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Sample records for identify predictive surrogate

  1. Multiple surrogates for prediction and optimization

    NASA Astrophysics Data System (ADS)

    Viana, Felipe A. C.

    2011-12-01

    Statistical modeling of computer experiments embraces the set of methodologies for generating a surrogate model (also known as metamodel or response surface approximation) used to replace an expensive simulation code. The aim of surrogate modeling is to construct an approximation of a response of interest based on a limited number of expensive simulations. Nevertheless, after years of intensive research on the field, surrogate-based analysis and optimization is still a struggle to achieve maximum accuracy for a given number of simulations. In this dissertation, we have taken advantage of multiple surrogates to address the issues that we face when we (i) want to build an accurate surrogate model under limited computational budget, (ii) use the surrogate for constrained optimization and the exact analysis shows that the solution is infeasible, and (iii) use the surrogate for global optimization and do not know where to place a set of points in which we are most likely to have improvement. In terms of prediction accuracy, we have found that multiple surrogates work as insurance against poorly fitted models. Additionally, we propose the use of safety margins to conservatively compensate for fitting errors associated with surrogates. We were able to estimate the safety margin for a specific conservativeness level, and we found that it is possible to select a surrogate with the best compromise between conservativeness and loss of accuracy. In terms of optimization, we proposed two strategies for enabling surrogate-based global optimization with parallel function evaluations. The first one is based on the simultaneous use of multiple surrogates (a set of surrogates collaboratively provide multiple points). The second strategy uses a single surrogate and one cheap to evaluate criterion (probability of improvement) for multiple point selection approximation. In both cases, we found that we could successfully speed up the optimization convergence without clear penalties as

  2. APPLICATION OF A TIERED SURROGATE APPROACH TO IDENTIFY TOXICITY SURROGATES FOR HUMAN HEALTH RISK ASSESSMENT

    EPA Science Inventory

    APPLICATION OF A TIERED SURROGATE APPROACH TO IDENTIFY TOXICITY SURROGATES FOR HUMAN HEALTH RISK ASSESSMENT. P.R. Dodmane1, L.E. Lizarraga1, J.P. Kaiser2, S.C. Wesselkamper2, Q.J. Zhao2. 1ORISE Participant, U.S. EPA, National Center for Environmental Assessment (NCEA), Cincinnati...

  3. Identifying experimental surrogates for Bacillus anthracis spores: a review

    PubMed Central

    2010-01-01

    Bacillus anthracis, the causative agent of anthrax, is a proven biological weapon. In order to study this threat, a number of experimental surrogates have been used over the past 70 years. However, not all surrogates are appropriate for B. anthracis, especially when investigating transport, fate and survival. Although B. atrophaeus has been widely used as a B. anthracis surrogate, the two species do not always behave identically in transport and survival models. Therefore, we devised a scheme to identify a more appropriate surrogate for B. anthracis. Our selection criteria included risk of use (pathogenicity), phylogenetic relationship, morphology and comparative survivability when challenged with biocides. Although our knowledge of certain parameters remains incomplete, especially with regards to comparisons of spore longevity under natural conditions, we found that B. thuringiensis provided the best overall fit as a non-pathogenic surrogate for B. anthracis. Thus, we suggest focusing on this surrogate in future experiments of spore fate and transport modelling. PMID:21092338

  4. Statistical identifiability and the surrogate endpoint problem, with application to vaccine trials

    PubMed Central

    2013-01-01

    Summary Given a randomized treatment Z, a clinical outcome Y, and a biomarker S measured some fixed time after Z is administered, we may be interested in addressing the surrogate endpoint problem by evaluating whether S can be used to reliably predict the effect of Z on Y. Several recent proposals for the statistical evaluation of surrogate value have been based on the framework of principal stratification. In this paper, we consider two principal stratification estimands: joint risks and marginal risks. Joint risks measure causal associations of treatment effects on S and Y, providing insight into the surrogate value of the biomarker, but are not statistically identifiable from vaccine trial data. While marginal risks do not measure causal associations of treatment effects, they nevertheless provide guidance for future research, and we describe a data collection scheme and assumptions under which the marginal risks are statistically identifiable. We show how different sets of assumptions affect the identifiability of these estimands; in particular, we depart from previous work by considering the consequences of relaxing the assumption of no individual treatment effects on Y before S is measured. Based on algebraic relationships between joint and marginal risks, we propose a sensitivity analysis approach for assessment of surrogate value, and show that in many cases the surrogate value of a biomarker may be hard to establish, even when the sample size is large. PMID:20105158

  5. The value of surrogate endpoints for predicting real-world survival across five cancer types.

    PubMed

    Shafrin, Jason; Brookmeyer, Ron; Peneva, Desi; Park, Jinhee; Zhang, Jie; Figlin, Robert A; Lakdawalla, Darius N

    2016-04-01

    Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints - progression-free survival (PFS) and time to progression (TTP) - to predict real-world OS across five cancers. Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan-Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991-2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R(2) from linear regressions. Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P = 0.026). Among all real-world patients using sample treatments (N = 309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P = 0.194). Results were qualitatively similar using median absolute prediction error and R(2) metrics. Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone. PMID:26743800

  6. Fast Prediction and Evaluation of Gravitational Waveforms Using Surrogate Models

    NASA Astrophysics Data System (ADS)

    Field, Scott E.; Galley, Chad R.; Hesthaven, Jan S.; Kaye, Jason; Tiglio, Manuel

    2014-07-01

    We propose a solution to the problem of quickly and accurately predicting gravitational waveforms within any given physical model. The method is relevant for both real-time applications and more traditional scenarios where the generation of waveforms using standard methods can be prohibitively expensive. Our approach is based on three offline steps resulting in an accurate reduced order model in both parameter and physical dimensions that can be used as a surrogate for the true or fiducial waveform family. First, a set of m parameter values is determined using a greedy algorithm from which a reduced basis representation is constructed. Second, these m parameters induce the selection of m time values for interpolating a waveform time series using an empirical interpolant that is built for the fiducial waveform family. Third, a fit in the parameter dimension is performed for the waveform's value at each of these m times. The cost of predicting L waveform time samples for a generic parameter choice is of order O(mL+mcfit) online operations, where cfit denotes the fitting function operation count and, typically, m ≪L. The result is a compact, computationally efficient, and accurate surrogate model that retains the original physics of the fiducial waveform family while also being fast to evaluate. We generate accurate surrogate models for effective-one-body waveforms of nonspinning binary black hole coalescences with durations as long as 105M, mass ratios from 1 to 10, and for multiple spherical harmonic modes. We find that these surrogates are more than 3 orders of magnitude faster to evaluate as compared to the cost of generating effective-one-body waveforms in standard ways. Surrogate model building for other waveform families and models follows the same steps and has the same low computational online scaling cost. For expensive numerical simulations of binary black hole coalescences, we thus anticipate extremely large speedups in generating new waveforms with a

  7. Identifying Novel Clinical Surrogates to Assess Human Bone Fracture Toughness.

    PubMed

    Granke, Mathilde; Makowski, Alexander J; Uppuganti, Sasidhar; Does, Mark D; Nyman, Jeffry S

    2015-07-01

    Fracture risk does not solely depend on strength but also on fracture toughness; ie, the ability of bone material to resist crack initiation and propagation. Because resistance to crack growth largely depends on bone properties at the tissue level, including collagen characteristics, current X-ray based assessment tools may not be suitable to identify age-related, disease-related, or treatment-related changes in fracture toughness. To identify useful clinical surrogates that could improve the assessment of fracture resistance, we investigated the potential of (1)H nuclear magnetic resonance spectroscopy (NMR) and reference point indentation (RPI) to explain age-related variance in fracture toughness. Harvested from cadaveric femurs (62 human donors), single-edge notched beam (SENB) specimens of cortical bone underwent fracture toughness testing (R-curve method). NMR-derived bound water showed the strongest correlation with fracture toughness properties (r = 0.63 for crack initiation, r = 0.35 for crack growth, and r = 0.45 for overall fracture toughness; p < 0.01). Multivariate analyses indicated that the age-related decrease in different fracture toughness properties were best explained by a combination of NMR properties including pore water and RPI-derived tissue stiffness with age as a significant covariate (adjusted R(2)  = 53.3%, 23.9%, and 35.2% for crack initiation, crack growth, and overall toughness, respectively; p < 0.001). These findings reflect the existence of many contributors to fracture toughness and emphasize the utility of a multimodal assessment of fracture resistance. Exploring the mechanistic origin of fracture toughness, glycation-mediated nonenzymatic collagen crosslinks and intracortical porosity are possible determinants of bone fracture toughness and could explain the sensitivity of NMR to changes in fracture toughness. Assuming fracture toughness is clinically important to the ability of bone to resist fracture

  8. Identifying novel clinical surrogates to assess human bone fracture toughness

    PubMed Central

    Granke, Mathilde; Makowski, Alexander J; Uppuganti, Sasidhar; Does, Mark D; Nyman, Jeffry S

    2015-01-01

    Fracture risk does not solely depend on strength but also on fracture toughness, i.e. the ability of bone material to resist crack initiation and propagation. Because resistance to crack growth largely depends on bone properties at the tissue level including collagen characteristics, current X-ray based assessment tools may not be suitable to identify age-, disease-, or treatment-related changes in fracture toughness. To identify useful clinical surrogates that could improve the assessment of fracture resistance, we investigated the potential of 1H nuclear magnetic resonance spectroscopy (NMR) and reference point indentation (RPI) to explain age-related variance in fracture toughness. Harvested from cadaveric femurs (62 human donors), single-edge notched beam (SENB) specimens of cortical bone underwent fracture toughness testing (R-curve method). NMR-derived bound water showed the strongest correlation with fracture toughness properties (r=0.63 for crack initiation, r=0.35 for crack growth, and r=0.45 for overall fracture toughness; p<0.01). Multivariate analyses indicated that the age-related decrease in different fracture toughness properties were best explained by a combination of NMR properties including pore water and RPI-derived tissue stiffness with age as a significant covariate (adjusted R2 = 53.3%, 23.9%, and 35.2% for crack initiation, crack growth, and overall toughness, respectively; p<0.001). These findings reflect the existence of many contributors to fracture toughness and emphasize the utility of a multimodal assessment of fracture resistance. Exploring the mechanistic origin of fracture toughness, glycation-mediated, non-enzymatic collagen crosslinks and intra-cortical porosity are possible determinants of bone fracture toughness and could explain the sensitivity of NMR to changes in fracture toughness. Assuming fracture toughness is clinically important to the ability of bone to resist fracture, our results suggest that improvements in fracture

  9. On identified predictive control

    NASA Technical Reports Server (NTRS)

    Bialasiewicz, Jan T.

    1993-01-01

    Self-tuning control algorithms are potential successors to manually tuned PID controllers traditionally used in process control applications. A very attractive design method for self-tuning controllers, which has been developed over recent years, is the long-range predictive control (LRPC). The success of LRPC is due to its effectiveness with plants of unknown order and dead-time which may be simultaneously nonminimum phase and unstable or have multiple lightly damped poles (as in the case of flexible structures or flexible robot arms). LRPC is a receding horizon strategy and can be, in general terms, summarized as follows. Using assumed long-range (or multi-step) cost function the optimal control law is found in terms of unknown parameters of the predictor model of the process, current input-output sequence, and future reference signal sequence. The common approach is to assume that the input-output process model is known or separately identified and then to find the parameters of the predictor model. Once these are known, the optimal control law determines control signal at the current time t which is applied at the process input and the whole procedure is repeated at the next time instant. Most of the recent research in this field is apparently centered around the LRPC formulation developed by Clarke et al., known as generalized predictive control (GPC). GPC uses ARIMAX/CARIMA model of the process in its input-output formulation. In this paper, the GPC formulation is used but the process predictor model is derived from the state space formulation of the ARIMAX model and is directly identified over the receding horizon, i.e., using current input-output sequence. The underlying technique in the design of identified predictive control (IPC) algorithm is the identification algorithm of observer/Kalman filter Markov parameters developed by Juang et al. at NASA Langley Research Center and successfully applied to identification of flexible structures.

  10. Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China

    PubMed Central

    Yang, Feiling; Hu, Jinming; Wu, Ruidong

    2016-01-01

    Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan’s protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan. PMID:27538537

  11. Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China.

    PubMed

    Yang, Feiling; Hu, Jinming; Wu, Ruidong

    2016-01-01

    Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan's protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan. PMID:27538537

  12. Inaccuracies in predicting human norovirus inactivation using surrogate viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human norovirus (NoV) cannot be propagated in cell culture, so virus inactivation studies, including processing interventions, are generally performed on virus surrogates that may be readily quantified in the laboratory. However, there are fundamental differences in many closely related viruses, di...

  13. Fast and Accurate Prediction of Numerical Relativity Waveforms from Binary Black Hole Coalescences Using Surrogate Models

    NASA Astrophysics Data System (ADS)

    Blackman, Jonathan; Field, Scott E.; Galley, Chad R.; Szilágyi, Béla; Scheel, Mark A.; Tiglio, Manuel; Hemberger, Daniel A.

    2015-09-01

    Simulating a binary black hole coalescence by solving Einstein's equations is computationally expensive, requiring days to months of supercomputing time. Using reduced order modeling techniques, we construct an accurate surrogate model, which is evaluated in a millisecond to a second, for numerical relativity (NR) waveforms from nonspinning binary black hole coalescences with mass ratios in [1, 10] and durations corresponding to about 15 orbits before merger. We assess the model's uncertainty and show that our modeling strategy predicts NR waveforms not used for the surrogate's training with errors nearly as small as the numerical error of the NR code. Our model includes all spherical-harmonic -2Yℓm waveform modes resolved by the NR code up to ℓ=8 . We compare our surrogate model to effective one body waveforms from 50 M⊙ to 300 M⊙ for advanced LIGO detectors and find that the surrogate is always more faithful (by at least an order of magnitude in most cases).

  14. Ensemble of surrogates-based optimization for identifying an optimal surfactant-enhanced aquifer remediation strategy at heterogeneous DNAPL-contaminated sites

    NASA Astrophysics Data System (ADS)

    Jiang, Xue; Lu, Wenxi; Hou, Zeyu; Zhao, Haiqing; Na, Jin

    2015-11-01

    The purpose of this study was to identify an optimal surfactant-enhanced aquifer remediation (SEAR) strategy for aquifers contaminated by dense non-aqueous phase liquid (DNAPL) based on an ensemble of surrogates-based optimization technique. A saturated heterogeneous medium contaminated by nitrobenzene was selected as case study. A new kind of surrogate-based SEAR optimization employing an ensemble surrogate (ES) model together with a genetic algorithm (GA) is presented. Four methods, namely radial basis function artificial neural network (RBFANN), kriging (KRG), support vector regression (SVR), and kernel extreme learning machines (KELM), were used to create four individual surrogate models, which were then compared. The comparison enabled us to select the two most accurate models (KELM and KRG) to establish an ES model of the SEAR simulation model, and the developed ES model as well as these four stand-alone surrogate models was compared. The results showed that the average relative error of the average nitrobenzene removal rates between the ES model and the simulation model for 20 test samples was 0.8%, which is a high approximation accuracy, and which indicates that the ES model provides more accurate predictions than the stand-alone surrogate models. Then, a nonlinear optimization model was formulated for the minimum cost, and the developed ES model was embedded into this optimization model as a constrained condition. Besides, GA was used to solve the optimization model to provide the optimal SEAR strategy. The developed ensemble surrogate-optimization approach was effective in seeking a cost-effective SEAR strategy for heterogeneous DNAPL-contaminated sites. This research is expected to enrich and develop the theoretical and technical implications for the analysis of remediation strategy optimization of DNAPL-contaminated aquifers.

  15. Surrogate Modeling of High-Fidelity Fracture Simulations for Real-Time Residual Strength Predictions

    NASA Technical Reports Server (NTRS)

    Spear, Ashley D.; Priest, Amanda R.; Veilleux, Michael G.; Ingraffea, Anthony R.; Hochhalter, Jacob D.

    2011-01-01

    A surrogate model methodology is described for predicting in real time the residual strength of flight structures with discrete-source damage. Starting with design of experiment, an artificial neural network is developed that takes as input discrete-source damage parameters and outputs a prediction of the structural residual strength. Target residual strength values used to train the artificial neural network are derived from 3D finite element-based fracture simulations. A residual strength test of a metallic, integrally-stiffened panel is simulated to show that crack growth and residual strength are determined more accurately in discrete-source damage cases by using an elastic-plastic fracture framework rather than a linear-elastic fracture mechanics-based method. Improving accuracy of the residual strength training data would, in turn, improve accuracy of the surrogate model. When combined, the surrogate model methodology and high-fidelity fracture simulation framework provide useful tools for adaptive flight technology.

  16. Surrogate Modeling of High-Fidelity Fracture Simulations for Real-Time Residual Strength Predictions

    NASA Technical Reports Server (NTRS)

    Spear, Ashley D.; Priest, Amanda R.; Veilleux, Michael G.; Ingraffea, Anthony R.; Hochhalter, Jacob D.

    2011-01-01

    A surrogate model methodology is described for predicting, during flight, the residual strength of aircraft structures that sustain discrete-source damage. Starting with design of experiment, an artificial neural network is developed that takes as input discrete-source damage parameters and outputs a prediction of the structural residual strength. Target residual strength values used to train the artificial neural network are derived from 3D finite element-based fracture simulations. Two ductile fracture simulations are presented to show that crack growth and residual strength are determined more accurately in discrete-source damage cases by using an elastic-plastic fracture framework rather than a linear-elastic fracture mechanics-based method. Improving accuracy of the residual strength training data does, in turn, improve accuracy of the surrogate model. When combined, the surrogate model methodology and high fidelity fracture simulation framework provide useful tools for adaptive flight technology.

  17. Fast and Accurate Prediction of Numerical Relativity Waveforms from Binary Black Hole Coalescences Using Surrogate Models.

    PubMed

    Blackman, Jonathan; Field, Scott E; Galley, Chad R; Szilágyi, Béla; Scheel, Mark A; Tiglio, Manuel; Hemberger, Daniel A

    2015-09-18

    Simulating a binary black hole coalescence by solving Einstein's equations is computationally expensive, requiring days to months of supercomputing time. Using reduced order modeling techniques, we construct an accurate surrogate model, which is evaluated in a millisecond to a second, for numerical relativity (NR) waveforms from nonspinning binary black hole coalescences with mass ratios in [1, 10] and durations corresponding to about 15 orbits before merger. We assess the model's uncertainty and show that our modeling strategy predicts NR waveforms not used for the surrogate's training with errors nearly as small as the numerical error of the NR code. Our model includes all spherical-harmonic _{-2}Y_{ℓm} waveform modes resolved by the NR code up to ℓ=8. We compare our surrogate model to effective one body waveforms from 50M_{⊙} to 300M_{⊙} for advanced LIGO detectors and find that the surrogate is always more faithful (by at least an order of magnitude in most cases). PMID:26430979

  18. Predicting trace organic compound breakthrough in granular activated carbon using fluorescence and UV absorbance as surrogates.

    PubMed

    Anumol, Tarun; Sgroi, Massimiliano; Park, Minkyu; Roccaro, Paolo; Snyder, Shane A

    2015-06-01

    This study investigated the applicability of bulk organic parameters like dissolved organic carbon (DOC), UV absorbance at 254 nm (UV254), and total fluorescence (TF) to act as surrogates in predicting trace organic compound (TOrC) removal by granular activated carbon in water reuse applications. Using rapid small-scale column testing, empirical linear correlations for thirteen TOrCs were determined with DOC, UV254, and TF in four wastewater effluents. Linear correlations (R(2) > 0.7) were obtained for eight TOrCs in each water quality in the UV254 model, while ten TOrCs had R(2) > 0.7 in the TF model. Conversely, DOC was shown to be a poor surrogate for TOrC breakthrough prediction. When the data from all four water qualities was combined, good linear correlations were still obtained with TF having higher R(2) than UV254 especially for TOrCs with log Dow>1. Excellent linear relationship (R(2) > 0.9) between log Dow and the removal of TOrC at 0% surrogate removal (y-intercept) were obtained for the five neutral TOrCs tested in this study. Positively charged TOrCs had enhanced removals due to electrostatic interactions with negatively charged GAC that caused them to deviate from removals that would be expected with their log Dow. Application of the empirical linear correlation models to full-scale samples provided good results for six of seven TOrCs (except meprobamate) tested when comparing predicted TOrC removal by UV254 and TF with actual removals for GAC in all the five samples tested. Surrogate predictions using UV254 and TF provide valuable tools for rapid or on-line monitoring of GAC performance and can result in cost savings by extended GAC run times as compared to using DOC breakthrough to trigger regeneration or replacement. PMID:25792436

  19. Experimental verification of ion stopping power prediction from dual energy CT data in tissue surrogates.

    PubMed

    Hünemohr, Nora; Krauss, Bernhard; Tremmel, Christoph; Ackermann, Benjamin; Jäkel, Oliver; Greilich, Steffen

    2014-01-01

    We present an experimental verification of stopping-power-ratio (SPR) prediction from dual energy CT (DECT) with potential use for dose planning in proton and ion therapy. The approach is based on DECT images converted to electron density relative to water ϱe/ϱe, w and effective atomic number Zeff. To establish a parameterization of the I-value by Zeff, 71 tabulated tissue compositions were used. For the experimental assessment of the method we scanned 20 materials (tissue surrogates, polymers, aluminum, titanium) at 80/140Sn kVp and 100/140Sn kVp (Sn: additional tin filtration) and computed the ϱe/ϱe, w and Zeff with a purely image based algorithm. Thereby, we found that ϱe/ϱe, w (Zeff) could be determined with an accuracy of 0.4% (1.7%) for the tissue surrogates with known elemental compositions. SPRs were predicted from DECT images for all 20 materials using the presented approach and were compared to measured water-equivalent path lengths (closely related to SPR). For the tissue surrogates the presented DECT approach was found to predict the experimental values within 0.6%, for aluminum and titanium within an accuracy of 1.7% and 9.4% (from 16-bit reconstructed DECT images). PMID:24334601

  20. Surrogate modelling and optimization using shape-preserving response prediction: A review

    NASA Astrophysics Data System (ADS)

    Leifsson, Leifur; Koziel, Slawomir

    2016-03-01

    Computer simulation models are ubiquitous in modern engineering design. In many cases, they are the only way to evaluate a given design with sufficient fidelity. Unfortunately, an added computational expense is associated with higher fidelity models. Moreover, the systems being considered are often highly nonlinear and may feature a large number of designable parameters. Therefore, it may be impractical to solve the design problem with conventional optimization algorithms. A promising approach to alleviate these difficulties is surrogate-based optimization (SBO). Among proven SBO techniques, the methods utilizing surrogates constructed from corrected physics-based low-fidelity models are, in many cases, the most efficient. This article reviews a particular technique of this type, namely, shape-preserving response prediction (SPRP), which works on the level of the model responses to correct the underlying low-fidelity models. The formulation and limitations of SPRP are discussed. Applications to several engineering design problems are provided.

  1. Measure profile surrogates: A method to validate the performance of epileptic seizure prediction algorithms

    NASA Astrophysics Data System (ADS)

    Kreuz, Thomas; Andrzejak, Ralph G.; Mormann, Florian; Kraskov, Alexander; Stögbauer, Harald; Elger, Christian E.; Lehnertz, Klaus; Grassberger, Peter

    2004-06-01

    In a growing number of publications it is claimed that epileptic seizures can be predicted by analyzing the electroencephalogram (EEG) with different characterizing measures. However, many of these studies suffer from a severe lack of statistical validation. Only rarely are results passed to a statistical test and verified against some null hypothesis H0 in order to quantify their significance. In this paper we propose a method to statistically validate the performance of measures used to predict epileptic seizures. From measure profiles rendered by applying a moving-window technique to the electroencephalogram we first generate an ensemble of surrogates by a constrained randomization using simulated annealing. Subsequently the seizure prediction algorithm is applied to the original measure profile and to the surrogates. If detectable changes before seizure onset exist, highest performance values should be obtained for the original measure profiles and the null hypothesis. “The measure is not suited for seizure prediction” can be rejected. We demonstrate our method by applying two measures of synchronization to a quasicontinuous EEG recording and by evaluating their predictive performance using a straightforward seizure prediction statistics. We would like to stress that the proposed method is rather universal and can be applied to many other prediction and detection problems.

  2. Development of surrogate correlation models to predict trace organic contaminant oxidation and microbial inactivation during ozonation.

    PubMed

    Gerrity, Daniel; Gamage, Sujanie; Jones, Darryl; Korshin, Gregory V; Lee, Yunho; Pisarenko, Aleksey; Trenholm, Rebecca A; von Gunten, Urs; Wert, Eric C; Snyder, Shane A

    2012-12-01

    The performance of ozonation in wastewater depends on water quality and the ability to form hydroxyl radicals (·OH) to meet disinfection or contaminant transformation objectives. Since there are no on-line methods to assess ozone and ·OH exposure in wastewater, many agencies are now embracing indicator frameworks and surrogate monitoring for regulatory compliance. Two of the most promising surrogate parameters for ozone-based treatment of secondary and tertiary wastewater effluents are differential UV(254) absorbance (ΔUV(254)) and total fluorescence (ΔTF). In the current study, empirical correlations for ΔUV(254) and ΔTF were developed for the oxidation of 18 trace organic contaminants (TOrCs), including 1,4-dioxane, atenolol, atrazine, bisphenol A, carbamazepine, diclofenac, gemfibrozil, ibuprofen, meprobamate, naproxen, N,N-diethyl-meta-toluamide (DEET), para-chlorobenzoic acid (pCBA), phenytoin, primidone, sulfamethoxazole, triclosan, trimethoprim, and tris-(2-chloroethyl)-phosphate (TCEP) (R(2) = 0.50-0.83) and the inactivation of three microbial surrogates, including Escherichia coli, MS2, and Bacillus subtilis spores (R(2) = 0.46-0.78). Nine wastewaters were tested in laboratory systems, and eight wastewaters were evaluated at pilot- and full-scale. A predictive model for OH exposure based on ΔUV(254) or ΔTF was also proposed. PMID:23062789

  3. Development and application of a green fluorescent protein (GFP) expressing E. coli O103 surrogate for tracking contamination through grinding and identifying persistent points of contamination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To 1.) develop and validate an easily trackable E. coli O157:H7/non-O157 STEC surrogate that can be detected to the same level of sensitivity as E. coli O157:H7; and 2.) apply the trackable surrogate to model contamination passage through grinding and identify points where contamination ...

  4. SU-C-BRF-07: A Pattern Fusion Algorithm for Multi-Step Ahead Prediction of Surrogate Motion

    SciTech Connect

    Zawisza, I; Yan, H; Yin, F

    2014-06-15

    Purpose: To assure that tumor motion is within the radiation field during high-dose and high-precision radiosurgery, real-time imaging and surrogate monitoring are employed. These methods are useful in providing real-time tumor/surrogate motion but no future information is available. In order to anticipate future tumor/surrogate motion and track target location precisely, an algorithm is developed and investigated for estimating surrogate motion multiple-steps ahead. Methods: The study utilized a one-dimensional surrogate motion signal divided into three components: (a) training component containing the primary data including the first frame to the beginning of the input subsequence; (b) input subsequence component of the surrogate signal used as input to the prediction algorithm: (c) output subsequence component is the remaining signal used as the known output of the prediction algorithm for validation. The prediction algorithm consists of three major steps: (1) extracting subsequences from training component which best-match the input subsequence according to given criterion; (2) calculating weighting factors from these best-matched subsequence; (3) collecting the proceeding parts of the subsequences and combining them together with assigned weighting factors to form output. The prediction algorithm was examined for several patients, and its performance is assessed based on the correlation between prediction and known output. Results: Respiratory motion data was collected for 20 patients using the RPM system. The output subsequence is the last 50 samples (∼2 seconds) of a surrogate signal, and the input subsequence was 100 (∼3 seconds) frames prior to the output subsequence. Based on the analysis of correlation coefficient between predicted and known output subsequence, the average correlation is 0.9644±0.0394 and 0.9789±0.0239 for equal-weighting and relative-weighting strategies, respectively. Conclusion: Preliminary results indicate that the prediction

  5. Evaluation of a bacterial bioluminescence bioassay as a predictive surrogate for mysid chronic estimator tests with produced water

    SciTech Connect

    Korenaga, G.L.; Stine, E.R.; Henry, L.R.

    1995-12-01

    Toxicity limits are appearing more frequently in permits for produced water discharges. A bioluminescent bacteria bioassay has been proposed as a screening tool to predict toxicity in higher organisms, which are more expensive and require longer testing times. Before such a surrogate screen can be used, a correlation must be demonstrated between toxicity in the surrogate and the species of interest. This paper describes tests comparing produced water toxicity in the bioluminescent bacteria test and in the myoid shrimp chronic estimator test, which is frequently required in Gulf of Mexico discharge Under these test conditions, the bacteria test was not adequately predictive of produced water chronic toxicity to the myoid shrimp.

  6. Serum creatinine level, a surrogate of muscle mass, predicts mortality in critically ill patients

    PubMed Central

    Thongprayoon, Charat; Cheungpasitporn, Wisit

    2016-01-01

    Serum creatinine (SCr) has been widely used to estimate glomerular filtration rate (GFR). Creatinine generation could be reduced in the setting of low skeletal muscle mass. Thus, SCr has also been used as a surrogate of muscle mass. Low muscle mass is associated with reduced survival in hospitalized patients, especially in the intensive care unit (ICU) settings. Recently, studies have demonstrated high mortality in ICU patients with low admission SCr levels, reflecting that low muscle mass or malnutrition, are associated with increased mortality. However, SCr levels can also be influenced by multiple GFR- and non-GFR-related factors including age, diet, exercise, stress, pregnancy, and kidney disease. Imaging techniques, such as computed tomography (CT) and ultrasound, have recently been studied for muscle mass assessment and demonstrated promising data. This article aims to present the perspectives of the uses of SCr and other methods for prediction of muscle mass and outcomes of ICU patients. PMID:27162688

  7. Serum creatinine level, a surrogate of muscle mass, predicts mortality in critically ill patients.

    PubMed

    Thongprayoon, Charat; Cheungpasitporn, Wisit; Kashani, Kianoush

    2016-05-01

    Serum creatinine (SCr) has been widely used to estimate glomerular filtration rate (GFR). Creatinine generation could be reduced in the setting of low skeletal muscle mass. Thus, SCr has also been used as a surrogate of muscle mass. Low muscle mass is associated with reduced survival in hospitalized patients, especially in the intensive care unit (ICU) settings. Recently, studies have demonstrated high mortality in ICU patients with low admission SCr levels, reflecting that low muscle mass or malnutrition, are associated with increased mortality. However, SCr levels can also be influenced by multiple GFR- and non-GFR-related factors including age, diet, exercise, stress, pregnancy, and kidney disease. Imaging techniques, such as computed tomography (CT) and ultrasound, have recently been studied for muscle mass assessment and demonstrated promising data. This article aims to present the perspectives of the uses of SCr and other methods for prediction of muscle mass and outcomes of ICU patients. PMID:27162688

  8. Waterlow score as a surrogate marker for predicting adverse outcome in acute pancreatitis.

    PubMed

    Gillick, K; Elbeltagi, H; Bhattacharya, S

    2016-01-01

    Introduction Introduced originally to stratify risk for developing decubitus ulcers, the Waterlow scoring system is recorded routinely for surgical admissions. It is a composite score, reflecting patients' general condition and co-morbidities. The aim of this study was to investigate whether the Waterlow score can be used as an independent surrogate marker to predict severity and adverse outcome in acute pancreatitis. Methods In this retrospective analysis, a consecutive cohort was studied of 250 patients presenting with acute pancreatitis, all of whom had their Waterlow score calculated on admission. Primary outcome measures were length of hospital stay and mortality. Secondary outcome measures included rate of intensive care unit (ICU) admission and development of complications such as peripancreatic free fluid, pancreatic necrosis and pseudocyst formation. Correlation of the Waterlow score with some known markers of disease severity and outcomes was also analysed. Results The Waterlow score correlated strongly with the most commonly used marker of disease severity, the Glasgow score (analysis of variance, p=0.0012). Inpatient mortality, rate of ICU admission and length of hospital stay increased with a higher Waterlow score (Mann-Whitney U test, p=0.0007, p=0.049 and p=0.0002 respectively). There was, however, no significant association between the Waterlow score and the incidence of three known complications of pancreatitis: presence of peripancreatic fluid, pancreatic pseudocyst formation and pancreatic necrosis. Receiver operating characteristic curve analysis demonstrated good predictive power of the Waterlow score for mortality (area under the curve [AUC]: 0.73), ICU admission (AUC: 0.65) and length of stay >7 days (AUC: 0.64). This is comparable with the predictive power of the Glasgow score and C-reactive protein. Conclusions The Waterlow score for patients admitted with acute pancreatitis could provide a useful tool in prospective assessment of disease

  9. A Kriging surrogate model coupled in simulation-optimization approach for identifying release history of groundwater sources

    NASA Astrophysics Data System (ADS)

    Zhao, Ying; Lu, Wenxi; Xiao, Chuanning

    2016-02-01

    As the incidence frequency of groundwater pollution increases, many methods that identify source characteristics of pollutants are being developed. In this study, a simulation-optimization approach was applied to determine the duration and magnitude of pollutant sources. Such problems are time consuming because thousands of simulation models are required to run the optimization model. To address this challenge, the Kriging surrogate model was proposed to increase computational efficiency. Accuracy, time consumption, and the robustness of the Kriging model were tested on both homogenous and non-uniform media, as well as steady-state and transient flow and transport conditions. The results of three hypothetical cases demonstrate that the Kriging model has the ability to solve groundwater contaminant source problems that could occur during field site source identification problems with a high degree of accuracy and short computation times and is thus very robust.

  10. Predicting analysis time in events-driven clinical trials using accumulating time-to-event surrogate information.

    PubMed

    Wang, Jianming; Ke, Chunlei; Yu, Zhinuan; Fu, Lei; Dornseif, Bruce

    2016-05-01

    For clinical trials with time-to-event endpoints, predicting the accrual of the events of interest with precision is critical in determining the timing of interim and final analyses. For example, overall survival (OS) is often chosen as the primary efficacy endpoint in oncology studies, with planned interim and final analyses at a pre-specified number of deaths. Often, correlated surrogate information, such as time-to-progression (TTP) and progression-free survival, are also collected as secondary efficacy endpoints. It would be appealing to borrow strength from the surrogate information to improve the precision of the analysis time prediction. Currently available methods in the literature for predicting analysis timings do not consider utilizing the surrogate information. In this article, using OS and TTP as an example, a general parametric model for OS and TTP is proposed, with the assumption that disease progression could change the course of the overall survival. Progression-free survival, related both to OS and TTP, will be handled separately, as it can be derived from OS and TTP. The authors seek to develop a prediction procedure using a Bayesian method and provide detailed implementation strategies under certain assumptions. Simulations are performed to evaluate the performance of the proposed method. An application to a real study is also provided. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26689725

  11. Quantitative prediction of respiratory tidal volume based on the external torso volume change: a potential volumetric surrogate

    NASA Astrophysics Data System (ADS)

    Li, Guang; Arora, Naveen C.; Xie, Huchen; Ning, Holly; Lu, Wei; Low, Daniel; Citrin, Deborah; Kaushal, Aradhana; Zach, Leor; Camphausen, Kevin; Miller, Robert W.

    2009-04-01

    An external respiratory surrogate that not only highly correlates with but also quantitatively predicts internal tidal volume should be useful in guiding four-dimensional computed tomography (4DCT), as well as 4D radiation therapy (4DRT). A volumetric surrogate should have advantages over external fiducial point(s) for monitoring respiration-induced motion of the torso, which deforms in synchronization with a patient-specific breathing pattern. This study establishes a linear relationship between the external torso volume change (TVC) and lung air volume change (AVC) by validating a proposed volume conservation hypothesis (TVC = AVC) throughout the respiratory cycle using 4DCT and spirometry. Fourteen patients' torso 4DCT images and corresponding spirometric tidal volumes were acquired to examine this hypothesis. The 4DCT images were acquired using dual surrogates in ciné mode and amplitude-based binning in 12 respiratory stages, minimizing residual motion artifacts. Torso and lung volumes were calculated using threshold-based segmentation algorithms and volume changes were calculated relative to the full-exhalation stage. The TVC and AVC, as functions of respiratory stages, were compared, showing a high correlation (r = 0.992 ± 0.005, p < 0.0001) as well as a linear relationship (slope = 1.027 ± 0.061, R2 = 0.980) without phase shift. The AVC was also compared to the spirometric tidal volumes, showing a similar linearity (slope = 1.030 ± 0.092, R2 = 0.947). In contrast, the thoracic and abdominal heights measured from 4DCT showed relatively low correlation (0.28 ± 0.44 and 0.82 ± 0.30, respectively) and location-dependent phase shifts. This novel approach establishes the foundation for developing an external volumetric respiratory surrogate.

  12. Statistical surrogate models for prediction of high-consequence climate change.

    SciTech Connect

    Constantine, Paul; Field, Richard V., Jr.; Boslough, Mark Bruce Elrick

    2011-09-01

    In safety engineering, performance metrics are defined using probabilistic risk assessments focused on the low-probability, high-consequence tail of the distribution of possible events, as opposed to best estimates based on central tendencies. We frame the climate change problem and its associated risks in a similar manner. To properly explore the tails of the distribution requires extensive sampling, which is not possible with existing coupled atmospheric models due to the high computational cost of each simulation. We therefore propose the use of specialized statistical surrogate models (SSMs) for the purpose of exploring the probability law of various climate variables of interest. A SSM is different than a deterministic surrogate model in that it represents each climate variable of interest as a space/time random field. The SSM can be calibrated to available spatial and temporal data from existing climate databases, e.g., the Program for Climate Model Diagnosis and Intercomparison (PCMDI), or to a collection of outputs from a General Circulation Model (GCM), e.g., the Community Earth System Model (CESM) and its predecessors. Because of its reduced size and complexity, the realization of a large number of independent model outputs from a SSM becomes computationally straightforward, so that quantifying the risk associated with low-probability, high-consequence climate events becomes feasible. A Bayesian framework is developed to provide quantitative measures of confidence, via Bayesian credible intervals, in the use of the proposed approach to assess these risks.

  13. Utility of surrogate markers for the prediction of relapses in inflammatory bowel diseases.

    PubMed

    Musci, Jason Orlando Dimitri; Cornish, Jack Stephen; Däbritz, Jan

    2016-06-01

    Patients with diagnosed inflammatory bowel disease (IBD) will commonly experience a clinical relapse in spite of a prolonged therapy-induced period of clinical remission. The current methods of assessing subclinical levels of low-grade inflammation which predispose patients to relapse are not optimal when considering both cost and patient comfort. Over the past few decades, much investigation has discovered that proteins such as calprotectin that are released from inflammatory cells are capable of indicating disease activity. Along with C-reactive protein and erythrocyte sedimentation rate, calprotectin has now become part of the current methodology for assessing IBD activity. More recently, research has identified that other fecal and serum biomarkers such as lactoferrin, S100A12, GM-CSF autoantibodies, α1-antitrypsin, eosinophil-derived proteins, and cytokine concentrations have variable degrees of utility in monitoring gastrointestinal tract inflammation. In order to provide direction toward novel methods of predicting relapse in IBD, we provide an up-to-date review of these biomarkers and their potential utility in the prediction of clinical relapse, given their observed activities during various stages of clinical remission. PMID:26975751

  14. Surrogate gas prediction model as a proxy for Δ14C-based measurements of fossil fuel CO2

    NASA Astrophysics Data System (ADS)

    Coakley, Kevin J.; Miller, John B.; Montzka, Stephen A.; Sweeney, Colm; Miller, Ben R.

    2016-06-01

    The measured 14C:12C isotopic ratio of atmospheric CO2 (and its associated derived Δ14C value) is an ideal tracer for determination of the fossil fuel derived CO2 enhancement contributing to any atmospheric CO2 measurement (Cff). Given enough such measurements, independent top-down estimation of U.S. fossil fuel CO2 emissions should be possible. However, the number of Δ14C measurements is presently constrained by cost, available sample volume, and availability of mass spectrometer measurement facilities. Δ14C is therefore measured in just a small fraction of samples obtained by flask air sampling networks around the world. Here we develop a projection pursuit regression (PPR) model to predict Cff as a function of multiple surrogate gases acquired within the NOAA/Earth System Research Laboratory (ESRL) Global Greenhouse Gas Reference Network (GGGRN). The surrogates consist of measured enhancements of various anthropogenic trace gases, including CO, SF6, and halocarbon and hydrocarbon acquired in vertical airborne sampling profiles near Cape May, NJ and Portsmouth, NH from 2005 to 2010. Model performance for these sites is quantified based on predicted values corresponding to test data excluded from the model building process. Chi-square hypothesis test analysis indicates that these predictions and corresponding observations are consistent given our uncertainty budget which accounts for random effects and one particular systematic effect. However, quantification of the combined uncertainty of the prediction due to all relevant systematic effects is difficult because of the limited range of the observations and their relatively high fractional uncertainties at the sampling sites considered here. To account for the possibility of additional systematic effects, we incorporate another component of uncertainty into our budget. Expanding the number of Δ14C measurements in the NOAA GGGRN and building new PPR models at additional sites would improve our understanding of

  15. Investigation of a breathing surrogate prediction algorithm for prospective pulmonary gating

    SciTech Connect

    White, Benjamin M.; Low, Daniel A.; Zhao Tianyu; Wuenschel, Sara; Lu, Wei; Lamb, James M.; Mutic, Sasa; Bradley, Jeffrey D.; El Naqa, Issam

    2011-03-15

    Purpose: A major challenge of four dimensional computed tomography (4DCT) in treatment planning and delivery has been the lack of respiration amplitude and phase reproducibility during image acquisition. The implementation of a prospective gating algorithm would ensure that images would be acquired only during user-specified breathing phases. This study describes the development and testing of an autoregressive moving average (ARMA) model for human respiratory phase prediction under quiet respiration conditions. Methods: A total of 47 4DCT patient datasets and synchronized respiration records was utilized in this study. Three datasets were used in model development and were removed from further evaluation of the ARMA model. The remaining 44 patient datasets were evaluated with the ARMA model for prediction time steps from 50 to 1000 ms in increments of 50 and 100 ms. Thirty-five of these datasets were further used to provide a comparison between the proposed ARMA model and a commercial algorithm with a prediction time step of 240 ms. Results: The optimal number of parameters for the ARMA model was based on three datasets reserved for model development. Prediction error was found to increase as the prediction time step increased. The minimum prediction time step required for prospective gating was selected to be half of the gantry rotation period. The maximum prediction time step with a conservative 95% confidence criterion was found to be 0.3 s. The ARMA model predicted peak inhalation and peak exhalation phases significantly better than the commercial algorithm. Furthermore, the commercial algorithm had numerous instances of missed breath cycles and falsely predicted breath cycles, while the proposed model did not have these errors. Conclusions: An ARMA model has been successfully applied to predict human respiratory phase occurrence. For a typical CT scanner gantry rotation period of 0.4 s (0.2 s prediction time step), the absolute error was relatively small, 0

  16. Building Chinese wind data for Wind Erosion Prediction System using surrogate US data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wind erosion is a global problem, especially in arid and semiarid regions of the world, which leads to land degradation and atmosphere pollution. The process-based Wind Erosion Prediction System (WEPS), developed by the USDA, is capable of simulating the windblown soil loss with changing weather and...

  17. The Low Fall as a Surrogate Marker of Frailty Predicts Long-Term Mortality in Older Trauma Patients

    PubMed Central

    Wong, Ting Hway; Nguyen, Hai V.; Chiu, Ming Terk; Chow, Khuan Yew; Ong, Marcus Eng Hock; Lim, Gek Hsiang; Nadkarni, Nivedita Vikas; Bautista, Dianne Carrol Tan; Cheng, Jolene Yu Xuan; Loo, Lynette Mee Ann; Seow, Dennis Chuen Chai

    2015-01-01

    Background Frailty is associated with adverse outcomes including disability, mortality and risk of falls. Trauma registries capture a broad range of injuries. However, frail patients who fall comprise a large proportion of the injuries occurring in ageing populations and are likely to have different outcomes compared to non-frail injured patients. The effect of frail fallers on mortality is under-explored but potentially significant. Currently, many trauma registries define low falls as less than three metres, a height that is likely to include non-frailty falls. We hypothesized that the low fall from less than 0.5 metres, including same-level falls, is a surrogate marker of frailty and predicts long-term mortality in older trauma patients. Methods Using data from the Singapore National Trauma Registry, 2011–2013, matched till September 2014 to the death registry, we analysed adults aged over 45 admitted via the emergency department in public hospitals sustaining blunt injuries with an injury severity score (ISS) of 9 or more, excluding isolated hip fractures from same-level falls in the over 65. Patients injured by a low fall were compared to patients injured by high fall and other blunt mechanisms. Logistic regression was used to analyze 12-month mortality, controlling for mechanism of injury, ISS, revised trauma score (RTS), co-morbidities, gender, age and age-gender interaction. Different low fall height definitions, adjusting for injury regions, and analyzing the entire adult cohort were used in sensitivity analyses and did not change our findings. Results Of the 8111 adults in our cohort, patients who suffered low falls were more likely to die of causes unrelated to their injuries (p<0.001), compared to other blunt trauma and higher fall heights. They were at higher risk of 12-month mortality (OR 1.75, 95% CI 1.18–2.58, p = 0.005), independent of ISS, RTS, age, gender, age-gender interaction and co-morbidities. Falls that were higher than 0.5m did not

  18. Quality of Communication in the ICU and Surrogate's Understanding of Prognosis

    PubMed Central

    Chiarchiaro, Jared; Buddadhumaruk, Praewpannarai; Arnold, Robert M.; White, Douglas B.

    2014-01-01

    Objective Although misperceptions about prognosis by surrogates in ICUs are common and influence treatment decisions, there is no validated, practical way to measure the effectiveness of prognostic communication. Surrogates' subjective ratings of quality of communication have been used in other domains as markers of effectiveness of communication. We sought to determine whether surrogates' subjective ratings of the quality of prognostic communication predicts accurate expectation about prognosis by surrogates. Design We performed a cross sectional cohort study. Surrogates rated the quality of prognostic communication by survey. Physicians and surrogates gave their percentage estimate of patient survival on ICU day 3 on a 0-100 probability scale. We defined discordance about prognosis as a difference in the physician's and surrogate's estimates of ≥ +/-20%. We used multi-level logistic regression modeling to account for clustering under physicians and patients and adjust for confounders. Patients 275 patients with acute respiratory distress syndrome at high risk of death or severe functional impairment, their 546 surrogate decision makers, and their 150 physicians. Measurements and Main Results There was no predictive utility of surrogates' ratings of the quality of communication about prognosis to identify inaccurate expectations about prognosis. (OR 1.04 +/- 0.07, p 0.54). Surrogates' subjective ratings of the quality of communication about prognosis were high, as assessed with a variety of questions. Discordant prognostic estimates were present in 63.5% (95% CI: 59.0%-67.9%) of physician-surrogate pairs. Conclusions Although most surrogates rate the quality of prognostic communication highly, inaccurate expectations about prognosis are common among surrogates. Surrogates' ratings of the quality of prognostic communication do not reliably predict an accurate expectation about prognosis. PMID:25687030

  19. Performance predictions of a tubular SOFC operating on a partially reformed JP-8 surrogate

    NASA Astrophysics Data System (ADS)

    Gupta, Gaurav K.; Marda, Jonathan R.; Dean, Anthony M.; Colclasure, Andrew M.; Zhu, Huayang; Kee, Robert J.

    This paper uses chemically reacting flow models to explore the effect of upstream JP-8 steam reforming on the performance of a tubular, anode-supported, solid-oxide fuel cell. In all cases studied in this paper, a steam-carbon ratio of 3 is used for the reformer inlet. However, by varying the reformer temperature, the methane concentration in the reformate stream can be varied. In this study methane mole fractions are varied between 0 and 20%, on a dry basis. The methane mole fraction is found to have a substantial effect on fuel-cell efficiency, power density, and heat-release profiles. The paper also explores the effects of internal reforming chemistry and electrochemical charge transfer on the gas-phase kinetics and propensity for deposit formation. A detailed reaction mechanism is used to describe methane steam reforming on Ni within the anode, while a detailed gas-phase mechanism is used to predict the gas-phase composition in the fuel channel.

  20. Information Packet on Surrogate Parents.

    ERIC Educational Resources Information Center

    Moore, Jean J.; Mason, Doris M.

    The information packet focuses on the role of the surrogate parent with emphasis on the rights of the handicapped child as mandated by P.L. 94-142, the Education for All Handicapped Children Act. Included are the following: a discussion of 10 surrogate parent issues identified through a literature search and survey of five states (Connecticut,…

  1. Projection in surrogate decisions about life-sustaining medical treatments.

    PubMed

    Fagerlin, A; Ditto, P H; Danks, J H; Houts, R M; Smucker, W D

    2001-05-01

    To honor the wishes of an incapacitated patient, surrogate decision makers must predict the treatment decisions patients would make for themselves if able. Social psychological research, however, suggests that surrogates' own treatment preferences may influence their predictions of others' preferences. In 2 studies (1 involving 60 college student surrogates and a parent, the other involving 361 elderly outpatients and their chosen surrogate decision maker), surrogates predicted whether a close other would want life-sustaining treatment in hypothetical end-of-life scenarios and stated their own treatment preferences in the same scenarios. Surrogate predictions more closely resembled surrogates' own treatment wishes than they did the wishes of the individual they were trying to predict. Although the majority of prediction errors reflected inaccurate use of surrogates' own treatment preferences, projection was also found to result in accurate prediction more often than counterprojective predictions. The rationality and accuracy of projection in surrogate decision making is discussed. PMID:11403214

  2. Structure-Based Prediction of Drug Distribution Across the Headgroup and Core Strata of a Phospholipid Bilayer Using Surrogate Phases

    PubMed Central

    2015-01-01

    Solvation of drugs in the core (C) and headgroup (H) strata of phospholipid bilayers affects their physiological transport rates and accumulation. These characteristics, especially a complete drug distribution profile across the bilayer strata, are tedious to obtain experimentally, to the point that even simplified preferred locations are only available for a few dozen compounds. Recently, we showed that the partition coefficient (P) values in the system of hydrated diacetyl phosphatidylcholine (DAcPC) and n-hexadecane (C16), as surrogates of the H- and C-strata of the bilayer composed of the most abundant mammalian phospholipid, PC, agree well with the preferred bilayer location of compounds. High P values are typical for lipophiles accumulating in the core, and low P values are characteristic of cephalophiles preferring the headgroups. This simple pattern does not hold for most compounds, which usually have more even distribution and may also accumulate at the H/C interface. To model complete distribution, the correlates of solvation energies are needed for each drug state in the bilayer: (1) for the H-stratum it is the DAcPC/W P value, calculated as the ratio of the C16/W and C16/DAcPC (W for water) P values; (2) for the C-stratum, the C16/W P value; (3) for the H/C interface, the P values for all plausible molecular poses are characterized using the fragment DAcPC/W and C16/W solvation parameters for the parts of the molecule embedded in the H- and C-strata, respectively. The correlates, each scaled by two Collander coefficients, were used in a nonlinear, mass-balance based model of intrabilayer distribution, which was applied to the easily measurable overall P values of compounds in the DMPC (M = myristoyl) bilayers and monolayers as the dependent variables. The calibrated model for 107 neutral compounds explains 94% of experimental variance, achieves similar cross-validation levels, and agrees well with the nontrivial, experimentally determined bilayer

  3. A comparison of lung motion measured using implanted electromagnetic transponders and motion algorithmically predicted using external surrogates as an alternative to respiratory correlated CT imaging

    NASA Astrophysics Data System (ADS)

    Lechleiter, Kristen M.; Low, Daniel A.; Chaudhari, Amir; Lu, Wei; Hubenschmidt, James P.; Mayse, Martin L.; Dimmer, Steven C.; Bradley, Jeffrey D.; Parikh, Parag J.

    2007-03-01

    Three-dimensional volumetric imaging correlated with respiration (4DCT) typically utilizes external breathing surrogates and phase-based models to determine lung tissue motion. However, 4DCT requires time consuming post-processing and the relationship between external breathing surrogates and lung tissue motion is not clearly defined. This study compares algorithms using external respiratory motion surrogates as predictors of internal lung motion tracked in real-time by electromagnetic transponders (Calypso® Medical Technologies) implanted in a canine model. Simultaneous spirometry, bellows, and transponder positions measurements were acquired during free breathing and variable ventilation respiratory patterns. Functions of phase, amplitude, tidal volume, and airflow were examined by least-squares regression analysis to determine which algorithm provided the best estimate of internal motion. The cosine phase model performed the worst of all models analyzed (R2 = 31.6%, free breathing, and R2 = 14.9%, variable ventilation). All algorithms performed better during free breathing than during variable ventilation measurements. The 5D model of tidal volume and airflow predicted transponder location better than amplitude or either of the two phasebased models analyzed, with correlation coefficients of 66.1% and 64.4% for free breathing and variable ventilation respectively. Real-time implanted transponder based measurements provide a direct method for determining lung tissue location. Current phase-based or amplitude-based respiratory motion algorithms cannot as accurately predict lung tissue motion in an irregularly breathing subject as a model including tidal volume and airflow. Further work is necessary to quantify the long term stability of prediction capabilities using amplitude and phase based algorithms for multiple lung tumor positions over time.

  4. Protein signatures as potential surrogate biomarkers for stratification and prediction of treatment response in chronic myeloid leukemia patients

    PubMed Central

    Alaiya, Ayodele A.; Aljurf, Mahmoud; Shinwari, Zakia; Almohareb, Fahad; Malhan, Hafiz; Alzahrani, Hazzaa; Owaidah, Tarek; Fox, Jonathan; Alsharif, Fahad; Mohamed, Said Y.; Rasheed, Walid; Aldawsari, Ghuzayel; Hanbali, Amr; Ahmed, Syed Osman; Chaudhri, Naeem

    2016-01-01

    There is unmet need for prediction of treatment response for chronic myeloid leukemia (CML) patients. The present study aims to identify disease-specific/disease-associated protein biomarkers detectable in bone marrow and peripheral blood for objective prediction of individual’s best treatment options and prognostic monitoring of CML patients. Bone marrow plasma (BMP) and peripheral blood plasma (PBP) samples from newly-diagnosed chronic-phase CML patients were subjected to expression-proteomics using quantitative two-dimensional gel electrophoresis (2-DE) and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of 2-DE protein fingerprints preceding therapy commencement accurately predicts 13 individuals that achieved major molecular response (MMR) at 6 months from 12 subjects without MMR (No-MMR). Results were independently validated using LC-MS/MS analysis of BMP and PBP from patients that have more than 24 months followed-up. One hundred and sixty-four and 138 proteins with significant differential expression profiles were identified from PBP and BMP, respectively and only 54 proteins overlap between the two datasets. The protein panels also discriminates accurately patients that stay on imatinib treatment from patients ultimately needing alternative treatment. Among the identified proteins are TYRO3, a member of TAM family of receptor tyrosine kinases (RTKs), the S100A8, and MYC and all of which have been implicated in CML. Our findings indicate analyses of a panel of protein signatures is capable of objective prediction of molecular response and therapy choice for CML patients at diagnosis as ‘personalized-medicine-model’. PMID:27573699

  5. Protein signatures as potential surrogate biomarkers for stratification and prediction of treatment response in chronic myeloid leukemia patients.

    PubMed

    Alaiya, Ayodele A; Aljurf, Mahmoud; Shinwari, Zakia; Almohareb, Fahad; Malhan, Hafiz; Alzahrani, Hazzaa; Owaidah, Tarek; Fox, Jonathan; Alsharif, Fahad; Mohamed, Said Y; Rasheed, Walid; Aldawsari, Ghuzayel; Hanbali, Amr; Ahmed, Syed Osman; Chaudhri, Naeem

    2016-09-01

    There is unmet need for prediction of treatment response for chronic myeloid leukemia (CML) patients. The present study aims to identify disease-specific/disease-associated protein biomarkers detectable in bone marrow and peripheral blood for objective prediction of individual's best treatment options and prognostic monitoring of CML patients. Bone marrow plasma (BMP) and peripheral blood plasma (PBP) samples from newly-diagnosed chronic-phase CML patients were subjected to expression-proteomics using quantitative two-dimensional gel electrophoresis (2-DE) and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of 2-DE protein fingerprints preceding therapy commencement accurately predicts 13 individuals that achieved major molecular response (MMR) at 6 months from 12 subjects without MMR (No-MMR). Results were independently validated using LC-MS/MS analysis of BMP and PBP from patients that have more than 24 months followed-up. One hundred and sixty-four and 138 proteins with significant differential expression profiles were identified from PBP and BMP, respectively and only 54 proteins overlap between the two datasets. The protein panels also discriminates accurately patients that stay on imatinib treatment from patients ultimately needing alternative treatment. Among the identified proteins are TYRO3, a member of TAM family of receptor tyrosine kinases (RTKs), the S100A8, and MYC and all of which have been implicated in CML. Our findings indicate analyses of a panel of protein signatures is capable of objective prediction of molecular response and therapy choice for CML patients at diagnosis as 'personalized-medicine-model'. PMID:27573699

  6. Software Surrogate

    NASA Technical Reports Server (NTRS)

    1999-01-01

    In 1994, Blackboard Technology received a NASA Phase I SBIR award entitled "A Blackboard-Based Framework for Mixed-Initiative, Crewed- Space-System Applications." This research continued in Phase II at JSC, where a generic architecture was developed in which a software surrogate serves as the operator's representative in the fast-paced realm of nearly autonomous, intelligent systems. This SBIR research effort addressed the need to support human-operator monitoring and intervention with intelligent systems such as those being developed for NASA's crewed space program.

  7. Predicting missing links and identifying spurious links via likelihood analysis

    NASA Astrophysics Data System (ADS)

    Pan, Liming; Zhou, Tao; Lü, Linyuan; Hu, Chin-Kun

    2016-03-01

    Real network data is often incomplete and noisy, where link prediction algorithms and spurious link identification algorithms can be applied. Thus far, it lacks a general method to transform network organizing mechanisms to link prediction algorithms. Here we use an algorithmic framework where a network’s probability is calculated according to a predefined structural Hamiltonian that takes into account the network organizing principles, and a non-observed link is scored by the conditional probability of adding the link to the observed network. Extensive numerical simulations show that the proposed algorithm has remarkably higher accuracy than the state-of-the-art methods in uncovering missing links and identifying spurious links in many complex biological and social networks. Such method also finds applications in exploring the underlying network evolutionary mechanisms.

