gómez, A; Ballesteros, O; Navalón, A
2014-12-01
In recent decades, in parallel to industrial development, a large amount of new chemicals have emerged that are able to produce disorders in human endocrine system. These groups of substances, so-called endocrine disrupting chemicals (EDCs), include many families of compounds, such as parabens, benzophenone-UV filters and bisphenols. Given the demonstrated biological activity of those compounds, it is necessary to develop new analytical procedures to evaluate the exposure with the final objective of establishing, in an accurate way, relationships between EDCs concentrations and the harmful health effects observed in population. In the present work, a method based on a simplified sample treatment involving steps of precipitation, evaporation and clean-up of the extracts with C18 followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis for the determination of bisphenol A and its chlorinated derivatives (monochloro-, dichloro-, trichloro- and tetrachlorobisphenol A), parabens (methyl-, ethyl-, propyl- and butylparaben) and benzophenone-UV filters (benzophenone -1,-2, -3, -6, -8 and 4-hydroxybenzophenone) in human breast milk samples is proposed and validated. The limits of detections found ranged from 0.02 to 0.05 ng mL(-1). The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 91% to 110% and the precision (evaluated as relative standard deviation) was lower than 15% for all compounds, being within the acceptable limits for the selected bioanalytical method validation guide. The method was satisfactorily applied for the determination of these compounds in human breast milk samples collected from 10 randomly selected women. Copyright © 2014 Elsevier B.V. All rights reserved.
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Jensen, Pamela K; Wujcik, Chad E; McGuire, Michelle K; McGuire, Mark A
2016-01-01
Simple high-throughput procedures were developed for the direct analysis of glyphosate [N-(phosphonomethyl)glycine] and aminomethylphosphonic acid (AMPA) in human and bovine milk and human urine matrices. Samples were extracted with an acidified aqueous solution on a high-speed shaker. Stable isotope labeled internal standards were added with the extraction solvent to ensure accurate tracking and quantitation. An additional cleanup procedure using partitioning with methylene chloride was required for milk matrices to minimize the presence of matrix components that can impact the longevity of the analytical column. Both analytes were analyzed directly, without derivatization, by liquid chromatography tandem mass spectrometry using two separate precursor-to-product transitions that ensure and confirm the accuracy of the measured results. Method performance was evaluated during validation through a series of assessments that included linearity, accuracy, precision, selectivity, ionization effects and carryover. Limits of quantitation (LOQ) were determined to be 0.1 and 10 µg/L (ppb) for urine and milk, respectively, for both glyphosate and AMPA. Mean recoveries for all matrices were within 89-107% at three separate fortification levels including the LOQ. Precision for replicates was ≤ 7.4% relative standard deviation (RSD) for milk and ≤ 11.4% RSD for urine across all fortification levels. All human and bovine milk samples used for selectivity and ionization effects assessments were free of any detectable levels of glyphosate and AMPA. Some of the human urine samples contained trace levels of glyphosate and AMPA, which were background subtracted for accuracy assessments. Ionization effects testing showed no significant biases from the matrix. A successful independent external validation was conducted using the more complicated milk matrices to demonstrate method transferability.
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Chen, Guoqiang; Hoptroff, Michael; Fei, Xiaoqing; Su, Ya; Janssen, Hans-Gerd
2013-11-22
A sensitive and specific ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the measurement of climbazole deposition from hair care products onto artificial skin and human scalp. Deuterated climbazole was used as the internal standard. Atmospheric pressure chemical ionization (APCI) in positive mode was applied for the detection of climbazole. For quantification, multiple reaction monitoring (MRM) transition 293.0>69.0 was monitored for climbazole, and MRM transition 296.0>225.1 for the deuterated climbazole. The linear range ran from 4 to 2000 ng mL(-1). The limit of detection (LOD) and the limit of quantification (LOQ) were 1 ng mL(-1) and 4 ng mL(-1), respectively, which enabled quantification of climbazole on artificial skin and human scalp at ppb level (corresponding to 16 ng cm(-2)). For the sampling of climbazole from human scalp the buffer scrub method using a surfactant-modified phosphate buffered saline (PBS) solution was selected based on a performance comparison of tape stripping, the buffer scrub method and solvent extraction in in vitro studies. Using this method, climbazole deposition in in vitro and in vivo studies was successfully quantified. Copyright © 2013 Elsevier B.V. All rights reserved.
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Meisser Redeuil, Karine; Longet, Karin; Bénet, Sylvie; Munari, Caroline; Campos-Giménez, Esther
2015-11-27
This manuscript reports a validated analytical approach for the quantification of 21 water soluble vitamins and their main circulating forms in human plasma. Isotope dilution-based sample preparation consisted of protein precipitation using acidic methanol enriched with stable isotope labelled internal standards. Separation was achieved by reversed-phase liquid chromatography and detection performed by tandem mass spectrometry in positive electrospray ionization mode. Instrumental lower limits of detection and quantification reached <0.1-10nM and 0.2-25nM, respectively. Commercially available pooled human plasma was used to build matrix-matched calibration curves ranging 2-500, 5-1250, 20-5000 or 150-37500nM depending on the analyte. The overall performance of the method was considered adequate, with 2.8-20.9% and 5.2-20.0% intra and inter-day precision, respectively and averaged accuracy reaching 91-108%. Recovery experiments were also performed and reached in average 82%. This analytical approach was then applied for the quantification of circulating water soluble vitamins in human plasma single donor samples. The present report provides a sensitive and reliable approach for the quantification of water soluble vitamins and main circulating forms in human plasma. In the future, the application of this analytical approach will give more confidence to provide a comprehensive assessment of water soluble vitamins nutritional status and bioavailability studies in humans. Copyright © 2015 Elsevier B.V. All rights reserved.
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Morin, Ruth T; Axelrod, Bradley N
Latent Class Analysis (LCA) was used to classify a heterogeneous sample of neuropsychology data. In particular, we used measures of performance validity, symptom validity, cognition, and emotional functioning to assess and describe latent groups of functioning in these areas. A data-set of 680 neuropsychological evaluation protocols was analyzed using a LCA. Data were collected from evaluations performed for clinical purposes at an urban medical center. A four-class model emerged as the best fitting model of latent classes. The resulting classes were distinct based on measures of performance validity and symptom validity. Class A performed poorly on both performance and symptom validity measures. Class B had intact performance validity and heightened symptom reporting. The remaining two Classes performed adequately on both performance and symptom validity measures, differing only in cognitive and emotional functioning. In general, performance invalidity was associated with worse cognitive performance, while symptom invalidity was associated with elevated emotional distress. LCA appears useful in identifying groups within a heterogeneous sample with distinct performance patterns. Further, the orthogonal nature of performance and symptom validities is supported.
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Chang, Yuanhan; Tambe, Abhijit Anil; Maeda, Yoshinobu; Wada, Masahiro; Gonda, Tomoya
2018-03-08
A literature review of finite element analysis (FEA) studies of dental implants with their model validation process was performed to establish the criteria for evaluating validation methods with respect to their similarity to biological behavior. An electronic literature search of PubMed was conducted up to January 2017 using the Medical Subject Headings "dental implants" and "finite element analysis." After accessing the full texts, the context of each article was searched using the words "valid" and "validation" and articles in which these words appeared were read to determine whether they met the inclusion criteria for the review. Of 601 articles published from 1997 to 2016, 48 that met the eligibility criteria were selected. The articles were categorized according to their validation method as follows: in vivo experiments in humans (n = 1) and other animals (n = 3), model experiments (n = 32), others' clinical data and past literature (n = 9), and other software (n = 2). Validation techniques with a high level of sufficiency and efficiency are still rare in FEA studies of dental implants. High-level validation, especially using in vivo experiments tied to an accurate finite element method, needs to become an established part of FEA studies. The recognition of a validation process should be considered when judging the practicality of an FEA study.
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Tay-Sontheimer, Jessica; Shireman, Laura M; Beyer, Richard P; Senn, Taurence; Witten, Daniela; Pearce, Robin E; Gaedigk, Andrea; Gana Fomban, Cletus L; Lutz, Justin D; Isoherranen, Nina; Thummel, Kenneth E; Fiehn, Oliver; Leeder, J Steven; Lin, Yvonne S
2014-12-01
We sought to discover endogenous urinary biomarkers of human CYP2D6 activity. Healthy pediatric subjects (n = 189) were phenotyped using dextromethorphan and randomized for candidate biomarker selection and validation. Global urinary metabolomics was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Candidate biomarkers were tested in adults receiving fluoxetine, a CYP2D6 inhibitor. A biomarker, M1 (m/z 444.3102) was correlated with CYP2D6 activity in both the pediatric training and validation sets. Poor metabolizers had undetectable levels of M1, whereas it was present in subjects with other phenotypes. In adult subjects, a 9.56-fold decrease in M1 abundance was observed during CYP2D6 inhibition. Identification and validation of M1 may provide a noninvasive means of CYP2D6 phenotyping.
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Development of Metabolic Function Biomarkers in the Common Marmoset, Callithrix jacchus
Ziegler, Toni E.; Colman, Ricki J.; Tardif, Suzette D.; Sosa, Megan E.; Wegner, Fredrick H.; Wittwer, Daniel J.; Shrestha, Hemanta
2013-01-01
Metabolic assessment of a nonhuman primate model of metabolic syndrome and obesity requires the necessary biomarkers specific to the species. While the rhesus monkey has a number of specific assays for assessing metabolic syndrome, the marmoset does not. Furthermore, the common marmoset (Callithrix jacchus) has a small blood volume that necessitates using a single blood volume for multiple analyses. The common marmoset holds a great potential as an alternative primate model for the study of human disease but assay methods need to be developed and validated for the biomarkers of metabolic syndrome. Here we report on the adaptation, development and validation of commercially available immunoassays for common marmoset samples in small volumes. We have performed biological validations for insulin, adiponectin, leptin, and ghrelin to demonstrate the use of these biomarkers in examining metabolic syndrome and other related diseases in the common marmoset. PMID:23447060
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Evidence of MAOA genotype involvement in spatial ability in males
Mueller, Sven C.; Cornwell, Brian R.; Grillon, Christian; MacIntyre, Jessica; Gorodetsky, Elena; Goldman, David; Pine, Daniel S.; Ernst, Monique
2014-01-01
Although the Monoamine Oxidase-A (MAOA) gene has been linked to spatial learning and memory in animal models, convincing evidence in humans is lacking. Performance on an ecologically-valid, virtual computer-based equivalent of the Morris Water Maze task was compared between 28 healthy males with the low MAOA transcriptional activity and 41 healthy age- and IQ-matched males with the high MAOA transcriptional activity. The results revealed consistently better performance (reduced heading error, shorter path length, and reduced failed trials) for the high MAOA activity individuals relative to the low activity individuals. By comparison, groups did not differ on pre-task variables or strategic measures such as first-move latency. The results provide novel evidence of MAOA gene involvement in human spatial navigation using a virtual analogue of the Morris Water Maze task. PMID:24671068
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NASA Astrophysics Data System (ADS)
Nunez, F.; Romero, A.; Clua, J.; Mas, J.; Tomas, A.; Catalan, A.; Castellsaguer, J.
2005-08-01
MARES (Muscle Atrophy Research and Exercise System) is a computerized ergometer for neuromuscular research to be flown and installed onboard the International Space Station in 2007. Validity of data acquired depends on controlling and reducing all significant error sources. One of them is the misalignment of the joint rotation axis with respect to the motor axis.The error induced on the measurements is proportional to the misalignment between both axis. Therefore, the restraint system's performance is critical [1]. MARES HRS (Human Restraint System) assures alignment within an acceptable range while performing the exercise (results: elbow movement:13.94mm+/-5.45, Knee movement: 22.36mm+/- 6.06 ) and reproducibility of human positioning (results: elbow movement: 2.82mm+/-1.56, Knee movement 7.45mm+/-4.8 ). These results allow limiting measurement errors induced by misalignment.