  8. Predicting missing links and identifying spurious links via likelihood analysis

    PubMed Central

    Pan, Liming; Zhou, Tao; Lü, Linyuan; Hu, Chin-Kun

    2016-01-01

    Real network data is often incomplete and noisy, where link prediction algorithms and spurious link identification algorithms can be applied. Thus far, it lacks a general method to transform network organizing mechanisms to link prediction algorithms. Here we use an algorithmic framework where a network’s probability is calculated according to a predefined structural Hamiltonian that takes into account the network organizing principles, and a non-observed link is scored by the conditional probability of adding the link to the observed network. Extensive numerical simulations show that the proposed algorithm has remarkably higher accuracy than the state-of-the-art methods in uncovering missing links and identifying spurious links in many complex biological and social networks. Such method also finds applications in exploring the underlying network evolutionary mechanisms. PMID:26961965

  9. Predicting missing links and identifying spurious links via likelihood analysis.

    PubMed

    Pan, Liming; Zhou, Tao; Lü, Linyuan; Hu, Chin-Kun

    2016-01-01

    Real network data is often incomplete and noisy, where link prediction algorithms and spurious link identification algorithms can be applied. Thus far, it lacks a general method to transform network organizing mechanisms to link prediction algorithms. Here we use an algorithmic framework where a network's probability is calculated according to a predefined structural Hamiltonian that takes into account the network organizing principles, and a non-observed link is scored by the conditional probability of adding the link to the observed network. Extensive numerical simulations show that the proposed algorithm has remarkably higher accuracy than the state-of-the-art methods in uncovering missing links and identifying spurious links in many complex biological and social networks. Such method also finds applications in exploring the underlying network evolutionary mechanisms. PMID:26961965

  10. Identifying predictive morphologic features of malignancy in eyelid lesions

    PubMed Central

    Leung, Christina; Johnson, Davin; Pang, Renee; Kratky, Vladimir

    2015-01-01

    Abstract Objective To determine features of eyelid lesions most predictive of malignancy, and to design a key to assist general practitioners in the triaging of such lesions. Design Prospective observational study. Setting Department of Ophthalmology at Queen’s University in Kingston, Ont. Participants A total of 199 consecutive periocular lesions requiring biopsy or excision were included. Main outcome measures First, potential features suggestive of malignancy for eyelid lesions were identified based on a survey sent to Canadian oculoplastic surgeons. The sensitivity, specificity, and odds ratios (ORs) of these features were then determined using 199 consecutive photographed eyelid lesions of patients who presented to the Department of Ophthalmology and underwent biopsy or excision. A triage key was then created based on the features with the highest ORs, and it was pilot-tested by a group of medical students. Results Of the 199 lesions included, 161 (80.9%) were benign and 38 (19.1%) were malignant. The 3 features with the highest ORs in predicting malignancy were infiltration (OR = 18.2, P < .01), ulceration (OR = 14.7, P < .01), and loss of eyelashes (OR = 6.0, P < .01). The acronym LUI (loss of eyelashes, ulceration, infiltration) was created to assist in memory recall. After watching a video describing the LUI triage key, the mean total score of a group of medical students for correctly identifying malignant lesions increased from 46% to 70% (P < .001). Conclusion Differentiating benign from malignant eyelid lesions can be difficult even for experienced physicians. The LUI triage key provides physicians with an evidence-based, easy-to-remember system for assisting in the triaging of these lesions. PMID:25756148

  11. A new framework for selecting environmental surrogates.

    PubMed

    Lindenmayer, David; Pierson, Jennifer; Barton, Philip; Beger, Maria; Branquinho, Cristina; Calhoun, Aram; Caro, Tim; Greig, Hamish; Gross, John; Heino, Jani; Hunter, Malcolm; Lane, Peter; Longo, Catherine; Martin, Kathy; McDowell, William H; Mellin, Camille; Salo, Hanna; Tulloch, Ayesha; Westgate, Martin

    2015-12-15

    Surrogate concepts are used in all sub-disciplines of environmental science. However, controversy remains regarding the extent to which surrogates are useful for resolving environmental problems. Here, we argue that conflicts about the utility of surrogates (and the related concepts of indicators and proxies) often reflect context-specific differences in trade-offs between measurement accuracy and practical constraints. By examining different approaches for selecting and applying surrogates, we identify five trade-offs that correspond to key points of contention in the application of surrogates. We then present an 8-step Adaptive Surrogacy Framework that incorporates cross-disciplinary perspectives from a wide spectrum of the environmental sciences, aiming to unify surrogate concepts across disciplines and applications. Our synthesis of the science of surrogates is intended as a first step towards fully leveraging knowledge accumulated across disciplines, thus consolidating lessons learned so that they may be accessible to all those operating in different fields, yet facing similar hurdles. PMID:26298409

  12. Surrogate motherhood.

    PubMed

    Chang, Curtis Li-ming

    2004-03-01

    A "surrogate mother" is a woman who, for financial or other reasons, agrees to bear a child for another woman who is incapable to conceive herself. In other words, she is a "substitute mother" that conceives, gestates and delivers a baby on behalf of another woman who is subsequently to be seen as the "real" (social and legal) mother of the child. Though the practice of surrogacy has already become a big market in western countries, it has also generated countless challenges for the law because it adds a third dimension to the meaning of motherhood. Like adoption, surrogacy separates the role of rearing mother from what the law has called the natural mother, but gestational surrogacy breaks the latter down into the roles of genetic mother and birth mother, leaving two women with biological connections to the child. Because surrogacy tends to commodify and dehumanize people, and because of all its legal, social, and psychological complications, it is obviously not wise to accept surrogacy as an alternative way of procreation. PMID:15460596

  13. Use of surrogate outcomes in US FDA drug approvals, 2003–2012: a survey

    PubMed Central

    Yu, Tsung; Hsu, Yea-Jen; Fain, Kevin M; Boyd, Cynthia M; Holbrook, Janet T; Puhan, Milo A

    2015-01-01

    Objective To evaluate, across a spectrum of diseases, how often surrogate outcomes are used as a basis for drug approvals by the US Food and Drug Administration (FDA), and whether and how the rationale for using treatment effects on surrogates as predictors of treatment effects on patient-centred outcomes is discussed. Study design and setting We used the Drugs@FDA website to identify drug approvals produced from 2003 to 2012 by the FDA. We focused on four diseases (chronic obstructive pulmonary disease (COPD), type 1 or 2 diabetes, glaucoma and osteoporosis) for which surrogates are commonly used in trials. We reviewed the drug labels and medical reviews to provide empirical evidence on how surrogate outcomes are handled by the FDA. Results Of 1043 approvals screened, 58 (6%) were for the four diseases of interest. Most drugs for COPD (7/9, 78%), diabetes (26/26, 100%) and glaucoma (9/9, 100%) were approved based on surrogates while for osteoporosis, most drugs (10/14, 71%) were also approved for patient-centred outcomes (fractures). The rationale for using surrogates was discussed in 11 of the 43 (26%) drug approvals based on surrogates. In these drug approvals, we found drug approvals for diabetes are more likely than the other examined conditions to contain a discussion of trial evidence demonstrating that treatment effects on surrogate outcomes predict treatment effects on patient-centred outcomes. Conclusions Our results suggest that the FDA did not use a consistent approach to address surrogates in assessing the benefits and harms of drugs for COPD, type 1 or 2 diabetes, glaucoma and osteoporosis. For evaluating new drugs, patient-centred outcomes should be chosen whenever possible. If the use of surrogate outcomes is necessary, then a consistent approach is important to review the evidence for surrogacy and consider surrogate's usage in the treatment and population under study. PMID:26614616

  14. Surrogate consent to non-beneficial research: erring on the right side when substituted judgments may be inaccurate.

    PubMed

    Johansson, Mats; Broström, Linus

    2016-04-01

    Part of the standard protection of decisionally incapacitated research subjects is a prohibition against enrolling them unless surrogate decision makers authorize it. A common view is that surrogates primarily ought to make their decisions based on what the decisionally incapacitated subject would have wanted regarding research participation. However, empirical studies indicate that surrogate predictions about such preferences are not very accurate. The focus of this article is the significance of surrogate accuracy in the context of research that is not expected to benefit the research subject. We identify three morally relevant asymmetries between being enrolled and not being enrolled in such non-beneficial research, and conclude that when there is a non-negligible probability that surrogates' predictions are wrong, it will generally be better to err on the side of not authorizing enrollment. PMID:27130296

  15. A Surrogate Approach to the Experimental Optimization of Multielement Airfoils

    NASA Technical Reports Server (NTRS)

    Otto, John C.; Landman, Drew; Patera, Anthony T.

    1996-01-01

    The incorporation of experimental test data into the optimization process is accomplished through the use of Bayesian-validated surrogates. In the surrogate approach, a surrogate for the experiment (e.g., a response surface) serves in the optimization process. The validation step of the framework provides a qualitative assessment of the surrogate quality, and bounds the surrogate-for-experiment error on designs "near" surrogate-predicted optimal designs. The utility of the framework is demonstrated through its application to the experimental selection of the trailing edge ap position to achieve a design lift coefficient for a three-element airfoil.

  16. Identifying Future Scientists: Predicting Persistence into Research Training

    ERIC Educational Resources Information Center

    McGee, Richard; Keller, Jill L.

    2007-01-01

    This study used semistructured interviews and grounded theory to look for characteristics among college undergraduates that predicted persistence into Ph.D. and M.D./Ph.D. training. Participants in the summer undergraduate and postbaccalaureate research programs at the Mayo Clinic College of Medicine were interviewed at the start, near the end,…

  17. Use of a simple anthropometric measurement to predict birth weight. WHO Collaborative Study of Birth Weight Surrogates.

    PubMed Central

    1993-01-01

    Low-birth-weight babies are most at risk of infant mortality. Unfortunately, in many developing countries it is not possible to weigh babies accurately because of the lack of robust scales. This article describes the results of a WHO Collaborative Study to investigate whether birth weight can be predicted accurately using chest circumference and/or arm circumference. The implications of the results for paediatric practice in developing countries are discussed. PMID:8490977

  18. Assessing the Surrogate Susceptibility of Oxacillin and Cefoxitin for Commonly Utilized Parenteral Agents against Methicillin-Susceptible Staphylococcus aureus: Focus on Ceftriaxone Discordance between Predictive Susceptibility and in Vivo Exposures

    PubMed Central

    Kang, Nayon; Housman, Seth T.; Nicolau, David P.

    2015-01-01

    Susceptibility testing with the use of surrogate agents is common among clinical microbiology laboratories. One such example is oxacillin and cefoxitin for β-lactams against methicillin-susceptible Staphylococcus aureus (MSSA). This study aimed to assess the surrogate predictive value (SPV) of oxacillin and cefoxitin for the susceptibility of commonly utilized parenteral β-lactams against MSSA as well as to evaluate the concordance between predictive susceptibility testing and the in vivo exposures for ceftriaxone. Broth microdilution MICs were determined for cefazolin, cefoxitin, ceftaroline, ceftriaxone, nafcillin, and oxacillin against a national collection of 1238 MSSA from US hospitals. Pharmacodynamic profiling was utilized to establish a clinical breakpoint for commonly utilized doses of ceftriaxone. Oxacillin had good SPVs for all the β-lactams tested, whereas cefoxitin produced unacceptable major errors for all four agents and thus appears to be an unacceptable susceptibility surrogate. While oxacillin is an adequate surrogate based on the currently defined laboratory criteria, our data also suggest that caution should be exercised when incorporating this testing approach in the clinical setting in view of the fact that the MIC distribution of MSSA coupled with the commonly utilized low doses of ceftriaxone may result in inadequate in vivo exposures against this pathogen. PMID:26264030

  19. Assessing the Surrogate Susceptibility of Oxacillin and Cefoxitin for Commonly Utilized Parenteral Agents against Methicillin-Susceptible Staphylococcus aureus: Focus on Ceftriaxone Discordance between Predictive Susceptibility and in Vivo Exposures.

    PubMed

    Kang, Nayon; Housman, Seth T; Nicolau, David P

    2015-01-01

    Susceptibility testing with the use of surrogate agents is common among clinical microbiology laboratories. One such example is oxacillin and cefoxitin for β-lactams against methicillin-susceptible Staphylococcus aureus (MSSA). This study aimed to assess the surrogate predictive value (SPV) of oxacillin and cefoxitin for the susceptibility of commonly utilized parenteral β-lactams against MSSA as well as to evaluate the concordance between predictive susceptibility testing and the in vivo exposures for ceftriaxone. Broth microdilution MICs were determined for cefazolin, cefoxitin, ceftaroline, ceftriaxone, nafcillin, and oxacillin against a national collection of 1238 MSSA from US hospitals. Pharmacodynamic profiling was utilized to establish a clinical breakpoint for commonly utilized doses of ceftriaxone. Oxacillin had good SPVs for all the β-lactams tested, whereas cefoxitin produced unacceptable major errors for all four agents and thus appears to be an unacceptable susceptibility surrogate. While oxacillin is an adequate surrogate based on the currently defined laboratory criteria, our data also suggest that caution should be exercised when incorporating this testing approach in the clinical setting in view of the fact that the MIC distribution of MSSA coupled with the commonly utilized low doses of ceftriaxone may result in inadequate in vivo exposures against this pathogen. PMID:26264030

  20. Identifying Future Scientists: Predicting Persistence into Research Training

    PubMed Central

    2007-01-01

    This study used semistructured interviews and grounded theory to look for characteristics among college undergraduates that predicted persistence into Ph.D. and M.D./Ph.D. training. Participants in the summer undergraduate and postbaccalaureate research programs at the Mayo Clinic College of Medicine were interviewed at the start, near the end, and 8–12 months after their research experience. Of more than 200 themes considered, five characteristics predicted those students who went on to Ph.D. and M.D./Ph.D. training or to M.D. training intending to do research: 1) Curiosity to discover the unknown, 2) Enjoyment of problem solving, 3) A high level of independence, 4) The desire to help others indirectly through research, and 5) A flexible, minimally structured approach to the future. Web-based surveys with different students confirmed the high frequency of curiosity and/or problem solving as the primary reason students planned research careers. No evidence was found for differences among men, women, and minority and nonminority students. Although these results seem logical compared with successful scientists, their constancy, predictive capabilities, and sharp contrast to students who chose clinical medicine were striking. These results provide important insights into selection and motivation of potential biomedical scientists and the early experiences that will motivate them toward research careers. PMID:18056303

  1. Identifying future scientists: predicting persistence into research training.

    PubMed

    McGee, Richard; Keller, Jill L

    2007-01-01

    This study used semistructured interviews and grounded theory to look for characteristics among college undergraduates that predicted persistence into Ph.D. and M.D./Ph.D. training. Participants in the summer undergraduate and postbaccalaureate research programs at the Mayo Clinic College of Medicine were interviewed at the start, near the end, and 8-12 months after their research experience. Of more than 200 themes considered, five characteristics predicted those students who went on to Ph.D. and M.D./Ph.D. training or to M.D. training intending to do research: 1) Curiosity to discover the unknown, 2) Enjoyment of problem solving, 3) A high level of independence, 4) The desire to help others indirectly through research, and 5) A flexible, minimally structured approach to the future. Web-based surveys with different students confirmed the high frequency of curiosity and/or problem solving as the primary reason students planned research careers. No evidence was found for differences among men, women, and minority and nonminority students. Although these results seem logical compared with successful scientists, their constancy, predictive capabilities, and sharp contrast to students who chose clinical medicine were striking. These results provide important insights into selection and motivation of potential biomedical scientists and the early experiences that will motivate them toward research careers. PMID:18056303

  2. Evaluation of Non-Viral Surrogate Markers as Predictive Indicators for Monitoring Progression of Human Immunodeficiency Virus Infection: An Eight-Year Analysis in a Regional Center.

    PubMed

    Rafatpanah, Houshang; Essmailian, Leila; Hedayati-Moghaddam, Mohammad Reza; Vakili, Rosita; Norouzi, Mehdi; Sarvghad, Mohammad Reza; Hosseinpour, Ali Mohammad; Sharebiani, Hiva; Rezaee, S A Rahim

    2016-01-01

    Suitable methods for clinical monitoring of HIV-infected patients are crucial in resource-poor settings. Demographic data, clinical staging, and laboratory findings for 112 asymptomatic subjects positive for HIV were assessed at the first admission and the last visit from 2002 to 2010. Cox regression analysis showed hemoglobin (Hb) (HR = 0.643, P = 0.021) to be a predictive indicator for disease progression, while CD4, CD8, and platelet counts showed low HRs, despite having significant probability values. Hb and total lymphocyte count (TLC) rapidly declined from stage II to III (10.9 and 29.6%, respectively). Reduced CD4 and platelet counts and Hb during stage I were associated with disease progression, and TLC was correlated with CD4 counts at the last follow-up (P < 0.001). However, WHO TLC cutoff of 1,200 cell/mm(3) had 26.1% sensitivity and 98.6% specificity. ROC curve analysis suggested that a TLC cutoff of 1,800 cell/mm(3) was more reliable in this region. Statistical analysis and data mining findings showed that Hb and TLC, and their rapid decline from stage II to III, in addition to reduced platelet count, could be valuable markers for a surrogate algorithm for monitoring of HIV-infected subjects and starting anti-viral therapy in the absence of sophisticated detection assays. PMID:25971319

  3. Feasibility of High-Power Diode Laser Array Surrogate to Support Development of Predictive Laser Lethality Model

    SciTech Connect

    Lowdermilk, W H; Rubenchik, A M; Springer, H K

    2011-01-13

    Predictive modeling and simulation of high power laser-target interactions is sufficiently undeveloped that full-scale, field testing is required to assess lethality of military directed-energy (DE) systems. The cost and complexity of such testing programs severely limit the ability to vary and optimize parameters of the interaction. Thus development of advanced simulation tools, validated by experiments under well-controlled and diagnosed laboratory conditions that are able to provide detailed physics insight into the laser-target interaction and reduce requirements for full-scale testing will accelerate development of DE weapon systems. The ultimate goal is a comprehensive end-to-end simulation capability, from targeting and firing the laser system through laser-target interaction and dispersal of target debris; a 'Stockpile Science' - like capability for DE weapon systems. To support development of advanced modeling and simulation tools requires laboratory experiments to generate laser-target interaction data. Until now, to make relevant measurements required construction and operation of very high power and complex lasers, which are themselves costly and often unique devices, operating in dedicated facilities that don't permit experiments on targets containing energetic materials. High power diode laser arrays, pioneered by LLNL, provide a way to circumvent this limitation, as such arrays capable of delivering irradiances characteristic of De weapon requires are self-contained, compact, light weight and thus easily transportable to facilities, such as the High Explosives Applications Facility (HEAF) at Lawrence Livermore National Laboratory (LLNL) where testing with energetic materials can be performed. The purpose of this study was to establish the feasibility of using such arrays to support future development of advanced laser lethality and vulnerability simulation codes through providing data for materials characterization and laser-material interaction

  4. Proteomic analysis of Plasmodium falciparum induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity.

    PubMed

    Ray, Sandipan; Kumar, Vipin; Bhave, Amruta; Singh, Vaidhvi; Gogtay, Nithya J; Thatte, Urmila M; Talukdar, Arunansu; Kochar, Sanjay K; Patankar, Swati; Srivastava, Sanjeeva

    2015-09-01

    India significantly contributes to the global malaria burden and has the largest population in the world at risk of malaria. This study aims to analyze alterations in the human serum proteome as a consequence of non-severe and severe infections by the malaria parasite Plasmodium falciparum to identify markers related to disease severity and to obtain mechanistic insights about disease pathogenesis and host immune responses. In discovery phase of the study, a comprehensive quantitative proteomic analysis was performed using gel-based (2D-DIGE) and gel-free (iTRAQ) techniques on two independent mass spectrometry platforms (ESI-Q-TOF and Q-Exactive mass spectrometry), and selected targets were validated by ELISA. Proteins showing altered serum abundance in falciparum malaria patients revealed the modulation of different physiological pathways including chemokine and cytokine signaling, IL-12 signaling and production in macrophages, complement cascades, blood coagulation, and protein ubiquitination pathways. Some muscle related and cytoskeletal proteins such as titin and galectin-3-binding protein were found to be up-regulated in severe malaria patients. Hemoglobin levels and platelet counts were also found to be drastically lower in severe malaria patients. Identified proteins including serum amyloid A, C-reactive protein, apolipoprotein E and haptoglobin, which exhibited sequential alterations in their serum abundance in different severity levels of malaria, could serve as potential predictive markers for disease severity. To the best of our information, we report here the first comprehensive analysis describing the serum proteomic alterations observed in severe P. falciparum infected patients from different malaria endemic regions of India. This article is part of a Special Issue entitled: Proteomics in India. PMID:25982387

  5. The oxidation of a gasoline surrogate in the negative temperature coefficient region

    SciTech Connect

    Lenhert, David B.; Miller, David L.; Cernansky, Nicholas P.; Owens, Kevin G.

    2009-03-15

    This experimental study investigated the preignition reactivity behavior of a gasoline surrogate in a pressurized flow reactor over the low and intermediate temperature regime (600-800 K) at elevated pressure (8 atm). The surrogate mixture, a volumetric blend of 4.6% 1-pentene, 31.8% toluene, 14.0% n-heptane, and 49.6% 2,2,4-trimethyl-pentane (iso-octane), was shown to reproduce the low and intermediate temperature reactivity of full boiling range fuels in a previous study. Each of the surrogate components were examined individually to identify the major intermediate species in order to improve existing kinetic models, where appropriate, and to provide a basis for examining constituent interactions in the surrogate mixture. n-Heptane and 1-pentene started reacting at 630 K and 640 K, respectively, and both fuels exhibited a strong negative temperature coefficient (NTC) behavior starting at 700 and 710 K, respectively. Iso-octane showed a small level of reactivity at 630 K and a weak NTC behavior starting at 665 K. Neat toluene was unreactive at these temperatures. The surrogate started reacting at 630 K and exhibited a strong NTC behavior starting at 693 K. The extent of fuel consumption varied for each of the surrogate constituents and was related to their general autoignition behavior. Most of the intermediates identified during the surrogate oxidation were species observed during the oxidation of the neat constituents; however, the surrogate mixture did exhibit a significant increase in intermediates associated with iso-octane oxidation, but not from n-heptane. While neat toluene was unreactive at these temperatures, in the mixture it reacted with the radical pool generated by the other surrogate components, forming benzaldehyde, benzene, phenol, and ethyl-benzene. The observed n-heptane, iso-octane, and surrogate oxidation behavior was compared to predictions using existing kinetic models. The n-heptane model reasonably predicted the disappearance of the fuel

  6. Surrogate screening models for the low physical activity criterion of frailty

    PubMed Central

    Eckel, Sandrah P.; Bandeen-Roche, Karen; Chaves, Paulo H.M.; Fried, Linda P.; Louis, Thomas A.

    2012-01-01

    Background and Aims Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized, semi-quantitative questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women’s Health and Aging Study (WHAS). Methods Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by “relative influence” in predicting low physical activity. We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality. Results Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive. Conclusions We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included. PMID:21993168

  7. Jet Pump Design Optimization by Multi-Surrogate Modeling

    NASA Astrophysics Data System (ADS)

    Mohan, S.; Samad, A.

    2015-01-01

    A basic approach to reduce the design and optimization time via surrogate modeling is to select a right type of surrogate model for a particular problem, where the model should have better accuracy and prediction capability. A multi-surrogate approach can protect a designer to select a wrong surrogate having high uncertainty in the optimal zone of the design space. Numerical analysis and optimization of a jet pump via multi-surrogate modeling have been reported in this work. Design variables including area ratio, mixing tube length to diameter ratio and setback ratio were introduced to increase the hydraulic efficiency of the jet pump. Reynolds-averaged Navier-Stokes equations were solved and responses were computed. Among different surrogate models, Sheppard function based surrogate shows better accuracy in data fitting while the radial basis neural network produced highest enhanced efficiency. The efficiency enhancement was due to the reduction of losses in the flow passage.

  8. Development and Validation of a Clinic-Based Prediction Tool to Identify Female Athletes at High Risk for Anterior Cruciate Ligament Injury

    PubMed Central

    Myer, Gregory D.; Ford, Kevin R.; Khoury, Jane; Succop, Paul; Hewett, Timothy E.

    2012-01-01

    Background Prospective measures of high knee abduction moment (KAM) during landing identify female athletes at high risk for anterior cruciate ligament injury. Laboratory-based measurements demonstrate 90% accuracy in prediction of high KAM. Clinic-based prediction algorithms that employ correlates derived from laboratory-based measurements also demonstrate high accuracy for prediction of high KAM mechanics during landing. Hypotheses Clinic-based measures derived from highly predictive laboratory-based models are valid for the accurate prediction of high KAM status, and simultaneous measurements using laboratory-based and clinic-based techniques highly correlate. Study Design Cohort study (diagnosis); Level of evidence, 2. Methods One hundred female athletes (basketball, soccer, volleyball players) were tested using laboratory-based measures to confirm the validity of identified laboratory-based correlate variables to clinic-based measures included in a prediction algorithm to determine high KAM status. To analyze selected clinic-based surrogate predictors, another cohort of 20 female athletes was simultaneously tested with both clinic-based and laboratory-based measures. Results The prediction model (odds ratio: 95% confidence interval), derived from laboratory-based surrogates including (1) knee valgus motion (1.59: 1.17-2.16 cm), (2) knee flexion range of motion (0.94: 0.89°-1.00°), (3) body mass (0.98: 0.94-1.03 kg), (4) tibia length (1.55: 1.20-2.07 cm), and (5) quadriceps-to-hamstrings ratio (1.70: 0.48%-6.0%), predicted high KAM status with 84% sensitivity and 67% specificity (P < .001). Clinic-based techniques that used a calibrated physician’s scale, a standard measuring tape, standard camcorder, ImageJ software, and an isokinetic dynamometer showed high correlation (knee valgus motion, r = .87; knee flexion range of motion, r = .95; and tibia length, r = .98) to simultaneous laboratory-based measurements. Body mass and quadriceps-to-hamstrings ratio

  9. Surrogate waveform models

    NASA Astrophysics Data System (ADS)

    Blackman, Jonathan; Field, Scott; Galley, Chad; Scheel, Mark; Szilagyi, Bela; Tiglio, Manuel

    2015-04-01

    With the advanced detector era just around the corner, there is a strong need for fast and accurate models of gravitational waveforms from compact binary coalescence. Fast surrogate models can be built out of an accurate but slow waveform model with minimal to no loss in accuracy, but may require a large number of evaluations of the underlying model. This may be prohibitively expensive if the underlying is extremely slow, for example if we wish to build a surrogate for numerical relativity. We examine alternate choices to building surrogate models which allow for a more sparse set of input waveforms. Research supported in part by NSERC.

  10. Surrogate clinical endpoints to predict overall survival in non-small cell lung cancer trials—are we in a new era?

    PubMed Central

    Wang, Xiaofei; Ready, Neal E.

    2015-01-01

    Surrogate endpoints for clinical trials in oncology offer an alternative metric for measuring clinical benefit, allowing for shorter trial duration, smaller patient cohorts, and single arm design. The correlation of surrogate endpoints with overall survival (OS) in therapeutic studies is a central consideration to their validity. The Food and Drug Administration (FDA) recently published an analysis of fourteen clinical trials in advanced non-small cell lung cancer (NSCLC), and discovered a strong association between response rate and progression free survival. Furthermore, a correlation between response rate and OS is demonstrated when analyzing the experimental treatment arm separately, minimizing bias from patient crossover. We also highlight multiple, important considerations when using response as an endpoint in clinical trials involving NSCLC patients. PMID:26798592

  11. Identifying developmental vascular disruptor compounds using a predictive signature and alternative toxicity models

    EPA Science Inventory

    Identifying Developmental Vascular Disruptor Compounds Using a Predictive Signature and Alternative Toxicity Models Presenting Author: Tamara Tal Affiliation: U.S. EPA/ORD/ISTD, RTP, NC, USA Chemically induced vascular toxicity during embryonic development can result in a wide...

  12. Intersecting pentagons as surrogate for identifying the use of mini mental state examination in assessment of dementia in a largely illiterate population

    PubMed Central

    Raina, SK; Maria, A; Chander, V; Raina, S

    2015-01-01

    Background and Rationale: The mini-mental state evaluation (MMSE) is often used to identify patients with dementia. One component of the MMSE is the intersecting pentagon copying (IPC) test, which may be difficult to be used in an illiterate population. Materials and Methods: A post hoc analysis on an elderly population (60 years and above) from Himachal Pradesh was carried out. The data of only 1,513 elderly individuals out of a total of 2,000 participants with a score of more than 26 (nondemented) out of a possible score of 30 on cognitive battery available were used. The scores on the IPC were evaluated and their association with some demographic variables was also assessed. Results: Illiterate participants, female participants, those with greater age, and the rural/tribal population groups faced the most difficulty in drawing the intersecting pentagons and even greater difficulty in drawing them correctly. Discussion: The IPC presents challenges for people who are illiterate and the scoring method needs to be addressed and changed particularly when the test is used in largely illiterate populations. PMID:26440395

  13. Assessing the Validity of Surrogate Outcomes for ESRD: A Meta-Analysis.

    PubMed

    Jun, Min; Turin, Tanvir Chowdhury; Woodward, Mark; Perkovic, Vlado; Lambers Heerspink, Hiddo J; Manns, Braden J; Tonelli, Marcello; Hemmelgarn, Brenda R

    2015-09-01

    Validation of current and promising surrogate outcomes for ESRD in randomized controlled trials (RCTs) has been limited. We conducted a systematic review and meta-analysis of RCTs to further inform the ability of surrogate outcomes for ESRD to predict the efficacy of various interventions on ESRD. MEDLINE, EMBASE, and CENTRAL (from inception through September 2013) were searched. All RCTs in adults with proteinuria, diabetes, or CKD stages 1-4 or renal transplant recipients reporting ≥10 ESRD events and a surrogate outcome (change in proteinuria or doubling of serum creatinine [DSCR]) for ESRD during a ≥1-year follow-up were included. Two reviewers abstracted trial characteristics and outcome data independently. To assess the correlation between the surrogate outcomes and ESRD, we determined the treatment effect ratio (TER), defined as the ratio of the treatment effects on ESRD and the effects on the change in surrogate outcomes. TERs close to 1 indicate greater agreement between ESRD and the surrogate, and these ratios were pooled across interventions. We identified 27 trials (97,458 participants; 4187 participants with ESRD). Seven trials reported the effects on change in proteinuria and showed consistent effects for proteinuria and ESRD (TER, 0.82; 95% confidence interval, 0.59 to 1.16), with minimal heterogeneity. Twenty trials reported on DSCR. Treatment effects on DSCR were consistent with the effects on ESRD (TER, 0.98; 95% confidence interval, 0.85 to 1.14), with moderate heterogeneity. In conclusion, DSCR is generally a good surrogate for ESRD, whereas data on proteinuria were limited. Further assessment of the surrogacy of proteinuria using prospective RCTs is warranted. PMID:25556165

  14. MRI Surrogates for Molecular Subgroups of Medulloblastoma

    PubMed Central

    Perreault, S.; Ramaswamy, V.; Achrol, A.S.; Chao, K.; Liu, T.T.; Shih, D.; Remke, M.; Schubert, S.; Bouffet, E.; Fisher, P.G.; Partap, S.; Vogel, H.; Taylor, M.D.; Cho, Y.J.; Yeom, K.W.

    2016-01-01

    BACKGROUND AND PURPOSE Recently identified molecular subgroups of medulloblastoma have shown potential for improved risk stratification. We hypothesized that distinct MR imaging features can predict these subgroups. MATERIALS AND METHODS All patients with a diagnosis of medulloblastoma at one institution, with both pretherapy MR imaging and surgical tissue, served as the discovery cohort (n = 47). MR imaging features were assessed by 3 blinded neuroradiologists. NanoString-based assay of tumor tissues was conducted to classify the tumors into the 4 established molecular subgroups (wingless, sonic hedgehog, group 3, and group 4). A second pediatric medulloblastoma cohort (n = 52) from an independent institution was used for validation of the MR imaging features predictive of the molecular subtypes. RESULTS Logistic regression analysis within the discovery cohort revealed tumor location (P < .001) and enhancement pattern (P = .001) to be significant predictors of medulloblastoma subgroups. Stereospecific computational analyses confirmed that group 3 and 4 tumors predominated within the midline fourth ventricle (100%, P = .007), wingless tumors were localized to the cerebellar peduncle/cerebellopontine angle cistern with a positive predictive value of 100% (95% CI, 30%–100%), and sonic hedgehog tumors arose in the cerebellar hemispheres with a positive predictive value of 100% (95% CI, 59%–100%). Midline group 4 tumors presented with minimal/no enhancement with a positive predictive value of 91% (95% CI, 59%–98%). When we used the MR imaging feature–based regression model, 66% of medulloblastomas were correctly predicted in the discovery cohort, and 65%, in the validation cohort. CONCLUSIONS Tumor location and enhancement pattern were predictive of molecular subgroups of pediatric medulloblastoma and may potentially serve as a surrogate for genomic testing. PMID:24831600

  15. Plutonium radiation surrogate

    DOEpatents

    Frank, Michael I.

    2010-02-02

    A self-contained source of gamma-ray and neutron radiation suitable for use as a radiation surrogate for weapons-grade plutonium is described. The source generates a radiation spectrum similar to that of weapons-grade plutonium at 5% energy resolution between 59 and 2614 keV, but contains no special nuclear material and emits little .alpha.-particle radiation. The weapons-grade plutonium radiation surrogate also emits neutrons having fluxes commensurate with the gamma-radiation intensities employed.

  16. GeneValidator: identify problems with protein-coding gene predictions

    PubMed Central

    Drăgan, Monica-Andreea; Moghul, Ismail; Priyam, Anurag; Bustos, Claudio; Wurm, Yannick

    2016-01-01

    Summary: Genomes of emerging model organisms are now being sequenced at very low cost. However, obtaining accurate gene predictions remains challenging: even the best gene prediction algorithms make substantial errors and can jeopardize subsequent analyses. Therefore, many predicted genes must be time-consumingly visually inspected and manually curated. We developed GeneValidator (GV) to automatically identify problematic gene predictions and to aid manual curation. For each gene, GV performs multiple analyses based on comparisons to gene sequences from large databases. The resulting report identifies problematic gene predictions and includes extensive statistics and graphs for each prediction to guide manual curation efforts. GV thus accelerates and enhances the work of biocurators and researchers who need accurate gene predictions from newly sequenced genomes. Availability and implementation: GV can be used through a web interface or in the command-line. GV is open-source (AGPL), available at https://wurmlab.github.io/tools/genevalidator. Contact: y.wurm@qmul.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26787666

  17. Detailed Kinetic Modeling of Gasoline Surrogate Mixtures

    SciTech Connect

    Mehl, M; Curran, H J; Pitz, W J; Westbrook, C K

    2009-03-09

    Real fuels are complex mixtures of thousands of hydrocarbon compounds including linear and branched paraffins, naphthenes, olefins and aromatics. It is generally agreed that their behavior can be effectively reproduced by simpler fuel surrogates containing a limited number of components. In this work, a recently revised version of the kinetic model by the authors is used to analyze the combustion behavior of several components relevant to gasoline surrogate formulation. Particular attention is devoted to linear and branched saturated hydrocarbons (PRF mixtures), olefins (1-hexene) and aromatics (toluene). Model predictions for pure components, binary mixtures and multi-component gasoline surrogates are compared with recent experimental information collected in rapid compression machine, shock tube and jet stirred reactors covering a wide range of conditions pertinent to internal combustion engines. Simulation results are discussed focusing attention on the mixing effects of the fuel components.

  18. [Immunological surrogate endpoints to evaluate vaccine efficacy].

    PubMed

    Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai

    2015-12-01

    An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description. PMID:26887309

  19. The Surrogate Self

    ERIC Educational Resources Information Center

    Gunnison, Hugh

    1976-01-01

    The use of the "surrogate self" in counseling is a simple Gestalt-like role-playing technique (Perls 1969) that can be especially effective when the client has begun to see the counselor as a trusted, caring, and understanding person. The role-playing is described. (Author/EJT)

  20. Using complete genome comparisons to identify sequences whose presence accurately predicts clinically important phenotypes.

    PubMed

    Hall, Barry G; Cardenas, Heliodoro; Barlow, Miriam

    2013-01-01

    In clinical settings it is often important to know not just the identity of a microorganism, but also the danger posed by that particular strain. For instance, Escherichia coli can range from being a harmless commensal to being a very dangerous enterohemorrhagic (EHEC) strain. Determining pathogenic phenotypes can be both time consuming and expensive. Here we propose a simple, rapid, and inexpensive method of predicting pathogenic phenotypes on the basis of the presence or absence of short homologous DNA segments in an isolate. Our method compares completely sequenced genomes without the necessity of genome alignments in order to identify the presence or absence of the segments to produce an automatic alignment of the binary string that describes each genome. Analysis of the segment alignment allows identification of those segments whose presence strongly predicts a phenotype. Clinical application of the method requires nothing more that PCR amplification of each of the set of predictive segments. Here we apply the method to identifying EHEC strains of E. coli and to distinguishing E. coli from Shigella. We show in silico that with as few as 8 predictive sequences, if even three of those predictive sequences are amplified the probability of being EHEC or Shigella is >0.99. The method is thus very robust to the occasional amplification failure for spurious reasons. Experimentally, we apply the method to screening a set of 98 isolates to distinguishing E. coli from Shigella, and EHEC from non-EHEC E. coli strains and show that all isolates are correctly identified. PMID:23935901

  1. Predicting Recidivism Among Adjudicated Delinquents: A Model to Identify High Risk Offenders.

    ERIC Educational Resources Information Center

    Grenier, Charles E.; Roundtree, George A.

    1987-01-01

    Studied 100 clients of the East Baton Rouge Parish Family Court to develop predictive model for identifying offenders at high risk for recidivism. Found important predictor variables to be presence of delinquent siblings or friends, school problems, type of offense committed, and gender of delinquent. (Author/NB)

  2. Trajectories of Substance Use Disorders in Youth: Identifying and Predicting Group Memberships

    ERIC Educational Resources Information Center

    Lee, Chih-Yuan S.; Winters, Ken C.; Wall, Melanie M.

    2010-01-01

    This study used latent class regression to identify latent trajectory classes based on individuals' diagnostic course of substance use disorders (SUDs) from late adolescence to early adulthood as well as to examine whether several psychosocial risk factors predicted the trajectory class membership. The study sample consisted of 310 individuals…

  3. Use of NMR and NMR Prediction Software to Identify Components in Red Bull Energy Drinks

    ERIC Educational Resources Information Center

    Simpson, Andre J.; Shirzadi, Azadeh; Burrow, Timothy E.; Dicks, Andrew P.; Lefebvre, Brent; Corrin, Tricia

    2009-01-01

    A laboratory experiment designed as part of an upper-level undergraduate analytical chemistry course is described. Students investigate two popular soft drinks (Red Bull Energy Drink and sugar-free Red Bull Energy Drink) by NMR spectroscopy. With assistance of modern NMR prediction software they identify and quantify major components in each…

  4. Using Predictive Modelling to Identify Students at Risk of Poor University Outcomes

    ERIC Educational Resources Information Center

    Jia, Pengfei; Maloney, Tim

    2015-01-01

    Predictive modelling is used to identify students at risk of failing their first-year courses and not returning to university in the second year. Our aim is twofold. Firstly, we want to understand the factors that lead to poor first-year experiences at university. Secondly, we want to develop simple, low-cost tools that would allow universities to…

  5. Sooting characteristics of surrogates for jet fuels

    SciTech Connect

    Mensch, Amy; Santoro, Robert J.; Litzinger, Thomas A.; Lee, S.-Y.

    2010-06-15

    Currently, modeling the combustion of aviation fuels, such as JP-8 and JetA, is not feasible due to the complexity and compositional variation of these practical fuels. Surrogate fuel mixtures, composed of a few pure hydrocarbon compounds, are a key step toward modeling the combustion of practical aviation fuels. For the surrogate to simulate the practical fuel, the composition must be designed to reproduce certain pre-designated chemical parameters such as sooting tendency, H/C ratio, autoignition, as well as physical parameters such as boiling range and density. In this study, we focused only on the sooting characteristics based on the Threshold Soot Index (TSI). New measurements of TSI values derived from the smoke point along with other sooting tendency data from the literature have been combined to develop a set of recommended TSI values for pure compounds used to make surrogate mixtures. When formulating the surrogate fuel mixtures, the TSI values of the components are used to predict the TSI of the mixture. To verify the empirical mixture rule for TSI, the TSI values of several binary mixtures of candidate surrogate components were measured. Binary mixtures were also used to derive a TSI for iso-cetane, which had not previously been measured, and to verify the TSI for 1-methylnaphthalene, which had a low smoke point and large relative uncertainty as a pure compound. Lastly, surrogate mixtures containing three components were tested to see how well the measured TSI values matched the predicted values, and to demonstrate that a target value for TSI can be maintained using various components, while also holding the H/C ratio constant. (author)

  6. Multidimensional Scaling of Video Surrogates.

    ERIC Educational Resources Information Center

    Goodrum, Abby A.

    2001-01-01

    Four types of video surrogates were compared under two tasks. Multidimensional scaling was used to map dimensional dispersions of users' judgments of similarity between videos and surrogates. Congruence between these maps was used to evaluate representativeness of each surrogate type. Congruence was greater for image-based than for text-based…

  7. Predicting performance at medical school: can we identify at-risk students?

    PubMed Central

    Shaban, Sami; McLean, Michelle

    2011-01-01

    Background The purpose of this study was to examine the predictive potential of multiple indicators (eg, preadmission scores, unit, module and clerkship grades, course and examination scores) on academic performance at medical school, with a view to identifying students at risk. Methods An analysis was undertaken of medical student grades in a 6-year medical school program at the Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates, over the past 14 years. Results While high school scores were significantly (P < 0.001) correlated with the final integrated examination, predictability was only 6.8%. Scores for the United Arab Emirates university placement assessment (Common Educational Proficiency Assessment) were only slightly more promising as predictors with 14.9% predictability for the final integrated examination. Each unit or module in the first four years was highly correlated with the next unit or module, with 25%–60% predictability. Course examination scores (end of years 2, 4, and 6) were significantly correlated (P < 0.001) with the average scores in that 2-year period (59.3%, 64.8%, and 55.8% predictability, respectively). Final integrated examination scores were significantly correlated (P < 0.001) with National Board of Medical Examiners scores (35% predictability). Multivariate linear regression identified key grades with the greatest predictability of the final integrated examination score at three stages in the program. Conclusion This study has demonstrated that it may be possible to identify “at-risk” students relatively early in their studies through continuous data archiving and regular analysis. The data analysis techniques used in this study are not unique to this institution. PMID:23745085

  8. High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury

    PubMed Central

    Wills, Lauren P.; Beeson, Gyda C.; Trager, Richard E.; Lindsey, Christopher C.; Beeson, Craig C.; Peterson, Yuri K.; Schnellmann, Rick G.

    2014-01-01

    Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 μM) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet. This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment. PMID:23811330

  9. Characterization of Potential Surrogates for Produce Pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Escherichia coli (E. coli) is commonly used as a surrogate for pathogens in research to identify sources of agricultural contamination and to characterize how pathogens persist on plant surfaces. However, E. coli strains are highly diverse, exhibiting differences in physical, chemical and...

  10. Nitrate Salt Surrogate Blending Scoping Test Plan

    SciTech Connect

    Anast, Kurt Roy

    2015-11-13

    Test blending equipment identified in the “Engineering Options Assessment Report: Nitrate Salt Waste Stream Processing”. Determine if the equipment will provide adequate mixing of zeolite and surrogate salt/Swheat stream; optimize equipment type and operational sequencing; impact of baffles and inserts on mixing performance; and means of validating mixing performance

  11. Temporal Effects in Trend Prediction: Identifying the Most Popular Nodes in the Future

    PubMed Central

    Zhou, Yanbo; Zeng, An; Wang, Wei-Hong

    2015-01-01

    Prediction is an important problem in different science domains. In this paper, we focus on trend prediction in complex networks, i.e. to identify the most popular nodes in the future. Due to the preferential attachment mechanism in real systems, nodes’ recent degree and cumulative degree have been successfully applied to design trend prediction methods. Here we took into account more detailed information about the network evolution and proposed a temporal-based predictor (TBP). The TBP predicts the future trend by the node strength in the weighted network with the link weight equal to its exponential aging. Three data sets with time information are used to test the performance of the new method. We find that TBP have high general accuracy in predicting the future most popular nodes. More importantly, it can identify many potential objects with low popularity in the past but high popularity in the future. The effect of the decay speed in the exponential aging on the results is discussed in detail. PMID:25806810

  12. Identifying the predictable and unpredictable patterns of spring-to-autumn precipitation over eastern China

    NASA Astrophysics Data System (ADS)

    Ying, Kairan; Zheng, Xiaogu; Zhao, Tianbao; Frederiksen, Carsten S.; Quan, Xiao-Wei

    2016-06-01

    The patterns of interannual variability that arise from the slow (potentially predictable) and fast or intraseasonal (unpredictable) components of seasonal mean precipitation over eastern China are examined, based on observations from a network of 106 stations for the period 1951-2004. The analysis is done by using a variance decomposition method that allows identification of the sources of the predictability and the prediction uncertainty, from March-April-May (MAM) to September-October-November (SON). The average potential predictability (ratio of slow-to-total variance) of eastern China precipitation is generally moderate, with the highest value of 0.18 in June-July-August (JJA) and lowest value of 0.12 in April-May-June (AMJ). The leading predictable precipitation mode is significantly related to one-season-lead SST anomalies in the area of the Kuroshio Current during AMJ-to-JJA, the Indian-western Pacific SST in July-August-September (JAS), and the eastern tropical Pacific SST in MAM and SON. The prolonged linear trends, which are seen in the principal component time series associated with the second or third predictable precipitation modes in MJJ-to-ASO, also serve as a source of predictability for seasonal precipitation over eastern China. The predictive characteristics of the atmospheric circulation-precipitation relationship indicate that the western Pacific subtropical high plays a key role in eastern China precipitation. In addition, teleconnection patterns that are significantly related to the predictable precipitation component are also identified. The leading/second unpredictable precipitation modes from MAM to SON all show a monopole/dipole structure, which are accompanied by wavy circulation patterns that are related to intraseasonal events.

  13. Identifying combinations of risk and protective factors predicting physical activity change in high school students.

    PubMed

    Dunton, Genevieve Fridlund; Atienza, Audie A; Tscherne, James; Rodriguez, Daniel

    2011-02-01

    Research sought to identify combinations of risk and protective factors predicting change in physical activity (PA) over one year in high school students. Adolescents (N = 344; M = 15.7 years) participated in a longitudinal study with assessment of demographics, substance use/smoking exposure, height and weight, psychological factors, and PA in 10th and 11th grade. PA participation in 11th grade was greatest for adolescents who engaged in PA and had high sports competence (78%), and least for adolescents who did not engage in or enjoy PA (13%) in 10th grade. Identifying adolescent subgroups at risk for decreasing PA can inform the development of tailored interventions. PMID:21467595

  14. kmer-SVM: a web server for identifying predictive regulatory sequence features in genomic data sets

    PubMed Central

    Fletez-Brant, Christopher; Lee, Dongwon; McCallion, Andrew S.; Beer, Michael A.

    2013-01-01

    Massively parallel sequencing technologies have made the generation of genomic data sets a routine component of many biological investigations. For example, Chromatin immunoprecipitation followed by sequence assays detect genomic regions bound (directly or indirectly) by specific factors, and DNase-seq identifies regions of open chromatin. A major bottleneck in the interpretation of these data is the identification of the underlying DNA sequence code that defines, and ultimately facilitates prediction of, these transcription factor (TF) bound or open chromatin regions. We have recently developed a novel computational methodology, which uses a support vector machine (SVM) with kmer sequence features (kmer-SVM) to identify predictive combinations of short transcription factor-binding sites, which determine the tissue specificity of these genomic assays (Lee, Karchin and Beer, Discriminative prediction of mammalian enhancers from DNA sequence. Genome Res. 2011; 21:2167–80). This regulatory information can (i) give confidence in genomic experiments by recovering previously known binding sites, and (ii) reveal novel sequence features for subsequent experimental testing of cooperative mechanisms. Here, we describe the development and implementation of a web server to allow the broader research community to independently apply our kmer-SVM to analyze and interpret their genomic datasets. We analyze five recently published data sets and demonstrate how this tool identifies accessory factors and repressive sequence elements. kmer-SVM is available at http://kmersvm.beerlab.org. PMID:23771147

  15. Accurate structure prediction of peptide–MHC complexes for identifying highly immunogenic antigens

    SciTech Connect

    Park, Min-Sun; Park, Sung Yong; Miller, Keith R.; Collins, Edward J.; Lee, Ha Youn

    2013-11-01

    Designing an optimal HIV-1 vaccine faces the challenge of identifying antigens that induce a broad immune capacity. One factor to control the breadth of T cell responses is the surface morphology of a peptide–MHC complex. Here, we present an in silico protocol for predicting peptide–MHC structure. A robust signature of a conformational transition was identified during all-atom molecular dynamics, which results in a model with high accuracy. A large test set was used in constructing our protocol and we went another step further using a blind test with a wild-type peptide and two highly immunogenic mutants, which predicted substantial conformational changes in both mutants. The center residues at position five of the analogs were configured to be accessible to solvent, forming a prominent surface, while the residue of the wild-type peptide was to point laterally toward the side of the binding cleft. We then experimentally determined the structures of the blind test set, using high resolution of X-ray crystallography, which verified predicted conformational changes. Our observation strongly supports a positive association of the surface morphology of a peptide–MHC complex to its immunogenicity. Our study offers the prospect of enhancing immunogenicity of vaccines by identifying MHC binding immunogens.

  16. Nonspinning numerical relativity waveform surrogates: assessing the model

    NASA Astrophysics Data System (ADS)

    Field, Scott; Blackman, Jonathan; Galley, Chad; Scheel, Mark; Szilagyi, Bela; Tiglio, Manuel

    2015-04-01

    Recently, multi-modal gravitational waveform surrogate models have been built directly from data numerically generated by the Spectral Einstein Code (SpEC). I will describe ways in which the surrogate model error can be quantified. This task, in turn, requires (i) characterizing differences between waveforms computed by SpEC with those predicted by the surrogate model and (ii) estimating errors associated with the SpEC waveforms from which the surrogate is built. Both pieces can have numerous sources of numerical and systematic errors. We make an attempt to study the most dominant error sources and, ultimately, the surrogate model's fidelity. These investigations yield information about the surrogate model's uncertainty as a function of time (or frequency) and parameter, and could be useful in parameter estimation studies which seek to incorporate model error. Finally, I will conclude by comparing the numerical relativity surrogate model to other inspiral-merger-ringdown models. A companion talk will cover the building of multi-modal surrogate models.

  17. Reduced cost mission design using surrogate models

    NASA Astrophysics Data System (ADS)

    Feldhacker, Juliana D.; Jones, Brandon A.; Doostan, Alireza; Hampton, Jerrad

    2016-01-01

    This paper uses surrogate models to reduce the computational cost associated with spacecraft mission design in three-body dynamical systems. Sampling-based least squares regression is used to project the system response onto a set of orthogonal bases, providing a representation of the ΔV required for rendezvous as a reduced-order surrogate model. Models are presented for mid-field rendezvous of spacecraft in orbits in the Earth-Moon circular restricted three-body problem, including a halo orbit about the Earth-Moon L2 libration point (EML-2) and a distant retrograde orbit (DRO) about the Moon. In each case, the initial position of the spacecraft, the time of flight, and the separation between the chaser and the target vehicles are all considered as design inputs. The results show that sample sizes on the order of 102 are sufficient to produce accurate surrogates, with RMS errors reaching 0.2 m/s for the halo orbit and falling below 0.01 m/s for the DRO. A single function call to the resulting surrogate is up to two orders of magnitude faster than computing the same solution using full fidelity propagators. The expansion coefficients solved for in the surrogates are then used to conduct a global sensitivity analysis of the ΔV on each of the input parameters, which identifies the separation between the spacecraft as the primary contributor to the ΔV cost. Finally, the models are demonstrated to be useful for cheap evaluation of the cost function in constrained optimization problems seeking to minimize the ΔV required for rendezvous. These surrogate models show significant advantages for mission design in three-body systems, in terms of both computational cost and capabilities, over traditional Monte Carlo methods.

  18. High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury

    SciTech Connect

    Wills, Lauren P.; Beeson, Gyda C.; Trager, Richard E.; Lindsey, Christopher C.; Beeson, Craig C.; Peterson, Yuri K.; Schnellmann, Rick G.

    2013-10-15

    Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 μM) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet. This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment. - Highlights: • Respirometric assay conducted in RPTC to create mitochondrial toxicant database. • Chemically similar mitochondrial toxicants aligned as mitochondrial toxicophores • Mitochondrial toxicophore identifies five novel mitochondrial toxicants.

  19. Surrogate Reservoir Model

    NASA Astrophysics Data System (ADS)

    Mohaghegh, Shahab

    2010-05-01

    Surrogate Reservoir Model (SRM) is new solution for fast track, comprehensive reservoir analysis (solving both direct and inverse problems) using existing reservoir simulation models. SRM is defined as a replica of the full field reservoir simulation model that runs and provides accurate results in real-time (one simulation run takes only a fraction of a second). SRM mimics the capabilities of a full field model with high accuracy. Reservoir simulation is the industry standard for reservoir management. It is used in all phases of field development in the oil and gas industry. The routine of simulation studies calls for integration of static and dynamic measurements into the reservoir model. Full field reservoir simulation models have become the major source of information for analysis, prediction and decision making. Large prolific fields usually go through several versions (updates) of their model. Each new version usually is a major improvement over the previous version. The updated model includes the latest available information incorporated along with adjustments that usually are the result of single-well or multi-well history matching. As the number of reservoir layers (thickness of the formations) increases, the number of cells representing the model approaches several millions. As the reservoir models grow in size, so does the time that is required for each run. Schemes such as grid computing and parallel processing helps to a certain degree but do not provide the required speed for tasks such as: field development strategies using comprehensive reservoir analysis, solving the inverse problem for injection/production optimization, quantifying uncertainties associated with the geological model and real-time optimization and decision making. These types of analyses require hundreds or thousands of runs. Furthermore, with the new push for smart fields in the oil/gas industry that is a natural growth of smart completion and smart wells, the need for real time

  20. Bayesian calibration of the Community Land Model using surrogates

    SciTech Connect

    Ray, Jaideep; Hou, Zhangshuan; Huang, Maoyi; Swiler, Laura Painton

    2014-02-01

    We present results from the Bayesian calibration of hydrological parameters of the Community Land Model (CLM), which is often used in climate simulations and Earth system models. A statistical inverse problem is formulated for three hydrological parameters, conditional on observations of latent heat surface fluxes over 48 months. Our calibration method uses polynomial and Gaussian process surrogates of the CLM, and solves the parameter estimation problem using a Markov chain Monte Carlo sampler. Posterior probability densities for the parameters are developed for two sites with different soil and vegetation covers. Our method also allows us to examine the structural error in CLM under two error models. We find that surrogate models can be created for CLM in most cases. The posterior distributions are more predictive than the default parameter values in CLM. Climatologically averaging the observations does not modify the parameters' distributions significantly. The structural error model reveals a correlation time-scale which can be used to identify the physical process that could be contributing to it. While the calibrated CLM has a higher predictive skill, the calibration is under-dispersive.

  1. Bayesian Calibration of the Community Land Model using Surrogates

    SciTech Connect

    Ray, Jaideep; Hou, Zhangshuan; Huang, Maoyi; Sargsyan, K.; Swiler, Laura P.

    2015-01-01

    We present results from the Bayesian calibration of hydrological parameters of the Community Land Model (CLM), which is often used in climate simulations and Earth system models. A statistical inverse problem is formulated for three hydrological parameters, conditioned on observations of latent heat surface fluxes over 48 months. Our calibration method uses polynomial and Gaussian process surrogates of the CLM, and solves the parameter estimation problem using a Markov chain Monte Carlo sampler. Posterior probability densities for the parameters are developed for two sites with different soil and vegetation covers. Our method also allows us to examine the structural error in CLM under two error models. We find that accurate surrogate models can be created for CLM in most cases. The posterior distributions lead to better prediction than the default parameter values in CLM. Climatologically averaging the observations does not modify the parameters’ distributions significantly. The structural error model reveals a correlation time-scale which can potentially be used to identify physical processes that could be contributing to it. While the calibrated CLM has a higher predictive skill, the calibration is under-dispersive.

  2. A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children

    PubMed Central

    Nhi, Dang My; Huy, Nguyen Tien; Ohyama, Kaname; Kimura, Daisuke; Lan, Nguyen Thi Phuong; Uchida, Leo; Thuong, Nguyen Van; Nhon, Cao Thi My; Phuc, Le Hong; Mai, Nguyen Thi; Mizukami, Shusaku; Bao, Lam Quoc; Doan, Nguyen Ngoc; Binh, Nguyen Van Thanh; Quang, Luong Chan; Karbwang, Juntra; Yui, Katsuyuki; Morita, Kouichi; Huong, Vu Thi Que; Hirayama, Kenji

    2016-01-01

    Background Severe dengue with severe plasma leakage (SD-SPL) is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death. Methodology Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS). To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6–48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ) technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients. Principal findings Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05), with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy. Conclusion Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers. PMID:26895439

  3. Predicting Disease Risk, Identifying Stakeholders, and Informing Control Strategies: A Case Study of Anthrax in Montana.

    PubMed

    Morris, Lillian R; Blackburn, Jason K

    2016-06-01

    Infectious diseases that affect wildlife and livestock are challenging to manage and can lead to large-scale die-offs, economic losses, and threats to human health. The management of infectious diseases in wildlife and livestock is made easier with knowledge of disease risk across space and identifying stakeholders associated with high-risk landscapes. This study focuses on anthrax, caused by the bacterium Bacillus anthracis, risk to wildlife and livestock in Montana. There is a history of anthrax in Montana, but the spatial extent of disease risk and subsequent wildlife species at risk are not known. Our objective was to predict the potential geographic distribution of anthrax risk across Montana, identify wildlife species at risk and their distributions, and define stakeholders. We used an ecological niche model to predict the potential distribution of anthrax risk. We overlaid susceptible wildlife species distributions and land ownership delineations on our risk map. We found that there was an extensive region across Montana predicted as potential anthrax risk. These potentially risky landscapes overlapped the ranges of all 6 ungulate species considered in the analysis and livestock grazing allotments, and this overlap was on public and private land for all species. Our findings suggest that there is the potential for a multi-species anthrax outbreak on multiple landscapes across Montana. Our potential anthrax risk map can be used to prioritize landscapes for surveillance and for implementing livestock vaccination programs. PMID:27169560

  4. A predicted protein interactome identifies conserved global networks and disease resistance subnetworks in maize

    PubMed Central

    Musungu, Bryan; Bhatnagar, Deepak; Brown, Robert L.; Fakhoury, Ahmad M.; Geisler, Matt

    2015-01-01

    Interactomes are genome-wide roadmaps of protein-protein interactions. They have been produced for humans, yeast, the fruit fly, and Arabidopsis thaliana and have become invaluable tools for generating and testing hypotheses. A predicted interactome for Zea mays (PiZeaM) is presented here as an aid to the research community for this valuable crop species. PiZeaM was built using a proven method of interologs (interacting orthologs) that were identified using both one-to-one and many-to-many orthology between genomes of maize and reference species. Where both maize orthologs occurred for an experimentally determined interaction in the reference species, we predicted a likely interaction in maize. A total of 49,026 unique interactions for 6004 maize proteins were predicted. These interactions are enriched for processes that are evolutionarily conserved, but include many otherwise poorly annotated proteins in maize. The predicted maize interactions were further analyzed by comparing annotation of interacting proteins, including different layers of ontology. A map of pairwise gene co-expression was also generated and compared to predicted interactions. Two global subnetworks were constructed for highly conserved interactions. These subnetworks showed clear clustering of proteins by function. Another subnetwork was created for disease response using a bait and prey strategy to capture interacting partners for proteins that respond to other organisms. Closer examination of this subnetwork revealed the connectivity between biotic and abiotic hormone stress pathways. We believe PiZeaM will provide a useful tool for the prediction of protein function and analysis of pathways for Z. mays researchers and is presented in this paper as a reference tool for the exploration of protein interactions in maize. PMID:26089837

  5. Towards predictive data-driven simulations of wildfire spread - Part I: Reduced-cost Ensemble Kalman Filter based on a Polynomial Chaos surrogate model for parameter estimation

    NASA Astrophysics Data System (ADS)

    Rochoux, M. C.; Ricci, S.; Lucor, D.; Cuenot, B.; Trouvé, A.

    2014-11-01

    This paper is the first part in a series of two articles and presents a data-driven wildfire simulator for forecasting wildfire spread scenarios, at a reduced computational cost that is consistent with operational systems. The prototype simulator features the following components: an Eulerian front propagation solver FIREFLY that adopts a regional-scale modeling viewpoint, treats wildfires as surface propagating fronts, and uses a description of the local rate of fire spread (ROS) as a function of environmental conditions based on Rothermel's model; a series of airborne-like observations of the fire front positions; and a data assimilation (DA) algorithm based on an ensemble Kalman filter (EnKF) for parameter estimation. This stochastic algorithm partly accounts for the nonlinearities between the input parameters of the semi-empirical ROS model and the fire front position, and is sequentially applied to provide a spatially uniform correction to wind and biomass fuel parameters as observations become available. A wildfire spread simulator combined with an ensemble-based DA algorithm is therefore a promising approach to reduce uncertainties in the forecast position of the fire front and to introduce a paradigm-shift in the wildfire emergency response. In order to reduce the computational cost of the EnKF algorithm, a surrogate model based on a polynomial chaos (PC) expansion is used in place of the forward model FIREFLY in the resulting hybrid PC-EnKF algorithm. The performance of EnKF and PC-EnKF is assessed on synthetically generated simple configurations of fire spread to provide valuable information and insight on the benefits of the PC-EnKF approach, as well as on a controlled grassland fire experiment. The results indicate that the proposed PC-EnKF algorithm features similar performance to the standard EnKF algorithm, but at a much reduced computational cost. In particular, the re-analysis and forecast skills of DA strongly relate to the spatial and temporal

  6. Towards predictive data-driven simulations of wildfire spread - Part I: Reduced-cost Ensemble Kalman Filter based on a Polynomial Chaos surrogate model for parameter estimation

    NASA Astrophysics Data System (ADS)

    Rochoux, M. C.; Ricci, S.; Lucor, D.; Cuenot, B.; Trouvé, A.

    2014-05-01

    This paper is the first part in a series of two articles and presents a data-driven wildfire simulator for forecasting wildfire spread scenarios, at a reduced computational cost that is consistent with operational systems. The prototype simulator features the following components: a level-set-based fire propagation solver FIREFLY that adopts a regional-scale modeling viewpoint, treats wildfires as surface propagating fronts, and uses a description of the local rate of fire spread (ROS) as a function of environmental conditions based on Rothermel's model; a series of airborne-like observations of the fire front positions; and a data assimilation algorithm based on an ensemble Kalman filter (EnKF) for parameter estimation. This stochastic algorithm partly accounts for the non-linearities between the input parameters of the semi-empirical ROS model and the fire front position, and is sequentially applied to provide a spatially-uniform correction to wind and biomass fuel parameters as observations become available. A wildfire spread simulator combined with an ensemble-based data assimilation algorithm is therefore a promising approach to reduce uncertainties in the forecast position of the fire front and to introduce a paradigm-shift in the wildfire emergency response. In order to reduce the computational cost of the EnKF algorithm, a surrogate model based on a polynomial chaos (PC) expansion is used in place of the forward model FIREFLY in the resulting hybrid PC-EnKF algorithm. The performance of EnKF and PC-EnKF is assessed on synthetically-generated simple configurations of fire spread to provide valuable information and insight on the benefits of the PC-EnKF approach as well as on a controlled grassland fire experiment. The results indicate that the proposed PC-EnKF algorithm features similar performance to the standard EnKF algorithm, but at a much reduced computational cost. In particular, the re-analysis and forecast skills of data assimilation strongly relate

  7. Human mesenchymal stromal cells: identifying assays to predict potency for therapeutic selection.

    PubMed

    Deskins, Desirae L; Bastakoty, Dikshya; Saraswati, Sarika; Shinar, Andrew; Holt, Ginger E; Young, Pampee P

    2013-02-01

    Multipotent mesenchymal stromal cells (MSCs) have the potential to repair and regenerate damaged tissues, making them attractive candidates for cell-based therapies. To maximize efficacy of MSCs, prediction of their therapeutic abilities must be made so that only the best cells will be used. Our goal was to identify feasible and reproducible in vitro assays to predict MSC potency. We generated cell lines from 10 normal human bone marrow samples and used the International Society for Cellular Therapy's minimal criteria to define them as MSCs: plastic adherence, appropriate surface marker expression, and trilineage differentiation. Each MSC line was further characterized by its growth, proliferation, and viability as determined by cell count, bromodeoxyuridine incorporation, and cellular ATP levels, respectively. To determine whether these tests reliably predict the therapeutic aptitude of the MSCs, several lines were implanted in vivo to examine their capacity to engraft and form granulation tissue in a well-established murine wound model using polyvinyl alcohol sponges. Long-term engraftment of MSCs in the sponges was quantified through the presence of the human-specific Alu gene in sponge sections. Sections were also stained for proliferating cells, vascularity, and granulation tissue formation to determine successful engraftment and repair. We found that high performance in a combination of the in vitro tests accurately predicted which lines functioned well in vivo. These findings suggest that reliable and reproducible in vitro assays may be used to measure the functional potential of MSCs for therapeutic use. PMID:23362238

  8. Human plasma metabolomics for identifying differential metabolites and predicting molecular subtypes of breast cancer

    PubMed Central

    Chen, Zhuo; Li, Jin; Liu, Qun; Alolga, Raphael N; Chen, Yan; Lai, Mao-De; Li, Ping; Zhu, Wei; Qi, Lian-Wen

    2016-01-01

    Purpose This work aims to identify differential metabolites and predicting molecular subtypes of breast cancer (BC). Methods Plasma samples were collected from 96 BC patients and 79 normal participants. Metabolic profiles were determined by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry based on multivariate statistical data analysis. Results We observed 64 differential metabolites between BC and normal group. Compared to human epidermal growth factor receptor 2 (HER2)-negative patients, HER2-positive group showed elevated aerobic glycolysis, gluconeogenesis, and increased fatty acid biosynthesis with reduced Krebs cycle. Compared with estrogen receptor (ER)-negative group, ER-positive patients showed elevated alanine, aspartate and glutamate metabolism, decreased glycerolipid catabolism, and enhanced purine metabolism. A panel of 8 differential metabolites, including carnitine, lysophosphatidylcholine (20:4), proline, alanine, lysophosphatidylcholine (16:1), glycochenodeoxycholic acid, valine, and 2-octenedioic acid, was identified for the classification of BC subtypes. These markers showed potential diagnostic value with average area under the curve at 0.925 (95% CI 0.867-0.983) for the training set (n=51) and 0.893 (95% CI 0.847-0.939) for the test set (n=45). Conclusion Human plasma metabolomics is useful in identifying differential metabolites and predicting breast cancer subtypes. PMID:26848530

  9. Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success.

    PubMed

    Pogue, Brian W; Elliott, Jonathan T; Kanick, Stephen C; Davis, Scott C; Samkoe, Kimberley S; Maytin, Edward V; Pereira, Stephen P; Hasan, Tayyaba

    2016-04-01

    Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment

  10. Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success

    NASA Astrophysics Data System (ADS)

    Pogue, Brian W.; Elliott, Jonathan T.; Kanick, Stephen C.; Davis, Scott C.; Samkoe, Kimberley S.; Maytin, Edward V.; Pereira, Stephen P.; Hasan, Tayyaba

    2016-04-01

    Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment

  11. Comparison of Surrogate Markers as Measures of Uncomplicated Insulin Resistance in Korean Adults

    PubMed Central

    Kim, Tae Jong; Kim, Hye Jung; Kim, Young Bae; Lee, Jee Yon; Lee, Hye Sun; Hong, Jung Hwa

    2016-01-01

    Background Metabolic syndrome (MS) is known to increase the risk of various cardiometabolic diseases and in-sulin resistance (IR) has known to have central role in the development of MS. Many surrogate indices of IR have been proposed and the detection of MS might be a suitable model for assessing the accuracy of surrogate indices. The aims of our study are to invest the most appropriate index by assessment of the diagnostic capacity of IR among each surrogate index and identifying cut-off values for discriminating uncomplicated MS in Korean adults. Methods A cross-sectional study was performed, assessing 294 Korean adults, 85 of whom were diagnosed with uncomplicated MS. The sensitivities and specificities of five surrogate IR indices were compared to discriminate MS from healthy subjects; these included fasting serum insulin, homeostasis model assessment–insulin resistance index, quantitative insulin sensitivity check index, McAuley index, and Disse index. Correlations between each index value were assessed using Pearson's and Spearman's correlation methods. Results The McAuley index showed the highest area under the curve (0.85), specificity (86.12%), accuracy (82.31%), positive predictive value (68.13%), and negative predictive value (88.67%) to distinguish MS, with a cut-off point of 5.3 defined. Correlation coefficients of the five indices showed that the McAuley index had the strongest correlation with IR. Conclusion The McAuley index showed the best accuracy in the detection of MS as a surrogate marker of IR. To establish more effective and accurate standards of measuring IR, comprehensive and multi-scaled studies are required. PMID:27274391

  12. Precision Oncology: Identifying Predictive Biomarkers for the Treatment of Metastatic Renal Cell Carcinoma

    PubMed Central

    Modi, Parth K.; Farber, Nicholas J.; Singer, Eric A.

    2016-01-01

    The recent FDA approval of multiple new pharmaceutical agents for metastatic renal cell carcinoma (RCC) has left physicians with several options for first- and second- line therapy. With limited head-to-head comparisons, however, there is a paucity of evidence to recommend the use of one agent over another. To address this knowledge gap, Voss et al. identified serum biomarkers from specimens collected during the RECORD-3 trial, a comparative study of first-line sunitinib versus first-line everolimus. Of the biomarkers identified, the 5 most strongly associated with first-line everolimus progression-free survival (PFS1L) were combined to form a composite biomarker score (CBS). The CBS was significantly associated with everolimus PFS1L in multivariate regression analysis. This study is an example of the additional value offered by a randomized trial with prospective biospecimen collection and a significant step towards identifying predictive biomarkers for the treatment of metastatic RCC. As further comparative trials are performed, it will be essential that biomarkers are appropriately identified and validated in order to further the goal of precision oncology.

  13. Identifying the necessary and sufficient number of risk factors for predicting academic failure.

    PubMed

    Lucio, Robert; Hunt, Elizabeth; Bornovalova, Marina

    2012-03-01

    Identifying the point at which individuals become at risk for academic failure (grade point average [GPA] < 2.0) involves an understanding of which and how many factors contribute to poor outcomes. School-related factors appear to be among the many factors that significantly impact academic success or failure. This study focused on 12 school-related factors. Using a thorough 5-step process, we identified which unique risk factors place one at risk for academic failure. Academic engagement, academic expectations, academic self-efficacy, homework completion, school relevance, school safety, teacher relationships (positive relationship), grade retention, school mobility, and school misbehaviors (negative relationship) were uniquely related to GPA even after controlling for all relevant covariates. Next, a receiver operating characteristic curve was used to determine a cutoff point for determining how many risk factors predict academic failure (GPA < 2.0). Results yielded a cutoff point of 2 risk factors for predicting academic failure, which provides a way for early identification of individuals who are at risk. Further implications of these findings are discussed. PMID:22182300

  14. Father involvement: Identifying and predicting family members' shared and unique perceptions.

    PubMed

    Dyer, W Justin; Day, Randal D; Harper, James M

    2014-08-01

    Father involvement research has typically not recognized that reports of involvement contain at least two components: 1 reflecting a view of father involvement that is broadly recognized in the family, and another reflecting each reporter's unique perceptions. Using a longitudinal sample of 302 families, this study provides a first examination of shared and unique views of father involvement (engagement and warmth) from the perspectives of fathers, children, and mothers. This study also identifies influences on these shared and unique perspectives. Father involvement reports were obtained when the child was 12 and 14 years old. Mother reports overlapped more with the shared view than father or child reports. This suggests the mother's view may be more in line with broadly recognized father involvement. Regarding antecedents, for fathers' unique view, a compensatory model partially explains results; that is, negative aspects of family life were positively associated with fathers' unique view. Children's unique view of engagement may partially reflect a sentiment override with father antisocial behaviors being predictive. Mothers' unique view of engagement was predicted by father and mother work hours and her unique view of warmth was predicted by depression and maternal gatekeeping. Taken, together finding suggests a far more nuanced view of father involvement should be considered. PMID:25000130

  15. Parcel-scale urban coastal flood prediction: Identifying critical data and forcing requirements

    NASA Astrophysics Data System (ADS)

    Gallien, T.; Sanders, B. F.

    2012-12-01

    Coastal flooding represents a significant socio-economic and humanitarian threat to urbanized lowlands throughout the world. In California, sea levels are projected to rise 1-1.4 meters in the next century. Numerous coastal communities are currently at risk of flooding during high tides or large wave events and a significant body of evidence suggests climate change will exacerbate flooding in these low lying, and often highly populated, areas. Flood prediction in urbanized embayments pose a number of challenges including water level characterization, appropriate representation of both weir-like (i.e. wall) overflow and wave runup/overtopping volumes and the need for highly accurate local data and site knowledge. In addition, a paucity of high quality validation data fundamentally obstructs predictive flood modeling efforts. Here, a Southern California coastal community which benefits from two unique flood event validation data sets is modeled in context of current and future sea level scenarios. The uncalibrated hydrodynamic model resolves critical urban infrastructure and includes essential dynamic processes such as tidal amplification, weir-like overflow and spatially distributed wave overtopping volumes. Results identify data and forcing requirements that are essential to accurate parcel-scale (individual home or street) flood prediction in defended urban terrain.

  16. Environmental diversity as a surrogate for species representation.

    PubMed

    Beier, Paul; de Albuquerque, Fábio Suzart

    2015-10-01

    Because many species have not been described and most species ranges have not been mapped, conservation planners often use surrogates for conservation planning, but evidence for surrogate effectiveness is weak. Surrogates are well-mapped features such as soil types, landforms, occurrences of an easily observed taxon (discrete surrogates), and well-mapped environmental conditions (continuous surrogate). In the context of reserve selection, the idea is that a set of sites selected to span diversity in the surrogate will efficiently represent most species. Environmental diversity (ED) is a rarely used surrogate that selects sites to efficiently span multivariate ordination space. Because it selects across continuous environmental space, ED should perform better than discrete surrogates (which necessarily ignore within-bin and between-bin heterogeneity). Despite this theoretical advantage, ED appears to have performed poorly in previous tests of its ability to identify 50 × 50 km cells that represented vertebrates in Western Europe. Using an improved implementation of ED, we retested ED on Western European birds, mammals, reptiles, amphibians, and combined terrestrial vertebrates. We also tested ED on data sets for plants of Zimbabwe, birds of Spain, and birds of Arizona (United States). Sites selected using ED represented European mammals no better than randomly selected cells, but they represented species in the other 7 data sets with 20% to 84% effectiveness. This far exceeds the performance in previous tests of ED, and exceeds the performance of most discrete surrogates. We believe ED performed poorly in previous tests because those tests considered only a few candidate explanatory variables and used suboptimal forms of ED's selection algorithm. We suggest future work on ED focus on analyses at finer grain sizes more relevant to conservation decisions, explore the effect of selecting the explanatory variables most associated with species turnover, and investigate

  17. Cerium as a surrogate in the plutonium immobilization waste form

    NASA Astrophysics Data System (ADS)

    Marra, James Christopher

    In the aftermath of the Cold War, approximately 50 tonnes (MT) of weapons useable plutonium (Pu) has been identified as excess. The U.S. Department of Energy (DOE) has decided that at least a portion of this material will be immobilized in a titanate-based ceramic for final disposal in a geologic repository. The baseline formulation was designed to produce a ceramic consisting primarily of a highly substituted pyrochlore with minor amounts of brannerite and hafnia-substituted rutile. Since development studies with actual actinide materials is difficult, surrogates have been used to facilitate testing. Cerium has routinely been used as an actinide surrogate in actinide chemistry and processing studies. Although cerium appeared as an adequate physical surrogate for powder handling and general processing studies, cerium was found to act significantly different from a chemical perspective in the Pu ceramic form. The reduction of cerium at elevated temperatures caused different reaction paths toward densification of the respective forms resulting in different phase assemblages and microstructural features. Single-phase fabrication studies and cerium oxidation state analyses were performed to further quantify these behavioral differences. These studies indicated that the major phases in the final phase assemblages contained point defects likely leading to their stability. Additionally, thermochemical arguments predicted that the predominant pyrochlore phase in the ceramic was metastable. The apparent metastabilty associated with primary phase in the Pu ceramic form indicated that additional studies must be performed to evaluate the thermodynamic properties of these compounds. Moreover, the metastability of this predominant phase must be considered in assessment of long-term behavior (e.g. radiation stability) of this ceramic.

  18. Sulfur hexafluoride as a surrogate

    SciTech Connect

    Taylor, P.H.; Chadbourne, J.F.

    1987-06-01

    A viable chemical surrogate for monitoring the effectiveness of hazardous waste incinerators must include high thermal stability and low toxicity among its characteristics. The relationship between sulfur hexafluoride (SF6) and hazardous constituent thermal stability for a mixture of chlorinated hydrocarbons indicates that SF6 has the potential to satisfy the basic requirements of a chemical surrogate for hazardous waste incineration.

  19. Surrogate Endpoints in Suicide Research

    ERIC Educational Resources Information Center

    Wortzel, Hal S.; Gutierrez, Peter M.; Homaifar, Beeta Y.; Breshears, Ryan E.; Harwood, Jeri E.

    2010-01-01

    Surrogate endpoints frequently substitute for rare outcomes in research. The ability to learn about completed suicides by investigating more readily available and proximate outcomes, such as suicide attempts, has obvious appeal. However, concerns with surrogates from the statistical science perspective exist, and mounting evidence from…

  20. A Review of Surrogate Assisted Multiobjective Evolutionary Algorithms

    PubMed Central

    Díaz-Manríquez, Alan; Toscano, Gregorio; Barron-Zambrano, Jose Hugo; Tello-Leal, Edgar

    2016-01-01

    Multiobjective evolutionary algorithms have incorporated surrogate models in order to reduce the number of required evaluations to approximate the Pareto front of computationally expensive multiobjective optimization problems. Currently, few works have reviewed the state of the art in this topic. However, the existing reviews have focused on classifying the evolutionary multiobjective optimization algorithms with respect to the type of underlying surrogate model. In this paper, we center our focus on classifying multiobjective evolutionary algorithms with respect to their integration with surrogate models. This interaction has led us to classify similar approaches and identify advantages and disadvantages of each class. PMID:27382366

  1. Actual and Perceived Gender Differences in the Accuracy of Surrogate Decisions about Life-Sustaining Medical Treatment among Older Spouses

    ERIC Educational Resources Information Center

    Zettel-Watson, Laura; Ditto, Peter H.; Danks, Joseph H.; Smucker, William D.

    2008-01-01

    This study examined the influence of surrogate gender on the accuracy of substituted judgments about the use of life-sustaining treatment in a sample of 249 older adults and their self-selected surrogate decision-makers. Overall, wives were more accurate than husbands at predicting their spouses' treatment wishes. Surrogates' perceptions of their…

  2. Identifying influential data points in hydrological model calibration and their impact on streamflow predictions

    NASA Astrophysics Data System (ADS)

    Wright, David; Thyer, Mark; Westra, Seth

    2015-04-01

    Highly influential data points are those that have a disproportionately large impact on model performance, parameters and predictions. However, in current hydrological modelling practice the relative influence of individual data points on hydrological model calibration is not commonly evaluated. This presentation illustrates and evaluates several influence diagnostics tools that hydrological modellers can use to assess the relative influence of data. The feasibility and importance of including influence detection diagnostics as a standard tool in hydrological model calibration is discussed. Two classes of influence diagnostics are evaluated: (1) computationally demanding numerical "case deletion" diagnostics; and (2) computationally efficient analytical diagnostics, based on Cook's distance. These diagnostics are compared against hydrologically orientated diagnostics that describe changes in the model parameters (measured through the Mahalanobis distance), performance (objective function displacement) and predictions (mean and maximum streamflow). These influence diagnostics are applied to two case studies: a stage/discharge rating curve model, and a conceptual rainfall-runoff model (GR4J). Removing a single data point from the calibration resulted in differences to mean flow predictions of up to 6% for the rating curve model, and differences to mean and maximum flow predictions of up to 10% and 17%, respectively, for the hydrological model. When using the Nash-Sutcliffe efficiency in calibration, the computationally cheaper Cook's distance metrics produce similar results to the case-deletion metrics at a fraction of the computational cost. However, Cooks distance is adapted from linear regression with inherit assumptions on the data and is therefore less flexible than case deletion. Influential point detection diagnostics show great potential to improve current hydrological modelling practices by identifying highly influential data points. The findings of this

  3. BFH-OST, a new predictive screening tool for identifying osteoporosis in postmenopausal Han Chinese women

    PubMed Central

    Ma, Zhao; Yang, Yong; Lin, JiSheng; Zhang, XiaoDong; Meng, Qian; Wang, BingQiang; Fei, Qi

    2016-01-01

    Purpose To develop a simple new clinical screening tool to identify primary osteoporosis by dual-energy X-ray absorptiometry (DXA) in postmenopausal women and to compare its validity with the Osteoporosis Self-Assessment Tool for Asians (OSTA) in a Han Chinese population. Methods A cross-sectional study was conducted, enrolling 1,721 community-dwelling postmenopausal Han Chinese women. All the subjects completed a structured questionnaire and had their bone mineral density measured using DXA. Using logistic regression analysis, we assessed the ability of numerous potential risk factors examined in the questionnaire to identify women with osteoporosis. Based on this analysis, we build a new predictive model, the Beijing Friendship Hospital Osteoporosis Self-Assessment Tool (BFH-OST). Receiver operating characteristic curves were generated to compare the validity of the new model and OSTA in identifying postmenopausal women at increased risk of primary osteoporosis as defined according to the World Health Organization criteria. Results At screening, it was found that of the 1,721 subjects with DXA, 22.66% had osteoporosis and a further 47.36% had osteopenia. Of the items screened in the questionnaire, it was found that age, weight, height, body mass index, personal history of fracture after the age of 45 years, history of fragility fracture in either parent, current smoking, and consumption of three of more alcoholic drinks per day were all predictive of osteoporosis. However, age at menarche and menopause, years since menopause, and number of pregnancies and live births were irrelevant in this study. The logistic regression analysis and item reduction yielded a final tool (BFH-OST) based on age, body weight, height, and history of fracture after the age of 45 years. The BFH-OST index (cutoff =9.1), which performed better than OSTA, had a sensitivity of 73.6% and a specificity of 72.7% for identifying osteoporosis, with an area under the receiver operating

  4. Higher-order Lie symmetries in identifiability and predictability analysis of dynamic models.

    PubMed

    Merkt, Benjamin; Timmer, Jens; Kaschek, Daniel

    2015-07-01

    Parameter estimation in ordinary differential equations (ODEs) has manifold applications not only in physics but also in the life sciences. When estimating the ODE parameters from experimentally observed data, the modeler is frequently concerned with the question of parameter identifiability. The source of parameter nonidentifiability is tightly related to Lie group symmetries. In the present work, we establish a direct search algorithm for the determination of admitted Lie group symmetries. We clarify the relationship between admitted symmetries and parameter nonidentifiability. The proposed algorithm is applied to illustrative toy models as well as a data-based ODE model of the NFκB signaling pathway. We find that besides translations and scaling transformations also higher-order transformations play a role. Enabled by the knowledge about the explicit underlying symmetry transformations, we show how models with nonidentifiable parameters can still be employed to make reliable predictions. PMID:26274260

  5. Higher-order Lie symmetries in identifiability and predictability analysis of dynamic models

    NASA Astrophysics Data System (ADS)

    Merkt, Benjamin; Timmer, Jens; Kaschek, Daniel

    2015-07-01

    Parameter estimation in ordinary differential equations (ODEs) has manifold applications not only in physics but also in the life sciences. When estimating the ODE parameters from experimentally observed data, the modeler is frequently concerned with the question of parameter identifiability. The source of parameter nonidentifiability is tightly related to Lie group symmetries. In the present work, we establish a direct search algorithm for the determination of admitted Lie group symmetries. We clarify the relationship between admitted symmetries and parameter nonidentifiability. The proposed algorithm is applied to illustrative toy models as well as a data-based ODE model of the NFκ B signaling pathway. We find that besides translations and scaling transformations also higher-order transformations play a role. Enabled by the knowledge about the explicit underlying symmetry transformations, we show how models with nonidentifiable parameters can still be employed to make reliable predictions.

  6. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans

    PubMed Central

    Rhee, Eugene P.; Cheng, Susan; Larson, Martin G.; Walford, Geoffrey A.; Lewis, Gregory D.; McCabe, Elizabeth; Yang, Elaine; Farrell, Laurie; Fox, Caroline S.; O’Donnell, Christopher J.; Carr, Steven A.; Vasan, Ramachandran S.; Florez, Jose C.; Clish, Clary B.; Wang, Thomas J.; Gerszten, Robert E.

    2011-01-01

    Dyslipidemia is an independent risk factor for type 2 diabetes, although exactly which of the many plasma lipids contribute to this remains unclear. We therefore investigated whether lipid profiling can inform diabetes prediction by performing liquid chromatography/mass spectrometry–based lipid profiling in 189 individuals who developed type 2 diabetes and 189 matched disease-free individuals, with over 12 years of follow up in the Framingham Heart Study. We found that lipids of lower carbon number and double bond content were associated with an increased risk of diabetes, whereas lipids of higher carbon number and double bond content were associated with decreased risk. This pattern was strongest for triacylglycerols (TAGs) and persisted after multivariable adjustment for age, sex, BMI, fasting glucose, fasting insulin, total triglycerides, and HDL cholesterol. A combination of 2 TAGs further improved diabetes prediction. To explore potential mechanisms that modulate the distribution of plasma lipids, we performed lipid profiling during oral glucose tolerance testing, pharmacologic interventions, and acute exercise testing. Levels of TAGs associated with increased risk for diabetes decreased in response to insulin action and were elevated in the setting of insulin resistance. Conversely, levels of TAGs associated with decreased diabetes risk rose in response to insulin and were poorly correlated with insulin resistance. These studies identify a relationship between lipid acyl chain content and diabetes risk and demonstrate how lipid profiling could aid in clinical risk assessment. PMID:21403394

  7. Identifying and tracking pedestrians based on sensor fusion and motion stability predictions.

    PubMed

    Musleh, Basam; García, Fernando; Otamendi, Javier; Armingol, José Maria; de la Escalera, Arturo

    2010-01-01

    The lack of trustworthy sensors makes development of Advanced Driver Assistance System (ADAS) applications a tough task. It is necessary to develop intelligent systems by combining reliable sensors and real-time algorithms to send the proper, accurate messages to the drivers. In this article, an application to detect and predict the movement of pedestrians in order to prevent an imminent collision has been developed and tested under real conditions. The proposed application, first, accurately measures the position of obstacles using a two-sensor hybrid fusion approach: a stereo camera vision system and a laser scanner. Second, it correctly identifies pedestrians using intelligent algorithms based on polylines and pattern recognition related to leg positions (laser subsystem) and dense disparity maps and u-v disparity (vision subsystem). Third, it uses statistical validation gates and confidence regions to track the pedestrian within the detection zones of the sensors and predict their position in the upcoming frames. The intelligent sensor application has been experimentally tested with success while tracking pedestrians that cross and move in zigzag fashion in front of a vehicle. PMID:22163639

  8. Identifying and Tracking Pedestrians Based on Sensor Fusion and Motion Stability Predictions

    PubMed Central

    Musleh, Basam; García, Fernando; Otamendi, Javier; Armingol, José Mª; de la Escalera, Arturo

    2010-01-01

    The lack of trustworthy sensors makes development of Advanced Driver Assistance System (ADAS) applications a tough task. It is necessary to develop intelligent systems by combining reliable sensors and real-time algorithms to send the proper, accurate messages to the drivers. In this article, an application to detect and predict the movement of pedestrians in order to prevent an imminent collision has been developed and tested under real conditions. The proposed application, first, accurately measures the position of obstacles using a two-sensor hybrid fusion approach: a stereo camera vision system and a laser scanner. Second, it correctly identifies pedestrians using intelligent algorithms based on polylines and pattern recognition related to leg positions (laser subsystem) and dense disparity maps and u-v disparity (vision subsystem). Third, it uses statistical validation gates and confidence regions to track the pedestrian within the detection zones of the sensors and predict their position in the upcoming frames. The intelligent sensor application has been experimentally tested with success while tracking pedestrians that cross and move in zigzag fashion in front of a vehicle. PMID:22163639

  9. Prediction trajectory of moving target based on parameter identify in RLS filtering with forget factor

    NASA Astrophysics Data System (ADS)

    Yin, Yili; Tian, Yan; Li, Zhang

    2015-10-01

    A moving target should be missing from a photoelectric theodolite tracker, when the clouds and other special conditions encountered in the course of a theodolite tracking a moving object, and this condition should cause the interruption of tracking process. In view of this problem, an algorithm based on the frame of parameter identification and rolling prediction to trajectory was presented to predicting the target trajectory when it missing. Firstly, the article makes a specification of photoelectric theodolite and it operating mechanism detailed. The reasons of flying target imaging disappear from the field of theodolite telescope and the traditional solution to this problem, the least square curve fitting of trajectory quadratic function of time, were narrated secondly. The algorithm based on recursive least square with forget factor, identify the parameters of target motion using the data of position from single theodolite, then the forecasting trajectory of moving targets was presented afterwards ,in the filtering approach of past data rolling smooth with the weight of last procedure. By simulation with tracking moving targets synthetic corner from a real tracking routine of photoelectric theodolite, the algorithm was testified, and the simulation of curve fitting a quadratic function of time was compared at the last part.

  10. Surrogate mothers: the legal issues.

    PubMed

    Mady, T M

    1981-01-01

    Increasing numbers of couples have benefitted from, or may be considering use of, the surrogate mother procedure. In this procedure, a couple, usually a husband and wife, enters into a contract with a surrogate mother. Under the terms of the contract, the surrogate mother is artificially inseminated, bears a child, and relinquishes all rights regarding that child to the semen donor and his wife. In exchange for bearing a child, the surrogate mother often receives a fee. In light of such increased use of the procedure, the issue of whether or not the arrangement is legal has particular importance. Questions of legality involve possible violations of criminal baby-selling statutes. Issues of whether adoption is necessary and whether the child is legitimate also are inherent in the surrogate mother arrangement. This Note argues that these questions should be resolved in favor of finding no impediment to the use of the surrogate mother procedure, at least within certain guidelines. However, even in the absence of legal impediment, detailed contracts and thorough medical screening for genetic, physical and psychological problems would further eliminate ambiguities regarding liability. In addition, the Note concludes that legislation should be enacted to deal with the legal ambiguities of the surrogate mother arrangement. This legislation should regulate the parties that enter into such an arrangement and the rights and responsibilities of these parties. PMID:7332012

  11. An Evaluation of Two Internal Surrogates for Determining the Three-Dimensional Position of Peripheral Lung Tumors

    SciTech Connect

    Spoelstra, Femke Soernsen de Koste, John R. van; Vincent, Andrew; Cuijpers, Johan P.; Slotman, Ben J.; Senan, Suresh

    2009-06-01

    Purpose: Both carina and diaphragm positions have been used as surrogates during respiratory-gated radiotherapy. We studied the correlation of both surrogates with three-dimensional (3D) tumor position. Methods and Materials: A total of 59 repeat artifact-free four-dimensional (4D) computed tomography (CT) scans, acquired during uncoached breathing, were identified in 23 patients with Stage I lung cancer. Repeat scans were co-registered to the initial 4D CT scan, and tumor, carina, and ipsilateral diaphragm were manually contoured in all phases of each 4D CT data set. Correlation between positions of carina and diaphragm with 3D tumor position was studied by use of log-likelihood ratio statistics. Models to predict 3D tumor position from internal surrogates at end inspiration (EI) and end expiration (EE) were developed, and model accuracy was tested by calculating SDs of differences between predicted and actual tumor positions. Results: Motion of both the carina and diaphragm significantly correlated with tumor motion, but log-likelihood ratios indicated that the carina was more predictive for tumor position. When craniocaudal tumor position was predicted by use of craniocaudal carina positions, the SDs of the differences between the predicted and observed positions were 2.2 mm and 2.4 mm at EI and EE, respectively. The corresponding SDs derived with the diaphragm positions were 3.7 mm and 3.9 mm at EI and EE, respectively. Prediction errors in the other directions were comparable. Prediction accuracy was similar at EI and EE. Conclusions: The carina is a better surrogate of 3D tumor position than diaphragm position. Because residual prediction errors were observed in this analysis, additional studies will be performed using audio-coached scans.

  12. miRTar Hunter: A Prediction System for Identifying Human microRNA Target Sites

    PubMed Central

    Park, Kiejung; Kim, Ki-Bong

    2013-01-01

    MicroRNAs (miRNAs) are important regulators of gene expression and play crucial roles in many biological processes including apoptosis, differentiation, development, and tumorigenesis. Recent estimates suggest that more than 50% of human protein coding genes may be regulated by miRNAs and that each miRNA may bind to 300–400 target genes. Approximately 1, 000 human miRNAs have been identified so far with each having up to hundreds of unique target mRNAs. However, the targets for a majority of these miRNAs have not been identified due to the lack of large-scale experimental detection techniques. Experimental detection of miRNA target sites is a costly and time-consuming process, even though identification of miRNA targets is critical to unraveling their functions in various biological processes. To identify miRNA targets, we developed miRTar Hunter, a novel computational approach for predicting target sites regardless of the presence or absence of a seed match or evolutionary sequence conservation. Our approach is based on a dynamic programming algorithm that incorporates more sequence-specific features and reflects the properties of various types of target sites that determine diverse aspects of complementarities between miRNAs and their targets. We evaluated the performance of our algorithm on 532 known human miRNA:target pairs and 59 experimentally-verified negative miRNA:target pairs, and also compared our method with three popular programs for 481 miRNA:target pairs. miRTar Hunter outperformed three popular existing algorithms in terms of recall and precision, indicating that our unique scheme to quantify the determinants of complementary sites is effective at detecting miRNA targets. miRTar Hunter is now available at http://203.230.194.162/~kbkim. PMID:23475422

  13. Surrogate markers of long-term outcome in primary total hip arthroplasty

    PubMed Central

    Malak, T. T.; Broomfield, J. A. J.; Palmer, A. J. R.; Hopewell, S.; Carr, A.; Brown, C.; Prieto-Alhambra, D.

    2016-01-01

    Objectives High failure rates of metal-on-metal hip arthroplasty implants have highlighted the need for more careful introduction and monitoring of new implants and for the evaluation of the safety of medical devices. The National Joint Registry and other regulatory services are unable to detect failing implants at an early enough stage. We aimed to identify validated surrogate markers of long-term outcome in patients undergoing primary total hip arthroplasty (THA). Methods We conducted a systematic review of studies evaluating surrogate markers for predicting long-term outcome in primary THA. Long-term outcome was defined as revision rate of an implant at ten years according to National Institute of Health and Care Excellence guidelines. We conducted a search of Medline and Embase (OVID) databases. Separate search strategies were devised for the Cochrane database and Google Scholar. Each search was performed to include articles from the date of their inception to June 8, 2015. Results Our search strategy identified 1082 studies of which 115 studies were included for full article review. Following review, 17 articles were found that investigated surrogate markers of long-term outcome. These included one systematic review, one randomised control trial (RCT), one case control study and 13 case series. Validated surrogate markers included Radiostereometric Analysis (RSA) and Einzel-Bild-Röntgen-Analyse (EBRA), each measuring implant migration and wear. We identified five RSA studies (one systematic review and four case series) and four EBRA studies (one RCT and three case series). Patient Reported Outcome Measures (PROMs) at six months have been investigated but have not been validated against long-term outcomes. Conclusions This systematic review identified two validated surrogate markers of long-term primary THA outcome: RSA and EBRA, each measuring implant migration and wear. We recommend the consideration of RSA in the pre-market testing of new implants. EBRA can

  14. Electrocardiogram PR Interval Is a Surrogate Marker to Predict New Occurrence of Atrial Fibrillation in Patients with Frequent Premature Atrial Contractions.

    PubMed

    Chun, Kwang Jin; Hwang, Jin Kyung; Choi, So Ra; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Kyoung-Min

    2016-04-01

    The clinical significance of prolonged PR interval has not been evaluated in patients with frequent premature atrial contractions (PACs). We investigated whether prolonged PR interval could predict new occurrence of atrial fibrillation (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684 patients, 626 patients had normal PR intervals (group A) and 58 patients had prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14 patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group A (P < 0.001). Cox regression analysis showed that prolonged PR interval (hazard ratio [HR], 1.950; 95% CI, 1.029-3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006-1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012-1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval, advanced age, and enlarged LA dimension are independent risk factors of AF occurrence in patients with frequent PACs. PMID:27051234

  15. Electrocardiogram PR Interval Is a Surrogate Marker to Predict New Occurrence of Atrial Fibrillation in Patients with Frequent Premature Atrial Contractions

    PubMed Central

    Hwang, Jin Kyung; Choi, So Ra; Park, Seung-Jung; Kim, June Soo

    2016-01-01

    The clinical significance of prolonged PR interval has not been evaluated in patients with frequent premature atrial contractions (PACs). We investigated whether prolonged PR interval could predict new occurrence of atrial fibrillation (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684 patients, 626 patients had normal PR intervals (group A) and 58 patients had prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14 patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group A (P < 0.001). Cox regression analysis showed that prolonged PR interval (hazard ratio [HR], 1.950; 95% CI, 1.029–3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006–1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012–1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval, advanced age, and enlarged LA dimension are independent risk factors of AF occurrence in patients with frequent PACs. PMID:27051234

  16. Evolving issues in surrogate motherhood.

    PubMed

    Erlen, J A; Holzman, I R

    1990-01-01

    Surrogate mothering is an arrangement whereby a woman who gives birth to an infant intends--through a contractual agreement--to give that baby to another couple. The recent Baby M case in the United States has raised numerous legal concerns causing many legislative bodies to consider possible statutes to regulate or prohibit surrogacy. The competing interests among and between the individuals involved in this relationship (i.e., the surrogate mother, the couple, the baby, and society) suggest various ethical issues related to benefits, risks, and autonomy. Legal and ethical concerns surrounding the technologically possible procedure of surrogate motherhood are discussed. PMID:2391288

  17. On the processes generating latitudinal richness gradients: identifying diagnostic patterns and predictions

    PubMed Central

    Hurlbert, Allen H.; Stegen, James C.

    2014-01-01

    We use a simulation model to examine four of the most common hypotheses for the latitudinal richness gradient and identify patterns that might be diagnostic of those four hypotheses. The hypotheses examined include (1) tropical niche conservatism, or the idea that the tropics are more diverse because a tropical clade origin has allowed more time for diversification in the tropics and has resulted in few species adapted to extra-tropical climates. (2) The ecological limits hypothesis suggests that species richness is limited by the amount of biologically available energy in a region. (3) The speciation rates hypothesis suggests that the latitudinal gradient arises from a gradient in speciation rates. (4) Finally, the tropical stability hypothesis argues that climatic fluctuations and glacial cycles in extratropical regions have led to greater extinction rates and less opportunity for specialization relative to the tropics. We found that tropical niche conservatism can be distinguished from the other three scenarios by phylogenies which are more balanced than expected, no relationship between mean root distance (MRD) and richness across regions, and a homogeneous rate of speciation across clades and through time. The energy gradient, speciation gradient, and disturbance gradient scenarios all produced phylogenies which were more imbalanced than expected, showed a negative relationship between MRD and richness, and diversity-dependence of speciation rate estimates through time. We found that the relationship between speciation rates and latitude could distinguish among these three scenarios, with no relation expected under the ecological limits hypothesis, a negative relationship expected under the speciation rates hypothesis, and a positive relationship expected under the tropical stability hypothesis. We emphasize the importance of considering multiple hypotheses and focusing on diagnostic predictions instead of predictions that are consistent with multiple

  18. Improved mutation tagging with gene identifiers applied to membrane protein stability prediction

    PubMed Central

    Winnenburg, Rainer; Plake, Conrad; Schroeder, Michael

    2009-01-01

    Background The automated retrieval and integration of information about protein point mutations in combination with structure, domain and interaction data from literature and databases promises to be a valuable approach to study structure-function relationships in biomedical data sets. Results We developed a rule- and regular expression-based protein point mutation retrieval pipeline for PubMed abstracts, which shows an F-measure of 87% for the mutation retrieval task on a benchmark dataset. In order to link mutations to their proteins, we utilize a named entity recognition algorithm for the identification of gene names co-occurring in the abstract, and establish links based on sequence checks. Vice versa, we could show that gene recognition improved from 77% to 91% F-measure when considering mutation information given in the text. To demonstrate practical relevance, we utilize mutation information from text to evaluate a novel solvation energy based model for the prediction of stabilizing regions in membrane proteins. For five G protein-coupled receptors we identified 35 relevant single mutations and associated phenotypes, of which none had been annotated in the UniProt or PDB database. In 71% reported phenotypes were in compliance with the model predictions, supporting a relation between mutations and stability issues in membrane proteins. Conclusion We present a reliable approach for the retrieval of protein mutations from PubMed abstracts for any set of genes or proteins of interest. We further demonstrate how amino acid substitution information from text can be utilized for protein structure stability studies on the basis of a novel energy model. PMID:19758467

  19. PREDICT-PD: Identifying risk of Parkinson's disease in the community: methods and baseline results

    PubMed Central

    Noyce, Alastair J; Bestwick, Jonathan P; Silveira-Moriyama, Laura; Hawkes, Christopher H; Knowles, Charles H; Hardy, John; Giovannoni, Gavin; Nageshwaran, Saiji; Osborne, Curtis; Lees, Andrew J; Schrag, Anette

    2014-01-01

    Objectives To present methods and baseline results for an online screening tool to identify increased risk for Parkinson's disease (PD) in the UK population. Methods Risk estimates for future PD were derived from the results of a systematic review of risk factors and early features of PD. Participants aged 60–80 years without PD were recruited by self-referral. They completed an online survey (including family history, non-motor symptoms and lifestyle factors), a keyboard-tapping task and the University of Pennsylvania Smell Identification Test. Risk scores were calculated based on survey answers. Preliminary support for the validity of this algorithm was assessed by comparing those estimated to be higher risk for PD with those at lower risk using proxies, including smell loss, REM-sleep behaviour disorder and reduced tapping speed, and by assessing associations in the whole group. Results 1324 eligible participants completed the survey and 1146 undertook the keyboard-tapping task. Smell tests were sent to 1065 participants. Comparing the 100 highest-risk participants and 100 lowest-risk participants, median University of Pennsylvania Smell Identification Test scores were 30/40 versus 33/40 (p<0.001), mean number of key taps in 30 s were 55 versus 58 (p=0.045), and 24% versus 10% scored above cut-off for REM-sleep behaviour disorder (p=0.008). Regression analyses showed increasing risk scores were associated with worse scores in the three proxies across the whole group (p≤0.001). Conclusions PREDICT-PD is the first study to systematically combine risk factors for PD in the general population. Validity to predict risk of PD will be tested through longitudinal follow-up of incident PD diagnosis. PMID:23828833

  20. On the processes generating latitudinal richness gradients: identifying diagnostic patterns and predictions

    SciTech Connect

    Hurlbert, Allen H.; Stegen, James C.

    2014-12-02

    Many processes have been put forward to explain the latitudinal gradient in species richness. Here, we use a simulation model to examine four of the most common hypotheses and identify patterns that might be diagnostic of those four hypotheses. The hypotheses examined include (1) tropical niche conservatism, or the idea that the tropics are more diverse because a tropical clade origin has allowed more time for diversification in the tropics and has resulted in few species adapted to extra-tropical climates. (2) The productivity, or energetic constraints, hypothesis suggests that species richness is limited by the amount of biologically available energy in a region. (3) The tropical stability hypothesis argues that major climatic fluctuations and glacial cycles in extratropical regions have led to greater extinction rates and less opportunity for specialization relative to the tropics. (4) Finally, the speciation rates hypothesis suggests that the latitudinal richness gradient arises from a parallel gradient in rates of speciation. We found that tropical niche conservatism can be distinguished from the other three scenarios by phylogenies which are more balanced than expected, no relationship between mean root distance and richness across regions, and a homogeneous rate of speciation across clades and through time. The energy gradient, speciation gradient, and disturbance gradient scenarios all exhibited phylogenies which were more imbalanced than expected, showed a negative relationship between mean root distance and richness, and diversity-dependence of speciation rate estimates through time. Using Bayesian Analysis of Macroevolutionary Mixtures on the simulated phylogenies, we found that the relationship between speciation rates and latitude could distinguish among these three scenarios. We emphasize the importance of considering multiple hypotheses and focusing on diagnostic predictions instead of predictions that are consistent with more than one hypothesis.

  1. Numeracy and Literacy Independently Predict Patients’ Ability to Identify Out-of-Range Test Results

    PubMed Central

    Exe, Nicole L; Witteman, Holly O

    2014-01-01

    .12-1.58, P=.001). Predicted probabilities suggested 77% of higher numeracy and health literacy participants, but only 38% of lower numeracy and literacy participants, could correctly identify the hemoglobin A1c levels as outside the reference range. Correct identification reduced perceived blood glucose control (mean difference 1.68-1.71 points on a 0-10 scale, P<.001). For participants with diabetes, increased health literacy reduced the likelihood of calling one’s doctor when hemoglobin A1c=7.1% (OR 0.66 per unit, 95% CI 0.52-0.82, P<.001) and increased numeracy increased intention to call when hemoglobin A1c=8.4% (OR 1.36 per unit, 95% CI 1.10-1.69, P=.005). Conclusions Limited health literacy and numeracy skills are significant barriers to basic use of laboratory test result data as currently presented in some EHR portals. Regarding contacting their doctor, less numerate and literate participants with diabetes appear insensitive to the hemoglobin A1c level shown, whereas highly numerate and literate participants with diabetes appear very sensitive. Alternate approaches appear necessary to make test results more meaningful. PMID:25135688

  2. Anaerobic biodegradation of surrogate naphthenic acids.

    PubMed

    Clothier, Lindsay N; Gieg, Lisa M

    2016-03-01

    Surface bitumen extraction from the Alberta's oil sands region generates large settling basins known as tailings ponds. The oil sands process-affected water (OSPW) stored in these ponds contain solid and residual bitumen-associated compounds including naphthenic acids (NAs) that can potentially be biodedgraded by indigenous tailings microorganisms. While the biodegradation of some NAs is known to occur under aerobic conditions, little is understood about anaerobic NA biodegradation even though tailings ponds are mainly anoxic. Here, we investigated the potential for anaerobic NA biodegradation by indigenous tailings microorganisms. Enrichment cultures were established from anoxic tailings that were amended with 5 single-ringed surrogate NAs or acid-extractable organics (AEO) from OSPW and incubated under nitrate-, sulfate-, iron-reducing, and methanogenic conditions. Surrogate NA depletion was observed under all anaerobic conditions tested to varying extents, correlating to losses in the respective electron acceptor (sulfate or nitrate) or the production of predicted products (Fe(II) or methane). Tailings-containing cultures incubated under the different electron-accepting conditions resulted in the enrichment and putative identification of microbial community members that may function in metabolizing surrogate NAs under the various anoxic conditions. In addition, more complex NAs (in the form of AEO) was observed to drive sulfate and iron reduction relative to controls. Overall, this study has shown that simple surrogate NAs can be biodegraded under a variety of anoxic conditions, a key first step in understanding the potential anaerobic metabolism of NAs in oil sands tailings ponds and other industrial wastewaters. PMID:26724449

  3. Identifying Precipitation Types Using Dual-Polarization-Based Radar and Numerical Weather Prediction Model Data

    NASA Astrophysics Data System (ADS)

    Seo, B. C.; Bradley, A.; Krajewski, W. F.

    2015-12-01

    The recent upgrade of dual-polarization with NEXRAD radars has assisted in improving the characterization of microphysical processes in precipitation and thus has enabled precipitation estimation based on the identified precipitation types. While this polarimetric capability promises the potential for the enhanced accuracy in quantitative precipitation estimation (QPE), recent studies show that the polarimetric estimates are still affected by uncertainties arising from the radar beam geometry/sampling space associated with the vertical variability of precipitation. The authors, first of all, focus on evaluating the NEXRAD hydrometeor classification product using ground reference data (e.g., ASOS) that provide simple categories of the observed precipitation types (e.g., rain, snow, and freezing rain). They also investigate classification uncertainty features caused by the variability of precipitation between the ground and the altitudes where radar samples. Since this variability is closely related to the atmospheric conditions (e.g., temperature) at near surface, useful information (e.g., critical thickness and temperature profile) that is not available in radar observations is retrieved from the numerical weather prediction (NWP) model data such as Rapid Refresh (RAP)/High Resolution Rapid Refresh (HRRR). The NWP retrieved information and polarimetric radar data are used together to improve the accuracy of precipitation type identification at near surface. The authors highlight major improvements and discuss limitations in the real-time application.

  4. Molecular dissection of valproic acid effects in acute myeloid leukemia identifies predictive networks.

    PubMed

    Rücker, Frank G; Lang, Katharina M; Fütterer, Markus; Komarica, Vladimir; Schmid, Mathias; Döhner, Hartmut; Schlenk, Richard F; Döhner, Konstanze; Knudsen, Steen; Bullinger, Lars

    2016-07-01

    Histone deacetylase inhibitors (HDACIs) like valproic acid (VPA) display activity in leukemia models and induce tumor-selective cytotoxicity against acute myeloid leukemia (AML) blasts. As there are limited data on HDACIs effects, we aimed to dissect VPA effects in vitro using myeloid cell lines with the idea to integrate findings with in vivo data from AML patients treated with VPA additionally to intensive chemotherapy (n = 12). By gene expression profiling we identified an in vitro VPA response signature enriched for genes/pathways known to be implicated in cell cycle arrest, apoptosis, and DNA repair. Following VPA treatment in vivo, gene expression changes in AML patients showed concordant results with the in vitro VPA response despite concomitant intensive chemotherapy. Comparative miRNA profiling revealed VPA-associated miRNA expression changes likely contributing to a VPA-induced reversion of deregulated gene expression. In addition, we were able to define markers predicting VPA response in vivo such as CXCR4 and LBH. These could be validated in an independent cohort of VPA and intensive chemotherapy treated AML patients (n = 114) in which they were inversely correlated with relapse-free survival. In summary, our data provide new insights into the molecular mechanisms of VPA in myeloid blasts, which might be useful in further advancing HDAC inhibition based treatment approaches in AML. PMID:27309669

  5. Identifying Psychosocial Variables That Predict Safer Sex Intentions in Adolescents and Young Adults.

    PubMed

    Brüll, Phil; Ruiter, Robert A C; Wiers, Reinout W; Kok, Gerjo

    2016-01-01

    Young people are especially vulnerable to sexually transmitted infections (STIs). The triad of deliberate and effective safer sex behavior encompasses condom use, combined with additional information about a partner's sexual health, and the kind of sex acts usually performed. To identify psychosocial predictors of young people's intentions to have safer sex, as related to this triad, we conducted an online study with 211 sexually active participants aged between 18 and 24 years. Predictors [i.e., perceived behavioral control (PBC), subjective norms, and intention] taken from Fishbein and Ajzen's Reasoned Action Approach (RAA), were combined with more distal variables (e.g., behavioral inhibition, sensation seeking, parental monitoring, and knowledge about STIs). Beyond the highly predictive power of RAA variables, additional variance was explained by the number of instances of unprotected sexual intercourse (SI) during the last 12 months and reasons for using barrier protection during first SI. In particular, past condom non-use behavior moderated PBC related to intended condom use. Further, various distal variables showed significant univariate associations with intentions related to the three behaviors of interest. It may, therefore, be helpful to include measures of past behavior as well as certain additional distal variables in future safer sex programs designed to promote health-sustaining sexual behavior. PMID:27148520

  6. Mass Spectrometry-Based Metabolomics Identifies Longitudinal Urinary Metabolite Profiles Predictive of Radiation-Induced Cancer.

    PubMed

    Cook, John A; Chandramouli, Gadisetti V R; Anver, Miriam R; Sowers, Anastasia L; Thetford, Angela; Krausz, Kristopher W; Gonzalez, Frank J; Mitchell, James B; Patterson, Andrew D

    2016-03-15

    Nonlethal exposure to ionizing radiation (IR) is a public concern due to its known carcinogenic effects. Although latency periods for IR-induced neoplasms are relatively long, the ability to detect cancer as early as possible is highly advantageous for effective therapeutic intervention. Therefore, we hypothesized that metabolites in the urine from mice exposed to total body radiation (TBI) would predict for the presence of cancer before a palpable mass was detected. In this study, we exposed mice to 0 or 5.4 Gy TBI, collected urine samples periodically over 1 year, and assayed urine metabolites by using mass spectrometry. Longitudinal data analysis within the first year post-TBI revealed that cancers, including hematopoietic, solid, and benign neoplasms, could be distinguished by unique urinary signatures as early as 3 months post-TBI. Furthermore, a distinction among different types of malignancies could be clearly delineated as early as 3 months post-TBI for hematopoietic neoplasms, 6 months for solid neoplasms, and by 1 year for benign neoplasms. Moreover, the feature profile for radiation-exposed mice 6 months post-TBI was found to be similar to nonirradiated control mice at 18 months, suggesting that TBI accelerates aging. These results demonstrate that urine feature profiles following TBI can identify cancers in mice prior to macroscopic detection, with important implications for the early diagnosis and treatment. PMID:26880804

  7. Learning impairments identified early in life are predictive of future impairments associated with aging

    PubMed Central

    Hullinger, Rikki; Burger, Corinna

    2016-01-01

    The Morris water maze (MWM) behavioral paradigm is commonly used to measure spatial learning and memory in rodents. It is widely accepted that performance in the MWM declines with age. However, young rats ubiquitously perform very well on established versions of the water maze, suggesting that more challenging tasks may be required to reveal subtle differences in young animals. Therefore, we have used a one-day water maze and novel object recognition to test whether more sensitive paradigms of memory in young animals could identify subtle cognitive impairments early in life that might become accentuated later with senescence. We have found that these two tasks reliably separate young rats into inferior and superior learners, are highly correlated, and that performance on these tasks early in life is predictive of performance at 12 months of age. Furthermore, we have found that repeated training in this task selectively improves the performance of inferior learners, suggesting that behavioral training from an early age may provide a buffer against age-related cognitive decline. PMID:26283528

  8. Identifying Psychosocial Variables That Predict Safer Sex Intentions in Adolescents and Young Adults

    PubMed Central

    Brüll, Phil; Ruiter, Robert A. C.; Wiers, Reinout W.; Kok, Gerjo

    2016-01-01

    Young people are especially vulnerable to sexually transmitted infections (STIs). The triad of deliberate and effective safer sex behavior encompasses condom use, combined with additional information about a partner’s sexual health, and the kind of sex acts usually performed. To identify psychosocial predictors of young people’s intentions to have safer sex, as related to this triad, we conducted an online study with 211 sexually active participants aged between 18 and 24 years. Predictors [i.e., perceived behavioral control (PBC), subjective norms, and intention] taken from Fishbein and Ajzen’s Reasoned Action Approach (RAA), were combined with more distal variables (e.g., behavioral inhibition, sensation seeking, parental monitoring, and knowledge about STIs). Beyond the highly predictive power of RAA variables, additional variance was explained by the number of instances of unprotected sexual intercourse (SI) during the last 12 months and reasons for using barrier protection during first SI. In particular, past condom non-use behavior moderated PBC related to intended condom use. Further, various distal variables showed significant univariate associations with intentions related to the three behaviors of interest. It may, therefore, be helpful to include measures of past behavior as well as certain additional distal variables in future safer sex programs designed to promote health-sustaining sexual behavior. PMID:27148520

  9. The Creation of Surrogate Models for Fast Estimation of Complex Model Outcomes

    PubMed Central

    Pruett, W. Andrew; Hester, Robert L.

    2016-01-01

    A surrogate model is a black box model that reproduces the output of another more complex model at a single time point. This is to be distinguished from the method of surrogate data, used in time series. The purpose of a surrogate is to reduce the time necessary for a computation at the cost of rigor and generality. We describe a method of constructing surrogates in the form of support vector machine (SVM) regressions for the purpose of exploring the parameter space of physiological models. Our focus is on the methodology of surrogate creation and accuracy assessment in comparison to the original model. This is done in the context of a simulation of hemorrhage in one model, “Small”, and renal denervation in another, HumMod. In both cases, the surrogate predicts the drop in mean arterial pressure following the intervention. We asked three questions concerning surrogate models: (1) how many training examples are necessary to obtain an accurate surrogate, (2) is surrogate accuracy homogeneous, and (3) how much can computation time be reduced when using a surrogate. We found the minimum training set size that would guarantee maximal accuracy was widely variable, but could be algorithmically generated. The average error for the pressure response to the protocols was -0.05±2.47 in Small, and -0.3 +/- 3.94 mmHg in HumMod. In the Small model, error grew with actual pressure drop, and in HumMod, larger pressure drops were overestimated by the surrogates. Surrogate use resulted in a 6 order of magnitude decrease in computation time. These results suggest surrogate modeling is a valuable tool for generating predictions of an integrative model’s behavior on densely sampled subsets of its parameter space. PMID:27258010

  10. Statistical evaluation of surrogate endpoints with examples from cancer clinical trials.

    PubMed

    Buyse, Marc; Molenberghs, Geert; Paoletti, Xavier; Oba, Koji; Alonso, Ariel; Van der Elst, Wim; Burzykowski, Tomasz

    2016-01-01

    A surrogate endpoint is intended to replace a clinical endpoint for the evaluation of new treatments when it can be measured more cheaply, more conveniently, more frequently, or earlier than that clinical endpoint. A surrogate endpoint is expected to predict clinical benefit, harm, or lack of these. Besides the biological plausibility of a surrogate, a quantitative assessment of the strength of evidence for surrogacy requires the demonstration of the prognostic value of the surrogate for the clinical outcome, and evidence that treatment effects on the surrogate reliably predict treatment effects on the clinical outcome. We focus on these two conditions, and outline the statistical approaches that have been proposed to assess the extent to which these conditions are fulfilled. When data are available from a single trial, one can assess the "individual level association" between the surrogate and the true endpoint. When data are available from several trials, one can additionally assess the "trial level association" between the treatment effect on the surrogate and the treatment effect on the true endpoint. In the latter case, the "surrogate threshold effect" can be estimated as the minimum effect on the surrogate endpoint that predicts a statistically significant effect on the clinical endpoint. All these concepts are discussed in the context of randomized clinical trials in oncology, and illustrated with two meta-analyses in gastric cancer. PMID:25682941

  11. MELANCHOLIC DEPRESSION PREDICTION BY IDENTIFYING REPRESENTATIVE FEATURES IN METABOLIC AND MICROARRAY PROFILES WITH MISSING VALUES

    PubMed Central

    Nie, Zhi; Yang, Tao; Liu, Yashu; Lin, Binbin; Li, Qingyang; Narayan, Vaibhav A; Wittenberg, Gayle; Ye, Jieping

    2014-01-01

    Recent studies have revealed that melancholic depression, one major subtype of depression, is closely associated with the concentration of some metabolites and biological functions of certain genes and pathways. Meanwhile, recent advances in biotechnologies have allowed us to collect a large amount of genomic data, e.g., metabolites and microarray gene expression. With such a huge amount of information available, one approach that can give us new insights into the understanding of the fundamental biology underlying melancholic depression is to build disease status prediction models using classification or regression methods. However, the existence of strong empirical correlations, e.g., those exhibited by genes sharing the same biological pathway in microarray profiles, tremendously limits the performance of these methods. Furthermore, the occurrence of missing values which are ubiquitous in biomedical applications further complicates the problem. In this paper, we hypothesize that the problem of missing values might in some way benefit from the correlation between the variables and propose a method to learn a compressed set of representative features through an adapted version of sparse coding which is capable of identifying correlated variables and addressing the issue of missing values simultaneously. An efficient algorithm is also developed to solve the proposed formulation. We apply the proposed method on metabolic and microarray profiles collected from a group of subjects consisting of both patients with melancholic depression and healthy controls. Results show that the proposed method can not only produce meaningful clusters of variables but also generate a set of representative features that achieve superior classification performance over those generated by traditional clustering and data imputation techniques. In particular, on both datasets, we found that in comparison with the competing algorithms, the representative features learned by the proposed

  12. Melancholic depression prediction by identifying representative features in metabolic and microarray profiles with missing values.

    PubMed

    Nie, Zhi; Yang, Tao; Liu, Yashu; Li, Qingyang; Narayan, Vaibhav A; Wittenberg, Gayle; Ye, Jieping

    2015-01-01

    Recent studies have revealed that melancholic depression, one major subtype of depression, is closely associated with the concentration of some metabolites and biological functions of certain genes and pathways. Meanwhile, recent advances in biotechnologies have allowed us to collect a large amount of genomic data, e.g., metabolites and microarray gene expression. With such a huge amount of information available, one approach that can give us new insights into the understanding of the fundamental biology underlying melancholic depression is to build disease status prediction models using classification or regression methods. However, the existence of strong empirical correlations, e.g., those exhibited by genes sharing the same biological pathway in microarray profiles, tremendously limits the performance of these methods. Furthermore, the occurrence of missing values which are ubiquitous in biomedical applications further complicates the problem. In this paper, we hypothesize that the problem of missing values might in some way benefit from the correlation between the variables and propose a method to learn a compressed set of representative features through an adapted version of sparse coding which is capable of identifying correlated variables and addressing the issue of missing values simultaneously. An efficient algorithm is also developed to solve the proposed formulation. We apply the proposed method on metabolic and microarray profiles collected from a group of subjects consisting of both patients with melancholic depression and healthy controls. Results show that the proposed method can not only produce meaningful clusters of variables but also generate a set of representative features that achieve superior classification performance over those generated by traditional clustering and data imputation techniques. In particular, on both datasets, we found that in comparison with the competing algorithms, the representative features learned by the proposed

  13. Predicting 3-year outcomes of early-identified children with hearing impairment

    PubMed Central

    Ching, T.Y.C.; Day, J.; Seeto, M.; Dillon, H.; Marnane, V.; Street, L.