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Petruczynik, Anna; Wroblewski, Karol; Szultka-Mlynska, Malgorzata; Buszewsk, Boguslaw; Karakula-Juchnowicz, Hanna; Gajewski, Jacek; Morylowska-Topolska, Justyna; Waksmundzka-Hajnosi, Monika
2017-05-01
A high performance liquid chromatography (HPLC) method for simultaneous analysis of venlafaxine and its major metabolite 0-desmethylvenlafaxine and vilazodone and its methabolite M10 have been devel- oped and validated. Chromatography was performed on the Phenyl-Hexyl column with mobile phase containing methanol, acetate buffer at pH 3.5 and diethylamine. The application of stationary phase with 7r-7c moieties and mobile phase containing diethylamine as silanol blocker lets to obtain double protection against silanols and thus very high theoretical plate numbers were obtained. The good separation selectivity, good peaks' symmetry and very high systems efficiency for all investigated compounds were obtained in applied chromatographic system. The method is very efficient and suitable for the analysis of investigated drugs and their metabolites in human serum for patients' pharmacotherapy control.
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Belal, F; Walash, M; El-Enany, N; Zayed, S
2013-12-01
An alternative method for analysis of aliskiren (ALI) and hydrochlorothiazde (HCT) in combined dosage forms by ion-pair reversed phase high performance liquid chromatography was developed and validated. The pharmaceutical preparations were analyzed using a C18 column (250 mm x 4.6 mm, 3 microm) with a mobile phase consisting of 25% methanol, 50% sodium monobasic phosphate aqueous solution containing 6 mM tetrabutylammonium bromide and 25% water at pH 7.2. Isocratic analysis was performed at a flow rate of 1 mL/min and a column temperature of 30 degrees C under direct UV detection at 210 nm. Paracetamol was used as internal standard. The validation was performed according to the ICH guidelines. The proposed method was linear over the concentration range of 0.250 to 60 and 0.1 to 10 microg/mL for ALI and HCT, respectively. The limits of detection and quantitation (LOD and LOQ) were 0.075 and 0.198 microg/mL, respectively, for ALI and 0.04 and 0.062 microg/mL, respectively, for HCT. The method proved to be specific, sensitive, precise and accurate with mean recovery values of 101.1 +/- 0.32% and 100.9 +/- 0.41% for ALI and HCT, respectively. The method robustness was evaluated by means of an experimental design. The proposed method was applied successfully to spiked human urine samples with mean recoveries of 98.8 +/- 0.36% and 98.1 +/- 0.21% for ALI and HCT, respectively.
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Luo, Jiawei; Xiao, Qiu
2017-02-01
MicroRNAs (miRNAs) play a critical role by regulating their targets in post-transcriptional level. Identification of potential miRNA-disease associations will aid in deciphering the pathogenesis of human polygenic diseases. Several computational models have been developed to uncover novel miRNA-disease associations based on the predicted target genes. However, due to the insufficient number of experimentally validated miRNA-target interactions as well as the relatively high false-positive and false-negative rates of predicted target genes, it is still challenging for these prediction models to obtain remarkable performances. The purpose of this study is to prioritize miRNA candidates for diseases. We first construct a heterogeneous network, which consists of a disease similarity network, a miRNA functional similarity network and a known miRNA-disease association network. Then, an unbalanced bi-random walk-based algorithm on the heterogeneous network (BRWH) is adopted to discover potential associations by exploiting bipartite subgraphs. Based on 5-fold cross validation, the proposed network-based method achieves AUC values ranging from 0.782 to 0.907 for the 22 human diseases and an average AUC of almost 0.846. The experiments indicated that BRWH can achieve better performances compared with several popular methods. In addition, case studies of some common diseases further demonstrated the superior performance of our proposed method on prioritizing disease-related miRNA candidates. Copyright © 2017 Elsevier Inc. All rights reserved.
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HAMDA: Hybrid Approach for MiRNA-Disease Association prediction.
Chen, Xing; Niu, Ya-Wei; Wang, Guang-Hui; Yan, Gui-Ying
2017-12-01
For decades, enormous experimental researches have collectively indicated that microRNA (miRNA) could play indispensable roles in many critical biological processes and thus also the pathogenesis of human complex diseases. Whereas the resource and time cost required in traditional biology experiments are expensive, more and more attentions have been paid to the development of effective and feasible computational methods for predicting potential associations between disease and miRNA. In this study, we developed a computational model of Hybrid Approach for MiRNA-Disease Association prediction (HAMDA), which involved the hybrid graph-based recommendation algorithm, to reveal novel miRNA-disease associations by integrating experimentally verified miRNA-disease associations, disease semantic similarity, miRNA functional similarity, and Gaussian interaction profile kernel similarity into a recommendation algorithm. HAMDA took not only network structure and information propagation but also node attribution into consideration, resulting in a satisfactory prediction performance. Specifically, HAMDA obtained AUCs of 0.9035 and 0.8395 in the frameworks of global and local leave-one-out cross validation, respectively. Meanwhile, HAMDA also achieved good performance with AUC of 0.8965 ± 0.0012 in 5-fold cross validation. Additionally, we conducted case studies about three important human cancers for performance evaluation of HAMDA. As a result, 90% (Lymphoma), 86% (Prostate Cancer) and 92% (Kidney Cancer) of top 50 predicted miRNAs were confirmed by recent experiment literature, which showed the reliable prediction ability of HAMDA. Copyright © 2017 Elsevier Inc. All rights reserved.
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WORMHOLE: Novel Least Diverged Ortholog Prediction through Machine Learning
Sutphin, George L.; Mahoney, J. Matthew; Sheppard, Keith; Walton, David O.; Korstanje, Ron
2016-01-01
The rapid advancement of technology in genomics and targeted genetic manipulation has made comparative biology an increasingly prominent strategy to model human disease processes. Predicting orthology relationships between species is a vital component of comparative biology. Dozens of strategies for predicting orthologs have been developed using combinations of gene and protein sequence, phylogenetic history, and functional interaction with progressively increasing accuracy. A relatively new class of orthology prediction strategies combines aspects of multiple methods into meta-tools, resulting in improved prediction performance. Here we present WORMHOLE, a novel ortholog prediction meta-tool that applies machine learning to integrate 17 distinct ortholog prediction algorithms to identify novel least diverged orthologs (LDOs) between 6 eukaryotic species—humans, mice, zebrafish, fruit flies, nematodes, and budding yeast. Machine learning allows WORMHOLE to intelligently incorporate predictions from a wide-spectrum of strategies in order to form aggregate predictions of LDOs with high confidence. In this study we demonstrate the performance of WORMHOLE across each combination of query and target species. We show that WORMHOLE is particularly adept at improving LDO prediction performance between distantly related species, expanding the pool of LDOs while maintaining low evolutionary distance and a high level of functional relatedness between genes in LDO pairs. We present extensive validation, including cross-validated prediction of PANTHER LDOs and evaluation of evolutionary divergence and functional similarity, and discuss future applications of machine learning in ortholog prediction. A WORMHOLE web tool has been developed and is available at http://wormhole.jax.org/. PMID:27812085
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Solid Lubricants and Coatings for Extreme Environments: State-of-the-Art Survey
NASA Technical Reports Server (NTRS)
Miyoshi, Kazuhisa
2007-01-01
An investigation was conducted to survey anticipated requirements for solid lubricants in lunar and Martian environments, as well as the effects of these environments on lubricants and their performance and durability. The success of habitats and vehicles on the Moon and Mars, and ultimately, of the human exploration of and permanent human presence on the Moon and Mars, are critically dependent on the correct and reliable operation of many moving mechanical assemblies and tribological components. The coefficient of friction and lifetime of any lubricant generally vary with the environment, and lubricants have very different characteristics under different conditions. It is essential, therefore, to select the right lubrication technique and lubricant for each mechanical and tribological application. Several environmental factors are hazardous to performance integrity on the Moon and Mars. Potential threats common to both the Moon and Mars are low ambient temperatures, wide daily temperature swings (thermal cycling), solar flux, cosmic radiation, and large quantities of dust. The surface of Mars has the additional challenges of dust storms, winds, and a carbon dioxide atmosphere. Solid lubricants and coatings are needed for lunar and Martian applications, where liquid lubricants are ineffective and undesirable, and these lubricants must perform well in the extreme environments of the Moon, Mars, and space, as well as on Earth, where they will be assembled and tested. No solid lubricants and coatings and their systems currently exist or have been validated that meet these requirements, so new solid lubricants must be designed and validated for these applications.
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WORMHOLE: Novel Least Diverged Ortholog Prediction through Machine Learning.
Sutphin, George L; Mahoney, J Matthew; Sheppard, Keith; Walton, David O; Korstanje, Ron
2016-11-01
The rapid advancement of technology in genomics and targeted genetic manipulation has made comparative biology an increasingly prominent strategy to model human disease processes. Predicting orthology relationships between species is a vital component of comparative biology. Dozens of strategies for predicting orthologs have been developed using combinations of gene and protein sequence, phylogenetic history, and functional interaction with progressively increasing accuracy. A relatively new class of orthology prediction strategies combines aspects of multiple methods into meta-tools, resulting in improved prediction performance. Here we present WORMHOLE, a novel ortholog prediction meta-tool that applies machine learning to integrate 17 distinct ortholog prediction algorithms to identify novel least diverged orthologs (LDOs) between 6 eukaryotic species-humans, mice, zebrafish, fruit flies, nematodes, and budding yeast. Machine learning allows WORMHOLE to intelligently incorporate predictions from a wide-spectrum of strategies in order to form aggregate predictions of LDOs with high confidence. In this study we demonstrate the performance of WORMHOLE across each combination of query and target species. We show that WORMHOLE is particularly adept at improving LDO prediction performance between distantly related species, expanding the pool of LDOs while maintaining low evolutionary distance and a high level of functional relatedness between genes in LDO pairs. We present extensive validation, including cross-validated prediction of PANTHER LDOs and evaluation of evolutionary divergence and functional similarity, and discuss future applications of machine learning in ortholog prediction. A WORMHOLE web tool has been developed and is available at http://wormhole.jax.org/.