    2013-01-01

    Problem/Objectives Permanent childhood hearing loss has major negative impacts on children’s health and development. To improve outcomes, universal newborn hearing screening (UNHS) has been implemented widely. However, high-quality evidence on its efficacy was lacking. To address this evidence gap, we conducted the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study to directly compare outcomes of early- and late-identified children. This paper investigates whether early performance measured shortly after initial amplification predicts language development at 3 years of age. Methodology This is a prospective, population-based study. We assessed outcomes at 6- and 12-months after amplification, and then at 3 and 5 years of age. Main outcome measures included directly-assessed language, receptive vocabulary, speech production; and parent-reported functional performance in everyday life. A range of demographic and audiological information was also collected at evaluation intervals. Results About 450 children participated, and 3-year outcomes scores were available for 356 participants. Multiple regression analysis revealed that early language scores or functional performance ratings were significant predictors of 3-year outcomes. Other significant predictors included the presence or absence of additional disabilities, severity of hearing loss, and age at cochlear implant activation. Conclusions Early performance, either directly-assessed language ability (PLS-4) or parent-reported functional ratings (PEACH), were significant predictors of 3-year outcomes; along with presence or absence of additional disabilities, severity of hearing loss, and age at CI activation. Earlier implantation is possible with early detection of hearing loss via UNHS. Monitoring performance after initial amplification allows preventive strategies to be implemented early to improve outcomes. PMID:24383228

  14. Psychosocial aspects of surrogate motherhood.

    PubMed

    van den Akker, Olga B A

    2007-01-01

    This review addresses the psychosocial research carried out on surrogacy triads (surrogate mothers, commissioning mothers and offspring) and shows that research has focused on a number of specific issues: attachment and disclosure to surrogate offspring; experiences, characteristics and motivations of surrogate mothers; and changes in profiles of the commissioning/intended mothers. Virtually all studies have used highly selected samples making generalizations difficult. There have been a notable lack of theory, no interventions and only a handful of longitudinal studies or studies comparing different populations. Few studies have specifically questioned the meaning of and need for a family or the influence and impact that professionals, treatment availability and financial factors have on the choices made for surrogate and intended mothers. Societal attitudes have changed somewhat; however, according to public opinion, women giving up babies still fall outside the acceptable remit. Surrogate and intended mothers appear to reconcile their unusual choice through a process of cognitive restructuring, and the success or failure of this cognitive appraisal affects people's willingness to be open and honest about their choices. Normal population surveys, on the contrary, are less accepting of third party reproduction; they have no personal need to reconsider and hence maintain their original normative cognitively consonant state. PMID:16936307

  15. Relaxation rates for inverse power law particle interactions and their variable hard sphere surrogates

    NASA Astrophysics Data System (ADS)

    Rubinstein, Robert

    2015-11-01

    It is well known that collision models based on an assumed intermolecular potential (IPL, LJ, ...) can be successfully replaced by simplified surrogates (VHS, VSS, VS, ...) in DSMC calculations. But these surrogates only reproduce certain gross properties of the molecular model, for example, the temperature dependence of the viscosity; they do not approximate, and even mis-state, the details of the particle interactions. The success of the simplified models in problems at finite Knudsen number, where the Navier-Stokes approximation is not valid, may therefore seem surprising. To understand this success in a very special case, we showed that the first seven relaxation rates of the linearized Boltzmann equation for Maxwellian molecules are well approximated by the corresponding relaxation rates of its VHS surrogate. We will show that this analysis can be extended in somewhat less generality to IPL interactions, and to some extent to more realistic models including LJ. We believe that this analysis can help address the more general problem of identifying the properties of the collision model that dominate the predictions of the Boltzmann equation.

  16. Surrogate insulin-producing cells

    PubMed Central

    Wong, Adrianne L.; Hwa, Albert; Hellman, Dov

    2012-01-01

    Diabetes, a large and growing worldwide health concern, affects the functional mass of the pancreatic beta cell, which in turn affects the glucose regulation of the body. Successful transplantation of cadaveric islets and pancreata for patients with uncontrolled type 1 diabetes has provided proof-of-concept for the development of commercial cell therapy approaches to treat diabetes. Three broad issues must be addressed before surrogate insulin-producing cells can become a reality: the development of a surrogate beta-cell source, immunoprotection, and translation. Cell therapy for diabetes is a real possibility, but many questions remain; through the collaborative efforts of multiple stakeholders this may become a reality. PMID:22891077

  17. Identifying the causes of the poor decadal climate prediction skill over the North Pacific

    NASA Astrophysics Data System (ADS)

    Guemas, V.; Doblas-Reyes, F. J.; Lienert, F.; Soufflet, Y.; Du, H.

    2012-10-01

    While the North Pacific region has a strong influence on North American and Asian climate, it is also the area with the worst performance in several state-of-the-art decadal climate predictions in terms of correlation and root mean square error scores. The failure to represent two major warm sea surface temperature events occurring around 1963 and 1968 largely contributes to this poor skill. The magnitude of these events competes with the largest observed temperature anomalies in the twenty-first century that might be associated with the long-term warming. Understanding the causes of these major warm events is thus of primary concern to improve prediction of North Pacific, North American and Asian climate. The 1963 warm event stemmed from the propagation of a warm ocean heat content anomaly along the Kuroshio-Oyashio extension. The 1968 warm event originated from the upward transfer of a warm water mass centered at 200 m depth. For being associated with long-lived ocean heat content anomalies, we expect those events to be, at least partially, predictable. Biases in ocean mixing processes present in many climate prediction models seem to explain the inability to predict these two major events. Such currently unpredictable warm events, if occurring again in the next decade, would substantially enhance the effect of long-term warming in the region.

  18. Predicting crash risk and identifying crash precursors on Korean expressways using loop detector data.

    PubMed

    Kwak, Ho-Chan; Kho, Seungyoung

    2016-03-01

    In order to improve traffic safety on expressways, it is important to develop proactive safety management strategies with consideration for segment types and traffic flow states because crash mechanisms have some differences by each condition. The primary objective of this study is to develop real-time crash risk prediction models for different segment types and traffic flow states on expressways. The mainline of expressways is divided into basic segment and ramp vicinity, and the traffic flow states are classified into uncongested and congested conditions. Also, Korean expressways have irregular intervals between loop detector stations. Therefore, we investigated on the effect and application of the detector stations at irregular intervals for the crash risk prediction on expressways. The most significant traffic variables were selected by conditional logistic regression analysis which could control confounding factors. Based on the selected traffic variables, separate models to predict crash risk were developed using genetic programming technique. The model estimation results showed that the traffic flow characteristics leading to crashes are differed by segment type and traffic flow state. Especially, the variables related to the intervals between detector stations had a significant influence on crash risk prediction under the uncongested condition. Finally, compared with the single model for all crashes and the logistic models used in previous studies, the proposed models showed higher prediction performance. The results of this study can be applied to develop more effective proactive safety management strategies for different segment types and traffic flow states on expressways with loop detector stations at irregular intervals. PMID:26710266

  19. Shape Optimization by Bayesian-Validated Computer-Simulation Surrogates

    NASA Technical Reports Server (NTRS)

    Patera, Anthony T.

    1997-01-01

    A nonparametric-validated, surrogate approach to optimization has been applied to the computational optimization of eddy-promoter heat exchangers and to the experimental optimization of a multielement airfoil. In addition to the baseline surrogate framework, a surrogate-Pareto framework has been applied to the two-criteria, eddy-promoter design problem. The Pareto analysis improves the predictability of the surrogate results, preserves generality, and provides a means to rapidly determine design trade-offs. Significant contributions have been made in the geometric description used for the eddy-promoter inclusions as well as to the surrogate framework itself. A level-set based, geometric description has been developed to define the shape of the eddy-promoter inclusions. The level-set technique allows for topology changes (from single-body,eddy-promoter configurations to two-body configurations) without requiring any additional logic. The continuity of the output responses for input variations that cross the boundary between topologies has been demonstrated. Input-output continuity is required for the straightforward application of surrogate techniques in which simplified, interpolative models are fitted through a construction set of data. The surrogate framework developed previously has been extended in a number of ways. First, the formulation for a general, two-output, two-performance metric problem is presented. Surrogates are constructed and validated for the outputs. The performance metrics can be functions of both outputs, as well as explicitly of the inputs, and serve to characterize the design preferences. By segregating the outputs and the performance metrics, an additional level of flexibility is provided to the designer. The validated outputs can be used in future design studies and the error estimates provided by the output validation step still apply, and require no additional appeals to the expensive analysis. Second, a candidate-based a posteriori

  20. Computationally efficient calibration of WATCLASS Hydrologic models using surrogate optimization

    NASA Astrophysics Data System (ADS)

    Kamali, M.; Ponnambalam, K.; Soulis, E. D.

    2007-07-01

    In this approach, exploration of the cost function space was performed with an inexpensive surrogate function, not the expensive original function. The Design and Analysis of Computer Experiments(DACE) surrogate function, which is one type of approximate models, which takes correlation function for error was employed. The results for Monte Carlo Sampling, Latin Hypercube Sampling and Design and Analysis of Computer Experiments(DACE) approximate model have been compared. The results show that DACE model has a good potential for predicting the trend of simulation results. The case study of this document was WATCLASS hydrologic model calibration on Smokey-River watershed.

  1. Evaluating two sparse grid surrogates and two adaptation criteria for groundwater Bayesian uncertainty quantification

    NASA Astrophysics Data System (ADS)

    Zeng, Xiankui; Ye, Ming; Burkardt, John; Wu, Jichun; Wang, Dong; Zhu, Xiaobin

    2016-04-01

    Sparse grid (SG) stochastic collocation methods have been recently used to build accurate but cheap-to-run surrogates for groundwater models to reduce the computational burden of Bayesian uncertainty analysis. The surrogates can be built for either a log-likelihood function or state variables such as hydraulic head and solute concentration. Using a synthetic groundwater flow model, this study evaluates the log-likelihood and head surrogates in terms of the computational cost of building them, the accuracy of the surrogates, and the accuracy of the distributions of model parameters and predictions obtained using the surrogates. The head surrogates outperform the log-likelihood surrogates for the following four reasons: (1) the shape of the head response surface is smoother than that of the log-likelihood response surface in parameter space, (2) the head variation is smaller than the log-likelihood variation in parameter space, (3) the interpolation error of the head surrogates does not accumulate to be larger than the interpolation error of the log-likelihood surrogates, and (4) the model simulations needed for building one head surrogate can be recycled for building others. For both log-likelihood and head surrogates, adaptive sparse grids are built using two indicators: absolute error and relative error. The adaptive head surrogates are insensitive to the error indicators, because the ratio between the two indicators is hydraulic head, which has small variation in the parameter space. The adaptive log-likelihood surrogates based on the relative error indicators outperform those based on the absolute error indicators, because adaptation based on the relative error indicator puts more sparse-grid nodes in the areas in the parameter space where the log-likelihood is high. While our numerical study suggests building state-variable surrogates and using the relative error indicator for building log-likelihood surrogates, selecting appropriate type of surrogates and

  2. Dynamic impact indentation of hydrated biological tissues and tissue surrogate gels

    NASA Astrophysics Data System (ADS)

    Ilke Kalcioglu, Z.; Qu, Meng; Strawhecker, Kenneth E.; Shazly, Tarek; Edelman, Elazer; VanLandingham, Mark R.; Smith, James F.; Van Vliet, Krystyn J.

    2011-03-01

    For both materials engineering research and applied biomedicine, a growing need exists to quantify mechanical behaviour of tissues under defined hydration and loading conditions. In particular, characterisation under dynamic contact-loading conditions can enable quantitative predictions of deformation due to high rate 'impact' events typical of industrial accidents and ballistic insults. The impact indentation responses were examined of both hydrated tissues and candidate tissue surrogate materials. The goals of this work were to determine the mechanical response of fully hydrated soft tissues under defined dynamic loading conditions, and to identify design principles by which synthetic, air-stable polymers could mimic those responses. Soft tissues from two organs (liver and heart), a commercially available tissue surrogate gel (Perma-Gel™) and three styrenic block copolymer gels were investigated. Impact indentation enabled quantification of resistance to penetration and energy dissipative constants under the rates and energy densities of interest for tissue surrogate applications. These analyses indicated that the energy dissipation capacity under dynamic impact increased with increasing diblock concentration in the styrenic gels. Under the impact rates employed (2 mm/s to 20 mm/s, corresponding to approximate strain energy densities from 0.4 kJ/m3 to 20 kJ/m3), the energy dissipation capacities of fully hydrated soft tissues were ultimately well matched by a 50/50 triblock/diblock composition that is stable in ambient environments. More generally, the methodologies detailed here facilitate further optimisation of impact energy dissipation capacity of polymer-based tissue surrogate materials, either in air or in fluids.

  3. Paper Highlight: Biomarker Identified for Predicting Early Prostate Cancer Aggressiveness — Site

    Cancer.gov

    A team led by Cory Abate-Shen, Michael Shen, and Andrea Califano at Columbia University found that measuring the expression levels of three genes associated with aging can be used to predict the aggressiveness of seemingly low-risk prostate cancer.

  4. An Evaluation of the Predictive Validity of Confidence Ratings in Identifying Functional Behavioral Assessment Hypothesis Statements

    ERIC Educational Resources Information Center

    Borgmeier, Chris; Horner, Robert H.

    2006-01-01

    Faced with limited resources, schools require tools that increase the accuracy and efficiency of functional behavioral assessment. Yarbrough and Carr (2000) provided evidence that informant confidence ratings of the likelihood of problem behavior in specific situations offered a promising tool for predicting the accuracy of function-based…

  5. Bayesian calibration of the Community Land Model using surrogates

    NASA Astrophysics Data System (ADS)

    Ray, J.; Sargsyan, K.; Huang, M.; Hou, Z.

    2012-12-01

    We present results from a calibration effort of the Community Land Model (CLM) using surrogates. Three parameters, governing subsurface runoff and groundwater dynamics, were targeted and calibrated to observations from the Missouri Ozark Ameriflux tower site (US-Moz) spanning 1996-2004. We adopt a Bayesian approach for calibration where the parameters were estimated as probability distributions to account for the uncertainty due to modelling and observation errors. The model fitting was performed using an adaptive Markov chain Monte Carlo method. Since the sampling-based calibration of CLM could be computationally expensive, we first developed surrogates as alternatives to the CLM. The three-dimensional parameter space was sampled and CLM was used to produce monthly averaged predictions of runoff and latent/sensible heat fluxes. Multiple polynomial "trend" models were proposed, fitted to the CLM simulations via regression, and tested for over-fitting. A quadratic model was ultimately selected and bias-corrected using the universal kriging approach, to produce surrogates with errors less than 10% at any arbitrary point in the parameter-space. This "trend+kriged" model was then used as an inexpensive CLM surrogate, in an MCMC sampler, to solve the calibration problem. Joint densities were developed for the parameters, along with an estimate of the structural error of the surrogates.

  6. Surrogate modeling of deformable joint contact using artificial neural networks.

    PubMed

    Eskinazi, Ilan; Fregly, Benjamin J

    2015-09-01

    Deformable joint contact models can be used to estimate loading conditions for cartilage-cartilage, implant-implant, human-orthotic, and foot-ground interactions. However, contact evaluations are often so expensive computationally that they can be prohibitive for simulations or optimizations requiring thousands or even millions of contact evaluations. To overcome this limitation, we developed a novel surrogate contact modeling method based on artificial neural networks (ANNs). The method uses special sampling techniques to gather input-output data points from an original (slow) contact model in multiple domains of input space, where each domain represents a different physical situation likely to be encountered. For each contact force and torque output by the original contact model, a multi-layer feed-forward ANN is defined, trained, and incorporated into a surrogate contact model. As an evaluation problem, we created an ANN-based surrogate contact model of an artificial tibiofemoral joint using over 75,000 evaluations of a fine-grid elastic foundation (EF) contact model. The surrogate contact model computed contact forces and torques about 1000 times faster than a less accurate coarse grid EF contact model. Furthermore, the surrogate contact model was seven times more accurate than the coarse grid EF contact model within the input domain of a walking motion. For larger input domains, the surrogate contact model showed the expected trend of increasing error with increasing domain size. In addition, the surrogate contact model was able to identify out-of-contact situations with high accuracy. Computational contact models created using our proposed ANN approach may remove an important computational bottleneck from musculoskeletal simulations or optimizations incorporating deformable joint contact models. PMID:26220591

  7. IDENTIFYING AND PREDICTING DIVING PLUME BEHAVIOR AT GROUNDWATER SITES CONTAINING MTBE: PART 1 SUPPLEMENTAL FUNDING FOR ACTIVITIES IN FY 2002

    EPA Science Inventory

    This work will complete work began under Identifying and Predicting Plume Diving Behavior at Groundwater Sites Containing MTBE: Part 1. As of September 2001, ORD Staff and ORD Contractors have characterized dividing MTBE plumes at Spring Green, Wisconsin; Milford, Michigan; and ...

  8. Taxi-Aware Map: Identifying and Predicting Vacant Taxis in the City

    NASA Astrophysics Data System (ADS)

    Phithakkitnukoon, Santi; Veloso, Marco; Bento, Carlos; Biderman, Assaf; Ratti, Carlo

    Knowing where vacant taxis are and will be at a given time and location helps the users in daily planning and scheduling, as well as the taxi service providers in dispatching. In this paper, we present a predictive model for the number of vacant taxis in a given area based on time of the day, day of the week, and weather condition. The history is used to build the prior probability distributions for our inference engine, which is based on the naïve Bayesian classifier with developed error-based learning algorithm and method for detecting adequacy of historical data using mutual information. Based on 150 taxis in Lisbon, Portugal, we are able to predict for each hour with the overall error rate of 0.8 taxis per 1x1 km2 area.

  9. Predictive markers of capecitabine sensitivity identified from the expression profile of pyrimidine nucleoside-metabolizing enzymes.

    PubMed

    Yasuno, Hideyuki; Kurasawa, Mitsue; Yanagisawa, Mieko; Sato, Yasuko; Harada, Naoki; Mori, Kazushige

    2013-02-01

    Molecular markers predicting sensitivity to anticancer drugs are important and useful not only for selecting potential responders but also for developing new combinations. In the present study, we analyzed the difference in the sensitivity of xenograft models to capecitabine (Xeloda®), 5'-deoxy-5-fluorouridine (5'-DFUR, doxifluridine, Furtulon®) and 5-FU by comparing the mRNA levels of 12 pyrimidine nucleoside-metabolizing enzymes. Amounts of mRNA in the tumor tissues of 80 xenograft models were determined by real-time RT-PCR and mutual correlations were examined. A clustering analysis revealed that the 12 enzymes were divided into two groups; one group consisted of 8 enzymes, including orotate phosphoribosyl transferase (OPRT), TMP kinase (TMPK) and UMP kinase (UMPK), and was related to the de novo synthesis pathway for nucleotides, with mRNA expression levels showing significant mutual correlation. In the other group, 4 enzymes, including thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD), were involved in the salvage/degradation pathway of the nucleotides, and the mRNA levels of this group were dispersed more widely than that of the de novo group. Antitumor activity was assessed in 24 xenograft models for each drug. The antitumor activity of capecitabine and 5'-DFUR correlated significantly with the mRNA levels of TP and with the TP/DPD ratio, whereas the activity of 5-FU correlated significantly with OPRT, TMPK, UMPK and CD. In a stepwise regression analysis, TP and DPD were found to be independent predictive factors of sensitivity to capecitabine and 5'-DFUR, and UMPK was predictive of sensitivity to 5-FU. These results indicate that the predictive factors for sensitivity to capecitabine and 5'-DFUR in xenograft models may be different from those for 5-FU, suggesting that these drugs may have different responders in clinical usage. PMID:23229803

  10. Predicting the Risk of Clostridium difficile Infection upon Admission: A Score to Identify Patients for Antimicrobial Stewardship Efforts

    PubMed Central

    Kuntz, Jennifer L; Smith, David H; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Barton, Tracy; Barton, Karen; Labreche, Matthew; Spindel, Steven J; Johnson, Eric S

    2016-01-01

    Introduction: Increasing morbidity and health care costs related to Clostridium difficile infection (CDI) have heightened interest in methods to identify patients who would most benefit from interventions to mitigate the likelihood of CDI. Objective: To develop a risk score that can be calculated upon hospital admission and used by antimicrobial stewards, including pharmacists and clinicians, to identify patients at risk for CDI who would benefit from enhanced antibiotic review and patient education. Methods: We assembled a cohort of Kaiser Permanente Northwest patients with a hospital admission from July 1, 2005, through December 30, 2012, and identified CDI in the six months following hospital admission. Using Cox regression, we constructed a score to identify patients at high risk for CDI on the basis of preadmission characteristics. We calculated and plotted the observed six-month CDI risk for each decile of predicted risk. Results: We identified 721 CDIs following 54,186 hospital admissions—a 6-month incidence of 13.3 CDIs/1000 patient admissions. Patients with the highest predicted risk of CDI had an observed incidence of 53 CDIs/1000 patient admissions. The score differentiated between patients who do and do not develop CDI, with values for the extended C-statistic of 0.75. Predicted risk for CDI agreed closely with observed risk. Conclusion: Our risk score accurately predicted six-month risk for CDI using preadmission characteristics. Accurate predictions among the highest-risk patient subgroups allow for the identification of patients who could be targeted for and who would likely benefit from review of inpatient antibiotic use or enhanced educational efforts at the time of discharge planning. PMID:26845084

  11. Surviving Surrogate Decision-Making: What Helps and Hampers the Experience of Making Medical Decisions for Others

    PubMed Central

    Starks, Helene; Taylor, Janelle S.; Hopley, Elizabeth K.; Fryer-Edwards, Kelly

    2007-01-01

    BACKGROUND A majority of end-of-life medical decisions are made by surrogate decision-makers who have varying degrees of preparation and comfort with their role. Having a seriously ill family member is stressful for surrogates. Moreover, most clinicians have had little training in working effectively with surrogates. OBJECTIVES To better understand the challenges of decision-making from the surrogate’s perspective. DESIGN Semistructured telephone interview study of the experience of surrogate decision-making. PARTICIPANTS Fifty designated surrogates with previous decision-making experience. APPROACH We asked surrogates to describe and reflect on their experience of making medical decisions for others. After coding transcripts, we conducted a content analysis to identify and categorize factors that made decision-making more or less difficult for surrogates. RESULTS Surrogates identified four types of factors: (1) surrogate characteristics and life circumstances (such as coping strategies and competing responsibilities), (2) surrogates’ social networks (such as intrafamily discord about the “right” decision), (3) surrogate–patient relationships and communication (such as difficulties with honoring known preferences), and (4) surrogate–clinician communication and relationship (such as interacting with a single physician whom the surrogate recognizes as the clinical spokesperson vs. many clinicians). CONCLUSIONS These data provide insights into the challenges that surrogates encounter when making decisions for loved ones and indicate areas where clinicians could intervene to facilitate the process of surrogate decision-making. Clinicians may want to include surrogates in advance care planning prior to decision-making, identify and address surrogate stressors during decision-making, and designate one person to communicate information about the patient’s condition, prognosis, and treatment options. PMID:17619223

  12. Predicting General Academic Performance and Identifying the Differential Contribution of Participating Variables Using Artificial Neural Networks

    ERIC Educational Resources Information Center

    Musso, Mariel F.; Kyndt, Eva; Cascallar, Eduardo C.; Dochy, Filip

    2013-01-01

    Many studies have explored the contribution of different factors from diverse theoretical perspectives to the explanation of academic performance. These factors have been identified as having important implications not only for the study of learning processes, but also as tools for improving curriculum designs, tutorial systems, and students'…

  13. Predicting the Unpredictable? Identifying High-Risk versus Low-Risk Parents with Intellectual Disabilities

    ERIC Educational Resources Information Center

    McGaw, Sue; Scully, Tamara; Pritchard, Colin

    2010-01-01

    Objectives: This study set out to identify risk factors affecting parents with intellectual disabilities (IDs) by determining: (i) whether perception of family support differs between parents with IDs, referring professionals, and a specialist parenting service; (ii) whether multivariate familial and demographic factors differentiates "high-risk"…

  14. Predicting School Readiness for Low-Income Children with Disability Risks Identified Early

    ERIC Educational Resources Information Center

    Jeon, Hyun-Joo; Peterson, Carla A.; Wall, Shavaun; Carta, Judith J.; Luze, Gayle; Eshbaugh, Elaine M.; Swanson, Mark

    2011-01-01

    This study examined school readiness at kindergarten entry for low-income children whose disability indicators were identified before age 3. Data were collected as part of the Early Head Start Research and Evaluation Longitudinal Follow-Up study. Children who had suspected developmental delays and did not receive Part C services had lower…

  15. On the use of abiotic surrogates to describe marine benthic biodiversity

    NASA Astrophysics Data System (ADS)

    McArthur, M. A.; Brooke, B. P.; Przeslawski, R.; Ryan, D. A.; Lucieer, V. L.; Nichol, S.; McCallum, A. W.; Mellin, C.; Cresswell, I. D.; Radke, L. C.

    2010-06-01

    are not direct drivers of biodiversity patterns but often correspond with driving gradients and can be of some use in prediction. In such cases it would be better to identify what the spatial variable is acting as a proxy for so boundaries for that variable are not overlooked. The utility of these potential surrogates vary across spatial scales, quality of data, and management needs. A continued focus on surrogate research will address the need of marine scientists and resource managers worldwide for accurate and robust predictions, extending from simple measures of diversity to species distributions and patterns of assemblage.

  16. Identifying the role of Wilms tumor 1 associated protein in cancer prediction using integrative genomic analyses.

    PubMed

    Wu, Li-Sheng; Qian, Jia-Yi; Wang, Minghai; Yang, Haiwei

    2016-09-01

    The Wilms tumor suppressor, WT1 was first identified due to its essential role in the normal development of the human genitourinary system. Wilms tumor 1 associated protein (WTAP) was subsequently revealed to interact with WT1 using yeast two-hybrid screening. The present study identified 44 complete WTAP genes in the genomes of vertebrates, including fish, amphibians, birds and mammals. The vertebrate WTAP proteins clustered into the primate, rodent and teleost lineages using phylogenetic tree analysis. From 1,347 available SNPs in the human WTAP gene, 19 were identified to cause missense mutations. WTAP was expressed in bladder, blood, brain, breast, colorectal, esophagus, eye, head and neck, lung, ovarian, prostate, skin and soft tissue cancers. A total of 17 out of 328 microarrays demonstrated an association between WTAP gene expression and cancer prognosis. However, the association between WTAP gene expression and prognosis varied in distinct types of cancer, and even in identical types of cancer from separate microarray databases. By searching the Catalogue of Somatic Mutations in Cancer database, 65 somatic mutations were identified in the human WTAP gene from the cancer tissue samples. These results suggest that the function of WTAP in tumor formation may be multidimensional. Furthermore, signal transducer and activator of transcription 1, forkhead box protein O1, interferon regulatory factor 1, glucocorticoid receptor and peroxisome proliferator-activated receptor γ transcription factor binding sites were identified in the upstream (promoter) region of the human WTAP gene, suggesting that these transcription factors may be involved in WTAP functions in tumor formation. PMID:27430156

  17. Prospective large-scale field study generates predictive model identifying major contributors to colony losses.

    PubMed

    Kielmanowicz, Merav Gleit; Inberg, Alex; Lerner, Inbar Maayan; Golani, Yael; Brown, Nicholas; Turner, Catherine Louise; Hayes, Gerald J R; Ballam, Joan M

    2015-04-01

    Over the last decade, unusually high losses of colonies have been reported by beekeepers across the USA. Multiple factors such as Varroa destructor, bee viruses, Nosema ceranae, weather, beekeeping practices, nutrition, and pesticides have been shown to contribute to colony losses. Here we describe a large-scale controlled trial, in which different bee pathogens, bee population, and weather conditions across winter were monitored at three locations across the USA. In order to minimize influence of various known contributing factors and their interaction, the hives in the study were not treated with antibiotics or miticides. Additionally, the hives were kept at one location and were not exposed to potential stress factors associated with migration. Our results show that a linear association between load of viruses (DWV or IAPV) in Varroa and bees is present at high Varroa infestation levels (>3 mites per 100 bees). The collection of comprehensive data allowed us to draw a predictive model of colony losses and to show that Varroa destructor, along with bee viruses, mainly DWV replication, contributes to approximately 70% of colony losses. This correlation further supports the claim that insufficient control of the virus-vectoring Varroa mite would result in increased hive loss. The predictive model also indicates that a single factor may not be sufficient to trigger colony losses, whereas a combination of stressors appears to impact hive health. PMID:25875764

  18. Prospective Large-Scale Field Study Generates Predictive Model Identifying Major Contributors to Colony Losses

    PubMed Central

    Kielmanowicz, Merav Gleit; Inberg, Alex; Lerner, Inbar Maayan; Golani, Yael; Brown, Nicholas; Turner, Catherine Louise; Hayes, Gerald J. R.; Ballam, Joan M.

    2015-01-01

    Over the last decade, unusually high losses of colonies have been reported by beekeepers across the USA. Multiple factors such as Varroa destructor, bee viruses, Nosema ceranae, weather, beekeeping practices, nutrition, and pesticides have been shown to contribute to colony losses. Here we describe a large-scale controlled trial, in which different bee pathogens, bee population, and weather conditions across winter were monitored at three locations across the USA. In order to minimize influence of various known contributing factors and their interaction, the hives in the study were not treated with antibiotics or miticides. Additionally, the hives were kept at one location and were not exposed to potential stress factors associated with migration. Our results show that a linear association between load of viruses (DWV or IAPV) in Varroa and bees is present at high Varroa infestation levels (>3 mites per 100 bees). The collection of comprehensive data allowed us to draw a predictive model of colony losses and to show that Varroa destructor, along with bee viruses, mainly DWV replication, contributes to approximately 70% of colony losses. This correlation further supports the claim that insufficient control of the virus-vectoring Varroa mite would result in increased hive loss. The predictive model also indicates that a single factor may not be sufficient to trigger colony losses, whereas a combination of stressors appears to impact hive health. PMID:25875764

  19. Surrogate motherhood: attachment, attitudes and social support.

    PubMed

    Fischer, S; Gillman, I

    1991-02-01

    In recent years, there has been a revival of interest in the procedure of using a surrogate mother to help infertile couples have a child. One of the issues brought into public awareness by the Baby M case, where the surrogate mother refused to give up the baby to the biological father, has been the nature of the attachment of the surrogate mother to the fetus. Thus far, research has not addressed this issue of attachment as well as it has considered other variables involved in the process of surrogacy. The current exploratory study focuses on differences between two groups of pregnant women - surrogate mothers and nonsurrogate mothers - in the degree and quality of attachment, attitudes toward pregnancy, and social support. An understanding of what pregnancy signifies for surrogate mothers is developed, based on objective measures and informal interviews with surrogate and nonsurrogate mothers. The implications of the various phenomena associated with surrogate motherhood are also considered. PMID:2023971

  20. Identifying Similar Patterns of Structural Flexibility in Proteins by Disorder Prediction and Dynamic Programming

    PubMed Central

    Petrovich, Aidan; Borne, Adam; Uversky, Vladimir N.; Xue, Bin

    2015-01-01

    Computational methods are prevailing in identifying protein intrinsic disorder. The results from predictors are often given as per-residue disorder scores. The scores describe the disorder propensity of amino acids of a protein and can be further represented as a disorder curve. Many proteins share similar patterns in their disorder curves. The similar patterns are often associated with similar functions and evolutionary origins. Therefore, finding and characterizing specific patterns of disorder curves provides a unique and attractive perspective of studying the function of intrinsically disordered proteins. In this study, we developed a new computational tool named IDalign using dynamic programming. This tool is able to identify similar patterns among disorder curves, as well as to present the distribution of intrinsic disorder in query proteins. The disorder-based information generated by IDalign is significantly different from the information retrieved from classical sequence alignments. This tool can also be used to infer functions of disordered regions and disordered proteins. The web server of IDalign is available at (http://labs.cas.usf.edu/bioinfo/service.html). PMID:26086829

  1. Commentary: Surrogate Decisionmaking and Communication.

    PubMed

    Mukherjee, Debjani

    2016-07-01

    Mr. Hope's family's expectations and his staff's concerns raise important issues about surrogate decisionmaking, communication regarding prognosis, and staff angst. Unfortunately, Mr. Hope himself is unable to reliably understand and communicate his preferences, especially for complex medical decisions, so the ethics consultant is left to negotiate the disagreement between his family and his healthcare providers, who presumably both believe they are acting in his best interest. PMID:27348843

  2. Commentary: The Reluctant Surrogate.

    PubMed

    Foreman, Thomas

    2016-04-01

    An individual's hesitance or outright refusal to function as a substitute decisionmaker creates a number of challenges for treating teams, as is highlighted by the case of KS. It is not uncommon for individuals who suddenly find themselves in the role of substitute decisionmaker (SDM) to experience feelings of inadequacy or of being overwhelmed. The natural apprehension that comes with realizing, or being informed, that you are now responsible for providing or refusing consent on behalf of a loved one is often exacerbated by the accompanying circumstances. Even though there are movements afoot to encourage and support advance care planning and the inclusion of those who will become SDMs in conversations about values and wishes, there is still much work to be done. Although the case as presented does not provide information regarding what, if any, processes have taken place prior to the current hospital admission with regard to including the patient's sister in discussions about future circumstances, it is clear that the sister feels unprepared to assume the role being thrust upon her. What, then, does a clinical ethics consultation have to offer in such situations? The following discussion highlights three ways in which ethics consultation can be of value to both the treating team and the identified SDM: ethics consultation (1) helps the care team and SDM navigate the regulatory landscape, (2) supports the treating team, and (3) supports the SDM. PMID:26957458

  3. Applying psychological theory to evidence-based clinical practice: identifying factors predictive of taking intra-oral radiographs.

    PubMed

    Bonetti, Debbie; Pitts, Nigel B; Eccles, Martin; Grimshaw, Jeremy; Johnston, Marie; Steen, Nick; Glidewell, Liz; Thomas, Ruth; Maclennan, Graeme; Clarkson, Jan E; Walker, Anne

    2006-10-01

    enabled the creation of a methodology that can be replicated for identifying factors predictive of clinical behaviour and for the design and choice of interventions to modify practice as new evidence emerges. PMID:16843579

  4. Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators.

    PubMed

    Hieronymus, Haley; Lamb, Justin; Ross, Kenneth N; Peng, Xiao P; Clement, Cristina; Rodina, Anna; Nieto, Maria; Du, Jinyan; Stegmaier, Kimberly; Raj, Srilakshmi M; Maloney, Katherine N; Clardy, Jon; Hahn, William C; Chiosis, Gabriela; Golub, Todd R

    2006-10-01

    Although androgen receptor (AR)-mediated signaling is central to prostate cancer, the ability to modulate AR signaling states is limited. Here we establish a chemical genomic approach for discovery and target prediction of modulators of cancer phenotypes, as exemplified by AR signaling. We first identify AR activation inhibitors, including a group of structurally related compounds comprising celastrol, gedunin, and derivatives. To develop an in silico approach for target pathway identification, we apply a gene expression-based analysis that classifies HSP90 inhibitors as having similar activity to celastrol and gedunin. Validating this prediction, we demonstrate that celastrol and gedunin inhibit HSP90 activity and HSP90 clients, including AR. Broadly, this work identifies new modes of HSP90 modulation through a gene expression-based strategy. PMID:17010675

  5. An empirical assessment and comparison of species-based and habitat-based surrogates: a case study of forest vertebrates and large old trees.

    PubMed

    Lindenmayer, David B; Barton, Philip S; Lane, Peter W; Westgate, Martin J; McBurney, Lachlan; Blair, David; Gibbons, Philip; Likens, Gene E

    2014-01-01

    A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1) the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3) a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat-based surrogates are likely

  6. An Empirical Assessment and Comparison of Species-Based and Habitat-Based Surrogates: A Case Study of Forest Vertebrates and Large Old Trees

    PubMed Central

    Lindenmayer, David B.; Barton, Philip S.; Lane, Peter W.; Westgate, Martin J.; McBurney, Lachlan; Blair, David; Gibbons, Philip; Likens, Gene E.

    2014-01-01

    A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1) the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3) a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat-based surrogates are likely

  7. Evaluating a surrogate endpoint at three levels, with application to vaccine development

    PubMed Central

    Gilbert, Peter B.; Qin, Li; Self, Steven G.

    2009-01-01

    SUMMARY Identification of an immune response to vaccination that reliably predicts protection from clinically significant infection, i.e. an immunological surrogate endpoint, is a primary goal of vaccine research. Using this problem of evaluating an immunological surrogate as an illustration, we describe a hierarchy of three criteria for a valid surrogate endpoint and statistical analysis frameworks for evaluating them. Based on a placebo-controlled vaccine efficacy trial, the first level entails assessing the correlation of an immune response with a study endpoint in the study groups, and the second level entails evaluating an immune response as a surrogate for the study endpoint that can be used for predicting vaccine efficacy for a setting similar to that of the vaccine trial. We show that baseline covariates, innovative study design, and a potential outcomes formulation can be helpful for this assessment. The third level entails validation of a surrogate endpoint via meta-analysis, where the goal is to evaluate how well the immune response can be used to predict vaccine efficacy for new settings (building bridges). A simulated vaccine trial and two example vaccine trials are presented, one supporting that certain anti-influenza antibody levels are an excellent surrogate for influenza illness and another supporting that certain anti-HIV antibody levels are not useful as a surrogate for HIV infection. PMID:17979212

  8. Biomarkers and Surrogate Endpoints In Clinical Trials

    PubMed Central

    Fleming, Thomas R.; Powers, John H

    2012-01-01

    One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures and radiological tests, often are considered as replacement endpoints or “surrogates” for clinically meaningful endpoints. We discuss the definitions of clinically meaningful endpoints and surrogate endpoints, and provide examples from recent clinical trials. We provide insight into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. We also discuss the nature of evidence that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and provide insights into why this reliability is specific to the context of use of the biomarker. . PMID:22711298

  9. Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards

    PubMed Central

    Plitt, Mark; Barnes, Kelly Anne; Martin, Alex

    2014-01-01

    Objectives Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MRI (rs-fMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis. Methods Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build a series of machine learning classifiers. Classification features were obtained using 3 sets of brain regions. Another set of classifiers was built from participants' scores on behavioral metrics. An additional age and IQ-matched cohort of 178 individuals (89 ASD; 89 TD) from the Autism Brain Imaging Data Exchange (ABIDE) open-access dataset (http://fcon_1000.projects.nitrc.org/indi/abide/) were included for replication. Results High classification accuracy was achieved through several rs-fMRI methods (peak accuracy 76.67%). However, classification via behavioral measures consistently surpassed rs-fMRI classifiers (peak accuracy 95.19%). The class probability estimates, P(ASD|fMRI data), from brain-based classifiers significantly correlated with scores on a measure of social functioning, the Social Responsiveness Scale (SRS), as did the most informative features from 2 of the 3 sets of brain-based features. The most informative connections predominantly originated from regions strongly associated with social functioning. Conclusions While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing. PMID:25685703

  10. Bedload-surrogate monitoring technologies

    USGS Publications Warehouse

    Gray, John R.; Laronne, Jonathan B.; Marr, Jeffrey D.G.

    2010-01-01

    Advances in technologies for quantifying bedload fluxes and in some cases bedload size distributions in rivers show promise toward supplanting traditional physical samplers and sampling methods predicated on the collection and analysis of physical bedload samples. Four workshops held from 2002 to 2007 directly or peripherally addressed bedload-surrogate technologies, and results from these workshops have been compiled to evaluate the state-of-the-art in bedload monitoring. Papers from the 2007 workshop are published for the first time with this report. Selected research and publications since the 2007 workshop also are presented. Traditional samplers used for some or all of the last eight decades include box or basket samplers, pan or tray samplers, pressure-difference samplers, and trough or pit samplers. Although still useful, the future niche of these devices may be as a means for calibrating bedload-surrogate technologies operating with active- and passive-type sensors, in many cases continuously and automatically at a river site. Active sensors include acoustic Doppler current profilers (ADCPs), sonar, radar, and smart sensors. Passive sensors include geophones (pipes or plates) in direct contact with the streambed, hydrophones deployed in the water column, impact columns, and magnetic detection. The ADCP for sand and geophones for gravel are currently the most developed techniques, several of which have been calibrated under both laboratory and field conditions. Although none of the bedload-surrogate technologies described herein are broadly accepted for use in large-scale monitoring programs, several are under evaluation. The benefits of verifying and operationally deploying selected bedload-surrogate monitoring technologies could be considerable, providing for more frequent and consistent, less expensive, and arguably more accurate bedload data obtained with reduced personal risk for use in managing the world's sedimentary resources. Twenty-six papers are

  11. Predictive Modelling to Identify Near-Shore, Fine-Scale Seabird Distributions during the Breeding Season

    PubMed Central

    Warwick-Evans, Victoria C.; Atkinson, Philip W.; Robinson, Leonie A.; Green, Jonathan A.

    2016-01-01

    During the breeding season seabirds are constrained to coastal areas and are restricted in their movements, spending much of their time in near-shore waters either loafing or foraging. However, in using these areas they may be threatened by anthropogenic activities such as fishing, watersports and coastal developments including marine renewable energy installations. Although many studies describe large scale interactions between seabirds and the environment, the drivers behind near-shore, fine-scale distributions are not well understood. For example, Alderney is an important breeding ground for many species of seabird and has a diversity of human uses of the marine environment, thus providing an ideal location to investigate the near-shore fine-scale interactions between seabirds and the environment. We used vantage point observations of seabird distribution, collected during the 2013 breeding season in order to identify and quantify some of the environmental variables affecting the near-shore, fine-scale distribution of seabirds in Alderney’s coastal waters. We validate the models with observation data collected in 2014 and show that water depth, distance to the intertidal zone, and distance to the nearest seabird nest are key predictors in the distribution of Alderney’s seabirds. AUC values for each species suggest that these models perform well, although the model for shags performed better than those for auks and gulls. While further unexplained underlying localised variation in the environmental conditions will undoubtedly effect the fine-scale distribution of seabirds in near-shore waters we demonstrate the potential of this approach in marine planning and decision making. PMID:27031616

  12. Predicting Fish Growth Potential and Identifying Water Quality Constraints: A Spatially-Explicit Bioenergetics Approach

    NASA Astrophysics Data System (ADS)

    Budy, Phaedra; Baker, Matthew; Dahle, Samuel K.

    2011-10-01

    Anthropogenic impairment of water bodies represents a global environmental concern, yet few attempts have successfully linked fish performance to thermal habitat suitability and fewer have distinguished co-varying water quality constraints. We interfaced fish bioenergetics, field measurements, and Thermal Remote Imaging to generate a spatially-explicit, high-resolution surface of fish growth potential, and next employed a structured hypothesis to detect relationships among measures of fish performance and co-varying water quality constraints. Our thermal surface of fish performance captured the amount and spatial-temporal arrangement of thermally-suitable habitat for three focal species in an extremely heterogeneous reservoir, but interpretation of this pattern was initially confounded by seasonal covariation of water residence time and water quality. Subsequent path analysis revealed that in terms of seasonal patterns in growth potential, catfish and walleye responded to temperature, positively and negatively, respectively; crappie and walleye responded to eutrophy (negatively). At the high eutrophy levels observed in this system, some desired fishes appear to suffer from excessive cultural eutrophication within the context of elevated temperatures whereas others appear to be largely unaffected or even enhanced. Our overall findings do not lead to the conclusion that this system is degraded by pollution; however, they do highlight the need to use a sensitive focal species in the process of determining allowable nutrient loading and as integrators of habitat suitability across multiple spatial and temporal scales. We provide an integrated approach useful for quantifying fish growth potential and identifying water quality constraints on fish performance at spatial scales appropriate for whole-system management.

  13. Predictive Modelling to Identify Near-Shore, Fine-Scale Seabird Distributions during the Breeding Season.

    PubMed

    Warwick-Evans, Victoria C; Atkinson, Philip W; Robinson, Leonie A; Green, Jonathan A

    2016-01-01

    During the breeding season seabirds are constrained to coastal areas and are restricted in their movements, spending much of their time in near-shore waters either loafing or foraging. However, in using these areas they may be threatened by anthropogenic activities such as fishing, watersports and coastal developments including marine renewable energy installations. Although many studies describe large scale interactions between seabirds and the environment, the drivers behind near-shore, fine-scale distributions are not well understood. For example, Alderney is an important breeding ground for many species of seabird and has a diversity of human uses of the marine environment, thus providing an ideal location to investigate the near-shore fine-scale interactions between seabirds and the environment. We used vantage point observations of seabird distribution, collected during the 2013 breeding season in order to identify and quantify some of the environmental variables affecting the near-shore, fine-scale distribution of seabirds in Alderney's coastal waters. We validate the models with observation data collected in 2014 and show that water depth, distance to the intertidal zone, and distance to the nearest seabird nest are key predictors in the distribution of Alderney's seabirds. AUC values for each species suggest that these models perform well, although the model for shags performed better than those for auks and gulls. While further unexplained underlying localised variation in the environmental conditions will undoubtedly effect the fine-scale distribution of seabirds in near-shore waters we demonstrate the potential of this approach in marine planning and decision making. PMID:27031616

  14. Realtime Prediction in Disturbed Landscapes: Identifying Highest Priority Disturbance Characteristics Impacting Streamflow Response in a CONUS-Scale Operational Model

    NASA Astrophysics Data System (ADS)

    Dugger, A. L.; Gochis, D. J.; Yu, W.; McCreight, J. L.; Barlage, M. J.

    2015-12-01

    The "next generation" of hydrologic prediction systems - targeting unified, process-based, real-time prediction of the total water cycle - bring with them an increased need for real-time land surface characterization. Climatologically-derived estimates may perform well under stationary conditions, however disturbance can significantly alter hydrologic behavior and may be poorly represented by mean historical conditions. Fortunately, remote sensing and on-the-ground observation networks are collecting snapshots of these land characteristics over an increasing fraction of the globe. Given the computing constraints of operating a large-domain, real-time prediction system, to take advantage of these data streams we need a way to prioritize which landscape characteristics are most important to hydrologic prediction post-disturbance. To address this need, we setup a model experiment over the contiguous US using the community WRF-Hydro system with the NoahMP land surface model to assess the value of incorporating various aspects of disturbed landscapes into a real-time streamflow prediction model. WRF-Hydro will serve as the initial operational model for the US National Weather Service's new national water prediction effort, so use of WRF-Hydro allows us to leverage both an existing CONUS-scale model implementation and a short research-to-operations path. We first identify USGS GAGES-II basins that experienced more than 25% forest loss between 2000 and 2013. Based on basin disturbance type, geophysical setting, and climate regime, we formulate a conceptual model of which "disturbed" landscape characteristics we expect to dominate streamflow response. We test our conceptual model using WRF-Hydro by modeling a baseline (no disturbance) case, and then bringing in empirically-derived model state shifts representing key disturbance characteristics (e.g., leaf area index, rooting depth, overland roughness, surface detention). For each state update and each basin, we quantify

  15. Predicting microRNA modulation in human prostate cancer using a simple String IDentifier (SID1.0).

    PubMed

    Albertini, Maria C; Olivieri, Fabiola; Lazzarini, Raffaella; Pilolli, Francesca; Galli, Francesco; Spada, Giorgio; Accorsi, Augusto; Rippo, Maria R; Procopio, Antonio D

    2011-08-01

    To make faster and efficient the identification of mRNA targets common to more than one miRNA, and to identify new miRNAs modulated in specific pathways, a computer program identified as SID1.0 (simple String IDentifier) was developed and successfully applied in the identification of deregulated miRNAs in prostate cancer cells. This computationally inexpensive Fortran program is based on the strategy of exhaustive search and specifically designed to screen shared data (target genes, miRNAs and pathways) available from PicTar and DIANA-MicroT 3.0 databases. As far as we know this is the first software designed to filter data retrieved from available miRNA databases. SID1.0 takes advantage of the standard Fortran intrinsic functions for manipulating text strings and requires ASCII input files. In order to demonstrate SID1.0 applicability, some miRNAs expected from the literature to associate with cancerogenesis (miR-125b, miR-148a and miR-141), were randomly identified as main entries for SID1.0 to explore matching sequences of mRNA targets and also to explore KEGG pathways for the presence of ID codes of targeted genes. Besides genes and pathways already described in the literature, SID1.0 has proven to useful for predicting other genes involved in prostate carcinoma. These latter were used to identify new deregulated miRNAs: miR-141, miR-148a, miR-19a and miR-19b. Prediction data were preliminary confirmed by expression analysis of the identified miRNAs in androgen-dependent (LNCaP) and independent (PC3) prostate carcinoma cell lines and in normal prostatic epithelial cells (PrEC). PMID:21334455

  16. Mechanical Properties of K Basin Sludge Constituents and Their Surrogates

    SciTech Connect

    Delegard, Calvin H.; Schmidt, Andrew J.; Chenault, Jeffrey W.

    2004-12-06

    A survey of the technical literature was performed to summarize the mechanical properties of inorganic components in K Basins sludge. The components included gibbsite, ferrihydrite, lepidocrocite and goethite, hematite, quartz, anorthite, calcite, basalt, Zircaloy, aluminum, and, in particular, irradiated uranium metal and uranium dioxide. Review of the technical literature showed that information on the hardness of uranium metal at irradiation exposures similar to those experienced by the N Reactor fuel present in the K Basins (typically up to 3000 MWd/t) were not available. Measurements therefore were performed to determine the hardness of coupons taken from three irradiated N Reactor uranium metal fuel elements taken from K Basins. Hardness values averaged 30 {+-} 8 Rockwell C units, similar to values previously reported for uranium irradiated to {approx}1200 MWd/t. The physical properties of candidate uranium metal and uranium dioxide surrogates were gathered and compared. Surrogates having properties closest to those of irradiated uranium metal appear to be alloys of tungsten. The surrogate for uranium dioxide, present both as particles and agglomerates in actual K Basin sludge, likely requires two materials. Cerium oxide, CeO2, was identified as a surrogate of the smaller UO2 particles while steel grit was identified for the UO2 agglomerates.

  17. Health information seeking on behalf of others: Characteristics of ‘surrogate seekers’

    PubMed Central

    Cutrona, Sarah L.; Mazor, Kathleen M.; Vieux, Sana N.; Luger, Tana M.; Volkman, Julie E.; Finney Rutten, Lila J.

    2014-01-01

    Understanding the behaviors of surrogate-seekers (those who seek health information for others) may guide efforts to improve health information transmission. We used 2011–2012 data from the Health Information National Trends Survey to describe behaviors of online surrogate-seekers. Respondents were asked about use of the Internet for surrogate-seeking over the prior 12 months. Data were weighted to calculate population estimates. Two-thirds (66.6%) reported surrogate-seeking. Compared to those who sought health information online for only themselves, surrogate-seekers were more likely to live in households with others (weighted percent 89.4% vs. 82.5% of self-seekers; p < 0.05); no significant differences in sex, race, income or education were observed. Surrogate-seekers were more likely to report activities requiring user-generated content: email communication with healthcare providers; visits to social networking sites to read and share about medical topics and participation in online health support groups. On multivariate analysis, those who had looked online for healthcare providers were more likely to be surrogate-seekers (OR 1.67, 95% CI 1.08–2.59). In addition to seeking health information, surrogate-seekers create and pass along communications that may influence medical care decisions. Research is needed to identify ways to facilitate transmission of accurate health information. PMID:24989816

  18. Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function

    SciTech Connect

    Xi, T; Jones, I M; Mohrenweiser, H W

    2003-11-03

    Over 520 different amino acid substitution variants have been previously identified in the systematic screening of 91 human DNA repair genes for sequence variation. Two algorithms were employed to predict the impact of these amino acid substitutions on protein activity. Sorting Intolerant From Tolerant (SIFT) classified 226 of 508 variants (44%) as ''Intolerant''. Polymorphism Phenotyping (PolyPhen) classed 165 of 489 amino acid substitutions (34%) as ''Probably or Possibly Damaging''. Another 9-15% of the variants were classed as ''Potentially Intolerant or Damaging''. The results from the two algorithms are highly associated, with concordance in predicted impact observed for {approx}62% of the variants. Twenty one to thirty one percent of the variant proteins are predicted to exhibit reduced activity by both algorithms. These variants occur at slightly lower individual allele frequency than do the variants classified as ''Tolerant'' or ''Benign''. Both algorithms correctly predicted the impact of 26 functionally characterized amino acid substitutions in the APE1 protein on biochemical activity, with one exception. It is concluded that a substantial fraction of the missense variants observed in the general human population are functionally relevant. These variants are expected to be the molecular genetic and biochemical basis for the associations of reduced DNA repair capacity phenotypes with elevated cancer risk.

  19. Surrogate Reactions in the Actinide Region

    SciTech Connect

    Burke, J T; Bernstein, L A; Scielzo, N D; Bleuel, D L; Lesher, S R; Escher, J; Ahle, L; Dietrich, F S; Hoffman, R D; Norman, E B; Sheets, S A; Phair, L; Fallon, P; Clark, R M; Gibelin, J; Jewett, C; Lee, I Y; Macchiavelli, A O; McMahan, M A; Moretto, L G; Rodriguez-Vieitez, E; Wiedeking, M; Lyles, B F; Beausang, C W; Allmond, J M; Ai, H; Cizewski, J A; Hatarik, R; O'Malley, P D; Swan, T

    2008-01-30

    Over the past three years we have studied various surrogate reactions (d,p), ({sup 3}He,t), ({alpha},{alpha}{prime}) on several uranium isotopes {sup 234}U, {sup 235}U, {sup 236}U, and {sup 238}U. An overview of the STARS/LIBERACE surrogate research program as it pertains to the actinides is discussed. A summary of results to date will be presented along with a discussion of experimental difficulties encountered in surrogate experiments and future research directions.

  20. A Network-Based Model of Oncogenic Collaboration for Prediction of Drug Sensitivity

    PubMed Central

    Laderas, Ted G.; Heiser, Laura M.; Sönmez, Kemal

    2015-01-01

    Tumorigenesis is a multi-step process, involving the acquisition of multiple oncogenic mutations that transform cells, resulting in systemic dysregulation that enables proliferation, invasion, and other cancer hallmarks. The goal of precision medicine is to identify therapeutically-actionable mutations from large-scale omic datasets. However, the multiplicity of oncogenes required for transformation, known as oncogenic collaboration, makes assigning effective treatments difficult. Motivated by this observation, we propose a new type of oncogenic collaboration where mutations in genes that interact with an oncogene may contribute to the oncogene’s deleterious potential, a new genomic feature that we term “surrogate oncogenes.” Surrogate oncogenes are representatives of these mutated subnetworks that interact with oncogenes. By mapping mutations to a protein–protein interaction network, we determine the significance of the observed distribution using permutation-based methods. For a panel of 38 breast cancer cell lines, we identified a significant number of surrogate oncogenes in known oncogenes such as BRCA1 and ESR1, lending credence to this approach. In addition, using Random Forest Classifiers, we show that these significant surrogate oncogenes predict drug sensitivity for 74 drugs in the breast cancer cell lines with a mean error rate of 30.9%. Additionally, we show that surrogate oncogenes are predictive of survival in patients. The surrogate oncogene framework incorporates unique or rare mutations from a single sample, and therefore has the potential to integrate patient-unique mutations into drug sensitivity predictions, suggesting a new direction in precision medicine and drug development. Additionally, we show the prevalence of significant surrogate oncogenes in multiple cancers from The Cancer Genome Atlas, suggesting that surrogate oncogenes may be a useful genomic feature for guiding pancancer analyses and assigning therapies across many tissue

  1. SVM-based prediction of propeptide cleavage sites in spider toxins identifies toxin innovation in an Australian tarantula.

    PubMed

    Wong, Emily S W; Hardy, Margaret C; Wood, David; Bailey, Timothy; King, Glenn F

    2013-01-01

    Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the Spider

  2. SVM-Based Prediction of Propeptide Cleavage Sites in Spider Toxins Identifies Toxin Innovation in an Australian Tarantula

    PubMed Central

    Wong, Emily S. W.; Hardy, Margaret C.; Wood, David; Bailey, Timothy; King, Glenn F.

    2013-01-01

    Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the Spider

  3. The diaphragm as an anatomic surrogate for lung tumor motion

    NASA Astrophysics Data System (ADS)

    Cerviño, Laura I.; Chao, Alvin K. Y.; Sandhu, Ajay; Jiang, Steve B.

    2009-06-01

    Lung tumor motion due to respiration poses a challenge in the application of modern three-dimensional conformal radiotherapy. Direct tracking of the lung tumor during radiation therapy is very difficult without implanted fiducial markers. Indirect tracking relies on the correlation of the tumor's motion and the surrogate's motion. The present paper presents an analysis of the correlation between tumor motion and diaphragm motion in order to evaluate the potential use of diaphragm as a surrogate for tumor motion. We have analyzed the correlation between diaphragm motion and superior-inferior lung tumor motion in 32 fluoroscopic image sequences from ten lung cancer patients. A simple linear model and a more complex linear model that accounts for phase delays between the two motions have been used. Results show that the diaphragm is a good surrogate for tumor motion prediction for most patients, resulting in an average correlation factor of 0.94 and 0.98 with each model respectively. The model that accounts for delays leads to an average localization prediction error of 0.8 mm and an error at the 95% confidence level of 2.1 mm. However, for one patient studied, the correlation is much weaker compared to other patients. This indicates that, before using diaphragm for lung tumor prediction, the correlation should be examined on a patient-by-patient basis.

  4. A surrogate-based uncertainty quantification with quantifiable errors

    SciTech Connect

    Bang, Y.; Abdel-Khalik, H. S.

    2012-07-01

    Surrogate models are often employed to reduce the computational cost required to complete uncertainty quantification, where one is interested in propagating input parameters uncertainties throughout a complex engineering model to estimate responses uncertainties. An improved surrogate construction approach is introduced here which places a premium on reducing the associated computational cost. Unlike existing methods where the surrogate is constructed first, then employed to propagate uncertainties, the new approach combines both sensitivity and uncertainty information to render further reduction in the computational cost. Mathematically, the reduction is described by a range finding algorithm that identifies a subspace in the parameters space, whereby parameters uncertainties orthogonal to the subspace contribute negligible amount to the propagated uncertainties. Moreover, the error resulting from the reduction can be upper-bounded. The new approach is demonstrated using a realistic nuclear assembly model and compared to existing methods in terms of computational cost and accuracy of uncertainties. Although we believe the algorithm is general, it will be applied here for linear-based surrogates and Gaussian parameters uncertainties. The generalization to nonlinear models will be detailed in a separate article. (authors)

  5. Evaluation of bone surrogates for indirect and direct ballistic fractures.

    PubMed

    Bir, Cynthia; Andrecovich, Chris; DeMaio, Marlene; Dougherty, Paul J

    2016-04-01

    The mechanism of injury for fractures to long bones has been studied for both direct ballistic loading as well as indirect. However, the majority of these studies have been conducted on both post-mortem human subjects (PMHS) and animal surrogates which have constraints in terms of storage, preparation and testing. The identification of a validated bone surrogate for use in forensic, medical and engineering testing would provide the ability to investigate ballistic loading without these constraints. Two specific bone surrogates, Sawbones and Synbone, were evaluated in comparison to PMHS for both direct and indirect ballistic loading. For the direct loading, the mean velocity to produce fracture was 121 ± 19 m/s for the PMHS, which was statistically different from the Sawbones (140 ± 7 m/s) and Synbone (146 ± 3 m/s). The average distance to fracture in the indirect loading was .70 cm for the PMHS. The Synbone had a statistically similar average distance to fracture (.61 cm, p=0.54) however the Sawbones average distance to fracture was statistically different (.41 cm, p<0.05). Fractures patterns were found to be comparable to the PMHS for tests conducted with Synbones, however the input parameters were slightly varied to produce similar results. The fractures patterns with the Sawbones were not found to be as comparable to the PMHS. An ideal bone surrogate for ballistic testing was not identified and future work is warranted. PMID:26867672

  6. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets

    SciTech Connect

    Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.; Fournier, Marcia V.

    2008-10-20

    One of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively. Our results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome. The 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic

  7. Heat–Health Warning Systems: A Comparison of the Predictive Capacity of Different Approaches to Identifying Dangerously Hot Days

    PubMed Central

    Sheridan, Scott C.; Allen, Michael J.; Pascal, Mathilde; Laaidi, Karine; Yagouti, Abderrahmane; Bickis, Ugis; Tobias, Aurelio; Bourque, Denis; Armstrong, Ben G.; Kosatsky, Tom

    2010-01-01

    Objectives. We compared the ability of several heat–health warning systems to predict days of heat-associated mortality using common data sets. Methods. Heat–health warning systems initiate emergency public health interventions once forecasts have identified weather conditions to breach predetermined trigger levels. We examined 4 commonly used trigger-setting approaches: (1) synoptic classification, (2) epidemiologic assessment of the temperature–mortality relationship, (3) temperature–humidity index, and (4) physiologic classification. We applied each approach in Chicago, Illinois; London, United Kingdom; Madrid, Spain; and Montreal, Canada, to identify days expected to be associated with the highest heat-related mortality. Results. We found little agreement across the approaches in which days were identified as most dangerous. In general, days identified by temperature–mortality assessment were associated with the highest excess mortality. Conclusions. Triggering of alert days and ultimately the initiation of emergency responses by a heat–health warning system varies significantly across approaches adopted to establish triggers. PMID:20395585

  8. Cell-Line Selectivity Improves the Predictive Power of Pharmacogenomic Analyses and Helps Identify NADPH as Biomarker for Ferroptosis Sensitivity.

    PubMed

    Shimada, Kenichi; Hayano, Miki; Pagano, Nen C; Stockwell, Brent R

    2016-02-18

    Precision medicine in oncology requires not only identification of cancer-associated mutations but also effective drugs for each cancer genotype, which is still a largely unsolved problem. One approach for the latter challenge has been large-scale testing of small molecules in genetically characterized cell lines. We hypothesized that compounds with high cell-line-selective lethality exhibited consistent results across such pharmacogenomic studies. We analyzed the compound sensitivity data of 6,259 lethal compounds from the NCI-60 project. A total of 2,565 cell-line-selective lethal compounds were identified and grouped into 18 clusters based on their median growth inhibitory GI50 profiles across the 60 cell lines, which were shown to represent distinct mechanisms of action. Further transcriptome analysis revealed a biomarker, NADPH abundance, for predicting sensitivity to ferroptosis-inducing compounds, which we experimentally validated. In summary, incorporating cell-line-selectivity filters improves the predictive power of pharmacogenomic analyses and enables discovery of biomarkers that predict the sensitivity of cells to specific cell death inducers. PMID:26853626

  9. Comparing human norovirus surrogates: murine norovirus and Tulane virus.

    PubMed

    Hirneisen, Kirsten A; Kniel, Kalmia E

    2013-01-01

    Viral surrogates are widely used by researchers to predict human norovirus behavior. Murine norovirus (MNV) is currently accepted as the best surrogate and is assumed to mimic the survival and inactivation of human noroviruses. Recently, a new calicivirus, the Tulane virus (TV), was discovered, and its potential as a human norovirus surrogate is being explored. This study aimed to compare the behavior of the two potential surrogates under varying treatments of pH (2.0 to 10.0), chlorine (0.2 to 2,000 ppm), heat (50 to 75°C), and survival in tap water at room (20°C) and refrigeration (4°C) temperatures for up to 30 days. Viral infectivity was determined by the plaque assay for both MNV and TV. There was no significant difference between the inactivation of MNV and TV in all heat treatments, and for both MNV and TV survival in tap water at 20°C over 30 days. At 4°C, MNV remained infectious over 30 days at a titer of approximately 5 log PFU/ml, whereas TV titers decreased significantly by 5 days. MNV was more pH stable, as TV titers were reduced significantly at pH 2.0, 9.0, and 10.0, as compared with pH 7.0, whereas MNV titers were only significantly reduced at pH 10.0. After chlorine treatment, there was no significant difference in virus with the exception of at 2 ppm, where TV decreased significantly compared with MNV. Compared with TV, MNV is likely a better surrogate for human noroviruses, as MNV persisted over a wider range of pH values, at 2 ppm of chlorine, and without a loss of titer at 4°C. PMID:23317870

  10. Advance Care Planning Beyond Advance Directives: Perspectives from Patients and Surrogates

    PubMed Central

    McMahan, Ryan; Knight, Sara J.; Fried, Terri R.; Sudore, Rebecca L.

    2014-01-01

    Context Advance care planning (ACP) has focused on documenting life-sustaining treatment preferences in advance directives (ADs). ADs alone may be insufficient to prepare diverse patients and surrogates for complex medical decisions. Objectives To understand what steps best prepare patients and surrogates for decision making. Methods We conducted 13 English/Spanish focus groups with participants from a Veterans Affairs and county hospital and the community. Seven groups included patients (n=38) aged ≥65 years, who reported making serious medical decisions. Six separate groups included surrogates (n=31), aged ≥18 years, who made decisions for others. Semi-structured focus groups asked what activities best prepared participants for decision making. Two investigators independently coded data and performed thematic content analysis. Disputes were resolved by consensus. Results Mean±SD patient age was 78±8 years and 61% were non-white. Mean±SD surrogate age was 57±10 years and 91% were non-white. Qualitative analysis identified four overarching themes about how to best prepare for decision making: 1) identify values based on past experiences and quality of life, 2) choose surrogates wisely and verify they understand their role, 3) decide whether to grant leeway in surrogate decision making, and 4) inform other family and friends of one's wishes to prevent conflict. Conclusion Beyond ADs, patients and surrogates recommend several additional steps to prepare for medical decision making including using past experiences to identify values, verifying the surrogate understands their role, deciding whether to grant surrogates leeway, and informing other family and friends of one's wishes. Future ACP interventions should consider incorporating these additional ACP activities. PMID:23200188

  11. RNAseq versus genome-predicted transcriptomes: a large population of novel transcripts identified in an Illumina-454 Hydra transcriptome

    PubMed Central

    2013-01-01

    Background Evolutionary studies benefit from deep sequencing technologies that generate genomic and transcriptomic sequences from a variety of organisms. Genome sequencing and RNAseq have complementary strengths. In this study, we present the assembly of the most complete Hydra transcriptome to date along with a comparative analysis of the specific features of RNAseq and genome-predicted transcriptomes currently available in the freshwater hydrozoan Hydra vulgaris. Results To produce an accurate and extensive Hydra transcriptome, we combined Illumina and 454 Titanium reads, giving the primacy to Illumina over 454 reads to correct homopolymer errors. This strategy yielded an RNAseq transcriptome that contains 48’909 unique sequences including splice variants, representing approximately 24’450 distinct genes. Comparative analysis to the available genome-predicted transcriptomes identified 10’597 novel Hydra transcripts that encode 529 evolutionarily-conserved proteins. The annotation of 170 human orthologs points to critical functions in protein biosynthesis, FGF and TOR signaling, vesicle transport, immunity, cell cycle regulation, cell death, mitochondrial metabolism, transcription and chromatin regulation. However, a majority of these novel transcripts encodes short ORFs, at least 767 of them corresponding to pseudogenes. This RNAseq transcriptome also lacks 11’270 predicted transcripts that correspond either to silent genes or to genes expressed below the detection level of this study. Conclusions We established a simple and powerful strategy to combine Illumina and 454 reads and we produced, with genome assistance, an extensive and accurate Hydra transcriptome. The comparative analysis of the RNAseq transcriptome with genome-predicted transcriptomes lead to the identification of large populations of novel as well as missing transcripts that might reflect Hydra-specific evolutionary events. PMID:23530871

  12. The Impact of Climate Change on Indigenous Arabica Coffee (Coffea arabica): Predicting Future Trends and Identifying Priorities

    PubMed Central

    Gole, Tadesse Woldemariam; Baena, Susana

    2012-01-01

    Precise modelling of the influence of climate change on Arabica coffee is limited; there are no data available for indigenous populations of this species. In this study we model the present and future predicted distribution of indigenous Arabica, and identify priorities in order to facilitate appropriate decision making for conservation, monitoring and future research. Using distribution data we perform bioclimatic modelling and examine future distribution with the HadCM3 climate model for three emission scenarios (A1B, A2A, B2A) over three time intervals (2020, 2050, 2080). The models show a profoundly negative influence on indigenous Arabica. In a locality analysis the most favourable outcome is a c. 65% reduction in the number of pre-existing bioclimatically suitable localities, and at worst an almost 100% reduction, by 2080. In an area analysis the most favourable outcome is a 38% reduction in suitable bioclimatic space, and the least favourable a c. 90% reduction, by 2080. Based on known occurrences and ecological tolerances of Arabica, bioclimatic unsuitability would place populations in peril, leading to severe stress and a high risk of extinction. This study establishes a fundamental baseline for assessing the consequences of climate change on wild populations of Arabica coffee. Specifically, it: (1) identifies and categorizes localities and areas that are predicted to be under threat from climate change now and in the short- to medium-term (2020–2050), representing assessment priorities for ex situ conservation; (2) identifies ‘core localities’ that could have the potential to withstand climate change until at least 2080, and therefore serve as long-term in situ storehouses for coffee genetic resources; (3) provides the location and characterization of target locations (populations) for on-the-ground monitoring of climate change influence. Arabica coffee is confimed as a climate sensitivite species, supporting data and inference that existing

  13. The Reparative Motive in Surrogate Mothers.

    ERIC Educational Resources Information Center

    Kanefield, Linda

    1999-01-01

    Explores the motivations of surrogate mothers, focusing on underlying reparative motive--to compensate for or repair an earlier loss or sense of damage. Provides an overview of the typical surrogate's characteristics and personality, discusses the theoretical underpinnings of the reparative motive, and considers the tension between reparation and…

  14. Applying psychological theories to evidence-based clinical practice: Identifying factors predictive of managing upper respiratory tract infections without antibiotics

    PubMed Central

    Eccles, Martin P; Grimshaw, Jeremy M; Johnston, Marie; Steen, Nick; Pitts, Nigel B; Thomas, Ruth; Glidewell, Elizabeth; Maclennan, Graeme; Bonetti, Debbie; Walker, Anne

    2007-01-01

    use of antibiotics made significantly fewer scenario-based decisions to prescribe. In the cross theory analysis, perceived behavioural control (TPB), evidence of habitual behaviour (OLT), CS-SRM cause (chance/bad luck), and intention entered the equation, together explaining 36% of the variance. When predicting intention, at the theory level, the proportion of variance explained was: TPB, 30%; SCT, 29%; CS-SRM 27%; OLT, 43%. GPs who reported that they had already decided to change their management to try to avoid the use of antibiotics had a significantly higher intention to manage URTIs without prescribing antibiotics. In the cross theory analysis, OLT evidence of habitual behaviour, TPB attitudes, risk perception, CS-SRM control by doctor, TPB perceived behavioural control and CS-SRM control by treatment entered the equation, together explaining 49% of the variance in intention. Conclusion The study provides evidence that psychological models can be useful in understanding and predicting clinical behaviour. Taking a theory-based approach enables the creation of a replicable methodology for identifying factors that predict clinical behaviour. However, a number of conceptual and methodological challenges remain. PMID:17683558

  15. Identifying Individuals at High Risk of Psychosis: Predictive Utility of Support Vector Machine using Structural and Functional MRI Data

    PubMed Central

    Valli, Isabel; Marquand, Andre F.; Mechelli, Andrea; Raffin, Marie; Allen, Paul; Seal, Marc L.; McGuire, Philip

    2016-01-01

    The identification of individuals at high risk of developing psychosis is entirely based on clinical assessment, associated with limited predictive potential. There is, therefore, increasing interest in the development of biological markers that could be used in clinical practice for this purpose. We studied 25 individuals with an at-risk mental state for psychosis and 25 healthy controls using structural MRI, and functional MRI in conjunction with a verbal memory task. Data were analyzed using a standard univariate analysis, and with support vector machine (SVM), a multivariate pattern recognition technique that enables statistical inferences to be made at the level of the individual, yielding results with high translational potential. The application of SVM to structural MRI data permitted the identification of individuals at high risk of psychosis with a sensitivity of 68% and a specificity of 76%, resulting in an accuracy of 72% (p < 0.001). Univariate volumetric between-group differences did not reach statistical significance. By contrast, the univariate fMRI analysis identified between-group differences (p < 0.05 corrected), while the application of SVM to the same data did not. Since SVM is well suited at identifying the pattern of abnormality that distinguishes two groups, whereas univariate methods are more likely to identify regions that individually are most different between two groups, our results suggest the presence of focal functional abnormalities in the context of a diffuse pattern of structural abnormalities in individuals at high clinical risk of psychosis. PMID:27092086

  16. Identifying Individuals at High Risk of Psychosis: Predictive Utility of Support Vector Machine using Structural and Functional MRI Data.

    PubMed

    Valli, Isabel; Marquand, Andre F; Mechelli, Andrea; Raffin, Marie; Allen, Paul; Seal, Marc L; McGuire, Philip

    2016-01-01

    The identification of individuals at high risk of developing psychosis is entirely based on clinical assessment, associated with limited predictive potential. There is, therefore, increasing interest in the development of biological markers that could be used in clinical practice for this purpose. We studied 25 individuals with an at-risk mental state for psychosis and 25 healthy controls using structural MRI, and functional MRI in conjunction with a verbal memory task. Data were analyzed using a standard univariate analysis, and with support vector machine (SVM), a multivariate pattern recognition technique that enables statistical inferences to be made at the level of the individual, yielding results with high translational potential. The application of SVM to structural MRI data permitted the identification of individuals at high risk of psychosis with a sensitivity of 68% and a specificity of 76%, resulting in an accuracy of 72% (p < 0.001). Univariate volumetric between-group differences did not reach statistical significance. By contrast, the univariate fMRI analysis identified between-group differences (p < 0.05 corrected), while the application of SVM to the same data did not. Since SVM is well suited at identifying the pattern of abnormality that distinguishes two groups, whereas univariate methods are more likely to identify regions that individually are most different between two groups, our results suggest the presence of focal functional abnormalities in the context of a diffuse pattern of structural abnormalities in individuals at high clinical risk of psychosis. PMID:27092086

  17. On Using Surrogates with Genetic Programming.

    PubMed

    Hildebrandt, Torsten; Branke, Jürgen

    2015-01-01

    One way to accelerate evolutionary algorithms with expensive fitness evaluations is to combine them with surrogate models. Surrogate models are efficiently computable approximations of the fitness function, derived by means of statistical or machine learning techniques from samples of fully evaluated solutions. But these models usually require a numerical representation, and therefore cannot be used with the tree representation of genetic programming (GP). In this paper, we present a new way to use surrogate models with GP. Rather than using the genotype directly as input to the surrogate model, we propose using a phenotypic characterization. This phenotypic characterization can be computed efficiently and allows us to define approximate measures of equivalence and similarity. Using a stochastic, dynamic job shop scenario as an example of simulation-based GP with an expensive fitness evaluation, we show how these ideas can be used to construct surrogate models and improve the convergence speed and solution quality of GP. PMID:24967694

  18. Surrogate Guderley Test Problem Definition

    SciTech Connect

    Ramsey, Scott D.; Shashkov, Mikhail J.

    2012-07-06

    The surrogate Guderley problem (SGP) is a 'spherical shock tube' (or 'spherical driven implosion') designed to ease the notoriously subtle initialization of the true Guderley problem, while still maintaining a high degree of fidelity. In this problem (similar to the Guderley problem), an infinitely strong shock wave forms and converges in one-dimensional (1D) cylindrical or spherical symmetry through a polytropic gas with arbitrary adiabatic index {gamma}, uniform density {rho}{sub 0}, zero velocity, and negligible pre-shock pressure and specific internal energy (SIE). This shock proceeds to focus on the point or axis of symmetry at r = 0 (resulting in ostensibly infinite pressure, velocity, etc.) and reflect back out into the incoming perturbed gas.

  19. The nematode Caenorhabditis elegans as a tool to predict chemical activity on mammalian development and identify mechanisms influencing toxicological outcome

    PubMed Central

    Harlow, Philippa H.; Perry, Simon J.; Widdison, Stephanie; Daniels, Shannon; Bondo, Eddie; Lamberth, Clemens; Currie, Richard A.; Flemming, Anthony J.

    2016-01-01

    To determine whether a C. elegans bioassay could predict mammalian developmental activity, we selected diverse compounds known and known not to elicit such activity and measured their effect on C. elegans egg viability. 89% of compounds that reduced C. elegans egg viability also had mammalian developmental activity. Conversely only 25% of compounds found not to reduce egg viability in C. elegans were also inactive in mammals. We conclude that the C. elegans egg viability assay is an accurate positive predictor, but an inaccurate negative predictor, of mammalian developmental activity. We then evaluated C. elegans as a tool to identify mechanisms affecting toxicological outcomes among related compounds. The difference in developmental activity of structurally related fungicides in C. elegans correlated with their rate of metabolism. Knockdown of the cytochrome P450s cyp-35A3 and cyp-35A4 increased the toxicity to C. elegans of the least developmentally active compounds to the level of the most developmentally active. This indicated that these P450s were involved in the greater rate of metabolism of the less toxic of these compounds. We conclude that C. elegans based approaches can predict mammalian developmental activity and can yield plausible hypotheses for factors affecting the biological potency of compounds in mammals. PMID:26987796

  20. Predictive factors of brain death in severe stroke patients identified by organ procurement and transplant coordination in Lorrain, France.

    PubMed

    Humbertjean, Lisa; Mione, Gioia; Fay, Renaud; Durin, Laurent; Planel, Sophie; Lacour, Jean-Christophe; Enea, Ana-Maria; Richard, Sébastien

    2016-03-01

    There are no established predictive factors to identify patients at the acute phase of severe stroke with a high probability of presenting brain death (BD). We retrospectively collected clinical and paraclinical data of consecutive patients at the acute phase of severe stroke with a potential progression to BD through the hospital organ procurement and transplant coordination system in five centres in Lorrain (France) between 1 January 2012 and 31 December 2013. Final endpoint was adjudicated BD. Of 400 included patients, 91 (23%) presented adjudicated BD. Initial Glasgow Coma Scale score ≤6 (P = 0.008), herniation (P = 0.009), hydrocephalus (P = 0.019), initial systolic blood pressure >150 mmHg (P = 0.002), past history of alcohol abuse (P = 0.019) and stroke volume >65 ml (P = 0.040) were significantly associated with BD progression. Two prognostic scores for stroke with unquantifiable or quantifiable volume were built according to the number of risk factors presented. Following internal validation, the respective bias-corrected predictive performance (c-index) of the two scores was 72% (95% confidence interval: 67-78%) and 77% (95% confidence interval: 72-82%). These scores could form the basis of a simple tool of six criteria to help physicians make the difficult decision of intensive care unit management to preserve organs in potential donors. PMID:26402792

  1. A general framework to learn surrogate relevance criterion for atlas based image segmentation.

    PubMed

    Zhao, Tingting; Ruan, Dan

    2016-09-01

    Multi-atlas based image segmentation sees great opportunities in the big data era but also faces unprecedented challenges in identifying positive contributors from extensive heterogeneous data. To assess data relevance, image similarity criteria based on various image features widely serve as surrogates for the inaccessible geometric agreement criteria. This paper proposes a general framework to learn image based surrogate relevance criteria to better mimic the behaviors of segmentation based oracle geometric relevance. The validity of its general rationale is verified in the specific context of fusion set selection for image segmentation. More specifically, we first present a unified formulation for surrogate relevance criteria and model the neighborhood relationship among atlases based on the oracle relevance knowledge. Surrogates are then trained to be small for geometrically relevant neighbors and large for irrelevant remotes to the given targets. The proposed surrogate learning framework is verified in corpus callosum segmentation. The learned surrogates demonstrate superiority in inferring the underlying oracle value and selecting relevant fusion set, compared to benchmark surrogates. PMID:27524268

  2. A computational tool for identifying minimotifs in protein-protein interactions and improving the accuracy of minimotif predictions.

    PubMed

    Rajasekaran, Sanguthevar; Merlin, Jerlin Camilus; Kundeti, Vamsi; Mi, Tian; Oommen, Aaron; Vyas, Jay; Alaniz, Izua; Chung, Keith; Chowdhury, Farah; Deverasatty, Sandeep; Irvey, Tenisha M; Lacambacal, David; Lara, Darlene; Panchangam, Subhasree; Rathnayake, Viraj; Watts, Paula; Schiller, Martin R

    2011-01-01

    Protein-protein interactions are important to understanding cell functions; however, our theoretical understanding is limited. There is a general discontinuity between the well-accepted physical and chemical forces that drive protein-protein interactions and the large collections of identified protein-protein interactions in various databases. Minimotifs are short functional peptide sequences that provide a basis to bridge this gap in knowledge. However, there is no systematic way to study minimotifs in the context of protein-protein interactions or vice versa. Here we have engineered a set of algorithms that can be used to identify minimotifs in known protein-protein interactions and implemented this for use by scientists in Minimotif Miner. By globally testing these algorithms on verified data and on 100 individual proteins as test cases, we demonstrate the utility of these new computation tools. This tool also can be used to reduce false-positive predictions in the discovery of novel minimotifs. The statistical significance of these algorithms is demonstrated by an ROC analysis (P = 0.001). PMID:20938975

  3. Comparison of predicted and derived measures of volatile organic compounds inside four relocatable classrooms due to identified interior finish sources

    SciTech Connect

    Hodgson, Alfred T.; Shendell, Derek G.; Fisk, William J.; Apte, Michael G.

    2003-06-01

    Indoor exposures to toxic and odorous volatile organic compounds (VOCs) are of general concern. Recently, VOCs in portable or relocatable classrooms (RCs) have received particular attention. However, very little was known about indoor environmental quality (IEQ) and the sources, composition, and indoor concentrations of VOCs in RCs. This project task focused on developing and demonstrating a process for selecting interior finish materials for RCs that have relatively low impacts with respect to their emissions of toxic and odorous VOCs. This task was part of a larger project to demonstrate the potential for simultaneous improvements in IEQ and energy efficiency in four new RCs equipped both with a continuously ventilating advanced heating, ventilating, and air conditioning system (HVAC) and a standard HVAC system. These HVACs were operated on alternate weeks. One RC per pair was constructed with standard interior finish materials, and the other included alternate interior materials identified in our prior laboratory study to have low VOC emissions. The RCs were sited in side-by-side pairs at two elementary schools in distinct northern California climate zones. Classroom VOC emission rates (mg hr{sup -1}) and concentrations were predicted based on VOC emission factors ({micro}g m{sup -2} hr{sup -1}) measured for individual materials in the laboratory, the quantities of installed materials and design ventilation rates. Predicted emission rates were compared to values derived from classroom measurements of VOC concentrations and ventilation rates made at pre-occupancy, eight weeks, and 27 weeks. Predicted concentrations were compared to measured integrated VOC indoor minus outdoor concentrations during school hours in the fall cooling season with the advanced HVAC operated. These measured concentrations also were compared between standard and material-modified RCs. Our combined laboratory and field process proved effective by correctly predicting that IEQ impacts of

  4. Hypothesis test for synchronization: Twin surrogates revisited

    NASA Astrophysics Data System (ADS)

    Romano, M. Carmen; Thiel, Marco; Kurths, Jürgen; Mergenthaler, Konstantin; Engbert, Ralf

    2009-03-01

    The method of twin surrogates has been introduced to test for phase synchronization of complex systems in the case of passive experiments. In this paper we derive new analytical expressions for the number of twins depending on the size of the neighborhood, as well as on the length of the trajectory. This allows us to determine the optimal parameters for the generation of twin surrogates. Furthermore, we determine the quality of the twin surrogates with respect to several linear and nonlinear statistics depending on the parameters of the method. In the second part of the paper we perform a hypothesis test for phase synchronization in the case of experimental data from fixational eye movements. These miniature eye movements have been shown to play a central role in neural information processing underlying the perception of static visual scenes. The high number of data sets (21 subjects and 30 trials per person) allows us to compare the generated twin surrogates with the "natural" surrogates that correspond to the different trials. We show that the generated twin surrogates reproduce very well all linear and nonlinear characteristics of the underlying experimental system. The synchronization analysis of fixational eye movements by means of twin surrogates reveals that the synchronization between the left and right eye is significant, indicating that either the centers in the brain stem generating fixational eye movements are closely linked, or, alternatively that there is only one center controlling both eyes.

  5. Development of a minimal kinase ensemble receptor (MKER) for surrogate AutoShim.

    PubMed

    Mukherjee, Prasenjit; Martin, Eric

    2011-10-24

    The target-tailored 3-D virtual screening (VS) method "Surrogate AutoShim" adds pharmacophoric shims to a 16-kinase crystal structure "Universal Kinase Ensemble Receptor" (UKER) to generate highly predictive, target-customized docking models. Predocking a corporate archive of millions of compounds into the 16-structure ensemble takes months. However, since the 16 UKER structures are always the same, docking need only be done once. The predocked results are then "shimmed" to reproduce experimental training data for any number of additional kinases far more accurately than conventional docking. Training new kinase models and predicting activity for millions of predocked compounds against dozens of kinases takes only hours. However reducing the predocking time would make the method even more advantageous. Sequential Floating Forward Search (SFFS) was employed to rationally identify a reduced subset using only 8 of the 16 structures, a "Minimal Kinase Ensemble Receptor" (MKER) that preserved the predictive accuracy for 20 kinase models. Furthermore, a performance evaluation of this subset on an extended set of 52 kinase targets and 100,000 compounds showed statistical model performance comparable to the original UKER. The MKER has halved the time for predocking large databases of internal and commercial compounds. For ad hoc virtual libraries, where predocking is not possible, 2- or 3-kinases "Approximate Kinase Ensemble Receptors" (AKER) were also identified with only a modest loss of prediction accuracy. PMID:21848284

  6. Benchmarking a surrogate reaction for neutron capture

    SciTech Connect

    Hatarik, R.; Cizewski, J. A.; Hatarik, A. M.; O'Malley, P. D.; Bernstein, L. A.; Bleuel, D. L.; Burke, J. T.; Escher, J. E.; Lesher, S. R.; Gibelin, J.; Phair, L.; Rodriguez-Vieitez, E.; Goldblum, B. L.; Swan, T.; Wiedeking, M.

    2010-01-15

    {sup 171,173}Yb(d,p{gamma}) reactions are measured, with the goal of extracting the neutron capture cross-section ratio as a function of the neutron energy using the external surrogate ratio method. The cross-section ratios obtained are compared to the known neutron capture cross sections. Although the Weisskopf-Ewing limit is demonstrated not to apply for these low neutron energies, a prescription for deducing surrogate cross sections is presented. The surrogate cross-section ratios deduced from the {sup 171,173}Yb(d,p{gamma}) measurements agree with the neutron capture results within 15%.

  7. Efficient Calibration of Computationally Intensive Groundwater Models through Surrogate Modelling with Lower Levels of Fidelity

    NASA Astrophysics Data System (ADS)

    Razavi, S.; Anderson, D.; Martin, P.; MacMillan, G.; Tolson, B.; Gabriel, C.; Zhang, B.

    2012-12-01

    Many sophisticated groundwater models tend to be computationally intensive as they rigorously represent detailed scientific knowledge about the groundwater systems. Calibration (model inversion), which is a vital step of groundwater model development, can require hundreds or thousands of model evaluations (runs) for different sets of parameters and as such demand prohibitively large computational time and resources. One common strategy to circumvent this computational burden is surrogate modelling which is concerned with developing and utilizing fast-to-run surrogates of the original computationally intensive models (also called fine models). Surrogates can be either based on statistical and data-driven models such as kriging and neural networks or simplified physically-based models with lower fidelity to the original system (also called coarse models). Fidelity in this context refers to the degree of the realism of a simulation model. This research initially investigates different strategies for developing lower-fidelity surrogates of a fine groundwater model and their combinations. These strategies include coarsening the fine model, relaxing the numerical convergence criteria, and simplifying the model geological conceptualisation. Trade-offs between model efficiency and fidelity (accuracy) are of special interest. A methodological framework is developed for coordinating the original fine model with its lower-fidelity surrogates with the objective of efficiently calibrating the parameters of the original model. This framework is capable of mapping the original model parameters to the corresponding surrogate model parameters and also mapping the surrogate model response for the given parameters to the original model response. This framework is general in that it can be used with different optimization and/or uncertainty analysis techniques available for groundwater model calibration and parameter/predictive uncertainty assessment. A real-world computationally

  8. Evaluation of a simulation-based surrogate safety metric.

    PubMed

    Wang, Chen; Stamatiadis, Nikiforos

    2014-10-01

    The development of surrogate safety measures is essential due to the problems of availability and quality of historical crash data. The Aggregate Conflict Propensity Metric (ACPM) is a surrogate metric recently proposed and it is based on conflict studies and traffic simulations. ACPM is expected to be capable of assessing the relative safety levels of traffic facilities and/or treatments in order to help traffic engineers to select appropriate treatments based on traffic safety estimates. This paper presents three experimental tests conducted to evaluate the reliability of ACPM. In each test, ACPM is compared to a traditional conflict indicator in terms of identifying and ranking safety of traffic conditions under various traffic volumes based on traffic simulations. ACPM shows its strength and reliability in all three tests, as it provides results highly consistent with the Highway Safety Manual. The experimental tests indicate that ACPM is a promising surrogate safety measure that can appropriately identify relative safety among traffic treatments and/or facilities and provide traffic engineers with useful information on potential safety impact. PMID:24892875

  9. Surrogate oracles, generalized dependency and simpler models

    NASA Technical Reports Server (NTRS)

    Wilson, Larry

    1990-01-01

    Software reliability models require the sequence of interfailure times from the debugging process as input. It was previously illustrated that using data from replicated debugging could greatly improve reliability predictions. However, inexpensive replication of the debugging process requires the existence of a cheap, fast error detector. Laboratory experiments can be designed around a gold version which is used as an oracle or around an n-version error detector. Unfortunately, software developers can not be expected to have an oracle or to bear the expense of n-versions. A generic technique is being investigated for approximating replicated data by using the partially debugged software as a difference detector. It is believed that the failure rate of each fault has significant dependence on the presence or absence of other faults. Thus, in order to discuss a failure rate for a known fault, the presence or absence of each of the other known faults needs to be specified. Also, in simpler models which use shorter input sequences without sacrificing accuracy are of interest. In fact, a possible gain in performance is conjectured. To investigate these propositions, NASA computers running LIC (RTI) versions are used to generate data. This data will be used to label the debugging graph associated with each version. These labeled graphs will be used to test the utility of a surrogate oracle, to analyze the dependent nature of fault failure rates and to explore the feasibility of reliability models which use the data of only the most recent failures.

  10. Predicting the spatial distribution of a seabird community to identify priority conservation areas in the Timor Sea.

    PubMed

    Lavers, Jennifer L; Miller, Mark G R; Carter, Michael J; Swann, George; Clarke, Rohan H

    2014-12-01

    Understanding spatial and temporal variability in the distribution of species is fundamental to the conservation of marine and terrestrial ecosystems. To support strategic decision making aimed at sustainable management of the oceans, such as the establishment of protected areas for marine wildlife, we identified areas predicted to support multispecies seabird aggregations in the Timor Sea. We developed species distribution models for 21 seabird species based on at-sea survey observations from 2000-2013 and oceanographic variables (e.g., bathymetry). We applied 4 statistical modeling techniques and combined the results into an ensemble model with robust performance. The ensemble model predicted the probability of seabird occurrence in areas where few or no surveys had been conducted and demonstrated 3 areas of high seabird richness that varied little between seasons. These were located within 150 km of Adele Island, Ashmore Reef, and the Lacepede Islands, 3 of the largest aggregations of breeding seabirds in Australia. Although these breeding islands were foci for high species richness, model performance was greatest for 3 nonbreeding migratory species that would have been overlooked had regional monitoring been restricted to islands. Our results indicate many seabird hotspots in the Timor Sea occur outside existing reserves (e.g., Ashmore Reef Marine Reserve), where shipping, fisheries, and offshore development likely pose a threat to resident and migratory populations. Our results highlight the need to expand marine spatial planning efforts to ensure biodiversity assets are appropriately represented in marine reserves. Correspondingly, our results support the designation of at least 4 new important bird areas, for example, surrounding Adele Island and Ashmore Reef. PMID:24976050

  11. Progress in Chemical Kinetic Modeling for Surrogate Fuels

    SciTech Connect

    Pitz, W J; Westbrook, C K; Herbinet, O; Silke, E J

    2008-06-06

    Gasoline, diesel, and other alternative transportation fuels contain hundreds to thousands of compounds. It is currently not possible to represent all these compounds in detailed chemical kinetic models. Instead, these fuels are represented by surrogate fuel models which contain a limited number of representative compounds. We have been extending the list of compounds for detailed chemical models that are available for use in fuel surrogate models. Detailed models for components with larger and more complicated fuel molecular structures are now available. These advancements are allowing a more accurate representation of practical and alternative fuels. We have developed detailed chemical kinetic models for fuels with higher molecular weight fuel molecules such as n-hexadecane (C16). Also, we can consider more complicated fuel molecular structures like cyclic alkanes and aromatics that are found in practical fuels. For alternative fuels, the capability to model large biodiesel fuels that have ester structures is becoming available. These newly addressed cyclic and ester structures in fuels profoundly affect the reaction rate of the fuel predicted by the model. Finally, these surrogate fuel models contain large numbers of species and reactions and must be reduced for use in multi-dimensional models for spark-ignition, HCCI and diesel engines.

  12. Identifying bereaved subjects at risk of complicated grief: Predictive value of questionnaire items in a cohort study

    PubMed Central

    2011-01-01

    Background Bereavement is a condition which most people experience several times during their lives. A small but noteworthy proportion of bereaved individuals experience a syndrome of prolonged psychological distress in relation to bereavement. The aim of the study was to develop a clinical tool to identify bereaved individuals who had a prognosis of complicated grief and to propose a model for a screening tool to identify those at risk of complicated grief applicable among bereaved patients in general practice and palliative care. Methods We examined the responses of 276 newly bereaved individuals to a variety of standardised and ad hoc questionnaire items eight weeks post loss. Inventory of Complicated Grief (ICG-R) was used as a gold standard of distress at six months after bereavement. Receiver operating characteristic (ROC) curves analysis was performed for all scales and items regarding ICG-R score. Sensitivity, specificity and area under curve (AUC) were calculated for scales and items with the most promising ROC curve analyses. Results Beck's Depression Inventory (BDI) was the scale with the highest AUC (0.83) and adding a single item question ('Even while my relative was dying, I felt a sense of purpose in my life') gave a sensitivity of 80% and specificity of 75%. The positive/negative predictive values for this combination of questions were 70% and 85%, respectively. With this screening tool bereaved people could be categorized into three groups where group 1 had 7%, group 2 had 23% and group 3 had 64% propensity of suffering from complicated grief six months post loss. Conclusions This study shows that the BDI in combination with a single item question eight weeks post loss may be used for clinical screening for risk of developing complicated grief after six months. The feasibility and clinical implications of the screening tool has to be tested in a clinical setting. PMID:21575239

  13. Coupled simulation-optimization model for coastal aquifer management using genetic programming-based ensemble surrogate models and multiple-realization optimization

    NASA Astrophysics Data System (ADS)

    Sreekanth, J.; Datta, Bithin

    2011-04-01

    Approximation surrogates are used to substitute the numerical simulation model within optimization algorithms in order to reduce the computational burden on the coupled simulation-optimization methodology. Practical utility of the surrogate-based simulation-optimization have been limited mainly due to the uncertainty in surrogate model simulations. We develop a surrogate-based coupled simulation-optimization methodology for deriving optimal extraction strategies for coastal aquifer management considering the predictive uncertainty of the surrogate model. Optimization models considering two conflicting objectives are solved using a multiobjective genetic algorithm. Objectives of maximizing the pumping from production wells and minimizing the barrier well pumping for hydraulic control of saltwater intrusion are considered. Density-dependent flow and transport simulation model FEMWATER is used to generate input-output patterns of groundwater extraction rates and resulting salinity levels. The nonparametric bootstrap method is used to generate different realizations of this data set. These realizations are used to train different surrogate models using genetic programming for predicting the salinity intrusion in coastal aquifers. The predictive uncertainty of these surrogate models is quantified and ensemble of surrogate models is used in the multiple-realization optimization model to derive the optimal extraction strategies. The multiple realizations refer to the salinity predictions using different surrogate models in the ensemble. Optimal solutions are obtained for different reliability levels of the surrogate models. The solutions are compared against the solutions obtained using a chance-constrained optimization formulation and single-surrogate-based model. The ensemble-based approach is found to provide reliable solutions for coastal aquifer management while retaining the advantage of surrogate models in reducing computational burden.

  14. Surrogate Motherhood II: Reflections after "Baby M."

    ERIC Educational Resources Information Center

    Schwartz, Lita Linzer

    1988-01-01

    Discusses the "Baby M" surrogate motherhood case which has produced heated debate in popular media, legal publications, and other professional journals. Summarizes arguments offered and reasoning behind actions of judiciary. (Author/ABL)

  15. Using the integrative model of behavioral prediction to identify promising message strategies to promote healthy sleep behavior among college students.

    PubMed

    Robbins, Rebecca; Niederdeppe, Jeff

    2015-01-01

    This research used the Integrative Model of Behavioral Prediction (IMBP) to examine cognitive predictors of intentions to engage in healthy sleep behavior among a population of college students. In doing so, we identify promising message strategies to increase healthy sleep behavior during college. In Phase 1, members of a small sample of undergraduates (n = 31) were asked to describe their beliefs about expected outcomes, norms, and perceived behavioral control associated with sleep on an open-ended questionnaire. We analyzed these qualitative responses to create a closed-ended survey about sleep-related attitudes, perceived norms, control beliefs, behavioral intentions, and behavior. In Phase 2, a larger sample of undergraduate students (n = 365) completed the survey. Attitudes and perceived behavioral control were the strongest predictors of both intentions to engage in sleep behavior and self-reported sleep behavior. Control beliefs associated with time management and stress also had substantial room to change, suggesting their potential as message strategies to better promote healthy sleep behavior in college. We conclude with a broader discussion of the study's implications for message design and intervention. PMID:24446927

  16. Surrogate burns in deactivation furnace system.

    PubMed

    Shah, J K

    1999-05-14

    The deactivation furnace system at the Deseret Chemical Depot in Utah is designed for processing explosive components from munitions containing nerve and mustard agents. The system was installed during the period of 1989 through 1993. The Utah Division of Solid and Hazardous Waste (UDSHW) required that trial burns be conducted using surrogate chemicals prior to introducing chemical agents into the system. The selected surrogate chemicals were monochlorobenzene and hexachloroethane based on the criteria established by the UDSHW. Three surrogate runs were conducted in October, 1995. The gaseous emissions and liquid and solid effluents were sampled and analyzed using approved EPA methods. The trial burns demonstrated the desirable destruction and removal efficiency for the selected surrogate chemicals. The pollution abatement system demonstrated the desired scrubbing efficiency for acid gases generated during incineration of chlorinated surrogate chemicals. The particulate removal efficiency during the trial burns was also considerably higher than required by regulations. After comprehensive review of the performance of the deactivation furnace system during the surrogate trial burns, UDSHW approved introduction of GB nerve agent into the system to prepare it for agent trial burns. PMID:10334826

  17. Augmented trial designs for evaluation of principal surrogates.

    PubMed

    Gabriel, Erin E; Follmann, Dean

    2016-07-01

    Observation of counterfactual intermediate responses, and evaluation of them as candidate surrogates, is complicated in a standard randomized trial as half of the responses are systematically missing by design. Although some augmentation procedures exist for obtaining counterfactual responses, they are specific to vaccine trials. We outline extensions to the existing augmentations and suggest augmentations of three trial designs outside the setting of vaccines. We outline the assumptions needed to identify the causal estimands of interest under each augmented design, under which standard likelihood-based methods can be used to evaluate intermediate responses as principal surrogates. Two of these designs, crossover and individual stepped-wedge, allow for the observation of clinical endpoints under both treatment and control for some subset of subjects and can therefore improve efficiency over standard parallel trial designs. The third, the treatment run-in design, allows for the observation of a baseline measure that may be as useful a surrogate as the true counterfactual intermediate response. As the evaluation methods rely on several assumptions, we also outline a remediation analysis, which can be used to help overcome assumption violations. We illustrate our suggested methods in an example from a drug-resistant tuberculosis treatment trial. PMID:26825099

  18. Predictive Value of C-Reactive Protein (CRP) in Identifying Fatal Outcome and Deep Infections in Staphylococcus aureus Bacteremia

    PubMed Central

    Ruotsalainen, Eeva; Rintala, Esa M.; Järvinen, Asko

    2016-01-01

    Introduction Clear cut-off levels could aid clinicians in identifying patients with a risk of fatal outcomes or complications such as deep infection foci in Staphylococcus aureus bacteremia (SAB). Cut-off levels for widely used clinical follow-up parameters including serum C-reactive protein (CRP) levels and white blood cell counts (WBC) have not been previously studied. Methods 430 adult SAB patients in Finland took part in prospective multicentre study in which their CRP levels and WBC counts were measured on the day of the positive blood culture, every other day during the first week, twice a week during hospitalization and at 30 days. Receiver operating characteristic (ROC) analysis was used to evaluate the prognostic value of CRP and WBC on the day of the positive blood culture and at days 4, 7, and 14 in predicting mortality and the presence of deep infections at 30 days. Adjusted hazard ratios (HR) for CRP level and WBC count cut-off values for mortality were calculated by the Cox regression analysis and adjusted odds ratios (OR) for cut-off values to predict the presence of deep infection by the binary logistic regression analysis. Results The succumbing patients could be distinguished from the survivors, starting on day 4 after the positive blood culture, by higher CRP levels. Cut-off values of CRP for day 30 mortality in adjusted analysis, that significantly predicted fatal outcome were at day 4 CRP >103 mg/L with sensitivity of 77%, specificity of 55%, and HR of 3.5 (95% CI, 1.2–10.3; p = 0.024), at day 14 CRP >61 mg/L with a sensitivity of 82%, specificity of 80% and HR of 3.6 (95% CI, 1.1–10.3; p<0.039) and cut-off value of WBC at day 14 >8.6 x109/L was prognostic with sensitivity of 77%, specificity of 78% and HR of 8.2 (95% CI, 2.9–23.1; p<0.0001). Cut-off values for deep infection in adjusted analysis were on the day of the positive blood culture CRP >108 mg/L with sensitivity of 77%, specificity of 60%, and HR of 2.6 (95% CI, 1.3–4.9; p = 0

  19. Dynamic Contrast-Enhanced MRI of Cervical Cancers: Temporal Percentile Screening of Contrast Enhancement Identifies Parameters for Prediction of Chemoradioresistance

    SciTech Connect

    Andersen, Erlend K.F.; Hole, Knut Hakon; Lund, Kjersti V.; Sundfor, Kolbein; Kristensen, Gunnar B.; Lyng, Heidi; Malinen, Eirik

    2012-03-01

    Purpose: To systematically screen the tumor contrast enhancement of locally advanced cervical cancers to assess the prognostic value of two descriptive parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods and Materials: This study included a prospectively collected cohort of 81 patients who underwent DCE-MRI with gadopentetate dimeglumine before chemoradiotherapy. The following descriptive DCE-MRI parameters were extracted voxel by voxel and presented as histograms for each time point in the dynamic series: normalized relative signal increase (nRSI) and normalized area under the curve (nAUC). The first to 100th percentiles of the histograms were included in a log-rank survival test, resulting in p value and relative risk maps of all percentile-time intervals for each DCE-MRI parameter. The maps were used to evaluate the robustness of the individual percentile-time pairs and to construct prognostic parameters. Clinical endpoints were locoregional control and progression-free survival. The study was approved by the institutional ethics committee. Results: The p value maps of nRSI and nAUC showed a large continuous region of percentile-time pairs that were significantly associated with locoregional control (p < 0.05). These parameters had prognostic impact independent of tumor stage, volume, and lymph node status on multivariate analysis. Only a small percentile-time interval of nRSI was associated with progression-free survival. Conclusions: The percentile-time screening identified DCE-MRI parameters that predict long-term locoregional control after chemoradiotherapy of cervical cancer.

  20. Estimating alcohol involvement in trauma patients: search for a surrogate.

    PubMed

    Treno, A J; Cooper, K; Roeper, P

    1994-12-01

    This study explores the potential for the development of a surrogate for alcohol-involved traumatic injury. It presents a bivariate probit analysis that simultaneously models likelihoods of patients being tested for blood alcohol content (BAC) and having positive BACs given testing using 17,356 adult trauma cases selected from the California Regional Trauma Registry. It concludes that patient and injury characteristics predict both testing and BAC, and that a weighting scheme may be profitably used to determine changes in levels of alcohol-involved trauma in populations over time in the absence of empirical measurement of BAC. PMID:7695022

  1. Coastal aquifer management under parameter uncertainty: Ensemble surrogate modeling based simulation-optimization

    NASA Astrophysics Data System (ADS)

    Janardhanan, S.; Datta, B.

    2011-12-01

    saltwater intrusion are considered. The salinity levels resulting at strategic locations due to these pumping are predicted using the ensemble surrogates and are constrained to be within pre-specified levels. Different realizations of the concentration values are obtained from the ensemble predictions corresponding to each candidate solution of pumping. Reliability concept is incorporated as the percent of the total number of surrogate models which satisfy the imposed constraints. The methodology was applied to a realistic coastal aquifer system in Burdekin delta area in Australia. It was found that all optimal solutions corresponding to a reliability level of 0.99 satisfy all the constraints and as reducing reliability level decreases the constraint violation increases. Thus ensemble surrogate model based simulation-optimization was found to be useful in deriving multi-objective optimal pumping strategies for coastal aquifers under parameter uncertainty.

  2. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    SciTech Connect

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-17

    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO2 production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  3. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    SciTech Connect

    Herbinet, O; Pitz, W J; Westbrook, C K

    2007-09-20

    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO{sub 2} production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  4. Bayesian meta-analytical methods to incorporate multiple surrogate endpoints in drug development process.

    PubMed

    Bujkiewicz, Sylwia; Thompson, John R; Riley, Richard D; Abrams, Keith R

    2016-03-30

    A number of meta-analytical methods have been proposed that aim to evaluate surrogate endpoints. Bivariate meta-analytical methods can be used to predict the treatment effect for the final outcome from the treatment effect estimate measured on the surrogate endpoint while taking into account the uncertainty around the effect estimate for the surrogate endpoint. In this paper, extensions to multivariate models are developed aiming to include multiple surrogate endpoints with the potential benefit of reducing the uncertainty when making predictions. In this Bayesian multivariate meta-analytic framework, the between-study variability is modelled in a formulation of a product of normal univariate distributions. This formulation is particularly convenient for including multiple surrogate endpoints and flexible for modelling the outcomes which can be surrogate endpoints to the final outcome and potentially to one another. Two models are proposed, first, using an unstructured between-study covariance matrix by assuming the treatment effects on all outcomes are correlated and second, using a structured between-study covariance matrix by assuming treatment effects on some of the outcomes are conditionally independent. While the two models are developed for the summary data on a study level, the individual-level association is taken into account by the use of the Prentice's criteria (obtained from individual patient data) to inform the within study correlations in the models. The modelling techniques are investigated using an example in relapsing remitting multiple sclerosis where the disability worsening is the final outcome, while relapse rate and MRI lesions are potential surrogates to the disability progression. PMID:26530518

  5. Skin penetration surrogate for the evaluation of less lethal kinetic energy munitions.

    PubMed

    Bir, Cynthia A; Resslar, Marianne; Stewart, Shelby

    2012-07-10

    Although the benefits of the use of less lethal kinetic energy munitions are numerous, there is a need to evaluate the munitions prior to deployment to ensure their intended effect. The objective of the current research was to validate a surrogate that could be used to predict the risk of penetration of these devices. Existing data from biomechanical testing with post-mortem human specimens (PMHS) served as the foundation for this research. Development of the surrogate involved simulating the various layers of the skin and underlying soft tissues using a combination of materials. A standardized 12-gauge impactor was used to assess each combination. The energy density that resulted in a 50% risk of penetration for the anterior thorax region (23.99 J/cm(2)) from the previous research was matched using a specific combination of layers. Twelve various combinations of materials were tested with the 50% risk of penetration determined. The final validated surrogate consisted of a Laceration Assessment Layer (LAL) of natural chamois and .6 cm of closed-cell foam over a Penetration Assessment Layer (PAL) of 20% ordnance gelatin. This surrogate predicted a 50% risk of penetration at 23.88 J/cm(2). Injury risk curves for the PMHS and surrogate development work are presented. PMID:22405483

  6. Surrogate-based Analysis and Optimization

    NASA Technical Reports Server (NTRS)

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

    2005-01-01

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

  7. Global Optimization Using Mixed Surrogates and Space Elimination in Computationally Intensive Engineering Designs

    NASA Astrophysics Data System (ADS)

    Younis, Adel; Dong, Zuomin

    2012-07-01

    Surrogate-based modeling is an effective search method for global design optimization over well-defined areas using complex and computationally intensive analysis and simulation tools. However, indentifying the appreciate surrogate models and their suitable areas remains a challenge that requires extensive human intervention. In this work, a new global optimization algorithm, namely Mixed Surrogate and Space Elimination (MSSE) method, is introduced. Representative surrogate models, including Quadratic Response Surface, Radial Basis function, and Kriging, are mixed with different weight ratios to form an adaptive metamodel with best tested performance. The approach divides the field of interest into several unimodal regions; identifies and ranks the regions that likely contain the global minimum; fits the weighted surrogate models over each promising region using additional design experiment data points from Latin Hypercube Designs and adjusts the weights according to the performance of each model; identifies its minimum and removes the processed region; and moves to the next most promising region until all regions are processed and the global optimum is identified. The proposed algorithm was tested using several benchmark problems for global optimization and compared with several widely used space exploration global optimization algorithms, showing reduced computation efforts, robust performance and comparable search accuracy, making the proposed method an excellent tool for computationally intensive global design optimization problems.

  8. Legal regulation of surrogate motherhood in Israel.

    PubMed

    Frenkel, D A

    2001-01-01

    The Israeli Law on surrogate motherhood demands a preconception agreement to include payments to be made to the surrogate mother. Surrogacy arrangements with family members are forbidden. Commercial surrogacy is allowed and encouraged. The Law causes many problems. Validity of consent given by surrogate mothers is doubtful. Possible future psychological harm are ignored. There is a danger of "commodification" of children. Abusing women of low socio-economic status as breeding machines may be another outcome. No clear responsibility is imposed on the "intended parents" for an impaired child. The law ignores possibility of divorce or death of the "intended parents" before the child's birth. Splitting motherhood is another social problem that has to be dealt with. So far the sperm of the husband from the "intended parents" has to be used, but further steps may follow. It is not certain that a policy of "positive eugenics" will not develop. PMID:11817392

  9. Parents and children: "surrogate" paradigm of modernity.

    PubMed

    Adam, Archimandrite; Akhaladze, Vakhtang

    2011-06-01

    The article provides an overview of surrogate motherhood--one of many currently available forms of Assisted Reproductive Technologies for couples who find themselves unable to conceive a child on their own. Within the years of its existence surrogate motherhood managed to accumulate lots of bioethical problems, paradoxes, dilemmas and collisions. Author represents some of them. Also the legal, moral and religious implications of surrogacy are addressed. The religious perspective from the Orthodox Christian, Catholic, Jewish, Hinduism, and Islamic points of view are provided. The author concludes that surrogate motherhood is not only the answer to childlessness but it supports metamorphosis of traditional attitude towards such human value as it is a family. PMID:21778532

  10. Attitudes toward surrogate motherhood in Canada.

    PubMed

    Krishnan, V

    1994-01-01

    The issue of surrogate motherhood captured worldwide attention with the Baby M case in the United States. Some medical practitioners now claim that the surrogate arrangement may be the answer for certain women who are unable to conceive children naturally. Feminist activists are highly critical about the issue. In her landmark book The Mother Machine, Corea (1985) called surrogates "breeders," women whose bodies are being used by men. Lawyers and ethicists debate whether surrogacy is baby selling or not, and religious fundamentalists have condemned any form of procreation outside the "normal" or "natural" form of sexual relations within a marriage. But what do Canadian women think about commercial surrogacy? Findings pertaining to this issue from the latest national fertility survey of 5,315 women in the reproductive ages of 18-49 are reported. PMID:8056650

  11. Surrogate mothers: not so novel after all.

    PubMed

    Robertson, J A

    1983-10-01

    A law professor examines the legal, psychological, social, and ethical issues that arise in surrogate mothering and the problems that this procedure may create for the biological and adoptive parents, the child, and the state. Robertson considers the central issue of this and other "collaborative reproduction" methods to be the extent and nature of third party involvement rather than the deliberate separation of biologic and social parentage. He believes that the state's power to regulate surrogate arrangements may be limited by a couple's constitutional right to make procreative decisions. An insert on page 31 of Robertson's article summarizes the guidelines on "Ethical Issues in Surrogate Motherhood" issued in May 1983 by the American College of Obstetricians and Gynecologists. PMID:6643034

  12. Perspectives of Decisional Surrogates and Patients Regarding Critical Illness Genetic Research

    PubMed Central

    Freeman, Bradley D.; Bolcic-Jankovic, Dragana; Kennedy, Carie R.; LeBlanc, Jessica; Eastman, Alexander; Barillas, Jennifer; Wittgen, Catherine M.; indsey, Kathryn; Mahmood, Rumel S.; Clarridge, Brian R.

    2015-01-01

    Background Critical illness research is challenging due to disease severity and because patients are frequently incapacitated. Surrogates called upon to provide consent might not accurately represent patient preferences. Though commonplace, genetic data collection adds complexity in this context. We undertook this investigation to understand whether surrogate decision makers would be receptive to permitting participation in a critical illness genetics study and whether their decision making was consistent with that of the patient represented. Methods We invited individuals identified as surrogates for critically ill adults, if required, as well as patients once recovered to participate in a survey designed to understand attitudes about genetic research. Associations between dependent (receptivity to participation, concordance of responses) and independent variables were tested using bivariate and multivariate logistic regression analyses. Results Most of the entire surrogate sample (n=439) reported familiarity with research, including genetic research; tended to view research as useful; and were receptive to allowing their family member participate (with 39.6% and 38.1% stating that this would be “very” and “somewhat likely,” respectively) even absent direct benefit. Willingness to participate was similar comparing genetic and non-genetic studies (χ2 [1,n=439]=0.00127, p=0.972), though respondents expressed worry regarding lack of confidentiality of genetic data. Responses were concordant in 70.8% of the 192 surrogate-patient pairs analyzed. In multivariate analysis, African American race was associated with less receptivity to genetic data collection (p<0.05). No factors associated with concordance of surrogate-patient response were identified. Conclusions Surrogates’ receptivity to critical illness research was not influenced by whether the study entailed collection of genetic data. While more than two-thirds of surrogate-patient responses for

  13. Surrogates and extra-familial interests.

    PubMed

    Baergen, Ralph; Woodhouse, William

    2013-01-01

    A case is presented in which the therapeutic interests of the patient conflict with the safety of a community, and in which the surrogate decision maker has very limited knowledge of or concern for the patient's preferences. The substituted judgment and best interest (or rational patient) standards for surrogate decision making are problematic in this case. It is argued that the interests of even those outside the family ought to be taken seriously when making decisions about such cases, and it is proposed that clinical ethics committees could play a new role here. This case also illustrates the difficulties of making decisions regarding the treatment of a very unlikable patient. PMID:24597420

  14. Tuberculosis Biomarker and Surrogate Endpoint Research Roadmap

    PubMed Central

    Saukkonen, Jussi; Kenzie, William R. Mac; Johnson, John L.; Phillips, Patrick P. J.; Andersen, Janet; Bliven-Sizemore, Erin; Belisle, John T.; Boom, W. Henry; Luetkemeyer, Annie; Campbell, Thomas B.; Eisenach, Kathleen D.; Hafner, Richard; Lennox, Jeffrey L.; Makhene, Mamodikoe; Swindells, Susan; Villarino, M. Elsa; Weiner, Marc; Benson, Constance; Burman, William

    2011-01-01

    The Centers for Disease Control and Prevention and National Institutes of Health convened a multidisciplinary meeting to discuss surrogate markers of treatment response in tuberculosis. The goals were to assess recent surrogate marker research and to provide specific recommendations for (1) the qualification and validation of biomarkers of treatment outcome; (2) the standardization of specimen and data collection for future clinical trials, including a minimum set of samples and collection time points; and (3) the creation of a specimen repository to support biomarker testing. This article summarizes these recommendations and provides a roadmap for their implementation. PMID:21737585

  15. A government bill on surrogate motherhood?

    PubMed

    Deitch, R

    1985-01-19

    Britain's Department of Health and Social Security (DHSS) seems to have badly miscalculated in discounting the political necessity of immediately introducing legislation to ban surrogate parenthood arrangements. After the birth of a baby in a case involving a financial arrangement among a surrogate mother, an agency, and the natural father and his wife, pressures from the House of Commons and from Prime Minister Thatcher are now forcing the DHSS to find a slot in the legislative timetable that would enable a government bill on the subject to be enacted this year. PMID:2857262

  16. Surrogate decision making in neurocritical care.

    PubMed

    Adelman, Eric E; Zahuranec, Darin B

    2012-06-01

    Patients with critical neurologic illness typically have impaired capacity to make their own medical decisions. In these cases, neurologists need to make medical decisions based on advance directives (such as a living will) or the decisions of a surrogate. A hypothetical case of a 60-year-old man with an intracerebral hemorrhage is used to highlight some of the difficulties that can occur when attempting to apply general statements made in a living will to a specific medical treatment decision. The ethical and legal issues surrounding surrogate decision making as they apply to acute critical neurologic disease are discussed, along with suggestions for how to resolve potential disagreements. PMID:22810254

  17. Chemically authentic surrogate mixture model for the thermophysical properties of a coal-derived liquid fuel

    SciTech Connect

    M.L. Huber; E.W. Lemmon; V. Diky; B.L. Smith; T.J. Bruno

    2008-09-15

    We developed a surrogate mixture model to represent the physical properties of a coal-derived liquid fuel using only information obtained from a gas chromatography-mass spectrometry analysis of the fuel and a recently developed 'advanced distillation curve'. We then predicted the density, speed of sound, and viscosity of the fuel and compared them to limited experimental data. The surrogate contains five components (n-propylcyclohexane, trans-decalin, {alpha}-methyldecalin, bicyclohexane, and n-hexadecane), yet comparisons to limited experimental data demonstrate that the model is able to represent the density, sound speed, and viscosity to within 1, 4, and 5%, respectively. 102 refs., 2 figs., 5 tabs.

  18. Value-Driven Design and Sensitivity Analysis of Hybrid Energy Systems using Surrogate Modeling

    SciTech Connect

    Wenbo Du; Humberto E. Garcia; William R. Binder; Christiaan J. J. Paredis

    2001-10-01

    A surrogate modeling and analysis methodology is applied to study dynamic hybrid energy systems (HES). The effect of battery size on the smoothing of variability in renewable energy generation is investigated. Global sensitivity indices calculated using surrogate models show the relative sensitivity of system variability to dynamic properties of key components. A value maximization approach is used to consider the tradeoff between system variability and required battery size. Results are found to be highly sensitive to the renewable power profile considered, demonstrating the importance of accurate renewable resource modeling and prediction. The documented computational framework and preliminary results represent an important step towards a comprehensive methodology for HES evaluation, design, and optimization.

  19. A prediction rule to identify severe cases among adult patients hospitalized with pandemic influenza A (H1N1) 2009.

    PubMed

    Oh, Won Sup; Lee, Seung-Joon; Lee, Chang-Seop; Hur, Ji-An; Hur, Ae-Chung; Park, Yoon Seon; Heo, Sang-Taek; Bae, In-Gyu; Park, Sang Won; Kim, Eu Suk; Kim, Hong Bin; Song, Kyoung-Ho; Lee, Kkot Sil; Lee, Sang-Rok; Yeom, Joon Sup; Lee, Su Jin; Kim, Baek-Nam; Kwak, Yee Gyung; Lee, Jae Hoon; Kim, Yong Keun; Kim, Hyo Youl; Kim, Nam Joong; Oh, Myoung-Don

    2011-04-01

    The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO(2)/FiO(2) ≤ 250), bilateral lung infiltration, and old age (≥ 65 yr) were independent risk factors for severe cases (all P < 0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of ≥ 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of ≥ 13. As a prediction rule, the presence of ≥ 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009. PMID:21468256

  20. Uncertainty quantification of squeal instability via surrogate modelling

    NASA Astrophysics Data System (ADS)

    Nobari, Amir; Ouyang, Huajiang; Bannister, Paul

    2015-08-01

    One of the major issues that car manufacturers are facing is the noise and vibration of brake systems. Of the different sorts of noise and vibration, which a brake system may generate, squeal as an irritating high-frequency noise costs the manufacturers significantly. Despite considerable research that has been conducted on brake squeal, the root cause of squeal is still not fully understood. The most common assumption, however, is mode-coupling. Complex eigenvalue analysis is the most widely used approach to the analysis of brake squeal problems. One of the major drawbacks of this technique, nevertheless, is that the effects of variability and uncertainty are not included in the results. Apparently, uncertainty and variability are two inseparable parts of any brake system. Uncertainty is mainly caused by friction, contact, wear and thermal effects while variability mostly stems from the manufacturing process, material properties and component geometries. Evaluating the effects of uncertainty and variability in the complex eigenvalue analysis improves the predictability of noise propensity and helps produce a more robust design. The biggest hurdle in the uncertainty analysis of brake systems is the computational cost and time. Most uncertainty analysis techniques rely on the results of many deterministic analyses. A full finite element model of a brake system typically consists of millions of degrees-of-freedom and many load cases. Running time of such models is so long that automotive industry is reluctant to do many deterministic analyses. This paper, instead, proposes an efficient method of uncertainty propagation via surrogate modelling. A surrogate model of a brake system is constructed in order to reproduce the outputs of the large-scale finite element model and overcome the issue of computational workloads. The probability distribution of the real part of an unstable mode can then be obtained by using the surrogate model with a massive saving of

  1. Kinetic Modeling of Gasoline Surrogate Components and Mixtures under Engine Conditions

    SciTech Connect

    Mehl, M; Pitz, W J; Westbrook, C K; Curran, H J

    2010-01-11

    Real fuels are complex mixtures of thousands of hydrocarbon compounds including linear and branched paraffins, naphthenes, olefins and aromatics. It is generally agreed that their behavior can be effectively reproduced by simpler fuel surrogates containing a limited number of components. In this work, an improved version of the kinetic model by the authors is used to analyze the combustion behavior of several components relevant to gasoline surrogate formulation. Particular attention is devoted to linear and branched saturated hydrocarbons (PRF mixtures), olefins (1-hexene) and aromatics (toluene). Model predictions for pure components, binary mixtures and multicomponent gasoline surrogates are compared with recent experimental information collected in rapid compression machine, shock tube and jet stirred reactors covering a wide range of conditions pertinent to internal combustion engines (3-50 atm, 650-1200K, stoichiometric fuel/air mixtures). Simulation results are discussed focusing attention on the mixing effects of the fuel components.