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Bolduc, Francois V; Lau, Amanda; Rosenfelt, Cory S; Langer, Steven; Wang, Nan; Smithson, Lisa; Lefebvre, Diana; Alexander, R Todd; Dickson, Clayton T; Li, Liang; Becker, Allan B; Subbarao, Padmaja; Turvey, Stuart E; Pei, Jacqueline; Sears, Malcolm R; Mandhane, Piush J
2016-06-01
In-utero nutrition is an under-studied aspect of cognitive development. Fruit has been an important dietary constituent for early hominins and humans. Among 808 eligible CHILD-Edmonton sub-cohort subjects, 688 (85%) had 1-year cognitive outcome data. We found that each maternal daily serving of fruit (sum of fruit plus 100% fruit juice) consumed during pregnancy was associated with a 2.38 point increase in 1-year cognitive development (95% CI 0.39, 4.37; p<0.05). Consistent with this, we found 30% higher learning Performance index (PI) scores in Drosophila offspring from parents who consumed 30% fruit juice supplementation prenatally (PI: 85.7; SE 1.8; p<0.05) compared to the offspring of standard diet parents (PI: 65.0 SE 3.4). Using the Drosophila model, we also show that the cyclic adenylate monophosphate (cAMP) pathway may be a major regulator of this effect, as prenatal fruit associated cognitive enhancement was blocked in Drosophila rutabaga mutants with reduced Ca(2+)-Calmodulin-dependent adenylyl cyclase. Moreover, gestation is a critical time for this effect as postnatal fruit intake did not enhance cognitive performance in either humans or Drosophila. Our study supports increased fruit consumption during pregnancy with significant increases in infant cognitive performance. Validation in Drosophila helps control for potential participant bias or unmeasured confounders. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
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Johnsen, Stig O; Kilskar, Stine Skaufel; Fossum, Knut Robert
2017-01-01
More attention has recently been given to Human Factors in petroleum accident investigations. The Human Factors areas examined in this article are organizational, cognitive and physical ergonomics. A key question to be explored is as follows: To what degree are the petroleum industry and safety authorities in Norway focusing on these Human Factors areas from the design phase? To investigate this, we conducted an innovative exploratory study of the development of four control centres in Norwegian oil and gas industry in collaboration between users, management and Human Factors experts. We also performed a literature survey and discussion with the professional Human Factors network in Norway. We investigated the Human Factors focus, reasons for not considering Human Factors and consequences of missing Human Factors in safety management. The results revealed an immature focus and organization of Human Factors. Expertise on organizational ergonomics and cognitive ergonomics are missing from companies and safety authorities and are poorly prioritized during the development. The easy observable part of Human Factors (i.e. physical ergonomics) is often in focus. Poor focus on Human Factors in the design process creates demanding conditions for human operators and impact safety and resilience. There is lack of non-technical skills such as communication and decision-making. New technical equipment such as Closed Circuit Television is implemented without appropriate use of Human Factors standards. Human Factors expertise should be involved as early as possible in the responsible organizations. Verification and validation of Human Factors should be improved and performed from the start, by certified Human Factors experts in collaboration with the workforce. The authorities should check-back that the regulatory framework of Human Factors is communicated, understood and followed. PMID:29278242
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Human System Simulation in Support of Human Performance Technical Basis at NPPs
DOE Office of Scientific and Technical Information (OSTI.GOV)
David Gertman; Katya Le Blanc; alan mecham
2010-06-01
This paper focuses on strategies and progress toward establishing the Idaho National Laboratory’s (INL’s) Human Systems Simulator Laboratory at the Center for Advanced Energy Studies (CAES), a consortium of Idaho State Universities. The INL is one of the National Laboratories of the US Department of Energy. One of the first planned applications for the Human Systems Simulator Laboratory is implementation of a dynamic nuclear power plant simulation (NPP) where studies of operator workload, situation awareness, performance and preference will be carried out in simulated control rooms including nuclear power plant control rooms. Simulation offers a means by which to reviewmore » operational concepts, improve design practices and provide a technical basis for licensing decisions. In preparation for the next generation power plant and current government and industry efforts in support of light water reactor sustainability, human operators will be attached to a suite of physiological measurement instruments and, in combination with traditional Human Factors Measurement techniques, carry out control room tasks in simulated advanced digital and hybrid analog/digital control rooms. The current focus of the Human Systems Simulator Laboratory is building core competence in quantitative and qualitative measurements of situation awareness and workload. Of particular interest is whether introduction of digital systems including automated procedures has the potential to reduce workload and enhance safety while improving situation awareness or whether workload is merely shifted and situation awareness is modified in yet to be determined ways. Data analysis is carried out by engineers and scientists and includes measures of the physical and neurological correlates of human performance. The current approach supports a user-centered design philosophy (see ISO 13407 “Human Centered Design Process for Interactive Systems, 1999) wherein the context for task performance along with the requirements of the end-user are taken into account during the design process and the validity of design is determined through testing of real end users« less
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Human Factors Experimental Design and Analysis Reference
2007-07-01
Equipment 1.4.5. Pretesting 1.5. Research Design Alternatives ………………………………………………………...30 1.6. Analyzing Results ……………………………………………………………………….31 1.7...46 2.1.1. Threats to Validity 2.1.2. Quantitative Research Approach 2.2. Experimental Design Alternatives...with a discussion of quantitative models in research that are used to predict human performance. Next empirical model building using polynomial
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Spacelab Life Sciences 1 - The stepping stone
NASA Technical Reports Server (NTRS)
Dalton, B. P.; Leon, H.; Hogan, R.; Clarke, B.; Tollinger, D.
1988-01-01
The Spacelab Life Sciences (SLS-1) mission scheduled for launch in March 1990 will study the effects of microgravity on physiological parameters of humans and animals. The data obtained will guide equipment design, performance of activities involving the use of animals, and prediction of human physiological responses during long-term microgravity exposure. The experiments planned for the SLS-1 mission include a particulate-containment demonstration test, integrated rodent experiments, jellyfish experiments, and validation of the small-mass measuring instrument. The design and operation of the Research Animal Holding Facility, General-Purpose Work Station, General-Purpose Transfer Unit, and Animal Enclosure Module are discussed and illustrated with drawings and diagrams.
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Deep Learning to Classify Radiology Free-Text Reports.
Chen, Matthew C; Ball, Robyn L; Yang, Lingyao; Moradzadeh, Nathaniel; Chapman, Brian E; Larson, David B; Langlotz, Curtis P; Amrhein, Timothy J; Lungren, Matthew P
2018-03-01
Purpose To evaluate the performance of a deep learning convolutional neural network (CNN) model compared with a traditional natural language processing (NLP) model in extracting pulmonary embolism (PE) findings from thoracic computed tomography (CT) reports from two institutions. Materials and Methods Contrast material-enhanced CT examinations of the chest performed between January 1, 1998, and January 1, 2016, were selected. Annotations by two human radiologists were made for three categories: the presence, chronicity, and location of PE. Classification of performance of a CNN model with an unsupervised learning algorithm for obtaining vector representations of words was compared with the open-source application PeFinder. Sensitivity, specificity, accuracy, and F1 scores for both the CNN model and PeFinder in the internal and external validation sets were determined. Results The CNN model demonstrated an accuracy of 99% and an area under the curve value of 0.97. For internal validation report data, the CNN model had a statistically significant larger F1 score (0.938) than did PeFinder (0.867) when classifying findings as either PE positive or PE negative, but no significant difference in sensitivity, specificity, or accuracy was found. For external validation report data, no statistical difference between the performance of the CNN model and PeFinder was found. Conclusion A deep learning CNN model can classify radiology free-text reports with accuracy equivalent to or beyond that of an existing traditional NLP model. © RSNA, 2017 Online supplemental material is available for this article.
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Dwivedi, Jaya; Namdev, Kuldeep K; Chilkoti, Deepak C; Verma, Surajpal; Sharma, Swapnil
2018-06-06
Therapeutic drug monitoring (TDM) of anti-epileptic drugs provides a valid clinical tool in optimization of overall therapy. However, TDM is challenging due to the high biological samples (plasma/blood) storage/shipment costs and the limited availability of laboratories providing TDM services. Sampling in the form of dry plasma spot (DPS) or dry blood spot (DBS) is a suitable alternative to overcome these issues. An improved, simple, rapid, and stability indicating method for quantification of pregabalin in human plasma and DPS has been developed and validated. Analyses were performed on liquid chromatography tandem mass spectrometer under positive ionization mode of electrospray interface. Pregabain-d4 was used as internal standard, and the chromatographic separations were performed on Poroshell 120 EC-C18 column using an isocratic mobile phase flow rate of 1 mL/min. Stability of pregabalin in DPS was evaluated under simulated real-time conditions. Extraction procedures from plasma and DPS samples were compared using statistical tests. The method was validated considering the FDA method validation guideline. The method was linear over the concentration range of 20-16000 ng/mL and 100-10000 ng/mL in plasma and DPS, respectively. DPS samples were found stable for only one week upon storage at room temperature and for at least four weeks at freezing temperature (-20 ± 5 °C). Method was applied for quantification of pregabalin in over 600 samples of a clinical study. Statistical analyses revealed that two extraction procedures in plasma and DPS samples showed statistically insignificant difference and can be used interchangeably without any bias. Proposed method involves simple and rapid steps of sample processing that do not require a pre- or post-column derivatization procedure. The method is suitable for routine pharmacokinetic analysis and therapeutic monitoring of pregabalin.
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Namdev, Kuldeep Kumar; Dwivedi, Jaya; Chilkoti, Deepak Chandra; Sharma, Swapnil
2018-01-01
Lamotrigine (LTZ) is a phenyltriazine derivative which belongs to anti-epileptic drugs (AEDs) class and prescribed as mono- or adjunctive-therapy in treatment of epilepsy. Therapeutic drug monitoring (TDM) of AEDs provides a valid clinical tool in optimization of overall therapy. However, TDM is challenging due to the high biological samples (plasma/blood) storage/shipment costs and the limited availability of laboratories providing TDM services. Sampling in the form of dry plasma spot (DPS) or dry blood spot (DBS) are suitable alternative to overcome these issues. We developed and validated a new method for quantification of LTZ in human plasma and DPS. The extraction of LTZ from plasma and DPS was performed using liquid-liquid extraction with diethyl ether and an extraction solution composed of diethyl ether- methyl tert-butyl ether- acetone (50:30:20, v/v/v), respectively. Lamotrigine- 13C3, d3 was used as internal standard (ISTD) and the chromatographic separation was achieved on Hypurity Advance C18 column (150×4.6mm, 5μm). Quantitative estimation of LTZ and ISTD was performed on a liquid chromatography tandem mass spectrometer coupled with electrospray ionization interface operated under positive mode of ionization. Calibration curves were linear (r 2 >0.99) over the concentration range of 10-3020ng/mL for both plasma and DPS. Statistical analysis provides insignificant difference between LTZ concentration extracted from plasma and DPS samples. The method is found suitable for application in clinical study and in therapeutic monitoring of LTZ. To the best of our knowledge this is the first report which describing a validated stability indicating assay for quantification of LTZ in dry plasma spot. Copyright © 2017 Elsevier B.V. All rights reserved.
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Makris, Susan L.; Raffaele, Kathleen; Allen, Sandra; Bowers, Wayne J.; Hass, Ulla; Alleva, Enrico; Calamandrei, Gemma; Sheets, Larry; Amcoff, Patric; Delrue, Nathalie; Crofton, Kevin M.
2009-01-01
Objective We conducted a review of the history and performance of developmental neurotoxicity (DNT) testing in support of the finalization and implementation of Organisation of Economic Co-operation and Development (OECD) DNT test guideline 426 (TG 426). Information sources and analysis In this review we summarize extensive scientific efforts that form the foundation for this testing paradigm, including basic neurotoxicology research, interlaboratory collaborative studies, expert workshops, and validation studies, and we address the relevance, applicability, and use of the DNT study in risk assessment. Conclusions The OECD DNT guideline represents the best available science for assessing the potential for DNT in human health risk assessment, and data generated with this protocol are relevant and reliable for the assessment of these end points. The test methods used have been subjected to an extensive history of international validation, peer review, and evaluation, which is contained in the public record. The reproducibility, reliability, and sensitivity of these methods have been demonstrated, using a wide variety of test substances, in accordance with OECD guidance on the validation and international acceptance of new or updated test methods for hazard characterization. Multiple independent, expert scientific peer reviews affirm these conclusions. PMID:19165382
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Carlier, Mieke; Stove, Veronique; Roberts, Jason A; Van de Velde, Eric; De Waele, Jan J; Verstraete, Alain G
2012-11-01
There is an increasing interest in monitoring plasma concentrations of β-lactam antibiotics. The objective of this work was to develop and validate a rapid ultra-performance liquid chromatographic method with tandem mass spectrometric detection (UPLC-MS/MS) for simultaneous quantification of amoxicillin, ampicillin, cefuroxime, cefazolin, ceftazidime, meropenem, piperacillin, clavulanic acid and tazobactam. Sample clean-up included protein precipitation with acetonitrile and back-extraction of acetonitrile with dichloromethane. Six deuterated β-lactam antibiotics were used as internal standards. Chromatographic separation was performed on a Waters ACQUITY UPLC system using a BEH C(18) column (1.7 μm, 100 mm×2.1 mm) applying a binary gradient elution of water and acetonitrile both containing 0.1% formic acid. The total run time was 5.5 min. The developed method was validated in terms of precision, accuracy, linearity, matrix effect and recovery. The assay has now been successfully used to determine concentrations of amoxicillin/clavulanic acid, cefuroxime and meropenem in plasma samples from intensive care patients. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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Attentional validity effect across the human menstrual cycle varies with basal temperature changes.