  2. Development of a multi-objective optimization algorithm using surrogate models for coastal aquifer management

    NASA Astrophysics Data System (ADS)

    Kourakos, George; Mantoglou, Aristotelis

    2013-02-01

    SummaryThe demand for fresh water in coastal areas and islands can be very high due to increased local needs and tourism. A multi-objective optimization methodology is developed, involving minimization of economic and environmental costs while satisfying water demand. The methodology considers desalinization of pumped water and injection of treated water into the aquifer. Variable density aquifer models are computationally intractable when integrated in optimization algorithms. In order to alleviate this problem, a multi-objective optimization algorithm is developed combining surrogate models based on Modular Neural Networks [MOSA(MNNs)]. The surrogate models are trained adaptively during optimization based on a genetic algorithm. In the crossover step, each pair of parents generates a pool of offspring which are evaluated using the fast surrogate model. Then, the most promising offspring are evaluated using the exact numerical model. This procedure eliminates errors in Pareto solution due to imprecise predictions of the surrogate model. The method has important advancements compared to previous methods such as precise evaluation of the Pareto set and alleviation of propagation of errors due to surrogate model approximations. The method is applied to an aquifer in the Greek island of Santorini. The results show that the new MOSA(MNN) algorithm offers significant reduction in computational time compared to previous methods (in the case study it requires only 5% of the time required by other methods). Further, the Pareto solution is better than the solution obtained by alternative algorithms.

  3. 34 CFR 303.406 - Surrogate parents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Surrogate parents. 303.406 Section 303.406 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS...

  4. CEM ORGANIC SURROGATES, SAMPLING AND FORMATION

    EPA Science Inventory

    Field demonstrations of online monitors were completed in 2004 and samples are being analyzed to determine surrogate/dioxin toxic equivalent (TEQ) relationships. Establishing these relationships is critical the to success of real-time monitoring, since monitors can only examine a...

  5. Surrogate Motherhood I: Responses to Infertility.

    ERIC Educational Resources Information Center

    Schwartz, Lita Linzer

    1987-01-01

    Surrogate motherhood is a path to parenthood filled with legal "potholes" and psychological "rocks." Mental health specialists, especially marital and family therapists, may well be called upon to provide their professional services to people attempting to negotiate it. Introduces a number of potential hazards, presenting the points at which…

  6. RELIABILITY OF SURROGATES FOR DETERMINING CRYPTOSPORIDIUM REMOVAL

    EPA Science Inventory

    Testing of field-scale bag filtration systems yielded results indicating that 4-6-um polystyrene microspheres can be used as a reliable surrogate for determining Cryptosporidium oocyst removal in bag filtration process. A nearly perfect linear correlation was observed between log...

  7. 34 CFR 300.519 - Surrogate parents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Surrogate parents. 300.519 Section 300.519 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN...

  8. 34 CFR 300.519 - Surrogate parents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true Surrogate parents. 300.519 Section 300.519 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN...

  9. 34 CFR 303.406 - Surrogate parents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true Surrogate parents. 303.406 Section 303.406 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS...

  10. Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

    SciTech Connect

    Malinowski, Kathleen T.; McAvoy, Thomas J.; George, Rohini; Dieterich, Sonja; D'Souza, Warren D.

    2012-04-01

    Purpose: To investigate the effect of tumor site, measurement precision, tumor-surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor-surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor-surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3-3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

  11. The Effectiveness of Predict-Observe-Explain Tasks in Diagnosing Students' Understanding of Science and in Identifying Their Levels of Achievement.

    ERIC Educational Resources Information Center

    Liew, Chong-Wah; Treagust, David F.

    This study involves action research to explore the effectiveness of the Predict-Observe-Explain (POE) technique in diagnosing students' understanding of science and identifying their levels of achievement. A multidimensional interpretive framework is used to interpret students' understanding of science. The research methodology incorporated…

  12. Robust estimation of the proportion of treatment effect explained by surrogate marker information.

    PubMed

    Parast, Layla; McDermott, Mary M; Tian, Lu

    2016-05-10

    In randomized treatment studies where the primary outcome requires long follow-up of patients and/or expensive or invasive obtainment procedures, the availability of a surrogate marker that could be used to estimate the treatment effect and could potentially be observed earlier than the primary outcome would allow researchers to make conclusions regarding the treatment effect with less required follow-up time and resources. The Prentice criterion for a valid surrogate marker requires that a test for treatment effect on the surrogate marker also be a valid test for treatment effect on the primary outcome of interest. Based on this criterion, methods have been developed to define and estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on the surrogate marker. These methods aim to identify useful statistical surrogates that capture a large proportion of the treatment effect. However, current methods to estimate this proportion usually require restrictive model assumptions that may not hold in practice and thus may lead to biased estimates of this quantity. In this paper, we propose a nonparametric procedure to estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on a potential surrogate marker and extend this procedure to a setting with multiple surrogate markers. We compare our approach with previously proposed model-based approaches and propose a variance estimation procedure based on a perturbation-resampling method. Simulation studies demonstrate that the procedure performs well in finite samples and outperforms model-based procedures when the specified models are not correct. We illustrate our proposed procedure using a data set from a randomized study investigating a group-mediated cognitive behavioral intervention for peripheral artery disease participants. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26631934

  13. Markers predicting progression of human immunodeficiency virus-related disease.

    PubMed Central

    Tsoukas, C M; Bernard, N F

    1994-01-01

    Human immunodeficiency virus (HIV) interacts with the immune system throughout the course of infection. For most of the disease process, HIV activates the immune system, and the degree of activation can be assessed by measuring serum levels of molecules such as beta 2-microglobulin and neopterin, as well as other serum and cell surface phenotype markers. The levels of some of these markers correlate with clinical progression of HIV disease, and these markers may be useful as surrogate markers for development of clinical AIDS. Because the likelihood and timing of development of clinical AIDS following seroconversion, for any particular individual, are not readily predictable, the use of nonclinical disease markers has become critically important to patient management. Surrogate markers of HIV infection are, by definition, measurable traits that correlate with disease progression. An ideal marker should identify patients at highest risk of disease progression, provide information on how long an individual has been infected, help in staging HIV disease, predict development of opportunistic infections associated with AIDS, monitor the therapeutic efficacy of immunomodulating or antiviral treatments, and the easily quantifiable, reliable, clinically available, and affordable. This review examines the current state of knowledge and the role of surrogate markers in the natural history and treatment of HIV infection. The clinical usefulness of each marker is assessed with respect to the criteria outlined for the ideal surrogate marker for HIV disease progression. PMID:8118788

  14. Surrogate analysis and index developer (SAID) tool and real-time data dissemination utilities

    USGS Publications Warehouse

    Domanski, Marian M.; Straub, Timothy D.; Wood, Molly S.; Landers, Mark N.; Wall, Gary R.; Brady, Steven J.

    2015-01-01

    The use of acoustic and other parameters as surrogates for suspended-sediment concentrations (SSC) in rivers has been successful in multiple applications across the Nation. Critical to advancing the operational use of surrogates are tools to process and evaluate the data along with the subsequent development of regression models from which real-time sediment concentrations can be made available to the public. Recent developments in both areas are having an immediate impact on surrogate research, and on surrogate monitoring sites currently in operation. The Surrogate Analysis and Index Developer (SAID) standalone tool, under development by the U.S. Geological Survey (USGS), assists in the creation of regression models that relate response and explanatory variables by providing visual and quantitative diagnostics to the user. SAID also processes acoustic parameters to be used as explanatory variables for suspended-sediment concentrations. The sediment acoustic method utilizes acoustic parameters from fixed-mount stationary equipment. The background theory and method used by the tool have been described in recent publications, and the tool also serves to support sediment-acoustic-index methods being drafted by the multi-agency Sediment Acoustic Leadership Team (SALT), and other surrogate guidelines like USGS Techniques and Methods 3-C4 for turbidity and SSC. The regression models in SAID can be used in utilities that have been developed to work with the USGS National Water Information System (NWIS) and for the USGS National Real-Time Water Quality (NRTWQ) Web site. The real-time dissemination of predicted SSC and prediction intervals for each time step has substantial potential to improve understanding of sediment-related water-quality and associated engineering and ecological management decisions.

  15. A rank-based transcriptional signature for predicting relapse risk of stage II colorectal cancer identified with proper data sources

    PubMed Central

    Zhao, Wenyuan; Chen, Beibei; Guo, Xin; Wang, Ruiping; Chang, Zhiqiang; Dong, Yu; Song, Kai; Wang, Wen; Qi, Lishuang; Gu, Yunyan; Wang, Chenguang; Yang, Da; Guo, Zheng

    2016-01-01

    The irreproducibility problem seriously hinders the studies on transcriptional signatures for predicting relapse risk of early stage colorectal cancer (CRC) patients. Through reviewing recently published 34 literatures for the development of CRC prognostic signatures based on gene expression profiles, we revealed a surprising phenomenon that 33 of these studies analyzed CRC samples with and without adjuvant chemotherapy together in the training and/or validation datasets. This data misuse problem could be partially attributed to the unclear and incomplete data annotation in public data sources. Furthermore, all the signatures proposed by these studies were based on risk scores summarized from gene expression levels, which are sensitive to experimental batch effects and risk compositions of the samples analyzed together. To avoid the above-mentioned problems, we carefully selected three qualified large datasets to develop and validate a signature consisting of three pairs of genes. The within-sample relative expression orderings of these gene pairs could robustly predict relapse risk of stage II CRC samples assessed in different laboratories. The transcriptional and functional analyses provided clear evidence that the high risk patients predicted by the proposed signature represent patients with micro-metastases. PMID:26967049

  16. Circulating Tumor Cell Biomarker Panel As an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

    Scher, Howard I.; Heller, Glenn; Molina, Arturo; Attard, Gerhardt; Danila, Daniel C.; Jia, Xiaoyu; Peng, Weimin; Sandhu, Shahneen K.; Olmos, David; Riisnaes, Ruth; McCormack, Robert; Burzykowski, Tomasz; Kheoh, Thian; Fleisher, Martin; Buyse, Marc; de Bono, Johann S.

    2015-01-01

    Purpose Trials in castration-resistant prostate cancer (CRPC) need new clinical end points that are valid surrogates for survival. We evaluated circulating tumor cell (CTC) enumeration as a surrogate outcome measure. Patients and Methods Examining CTCs alone and in combination with other biomarkers as a surrogate for overall survival was a secondary objective of COU-AA-301, a multinational, randomized, double-blind phase III trial of abiraterone acetate plus prednisone versus prednisone alone in patients with metastatic CRPC previously treated with docetaxel. The biomarkers were measured at baseline and 4, 8, and 12 weeks, with 12 weeks being the primary measure of interest. The Prentice criteria were applied to test candidate biomarkers as surrogates for overall survival at the individual-patient level. Results A biomarker panel using CTC count and lactate dehydrogenase (LDH) level was shown to satisfy the four Prentice criteria for individual-level surrogacy. Twelve-week surrogate biomarker data were available for 711 patients. The abiraterone acetate plus prednisone and prednisone-alone groups demonstrated a significant survival difference (P = .034); surrogate distribution at 12 weeks differed by treatment (P < .001); the discriminatory power of the surrogate to predict mortality was high (weighted c-index, 0.81); and adding the surrogate to the model eliminated the treatment effect on survival. Overall, 2-year survival of patients with CTCs < 5 (low risk) versus patients with CTCs ≥ 5 cells/7.5 mL of blood and LDH > 250 U/L (high risk) at 12 weeks was 46% and 2%, respectively. Conclusion A biomarker panel containing CTC number and LDH level was shown to be a surrogate for survival at the individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone alone for patients with metastatic CRPC. Additional trials are ongoing to validate the findings. PMID:25800753

  17. Reversible Bending Fatigue Testing on Zry-4 Surrogate Rods

    SciTech Connect

    Wang, Jy-An John; Wang, Hong; Bevard, Bruce Balkcom; Howard, Rob L

    2014-01-01

    Testing high-burnup spent nuclear fuel (SNF) presents many challenges in areas such as specimen preparation, specimen installation, mechanical loading, load control, measurements, data acquisition, and specimen disposal because these tasks are complicated by the radioactivity of the test specimens. Research and comparison studies conducted at Oak Ridge National Laboratory (ORNL) resulted in a new concept in 2010 for a U-frame testing setup on which to perform hot-cell reversible bending fatigue testing. Subsequently, the three-dimensional finite element analysis and the engineering design of components were completed. In 2013 the ORNL team finalized the upgrade of the U-frame testing setup and the integration of the U-frame setup into a Bose dual linear motor test bench to develop a cyclic integrated reversible-bending fatigue tester (CIRFT). A final check was conducted on the CIRFT test system in August 2013, and the CIRFT was installed in the hot cell in September 2013 to evaluate both the static and dynamic mechanical response of SNF rods under simulated loads. The fatigue responses of Zircaloy-4 (Zry-4) cladding and the role of pellet pellet and pellet clad interactions are critical to SNF vibration integrity, but such data are not available due to the unavailability of an effective testing system. While the deployment of the developed CIRFT test system in a hot cell will provide the opportunity to generate the data, the use of a surrogate rod has proven quite effective in identifying the underlying deformation mechanism of an SNF composite rod under an equivalent loading condition. This paper presents the experimental results of using surrogate rods under CIRFT reversible cyclic loading. Specifically, monotonic and cyclic bending tests were conducted on surrogate rods made of a Zry-4 tube and alumina pellet inserts, both with and without an epoxy bond.

  18. Identifying Dyslexia in Adults: An Iterative Method Using the Predictive Value of Item Scores and Self-Report Questions

    ERIC Educational Resources Information Center

    Tamboer, Peter; Vorst, Harrie C. M.; Oort, Frans J.

    2014-01-01

    Methods for identifying dyslexia in adults vary widely between studies. Researchers have to decide how many tests to use, which tests are considered to be the most reliable, and how to determine cut-off scores. The aim of this study was to develop an objective and powerful method for diagnosing dyslexia. We took various methodological measures,…

  19. Identifying preoperative language tracts and predicting postoperative functional recovery using HARDI q-ball fiber tractography in patients with gliomas.

    PubMed

    Caverzasi, Eduardo; Hervey-Jumper, Shawn L; Jordan, Kesshi M; Lobach, Iryna V; Li, Jing; Panara, Valentina; Racine, Caroline A; Sankaranarayanan, Vanitha; Amirbekian, Bagrat; Papinutto, Nico; Berger, Mitchel S; Henry, Roland G

    2016-07-01

    OBJECT Diffusion MRI has uniquely enabled in vivo delineation of white matter tracts, which has been applied to the segmentation of eloquent pathways for intraoperative mapping. The last decade has also seen the development from earlier diffusion tensor models to higher-order models, which take advantage of high angular resolution diffusion-weighted imaging (HARDI) techniques. However, these advanced methods have not been widely implemented for routine preoperative and intraoperative mapping. The authors report on the application of residual bootstrap q-ball fiber tracking for routine mapping of potentially functional language pathways, the development of a system for rating tract injury to evaluate the impact on clinically assessed language function, and initial results predicting long-term language deficits following glioma resection. METHODS The authors have developed methods for the segmentation of 8 putative language pathways including dorsal phonological pathways and ventral semantic streams using residual bootstrap q-ball fiber tracking. Furthermore, they have implemented clinically feasible preoperative acquisition and processing of HARDI data to delineate these pathways for neurosurgical application. They have also developed a rating scale based on the altered fiber tract density to estimate the degree of pathway injury, applying these ratings to a subset of 35 patients with pre- and postoperative fiber tracking. The relationships between specific pathways and clinical language deficits were assessed to determine which pathways are predictive of long-term language deficits following surgery. RESULTS This tracking methodology has been routinely implemented for preoperative mapping in patients with brain gliomas who have undergone awake brain tumor resection at the University of California, San Francisco (more than 300 patients to date). In this particular study the authors investigated the white matter structure status and language correlation in a

  20. Endoscopic ulcers as a surrogate marker of NSAID-induced mucosal damage

    PubMed Central

    2013-01-01

    The characteristic of a biomarker that makes it a useful surrogate is the ability to identify a high risk of clinically important benefits or harms occurring in the future. A number of definitions or descriptions of surrogate definition have been put forward. Most recently the Institute of Medicine of the National Academy of Sciences in the USA has put forward an evaluation scheme for biomarkers, looking at validation (assay performance), qualification (assessment of evidence), and utilisation (the context in which the surrogate is to be used). This paper examines the example of endoscopy as a surrogate marker of NSAID-induced mucosal damage using the Institute of Medicine criteria. The article finds extensive evidence that the detection of endoscopic ulcers is a valid marker. The process of qualification documents abundant evidence showing that endoscopic ulcers and serious upper gastrointestinal damage are influenced in the same direction and much the same magnitude by a variety of risk factors and interventions. Criticisms of validation and qualification for endoscopic ulcers have been examined, and dismissed. Context is the key, and in the context of serious NSAID-induced upper gastrointestinal harm, endoscopic ulcers represent a useful surrogate. Generalisability beyond this context is not considered. PMID:24267380

  1. Five Cryptic Species in the Amazonian Catfish Centromochlus existimatus Identified Based on Biogeographic Predictions and Genetic Data

    PubMed Central

    Cooke, Georgina M.; Chao, Ning L.; Beheregaray, Luciano B.

    2012-01-01

    Accurately quantifying biodiversity is fundamental for both evolutionary theory and conservation strategies. DNA-based studies are exposing high cryptic diversity irrespective of taxonomic group or environmental setting, and increasing the ever-growing estimates of global biodiversity. This has severe implications for under-sampled and species-rich tropical regions, such as the Amazon Basin. We used biogeographic predictions derived from geomorphological history and contemporary hydrochemical and genetic data to examine cryptic diversity in the Amazonian driftwood catfish Centromochlus existimatus. Using both nuclear and mitochondrial DNA markers, five deeply divergent cryptic lineages are reported, for which at least three are sympatric in distribution. These lineages appear relatively old, with divergence times dating back to middle Miocene. Diversification events appear to be chronologically associated with the formation of the modern Amazon River system, and perhaps influenced by hydrochemical gradients between tributaries. The cause of apparent morphological stasis in the C. existimatus species complex is speculated within the context of hydrochemistry and non-visual mating cues and a full taxonomic revision is recommended. Our findings suggest that the diversity of Amazonian ichthyofauna is vastly underestimated and highlight the relevance of biogeographic predictions to guide sampling efforts in ecologically complex and under-studied ecosystems. PMID:23144977

  2. Five cryptic species in the amazonian catfish Centromochlus existimatus identified based on biogeographic predictions and genetic data.

    PubMed

    Cooke, Georgina M; Chao, Ning L; Beheregaray, Luciano B

    2012-01-01

    Accurately quantifying biodiversity is fundamental for both evolutionary theory and conservation strategies. DNA-based studies are exposing high cryptic diversity irrespective of taxonomic group or environmental setting, and increasing the ever-growing estimates of global biodiversity. This has severe implications for under-sampled and species-rich tropical regions, such as the Amazon Basin. We used biogeographic predictions derived from geomorphological history and contemporary hydrochemical and genetic data to examine cryptic diversity in the Amazonian driftwood catfish Centromochlus existimatus. Using both nuclear and mitochondrial DNA markers, five deeply divergent cryptic lineages are reported, for which at least three are sympatric in distribution. These lineages appear relatively old, with divergence times dating back to middle Miocene. Diversification events appear to be chronologically associated with the formation of the modern Amazon River system, and perhaps influenced by hydrochemical gradients between tributaries. The cause of apparent morphological stasis in the C. existimatus species complex is speculated within the context of hydrochemistry and non-visual mating cues and a full taxonomic revision is recommended. Our findings suggest that the diversity of Amazonian ichthyofauna is vastly underestimated and highlight the relevance of biogeographic predictions to guide sampling efforts in ecologically complex and under-studied ecosystems. PMID:23144977

  3. Identifying sensitive areas of adaptive observations for prediction of the Kuroshio large meander using a shallow-water model

    NASA Astrophysics Data System (ADS)

    Zou, Guang'an; Wang, Qiang; Mu, Mu

    2016-09-01

    Sensitive areas for prediction of the Kuroshio large meander using a 1.5-layer, shallow-water ocean model were investigated using the conditional nonlinear optimal perturbation (CNOP) and first singular vector (FSV) methods. A series of sensitivity experiments were designed to test the sensitivity of sensitive areas within the numerical model. The following results were obtained: (1) the eff ect of initial CNOP and FSV patterns in their sensitive areas is greater than that of the same patterns in randomly selected areas, with the eff ect of the initial CNOP patterns in CNOP sensitive areas being the greatest; (2) both CNOP- and FSV-type initial errors grow more quickly than random errors; (3) the eff ect of random errors superimposed on the sensitive areas is greater than that of random errors introduced into randomly selected areas, and initial errors in the CNOP sensitive areas have greater eff ects on final forecasts. These results reveal that the sensitive areas determined using the CNOP are more sensitive than those of FSV and other randomly selected areas. In addition, ideal hindcasting experiments were conducted to examine the validity of the sensitive areas. The results indicate that reduction (or elimination) of CNOP-type errors in CNOP sensitive areas at the initial time has a greater forecast benefit than the reduction (or elimination) of FSV-type errors in FSV sensitive areas. These results suggest that the CNOP method is suitable for determining sensitive areas in the prediction of the Kuroshio large-meander path.

  4. A predicted T4 secretion system and conserved DNA-repeats identified in a subset of related Arthrobacter plasmids.

    PubMed

    Mihăşan, Marius; Brandsch, Roderich

    2016-10-01

    BLAST analysis of pAO1 ORFs of Arthrobacter nicotinovorans revealed 12 ORFs, including the ORF of a transcriptional regulator, predicted to encode the components of a T4-secretion system involved in bacterial conjugation. These ORFs were conserved and showed synteny among 14 Arthrobacter plasmids. A DNA repeat of about 370 nucleotides was found to be present 5' to the pAO1 ORFs of DUF4192-, DprA- and ParB-like proteins. Similar repeats were present in identical positions on 12 additional Arthrobacter plasmids. The DNA repeats on a particular plasmid are highly identical duplications. The DNA repeats contain alternating GC and AT reach sequences, potential protein DNA-binding sites and purine reach stretches. The sequences end with 5'ATG.AAC3' which results in the amino terminal sequence methionine (M) and asparagine (N) for all predicted DprA, DUF4192 and ParB proteins. The presences of conserved ORFs of a T4-secretion system and of similar DNA repeats suggest that these Arthrobacter plasmids are related and evolved from a common ancestor. The functional significance of the DNA repeats in a coordinated common mechanism of regulation of expression of the dprA-(involved in natural competence), parB- (involved in plasmid partitioning) and duf4192- (unknown function in plasmid life cycle) genes remains to be established. PMID:27524651

  5. RARE Grant- Atmospheric Dry Deposition: Quantification of Mercury and Nutrients using Novel Surrogate Surface Collector Techniques

    EPA Science Inventory

    This study will quantify the daily surrogate surface dry deposition of mercury and nutrient species, and evaluate its relative importance to wet deposition at two sites in Florida over a two-year period. It will identify the major sources contributing to the observed mercury and...

  6. Validating (d,p gamma) as a Surrogate for Neutron Capture

    SciTech Connect

    Ratkiewicz, A.; Cizewski, J.A.; Pain, S.D.; Adekola, A.S.; Burke, J.T.; Casperson, R.J.; Fotiades, N.; McCleskey, M.; Burcher, S.; Shand, C.M.; Austin, R.A.E.; Baugher, T.; Carpenter, M.P.; Devlin, M.; Escher, J.E.; Hardy, S.; Hatarik, R.; Howard, M.E.; Hughes, R.O.; Jones, K.L.; Kozub, R.L.; Lister, C.J.; Manning, B.; O’Donnell, J.M.; Peters, W.A.; Ross, T.J.; Scielzo, N.D.; Seweryniak, D.; Zhu, S.; Schwengner, R.; Zuber, K.

    2015-05-28

    The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate for (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions.

  7. Validating (d,p gamma) as a Surrogate for Neutron Capture

    DOE PAGESBeta

    Ratkiewicz, A.; Cizewski, J.A.; Pain, S.D.; Adekola, A.S.; Burke, J.T.; Casperson, R.J.; Fotiades, N.; McCleskey, M.; Burcher, S.; Shand, C.M.; et al

    2015-05-28

    The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate formore » (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions.« less

  8. Validating (d,pγ) as a surrogate for neutron capture

    SciTech Connect

    Ratkiewicz, A.; Cizewski, J. A.; Pain, S. D.; Adekola, A. S.; Burke, J. T.; Casperson, R. J.; Fotiadis, Nikolaos; McCleskey, M.; Burcher, S.; Shand, C. M; Austin, R. A. E.; Baugher, T.; Carpenter, M. P.; Devlin, Matthew James; Escher, J. E.; Hardy, S.; Hatarik, R.; Howard, M. E.; Hughes, R. O.; Jones, K. L.; Kozub, R. L.; Lister, C. J.; Manning, B.; O'Donnell, John M.; Peters, W. A.; Ross, T. J.; Scielzo, N. D.; Seweryniak, D.; Zhu, S.

    2015-02-13

    The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate for (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions.

  9. Validating (d,pγ) as a Surrogate for Neutron Capture

    NASA Astrophysics Data System (ADS)

    Ratkiewicz, A.; Cizewski, J. A.; Pain, S. D.; Adekola, A. S.; Burke, J. T.; Casperson, R. J.; Fotiades, N.; McCleskey, M.; Burcher, S.; Shand, C. M.; Austin, R. A. E.; Baugher, T.; Carpenter, M. P.; Devlin, M.; Escher, J. E.; Hardy, S.; Hatarik, R.; Howard, M. E.; Hughes, R. O.; Jones, K. L.; Kozub, R. L.; Lister, C. J.; Manning, B.; O'Donnell, J. M.; Peters, W. A.; Ross, T. J.; Scielzo, N. D.; Seweryniak, D.; Zhu, S.

    2015-05-01

    The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate for (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions.

  10. Methodology and application of surrogate plant PRA analysis to the Rancho Seco Power Plant: Final report

    SciTech Connect

    Gore, B.F.; Huenefeld, J.C.

    1987-07-01

    This report presents the development and the first application of generic probabilistic risk assessment (PRA) information for identifying systems and components important to public risk at nuclear power plants lacking plant-specific PRAs. A methodology is presented for using the results of PRAs for similar (surrogate) plants, along with plant-specific information about the plant of interest and the surrogate plants, to infer important failure modes for systems of the plant of interest. This methodology, and the rationale on which it is based, is presented in the context of its application to the Rancho Seco plant. The Rancho Seco plant has been analyzed using PRA information from two surrogate plants. This analysis has been used to guide development of considerable plant-specific information about Rancho Seco systems and components important to minimizing public risk, which is also presented herein.

  11. A surrogate-model-based identification of fractional viscoelastic constitutive parameters

    NASA Astrophysics Data System (ADS)

    Zhang, Guoqing; Yang, Haitian; Xu, Yongsheng

    2015-02-01

    In order to reduce the computational expense, a Kriging surrogate model is developed as an approximation of a numerical model based on FEM (finite element method) and FDM (finite difference method) to solve direct fractional viscoelastic problems and then is combined with a gridding-partition-based continuous ant colony algorithm to identify constitutive parameters of fractional viscoelastic materials. Three kinds of modeling strategies are presented to generate the Kriging surrogate model, that is, global modeling, piecewise modeling, and reduced modeling. Two numerical examples are given to illustrate the proposed approach in terms of computing accuracy and expense. The utilization of Kriging surrogate model not only can provide a sufficient computing accuracy, but also can significantly reduce the computational cost in solving inverse fractional viscoelastic problems. In addition, regional inhomogeneity and impact of noisy data are taken into account.

  12. Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

    SciTech Connect

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Tropsha, Alexander

    2015-04-15

    Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

  13. The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes

    PubMed Central

    Guo, Jing; Huang, Fengming; Liu, Jun; Chen, Yu; Wang, Wei; Cao, Bin; Zou, Zhen; Liu, Song; Pan, Jingcao; Bao, Changjun; Zeng, Mei; Xiao, Haixia; Gao, Hainv; Yang, Shigui; Zhao, Yan; Liu, Qiang; Zhou, Huandi; Zhu, Jingdong; Liu, Xiaoli; Liang, Weifeng; Yang, Yida; Zheng, Shufa; Yang, Jiezuan; Diao, Hongyan; Su, Kunkai; Shao, Li; Cao, Hongcui; Wu, Ying; Zhao, Min; Tan, Shuguang; Li, Hui; Xu, Xiaoqing; Wang, Chunmei; Zhang, Jianmin; Wang, Li; Wang, Jianwei; Xu, Jun; Li, Dangsheng; Zhong, Nanshan; Cao, Xuetao; Gao, George F.; Li, Lanjuan; Jiang, Chengyu

    2015-01-01

    The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor. PMID:26028236

  14. The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes.

    PubMed

    Guo, Jing; Huang, Fengming; Liu, Jun; Chen, Yu; Wang, Wei; Cao, Bin; Zou, Zhen; Liu, Song; Pan, Jingcao; Bao, Changjun; Zeng, Mei; Xiao, Haixia; Gao, Hainv; Yang, Shigui; Zhao, Yan; Liu, Qiang; Zhou, Huandi; Zhu, Jingdong; Liu, Xiaoli; Liang, Weifeng; Yang, Yida; Zheng, Shufa; Yang, Jiezuan; Diao, Hongyan; Su, Kunkai; Shao, Li; Cao, Hongcui; Wu, Ying; Zhao, Min; Tan, Shuguang; Li, Hui; Xu, Xiaoqing; Wang, Chunmei; Zhang, Jianmin; Wang, Li; Wang, Jianwei; Xu, Jun; Li, Dangsheng; Zhong, Nanshan; Cao, Xuetao; Gao, George F; Li, Lanjuan; Jiang, Chengyu

    2015-01-01

    The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor. PMID:26028236

  15. Identifying structural elements needed for development of a predictive life-history model for pallid and shovelnose sturgeons

    USGS Publications Warehouse

    Wildhaber, Mark L.; DeLonay, A.J.; Papoulias, D.M.; Galat, D.L.; Jacobson, R.B.; Simpkins, D.G.; Braaten, P.J.; Korschgen, C.E.; Mac, M.J.

    2011-01-01

    Intensive management of the Missouri and Mississippi Rivers has resulted in dramatic changes to the river systems and their biota. These changes have been implicated in the decline of the pallid sturgeon (Scaphirhynchus albus), which has been listed as a United States federal endangered species. The sympatric shovelnose sturgeon (S. platorynchus) is more common and widespread but has also been in decline. The decline of pallid sturgeon is considered symptomatic of poor reproductive success and low or no recruitment. In order to organize information about these species and provide a basis for future development of a predictive model to help guide recovery efforts, we present an expert-vetted, conceptual life-history framework that incorporates the factors that affect reproduction, growth, and survival of shovelnose and pallid sturgeons.

  16. Binary black hole simulations for surrogate modeling

    NASA Astrophysics Data System (ADS)

    Hemberger, Daniel; SXS Collaboration

    2016-03-01

    Analytic or data-driven models of binary black hole coalescences are used to densely cover the full parameter space, because it is computationally infeasible to do so using numerical relativity (NR). However, these models still need input from NR, either for calibration, or because the model is agnostic to the underlying physics. We use the Spectral Einstein Code (SpEC) to provide a large number of simulations to aid the construction of a NR surrogate model in a 5-dimensional subset of the parameter space. I will present an analysis of the simulations that were used to construct the surrogate model. I will also describe the infrastructure that was needed to efficiently perform a large number of simulations across many computational resources.

  17. A microbiological surrogate for evaluating treatment efficiency

    SciTech Connect

    Rice, E.W.; Fox, K.W.; Miltner, R.J.

    1995-10-01

    In this study we report on the use of a microbial surrogate system which can be used to evaluate the efficiency of various unit processes used in drinking water treatment for the removal of microbial contaminants. The proposed procedure uses Gram-positive, mesophilic, aerobic spore-forming bacteria as the surrogate organisms. These bacteria do not pose a public health threat and are naturally occurring in most surface water supplies. The aerobic spore-formers are easy to culture and are present throughout the treatment train. This group of organisms consists primarily of species of the genus Bacillus. These organisms form endospores which are ellipsoidal to spherical in shape and measure on average approximately 0.5 X 1.0 X 1.5 micrometers, and are environmentally resistant. Like pathogenic Giardia cysts and Cryptosporidium oocysts endospores of aerobic bacilli may be found far into the treatment train.

  18. Methodology for Formulating Diesel Surrogate Fuels with Accurate Compositional, Ignition-Quality, and Volatility Characteristics

    SciTech Connect

    Mueller, C. J.; Cannella, W. J.; Bruno, T. J.; Bunting, B.; Dettman, H. D.; Franz, J. A.; Huber, M. L.; Natarajan, M.; Pitz, W. J.; Ratcliff, M. A.; Wright, K.

    2012-06-21

    In this study, a novel approach was developed to formulate surrogate fuels having characteristics that are representative of diesel fuels produced from real-world refinery streams. Because diesel fuels typically consist of hundreds of compounds, it is difficult to conclusively determine the effects of fuel composition on combustion properties. Surrogate fuels, being simpler representations of these practical fuels, are of interest because they can provide a better understanding of fundamental fuel-composition and property effects on combustion and emissions-formation processes in internal-combustion engines. In addition, the application of surrogate fuels in numerical simulations with accurate vaporization, mixing, and combustion models could revolutionize future engine designs by enabling computational optimization for evolving real fuels. Dependable computational design would not only improve engine function, it would do so at significant cost savings relative to current optimization strategies that rely on physical testing of hardware prototypes. The approach in this study utilized the state-of-the-art techniques of {sup 13}C and {sup 1}H nuclear magnetic resonance spectroscopy and the advanced distillation curve to characterize fuel composition and volatility, respectively. The ignition quality was quantified by the derived cetane number. Two well-characterized, ultra-low-sulfur No.2 diesel reference fuels produced from refinery streams were used as target fuels: a 2007 emissions certification fuel and a Coordinating Research Council (CRC) Fuels for Advanced Combustion Engines (FACE) diesel fuel. A surrogate was created for each target fuel by blending eight pure compounds. The known carbon bond types within the pure compounds, as well as models for the ignition qualities and volatilities of their mixtures, were used in a multiproperty regression algorithm to determine optimal surrogate formulations. The predicted and measured surrogate-fuel properties were

  19. A Predictive Coexpression Network Identifies Novel Genes Controlling the Seed-to-Seedling Phase Transition in Arabidopsis thaliana1[OPEN

    PubMed Central

    Silva, Anderson Tadeu; Ribone, Pamela A.

    2016-01-01

    The transition from a quiescent dry seed to an actively growing photoautotrophic seedling is a complex and crucial trait for plant propagation. This study provides a detailed description of global gene expression in seven successive developmental stages of seedling establishment in Arabidopsis (Arabidopsis thaliana). Using the transcriptome signature from these developmental stages, we obtained a coexpression gene network that highlights interactions between known regulators of the seed-to-seedling transition and predicts the functions of uncharacterized genes in seedling establishment. The coexpressed gene data sets together with the transcriptional module indicate biological functions related to seedling establishment. Characterization of the homeodomain leucine zipper I transcription factor AtHB13, which is expressed during the seed-to-seedling transition, demonstrated that this gene regulates some of the network nodes and affects late seedling establishment. Knockout mutants for athb13 showed increased primary root length as compared with wild-type (Columbia-0) seedlings, suggesting that this transcription factor is a negative regulator of early root growth, possibly repressing cell division and/or cell elongation or the length of time that cells elongate. The signal transduction pathways present during the early phases of the seed-to-seedling transition anticipate the control of important events for a vigorous seedling, such as root growth. This study demonstrates that a gene coexpression network together with transcriptional modules can provide insights that are not derived from comparative transcript profiling alone. PMID:26888061

  20. Material design using surrogate optimization algorithm

    NASA Astrophysics Data System (ADS)

    Khadke, Kunal R.

    Nanocomposite ceramics have been widely studied in order to tailor desired properties at high temperatures. Methodologies for development of material design are still under effect . While finite element modeling (FEM) provides significant insight on material behavior, few design researchers have addressed the design paradox that accompanies this rapid design space expansion. A surrogate optimization model management framework has been proposed to make this design process tractable. In the surrogate optimization material design tool, the analysis cost is reduced by performing simulations on the surrogate model instead of high density finite element model. The methodology is incorporated to find the optimal number of silicon carbide (SiC) particles, in a silicon-nitride Si3N 4 composite with maximum fracture energy [2]. Along with a deterministic optimization algorithm, model uncertainties have also been considered with the use of robust design optimization (RDO) method ensuring a design of minimum sensitivity to changes in the parameters. These methodologies applied to nanocomposites design have a signicant impact on cost and design cycle time reduced.

  1. Surrogate formulations for thermal treatment of low-level mixed waste. Part 1: Radiological surrogates

    SciTech Connect

    Stockdale, J.A.D.; Bostick, W.D.; Hoffmann, D.P.; Lee, H.T.

    1994-01-01

    The evaluation and comparison of proposed thermal treatment systems for mixed wastes can be expedited by tests in which the radioactive components of the wastes are replaced by surrogate materials chosen to mimic, as far as is possible, the chemical and physical properties of the radioactive materials of concern. In this work, sponsored by the Mixed Waste Integrated Project of the US Department of Energy, the authors have examined reported experience with such surrogates and suggest a simplified standard list of materials for use in tests of thermal treatment systems. The chief radioactive nuclides of concern in the treatment of mixed wastes are {sup 239}Pu, {sup 238}U, {sup 235}U, {sup 137}Cs, {sup 103}Ru, {sup 99}Tc, and {sup 90}Sr. These nuclides are largely by-products of uranium enrichment, reactor fuel reprocessing, and weapons program activities. Cs, Ru, and Sr all have stable isotopes that can be used as perfect surrogates for the radioactive forms. Technetium exists only in radioactive form, as do plutonium and uranium. If one wishes to preclude radioactive contamination of the thermal treatment system under trial burn, surrogate elements must be chosen for these three. For technetium, the authors suggest the use of natural ruthenium, and for both plutonium and uranium, they recommend cerium. The seven radionuclides listed can therefore be simulated by a surrogate package containing stable isotopes of ruthenium, strontium, cesium, and cerium.

  2. Topology assessment, G protein-coupled receptor (GPCR) prediction, and in vivo interaction assays to identify plant candidate GPCRs.

    PubMed

    Gookin, Timothy E; Bendtsen, Jannick D

    2013-01-01

    Genomic sequencing has provided a vast resource for identifying interesting genes, but often an exact "gene-of-interest" is unknown and is only described as putatively present in a genome by an observed phenotype, or by the known presence of a conserved signaling cascade, such as that facilitated by the heterotrimeric G-protein. The low sequence similarity of G protein-coupled receptors (GPCRs) and the absence of a known ligand with an associated high-throughput screening system in plants hampers their identification by simple BLAST queries or brute force experimental assays. Combinatorial bioinformatic analysis is useful in that it can reduce a large pool of possible candidates to a number manageable by medium or even low-throughput methods. Here we describe a method for the bioinformatic identification of candidate GPCRs from whole proteomes and their subsequent in vivo analysis for G-protein coupling using a membrane based yeast two-hybrid variant (Gookin et al., Genome Biol 9:R120, 2008). Rather than present the bioinformatic process in a format requiring scripts or computer programming knowledge, we describe procedures here in a simple, biologist-friendly outline that only utilizes the basic syntax of regular expressions. PMID:23913030

  3. Critical review of norovirus surrogates in food safety research: rationale for considering volunteer studies.

    PubMed

    Richards, Gary P

    2012-03-01

    The inability to propagate human norovirus (NoV) or to clearly differentiate infectious from noninfectious virus particles has led to the use of surrogate viruses, like feline calicivirus (FCV) and murine norovirus-1 (MNV), which are propagatable in cell culture. The use of surrogates is predicated on the assumption that they generally mimic the viruses they represent; however, studies are proving this concept invalid. In direct comparisons between FCV and MNV, their susceptibility to temperatures, environmental and food processing conditions, and disinfectants are dramatically different. Differences have also been noted between the inactivation of NoV and its surrogates, thus questioning the validity of surrogates. Considerable research funding is provided globally each year to conduct surrogate studies on NoVs; however, there is little demonstrated benefit derived from these studies in regard to the development of virus inactivation techniques or food processing strategies. Human challenge studies are needed to determine which processing techniques are effective in reducing NoVs in foods. A major obstacle to clinical trials on NoVs is the perception that such trials are too costly and risky, but in reality, there is far more cost and risk in allowing millions of unsuspecting consumers to contract NoV illness each year, when practical interventions are only a few volunteer studies away. A number of clinical trials have been conducted, providing important insights into NoV inactivation. A shift in research priorities from surrogate research to volunteer studies is essential if we are to identify realistic, practical, and scientifically valid processing approaches to improve food safety. PMID:22408689

  4. Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds.

    PubMed

    Alves, Vinicius M; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H; Tropsha, Alexander

    2015-04-15

    Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71-88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. PMID:25560674

  5. Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

    PubMed Central

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

    2015-01-01

    Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using random forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers were 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the ScoreCard database of possible skin or sense organ toxicants as primary candidates for experimental validation. PMID:25560674

  6. Family Matters: Effects of Birth Order, Culture, and Family Dynamics on Surrogate Decision Making

    PubMed Central

    Su, Christopher T.; McMahan, Ryan D.; Williams, Brie A.; Sharma, Rashmi K.; Sudore, Rebecca L.

    2014-01-01

    Cultural attitudes about medical decision making and filial expectations may lead some surrogates to experience stress and family conflict. Thirteen focus groups with racially and ethnically diverse English- and Spanish-speakers from county and Veterans hospitals, senior centers, and cancer support groups were conducted to describe participants’ experiences making serious or end-of-life decisions for others. Filial expectations and family dynamics related to birth order and surrogate decision making were explored using qualitative, thematic content analysis and overarching themes from focus group transcripts were identified. The mean age of the 69 participants was 69 years ± 14 and 29% were African American, 26% were White, 26% were Asian/Pacific Islander, and 19% were Latino. Seventy percent of participants engaged in unprompted discussions about birth order and family dynamics. Six subthemes were identified within 3 overarching categories of communication, emotion, and conflict: Communication – (1) unspoken expectations and (2) discussion of death as taboo; Emotion – (3) emotional stress and (4) feelings of loneliness; and Conflict – (5) family conflict and (6) potential solutions to prevent conflict. These findings suggest that birth order and family dynamics can have profound effects on surrogate stress and coping. Clinicians should be aware of potential unspoken filial expectations for firstborns and help facilitate communication between the patient, surrogate, and extended family to reduce stress and conflict. PMID:24383459

  7. Predicting and analyzing DNA-binding domains using a systematic approach to identifying a set of informative physicochemical and biochemical properties

    PubMed Central

    2011-01-01

    Background Existing methods of predicting DNA-binding proteins used valuable features of physicochemical properties to design support vector machine (SVM) based classifiers. Generally, selection of physicochemical properties and determination of their corresponding feature vectors rely mainly on known properties of binding mechanism and experience of designers. However, there exists a troublesome problem for designers that some different physicochemical properties have similar vectors of representing 20 amino acids and some closely related physicochemical properties have dissimilar vectors. Results This study proposes a systematic approach (named Auto-IDPCPs) to automatically identify a set of physicochemical and biochemical properties in the AAindex database to design SVM-based classifiers for predicting and analyzing DNA-binding domains/proteins. Auto-IDPCPs consists of 1) clustering 531 amino acid indices in AAindex into 20 clusters using a fuzzy c-means algorithm, 2) utilizing an efficient genetic algorithm based optimization method IBCGA to select an informative feature set of size m to represent sequences, and 3) analyzing the selected features to identify related physicochemical properties which may affect the binding mechanism of DNA-binding domains/proteins. The proposed Auto-IDPCPs identified m=22 features of properties belonging to five clusters for predicting DNA-binding domains with a five-fold cross-validation accuracy of 87.12%, which is promising compared with the accuracy of 86.62% of the existing method PSSM-400. For predicting DNA-binding sequences, the accuracy of 75.50% was obtained using m=28 features, where PSSM-400 has an accuracy of 74.22%. Auto-IDPCPs and PSSM-400 have accuracies of 80.73% and 82.81%, respectively, applied to an independent test data set of DNA-binding domains. Some typical physicochemical properties discovered are hydrophobicity, secondary structure, charge, solvent accessibility, polarity, flexibility, normalized Van Der

  8. UQ -- Fast Surrogates Key to New Methodologies in an Operational and Research Volcanic Hazard Forecasting System

    NASA Astrophysics Data System (ADS)

    Hughes, C. G.; Stefanescu, R. E. R.; Patra, A. K.; Bursik, M. I.; Madankan, R.; Pouget, S.; Jones, M.; Singla, P.; Singh, T.; Pitman, E. B.; Morton, D.; Webley, P.

    2014-12-01

    As the decision to construct a hazard map is frequently precipitated by the sudden initiation of activity at a volcano that was previously considered dormant, timely completion of the map is imperative. This prohibits the calculation of probabilities through direct sampling of a numerical ash-transport and dispersion model. In developing a probabilistic forecast for ash cloud locations following an explosive volcanic eruption, we construct a number of possible meta-models (a model of the simulator) to act as fast surrogates for the time-expensive model. We will illustrate the new fast surrogates based on both polynomial chaos and multilevel sparse representations that have allowed us to conduct the Uncertainty Quantification (UQ) in a timely fashion. These surrogates allow orders of magnitude improvement in cost associated with UQ, and are likely to have a major impact in many related domains.This work will be part of an operational and research volcanic forecasting system (see the Webley et al companion presentation) moving towards using ensembles of eruption source parameters and Numerical Weather Predictions (NWPs), rather than single deterministic forecasts, to drive the ash cloud forecasting systems. This involves using an Ensemble Prediction System (EPS) as input to an ash transport and dispersion model, such as PUFF, to produce ash cloud predictions, which will be supported by a Decision Support System. Simulation ensembles with different input volcanic source parameters are intelligently chosen to predict the average and higher-order moments of the output correctly.

  9. The makings of a good human norovirus surrogate.

    PubMed

    Kniel, Kalmia E

    2014-02-01

    Norovirus is undoubtedly a leading cause of acute gastroenteritis. A large limitation to the study of human norovirus is the lack of consensus research using norovirus surrogates. Over two decades of research have included vast comparisons of norovirus surrogates within the Calicivirus family. A discussion on the continued use of norovirus surrogates includes use of surrogates to adequately assess environmental persistence and food preservation technologies. Choice of proper surrogate may be influenced by a myriad of issues, including ease of propagation, genetic similarities, and binding properties. While it remains impossible to routinely culture human norovirus in vitro the continued use of a variety of norovirus surrogates remains crucial to facilitate an understanding of norovirus in order to reduce the public health impact of the disease. PMID:24492067

  10. Dynamic role and importance of surrogate species for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

    PubMed

    Wach, Michael; Hellmich, Richard L; Layton, Raymond; Romeis, Jörg; Gadaleta, Patricia G

    2016-08-01

    Surrogate species have a long history of use in research and regulatory settings to understand the potentially harmful effects of toxic substances including pesticides. More recently, surrogate species have been used to evaluate the potential effects of proteins contained in genetically engineered insect resistant (GEIR) crops. Species commonly used in GEIR crop testing include beneficial organisms such as honeybees, arthropod predators, and parasitoids. The choice of appropriate surrogates is influenced by scientific factors such as the knowledge of the mode of action and the spectrum of activity as well as societal factors such as protection goals that assign value to certain ecosystem services such as pollination or pest control. The primary reasons for using surrogates include the inability to test all possible organisms, the restrictions on using certain organisms in testing (e.g., rare, threatened, or endangered species), and the ability to achieve greater sensitivity and statistical power by using laboratory testing of certain species. The acceptance of surrogate species data can allow results from one region to be applied or "transported" for use in another region. On the basis of over a decade of using surrogate species to evaluate potential effects of GEIR crops, it appears that the current surrogates have worked well to predict effects of GEIR crops that have been developed (Carstens et al. GM Crops Food 5:1-5, 2014), and it is expected that they should work well to predict effects of future GEIR crops based on similar technologies. PMID:26922585

  11. Recent Experimental Progress on Surrogate Reactions

    NASA Astrophysics Data System (ADS)

    Beausang, Cornelius

    2014-09-01

    Reactions on unstable nuclei are important in a wide variety of nuclear physics scenarios. Cross sections for neutron (or light charged particle) induced reactions on target nuclei spanning the chart of the nuclei are important for nuclear astrophysics (r-process, s-process rp- and p-processes etc.), for nuclear energy generation and for national security applications. Many such reactions occur on short-lived unstable nuclei. Even with the present generation of radioactive beam facilities, many such reactions are difficult, if not impossible, to measure directly. For these reactions, often the surrogate reaction technique provides the only option to provide some experimental guidance for the calculations. The experimental and theoretical techniques required are described in some detail in the recent review article by Escher et al.. Originally introduced in the 1970's the last decade has seen a resurgence of interest in the surrogate technique. Various ratio techniques, external, internal and hybrid, have been developed to minimize the effect of target contamination. In the actinide region, a large number of surrogate (n,f) cross sections have been measured. In general, these show agreement to within 5--10%, with directly measured (n,f) data where these data exist (benchmarking), for equivalent neutron energies ranging from ~100 keV up to tens of MeV. For (n, γ) reactions, measurements have been attempted for select nuclei in various mass regions (A ~ 90, 150 and 235) and for these the agreement with directly measured data is less good. The various experimental techniques employed will be described as well as the current state of the experimental data. Some future directions will be described. Reactions on unstable nuclei are important in a wide variety of nuclear physics scenarios. Cross sections for neutron (or light charged particle) induced reactions on target nuclei spanning the chart of the nuclei are important for nuclear astrophysics (r-process, s

  12. Correlation of lung tumor motion with external surrogate indicators of respiration

    SciTech Connect

    Hoisak, Jeremy D.P.; Sixel, Katharina E. . E-mail: Katharina.Sixel@sw.ca; Tirona, Romeo; Cheung, Patrick; Pignol, Jean-Philippe

    2004-11-15

    Purpose: To assess the correlation of respiratory volume and abdominal displacement with tumor motion as seen with X-ray fluoroscopy. Measurements throughout the patient's treatment course allowed an assessment of the interfractional reproducibility of this correlation. Methods and materials: Data were acquired from 11 patients; 5 were studied over multiple days. Measurements of respiratory volume by spirometry and abdominal displacement by a real-time position tracking system were correlated to simultaneously acquired X-ray fluoroscopy measurements of superior-inferior tumor displacement. The linear correlation coefficient was computed for each data acquisition. The phase relationship between the surrogate and tumor signals was estimated through cross-correlation delay analysis. Results: Correlation coefficients ranged from very high to very low (0.99-0.39, p < 0.0001). The correlation between tumor displacement and respiratory volume was higher and more reproducible from day to day than between tumor displacement and abdominal displacement. A nonzero phase relationship was observed in nearly all patients (-0.65 to +0.50 s). This relationship was observed to vary over inter- and intrafractional time scales. Only 1 of 5 patients studied over multiple days had a consistent relationship between tumor motion and either surrogate. Conclusions: Respiratory volume has a more reproducible correlation with tumor motion than does abdominal displacement. If forming a tumor-surrogate prediction model from a limited series of observations, the use of surrogates to guide treatment might result in geographic miss.

  13. Differences in surrogate threshold effect estimates between original and simplified correlation-based validation approaches.

    PubMed

    Schürmann, Christoph; Sieben, Wiebke

    2016-03-30

    Surrogate endpoint validation has been well established by the meta-analytical correlation-based approach as outlined in the seminal work of Buyse et al. (Biostatistics, 2000). Surrogacy can be assumed if strong associations on individual and study levels can be demonstrated. Alternatively, if an effect on a true endpoint is to be predicted from a surrogate endpoint in a new study, the surrogate threshold effect (STE, Burzykowski and Buyse, Pharmaceutical Statistics, 2006) can be used. In practice, as individual patient data (IPD) are hard to obtain, some authors use only aggregate data and perform simplified regression analyses. We are interested in to what extent such simplified analyses are biased compared with the ones from a full model with IPD. To this end, we conduct a simulation study with IPD and compute STEs from full and simplified analyses for varying data situations in terms of number of studies, correlations, variances and so on. In the scenarios considered, we show that, for normally distributed patient data, STEs derived from ordinary (weighted) linear regression generally underestimate STEs derived from the original model, whereas meta-regression often results in overestimation. Therefore, if individual data cannot be obtained, STEs from meta-regression may be used as conservative alternatives, but ordinary (weighted) linear regression should not be used for surrogate endpoint validation. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26522510

  14. Surrogate-based optimization of hydraulic fracturing in pre-existing fracture networks

    NASA Astrophysics Data System (ADS)

    Chen, Mingjie; Sun, Yunwei; Fu, Pengcheng; Carrigan, Charles R.; Lu, Zhiming; Tong, Charles H.; Buscheck, Thomas A.

    2013-08-01

    Hydraulic fracturing has been used widely to stimulate production of oil, natural gas, and geothermal energy in formations with low natural permeability. Numerical optimization of fracture stimulation often requires a large number of evaluations of objective functions and constraints from forward hydraulic fracturing models, which are computationally expensive and even prohibitive in some situations. Moreover, there are a variety of uncertainties associated with the pre-existing fracture distributions and rock mechanical properties, which affect the optimized decisions for hydraulic fracturing. In this study, a surrogate-based approach is developed for efficient optimization of hydraulic fracturing well design in the presence of natural-system uncertainties. The fractal dimension is derived from the simulated fracturing network as the objective for maximizing energy recovery sweep efficiency. The surrogate model, which is constructed using training data from high-fidelity fracturing models for mapping the relationship between uncertain input parameters and the fractal dimension, provides fast approximation of the objective functions and constraints. A suite of surrogate models constructed using different fitting methods is evaluated and validated for fast predictions. Global sensitivity analysis is conducted to gain insights into the impact of the input variables on the output of interest, and further used for parameter screening. The high efficiency of the surrogate-based approach is demonstrated for three optimization scenarios with different and uncertain ambient conditions. Our results suggest the critical importance of considering uncertain pre-existing fracture networks in optimization studies of hydraulic fracturing.

  15. Applying psychological theories to evidence-based clinical practice: identifying factors predictive of lumbar spine x-ray for low back pain in UK primary care practice

    PubMed Central

    2011-01-01

    explained by individual theories was TPB 25.0%, SCT 21.5%, CS-SRM 11.3%, OLT 26.3%, PAP 2.6%, and knowledge 2.3%, and in the cross-theory analysis constructs from TPB, SCT, CS-SRM, and OLT explained 33.5% variance in intention. Together these results suggest that physicians' beliefs about consequences and beliefs about capabilities are likely determinants of lumbar spine x-ray referrals. Conclusions The study provides evidence that taking a theory-based approach enables the creation of a replicable methodology for identifying factors that predict clinical behaviour. However, a number of conceptual and methodological challenges remain. PMID:21619689

  16. DNA Methylation as Surrogate Marker For Gastric Cancer

    PubMed Central

    Oh, Jung-Hwan; Jung, Sung-Hoon; Hong, Seung-Jin; Rhyu, Mun-Gan

    2015-01-01

    Stomach cancer remains, stubbornly, highly prevalent in East Asia. Still, stomach cancer has few biomarkers by which it can be predicted. Helicobacter pylori infection, a known carcinogen of stomach cancer, usually goes undetected prior to cancer diagnosis, due to the poor mucosal environments that its related gastric atrophy causes. We propose, herein, an endoscopic-biopsy-based cancer-predicting DNA methylation marker. We semi-quantitatively examined the methylation-variable sites near the CpG-island margins by radioisotope-labeling methylation-specific polymerase chain reaction in association with H. pylori, which increases age-related over-methylation in CpG islands of gastric mucosa. These age-related methylation patterns of the transitional-CpG sites are proposed as useful surrogate markers for stomach cancer. It would be helpful for setting the optimal screening interval for high-risk subjects as well as for estimating the prognosis and the predictability for recurrence of early gastric cancer in patients having undergone endoscopic submucosal dissection. New screening-interval guidelines for gastric cancer should be suggested considering individual risk based on age, severity of atrophy, H. pylori status, and DNA methylation pattern. PMID:26473155

  17. Surrogate Motherhood and Abortion for Fetal Abnormality.

    PubMed

    Walker, Ruth; van Zyl, Liezl

    2015-10-01

    A diagnosis of fetal abnormality presents parents with a difficult - even tragic - moral dilemma. Where this diagnosis is made in the context of surrogate motherhood there is an added difficulty, namely that it is not obvious who should be involved in making decisions about abortion, for the person who would normally have the right to decide - the pregnant woman - does not intend to raise the child. This raises the question: To what extent, if at all, should the intended parents be involved in decision-making? In commercial surrogacy it is thought that as part of the contractual agreement the intended parents acquire the right to make this decision. By contrast, in altruistic surrogacy the pregnant woman retains the right to make these decisions, but the intended parents are free to decide not to adopt the child. We argue that both these strategies are morally unsound, and that the problems encountered serve to highlight more fundamental defects within the commercial and altruistic models, as well as in the legal and institutional frameworks that support them. We argue in favour of the professional model, which acknowledges the rights and responsibilities of both parties and provides a legal and institutional framework that supports good decision-making. In particular, the professional model acknowledges the surrogate's right to decide whether to undergo an abortion, and the intended parents' obligation to accept legal custody of the child. While not solving all the problems that arise in surrogacy, the model provides a framework that supports good decision-making. PMID:25688455

  18. Testing for nonlinearity in time series: The method of surrogate data

    SciTech Connect

    Theiler, J.; Galdrikian, B.; Longtin, A. ); Eubank, S.; Farmer, J.D. Santa Fe Inst., NM )

    1991-01-01

    We describe a statistical approach for identifying nonlinearity in time series; in particular, we want to avoid claims of chaos when simpler models (such as linearly correlated noise) can explain the data. The method requires a careful statement of the null hypothesis which characterizes a candidate linear process, the generation of an ensemble of surrogate'' data sets which are similar to the original time series but consistent with the null hypothesis, and the computation of a discriminating statistic for the original and for each of the surrogate data sets. The idea is to test the original time series against the null hypothesis by checking whether the discriminating statistic computed for the original time series differs significantly from the statistics computed for each of the surrogate sets. We present algorithms for generating surrogate data under various null hypotheses, and we show the results of numerical experiments on artificial data using correlation dimension, Lyapunov exponent, and forecasting error as discriminating statistics. Finally, we consider a number of experimental time series -- including sunspots, electroencephalogram (EEG) signals, and fluid convection -- and evaluate the statistical significance of the evidence for nonlinear structure in each case. 56 refs., 8 figs.

  19. Use of aerobic spores as a surrogate for cryptosporidium oocysts in drinking water supplies.

    PubMed

    Headd, Brendan; Bradford, Scott A

    2016-03-01

    Waterborne illnesses are a growing concern among health and regulatory agencies worldwide. The United States Environmental Protection Agency has established several rules to combat the contamination of water supplies by cryptosporidium oocysts, however, the detection and study of cryptosporidium oocysts is hampered by methodological and financial constraints. As a result, numerous surrogates for cryptosporidium oocysts have been proposed by the scientific community and efforts are underway to evaluate many of the proposed surrogates. The purpose of this review is to evaluate the suitability of aerobic bacterial spores to serve as a surrogate for cryptosporidium oocysts in identifying contaminated drinking waters. To accomplish this we present a comparison of the biology and life cycles of aerobic spores and oocysts and compare their physical properties. An analysis of their surface properties is presented along with a review of the literature in regards to the transport, survival, and prevalence of aerobic spores and oocysts in the saturated subsurface environment. Aerobic spores and oocysts share many commonalities with regard to biology and survivability, and the environmental prevalence and ease of detection make aerobic spores a promising surrogate for cryptosporidium oocysts in surface and groundwater. However, the long-term transport and release of aerobic spores still needs to be further studied, and compared with available oocyst information. In addition, the surface properties and environmental interactions of spores are known to be highly dependent on the spore taxa and purification procedures, and additional research is needed to address these issues in the context of transport. PMID:26734779

  20. Systematic mutagenesis of genes encoding predicted autotransported proteins of Burkholderia pseudomallei identifies factors mediating virulence in mice, net intracellular replication and a novel protein conferring serum resistance.

    PubMed

    Lazar Adler, Natalie R; Stevens, Mark P; Dean, Rachel E; Saint, Richard J; Pankhania, Depesh; Prior, Joann L; Atkins, Timothy P; Kessler, Bianca; Nithichanon, Arnone; Lertmemongkolchai, Ganjana; Galyov, Edouard E

    2015-01-01

    Burkholderia pseudomallei is the causative agent of the severe tropical disease melioidosis, which commonly presents as sepsis. The B. pseudomallei K96243 genome encodes eleven predicted autotransporters, a diverse family of secreted and outer membrane proteins often associated with virulence. In a systematic study of these autotransporters, we constructed insertion mutants in each gene predicted to encode an autotransporter and assessed them for three pathogenesis-associated phenotypes: virulence in the BALB/c intra-peritoneal mouse melioidosis model, net intracellular replication in J774.2 murine macrophage-like cells and survival in 45% (v/v) normal human serum. From the complete repertoire of eleven autotransporter mutants, we identified eight mutants which exhibited an increase in median lethal dose of 1 to 2-log10 compared to the isogenic parent strain (bcaA, boaA, boaB, bpaA, bpaC, bpaE, bpaF and bimA). Four mutants, all demonstrating attenuation for virulence, exhibited reduced net intracellular replication in J774.2 macrophage-like cells (bimA, boaB, bpaC and bpaE). A single mutant (bpaC) was identified that exhibited significantly reduced serum survival compared to wild-type. The bpaC mutant, which demonstrated attenuation for virulence and net intracellular replication, was sensitive to complement-mediated killing via the classical and/or lectin pathway. Serum resistance was rescued by in trans complementation. Subsequently, we expressed recombinant proteins of the passenger domain of four predicted autotransporters representing each of the phenotypic groups identified: those attenuated for virulence (BcaA), those attenuated for virulence and net intracellular replication (BpaE), the BpaC mutant with defects in virulence, net intracellular replication and serum resistance and those displaying wild-type phenotypes (BatA). Only BcaA and BpaE elicited a strong IFN-γ response in a restimulation assay using whole blood from seropositive donors and were

  1. Systematic Mutagenesis of Genes Encoding Predicted Autotransported Proteins of Burkholderia pseudomallei Identifies Factors Mediating Virulence in Mice, Net Intracellular Replication and a Novel Protein Conferring Serum Resistance

    PubMed Central

    Adler, Natalie R. Lazar; Stevens, Mark P.; Dean, Rachel E.; Saint, Richard J.; Pankhania, Depesh; Prior, Joann L.; Atkins, Timothy P.; Kessler, Bianca; Nithichanon, Arnone; Lertmemongkolchai, Ganjana; Galyov, Edouard E.

    2015-01-01

    Burkholderia pseudomallei is the causative agent of the severe tropical disease melioidosis, which commonly presents as sepsis. The B. pseudomallei K96243 genome encodes eleven predicted autotransporters, a diverse family of secreted and outer membrane proteins often associated with virulence. In a systematic study of these autotransporters, we constructed insertion mutants in each gene predicted to encode an autotransporter and assessed them for three pathogenesis-associated phenotypes: virulence in the BALB/c intra-peritoneal mouse melioidosis model, net intracellular replication in J774.2 murine macrophage-like cells and survival in 45% (v/v) normal human serum. From the complete repertoire of eleven autotransporter mutants, we identified eight mutants which exhibited an increase in median lethal dose of 1 to 2-log10 compared to the isogenic parent strain (bcaA, boaA, boaB, bpaA, bpaC, bpaE, bpaF and bimA). Four mutants, all demonstrating attenuation for virulence, exhibited reduced net intracellular replication in J774.2 macrophage-like cells (bimA, boaB, bpaC and bpaE). A single mutant (bpaC) was identified that exhibited significantly reduced serum survival compared to wild-type. The bpaC mutant, which demonstrated attenuation for virulence and net intracellular replication, was sensitive to complement-mediated killing via the classical and/or lectin pathway. Serum resistance was rescued by in trans complementation. Subsequently, we expressed recombinant proteins of the passenger domain of four predicted autotransporters representing each of the phenotypic groups identified: those attenuated for virulence (BcaA), those attenuated for virulence and net intracellular replication (BpaE), the BpaC mutant with defects in virulence, net intracellular replication and serum resistance and those displaying wild-type phenotypes (BatA). Only BcaA and BpaE elicited a strong IFN-γ response in a restimulation assay using whole blood from seropositive donors and were

  2. Annual sediment flux estimates in a tidal strait using surrogate measurements

    NASA Astrophysics Data System (ADS)

    Ganju, Neil K.; Schoellhamer, David H.

    2006-08-01

    Annual suspended-sediment flux estimates through Carquinez Strait (the seaward boundary of Suisun Bay, California) are provided based on surrogate measurements for advective, dispersive, and Stokes drift flux. The surrogates are landward watershed discharge, suspended-sediment concentration at one location in the Strait, and the longitudinal salinity gradient. The first two surrogates substitute for tidally averaged discharge and velocity-weighted suspended-sediment concentration in the Strait, thereby providing advective flux estimates, while Stokes drift is estimated with suspended-sediment concentration alone. Dispersive flux is estimated using the product of longitudinal salinity gradient and the root-mean-square value of velocity-weighted suspended-sediment concentration as an added surrogate variable. Cross-sectional measurements validated the use of surrogates during the monitoring period. During high freshwater flow advective and dispersive flux were in the seaward direction, while landward dispersive flux dominated and advective flux approached zero during low freshwater flow. Stokes drift flux was consistently in the landward direction. Wetter than average years led to net export from Suisun Bay, while dry years led to net sediment import. Relatively low watershed sediment fluxes to Suisun Bay contribute to net export during the wet season, while gravitational circulation in Carquinez Strait and higher suspended-sediment concentrations in San Pablo Bay (seaward end of Carquinez Strait) are responsible for the net import of sediment during the dry season. Annual predictions of suspended-sediment fluxes, using these methods, will allow for a sediment budget for Suisun Bay, which has implications for marsh restoration and nutrient/contaminant transport. These methods also provide a general framework for estimating sediment fluxes in estuarine environments, where temporal and spatial variability of transport are large.

  3. Annual sediment flux estimates in a tidal strait using surrogate measurements

    USGS Publications Warehouse

    Ganju, N.K.; Schoellhamer, D.H.

    2006-01-01

    Annual suspended-sediment flux estimates through Carquinez Strait (the seaward boundary of Suisun Bay, California) are provided based on surrogate measurements for advective, dispersive, and Stokes drift flux. The surrogates are landward watershed discharge, suspended-sediment concentration at one location in the Strait, and the longitudinal salinity gradient. The first two surrogates substitute for tidally averaged discharge and velocity-weighted suspended-sediment concentration in the Strait, thereby providing advective flux estimates, while Stokes drift is estimated with suspended-sediment concentration alone. Dispersive flux is estimated using the product of longitudinal salinity gradient and the root-mean-square value of velocity-weighted suspended-sediment concentration as an added surrogate variable. Cross-sectional measurements validated the use of surrogates during the monitoring period. During high freshwater flow advective and dispersive flux were in the seaward direction, while landward dispersive flux dominated and advective flux approached zero during low freshwater flow. Stokes drift flux was consistently in the landward direction. Wetter than average years led to net export from Suisun Bay, while dry years led to net sediment import. Relatively low watershed sediment fluxes to Suisun Bay contribute to net export during the wet season, while gravitational circulation in Carquinez Strait and higher suspended-sediment concentrations in San Pablo Bay (seaward end of Carquinez Strait) are responsible for the net import of sediment during the dry season. Annual predictions of suspended-sediment fluxes, using these methods, will allow for a sediment budget for Suisun Bay, which has implications for marsh restoration and nutrient/contaminant transport. These methods also provide a general framework for estimating sediment fluxes in estuarine environments, where temporal and spatial variability of transport are large. ?? 2006 Elsevier Ltd. All rights

  4. TOXICITY OF PENTACHLOROPHENOL TO ENDANGERED AND SURROGATE FISH SPECIES

    EPA Science Inventory

    Water quality criteria (WQC) generally are based on the responses of easily cultured and tested surrogate species. Little is known about the relative sensitivity of surrogate and endangered species. The objective of this study was to compare acute and chronic (early life-stage) ...

  5. Inactivation of Tulane virus, a novel surrogate for human norovirus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human noroviruses (HuNoVs) are the major cause of non-bacterial epidemics of gastroenteritis. Due to the inability to cultivate HuNoVs and the lack of an efficient small animal model, surrogates are used to study HuNoV biology. Two such surrogates, the feline calicivirus (FCV) and the murine norovir...

  6. A Training Manual for Surrogate Parents: Rules and Responsibilities.

    ERIC Educational Resources Information Center

    Arkansas State Dept. of Education, Little Rock. Special Education Section.

    The manual is designed for training surrogate parents in identification, evaluation, placement, and programing for the handicapped child in Arkansas. General guidelines for the surrogate parent are listed, including meeting the child before requesting to see any school records, presuming that the agency has the child's best interest at heart, and…

  7. 26 CFR 1.7874-2 - Surrogate foreign corporation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... CFR part 1, revised as of April 1, 2012. ... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Surrogate foreign corporation. 1.7874-2 Section... TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.7874-2 Surrogate...

  8. 26 CFR 1.7874-2 - Surrogate foreign corporation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... CFR part 1, revised as of April 1, 2012. ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Surrogate foreign corporation. 1.7874-2 Section... TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.7874-2 Surrogate...

  9. Performance of Visual, Verbal, and Combined Video Surrogates.

    ERIC Educational Resources Information Center

    Ding, Wei; Soergel, Dagobert; Marchionini, Gary

    1999-01-01

    Investigates the information representation power of different modalities in the video data in order to collect empirical evidence for video surrogate creation and thus better support effective video browsing and information retrieval. Three types of video surrogates were created and compared under two user tasks--verbal comprehension and visual…

  10. Validation of the Health Care Surrogate Preferences Scale

    ERIC Educational Resources Information Center

    Buckey, Julia W.; Abell, Neil

    2004-01-01

    Recent advances in health care technology have increased the number of health care decisions made by acute care patients and those who act on their behalf, known as health care surrogates. This study reports on the validation of a new measure, the Health Care Surrogate Preferences Scale. Designed to assess the willingness of adults to perform and…

  11. INTEC SBW Solid Sludge Surrogate Recipe and Validation

    SciTech Connect

    Maio, Vince; Janikowski, Stuart; Johnson, Jim; Maio, Vince; Pao, Jenn-Hai

    2004-06-01

    A nonhazardous INTEC tank farm sludge surrogate that incorporated metathesis reactions to generate solids from solutions of known elements present in the radioactive INTEC tank farm sodium-bearing waste sludges was formulated. Elemental analyses, physical property analyses, and filtration testing were performed on waste surrogate and tank farm waste samples, and the results were compared. For testing physical systems associated with moving the tank farm solids, the surrogate described in this report is the best currently available choice. No other available surrogate exhibits the noted similarities in behavior to the sludges. The chemical morphology, particle size distribution, and settling and flow characteristics of the surrogate were similar to those exhibited by the waste sludges. Nonetheless, there is a difference in chemical makeup of the surrogate and the tank farm waste. If a chemical treatment process were to be evaluated for final treatment and disposition of the waste sludges, the surrogate synthesis process would likely require modification to yield a surrogate with a closer matching chemical composition.

  12. Results from Oritavancin Resistance Surveillance Programs (2011 to 2014): Clarification for Using Vancomycin as a Surrogate To Infer Oritavancin Susceptibility.

    PubMed

    Jones, Ronald N; Moeck, Greg; Arhin, Francis F; Dudley, Michael N; Rhomberg, Paul R; Mendes, Rodrigo E

    2016-05-01

    Measurement of vancomycin susceptibility has been shown to be highly predictive as a surrogate measure of oritavancin susceptibility among clinically indicated Gram-positive species. Results of studying over 30,000 pathogens (from 2011 to 2014) by cross-susceptibility analysis and determining the poor reproducibility of oritavancin-nonsusceptible results showed nearly perfect surrogate testing accuracy (99.86 to 99.94%). Any isolate of an indicated organism species with locally reproducible oritavancin-nonsusceptible results (extremely rare) should be referred to a reference laboratory for confirmation of the results and determination of the resistance mechanism. PMID:26926647

  13. Novel circular single-stranded DNA viruses identified in marine invertebrates reveal high sequence diversity and consistent predicted intrinsic disorder patterns within putative structural proteins

    PubMed Central

    Rosario, Karyna; Schenck, Ryan O.; Harbeitner, Rachel C.; Lawler, Stephanie N.; Breitbart, Mya

    2015-01-01

    Viral metagenomics has recently revealed the ubiquitous and diverse nature of single-stranded DNA (ssDNA) viruses that encode a conserved replication initiator protein (Rep) in the marine environment. Although eukaryotic circular Rep-encoding ssDNA (CRESS-DNA) viruses were originally thought to only infect plants and vertebrates, recent studies have identified these viruses in a number of invertebrates. To further explore CRESS-DNA viruses in the marine environment, this study surveyed CRESS-DNA viruses in various marine invertebrate species. A total of 27 novel CRESS-DNA genomes, with Reps that share less than 60.1% identity with previously reported viruses, were recovered from 21 invertebrate species, mainly crustaceans. Phylogenetic analysis based on the Rep revealed a novel clade of CRESS-DNA viruses that included approximately one third of the marine invertebrate associated viruses identified here and whose members may represent a novel family. Investigation of putative capsid proteins (Cap) encoded within the eukaryotic CRESS-DNA viral genomes from this study and those in GenBank demonstrated conserved patterns of predicted intrinsically disordered regions (IDRs), which can be used to complement similarity-based searches to identify divergent structural proteins within novel genomes. Overall, this study expands our knowledge of CRESS-DNA viruses associated with invertebrates and explores a new tool to evaluate divergent structural proteins encoded by these viruses. PMID:26217327

  14. CFD-based surrogate modeling of liquid rocket engine components via design space refinement and sensitivity assessment

    NASA Astrophysics Data System (ADS)

    Mack, Yolanda

    Computational fluid dynamics (CFD) can be used to improve the design and optimization of rocket engine components that traditionally rely on empirical calculations and limited experimentation. CFD based-design optimization can be made computationally affordable through the use of surrogate modeling which can then facilitate additional parameter sensitivity assessments. The present study investigates surrogate-based adaptive design space refinement (DSR) using estimates of surrogate uncertainty to probe the CFD analyses and to perform sensitivity assessments for complex fluid physics associated with liquid rocket engine components. Three studies were conducted. First, a surrogate-based preliminary design optimization was conducted to improve the efficiency of a compact radial turbine for an expander cycle rocket engine while maintaining low weight. Design space refinement was used to identify function constraints and to obtain a high accuracy surrogate model in the region of interest. A merit function formulation for multi-objective design point selection reduced the number of design points by an order of magnitude while maintaining good surrogate accuracy among the best trade-off points. Second, bluff body-induced flow was investigated to identify the physics and surrogate modeling issues related to the flow's mixing dynamics. Multiple surrogates and DSR were instrumental in identifying designs for which the CFD model was deficient and to help to pinpoint the nature of the deficiency. Next, a three-dimensional computational model was developed to explore the wall heat transfer of a GO2/GH2 shear coaxial single element injector. The interactions between turbulent recirculating flow structures, chemical kinetics, and heat transfer are highlighted. Finally, a simplified computational model of multi-element injector flows was constructed to explore the sensitivity of wall heating and improve combustion efficiency to injector element spacing. Design space refinement

  15. Predictive Ability of Positive Clinical Culture Results and International Classification of Diseases, Ninth Revision, to Identify and Classify Noninvasive Staphylococcus aureus Infections: A Validation Study

    PubMed Central

    Tracy, LaRee A.; Furuno, Jon P.; Harris, Anthony D.; Singer, Mary; Langenberg, Patricia; Roghmann, Mary-Claire

    2010-01-01

    OBJECTIVE To develop and validate an algorithm to identify and classify noninvasive infections due to Staphylococcus aureus by using positive clinical culture results and administrative data. DESIGN Retrospective cohort study. SETTING Veterans Affairs Maryland Health Care System. METHODS Data were collected retrospectively on all S. aureus clinical culture results from samples obtained from nonsterile body sites during October 1998 through September 2008 and associated administrative claims records. An algorithm was developed to identify noninvasive infections on the basis of a unique S. aureus–positive culture result from a nonsterile site sample with a matching International Classification of Diseases, Ninth Revision (ICD-9-CM), code for infection at time of sampling. Medical records of a subset of cases were reviewed to find the proportion of true noninvasive infections (cases that met the Centers for Disease Control and Prevention National Healthcare Safety Network [NHSN] definition of infection). Positive predictive value (PPV) and negative predictive value (NPV) were calculated for all infections and according to body site of infection. RESULTS We identified 4,621 unique S. aureus–positive culture results, of which 2,816 (60.9%) results met our algorithm definition of noninvasive S. aureus infection and 1,805 (39.1%) results lacked a matching ICD-9-CM code. Among 96 cases that met our algorithm criteria for noninvasive S. aureus infection, 76 also met the NHSN criteria (PPV, 79.2% [95% confidence interval, 70.0%–86.1%]). Among 98 cases that failed to meet the algorithm criteria, 80 did not meet the NHSN criteria (NPV, 81.6% [95% confidence interval, 72.8%–88.0%]). The PPV of all culture results was 55.4%. The algorithm was most predictive for skin and soft-tissue infections and bone and joint infections. CONCLUSION When culture-based surveillance methods are used, the addition of administrative ICD-9-CM codes for infection can increase the PPV of true

  16. Evaluating β Diversity as a Surrogate for Species Representation at Fine Scale.

    PubMed

    Beier, Paul; Albuquerque, Fábio

    2016-01-01

    Species turnover or β diversity is a conceptually attractive surrogate for conservation planning. However, there has been only 1 attempt to determine how well sites selected to maximize β diversity represent species, and that test was done at a scale too coarse (2,500 km2 sites) to inform most conservation decisions. We used 8 plant datasets, 3 bird datasets, and 1 mammal dataset to evaluate whether sites selected to span β diversity will efficiently represent species at finer scale (sites sizes < 1 ha to 625 km2). We used ordinations to characterize dissimilarity in species assemblages (β diversity) among plots (inventory data) or among grid cells (atlas data). We then selected sites to maximize β diversity and used the Species Accumulation Index, SAI, to evaluate how efficiently the surrogate (selecting sites for maximum β diversity) represented species in the same taxon. Across all 12 datasets, sites selected for maximum β diversity represented species with a median efficiency of 24% (i.e., the surrogate was 24% more effective than random selection of sites), and an interquartile range of 4% to 41% efficiency. β diversity was a better surrogate for bird datasets than for plant datasets, and for atlas datasets with 10-km to 14-km grid cells than for atlas datasets with 25-km grid cells. We conclude that β diversity is more than a mere descriptor of how species are distributed on the landscape; in particular β diversity might be useful to maximize the complementarity of a set of sites. Because we tested only within-taxon surrogacy, our results do not prove that β diversity is useful for conservation planning. But our results do justify further investigation to identify the circumstances in which β diversity performs well, and to evaluate it as a cross-taxon surrogate. PMID:26943170

  17. Evaluating β Diversity as a Surrogate for Species Representation at Fine Scale

    PubMed Central

    Beier, Paul; Albuquerque, Fábio

    2016-01-01

    Species turnover or β diversity is a conceptually attractive surrogate for conservation planning. However, there has been only 1 attempt to determine how well sites selected to maximize β diversity represent species, and that test was done at a scale too coarse (2,500 km2 sites) to inform most conservation decisions. We used 8 plant datasets, 3 bird datasets, and 1 mammal dataset to evaluate whether sites selected to span β diversity will efficiently represent species at finer scale (sites sizes < 1 ha to 625 km2). We used ordinations to characterize dissimilarity in species assemblages (β diversity) among plots (inventory data) or among grid cells (atlas data). We then selected sites to maximize β diversity and used the Species Accumulation Index, SAI, to evaluate how efficiently the surrogate (selecting sites for maximum β diversity) represented species in the same taxon. Across all 12 datasets, sites selected for maximum β diversity represented species with a median efficiency of 24% (i.e., the surrogate was 24% more effective than random selection of sites), and an interquartile range of 4% to 41% efficiency. β diversity was a better surrogate for bird datasets than for plant datasets, and for atlas datasets with 10-km to 14-km grid cells than for atlas datasets with 25-km grid cells. We conclude that β diversity is more than a mere descriptor of how species are distributed on the landscape; in particular β diversity might be useful to maximize the complementarity of a set of sites. Because we tested only within-taxon surrogacy, our results do not prove that β diversity is useful for conservation planning. But our results do justify further investigation to identify the circumstances in which β diversity performs well, and to evaluate it as a cross-taxon surrogate. PMID:26943170

  18. Surrogate Motherhood: A Trust-Based Approach.

    PubMed

    Beier, Katharina

    2015-12-01

    Because it is often argued that surrogacy should not be treated as contractual, the question arises in which terms this practice might then be couched. In this article, I argue that a phenomenology of surrogacy centering on the notion of trust provides a description that is illuminating from the moral point of view. My thesis is that surrogacy establishes a complex and extended reproductive unit--the "surrogacy triad" consisting of the surrogate mother, the child, and the intending parents--whose constituents are bound together by mutual trustful commitments. Even though a trust-based approach does not provide an ultimate answer to whether surrogacy should be sanctioned or prohibited, it allows for at least some practical suggestions. In particular, I will argue that, under certain conditions, surrogacy is tenable within familial or other significant relationships, and I will stress the necessity of acknowledging the new relationships and moral commitments that result from this practice. PMID:26449234

  19. Intentional parenthood: responsibilities in surrogate motherhood.

    PubMed

    Van Zyl, Liezl

    2002-01-01

    In recent years, a number of writers dealing with questions over parenthood that arise in the context of reproductive technologies and surrogate motherhood, have appealed to the notion of "intentional parenthood". Basing their argument on liberal values such as individual autonomy, the freedom to enter contracts, the right to privacy, and individual self-fulfilment, they argue that contractually stated intentions, rather than genetic or gestational relationships, should form the basis of parental rights. Against this I argue that parental rights do not derive from contractual agreements, but are based in their obligations towards the child. I then examine the nature of the obligations that the various parties have towards the child both pre- and postnatally. PMID:12216743

  20. Surrogates of plutonium for detection equipment testing

    NASA Astrophysics Data System (ADS)

    Peerani, Paolo; Tomanin, Alice

    2011-10-01

    Fight against illicit trafficking of nuclear material relies on the possibility to detect nuclear material concealed in vehicles, people or cargo containers. This is done by equipping and training law enforcement and security staff in border stations or other points of access to strategic places and critical infrastructures with radiation detection equipment. The design, development, testing and evaluation of these instruments ideally require the use of real nuclear material to assess, verify and certify their detection performance. Availability of special nuclear material may be an issue, especially for industry, since only few specialized laboratories are licensed for such material. This paper tries to analyse and describe the possibility to use suitable surrogates that may replace the use of real nuclear material in testing the detection capabilities of instruments used in nuclear security.

  1. Monte Carlo simulation of transfer reactions using extended R-matrix theory picturing surrogate-type WFCF features

    NASA Astrophysics Data System (ADS)

    Bouland, Olivier H.

    2016-03-01

    This article supplies an overview of issues related to the interpretation of surrogate measurement results for neutron-incident cross section predictions; difficulties that are somehow masked by the historical conversion route based on Weisskopf-Ewing approximation. Our proposal is to handle the various difficulties by using a more rigorous approach relying on Monte Carlo simulation of transfer reactions with extended R-matrix theory. The multiple deficiencies of the historical surrogate treatment are recalled but only one is examined in some details here; meaning the calculation of in-out-going channel Width Fluctuation Correction Factors (WFCF) which behavior witness partly the failure of Niels Bohr's compound nucleus theoretical landmark. Relevant WFCF calculations according to neutron-induced surrogate- and cross section-types as a function of neutron-induced fluctuating energy range [0 - 2.1 MeV] are presented and commented in the case of the 240Pu* and 241Pu* compound nucleus isotopes.

  2. Surrogate models of precessing numerical relativity gravitational waveforms for use in parameter estimation

    NASA Astrophysics Data System (ADS)

    Blackman, Jonathan; Field, Scott; Galley, Chad; Hemberger, Daniel; Scheel, Mark; Schmidt, Patricia; Smith, Rory; SXS Collaboration Collaboration

    2016-03-01

    We are now in the advanced detector era of gravitational wave astronomy, and the merger of two black holes (BHs) is one of the most promising sources of gravitational waves that could be detected on earth. To infer the BH masses and spins, the observed signal must be compared to waveforms predicted by general relativity for millions of binary configurations. Numerical relativity (NR) simulations can produce accurate waveforms, but are prohibitively expensive to use for parameter estimation. Other waveform models are fast enough but may lack accuracy in portions of the parameter space. Numerical relativity surrogate models attempt to rapidly predict the results of a NR code with a small or negligible modeling error, after being trained on a set of input waveforms. Such surrogate models are ideal for parameter estimation, as they are both fast and accurate, and have already been built for the case of non-spinning BHs. Using 250 input waveforms, we build a surrogate model for waveforms from the Spectral Einstein Code (SpEC) for a subspace of precessing systems.

  3. ZipperDB: Predictions of Fibril-forming Segments within Proteins Identified by the 3D Profile Method (from the UCLA-DOE Institute for Genomics and Proteomics)

    DOE Data Explorer

    Goldschmidt, L.; Teng, P. K.; Riek, R.; Eisenberg, D.

    ZipperDB contains predictions of fibril-forming segments within proteins identified by the 3D Profile Method. The UCLA-DOE Institute for Genomics and Proteomics has analyzed over 20,000 putative protein sequences for segments with high fibrillation propensity that could form a "steric zipper"ùtwo self-complementary beta sheets, giving rise to the spine of an amyloid fibril. The approach is unique in that structural information is used to evaluate the likelihood that a particular sequence can form fibrils. [copied with edits from http://www.doe-mbi.ucla.edu/]. In addition to searching the database, academic and non-profit users may also submit their protein sequences to the database.

  4. Development of a surrogate kinetic mechanism for photochemical smog. Final report

    SciTech Connect

    Leone, J.A.; Seinfeld, J.H.

    1985-01-01

    A surrogate condensed chemical reaction mechanism for photochemical smog containing the latest available kinetic and mechanistic data is developed here and is extensively tested against experimental data from two smog-chamber facilities. In addition, a counter species analysis has shown that the prediction of the individual portions of the surrogate mechanism are in good agreement with those of a detailed explicit mechanism for photochemical smog. The new mechanism contains 20 non-steady-state species, making it compact enough for use in multidimensional grid models of urban air pollution. A major advantage of the new mechanism is the ease with which it can be modified to incorporate new kinetic or mechanistic information because of the straightforward manner in which the mechanism was formulated from the detailed explicit chemistry.

  5. A Label-free Selected Reaction Monitoring Workflow Identifies a Subset of Pregnancy Specific Glycoproteins as Potential Predictive Markers of Early-onset Pre-eclampsia*

    PubMed Central

    Blankley, Richard T.; Fisher, Christal; Westwood, Melissa; North, Robyn; Baker, Philip N.; Walker, Michael J.; Williamson, Andrew; Whetton, Anthony D.; Lin, Wanchang; McCowan, Lesley; Roberts, Claire T.; Cooper, Garth J. S.; Unwin, Richard D.; Myers, Jenny E.

    2013-01-01

    Pre-eclampsia (PE) is a serious complication of pregnancy with potentially life threatening consequences for both mother and baby. Presently there is no test with the required performance to predict which healthy first-time mothers will go on to develop PE. The high specificity, sensitivity, and multiplexed nature of selected reaction monitoring holds great potential as a tool for the verification and validation of putative candidate biomarkersfor disease states. Realization of this potential involves establishing a high throughput, cost effective, reproducible sample preparation workflow. We have developed a semi-automated HPLC-based sample preparation workflow before a label-free selected reaction monitoring approach. This workflow has been applied to the search for novel predictive biomarkers for PE. To discover novel candidate biomarkers for PE, we used isobaric tagging to identify several potential biomarker proteins in plasma obtained at 15 weeks gestation from nulliparous women who later developed PE compared with pregnant women who remained healthy. Such a study generates a number of “candidate” biomarkers that require further testing in larger patient cohorts. As proof-of-principle, two of these proteins were taken forward for verification in a 100 women (58 PE, 42 controls) using label-free SRM. We obtained reproducible protein quantitation across the 100 samples and demonstrated significant changes in protein levels, even with as little as 20% change in protein concentration. The SRM data correlated with a commercial ELISA, suggesting that this is a robust workflow suitable for rapid, affordable, label-free verification of which candidate biomarkers should be taken forward for thorough investigation. A subset of pregnancy-specific glycoproteins (PSGs) had value as novel predictive markers for PE. PMID:23897580

  6. DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study

    PubMed Central

    Lin, Hon-Yi; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Huang, Tze-Ta; Tseng, Chih-En; Shih, Liang-Yu; Lin, Ru-Inn; Lin, Jora M.J.; Lai, Yi-Hui; Chang, Chia-Bin; Hsu, Feng-Chun; Chen, Liang-Cheng; Tsai, Shiang-Jiun; Su, Yu-Chieh; Li, Szu-Chi; Lai, Hung-Chih; Hsu, Wen-Lin; Liu, Dai-Wei; Tai, Chien-Kuo; Wu, Shu-Fen; Chan, Michael W.Y.

    2015-01-01

    Radioresistance is still an emerging problem for radiotherapy of oral cancer. Aberrant epigenetic alterations play an important role in cancer development, yet the role of such alterations in radioresistance of oral cancer is not fully explored. Using a methylation microarray, we identified promoter hypermethylation of FHIT (fragile histidine triad) in radioresistant OML1-R cells, established from hypo-fractionated irradiation of parental OML1 radiosensitive oral cancer cells. Further analysis confirmed that transcriptional repression of FHIT was due to promoter hypermethylation, H3K27me3 and overexpression of methyltransferase EZH2 in OML1-R cells. Epigenetic interventions or depletion of EZH2 restored FHIT expression. Ectopic expression of FHIT inhibited tumor growth in both in vitro and in vivo models, while also resensitizing radioresistant cancer cells to irradiation, by restoring Chk2 phosphorylation and G2/M arrest. Clinically, promoter hypermethylation of FHIT inversely correlated with its expression and independently predicted both locoregional control and overall survival in 40 match-paired oral cancer patient samples. Further in vivo therapeutic experiments confirmed that inhibition of DNA methylation significantly resensitized radioresistant oral cancer cell xenograft tumors. These results show that epigenetic silencing of FHIT contributes partially to radioresistance and predicts clinical outcomes in irradiated oral cancer. The radiosensitizing effect of epigenetic interventions warrants further clinical investigation. PMID:25460508

  7. Development of a Drug-Response Modeling Framework to Identify Cell Line Derived Translational Biomarkers That Can Predict Treatment Outcome to Erlotinib or Sorafenib

    PubMed Central

    Li, Bin; Shin, Hyunjin; Gulbekyan, Georgy; Pustovalova, Olga; Nikolsky, Yuri; Hope, Andrew; Bessarabova, Marina; Schu, Matthew; Kolpakova-Hart, Elona; Merberg, David; Dorner, Andrew; Trepicchio, William L.

    2015-01-01

    Development of drug responsive biomarkers from pre-clinical data is a critical step in drug discovery, as it enables patient stratification in clinical trial design. Such translational biomarkers can be validated in early clinical trial phases and utilized as a patient inclusion parameter in later stage trials. Here we present a study on building accurate and selective drug sensitivity models for Erlotinib or Sorafenib from pre-clinical in vitro data, followed by validation of individual models on corresponding treatment arms from patient data generated in the BATTLE clinical trial. A Partial Least Squares Regression (PLSR) based modeling framework was designed and implemented, using a special splitting strategy and canonical pathways to capture robust information for model building. Erlotinib and Sorafenib predictive models could be used to identify a sub-group of patients that respond better to the corresponding treatment, and these models are specific to the corresponding drugs. The model derived signature genes reflect each drug’s known mechanism of action. Also, the models predict each drug’s potential cancer indications consistent with clinical trial results from a selection of globally normalized GEO expression datasets. PMID:26107615

  8. Performance of the waist-to-height ratio in identifying obesity and predicting non-communicable diseases in the elderly population: A systematic literature review.

    PubMed

    Corrêa, Márcia Mara; Thumé, Elaine; De Oliveira, Elizabete Regina Araújo; Tomasi, Elaine

    2016-01-01

    A systematic review was carried out aiming to collect evidence on the use of the waist-to-height ratio (WHtR) on the elderly population, focusing on validity measures to identify the best anthropometric indicator in assessing obesity associated with non-communicable diseases. The review consisted in a search of papers published on the databases Pubmed, Web of Science, and Lilacs, with no restriction regarding period of publication, using the following combinations: abdominal fat or overweight or obesity and waist-to-height ratio or waist height or waist ht or WHtR or waist to stature ratio or wst stature or WSR or stature and girth. Sixteen papers were selected, most of which with high methodological quality. The receiver-operating characteristic (ROC) curves was the validity measure explored in 13 papers, followed by sensitivity and specificity measures. In all studies, the body mass index (BMI) and waist circumference (WC) received special attention for analysis along with WHtR. Five manuscripts showed evidence of WHtR being the best anthropometric index when used alone, four showed that both WHtR and WC had the best discriminatory power in predicting cardiovascular risk factors compared to the other indices, and two ranked WHtR at the same performance level as waist-to-hip ratio (WHR) and BMI. An association was shown of the obesity assessed by WHtR in predicting risk factors for cardiovascular diseases, metabolic syndrome, and diabetes compared to other anthropometric parameters. PMID:27061665

  9. Probabilistic Fatigue Damage Prognosis Using a Surrogate Model Trained Via 3D Finite Element Analysis

    NASA Technical Reports Server (NTRS)

    Leser, Patrick E.; Hochhalter, Jacob D.; Newman, John A.; Leser, William P.; Warner, James E.; Wawrzynek, Paul A.; Yuan, Fuh-Gwo

    2015-01-01

    Utilizing inverse uncertainty quantification techniques, structural health monitoring can be integrated with damage progression models to form probabilistic predictions of a structure's remaining useful life. However, damage evolution in realistic structures is physically complex. Accurately representing this behavior requires high-fidelity models which are typically computationally prohibitive. In the present work, a high-fidelity finite element model is represented by a surrogate model, reducing computation times. The new approach is used with damage diagnosis data to form a probabilistic prediction of remaining useful life for a test specimen under mixed-mode conditions.

  10. Development of the A-DIVA Scale: A Clinical Predictive Scale to Identify Difficult Intravenous Access in Adult Patients Based on Clinical Observations.

    PubMed

    van Loon, Fredericus H J; Puijn, Lisette A P M; Houterman, Saskia; Bouwman, Arthur R A

    2016-04-01

    Placement of a peripheral intravenous catheter is a routine procedure in clinical practice, but failure of intravenous cannulation regularly occurs. An accurate and reliable predictive scale for difficult venous access creates the possibility to use other techniques in an earlier time frame. We aimed to develop a predictive scale to identify adult patients with a difficult intravenous access prospectively: the A-DIVA scale. This prospective, observational, cross-sectional cohort study was conducted between January 2014 and January 2015, and performed at the department of anesthesiology of the Catharina Hospital (Eindhoven, The Netherlands). Patients 18 years or older were eligible if scheduled for any surgical procedure, regardless ASA classification, demographics, and medical history. Experienced and certified anesthesiologists and nurse anesthetists routinely obtained peripheral intravenous access. Cannulation was performed regarding standards for care. A failed peripheral intravenous cannulation on the first attempt was the outcome of interest. A population-based sample of 1063 patients was included. Failure of intravenous cannulation was observed in 182/1063 patients (17%). Five variables were associated with a failed first attempt of peripheral intravenous cannulation: palpability of the target vein (OR = 4.94, 95% CI [2.85-8.56]; P < 0.001), visibility of the target vein (OR = 3.63, 95% CI [2.09-6.32]; P < 0.001), a history of difficult peripheral intravenous cannulation (OR = 3.86, 95% CI [2.39-6.25]; P < 0.001), an unplanned indication for surgery (OR = 4.86, 95% CI [2.92-8.07]; P < 0.001), and the vein diameter of at most 2 millimeters (OR = 3.37, 95% CI [2.12-5.36]; P < 0.001). The scoring system was applied in 3 risk groups: 36/788 patients (5%) suffered from a failed first attempt in the low-risk group (A-DIVA score 0 or 1), whereas the medium (A-DIVA score 2 or 3) and high-risk group (A-DIVA score 4 plus

  11. Intermediate markers as surrogate endpoints in cancer research.

    PubMed

    Schatzkin, A

    2000-08-01

    Because studies with surrogate cancer endpoints can be smaller, faster, and substantially less expensive than those with frank cancer outcomes, the use of surrogate endpoints is undeniably attractive. This attractiveness is likely to grow in coming years as the rapidly advancing discoveries in cell and molecular biology generate new therapies requiring testing and new markers that could plausibly serve as surrogates for cancer. Surrogate endpoint studies can certainly be suggestive. They continue to play a legitimate role in phase II studies, and they may give the right answers about intervention effects on or exposure associations with cancer. The problem is the uncertainty attached to most potential surrogates. Except for those few surrogates that are both necessary for and developmentally relatively close to cancer, the existence of plausible alternative pathways makes inferences about cancer from many surrogates problematic. Merely being on the causal pathway to cancer does not in itself constitute surrogate validity. It is the totality of causal connections that is critical. There is, unfortunately, a fairly extensive history of quite plausible surrogate markers giving the wrong answer about various chronic disease therapies. There is no reason to believe that cancer surrogacy is immune to such inferential difficulties. This article is, in part, an invitation, even a plea, for researchers to carry out the investigations necessary to evaluate potential surrogates, particularly surrogate-cancer studies and intervention or exposure-surrogate-cancer mediation analyses. Such studies are needed to generalize from surrogate endpoint findings to cancer. There is, however, an implicit and perhaps unavoidable irony here: the large, long, expensive studies required to evaluate potential surrogates fully are precisely the studies that surrogates were designed to replace. The exposure dependence alluded to earlier complicates matters further: establishing validity for a

  12. Emotional experiences in surrogate mothers: A qualitative study

    PubMed Central

    Ahmari Tehran, Hoda; Tashi, Shohreh; Mehran, Nahid; Eskandari, Narges; Dadkhah Tehrani, Tahmineh

    2014-01-01

    Background: Surrogacy is one of the new techniques of assisted reproduction technology in which a woman carries and bears a child for another woman. In Iran, many Shia clerics and jurists considered it permissible so there is no religious prohibition for it. In addition to the risk of physical complications for complete surrogate mothers, the possibility of psychological complications resulted from emotional attachment to a living creature in the surrogate mother as another injury requires counseling and assessment prior to acceptance by infertile couples and complete surrogate mothers. Objective: The purpose of this study was to assess the emotional experiences of surrogate mothers. Materials and Methods: This was a qualitative, phenomenological study. We selected eight complete surrogate mothers in Isfahan. We used convenient sampling method and in-depth interview to collect the information. The data analysis was fulfilled via Colaizzi’s seven-stage method. Reliability and validity study of the roots in the four-axis was done. Results: The findings of these interviews were classified into two main themes and four sub themes: acquired experiences in pregnancy (feelings toward pregnancy, relationship with family, relatives and commissioning couple) and consequences of surrogacy (complications of pregnancy, religious and financial problems of surrogacy). Conclusion: Surrogacy pregnancy should be considered as high-risk emotional experience because many of surrogate mothers may face negative experiences. Therefore, it is recommended that surrogates should receive professional counseling prior to, during and following pregnancy. PMID:25114669

  13. Prenatal Arsenic Exposure and the Epigenome: Identifying Sites of 5-methylcytosine Alterations that Predict Functional Changes in Gene Expression in Newborn Cord Blood and Subsequent Birth Outcomes

    PubMed Central

    Rojas, Daniel; Rager, Julia E.; Smeester, Lisa; Bailey, Kathryn A.; Drobná, Zuzana; Rubio-Andrade, Marisela; Stýblo, Miroslav; García-Vargas, Gonzalo; Fry, Rebecca C.

    2015-01-01

    Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from subjects enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, who were exposed to a range of drinking water arsenic concentrations (0.456–236 µg/l). Changes in iAs-associated DNA 5-methylcytosine methylation were assessed across 424 935 CpG sites representing 18 761 genes and compared with corresponding mRNA expression levels and birth outcomes. In the context of arsenic exposure, a total of 2919 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyses identified DNA methylation changes that were most predictive of gene expression levels where CpG methylation within CpG islands positioned within the first exon, the 5′ untranslated region and 200 bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of 7 of these genes were associated with differences in birth outcomes including gestational age and head circumference.These data highlight the complex interplay between DNA methylation, functional changes in gene expression and health outcomes and underscore the need for functional analyses coupled to epigenetic assessments. PMID:25304211

  14. Surrogate motherhood as a medical treatment procedure for women's infertility.

    PubMed

    Jovic, Olga S

    2011-03-01

    The content of this work is conceived on the research of the consequences of surrogate motherhood as a process of assisted procreation, which represent a way of parenthood in cases when it is not possible to realize parenthood through a natural way. Surrogate motherhood is a process in which a woman (surrogate mother) agrees to carry a pregnancy with the intent to give the child to the couple with whom she has made a contract on surrogate maternity after the birth. This process of conception and birth makes the determination of the child's origin on its mother's side hard to determine, because of the distinction of the genetic and gestation phases of the two women. The concept of surrogate motherhood is to appear in two forms, depending on the existence or the non-existence of the genetic link between the surrogate mother and the child she gives birth to. There are gestation (full) and genetic (partial) surrogates each with different modalities and legal and ethical implications. In Serbia, Infertility Treatment and the Bio-medically Assisted Procreation Act from 2009 explicitly forbids surrogate motherhood, despite the fact that an infertile couple decides to use it, as a rule, after having tried all other treatment procedures, in cases when there is a diagnosis but the conventional treatment applied has not produced the desired results. Given the fact that no one has the right to ignore the sufferings of people who cannot procreate naturally, the medical practice and legal science in our country plead for a formulation of a legal framework in which to apply surrogate motherhood as an infertility treatment, under particular conditions. PMID:21528795

  15. Inferring Positions of Tumor and Nodes in Stage III Lung Cancer From Multiple Anatomical Surrogates Using Four-Dimensional Computed Tomography

    SciTech Connect

    Malinowski, Kathleen T.; Pantarotto, Jason R.; Senan, Suresh

    2010-08-01

    Purpose: To investigate the feasibility of modeling Stage III lung cancer tumor and node positions from anatomical surrogates. Methods and Materials: To localize their centroids, the primary tumor and lymph nodes from 16 Stage III lung cancer patients were contoured in 10 equal-phase planning four-dimensional (4D) computed tomography (CT) image sets. The centroids of anatomical respiratory surrogates (carina, xyphoid, nipples, mid-sternum) in each image set were also localized. The correlations between target and surrogate positions were determined, and ordinary least-squares (OLS) and partial least-squares (PLS) regression models based on a subset of respiratory phases (three to eight randomly selected) were created to predict the target positions in the remaining images. The three-phase image sets that provided the best predictive information were used to create models based on either the carina alone or all surrogates. Results: The surrogate most correlated with target motion varied widely. Depending on the number of phases used to build the models, mean OLS and PLS errors were 1.0 to 1.4 mm and 0.8 to 1.0 mm, respectively. Models trained on the 0%, 40%, and 80% respiration phases had mean ({+-} standard deviation) PLS errors of 0.8 {+-} 0.5 mm and 1.1 {+-} 1.1 mm for models based on all surrogates and carina alone, respectively. For target coordinates with motion >5 mm, the mean three-phase PLS error based on all surrogates was 1.1 mm. Conclusions: Our results establish the feasibility of inferring primary tumor and nodal motion from anatomical surrogates in 4D CT scans of Stage III lung cancer. Using inferential modeling to decrease the processing time of 4D CT scans may facilitate incorporation of patient-specific treatment margins.

  16. Surrogates of long-term vitamin d exposure and ovarian cancer risk in two prospective cohort studies.

    PubMed

    Prescott, Jennifer; Bertrand, Kimberly A; Poole, Elizabeth M; Rosner, Bernard A; Tworoger, Shelley S

    2013-01-01

    Experimental evidence and ecologic studies suggest a protective role of vitamin D in ovarian carcinogenesis. However, epidemiologic studies using individual level data have been inconsistent. We evaluated ultraviolet (UV)-B radiation, vitamin D intake, and predicted plasma 25-hydroxyvitamin D [25(OH)D] levels as long-term surrogates of vitamin D exposure within the Nurses' Health Study (NHS) and NHSII. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of overall ovarian cancer and by histologic subtype using Cox proportional hazards models. Between 1976 and 2010 in NHS and 1989 and 2011 in NHSII, we identified a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up. Cumulative average UV-B exposure was not associated with ovarian cancer risk in NHS (Ptrend = 0.08), but was associated with reduced risk in NHSII (highest vs. lowest category RR = 0.67; 95% CI: 0.50, 0.89; Ptrend < 0.01). When stratified by histologic subtype, UV-B flux was positively associated with risk of serous tumors in NHS (Ptrend < 0.01), but inversely associated in NHSII (Ptrend = 0.01). Adjusted for confounders, ovarian cancer risk was not associated with vitamin D intake from food or supplements or with predicted 25(OH)D levels. Our study does not strongly support a protective role for vitamin D in ovarian cancer risk. PMID:24351671

  17. Development of Depletion Code Surrogate Models for Uncertainty Propagation in Scenario Studies

    NASA Astrophysics Data System (ADS)

    Krivtchik, Guillaume; Coquelet-Pascal, Christine; Blaise, Patrick; Garzenne, Claude; Le Mer, Joël; Freynet, David

    2014-06-01

    The result of transition scenario studies, which enable the comparison of different options of the reactor fleet evolution and management of the future fuel cycle materials, allow to perform technical and economic feasibility studies. The COSI code is developed by CEA and used to perform scenario calculations. It allows to model any fuel type, reactor fleet, fuel facility, and permits the tracking of U, Pu, minor actinides and fission products nuclides on a large time scale. COSI is coupled with the CESAR code which performs the depletion calculations based on one-group cross-section libraries and nuclear data. Different types of uncertainties have an impact on scenario studies: nuclear data and scenario assumptions. Therefore, it is necessary to evaluate their impact on the major scenario results. The methodology adopted to propagate these uncertainties throughout the scenario calculations is a stochastic approach. Considering the amount of inputs to be sampled in order to perform a stochastic calculation of the propagated uncertainty, it appears necessary to reduce the calculation time. Given that evolution calculations represent approximately 95% of the total scenario simulation time, an optimization can be done, with the development and implementation of a surrogate models library of CESAR in COSI. The input parameters of CESAR are sampled with URANIE, the CEA uncertainty platform, and for every sample, the isotopic composition after evolution evaluated with CESAR is stored. Then statistical analysis of the input and output tables allow to model the behavior of CESAR on each CESAR library, i.e. building a surrogate model. Several quality tests are performed on each surrogate model to insure the prediction power is satisfying. Afterward, a new routine implemented in COSI reads these surrogate models and using them in replacement of CESAR calculations. A preliminary study of the calculation time gain shows that the use of surrogate models allows stochastic

  18. Methodology for Formulating Diesel Surrogate Fuels with Accurate Compositional, Ignition-Quality, and Volatility Characteristics

    SciTech Connect

    Mueller, Charles J.; Cannella, William J.; Bruno, Thomas J.; Bunting, Bruce G.; Dettman, Heather; Franz, James A.; Huber, Marcia L.; Natarajan, Mani; Pitz, William J.; Ratcliff, Matthew A.; Wright, Ken

    2012-07-26

    In this study, a novel approach was developed to formulate surrogate fuels having characteristics that are representative of diesel fuels produced from real-world refinery streams. Because diesel fuels typically consist of hundreds of compounds, it is difficult to conclusively determine the effects of fuel composition on combustion properties. Surrogate fuels, being simpler representations of these practical fuels, are of interest because they can provide a better understanding of fundamental fuel-composition and property effects on combustion and emissions-formation processes in internal-combustion engines. In addition, the application of surrogate fuels in numerical simulations with accurate vaporization, mixing, and combustion models could revolutionize future engine designs by enabling computational optimization for evolving real fuels. Dependable computational design would not only improve engine function, it would do so at significant cost savings relative to current optimization strategies that rely on physical testing of hardware prototypes. The approach in this study utilized the stateof- the-art techniques of 13C and 1H nuclear magnetic resonance spectroscopy and the advanced distillation curve to characterize fuel composition and volatility, respectively. The ignition quality was quantified by the derived cetane number. Two wellcharacterized, ultra-low-sulfur #2 diesel reference fuels produced from refinery streams were used as target fuels: a 2007 emissions certification fuel and a Coordinating Research Council (CRC) Fuels for Advanced Combustion Engines (FACE) diesel fuel. A surrogate was created for each target fuel by blending eight pure compounds. The known carbon bond types within the pure compounds, as well as models for the ignition qualities and volatilities of their mixtures, were used in a multiproperty regression algorithm to determine optimal surrogate formulations. The predicted and measured surrogate-fuel properties were quantitatively

  19. Surrogate model approach for improving the performance of reactive transport simulations

    NASA Astrophysics Data System (ADS)

    Jatnieks, Janis; De Lucia, Marco; Sips, Mike; Dransch, Doris

    2016-04-01

    Reactive transport models can serve a large number of important geoscientific applications involving underground resources in industry and scientific research. It is common for simulation of reactive transport to consist of at least two coupled simulation models. First is a hydrodynamics simulator that is responsible for simulating the flow of groundwaters and transport of solutes. Hydrodynamics simulators are well established technology and can be very efficient. When hydrodynamics simulations are performed without coupled geochemistry, their spatial geometries can span millions of elements even when running on desktop workstations. Second is a geochemical simulation model that is coupled to the hydrodynamics simulator. Geochemical simulation models are much more computationally costly. This is a problem that makes reactive transport simulations spanning millions of spatial elements very difficult to achieve. To address this problem we propose to replace the coupled geochemical simulation model with a surrogate model. A surrogate is a statistical model created to include only the necessary subset of simulator complexity for a particular scenario. To demonstrate the viability of such an approach we tested it on a popular reactive transport benchmark problem that involves 1D Calcite transport. This is a published benchmark problem (Kolditz, 2012) for simulation models and for this reason we use it to test the surrogate model approach. To do this we tried a number of statistical models available through the caret and DiceEval packages for R, to be used as surrogate models. These were trained on randomly sampled subset of the input-output data from the geochemical simulation model used in the original reactive transport simulation. For validation we use the surrogate model to predict the simulator output using the part of sampled input data that was not used for training the statistical model. For this scenario we find that the multivariate adaptive regression splines

  20. Enteric Viral Surrogate Reduction by Chitosan.

    PubMed

    Davis, Robert; Zivanovic, Svetlana; Davidson, P Michael; D'Souza, Doris H

    2015-12-01

    Enteric viruses are a major problem in the food industry, especially as human noroviruses are the leading cause of nonbacterial gastroenteritis. Chitosan is known to be effective against some enteric viral surrogates, but more detailed studies are needed to determine the precise application variables. The main objective of this work was to determine the effect of increasing chitosan concentration (0.7-1.5% w/v) on the cultivable enteric viral surrogates, feline calicivirus (FCV-F9), murine norovirus (MNV-1), and bacteriophages (MS2 and phiX174) at 37 °C. Two chitosans (53 and 222 kDa) were dissolved in water (53 kDa) or 1% acetic acid (222 KDa) at 0.7-1.5%, and were then mixed with each virus to obtain a titer of ~5 log plaque-forming units (PFU)/mL. These mixtures were incubated for 3 h at 37 °C. Controls included untreated viruses in phosphate-buffered saline and viruses were enumerated by plaque assays. The 53 kDa chitosan at the concentrations tested reduced FCV-F9, MNV-1, MS2, and phi X174 by 2.6-2.9, 0.1-0.4, 2.6-2.8, and 0.7-0.9 log PFU/mL, respectively, while reduction by 222 kDa chitosan was 2.2-2.4, 0.8-1.0, 2.6-5.2, and 0.5-0.8 log PFU/mL, respectively. The 222 kDa chitosan at 1 and 0.7% w/v in acetic acid (pH 4.5) caused the greatest reductions of MS2 by 5.2 logs and 2.6 logs, respectively. Overall, chitosan treatments showed the greatest reduction of MS2, followed by FCV-F9, phi X174, and MNV-1. These two chitosans may contribute to the reduction of enteric viruses at the concentrations tested but would require use of other hurdles to eliminate food borne viruses. PMID:26162243

  1. Carboxylate Surrogates Enhance the Antimycobacterial Activity of UDP-Galactopyranose Mutase Probes.

    PubMed

    Winton, Valerie J; Aldrich, Claudia; Kiessling, Laura L

    2016-08-12

    Uridine diphosphate galactopyranose mutase (UGM also known as Glf) is a biosynthetic enzyme required for construction of the galactan, an essential mycobacterial cell envelope polysaccharide. Our group previously identified two distinct classes of UGM inhibitors; each possesses a carboxylate moiety that is crucial for potency yet likely detrimental for cell permeability. To enhance the antimycobacterial potency, we sought to replace the carboxylate with a functional group mimic-an N-acylsulfonamide group. We therefore synthesized a series of N-acylsulfonamide analogs and tested their ability to inhibit UGM. For each inhibitor scaffold tested, the N-acylsulfonamide group functions as an effective carboxylate surrogate. Although the carboxylates and their surrogates show similar activity against UGM in a test tube, several N-acylsulfonamide derivatives more effectively block the growth of Mycobacterium smegmatis. These data suggest that the replacement of a carboxylate with an N-acylsulfonamide group could serve as a general strategy to augment antimycobacterial activity. PMID:27626294

  2. Identification of a physical metallurgy surrogate for the plutonium—1 wt. % gallium alloy

    NASA Astrophysics Data System (ADS)

    Gibbs, Frank E.; Olson, David L.; Hutchinson, William

    2000-07-01

    Future plutonium research is expected to be limited due to the downsizing of the nuclear weapons complex and an industry focus on environmental remediation and decommissioning of former manufacturing and research facilities. However, the need to further the understanding of the behavior of plutonium has not diminished. Disposition of high level residues, long-term storage of wastes, and certification of the nuclear stockpile through the Stockpile Stewardship Program are examples of the complex issues that must be addressed. Limited experimental facilities and the increasing cost of conducting plutonium research provide a strong argument for the development of surrogate materials. The purpose of this work was to identify a plutonium surrogate based on fundamental principles such as electronic structure, and then to experimentally demonstrate its viability.

  3. Use of SDWBA predictions for acoustic volume backscattering and the Self-Organizing Map to discern frequencies identifying Meganyctiphanes norvegica from mesopelagic fish species

    NASA Astrophysics Data System (ADS)

    Peña, M.; Calise, L.

    2016-04-01

    To acoustically assess the biomass of multiple species or taxa within a survey region, the volume backscatter data should be apportioned to the constituent sound scatterers. Typically, measured backscatter is attributed to certain species using predictions at different frequencies, mostly based on the difference in scattering at the frequencies of 38 and 120 kHz (dual frequency method). We used the full version of the stochastic distortedwave Born approximation (SDWBA) model to predict backscatter spectra for Meganyctiphanes norvegica and to explore the sensitivities of ΔMVBS to the model parameters, e.g. acoustic frequency and incidence angle, and animal density and sound speed contrast, length, and shape. The orientation is almost the unique parameter responsible for variation, with fatness affecting longer lengths. We present a summary of ΔMVBS that can serve as the basis for identification algorithms. Next, we simulate the scenario encountered in the Balearic Sea (western Mediterranean) where Northern krill are mixed with mesopelagic fish species (bristlemouths and lanternfishes), which are modeled with a prolate spheroid model. Simulated numerical data are employed to emulate the discrimination process with the most common identification techniques and typical survey frequencies. The importance of using density-independent techniques for acoustic classification is highlighted. Finally, an unsupervised neural network, the Self-Organizing Map (SOM), is used to cluster these theoretical data and identify the frequencies that provide, in this case, the most classification potential. The simulation results confirm that pairs of frequencies spanning the Rayleigh and geometric scattering regimes of the targets are the most useful for clustering; a minimum of four frequencies are necessary to separate the three species, while three frequencies are able to differentiate krill from mesopelagic fish species.

  4. Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity.

    PubMed

    Meulendijks, Didier; Henricks, Linda M; Amstutz, Ursula; Froehlich, Tanja K; Largiadèr, Carlo R; Beijnen, Jos H; de Boer, Anthonius; Deenen, Maarten J; Cats, Annemieke; Schellens, Jan H M

    2016-06-01

    The objective of this study was to determine whether genotyping of MIR27A polymorphisms rs895819A>G and rs11671784C>T can be used to improve the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity (FP-toxicity). Patients treated previously in a prospective study with fluoropyrimidine-based chemotherapy were genotyped for rs895819 and rs11671784, and DPYD c.2846A>T, c.1679T>G, c.1129-5923C>G and c.1601G>A. The predictive value of MIR27A variants for early-onset grade ≥3 FP-toxicity, alone or in combination with DPYD variants, was tested in multivariable logistic regression models. Random-effects meta-analysis was performed, including previously published data. A total of 1,592 patients were included. Allele frequencies of rs895819 and rs11671784 were 0.331 and 0.020, respectively. In DPYD wild-type patients, MIR27A variants did not affect risk of FP-toxicity (OR 1.3 for ≥1 variant MIR27A allele vs. none, 95% CI: 0.87-1.82, p = 0.228). In contrast, in patients carrying DPYD variants, the presence of ≥1 rs895819 variant allele was associated with increased risk of FP-toxicity (OR 4.9, 95% CI: 1.24-19.7, p = 0.023). Rs11671784 was not associated with FP-toxicity (OR 2.9, 95% CI: 0.47-18.0, p = 0.253). Patients carrying a DPYD variant and rs895819 were at increased risk of FP-toxicity compared to patients wild type for rs895819 and DPYD (OR 2.4, 95% CI: 1.27-4.37, p = 0.007), while patients with a DPYD variant but without a MIR27A variant were not (OR 0.3 95% CI: 0.06-1.17, p = 0.081). In meta-analysis, rs895819 remained significantly associated with FP-toxicity in DPYD variant allele carriers, OR 5.4 (95% CI: 1.83-15.7, p = 0.002). This study demonstrates the clinical validity of combined MIR27A/DPYD screening to identify patients at risk of severe FP-toxicity. PMID:26804235

  5. A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease

    PubMed Central

    Onken, Michael D.; Winkler, Ashley E.; Kanchi, Krishna-Latha; Chalivendra, Varun; Law, Jonathan H.; Rickert, Charles G.; Kallogjeri, Dorina; Judd, Nancy P.; Dunn, Gavin P.; Piccirillo, Jay F.; Lewis, James S.; Mardis, Elaine R.; Uppaluri, Ravindra

    2014-01-01

    Purpose Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance. Experimental Design Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature and we assessed its representation in 4 independent human datasets comprising 324 patients using weighted voting and Gene Set Enrichment Analysis (GSEA). Kaplan-Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A qRT-PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy. Results NGS revealed conservation of human driver pathway mutations in mouse OSCC including in Trp53, MAPK, PI3K, NOTCH, JAK/STAT and FAT1–4. Moreover, comparative analysis between The Cancer Genome Atlas (TCGA) and mouse samples defined AKAP9, MED12L and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in 4 independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified OSCC patients with a 93.5% accuracy. Conclusions These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. PMID:24668645

  6. Surrogate/spent fuel sabotage : aerosol ratio test program and Phase 2 test results.

    SciTech Connect

    Borek, Theodore Thaddeus III; Thompson, N. Slater; Sorenson, Ken Bryce; Hibbs, R.S.; Nolte, Oliver; Molecke, Martin Alan; Autrusson, Bruno; Young, F. I.; Koch, Wolfgang; Brochard, Didier; Pretzsch, Gunter Guido; Lange, Florentin

    2004-05-01

    A multinational test program is in progress to quantify the aerosol particulates produced when a high energy density device, HEDD, impacts surrogate material and actual spent fuel test rodlets. This program provides needed data that are relevant to some sabotage scenarios in relation to spent fuel transport and storage casks, and associated risk assessments; the program also provides significant political benefits in international cooperation. We are quantifying the spent fuel ratio, SFR, the ratio of the aerosol particles released from HEDD-impacted actual spent fuel to the aerosol particles produced from surrogate materials, measured under closely matched test conditions. In addition, we are measuring the amounts, nuclide content, size distribution of the released aerosol materials, and enhanced sorption of volatile fission product nuclides onto specific aerosol particle size fractions. These data are crucial for predicting radiological impacts. This document includes a thorough description of the test program, including the current, detailed test plan, concept and design, plus a description of all test components, and requirements for future components and related nuclear facility needs. It also serves as a program status report as of the end of FY 2003. All available test results, observations, and analyses - primarily for surrogate material Phase 2 tests using cerium oxide sintered ceramic pellets are included. This spent fuel sabotage - aerosol test program is coordinated with the international Working Group for Sabotage Concerns of Transport and Storage Casks, WGSTSC, and supported by both the U.S. Department of Energy and Nuclear Regulatory Commission.