Beaudoin, Jessica; Marrocco, Richard
2005-03-07
This study examined the correlation between covert attention and basal temperature change during menstrual cycle phase in 22 adult females. Previous work showing beneficial effects of estrogen on working memory led us to hypothesize that attentional function would be facilitated at the apparent time of ovulation. Menstrual phase was determined through questionnaires and objective measurements of basal body temperature (BBT) spikes over a 1 month period. The cued target detection (CTD) task was used to assess visuospatial attentional performance at three times during the menstrual cycle. The mean reaction times (RTs) to visual targets were measured as a function of menstrual cycle phase, cue type and target location. As predicted, the onset of ovulation showed decreased reaction times and a significant increase in the cue validity effect on the days immediately preceding and following ovulation. The magnitude of the attention validity effect was negatively correlated with the basal temperature rise. Women lacking basal temperature shifts failed to show these changes. Results support the conclusion that the natural fluctuations of body temperature, and possibly reproductive hormones, during the menstrual cycle may enhance the attentional component of cognitive performance.
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Eckstein, Miguel P; Mack, Stephen C; Liston, Dorion B; Bogush, Lisa; Menzel, Randolf; Krauzlis, Richard J
2013-06-07
Visual attention is commonly studied by using visuo-spatial cues indicating probable locations of a target and assessing the effect of the validity of the cue on perceptual performance and its neural correlates. Here, we adapt a cueing task to measure spatial cueing effects on the decisions of honeybees and compare their behavior to that of humans and monkeys in a similarly structured two-alternative forced-choice perceptual task. Unlike the typical cueing paradigm in which the stimulus strength remains unchanged within a block of trials, for the monkey and human studies we randomized the contrast of the signal to simulate more real world conditions in which the organism is uncertain about the strength of the signal. A Bayesian ideal observer that weights sensory evidence from cued and uncued locations based on the cue validity to maximize overall performance is used as a benchmark of comparison against the three animals and other suboptimal models: probability matching, ignore the cue, always follow the cue, and an additive bias/single decision threshold model. We find that the cueing effect is pervasive across all three species but is smaller in size than that shown by the Bayesian ideal observer. Humans show a larger cueing effect than monkeys and bees show the smallest effect. The cueing effect and overall performance of the honeybees allows rejection of the models in which the bees are ignoring the cue, following the cue and disregarding stimuli to be discriminated, or adopting a probability matching strategy. Stimulus strength uncertainty also reduces the theoretically predicted variation in cueing effect with stimulus strength of an optimal Bayesian observer and diminishes the size of the cueing effect when stimulus strength is low. A more biologically plausible model that includes an additive bias to the sensory response from the cued location, although not mathematically equivalent to the optimal observer for the case stimulus strength uncertainty, can approximate the benefits of the more computationally complex optimal Bayesian model. We discuss the implications of our findings on the field's common conceptualization of covert visual attention in the cueing task and what aspects, if any, might be unique to humans. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Development and validation of a septoplasty training model using 3-dimensional printing technology.
AlReefi, Mahmoud A; Nguyen, Lily H P; Mongeau, Luc G; Haq, Bassam Ul; Boyanapalli, Siddharth; Hafeez, Nauman; Cegarra-Escolano, Francois; Tewfik, Marc A
2017-04-01
Providing alternative training modalities may improve trainees' ability to perform septoplasty. Three-dimensional printing has been shown to be a powerful tool in surgical training. The objectives of this study were to explain the development of our 3-dimensional (3D) printed septoplasty training model, to assess its face and content validity, and to present evidence supporting its ability to distinguish between levels of surgical proficiency. Imaging data of a patient with a nasal septal deviation was selected for printing. Printing materials reproducing the mechanical properties of human tissues were selected based on literature review and prototype testing. Eight expert rhinologists, 6 senior residents, and 6 junior residents performed endoscopic septoplasties on the model and completed a postsimulation survey. Performance metrics in quality (final product analysis), efficiency (time), and safety (eg, perforation length, nares damage) were recorded and analyzed in a study-blind manner. The model was judged to be anatomically correct and the steps performed realistic, with scores of 4.05 ± 0.82 and 4.2 ± 1, respectively, on a 5-point Likert scale. Ninety-two percent of residents desired the simulator to be integrated into their teaching curriculum. There was a significant difference (p < 0.05) between the expert, intermediate, and novice groups in time taken and nares cuts, whereas other performance metrics showed no significant difference. To our knowledge, there are no other simulator training models for septoplasty. Our model incorporates 2 different materials mixed into the 3 relevant consistencies necessary to simulate septoplasty. Our findings provide evidence supporting the validity of the model. © 2016 ARS-AAOA, LLC.
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Matejić, Bojana; Milenović, Miodrag; Kisić Tepavčević, Darija; Simić, Dušica; Pekmezović, Tatjana; Worley, Jody A.
2015-01-01
We report findings from a validation study of the translated and culturally adapted Serbian version of Maslach Burnout Inventory-Human Services Survey (MBI-HSS), for a sample of anesthesiologists working in the tertiary healthcare. The results showed the sufficient overall reliability (Cronbach's α = 0.72) of the scores (items 1–22). The results of Bartlett's test of sphericity (χ 2 = 1983.75, df = 231, p < 0.001) and Kaiser-Meyer-Olkin measure of sampling adequacy (0.866) provided solid justification for factor analysis. In order to increase sensitivity of this questionnaire, we performed unfitted factor analysis model (eigenvalue greater than 1) which enabled us to extract the most suitable factor structure for our study instrument. The exploratory factor analysis model revealed five factors with eigenvalues greater than 1.0, explaining 62.0% of cumulative variance. Velicer's MAP test has supported five-factor model with the smallest average squared correlation of 0,184. This study indicated that Serbian version of the MBI-HSS is a reliable and valid instrument to measure burnout among a population of anesthesiologists. Results confirmed strong psychometric characteristics of the study instrument, with recommendations for interpretation of two new factors that may be unique to the Serbian version of the MBI-HSS. PMID:26090517
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Hériché, Jean-Karim; Lees, Jon G.; Morilla, Ian; Walter, Thomas; Petrova, Boryana; Roberti, M. Julia; Hossain, M. Julius; Adler, Priit; Fernández, José M.; Krallinger, Martin; Haering, Christian H.; Vilo, Jaak; Valencia, Alfonso; Ranea, Juan A.; Orengo, Christine; Ellenberg, Jan
2014-01-01
The advent of genome-wide RNA interference (RNAi)–based screens puts us in the position to identify genes for all functions human cells carry out. However, for many functions, assay complexity and cost make genome-scale knockdown experiments impossible. Methods to predict genes required for cell functions are therefore needed to focus RNAi screens from the whole genome on the most likely candidates. Although different bioinformatics tools for gene function prediction exist, they lack experimental validation and are therefore rarely used by experimentalists. To address this, we developed an effective computational gene selection strategy that represents public data about genes as graphs and then analyzes these graphs using kernels on graph nodes to predict functional relationships. To demonstrate its performance, we predicted human genes required for a poorly understood cellular function—mitotic chromosome condensation—and experimentally validated the top 100 candidates with a focused RNAi screen by automated microscopy. Quantitative analysis of the images demonstrated that the candidates were indeed strongly enriched in condensation genes, including the discovery of several new factors. By combining bioinformatics prediction with experimental validation, our study shows that kernels on graph nodes are powerful tools to integrate public biological data and predict genes involved in cellular functions of interest. PMID:24943848
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Matejić, Bojana; Milenović, Miodrag; Kisić Tepavčević, Darija; Simić, Dušica; Pekmezović, Tatjana; Worley, Jody A
2015-01-01
We report findings from a validation study of the translated and culturally adapted Serbian version of Maslach Burnout Inventory-Human Services Survey (MBI-HSS), for a sample of anesthesiologists working in the tertiary healthcare. The results showed the sufficient overall reliability (Cronbach's α = 0.72) of the scores (items 1-22). The results of Bartlett's test of sphericity (χ(2) = 1983.75, df = 231, p < 0.001) and Kaiser-Meyer-Olkin measure of sampling adequacy (0.866) provided solid justification for factor analysis. In order to increase sensitivity of this questionnaire, we performed unfitted factor analysis model (eigenvalue greater than 1) which enabled us to extract the most suitable factor structure for our study instrument. The exploratory factor analysis model revealed five factors with eigenvalues greater than 1.0, explaining 62.0% of cumulative variance. Velicer's MAP test has supported five-factor model with the smallest average squared correlation of 0,184. This study indicated that Serbian version of the MBI-HSS is a reliable and valid instrument to measure burnout among a population of anesthesiologists. Results confirmed strong psychometric characteristics of the study instrument, with recommendations for interpretation of two new factors that may be unique to the Serbian version of the MBI-HSS.
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International Space Station Medical Project
NASA Technical Reports Server (NTRS)
Starkey, Blythe A.
2008-01-01
The goals and objectives of the ISS Medical Project (ISSMP) are to: 1) Maximize the utilization the ISS and other spaceflight platforms to assess the effects of longduration spaceflight on human systems; 2) Devise and verify strategies to ensure optimal crew performance; 3) Enable development and validation of a suite of integrated physical (e.g., exercise), pharmacologic and/or nutritional countermeasures against deleterious effects of space flight that may impact mission success or crew health. The ISSMP provides planning, integration, and implementation services for Human Research Program research tasks and evaluation activities requiring access to space or related flight resources on the ISS, Shuttle, Soyuz, Progress, or other spaceflight vehicles and platforms. This includes pre- and postflight activities; 2) ISSMP services include operations and sustaining engineering for HRP flight hardware; experiment integration and operation, including individual research tasks and on-orbit validation of next generation on-orbit equipment; medical operations; procedures development and validation; and crew training tools and processes, as well as operation and sustaining engineering for the Telescience Support Center; and 3) The ISSMP integrates the HRP approved flight activity complement and interfaces with external implementing organizations, such as the ISS Payloads Office and International Partners, to accomplish the HRP's objectives. This effort is led by JSC with Baseline Data Collection support from KSC.
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NASA Astrophysics Data System (ADS)
Marquet, F.; Pernot, M.; Aubry, J.-F.; Montaldo, G.; Marsac, L.; Tanter, M.; Fink, M.
2009-05-01
A non-invasive protocol for transcranial brain tissue ablation with ultrasound is studied and validated in vitro. The skull induces strong aberrations both in phase and in amplitude, resulting in a severe degradation of the beam shape. Adaptive corrections of the distortions induced by the skull bone are performed using a previous 3D computational tomography scan acquisition (CT) of the skull bone structure. These CT scan data are used as entry parameters in a FDTD (finite differences time domain) simulation of the full wave propagation equation. A numerical computation is used to deduce the impulse response relating the targeted location and the ultrasound therapeutic array, thus providing a virtual time-reversal mirror. This impulse response is then time-reversed and transmitted experimentally by a therapeutic array positioned exactly in the same referential frame as the one used during CT scan acquisitions. In vitro experiments are conducted on monkey and human skull specimens using an array of 300 transmit elements working at a central frequency of 1 MHz. These experiments show a precise refocusing of the ultrasonic beam at the targeted location with a positioning error lower than 0.7 mm. The complete validation of this transcranial adaptive focusing procedure paves the way to in vivo animal and human transcranial HIFU investigations.
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Measurement of the Robot Motor Capability of a Robot Motor System: A Fitts's-Law-Inspired Approach
Lin, Hsien-I; George Lee, C. S.
2013-01-01
Robot motor capability is a crucial factor for a robot, because it affects how accurately and rapidly a robot can perform a motion to accomplish a task constrained by spatial and temporal conditions. In this paper, we propose and derive a pseudo-index of motor performance (pIp) to characterize robot motor capability with robot kinematics, dynamics and control taken into consideration. The proposed pIp provides a quantitative measure for a robot with revolute joints, which is inspired from an index of performance in Fitts's law of human skills. Computer simulations and experiments on a PUMA 560 industrial robot were conducted to validate the proposed pIp for performing a motion accurately and rapidly. PMID:23820745
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Measurement of the robot motor capability of a robot motor system: a Fitts's-law-inspired approach.
Lin, Hsien-I; Lee, C S George
2013-07-02
Robot motor capability is a crucial factor for a robot, because it affects how accurately and rapidly a robot can perform a motion to accomplish a task constrained by spatial and temporal conditions. In this paper, we propose and derive a pseudo-index of motor performance (pIp) to characterize robot motor capability with robot kinematics, dynamics and control taken into consideration. The proposed pIp provides a quantitative measure for a robot with revolute joints, which is inspired from an index of performance in Fitts's law of human skills. Computer simulations and experiments on a PUMA 560 industrial robot were conducted to validate the proposed pIp for performing a motion accurately and rapidly.
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Ultrasensitive biomolecular assays with amplifying nanowire FET biosensors
NASA Astrophysics Data System (ADS)
Chui, Chi On; Shin, Kyeong-Sik; Mao, Yufei
2013-09-01
In this paper, we review our recent development and validation of the ultrasensitive electronic biomolecular assays enabled by our novel amplifying nanowire field-effect transistor (nwFET) biosensors. Our semiconductor nwFET biosensor platform technology performs extreme proximity signal amplification in the electrical domain that requires neither labeling nor enzymes nor optics. We have designed and fabricated the biomolecular assay prototypes and developed the corresponding analytical procedures. We have also confirmed their analytical performance in quantitating key protein biomarker in human serum, demonstrating an ultralow limit of detection and concurrently high output current level for the first time.
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Assessing Upper Extremity Motor Function in Practice of Virtual Activities of Daily Living
Adams, Richard J.; Lichter, Matthew D.; Krepkovich, Eileen T.; Ellington, Allison; White, Marga; Diamond, Paul T.
2015-01-01
A study was conducted to investigate the criterion validity of measures of upper extremity (UE) motor function derived during practice of virtual activities of daily living (ADLs). Fourteen hemiparetic stroke patients employed a Virtual Occupational Therapy Assistant (VOTA), consisting of a high-fidelity virtual world and a Kinect™ sensor, in four sessions of approximately one hour in duration. An Unscented Kalman Filter-based human motion tracking algorithm estimated UE joint kinematics in real-time during performance of virtual ADL activities, enabling both animation of the user’s avatar and automated generation of metrics related to speed and smoothness of motion. These metrics, aggregated over discrete sub-task elements during performance of virtual ADLs, were compared to scores from an established assessment of UE motor performance, the Wolf Motor Function Test (WMFT). Spearman’s rank correlation analysis indicates a moderate correlation between VOTA-derived metrics and the time-based WMFT assessments, supporting the criterion validity of VOTA measures as a means of tracking patient progress during an UE rehabilitation program that includes practice of virtual ADLs. PMID:25265612
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Assessing upper extremity motor function in practice of virtual activities of daily living.
Adams, Richard J; Lichter, Matthew D; Krepkovich, Eileen T; Ellington, Allison; White, Marga; Diamond, Paul T
2015-03-01
A study was conducted to investigate the criterion validity of measures of upper extremity (UE) motor function derived during practice of virtual activities of daily living (ADLs). Fourteen hemiparetic stroke patients employed a Virtual Occupational Therapy Assistant (VOTA), consisting of a high-fidelity virtual world and a Kinect™ sensor, in four sessions of approximately one hour in duration. An unscented Kalman Filter-based human motion tracking algorithm estimated UE joint kinematics in real-time during performance of virtual ADL activities, enabling both animation of the user's avatar and automated generation of metrics related to speed and smoothness of motion. These metrics, aggregated over discrete sub-task elements during performance of virtual ADLs, were compared to scores from an established assessment of UE motor performance, the Wolf Motor Function Test (WMFT). Spearman's rank correlation analysis indicates a moderate correlation between VOTA-derived metrics and the time-based WMFT assessments, supporting the criterion validity of VOTA measures as a means of tracking patient progress during an UE rehabilitation program that includes practice of virtual ADLs.
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NASA Astrophysics Data System (ADS)
Coyne, Kevin Anthony
The safe operation of complex systems such as nuclear power plants requires close coordination between the human operators and plant systems. In order to maintain an adequate level of safety following an accident or other off-normal event, the operators often are called upon to perform complex tasks during dynamic situations with incomplete information. The safety of such complex systems can be greatly improved if the conditions that could lead operators to make poor decisions and commit erroneous actions during these situations can be predicted and mitigated. The primary goal of this research project was the development and validation of a cognitive model capable of simulating nuclear plant operator decision-making during accident conditions. Dynamic probabilistic risk assessment methods can improve the prediction of human error events by providing rich contextual information and an explicit consideration of feedback arising from man-machine interactions. The Accident Dynamics Simulator paired with the Information, Decision, and Action in a Crew context cognitive model (ADS-IDAC) shows promise for predicting situational contexts that might lead to human error events, particularly knowledge driven errors of commission. ADS-IDAC generates a discrete dynamic event tree (DDET) by applying simple branching rules that reflect variations in crew responses to plant events and system status changes. Branches can be generated to simulate slow or fast procedure execution speed, skipping of procedure steps, reliance on memorized information, activation of mental beliefs, variations in control inputs, and equipment failures. Complex operator mental models of plant behavior that guide crew actions can be represented within the ADS-IDAC mental belief framework and used to identify situational contexts that may lead to human error events. This research increased the capabilities of ADS-IDAC in several key areas. The ADS-IDAC computer code was improved to support additional branching events and provide a better representation of the IDAC cognitive model. An operator decision-making engine capable of responding to dynamic changes in situational context was implemented. The IDAC human performance model was fully integrated with a detailed nuclear plant model in order to realistically simulate plant accident scenarios. Finally, the improved ADS-IDAC model was calibrated, validated, and updated using actual nuclear plant crew performance data. This research led to the following general conclusions: (1) A relatively small number of branching rules are capable of efficiently capturing a wide spectrum of crew-to-crew variabilities. (2) Compared to traditional static risk assessment methods, ADS-IDAC can provide a more realistic and integrated assessment of human error events by directly determining the effect of operator behaviors on plant thermal hydraulic parameters. (3) The ADS-IDAC approach provides an efficient framework for capturing actual operator performance data such as timing of operator actions, mental models, and decision-making activities.
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Strbac, Matija; Isakovic, Milica; Belic, Minja; Popovic, Igor; Simanic, Igor; Farina, Dario; Keller, Thierry; Dosen, Strahinja
2017-11-01
Human motor control relies on a combination of feedback and feedforward strategies. The aim of this study was to longitudinally investigate artificial somatosensory feedback and feedforward control in the context of grasping with myoelectric prosthesis. Nine amputee subjects performed routine grasping trials, with the aim to produce four levels of force during four blocks of 60 trials across five days. The electrotactile force feedback was provided in the second and third block using multipad electrode and spatial coding. The first baseline and last validation block (open-loop control) evaluated the effects of long- (across sessions) and short-term (within session) learning, respectively. The outcome measures were the absolute error between the generated and target force, and the number of force saturations. The results demonstrated that the electrotactile feedback improved the performance both within and across sessions. In the validation block, the performance did not significantly decrease and the quality of open-loop control (baseline) improved across days, converging to the performance characterizing closed-loop control. This paper provides important insights into the feedback and feedforward processes in prosthesis control, contributing to the better understanding of the role and design of feedback in prosthetic systems.
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Schoenly, Kenneth G; Haskell, Neal H; Hall, Robert D; Gbur, J Robert
2007-09-01
Comparative performance and complementarity tests of four arthropod sampling methods (aerial netting, hand collection, pitfall traps, and sticky traps), used by forensic entomologists in death investigations, training workshops, and research trials, were conducted from simultaneously placed human and porcine subjects inside the Forensic Anthropology Center at the University of Tennessee, Knoxville, TN. A secondary aim investigated the widely held claim that pig carcasses are reliable surrogates for human corpses. Over a 35-d period in summer 1989, >72,000 invertebrates from three subjects (one human, two pigs) were sampled of which 93% were members of the forensically important (FI) fauna. Performance tests revealed that hand collections, when performed by an experienced forensic entomologist, consistently yielded the largest fraction of FI arthropods from the total invertebrate catch, followed by aerial netting, sticky traps, and pitfall traps, regardless of subject. Pitfall traps and hand collections were broadly effective at sampling both fly and beetle populations, whereas aerial netting and sticky traps mostly targeted flies. The best two-method combination, based on the highest combined catches of FI taxa, were hand collections and pitfall traps, regardless of subject. Between-subject comparisons revealed negligible preference by FI arthropods for human over pig remains. Insofar as our limited comparisons allow with only three study subjects, these results validated the concept of transferability of "best practices" from one subject to another and confirmed the claim that pig carcasses (of 23-27-kg starting mass) can substitute for human corpses in research and training programs, at least for summer-exposed and unconcealed remains in the first 5 wk postmortem.
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Lee, Hye-In; Choi, Chang-Ik; Byeon, Ji-Yeong; Lee, Jung-Eun; Park, So-Young; Kim, Young-Hoon; Kim, Se-Hyung; Lee, Yun-Jeong; Jang, Choon-Gon; Lee, Seok-Yong
2014-11-15
Flurbiprofen (FLB) is one of the phenylalkanoic acid derivatives of non-steroidal anti-inflammatory drugs used for the management of pain and inflammation in patients with arthritis. We developed and validated a rapid and sensitive high-performance liquid chromatography analytical method utilizing tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of FLB and its major metabolite, 4'-hydroxyflurbiprofen (4'-OH-FLB), in human plasma. Probenecid was used as an internal standard (IS). After liquid-liquid extraction with methyl t-butyl ether, chromatographic separation of the two analytes was achieved using a reversed-phase Luna C18 column (2.0mm×50mm, 5μm particles) with a mobile phase of 10mM ammonium formate buffer (pH 3.5)-methanol (15:85, v/v) and quantified by MS/MS detection in ESI negative ion mode. The flow rate of the mobile phase was 250μl/min and the retention times of FLB, 4'-OH-FLB, and IS were 1.1, 0.8, and 0.9min, respectively. The calibration curves were linear over a range of 0.01-10μg/ml for FLB and 0.01-1μg/ml for 4'-OH-FLB. The lower limit of quantifications using 100μl of human plasma was 0.01μg/ml for both analytes. The mean accuracy and precision for intra- and inter-run validation of FLB and 4'-OH-FLB were all within acceptable limits. The present HPLC-MS/MS method showed improved sensitivity for quantification of the FLB and its major metabolite in human plasma compared with previously described analytical methods. The validated method was successfully applied to a pharmacokinetic study in humans. Copyright © 2014 Elsevier B.V. All rights reserved.
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NASA Astrophysics Data System (ADS)
Ercan, Ziya; Carvalho, Ashwin; Tseng, H. Eric; Gökaşan, Metin; Borrelli, Francesco
2018-05-01
Haptic shared control framework opens up new perspectives on the design and implementation of the driver steering assistance systems which provide torque feedback to the driver in order to improve safety. While designing such a system, it is important to account for the human-machine interactions since the driver feels the feedback torque through the hand wheel. The controller should consider the driver's impact on the steering dynamics to achieve a better performance in terms of driver's acceptance and comfort. In this paper we present a predictive control framework which uses a model of driver-in-the-loop steering dynamics to optimise the torque intervention with respect to the driver's neuromuscular response. We first validate the system in simulations to compare the performance of the controller in nominal and model mismatch cases. Then we implement the controller in a test vehicle and perform experiments with a human driver. The results show the effectiveness of the proposed system in avoiding hazardous situations under different driver behaviours.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ronald Boring; Roger Lew; Thomas Ulrich
2014-03-01
As control rooms are modernized with new digital systems at nuclear power plants, it is necessary to evaluate the operator performance using these systems as part of a verification and validation process. There are no standard, predefined metrics available for assessing what is satisfactory operator interaction with new systems, especially during the early design stages of a new system. This report identifies the process and metrics for evaluating human system interfaces as part of control room modernization. The report includes background information on design and evaluation, a thorough discussion of human performance measures, and a practical example of how themore » process and metrics have been used as part of a turbine control system upgrade during the formative stages of design. The process and metrics are geared toward generalizability to other applications and serve as a template for utilities undertaking their own control room modernization activities.« less
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An Investigation of Large Aircraft Handling Qualities
NASA Astrophysics Data System (ADS)
Joyce, Richard D.
An analytical technique for investigating transport aircraft handling qualities is exercised in a study using models of two such vehicles, a Boeing 747 and Lockheed C-5A. Two flight conditions are employed for climb and directional tasks, and a third included for a flare task. The analysis technique is based upon a "structural model" of the human pilot developed by Hess. The associated analysis procedure has been discussed previously in the literature, but centered almost exclusively on the characteristics of high-performance fighter aircraft. The handling qualities rating level (HQRL) and pilot induced oscillation tendencies rating level (PIORL) are predicted for nominal configurations of the aircraft and for "damaged" configurations where actuator rate limits are introduced as nonlinearites. It is demonstrated that the analysis can accommodate nonlinear pilot/vehicle behavior and do so in the context of specific flight tasks, yielding estimates of handling qualities, pilot-induced oscillation tendencies and upper limits of task performance. A brief human-in-the-loop tracking study was performed to provide a limited validation of the pilot model employed.
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Predicting the Operational Acceptability of Route Advisories
NASA Technical Reports Server (NTRS)
Evans, Antony; Lee, Paul
2017-01-01
NASA envisions a future Air Traffic Management system that allows safe, efficient growth in global operations, enabled by increasing levels of automation and autonomy. In a safety-critical system, the introduction of increasing automation and autonomy has to be done in stages, making human-system integrated concepts critical in the foreseeable future. One example where this is relevant is for tools that generate more efficient flight routings or reroute advisories. If these routes are not operationally acceptable, they will be rejected by human operators, and the associated benefits will not be realized. Operational acceptance is therefore required to enable the increased efficiency and reduced workload benefits associated with these tools. In this paper, the authors develop a predictor of operational acceptability for reroute advisories. Such a capability has applications in tools that identify more efficient routings around weather and congestion and that better meet airline preferences. The capability is based on applying data mining techniques to flight plan amendment data reported by the Federal Aviation Administration and data on requested reroutes collected from a field trial of the NASA developed Dynamic Weather Routes tool, which advised efficient route changes to American Airlines dispatchers in 2014. 10-Fold cross validation was used for feature, model and parameter selection, while nested cross validation was used to validate the model. The model performed well in predicting controller acceptance or rejection of a route change as indicated by chosen performance metrics. Features identified as relevant to controller acceptance included the historical usage of the advised route, the location of the maneuver start point relative to the boundaries of the airspace sector containing the maneuver start (the maneuver start sector), the reroute deviation from the original flight plan, and the demand level in the maneuver start sector. A random forest with forty trees was the best performing of the five models evaluated in this paper.
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Bismark, Andrew W; Thomas, Michael L; Tarasenko, Melissa; Shiluk, Alexandra L; Rackelmann, Sonia Y; Young, Jared W; Light, Gregory A
2018-04-12
Attentional dysfunction contributes to functional impairments in schizophrenia (SZ). Sustained attention is typically assessed via continuous performance tasks (CPTs), though many CPTs have limited cross-species translational validity and place demands on additional cognitive domains. A reverse-translated 5-Choice Continuous Performance Task (5C-CPT) for human testing-originally developed for use in rodents-was designed to minimize demands on perceptual, visual learning, processing speed, or working memory functions. To-date, no studies have validated the 5C-CPT against gold standard attentional measures nor evaluated how 5C-CPT scores relate to cognition in SZ. Here we examined the relationship between the 5C-CPT and the CPT-Identical Pairs (CPT-IP), an established and psychometrically robust measure of vigilance from the MATRICS Consensus Cognitive Battery (MCCB) in a sample of SZ patients (n = 35). Relationships to global and individual subdomains of cognition were also assessed. 5C-CPT and CPT-IP measures of performance (d-prime) were strongly correlated (r = 0.60). In a regression model, the 5C-CPT and CPT-IP collectively accounted for 54% of the total variance in MCCB total scores, and 27.6% of overall cognitive variance was shared between the 5C-CPT and CPT-IP. These results indicate that the reverse translated 5C-CPT and the gold standard CPT-IP index a common attentional construct that also significantly overlaps with variance in general cognitive performance. The use of simple, cross-species validated behavioral indices of attentional/cognitive functioning such as the 5C-CPT could accelerate the development of novel generalized pro-cognitive therapeutics for SZ and related neuropsychiatric disorders.
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Attention in aviation. [to aircraft design and pilot performance
NASA Technical Reports Server (NTRS)
Wickens, Christopher D.
1987-01-01
The relevance of four principles or mechanisms of human attention to the design of aviation systems and the performance of pilots in multitask environments, including workload prediction and measurement, control-display integration, and the use of voice and head-up displays is discussed. The principles are: the mental energy that supplies task performance (resources), the resulting cross-talk between tasks as they are made more similar (confusion), the combination of different task elements (integration), and the way in which one task is processed and another is ignored (selection or tunneling). The introduction of greater levels of complexity into the validation of attentional theories in order to approach the demands of the cockpit or ATC console is proposed.
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Control Design and Performance Analysis for Autonomous Formation Flight Experimentss
NASA Astrophysics Data System (ADS)
Rice, Caleb Michael
Autonomous Formation Flight is a key approach for reducing greenhouse gas emissions and managing traffic in future high density airspace. Unmanned Aerial Vehicles (UAV's) have made it possible for the physical demonstration and validation of autonomous formation flight concepts inexpensively and eliminates the flight risk to human pilots. This thesis discusses the design, implementation, and flight testing of three different formation flight control methods, Proportional Integral and Derivative (PID); Fuzzy Logic (FL); and NonLinear Dynamic Inversion (NLDI), and their respective performance behavior. Experimental results show achievable autonomous formation flight and performance quality with a pair of low-cost unmanned research fixed wing aircraft and also with a solo vertical takeoff and landing (VTOL) quadrotor.
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Groeber, F; Schober, L; Schmid, F F; Traube, A; Kolbus-Hernandez, S; Daton, K; Hoffmann, S; Petersohn, D; Schäfer-Korting, M; Walles, H; Mewes, K R
2016-10-01
To replace the Draize skin irritation assay (OECD guideline 404) several test methods based on reconstructed human epidermis (RHE) have been developed and were adopted in the OECD test guideline 439. However, all validated test methods in the guideline are linked to RHE provided by only three companies. Thus, the availability of these test models is dependent on the commercial interest of the producer. To overcome this limitation and thus to increase the accessibility of in vitro skin irritation testing, an open source reconstructed epidermis (OS-REp) was introduced. To demonstrate the capacity of the OS-REp in regulatory risk assessment, a catch-up validation study was performed. The participating laboratories used in-house generated OS-REp to assess the set of 20 reference substances according to the performance standards amending the OECD test guideline 439. Testing was performed under blinded conditions. The within-laboratory reproducibility of 87% and the inter-laboratory reproducibility of 85% prove a high reliability of irritancy testing using the OS-REp protocol. In addition, the prediction capacity was with an accuracy of 80% comparable to previous published RHE based test protocols. Taken together the results indicate that the OS-REp test method can be used as a standalone alternative skin irritation test replacing the OECD test guideline 404. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
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The Benefit of Attention-to-Memory Depends on the Interplay of Memory Capacity and Memory Load
Lim, Sung-Joo; Wöstmann, Malte; Geweke, Frederik; Obleser, Jonas
2018-01-01
Humans can be cued to attend to an item in memory, which facilitates and enhances the perceptual precision in recalling this item. Here, we demonstrate that this facilitating effect of attention-to-memory hinges on the overall degree of memory load. The benefit an individual draws from attention-to-memory depends on her overall working memory performance, measured as sensitivity (d′) in a retroactive cue (retro-cue) pitch discrimination task. While listeners maintained 2, 4, or 6 auditory syllables in memory, we provided valid or neutral retro-cues to direct listeners’ attention to one, to-be-probed syllable in memory. Participants’ overall memory performance (i.e., perceptual sensitivity d′) was relatively unaffected by the presence of valid retro-cues across memory loads. However, a more fine-grained analysis using psychophysical modeling shows that valid retro-cues elicited faster pitch-change judgments and improved perceptual precision. Importantly, as memory load increased, listeners’ overall working memory performance correlated with inter-individual differences in the degree to which precision improved (r = 0.39, p = 0.029). Under high load, individuals with low working memory profited least from attention-to-memory. Our results demonstrate that retrospective attention enhances perceptual precision of attended items in memory but listeners’ optimal use of informative cues depends on their overall memory abilities. PMID:29520246
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Station Commander Job Analysis and Preliminary Test Validation Results
2005-10-01
Patrick W . Connell Personnel Decisions Research Institutes, Inc. Leonard A. White U.S. Army Research Institute Valentina B. Bruk-Lee, Lisa M. Penney, Walter ...of a "hyperdimensional" taxonomy of managerial competence. Human Performance, 13(3), 205-251. Tornow , W . W ., & Pinto, P. R. (1976). The development...5c. PROJECT NUMBER Kristen E. Horgen, U. Christean Kubisiak, Patrick W . A790 Connell (Personnel Decisions Research Institutes, Inc.); 5d. TASK NUMBER
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Primary Blast Injury Criteria for Animal/Human TBI Models using Field Validated Shock Tubes
2017-09-01
differential pathological response, which depends on the local tissue composition, and the response is to insult depends upon the cell type. regions...Neuroinflammation A single blast induces cell-type dependent increase in NADPH oxidase isoforms We have performed characterization of the spatial variations and...uniformly distribute and affect the whole brain. However, pathophysiological outcomes (e.g., NOX changes) in response to bTBI depend on the differential
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Little, K; Lu, Z; MacMahon, H
Purpose: To investigate the effect of varying system image processing parameters on lung nodule detectability in digital radiography. Methods: An anthropomorphic chest phantom was imaged in the posterior-anterior position using a GE Discovery XR656 digital radiography system. To simulate lung nodules, a polystyrene board with 6.35mm diameter PMMA spheres was placed adjacent to the phantom (into the x-ray path). Due to magnification, the projected simulated nodules had a diameter in the radiographs of approximately 7.5 mm. The images were processed using one of GE’s default chest settings (Factory3) and reprocessed by varying the “Edge” and “Tissue Contrast” processing parameters, whichmore » were the two user-configurable parameters for a single edge and contrast enhancement algorithm. For each parameter setting, the nodule signals were calculated by subtracting the chest-only image from the image with simulated nodules. Twenty nodule signals were averaged, Gaussian filtered, and radially averaged in order to generate an approximately noiseless signal. For each processing parameter setting, this noise-free signal and 180 background samples from across the lung were used to estimate ideal observer performance in a signal-known-exactly detection task. Performance was estimated using a channelized Hotelling observer with 10 Laguerre-Gauss channel functions. Results: The “Edge” and “Tissue Contrast” parameters each had an effect on the detectability as calculated by the model observer. The CHO-estimated signal detectability ranged from 2.36 to 2.93 and was highest for “Edge” = 4 and “Tissue Contrast” = −0.15. In general, detectability tended to decrease as “Edge” was increased and as “Tissue Contrast” was increased. A human observer study should be performed to validate the relation to human detection performance. Conclusion: Image processing parameters can affect lung nodule detection performance in radiography. While validation with a human observer study is needed, model observer detectability for common tasks could provide a means for optimizing image processing parameters.« less
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Developing operator capacity estimates for supervisory control of autonomous vehicles.
Cummings, M L; Guerlain, Stephanie
2007-02-01
This study examined operators' capacity to successfully reallocate highly autonomous in-flight missiles to time-sensitive targets while performing secondary tasks of varying complexity. Regardless of the level of autonomy for unmanned systems, humans will be necessarily involved in the mission planning, higher level operation, and contingency interventions, otherwise known as human supervisory control. As a result, more research is needed that addresses the impact of dynamic decision support systems that support rapid planning and replanning in time-pressured scenarios, particularly on operator workload. A dual screen simulation that allows a single operator the ability to monitor and control 8, 12, or 16 missiles through high level replanning was tested on 42 U.S. Navy personnel. The most significant finding was that when attempting to control 16 missiles, participants' performance on three separate objective performance metrics and their situation awareness were significantly degraded. These results mirror studies of air traffic control that demonstrate a similar decline in performance for controllers managing 17 aircraft as compared with those managing only 10 to 11 aircraft. Moreover, the results suggest that a 70% utilization (percentage busy time) score is a valid threshold for predicting significant performance decay and could be a generalizable metric that can aid in manning predictions. This research is relevant to human supervisory control of networked military and commercial unmanned vehicles in the air, on the ground, and on and under the water.
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NASA Astrophysics Data System (ADS)
Cha, Seung-Woo; Kang, Seok-Rae; Hwang, Yong-Hoon; Oh, Jong-Seok; Choi, Seung-Bok
2018-06-01
This paper proposes a new tactile device to realize the force of human-like organs using the viscoelastic property by combing a smart magneto-rheological (MR) fluid with a sponge (MR sponge in short). The effectiveness of the sensor is validated through the comparison of the force obtained through measurement and the proposed prediction model. As the first step, a conventional standard linear solid model is adopted to independently investigate the force characteristics of MR fluid and sponge. Force is measured using a 3-axis robot with a force sensor to obtain certain properties of MR fluid and sponge. In addition, to show that the proposed MR sponge can realize the force of human-like tissues, experiments are performed using three specimens, i.e., porcine heart, lung, and liver. Subsequently, a quasi-static model for predicting the field-dependent force of the MR sponge is formulated using empirical values. It is demonstrated through comparison that the proposed force model can accurately predict the force of the specimens without significant error. In addition, a psychophysical test is carried out by ordinary subjects to validate the effectiveness of the proposed tactile device. Results show that the MR sponge tactile device can easily produce various levels of the force of human-like tissues, such as the liver and lung of the porcine, by controlling input current.
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Face and Construct Validation of a Virtual Peg Transfer Simulator
Arikatla, Venkata S; Sankaranarayanan, Ganesh; Ahn, Woojin; Chellali, Amine; De, Suvranu; Caroline, GL; Hwabejire, John; DeMoya, Marc; Schwaitzberg, Steven; Jones, Daniel B.
2013-01-01
Background The Fundamentals of Laparascopic Surgery (FLS) trainer box is now established as a standard for evaluating minimally invasive surgical skills. A particularly simple task in this trainer box is the peg transfer task which is aimed at testing the surgeon’s bimanual dexterity, hand-eye coordination, speed and precision. The Virtual Basic Laparoscopic Skill Trainer (VBLaST©) is a virtual version of the FLS tasks which allows automatic scoring and real time, subjective quantification of performance without the need of a human proctor. In this paper we report validation studies of the VBLaST© peg transfer (VBLaST-PT©) simulator. Methods Thirty-five subjects with medical background were divided into two groups: experts (PGY 4-5, fellows and practicing surgeons) and novices (PGY 1-3). The subjects were asked to perform the peg transfer task on both the FLS trainer box and the VBLaST-PT© simulator and their performance was evaluated based on established metrics of error and time. A new length of trajectory (LOT) metric has also been introduced for offline analysis. A questionnaire was used to rate the realism of the virtual system on a 5-point Likert scale. Results Preliminary face validation of the VBLaST-PT© with 34 subjects rated on a 5-point Likert scale questionnaire revealed high scores for all aspects of simulation, with 3.53 being the lowest mean score across all questions. A two-tailed Mann-Whitney performed on the total scores showed significant (p=0.001) difference between the groups. A similar test performed on the task time (p=0.002) and the length of trajectory (p=0.004) separately showed statistically significant differences between the experts and novice groups (p<0.05). The experts appear to be traversing shorter overall trajectories in less time than the novices. Conclusion VBLaST-PT© showed both face and construct validity and has promise as a substitute for the FLS to training peg transfer skills. PMID:23263645
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A new method for quasi-reagent-free biomonitoring of mercury in human urine.
Schlathauer, Maria; Reitsam, Verena; Schierl, Rudolf; Leopold, Kerstin
2017-05-01
A novel analytical method for sampling and extraction of mercury (Hg) from human urine is presented in this work. The method is based on selective accumulation and separation of Hg from fresh urine sample onto active nanogold-coated silica material by highly efficient solid-phase extraction. After thermal desorption of Hg from the extractant, detection is performed by atomic fluorescence spectrometry (AFS). The feasibility and validity of the optimized, quasi-reagent-free approach was confirmed by recovery experiments in spiked real urine (recovery rate 96.13 ± 5.34%) and by comparison of found Hg concentrations in real urine samples - originating from occupationally exposed persons - with values obtained from reference methods cold vapor - atomic absorption spectrometry (CVAAS) and cold vapor - atomic fluorescence spectrometry (CV-AFS). A very good agreement of the found values reveals the validity of the proposed approach. The limit of detection (LOD) was found to be as low as 0.004 μg Hg L -1 and a high reproducibility with a relative standard deviations ≤4.2% (n = 6) is given. Moreover, storage of the samples for up to one week at an ambient temperature of 30 °C reveals no analyte losses or contamination. In conclusion, the proposed method enables easy-to-handle on-site extraction of total Hg from human urine ensuring at the same time reagent-free sample stabilization, providing quick and safe sampling, which can be performed by untrained persons. Copyright © 2017 Elsevier B.V. All rights reserved.
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Becker, Anton S; Mueller, Michael; Stoffel, Elina; Marcon, Magda; Ghafoor, Soleen; Boss, Andreas
2018-02-01
To train a generic deep learning software (DLS) to classify breast cancer on ultrasound images and to compare its performance to human readers with variable breast imaging experience. In this retrospective study, all breast ultrasound examinations from January 1, 2014 to December 31, 2014 at our institution were reviewed. Patients with post-surgical scars, initially indeterminate, or malignant lesions with histological diagnoses or 2-year follow-up were included. The DLS was trained with 70% of the images, and the remaining 30% were used to validate the performance. Three readers with variable expertise also evaluated the validation set (radiologist, resident, medical student). Diagnostic accuracy was assessed with a receiver operating characteristic analysis. 82 patients with malignant and 550 with benign lesions were included. Time needed for training was 7 min (DLS). Evaluation time for the test data set were 3.7 s (DLS) and 28, 22 and 25 min for human readers (decreasing experience). Receiver operating characteristic analysis revealed non-significant differences (p-values 0.45-0.47) in the area under the curve of 0.84 (DLS), 0.88 (experienced and intermediate readers) and 0.79 (inexperienced reader). DLS may aid diagnosing cancer on breast ultrasound images with an accuracy comparable to radiologists, and learns better and faster than a human reader with no prior experience. Further clinical trials with dedicated algorithms are warranted. Advances in knowledge: DLS can be trained classify cancer on breast ultrasound images high accuracy even with comparably few training cases. The fast evaluation speed makes real-time image analysis feasible.
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Wijemanne, Nimanthi; Soysa, Preethi; Wijesundara, Sulochana; Perera, Hemamali
2018-01-01
Uric acid and hypoxanthine are produced in the catabolism of purine. Abnormal urinary levels of these products are associated with many diseases and therefore it is necessary to have a simple and rapid method to detect them. Hence, we report a simple reverse phase high performance liquid chromatography (HPLC/UV) technique, developed and validated for simultaneous analysis of uric acid, hypoxanthine, and creatinine in human urine. Urine was diluted appropriately and eluted with C-18 column 100 mm × 4.6 mm with a C-18 precolumn 25 mm × 4.6 mm in series. Potassium phosphate buffer (20 mM, pH 7.25) at a flow rate of 0.40 mL/min was employed as the solvent and peaks were detected at 235 nm. Tyrosine was used as the internal standard. The experimental conditions offered a good separation of analytes without interference of endogenous substances. The calibration curves were linear for all test compounds with a regression coefficient, r 2 > 0.99. Uric acid, creatinine, tyrosine, and hypoxanthine were eluted at 5.2, 6.1, 7.2, and 8.3 min, respectively. Intraday and interday variability were less than 4.6% for all the analytes investigated and the recovery ranged from 98 to 102%. The proposed HPLC procedure is a simple, rapid, and low cost method with high accuracy with minimum use of organic solvents. This method was successfully applied for the determination of creatinine, hypoxanthine, and uric acid in human urine.
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Changes in blood volume and response to vaso-active drugs in horizontally casted primates
NASA Technical Reports Server (NTRS)
Dickey, D. T.; Teoh, K. K.; Sandler, H.; Stone, H. L.
1982-01-01
Experiments were performed on horizontally casted primates (male rhesus monkeys) in order to note changes in blood volume caused by horizontal restraint, to compare orthostatic tolerance before and after casting using the responses to upright tilting, to begin to uncover the cardiovascular and neural mechanisms involved in deconditioning, and to compare the data with that obtained from bed-rested human subjects and from humans exposed to weightlessness. Bolus injections of norepinephrine of 2.0 microgram/kg, phenylephrine of 4.0 microgram/kg, and nitroprusside of 2.0 microgram/kg were administered; and aortic pressure and heart rate were recorded during the injections. The results indicate that the horizontally casted primate is a valid animal model for studying the effects of simulated zero-G on the human cardiovascular system.
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Model-Based Reinforcement of Kinect Depth Data for Human Motion Capture Applications
Calderita, Luis Vicente; Bandera, Juan Pedro; Bustos, Pablo; Skiadopoulos, Andreas
2013-01-01
Motion capture systems have recently experienced a strong evolution. New cheap depth sensors and open source frameworks, such as OpenNI, allow for perceiving human motion on-line without using invasive systems. However, these proposals do not evaluate the validity of the obtained poses. This paper addresses this issue using a model-based pose generator to complement the OpenNI human tracker. The proposed system enforces kinematics constraints, eliminates odd poses and filters sensor noise, while learning the real dimensions of the performer's body. The system is composed by a PrimeSense sensor, an OpenNI tracker and a kinematics-based filter and has been extensively tested. Experiments show that the proposed system improves pure OpenNI results at a very low computational cost. PMID:23845933
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Feldsine, Philip; Kaur, Mandeep; Shah, Khyati; Immerman, Amy; Jucker, Markus; Lienau, Andrew
2015-01-01
Assurance GDSTM for Salmonella Tq has been validated according to the AOAC INTERNATIONAL Methods Committee Guidelines for Validation of Microbiological Methods for Food and Environmental Surfaces for the detection of selected foods and environmental surfaces (Official Method of AnalysisSM 2009.03, Performance Tested MethodSM No. 050602). The method also completed AFNOR validation (following the ISO 16140 standard) compared to the reference method EN ISO 6579. For AFNOR, GDS was given a scope covering all human food, animal feed stuff, and environmental surfaces (Certificate No. TRA02/12-01/09). Results showed that Assurance GDS for Salmonella (GDS) has high sensitivity and is equivalent to the reference culture methods for the detection of motile and non-motile Salmonella. As part of the aforementioned validations, inclusivity and exclusivity studies, stability, and ruggedness studies were also conducted. Assurance GDS has 100% inclusivity and exclusivity among the 100 Salmonella serovars and 35 non-Salmonella organisms analyzed. To add to the scope of the Assurance GDS for Salmonella method, a matrix extension study was conducted, following the AOAC guidelines, to validate the application of the method for selected spices, specifically curry powder, cumin powder, and chili powder, for the detection of Salmonella.
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Baietto, Lorena; D'Avolio, Antonio; Marra, Cristina; Simiele, Marco; Cusato, Jessica; Pace, Simone; Ariaudo, Alessandra; De Rosa, Francesco Giuseppe; Di Perri, Giovanni
2012-11-01
Therapeutic drug monitoring (TDM) of triazoles is widely used in clinical practice to optimize therapy. TDM is limited by technical problems and cost considerations, such as sample storage and dry-ice shipping. We aimed to develop and validate a new method to analyse itraconazole, posaconazole and voriconazole in plasma spotted on dry sample spot devices (DSSDs) and to quantify them by an HPLC system. Extraction from DSSDs was done using n-hexane/ethyl acetate and ammonia solution. Samples were analysed using HPLC with mass spectrometry (HPLC-MS). Accuracy and precision were assayed by inter- and intra-day validation. The stability of triazoles in plasma spotted on DSSDs was investigated at room temperature for 1 month. The method was compared with a validated standard HPLC method for quantification of triazoles in human plasma. Mean inter- and intra-day accuracy and precision were <15% for all compounds. Triazoles were stable for 2 weeks at room temperature. The method was linear (r(2) > 0.999) in the range 0.031-8 mg/L for itraconazole and posaconazole, and 0.058-15 mg/L for voriconazole. High sensitivity was observed; limits of detection were 0.008, 0.004 and 0.007 mg/L for itraconazole, posaconazole and voriconazole, respectively. A high degree of correlation (r(2) > 0.94) was obtained between the DSSD method and the standard method of analysis. The method that we developed and validated to quantify triazoles in human plasma spotted on DSSDs is accurate and precise. It overcomes problems related to plasma sample storage and shipment, allowing TDM to be performed in a cheaper and safer manner.
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Vathipadiekal, Vinod; Wang, Victoria; Wei, Wei; Waldron, Levi; Drapkin, Ronny; Gillette, Michael; Skates, Steven; Birrer, Michael
2015-11-01
To generate a comprehensive "Secretome" of proteins potentially found in the blood and derive a virtual Affymetrix array. To validate the utility of this database for the discovery of novel serum-based biomarkers using ovarian cancer transcriptomic data. The secretome was constructed by aggregating the data from databases of known secreted proteins, transmembrane or membrane proteins, signal peptides, G-protein coupled receptors, or proteins existing in the extracellular region, and the virtual array was generated by mapping them to Affymetrix probeset identifiers. Whole-genome microarray data from ovarian cancer, normal ovarian surface epithelium, and fallopian tube epithelium were used to identify transcripts upregulated in ovarian cancer. We established the secretome from eight public databases and a virtual array consisting of 16,521 Affymetrix U133 Plus 2.0 probesets. Using ovarian cancer transcriptomic data, we identified candidate blood-based biomarkers for ovarian cancer and performed bioinformatic validation by demonstrating rediscovery of known biomarkers including CA125 and HE4. Two novel top biomarkers (FGF18 and GPR172A) were validated in serum samples from an independent patient cohort. We present the secretome, comprising the most comprehensive resource available for protein products that are potentially found in the blood. The associated virtual array can be used to translate gene-expression data into cancer biomarker discovery. A list of blood-based biomarkers for ovarian cancer detection is reported and includes CA125 and HE4. FGF18 and GPR172A were identified and validated by ELISA as being differentially expressed in the serum of ovarian cancer patients compared with controls. ©2015 American Association for Cancer Research.
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Gross, S; Janssen, S W J; de Vries, B; Terao, E; Daas, A; Buchheit, K-H
2009-10-01
The European Pharmacopoeia (Ph. Eur.) monograph Human tetanus immunoglobulin (0398) gives a clear outline of the in vivo assay to be performed to determine the potency of human tetanus immunoglobulins during their development. Furthermore, it states that an in vitro method shall be validated for the batch potency estimation. Since no further guidance is given on the in vitro assay, every control laboratory concerned is free to design and validate an in-house method. At the moment there is no agreed in vitro method available. The aim of this study was to validate and compare 2 alternative in vitro assays, i.e. an enzyme-linked immunoassay (EIA) and a toxoid inhibition assay (TIA), through an international collaborative study, in view of their eventual inclusion into the Ph. Eur.. The study was run in the framework of the Biological Standardisation Programme (BSP), under the aegis of the European Commission and the Council of Europe. The collaborative study reported here involved 21 laboratories (public and industry) from 15 countries. Initially, 3 samples with low, medium and high potencies were tested by EIA and TIA. Results showed good reproducibility and repeatability of the 2 in vitro methods. The correlation of the data with the in vivo potency assigned by the manufacturers however appeared initially poor for high potency samples. Thorough re-examination of the data showed that the in vivo potencies assigned by the manufacturers had to be corrected: one for potency loss at the time of in vitro testing and one because of a reporting error. After these corrections the values obtained by in vivo and in vitro methods were in close agreement. A supplementary collaborative work was carried out to validate the 2 methods for immunoglobulin products with high potencies. Eight laboratories (public and industry) took part in this additional study to test 3 samples with medium and high potencies by EIA and TIA. Results confirmed that the 2 alternative methods are comparable in terms of assay repeatability, precision and reproducibility. In all laboratories, both methods discriminated between the low, medium and high potency samples. Analysis of the data collected in this study showed a good correlation between EIA and TIA potency estimates as well as a close agreement between values obtained by in vitro and in vivo methods. The study demonstrated that EIA and TIA are suitable quality control methods for polyclonal human tetanus immunoglobulin, which can be standardised in a quality control laboratory using a quality assurance system. Consequently, the Ph. Eur. Group of Experts 6B on Human Blood and Blood products decided in April 2009 to include both methods as examples in the Ph. Eur. monograph 0398 on Human Tetanus immunoglobulin.
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Luo, Heng; Ye, Hao; Ng, Hui; Shi, Leming; Tong, Weida; Mattes, William; Mendrick, Donna; Hong, Huixiao
2015-01-01
As the major histocompatibility complex (MHC), human leukocyte antigens (HLAs) are one of the most polymorphic genes in humans. Patients carrying certain HLA alleles may develop adverse drug reactions (ADRs) after taking specific drugs. Peptides play an important role in HLA related ADRs as they are the necessary co-binders of HLAs with drugs. Many experimental data have been generated for understanding HLA-peptide binding. However, efficiently utilizing the data for understanding and accurately predicting HLA-peptide binding is challenging. Therefore, we developed a network analysis based method to understand and predict HLA-peptide binding. Qualitative Class I HLA-peptide binding data were harvested and prepared from four major databases. An HLA-peptide binding network was constructed from this dataset and modules were identified by the fast greedy modularity optimization algorithm. To examine the significance of signals in the yielded models, the modularity was compared with the modularity values generated from 1,000 random networks. The peptides and HLAs in the modules were characterized by similarity analysis. The neighbor-edges based and unbiased leverage algorithm (Nebula) was developed for predicting HLA-peptide binding. Leave-one-out (LOO) validations and two-fold cross-validations were conducted to evaluate the performance of Nebula using the constructed HLA-peptide binding network. Nine modules were identified from analyzing the HLA-peptide binding network with a highest modularity compared to all the random networks. Peptide length and functional side chains of amino acids at certain positions of the peptides were different among the modules. HLA sequences were module dependent to some extent. Nebula archived an overall prediction accuracy of 0.816 in the LOO validations and average accuracy of 0.795 in the two-fold cross-validations and outperformed the method reported in the literature. Network analysis is a useful approach for analyzing large and sparse datasets such as the HLA-peptide binding dataset. The modules identified from the network analysis clustered peptides and HLAs with similar sequences and properties of amino acids. Nebula performed well in the predictions of HLA-peptide binding. We demonstrated that network analysis coupled with Nebula is an efficient approach to understand and predict HLA-peptide binding interactions and thus, could further our understanding of ADRs.
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2015-01-01
Background As the major histocompatibility complex (MHC), human leukocyte antigens (HLAs) are one of the most polymorphic genes in humans. Patients carrying certain HLA alleles may develop adverse drug reactions (ADRs) after taking specific drugs. Peptides play an important role in HLA related ADRs as they are the necessary co-binders of HLAs with drugs. Many experimental data have been generated for understanding HLA-peptide binding. However, efficiently utilizing the data for understanding and accurately predicting HLA-peptide binding is challenging. Therefore, we developed a network analysis based method to understand and predict HLA-peptide binding. Methods Qualitative Class I HLA-peptide binding data were harvested and prepared from four major databases. An HLA-peptide binding network was constructed from this dataset and modules were identified by the fast greedy modularity optimization algorithm. To examine the significance of signals in the yielded models, the modularity was compared with the modularity values generated from 1,000 random networks. The peptides and HLAs in the modules were characterized by similarity analysis. The neighbor-edges based and unbiased leverage algorithm (Nebula) was developed for predicting HLA-peptide binding. Leave-one-out (LOO) validations and two-fold cross-validations were conducted to evaluate the performance of Nebula using the constructed HLA-peptide binding network. Results Nine modules were identified from analyzing the HLA-peptide binding network with a highest modularity compared to all the random networks. Peptide length and functional side chains of amino acids at certain positions of the peptides were different among the modules. HLA sequences were module dependent to some extent. Nebula archived an overall prediction accuracy of 0.816 in the LOO validations and average accuracy of 0.795 in the two-fold cross-validations and outperformed the method reported in the literature. Conclusions Network analysis is a useful approach for analyzing large and sparse datasets such as the HLA-peptide binding dataset. The modules identified from the network analysis clustered peptides and HLAs with similar sequences and properties of amino acids. Nebula performed well in the predictions of HLA-peptide binding. We demonstrated that network analysis coupled with Nebula is an efficient approach to understand and predict HLA-peptide binding interactions and thus, could further our understanding of ADRs. PMID:26424483
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Thompson, S; Smith, M T
1985-11-01
It has been previously reported that the main diene-conjugated fatty acid in human plasma is a non-oxygen containing linoleic acid isomer (PL-9, 11-LA'). It has also been proposed that this isomer can be used as a specific marker of free radical-mediated lipid peroxidation in humans. Here we report that the in vitro induction of lipid peroxidation in human and rat blood with either UV irradiation or phenylhydrazine failed to increase the plasma levels of this isomer. The induction of lipid peroxidation in vivo in rats pretreated with either phenylhydrazine or bromotrichloromethane also failed to increase the plasma levels of this isomer. These findings demonstrate that PL-9, 11-LA' cannot be used as an in vivo marker of free radical-mediated lipid peroxidation in rats and casts doubts on its validity as a specific marker in humans.