  7. Evaluation of surrogate tissues as indicators of drug activity in a melanoma skin model.

    PubMed

    Parekh, Palak R; Choudhuri, Rohini; Weyemi, Urbain; Martin, Olga A; Bonner, William M; Redon, Christophe E

    2016-08-01

    The development of novel cancer treatments is a challenging task, partly because results from model systems often fail to predict drug efficacy in humans, and also tumors are often inaccessible for biochemical analysis, preventing effective monitoring of drug activity in vivo. Utilizing a model system, we evaluated the use of drug-induced DNA damage in surrogate tissues as indicators of drug efficacy. Samples of a commercially available melanoma skin model (Mattek MLNM-FT-A375) containing keratinocyte and fibroblast layers with melanoma nodules were subjected to various chemotherapeutic regimens for one, four, or eight days. At these times they were analyzed for DNA double-stranded breaks (γH2AX foci) and apoptosis (TUNEL). A wide range of drug responses in both tumor and normal tissues were observed and cataloged. For the melanoma, the most common drug response was apoptosis. The basal keratinocyte layer, which was the most reliable indicator of drug response in the melanoma skin model, responded with γH2AX foci formation that was abrupt and transient. The relationships between tumor and surrogate tissue drug responses are complex, indicating that while surrogate tissue drug responses may be useful clinical tools, careful control of variables such as the timing of sampling may be important in interpreting the results. PMID:27339860

  8. Sheepshead minnows (Cyprinodon variegatus) as a surrogate species in assessing contaminant risk to two endangered cyprinodontids

    SciTech Connect

    Brecken-Folse, J.; Albrecht, B.; Mayer, F.; Ellersieck, M.; Sappington, L.

    1995-12-31

    Sheepshead minnows (Cyprinodon variegatus) were tested as a surrogate species to assess contaminant risk for the endangered Leon Springs pupfish (C. bovinus) and desert pupfish (C. macularius). Acute toxicity tests were conducted with carbaryl, copper sulfate, 4-nonylphenol, pentachlorophenol, and permethrin in accordance with ASTM guidelines. Sheepshead minnows were always more sensitive than pupfish, but the differences were small. 96-h LC50s for sheepshead minnows and Leon Springs pupfish were, respectively: carbaryl (4.2 and 4.6 mg/L), copper sulfate (2.5 and 4.6 mg/L), 4-nonylphenol (0.46 and 0.48 mg/L), pentachlorophenol (0.05 and 0.08 mg/L), permethrin (1 7 and 21 ug/L). Only one test could be conducted with desert pupfish and carbaryl, with the sheepshead minnow being more sensitive (7.3 vs 4.2 mg/L). These data, along with other data from the US NBS, Columbia, MO (two surrogate and six endangered freshwater fishes), indicate that toxicity test data for surrogate fishes can be used reliably to predict chemical toxicity to endangered fishes by interspecies correlations. However, the correlations were generally best within a family, particularly with the Cyprinodontids.

  9. A Surrogate Hamiltonian study of femtosecond photodesorption of CO from NiO(100)

    NASA Astrophysics Data System (ADS)

    Asplund, Erik; Klüner, Thorsten

    2013-09-01

    In this paper, the Surrogate Hamiltonian approach is employed in order to study electronic relaxation in femtosecond laser-induced desorption experiments of CO from NiO(100). The study is based on ab initio calculations and a microscopic description of the NiO(100)-surface and the relaxation mechanism developed by Koch et al. The relaxation mechanism is assumed to be of dipole-dipole interaction nature, where the transition dipole moment of the adsorbate interacts with surface electron-hole pairs. In the Surrogate Hamiltonian approach the electron-hole pairs are treated as two-level systems and are described by excitation energy and a dipole charge. The Surrogate Hamiltonian parameters and potential energy surfaces used are obtained from ab initio calculations. The desorption probability and the velocity distributions of the desorbing molecules are calculated and an excited state lifetime is predicted. Throughout this paper atomic units, i.e. ℏ︀ = m e = e = a 0 = 1, have been used unless otherwise stated.

  10. Incidence of Changes in Respiration-Induced Tumor Motion and Its Relationship With Respiratory Surrogates During Individual Treatment Fractions

    SciTech Connect

    Malinowski, Kathleen; McAvoy, Thomas J.; George, Rohini; Dietrich, Sonja; D'Souza, Warren D.

    2012-04-01

    Purpose: To determine how frequently (1) tumor motion and (2) the spatial relationship between tumor and respiratory surrogate markers change during a treatment fraction in lung and pancreas cancer patients. Methods and Materials: A Cyberknife Synchrony system radiographically localized the tumor and simultaneously tracked three respiratory surrogate markers fixed to a form-fitting vest. Data in 55 lung and 29 pancreas fractions were divided into successive 10-min blocks. Mean tumor positions and tumor position distributions were compared across 10-min blocks of data. Treatment margins were calculated from both 10 and 30 min of data. Partial least squares (PLS) regression models of tumor positions as a function of external surrogate marker positions were created from the first 10 min of data in each fraction; the incidence of significant PLS model degradation was used to assess changes in the spatial relationship between tumors and surrogate markers. Results: The absolute change in mean tumor position from first to third 10-min blocks was >5 mm in 13% and 7% of lung and pancreas cases, respectively. Superior-inferior and medial-lateral differences in mean tumor position were significantly associated with the lobe of lung. In 61% and 54% of lung and pancreas fractions, respectively, margins calculated from 30 min of data were larger than margins calculated from 10 min of data. The change in treatment margin magnitude for superior-inferior motion was >1 mm in 42% of lung and 45% of pancreas fractions. Significantly increasing tumor position prediction model error (mean {+-} standard deviation rates of change of 1.6 {+-} 2.5 mm per 10 min) over 30 min indicated tumor-surrogate relationship changes in 63% of fractions. Conclusions: Both tumor motion and the relationship between tumor and respiratory surrogate displacements change in most treatment fractions for patient in-room time of 30 min.

  11. SURROGATE SPECIES IN ASSESSING CONTAMINANT RISK FOR ENDANGERED FISHES

    EPA Science Inventory

    Rainbow trout, fathead minnows, and sheepshead minnows were tested as surrogate species to assess contaminant risk for 17 endangered fishes and one toad species. Acute toxicity tests were conducted with carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin in accord...

  12. Bioaccessibility of metals in alloys: Evaluation of three surrogate biofluids

    PubMed Central

    Hillwalker, Wendy E.; Anderson, Kim A.

    2014-01-01

    Bioaccessibility in vitro tests measure the solubility of materials in surrogate biofluids. However, the lack of uniform methods and the effects of variable test parameters on material solubility limit interpretation. One aim of this study was to measure and compare bioaccessibility of selected economically important alloys and metals in surrogate physiologically based biofluids representing oral, inhalation and dermal exposures. A second aim was to experimentally test different biofluid formulations and residence times in vitro. A third aim was evaluation of dissolution behavior of alloys with in vitro lung and dermal biofluid surrogates. This study evaluated the bioaccessibility of sixteen elements in six alloys and 3 elemental/metal powders. We found that the alloys/metals, the chemical properties of the surrogate fluid, and residence time all had major impacts on metal solubility. The large variability of bioaccessibility indicates the relevancy of assessing alloys as toxicologically distinct relative to individual metals. PMID:24212234

  13. Altruistic surrogacy: the necessary objectification of surrogate mothers.

    PubMed

    Tieu, M M

    2009-03-01

    One of the major concerns about surrogacy is the potential harm that may be inflicted upon the surrogate mother and the child after relinquishment. Even if one were to take the liberal view that surrogacy should be presumptively allowed on the basis of autonomy and/or compassion, evidence of harm must be taken seriously. In this paper I review the evidence from psychological studies on the effect that relinquishing a child has on the surrogate mother and while it appears that many surrogates are able to cope with relinquishment, I argue that there are good reasons, grounded in empirical evidence, to support the view that the subsequent management of the relinquishment necessarily objectifies the surrogate mother. PMID:19251968

  14. Bacillus thuringiensis as a surrogate for Bacillus anthracis in aerosol research.

    PubMed

    Tufts, Jenia A M; Calfee, M Worth; Lee, Sang Don; Ryan, Shawn P

    2014-05-01

    Characterization of candidate surrogate spores prior to experimental use is critical to confirm that the surrogate characteristics are as closely similar as possible to those of the pathogenic agent of interest. This review compares the physical properties inherent to spores of Bacillus anthracis (Ba) and Bacillus thuringiensis (Bt) that impact their movement in air and interaction with surfaces, including size, shape, density, surface morphology, structure and hydrophobicity. Also evaluated is the impact of irradiation on the physical properties of both Bacillus species. Many physical features of Bt and Ba have been found to be similar and, while Bt is considered typically non-pathogenic, it is in the B. cereus group, as is Ba. When cultured and sporulated under similar conditions, both microorganisms share a similar cylindrical pellet shape, an aerodynamic diameter of approximately 1 μm (in the respirable size range), have an exosporium with a hairy nap, and have higher relative hydrophobicities than other Bacillus species. While spore size, morphology, and other physical properties can vary among strains of the same species, the variations can be due to growth/sporulation conditions and may, therefore, be controlled. Growth and sporulation conditions are likely among the most important factors that influence the representativeness of one species, or preparation, to another. All Bt spores may, therefore, not be representative of all Ba spores. Irradiated spores do not appear to be a good surrogate to predict the behavior of non-irradiated spores due to structural damage caused by the irradiation. While the use of Bt as a surrogate for Ba in aerosol testing appears to be well supported, this review does not attempt to narrow selection between Bt strains. Comparative studies should be performed to test the hypothesis that viable Ba and Bt spores will behave similarly when suspended in the air (as an aerosol) and to compare the known microscale characteristics

  15. Act relating to surrogate parenthood contracts, 10 February 1988.

    PubMed

    1988-01-01

    This Nebraska Act provides that surrogate parenthood contracts are void and unenforceable and that the "biological father of a child born pursuant to such a contract shall have all the rights and obligations imposed by law with respect to the child." A surrogate parenthood contract is defined as "a contract by which a woman is to be compensated for bearing a child of a man who is not her husband." PMID:12289630

  16. Plan of Action: JASPER Management Prestart Review (Surrogate Material Experiments)

    SciTech Connect

    Cooper, W.E.

    2000-09-29

    The Lawrence Livermore National Laboratory (LLNL) Joint Actinide Shock Physics Experimental Research (JASPER) Facility is being developed at the Nevada Test Site (NTS) to conduct shock physics experiments on special nuclear material and other actinide materials. JASPER will use a two-stage, light-gas gun to shoot projectiles at actinide targets. Projectile velocities will range from 1 to 8 km/s, inducing pressures in the target material up to 6 Mbar. The JASPER gas gun has been designed to match the critical dimensions of the two-stage, light-gas gun in Building 341 of LLNL. The goal in copying the LLNL gun design is to take advantage of the extensive ballistics database that exists and to minimize the effort spent on gun characterization in the initial facility start-up. A siting study conducted by an inter-Laboratory team identified Able Site in Area 27 of the NTS as the best location for the JASPER gas gun. Able Site consists of three major buildings that had previously been used to support the nuclear test program. In April 1999, Able Site was decommissioned as a Nuclear Explosive Assembly Facility and turned back to the DOE for other uses. Construction and facility modifications at Able Site to support the JASPER project started in April 1999 and were completed in September 1999. The gas gun and the secondary confinement chamber (SCC) were installed in early 2000. During the year, all facility and operational systems were brought on line. Initial system integration demonstrations were completed in September 2000. The facility is anticipated to be operational by August 2001, and the expected life cycle for the facility is 10 years. LLNL Nevada Experiments and Operations (N) Program has established a Management Prestart Review (MPR) team to determine the readiness of the JASPER personnel and facilities to initiate surrogate-material experiments. The review coincides with the completion of authorization-basis documents and physical subsystems, which have

  17. Plan of Action: JASPER Management Prestart Review (Surrogate Material Experiment)

    SciTech Connect

    Cooper, W E

    2000-12-05

    The Lawrence Livermore National Laboratory (LLNL) Joint Actinide Shock Physics Experimental Research (JASPER) Facility is being developed at the Nevada Test Site (NTS) to conduct shock physics experiments on special nuclear material and other actinide materials. JASPER will use a two-stage, light-gas gun to shoot projectiles at actinide targets. Projectile velocities will range from 1 to 8 km/s, inducing pressures in the target material up to 6 Mbar. The JASPER gas gun has been designed to match the critical dimensions of the two-stage, light-gas gun in Building 341 of LLNL. The goal in copying the LLNL gun design is to take advantage of the extensive ballistics database that exists and to minimize the effort spent on gun characterization in the initial facility start-up. A siting study conducted by an inter-Laboratory team identified Able Site in Area 27 of the NTS as the best location for the JASPER gas gun. Able Site consists of three major buildings that had previously been used to support the nuclear test program. In April 1999, Able Site was decommissioned as a Nuclear Explosive Assembly Facility and turned back to the DOE for other uses. Construction and facility modifications at Able Site to support the JASPER project started in April 1999 and were completed in September 1999. The gas gun and the secondary confinement chamber (SCC) were installed in early 2000. During the year, all facility and operational systems were brought on line. Initial system integration demonstrations were completed in September 2000. The facility is anticipated to be operational by August 2001, and the expected life cycle for the facility is 10 years. LLNL Nevada Experiments and Operations (N) Program has established a Management Prestart Review (MPR) team to determine the readiness of the JASPER personnel and facilities to initiate surrogate-material experiments. The review coincides with the completion of authorization-basis documents and physical subsystems, which have

  18. Bench-scale Analysis of Surrogates for Anaerobic Digestion Processes.

    PubMed

    Carroll, Zachary S; Long, Sharon C

    2016-05-01

    Frequent monitoring of anaerobic digestion processes for pathogen destruction is both cost and time prohibitive. The use of surrogates to supplement regulatory monitoring may be one solution. To evaluate surrogates, a semi-batch bench-scale anaerobic digester design was tested. Bench-scale reactors were operated under mesophilic (36 °C) and thermophilic (53-55 °C) conditions, with a 15 day solids retention time. Biosolids from different facilities and during different seasons were examined. USEPA regulated pathogens and surrogate organisms were enumerated at different times throughout each experiment. The surrogate organisms included fecal coliforms, E. coli, enterococci, male-specific and somatic coliphages, Clostridium perfringens, and bacterial spores. Male-specific coliphages tested well as a potential surrogate organism for virus inactivation. None of the tested surrogate organisms correlated well with helminth inactivation under the conditions studied. There were statistically significant differences in the inactivation rates between the facilities in this study, but not between seasons. PMID:27131309

  19. Coastal aquifer management based on surrogate models and multi-objective optimization

    NASA Astrophysics Data System (ADS)

    Mantoglou, A.; Kourakos, G.

    2011-12-01

    The demand for fresh water in coastal areas and islands can be very high, especially in summer months, due to increased local needs and tourism. In order to satisfy demand, a combined management plan is proposed which involves: i) desalinization (if needed) of pumped water to a potable level using reverse osmosis and ii) injection of biologically treated waste water into the aquifer. The management plan is formulated into a multiobjective optimization framework, where simultaneous minimization of economic and environmental costs is desired; subject to a constraint to satisfy demand. The method requires modeling tools, which are able to predict the salinity levels of the aquifer in response to different alternative management scenarios. Variable density models can simulate the interaction between fresh and saltwater; however, they are computationally intractable when integrated in optimization algorithms. In order to alleviate this problem, a multi objective optimization algorithm is developed combining surrogate models based on Modular Neural Networks [MOSA(MNN)]. The surrogate models are trained adaptively during optimization based on a Genetic Algorithm. In the crossover step of the genetic algorithm, each pair of parents generates a pool of offspring. All offspring are evaluated based on the fast surrogate model. Then only the most promising offspring are evaluated based on the exact numerical model. This eliminates errors in Pareto solution due to imprecise predictions of the surrogate model. Three new criteria for selecting the most promising offspring were proposed, which improve the Pareto set and maintain the diversity of the optimum solutions. The method has important advancements compared to previous methods, e.g. alleviation of propagation of errors due to surrogate model approximations. The method is applied to a real coastal aquifer in the island of Santorini which is a very touristy island with high water demands. The results show that the algorithm

  20. Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration.

    PubMed

    Levey, Andrew S; Cattran, Daniel; Friedman, Aaron; Miller, W Greg; Sedor, John; Tuttle, Katherine; Kasiske, Bertram; Hostetter, Thomas

    2009-08-01

    Changes in proteinuria have been suggested as a surrogate outcome for kidney disease progression to facilitate the conduct of clinical trials. This report summarizes a workshop sponsored by the National Kidney Foundation and US Food and Drug Administration (FDA) with the following goals: (1) to evaluate the strengths and limitations of criteria for assessment of proteinuria as a potential surrogate end point for clinical trials in chronic kidney disease (CKD), (2) to explore the strengths and limitations of available data for proteinuria as a potential surrogate end point, and (3) to delineate what more needs to be done to evaluate proteinuria as a potential surrogate end point. We review the importance of proteinuria in CKD, including the conceptual model for CKD, measurement of proteinuria and albuminuria, and epidemiological characteristics of albuminuria in the United States. We discuss surrogate end points in clinical trials of drug therapy, including criteria for drug approval, the definition of a surrogate end point, and criteria for evaluation of surrogacy based on biological plausibility, epidemiological characteristics, and clinical trials. Next, the report summarizes data for proteinuria as a potential surrogate outcome in 3 broad clinical areas: early diabetic kidney disease, nephrotic syndrome, and diseases with mild to moderate proteinuria. We conclude with a synthesis of data and recommendations for further research. At the present time, there appears to be sufficient evidence to recommend changes in proteinuria as a surrogate for kidney disease progression in only selected circumstances. Further research is needed to define additional contexts in which changes in proteinuria can be expected to predict treatment effect. We recommend collaboration among many groups, including academia, industry, the FDA, and the National Institutes of Health, to share data from past and future studies. PMID:19577347

  1. Gamma-ray Sptectrometric Characterization of Overpacked CC 104/107 RH-TRU Wastes: Surrogate Tests

    SciTech Connect

    Hartwell, John Kelvin; Mc Ilwain, Michael Edward; Klann, R. T.

    2000-04-01

    Development of the gamma-ray spectrometric technique termed GSAK (Gamma-Ray Spectrometry with Acceptable Knowledge) for the characterization of CC104/107 remote-handled transuranic (RH-TRU) wastes continued this year. Proof-of-principle measurements have been completed on the surrogate RH-TRU waste drums configured earlier this year. The GSAK technique uses conventional gamma-ray spectrometry to quantify the detectable fission product content of overpacked RH-TRU drums. These results are then coupled with the inventory report to characterize the waste drum content. The inventory report is based on process knowledge of the waste drum loading and calculations of the isotopic distribution in the spent fuel examined to generate the drummed wastes. Three RH-TRU surrogate drums were configured with encapsulated EBR-II driver fuel rod segments arranged in the surrogate drum assemblies. Segment-specific inventory calculations initially specified the radionuclide content of the fuel segments and thus the surrogate drums. Radiochemical assays performed on representative fuel element segments identified a problem in the accuracy of some of the fission and activation product inventory values and provided a basis for adjustment of the specified surrogate drum inventories. The three waste drum surrogates, contained within their 8.9 cm (3.5 inch) thick steel overpacks, were analyzed by gamma-ray spectrometry at the TREAT facility at Argonne National Laboratory-West. Seven fission and activation product radionuclides (54Mn, 60Co, 125Sb, 134Cs, 137Cs, 144CePr, and 154Eu) were reliably detected. The gamma-ray spectral accuracy was very good. In all cases, a two-sigma error bar constructed about the measured value included the actual drum activity.

  2. Gamma-Ray Spectrometric Characterization of Overpacked CC104/107 RH-TRU Wastes: Surrogate Tests

    SciTech Connect

    J. K. Hartwell; R. T. Klann; M. E. McIlwain

    2000-05-01

    Development of the gamma-ray spectrometric technique termed GSAK (Gamma-Ray Spectrometry with Acceptable Knowledge) for the characterization of CC104/107 remote-handled transuranic (RH-TRU) wastes continued this year. Proof-of-principle measurements have been completed on the surrogate RH-TRU waste drums configured earlier this year. The GSAK technique uses conventional gamma-ray spectrometry to quantify the detectable fission product content of overpacked RH-TRU drums. These results are then coupled with the inventory report to characterize the waste drum content. The inventory report is based on process knowledge of the waste drum loading and calculations of the isotopic distribution in the spent fuel examined to generate the drummed wastes. Three RH-TRU surrogate drums were configured with encapsulated EBR-II driver fuel rod segments arranged in the surrogate drum assemblies. Segment-specific inventory calculations initially specified the radionuclide content of the fuel segments and thus the surrogate drums. Radiochemical assays performed on representative fuel element segments identified a problem in the accuracy of some of the fission and activation product inventory values and provided a basis for adjustment of the specified surrogate drum inventories. The three waste drum surrogates, contained within their 8.9 cm (3.5 inch) thick steel overpacks, were analyzed by gamma-ray spectrometry at the TREAT facility at Argonne National Laboratory-West. Seven fission and activation product radionuclides ({sup 54}Mn, {sup 60}Co, {sup 125}Sb, {sup 134}Cs, {sup 137}Cs, {sup 144}CePr, and {sup 154}Eu) were reliably detected. The gamma-ray spectral accuracy was very good. In all cases, a two-sigma error bar constructed about the measured value included the actual drum activity.

  3. Project ATHENA Creates Surrogate Human Organ Systems

    SciTech Connect

    MacQueen, Luke; Knospel, Fanny; Sherrod, Stacy; Iyer, Rashi

    2015-06-15

    The development of miniature surrogate human organs, coupled with highly sensitive mass spectrometry technologies, could one day revolutionize the way new drugs and toxic agents are studied. “By developing this ‘homo minutus,’ we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs,” said Rashi Iyer, a senior scientist at Los Alamos National Laboratory. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is nearing the full integration of four human organ constructs — liver, heart, lung and kidney — each organ component is about the size of a smartphone screen, and the whole ATHENA “body” of interconnected organs will fit neatly on a desk. A new video available on the Los Alamos National Laboratory YouTube channel updates the ATHENA project as it begins to integrate the various organ systems into a single system (link to video here). Some 40 percent of pharmaceuticals fail their clinical trials and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success. ATHENA is funded by the Defense Threat Reduction Agency (DTRA) and is a collaboration of Los Alamos National Laboratory, Harvard University, Vanderbilt University, Charité Universitätsmedizin, Berlin, Germany, CFD Research Corporation, and the University of California San Francisco.

  4. Surrogate ratio methodology for the indirect determination of neutron capture cross sections

    NASA Astrophysics Data System (ADS)

    Goldblum, B. L.; Prussin, S. G.; Bernstein, L. A.; Younes, W.; Guttormsen, M.; Nyhus, H. T.

    2010-05-01

    The relative γ-decay probabilities of the Dy162 to Dy161 and Dy162 to Dy164 residual nuclei, produced using light-ion-induced direct reactions, were measured as a function of excitation energy using the CACTUS array at the Oslo Cyclotron Laboratory. The external surrogate ratio method (SRM) was used to convert these relative γ-decay probabilities into the Dy161(n,γ) cross section in an equivalent neutron energy range of 130-560 keV. The directly measured Dy161(n,γ) cross section, obtained from the Evaluated Nuclear Data Files (ENDF/B-VII.0), was compared to the experimentally determined surrogate Dy161(n,γ) cross section obtained using compound-nucleus pairs with both similar (Dy162 to Dy164) and dissimilar (Dy162 to Dy161) nuclear structures. A γ-ray energy threshold was identified, based upon pairing gap parameters, that provides a first-order correction to the statistical γ-ray tagging approach and improves the agreement between the surrogate cross-section data and the evaluated result.

  5. Surrogate ratio methodology for the indirect determination of neutron capture cross sections

    SciTech Connect

    Goldblum, B. L.; Prussin, S. G.; Bernstein, L. A.; Younes, W.; Guttormsen, M.; Nyhus, H. T.

    2010-05-15

    The relative gamma-decay probabilities of the {sup 162}Dy to {sup 161}Dy and {sup 162}Dy to {sup 164}Dy residual nuclei, produced using light-ion-induced direct reactions, were measured as a function of excitation energy using the CACTUS array at the Oslo Cyclotron Laboratory. The external surrogate ratio method (SRM) was used to convert these relative gamma-decay probabilities into the {sup 161}Dy(n,gamma) cross section in an equivalent neutron energy range of 130-560 keV. The directly measured {sup 161}Dy(n,gamma) cross section, obtained from the Evaluated Nuclear Data Files (ENDF/B-VII.0), was compared to the experimentally determined surrogate {sup 161}Dy(n,gamma) cross section obtained using compound-nucleus pairs with both similar ({sup 162}Dy to {sup 164}Dy) and dissimilar ({sup 162}Dy to {sup 161}Dy) nuclear structures. A gamma-ray energy threshold was identified, based upon pairing gap parameters, that provides a first-order correction to the statistical gamma-ray tagging approach and improves the agreement between the surrogate cross-section data and the evaluated result.

  6. Concentration and retention of Toxoplasma gondii surrogates from seawater by red abalone (Haliotis rufescens)

    USGS Publications Warehouse

    Schott, Kristen C; Krusor, Colin; Tinker, M. Tim; Moore, James G.; Conrad, Patricia A.; Shapiro, Karen

    2016-01-01

    Small marine snails and abalone have been identified as high- and low-risk prey items, respectively, for exposure of threatened southern sea otters to Toxoplasma gondii, a zoonotic parasite that can cause fatal encephalitis in animals and humans. While recent work has characterized snails as paratenic hosts for T. gondii, the ability of abalone to vector the parasite has not been evaluated. To further elucidate why abalone predation may be protective against T. gondii exposure, this study aimed to determine whether: (1) abalone are physiologically capable of acquiring T. gondii; and (2) abalone and snails differ in their ability to concentrate and retain the parasite. Abalone were exposed to T. gondii surrogate microspheres for 24 h, and fecal samples were examined for 2 weeks following exposure. Concentration of surrogates was 2–3 orders of magnitude greater in abalone feces than in the spiked seawater, and excretion of surrogates continued for 14 days post-exposure. These results indicate that, physiologically, abalone and snails can equally vector T. gondii as paratenic hosts. Reduced risk of T. gondii infection in abalone-specializing otters may therefore result from abalone's high nutritional value, which implies otters must consume fewer animals to meet their caloric needs.

  7. Agreement between Older Persons and their Surrogate Decision Makers Regarding Participation in Advance Care Planning

    PubMed Central

    Fried, Terri R.; Redding, Colleen A.; Robbins, Mark L.; O'Leary, John R.; Iannone, Lynne

    2014-01-01

    Objectives To examine agreement between older persons and their surrogates regarding participation in advance care planning (ACP). Design Observational cohort study. Setting Community Participants Persons age ≥ 65 and the individual they identified as most likely to make treatment decisions on their behalf. Measurements Older persons were asked about participation in four activities: 1. Completion of living will; 2. Completion of health care proxy; 3. Communication regarding views about life-sustaining treatment; 4. Communication regarding views about quality versus quantity of life. Surrogates were asked whether they believed the older person had completed these activities. Results Of 216 pairs, 81% agreed about whether a living will had been completed [k = .61, 95% confidence interval (CI) .51, .72]. Only 68% of pairs agreed about whether a health care proxy had been completed (k = .39, 95% CI .29, .50), 64% agreed about whether they had communicated regarding life-sustaining treatment (k = .22, 95% CI .09, .35), and 62% agreed about whether they had communicated regarding quality versus quantity of life (k = .23, 95% CI .11, .35). Conclusions While agreement between older persons and their surrogates regarding living will completion was good, agreement about participation in other aspects of ACP was fair to poor. Additional study is necessary to determine who is providing the most accurate report of objective ACP components and whether agreement regarding participation in ACP is associated with greater shared understanding of patients’ preferences. PMID:21649619

  8. Early analysis of surrogate endpoints for metastatic melanoma in immune checkpoint inhibitor trials.

    PubMed

    Petrelli, Fausto; Coinu, Andrea; Cabiddu, Mary; Borgonovo, Karen; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

    2016-06-01

    Recent major phase III trials led to the approval of immune checkpoint inhibitors (ipilimumab, pembrolizumab, and nivolumab) in metastatic malignant melanoma (MM). We aim to assess whether median progression-free survival, and 1 and 2-year overall survival (OS) rates are reliable surrogate endpoints for median OS through a meta-analysis of published trials involving immunotherapy. A systematic literature search in PubMed, EMBASE, Web of Science, and SCOPUS of published phase II to III trials with immunotherapy as the treatment for MM was conducted. Adjusted weighted linear regression was used to calculate Pearson correlations (R) between surrogates and median OS, and between treatment effects on surrogates and median OS. A total of 13 studies involving 3373 patients with MM were identified. The correlation of progression-free survival with OS was not significant (R = 0.45, P = .11). Conversely, the correlation between 1-year OS and median OS was very strong (R = 0.93, 95% confidence interval [CI] 0.84-0.96, P < .00001), as was the correlation between 2-year OS and OS (R = 0.79, 95% CI 0.51-0.91, P = .0001). The correlation between the treatment effects on 1-year OS and OS was also significant (R = -0.86, 95% CI -0.3 to 0.97, P = .01). Similar results were obtained for 2-year OS. According to the available study data, 1-year OS rate could be regarded as a potential surrogate for median OS in novel immunotherapy trials of metastatic MM. Waiting for ongoing studies (e.g., pembrolizumab), we suggest that this intermediate endpoint could be considered as a potential primary endpoint in future clinical trials. PMID:27368007

  9. Early analysis of surrogate endpoints for metastatic melanoma in immune checkpoint inhibitor trials

    PubMed Central

    Petrelli, Fausto; Coinu, Andrea; Cabiddu, Mary; Borgonovo, Karen; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

    2016-01-01

    Abstract Recent major phase III trials led to the approval of immune checkpoint inhibitors (ipilimumab, pembrolizumab, and nivolumab) in metastatic malignant melanoma (MM). We aim to assess whether median progression-free survival, and 1 and 2-year overall survival (OS) rates are reliable surrogate endpoints for median OS through a meta-analysis of published trials involving immunotherapy. A systematic literature search in PubMed, EMBASE, Web of Science, and SCOPUS of published phase II to III trials with immunotherapy as the treatment for MM was conducted. Adjusted weighted linear regression was used to calculate Pearson correlations (R) between surrogates and median OS, and between treatment effects on surrogates and median OS. A total of 13 studies involving 3373 patients with MM were identified. The correlation of progression-free survival with OS was not significant (R = 0.45, P = .11). Conversely, the correlation between 1-year OS and median OS was very strong (R = 0.93, 95% confidence interval [CI] 0.84–0.96, P < .00001), as was the correlation between 2-year OS and OS (R = 0.79, 95% CI 0.51–0.91, P = .0001). The correlation between the treatment effects on 1-year OS and OS was also significant (R = −0.86, 95% CI −0.3 to 0.97, P = .01). Similar results were obtained for 2-year OS. According to the available study data, 1-year OS rate could be regarded as a potential surrogate for median OS in novel immunotherapy trials of metastatic MM. Waiting for ongoing studies (e.g., pembrolizumab), we suggest that this intermediate endpoint could be considered as a potential primary endpoint in future clinical trials. PMID:27368007

  10. Parameter identification and calibration of the Xin'anjiang model using the surrogate modeling approach

    NASA Astrophysics Data System (ADS)

    Ye, Yan; Song, Xiaomeng; Zhang, Jianyun; Kong, Fanzhe; Ma, Guangwen

    2014-06-01

    Practical experience has demonstrated that single objective functions, no matter how carefully chosen, prove to be inadequate in providing proper measurements for all of the characteristics of the observed data. One strategy to circumvent this problem is to define multiple fitting criteria that measure different aspects of system behavior, and to use multi-criteria optimization to identify non-dominated optimal solutions. Unfortunately, these analyses require running original simulation models thousands of times. As such, they demand prohibitively large computational budgets. As a result, surrogate models have been used in combination with a variety of multi-objective optimization algorithms to approximate the true Pareto-front within limited evaluations for the original model. In this study, multi-objective optimization based on surrogate modeling (multivariate adaptive regression splines, MARS) for a conceptual rainfall-runoff model (Xin'anjiang model, XAJ) was proposed. Taking the Yanduhe basin of Three Gorges in the upper stream of the Yangtze River in China as a case study, three evaluation criteria were selected to quantify the goodness-of-fit of observations against calculated values from the simulation model. The three criteria chosen were the Nash-Sutcliffe efficiency coefficient, the relative error of peak flow, and runoff volume (REPF and RERV). The efficacy of this method is demonstrated on the calibration of the XAJ model. Compared to the single objective optimization results, it was indicated that the multi-objective optimization method can infer the most probable parameter set. The results also demonstrate that the use of surrogate-modeling enables optimization that is much more efficient; and the total computational cost is reduced by about 92.5%, compared to optimization without using surrogate modeling. The results obtained with the proposed method support the feasibility of applying parameter optimization to computationally intensive simulation

  11. Comparison of Orbital Parameters for GEO Debris Predicted by LEGEND and Observed by MODEST: Can Sources of Orbital Debris be Identified?

    NASA Astrophysics Data System (ADS)

    Barker, E.; Matney, M. J.; Liou, J.-C.; Abercromby, K.; Rodriguez, H.; Seitzer, P.

    Since 2002 the National Aeronautics and Space Administration (NASA) has carried out an optical survey of the debris environment in the geosynchronous Earth-orbit (GEO) region with the Michigan Orbital Debris Survey Telescope (MODEST) in Chile. The survey coverage has been similar for 4 of the 5 years allowing us to follow the orbital evolution of Correlated Targets (CTs), both controlled and un-controlled objects, and Un-Correlated Targets (UCTs). Under gravitational perturbations the distributions of uncontrolled objects, both CTs and UCTs, in GEO orbits will evolve in predictable patterns, particularly evident in the inclination and right ascension of the ascending node (RAAN) distributions. There are several clusters (others have used a "cloud" nomenclature) in observed distributions that show evolution from year to year in their inclination and ascending node elements. However, when MODEST is in survey mode (field-of-view ~1.3°) it provides only short 5-8 minute orbital arcs which can only be fit under the assumption of a circular orbit approximation (ACO) to determine the orbital parameters. These ACO elements are useful only in a statistical sense as dedicated observing runs would be required to obtain sufficient orbital coverage to determine a set of accurate orbital elements and then to follow their evolution. Identification of the source(s) for these "clusters of UCTs" would be advantageous to the overall definition of the GEO orbital debris environment. This paper will set out to determine if the ACO elements can be used to in a statistical sense to identify the source of the "clustering of UCTs" roughly centered on an inclination of 12° and a RAAN of 345°. The breakup of the Titan 3C-4 transtage on February 21, 1992 has been modeled using NASA's LEGEND (LEO-to-GEO Environment Debris) code to generate a GEO debris cloud. Breakup fragments are created based on the NASA Standard Breakup Model (including fragment size, area-to-mass (A/M), and delta

  12. Comparison of Orbital Parameters for GEO Debris Predicted by LEGEND and Observed by MODEST: Can Sources of Orbital Debris be Identified?

    NASA Technical Reports Server (NTRS)

    Barker, Edwin S.; Matney, M. J.; Liou, J.-C.; Abercromby, K. J.; Rodriquez, H. M.; Seitzer, P.

    2006-01-01

    Since 2002 the National Aeronautics and Space Administration (NASA) has carried out an optical survey of the debris environment in the geosynchronous Earth-orbit (GEO) region with the Michigan Orbital Debris Survey Telescope (MODEST) in Chile. The survey coverage has been similar for 4 of the 5 years allowing us to follow the orbital evolution of Correlated Targets (CTs), both controlled and un-controlled objects, and Un-Correlated Targets (UCTs). Under gravitational perturbations the distributions of uncontrolled objects, both CTs and UCTs, in GEO orbits will evolve in predictable patterns, particularly evident in the inclination and right ascension of the ascending node (RAAN) distributions. There are several clusters (others have used a "cloud" nomenclature) in observed distributions that show evolution from year to year in their inclination and ascending node elements. However, when MODEST is in survey mode (field-of-view approx.1.3deg) it provides only short 5-8 minute orbital arcs which can only be fit under the assumption of a circular orbit approximation (ACO) to determine the orbital parameters. These ACO elements are useful only in a statistical sense as dedicated observing runs would be required to obtain sufficient orbital coverage to determine a set of accurate orbital elements and then to follow their evolution. Identification of the source(s) for these "clusters of UCTs" would be advantageous to the overall definition of the GEO orbital debris environment. This paper will set out to determine if the ACO elements can be used to in a statistical sense to identify the source of the "clustering of UCTs" roughly centered on an inclination of 12deg and a RAAN of 345deg. The breakup of the Titan 3C-4 transtage on February 21, 1992 has been modeled using NASA s LEGEND (LEO-to-GEO Environment Debris) code to generate a GEO debris cloud. Breakup fragments are created based on the NASA Standard Breakup Model (including fragment size, area-to-mass (A/M), and

  13. Substituted quinoline quinones as surrogates for the PQQ cofactor: an electrochemical and computational study.

    PubMed

    Dorfner, Walter L; Carroll, Patrick J; Schelter, Eric J

    2015-04-17

    Pyrroloquinoline quinones (PQQ) are important cofactors that shuttle redox equivalents in diverse metalloproteins. Quinoline 7,8-quinones have been synthesized and characterized as surrogates for PQQ to elucidate redox energetics within metalloenzyme active sites. The quinoline 7,8-quinones were accessed using polymer-supported iodoxybenzoic acid and the compounds evaluated using solution electrochemistry. Together with a family of quinones, the products were evaluated computationally and used to generate a predictive correlation between a computed ΔG and the experimental reduction potentials. PMID:25826406

  14. Development of a Post-Intensive Care Unit Storytelling Intervention for Surrogates Involved in Decisions to Limit Life-Sustaining Treatment

    PubMed Central

    Schenker, Yael; Dew, Mary Amanda; Reynolds, Charles F.; Arnold, Robert M.; Tiver, Greer A.; Barnato, Amber E.

    2014-01-01

    Objectives Surrogates involved in decisions to limit life-sustaining treatment for a loved one in the intensive care unit (ICU) are at increased risk for adverse psychological outcomes lasting months to years after the ICU experience. Post-ICU interventions to reduce surrogate distress have not been developed. We sought to 1) describe a conceptual framework underlying the beneficial mental health effects of storytelling and 2) present formative work developing a storytelling intervention to reduce distress for recently bereaved surrogates. Methods An interdisciplinary team conceived the idea for a storytelling intervention based upon evidence from narrative theory that storytelling reduces distress from traumatic events through emotional disclosure, cognitive processing, and social connections. We developed an initial storytelling guide based upon this theory and the clinical perspectives of team members. We then conducted a case series with recently bereaved surrogates to iteratively test and modify the guide. Results The storytelling guide covered three key domains of the surrogate's experience of the patient's illness and death: antecedents, ICU experience, and aftermath. The facilitator focused on parts of the story that appeared to generate strong emotions and used non-judgmental statements to attend to these emotions. Between September 2012 and May 2013 we identified 28 eligible surrogates from 1 medical ICU and consented 20 for medical record review and recontact; 10 became eligible of whom 6 consented and completed the storytelling intervention. The single-session storytelling intervention lasted 40-92 minutes. All storytelling participants endorsed the intervention as acceptable, and 5 of 6 reported that it was helpful. Significance of Results Surrogate storytelling is an innovative and acceptable post-ICU intervention for recently bereaved surrogates and should be evaluated further. PMID:24524736

  15. Efficient Calibration/Uncertainty Analysis Using Paired Complex/Surrogate Models.

    PubMed

    Burrows, Wesley; Doherty, John

    2015-01-01

    The use of detailed groundwater models to simulate complex environmental processes can be hampered by (1) long run-times and (2) a penchant for solution convergence problems. Collectively, these can undermine the ability of a modeler to reduce and quantify predictive uncertainty, and therefore limit the use of such detailed models in the decision-making context. We explain and demonstrate a novel approach to calibration and the exploration of posterior predictive uncertainty, of a complex model, that can overcome these problems in many modelling contexts. The methodology relies on conjunctive use of a simplified surrogate version of the complex model in combination with the complex model itself. The methodology employs gradient-based subspace analysis and is thus readily adapted for use in highly parameterized contexts. In its most basic form, one or more surrogate models are used for calculation of the partial derivatives that collectively comprise the Jacobian matrix. Meanwhile, testing of parameter upgrades and the making of predictions is done by the original complex model. The methodology is demonstrated using a density-dependent seawater intrusion model in which the model domain is characterized by a heterogeneous distribution of hydraulic conductivity. PMID:25142272

  16. Limitations in dose-response and surrogate species methodologies for risk assessment of Cry toxins on arthropod natural enemies.

    PubMed

    Paula, Débora P; Andow, David A; Bellinati, André; Timbó, Renata Velozo; Souza, Lucas M; Pires, Carmen S S; Sujii, Edison R

    2016-04-01

    Dose-response assays and surrogate species are standard methods for risk analysis for environmental chemicals. These assume that individuals within a species have unimodal responses and that a surrogate species can predict responses of other related taxa. We exposed immature individuals of closely related aphidophagous coccinellid predators, Cycloneda sanguinea and Harmonia axyridis, to Cry1Ac and Cry1F toxins through uniform and constant artificial tritrophic exposure through Myzus persicae aphids. Both toxins were detected in coccinellid pupae, with individual and interspecific variation. Uptake was significantly higher in H. axyridis than in C. sanguinea, both in the proportion of individuals and the concentrations per individual. We also observed bimodal uptake of the Cry toxins by H. axyridis, which indicated that some individuals had low bioaccumulation and some had high bioaccumulation. This suggests that standard dose-response assays need to be interpreted with caution and future assays should examine the modality of the responses. In addition, the similarity in the biological effects of the Cry toxins in the two predators was due to different biological exposure mechanisms. The majority of H. axyridis were exposed both internally and in the gut, while C. sanguinea was exposed primarily in the gut. Thus, despite their close phylogenetic relatedness, these species would not be good surrogates for each other and the surrogate species methodology should be tested more rigorously. PMID:26846212

  17. Measurement of 55Fe(n ,p ) cross sections by the surrogate-reaction method for fusion technology applications

    NASA Astrophysics Data System (ADS)

    Pandey, Bhawna; Desai, V. V.; Suryanarayana, S. V.; Nayak, B. K.; Saxena, A.; Mirgule, E. T.; Santra, S.; Mahata, K.; Makawana, R.; Abhangi, M.; Basu, T. K.; Rao, C. V. S.; Jakhar, S.; Vala, S.; Sarkar, B.; Agrawal, H. M.; Kaur, G.; Prajapati, P. M.; Pal, Asim; Sarkar, D.; Kundu, A.

    2016-02-01

    We have measured the proton decay probabilities of the *56Fe and *47Ti compound systems which are populated by the transfer reactions 52Cr(6Li,d ) *56Fe (surrogate of n +55Fe→*56Fe→p +55Mn ) and 45Sc(6Li,α ) *47Ti (surrogate of n +46Ti→47Ti*→p +46Sc ) reactions, respectively. The 55Fe(n ,p ) cross sections were then obtained in the equivalent neutron energy range of 7.9 to 20.1 MeV within the framework of the surrogate-reaction method. The measured results were compared with predictions of the empire-3.2.3 statistical model code and various recent evaluated data libraries. The experimental cross-section data on 55Fe(n ,p ) are in reasonable agreement with EAF-2010, while the TENDL-2014 and ROSFOND-2010 data show some discrepancies. This study demonstrates the possibility of determining neutron-induced charged particle emission cross sections for unstable radionuclides relevant to fusion technology applications by the surrogate-reaction method.

  18. Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points

    PubMed Central

    Lee, L.; Wang, L.; Crump, M.

    2011-01-01

    Background: The correlation between efficacy end points in randomized controlled trials (RCTs) of systemic therapy for non-Hodgkin's lymphoma (NHL) was investigated to identify an appropriate surrogate end point for overall survival (OS). Methods: RCTs of previously untreated NHL published from 1990 to 2009 were identified. Associations between absolute differences in efficacy end points were determined using nonparametric Spearman's rank correlation coefficients (rs). Results: Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included. For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {rs of 0.90 [95% confidence interval (CI) 0.73–0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS. For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [rs 0.86 (95% CI 0.35–0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS. Conclusions: Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point. Definition of these relationships may inform future clinical trial design and interpretation of interim trial data. PMID:21266519

  19. Establishing a theory for deuteron induced surrogate reactions

    DOE PAGESBeta

    Potel, G; Nunes, F M; Thompson, I J

    2015-09-18

    Background: Deuteron-induced reactions serve as surrogates for neutron capture into compound states. Although these reactions are of great applicability, no theoretical efforts have been invested in this direction over the last decade. Purpose: The goal of this work is to establish on firm grounds a theory for deuteron-induced neutron-capture reactions. This includes formulating elastic and inelastic breakup in a consistent manner. Method: We describe this process both in post- and prior-form distorted wave Born approximation following previous works and discuss the differences in the formulation. While the convergence issues arising in the post formulation can be overcome in the priormore » formulation, in this case one still needs to take into account additional terms due to nonorthogonality. Results: We apply our method to the Nb93(d,p)X at Ed=15 and 25 MeV and are able to obtain a good description of the data. We then look at the various partial wave contributions, as well as elastic versus inelastic contributions. We also connect our formulation with transfer to neutron bound states.Conclusions: Our calculations demonstrate that the nonorthogonality term arising in the prior formulation is significant and is at the heart of the long-standing controversy between the post and the prior formulations of the theory. We also show that the cross sections for these reactions are angular-momentum dependent and therefore the commonly used Weisskopf limit is inadequate. We finally make important predictions for the relative contributions of elastic breakup and nonelastic breakup and call for elastic-breakup measurements to further constrain our model.« less

  20. Science Based Stockpile Stewardship, Uncertainty Quantification, and Surrogate Reactions

    SciTech Connect

    Stoyer, M A; McNabb, D P; Burke, J T; Bernstein, L A

    2009-08-06

    Stewardship of this nation's nuclear weapons is predicated on developing a fundamental scientific understanding of the physics and chemistry required to describe weapon performance without the need to resort to underground nuclear testing and to predict expected future performance as a result of intended or unintended modifications. In order to construct more reliable models, underground nuclear test data is being reanalyzed in novel ways. To improve the interpretation of these experiments with quantified uncertainties, improved nuclear data is required. As an example, the thermonuclear yield of a device was often inferred through the use of radiochemical detectors. Conversion of the detector activations observed to thermonuclear yield was accomplished through explosion code calculations (models) and a good set of nuclear reaction cross-sections. Because of the unique high-fluence environment of an exploding nuclear weapon, many reactions occurred on radioactive nuclides, for which only theoretically calculated cross-sections are available. Surrogate nuclear reactions at STARS/LIBERACE offer the opportunity to measure cross-sections on unstable nuclei and thus improve the quality of the nuclear reaction cross-section sets. One radiochemical detector that was loaded in devices was mono-isotopic yttrium ({sup 89}Y). Nuclear reactions produced {sup 87}Y and {sup 88}Y which could be quantified post-shot as a ratio of {sup 87}Y/{sup 88}Y. The yttrium cross-section set from 1988 is shown in Figure 1(a) and contains approximately 62 cross-sections interconnecting the yttrium nuclides. The 6 experimentally measured cross-sections are shown in Figure 1(b). Any measurement of cross-sections on {sup 87}Y or {sup 88}Y would improve the quality of the cross-section set. A recent re-evaluation of the yttrium cross-section set was performed with many more calculated reaction cross-sections included.

  1. Establishing a theory for deuteron induced surrogate reactions

    SciTech Connect

    Potel, G; Nunes, F M; Thompson, I J

    2015-09-18

    Background: Deuteron-induced reactions serve as surrogates for neutron capture into compound states. Although these reactions are of great applicability, no theoretical efforts have been invested in this direction over the last decade. Purpose: The goal of this work is to establish on firm grounds a theory for deuteron-induced neutron-capture reactions. This includes formulating elastic and inelastic breakup in a consistent manner. Method: We describe this process both in post- and prior-form distorted wave Born approximation following previous works and discuss the differences in the formulation. While the convergence issues arising in the post formulation can be overcome in the prior formulation, in this case one still needs to take into account additional terms due to nonorthogonality. Results: We apply our method to the Nb93(d,p)X at Ed=15 and 25 MeV and are able to obtain a good description of the data. We then look at the various partial wave contributions, as well as elastic versus inelastic contributions. We also connect our formulation with transfer to neutron bound states.Conclusions: Our calculations demonstrate that the nonorthogonality term arising in the prior formulation is significant and is at the heart of the long-standing controversy between the post and the prior formulations of the theory. We also show that the cross sections for these reactions are angular-momentum dependent and therefore the commonly used Weisskopf limit is inadequate. We finally make important predictions for the relative contributions of elastic breakup and nonelastic breakup and call for elastic-breakup measurements to further constrain our model.

  2. Establishing a theory for deuteron-induced surrogate reactions

    NASA Astrophysics Data System (ADS)

    Potel, G.; Nunes, F. M.; Thompson, I. J.

    2015-09-01

    Background: Deuteron-induced reactions serve as surrogates for neutron capture into compound states. Although these reactions are of great applicability, no theoretical efforts have been invested in this direction over the last decade. Purpose: The goal of this work is to establish on firm grounds a theory for deuteron-induced neutron-capture reactions. This includes formulating elastic and inelastic breakup in a consistent manner. Method: We describe this process both in post- and prior-form distorted wave Born approximation following previous works and discuss the differences in the formulation. While the convergence issues arising in the post formulation can be overcome in the prior formulation, in this case one still needs to take into account additional terms due to nonorthogonality. Results: We apply our method to the 93Nb(d ,p )X at Ed=15 and 25 MeV and are able to obtain a good description of the data. We look at the various partial wave contributions, as well as elastic versus inelastic contributions. We also connect our formulation with transfer to neutron bound states. Conclusions: Our calculations demonstrate that the nonorthogonality term arising in the prior formulation is significant and is at the heart of the long-standing controversy between the post and the prior formulations of the theory. We also show that the cross sections for these reactions are angular-momentum dependent and therefore the commonly used Weisskopf limit is inadequate. Finally, we make important predictions for the relative contributions of elastic breakup and nonelastic breakup and call for elastic-breakup measurements to further constrain our model.

  3. Uncertainty quantification for accident management using ACE surrogates

    SciTech Connect

    Varuttamaseni, A.; Lee, J. C.; Youngblood, R. W.

    2012-07-01

    The alternating conditional expectation (ACE) regression method is used to generate RELAP5 surrogates which are then used to determine the distribution of the peak clad temperature (PCT) during the loss of feedwater accident coupled with a subsequent initiation of the feed and bleed (F and B) operation in the Zion-1 nuclear power plant. The construction of the surrogates assumes conditional independence relations among key reactor parameters. The choice of parameters to model is based on the macroscopic balance statements governing the behavior of the reactor. The peak clad temperature is calculated based on the independent variables that are known to be important in determining the success of the F and B operation. The relationship between these independent variables and the plant parameters such as coolant pressure and temperature is represented by surrogates that are constructed based on 45 RELAP5 cases. The time-dependent PCT for different values of F and B parameters is calculated by sampling the independent variables from their probability distributions and propagating the information through two layers of surrogates. The results of our analysis show that the ACE surrogates are able to satisfactorily reproduce the behavior of the plant parameters even though a quasi-static assumption is primarily used in their construction. The PCT is found to be lower in cases where the F and B operation is initiated, compared to the case without F and B, regardless of the F and B parameters used. (authors)

  4. General Constraints on Cross Sections Deduced from Surrogate Reactions

    SciTech Connect

    Younes, W

    2003-08-14

    Cross sections that cannot be measured in the laboratory, e.g. because the target lifetime is too short, can be inferred indirectly from a different reaction forming the same compound system, but with a more accessible beam/target combination (the ''surrogate-reaction'' technique). The reactions share the same compound system and a common decay mechanism, but they involve different formation processes. Therefore, an implicit constraint is imposed on the inferred cross section deduced from the measured surrogate-reaction data, through the common decay mechanism. In this paper, the mathematical consequences of this implicit constraint are investigated. General formulas are derived from upper and lower bounds on the inferred cross section, estimated from surrogate data in a procedure which does not require any modeling of the common decay process. As an example, the formulas developed here are applied to the case of the {sup 235}U(n,f) cross section, deduced from {sup 234}U(t,pf) surrogate data. The calculated bounds are not very tight in this particular case. However, by introducing a few qualitative assumptions about the physics of the fission process, meaningful bounds on the deduced cross section are obtained. Upper and lower limits for the cross-section ratio of the (n,f) reaction on the {sup 235}U isomer at E{sub x} = 77 eV relative to the (n,f) reaction on the ground state are also calculated. The generalization of this technique to other surrogate reactions is discussed.

  5. Surrogate Model Development for Fuels for Advanced Combustion Engines

    SciTech Connect

    Anand, Krishnasamy; Ra, youngchul; Reitz, Rolf; Bunting, Bruce G

    2011-01-01

    The fuels used in internal-combustion engines are complex mixtures of a multitude of different types of hydrocarbon species. Attempting numerical simulations of combustion of real fuels with all of the hydrocarbon species included is highly unrealistic. Thus, a surrogate model approach is generally adopted, which involves choosing a few representative hydrocarbon species whose overall behavior mimics the characteristics of the target fuel. The present study proposes surrogate models for the nine fuels for advanced combustion engines (FACE) that have been developed for studying low-emission, high-efficiency advanced diesel engine concepts. The surrogate compositions for the fuels are arrived at by simulating their distillation profiles to within a maximum absolute error of 4% using a discrete multi-component (DMC) fuel model that has been incorporated in the multi-dimensional computational fluid dynamics (CFD) code, KIVA-ERC-CHEMKIN. The simulated surrogate compositions cover the range and measured concentrations of the various hydrocarbon classes present in the fuels. The fidelity of the surrogate fuel models is judged on the basis of matching their specific gravity, lower heating value, hydrogen/carbon (H/C) ratio, cetane number, and cetane index with the measured data for all nine FACE fuels.

  6. Surrogate Analysis and Index Developer (SAID) tool

    USGS Publications Warehouse

    Domanski, Marian M.; Straub, Timothy D.; Landers, Mark N.

    2015-01-01

    The regression models created in SAID can be used in utilities that have been developed to work with the USGS National Water Information System (NWIS) and for the USGS National Real-Time Water Quality (NRTWQ) Web site. The real-time dissemination of predicted SSC and prediction intervals for each time step has substantial potential to improve understanding of sediment-related water quality and associated engineering and ecological management decisions.

  7. Statistical Surrogate Models for Estimating Probability of High-Consequence Climate Change

    NASA Astrophysics Data System (ADS)

    Field, R.; Constantine, P.; Boslough, M.

    2011-12-01

    We have posed the climate change problem in a framework similar to that used in safety engineering, by acknowledging that probabilistic risk assessments focused on low-probability, high-consequence climate events are perhaps more appropriate than studies focused simply on best estimates. To properly explore the tails of the distribution requires extensive sampling, which is not possible with existing coupled atmospheric models due to the high computational cost of each simulation. We have developed specialized statistical surrogate models (SSMs) that can be used to make predictions about the tails of the associated probability distributions. A SSM is different than a deterministic surrogate model in that it represents each climate variable of interest as a space/time random field, that is, a random variable for every fixed location in the atmosphere at all times. The SSM can be calibrated to available spatial and temporal data from existing climate databases, or to a collection of outputs from general circulation models. Because of its reduced size and complexity, the realization of a large number of independent model outputs from a SSM becomes computationally straightforward, so that quantifying the risk associated with low-probability, high-consequence climate events becomes feasible. A Bayesian framework was also developed to provide quantitative measures of confidence, via Bayesian credible intervals, to assess these risks. To illustrate the use of the SSM, we considered two collections of NCAR CCSM 3.0 output data. The first collection corresponds to average December surface temperature for years 1990-1999 based on a collection of 8 different model runs obtained from the Program for Climate Model Diagnosis and Intercomparison (PCMDI). We calibrated the surrogate model to the available model data and make various point predictions. We also analyzed average precipitation rate in June, July, and August over a 54-year period assuming a cyclic Y2K ocean model. We

  8. A Global Genomic and Genetic Strategy to Identify, Validate and Use Gene Signatures of Xenobiotic-Responsive Transcription Factors in Prediction of Pathway Activation in the Mouse Liver

    EPA Science Inventory

    Many drugs and environmentally-relevant chemicals activate xenobiotic-responsive transcription factors. Identification of target genes of these factors would be useful in predicting pathway activation in in vitro chemical screening as well as their involvement in disease states. ...

  9. Surrogate pregnancy: a guide for Canadian prenatal health care providers

    PubMed Central

    Reilly, Dan R.

    2007-01-01

    Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is limited evidence about the medical and psychological risks ofsurrogacy. Whether theoretical concerns about these risks are clinically relevant remains unknown. In the face of these uncertainties, the prenatal health care provider should have a low threshold for seeking obstetrical, social work, ethical and legal support. PMID:17296962

  10. Successful induced non-puerperal lactation in surrogate mothers.

    PubMed

    Banapurmath, C R; Banapurmath, S; Kesaree, N

    1993-01-01

    Ten surrogate mothers seen between 1986-91 were encouraged to breast-feed their babies varying in age between 8 days to 5 months. All the 10 surrogate mothers had experienced pregnancy and child birth in the past. The lactational gap varied from 1 year to 16 years. Presence of milk was noted on 3rd to 8th day after attempting induced lactation in 5 mothers. No milk was seen on manual expression of the nipple even after 2 weeks in the other 5 surrogate mothers. Two mothers achieved complete breast-feeding and they fed their babies for 2 years. Three mothers could achieve partial lactation and these mothers fed for 1 year or more. All these 5 babies registered satisfactory growth. PMID:8157333

  11. Nonspinning numerical relativity waveform surrogates: Building the model

    NASA Astrophysics Data System (ADS)

    Galley, Chad

    2015-04-01

    Simulating binary black hole coalescences involves solving Einstein's equations with large-scale computing resources that can take months to complete for a single numerical solution. This engenders a computationally intractable problem for multiple-query applications related to parameter space exploration, data analysis for gravitational wave detectors like LIGO, and semi-analytical waveform fits. I discuss how reduced order modeling techniques are used to build accurate surrogates that can be evaluated quickly in place of numerically solving Einstein's equations for generating gravitational waveforms of nonspinning binary black hole coalescences. To within error, the surrogate can model all modes available from a numerical simulation including, for example, troublesome modes such as the (3,2) mode and memory modes. A companion talk will cover quantifying the best surrogate model's errors. The results of this work represent a significant advance by making it possible to use numerical relativity waveforms for multiple-query applications.

  12. Surrogate pregnancy: a guide for Canadian prenatal health care providers.

    PubMed

    Reilly, Dan R

    2007-02-13

    Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is limited evidence about the medical and psychological risks of surrogacy. Whether theoretical concerns about these risks are clinically relevant remains unknown. In the face of these uncertainties, the prenatal health care provider should have a low threshold for seeking obstetrical, social work, ethical and legal support. PMID:17296962

  13. Mother-daughter in vitro fertilization triplet surrogate pregnancy.

    PubMed

    Michelow, M C; Bernstein, J; Jacobson, M J; McLoughlin, J L; Rubenstein, D; Hacking, A I; Preddy, S; Van der Wat, I J

    1988-02-01

    A successful triplet pregnancy has been established in a surrogate gestational mother following the transfer of five embryos fertilized in vitro. The oocytes were donated by her biological daughter, and the sperm obtained from the daughter's husband. The daughter's infertility followed a total abdominal hysterectomy performed for a postpartum hemorrhage as a result of a placenta accreta. Synchronization of both their menstrual cycles was obtained using oral contraceptive suppression for 2 months, followed by stimulation of both the surrogate gestational mother and her daughter such that embryo transfer would occur at least 48 hr after the surrogate gestational mother's own ovulation. This case raises a number of medical, social, psychological, and ethical issues. PMID:3367072

  14. A tree-structured crash surrogate measure for freeways.

    PubMed

    Kuang, Yan; Qu, Xiaobo; Wang, Shuaian

    2015-04-01

    In this paper, we propose a novel methodology to define and estimate a surrogate measure. By imposing a hypothetical disturbance to the leading vehicle, the following vehicle's action is represented as a probabilistic causal model. After that, a tree is built to describe the eight possible conflict types under the model. The surrogate measure, named Aggregated Crash Index (ACI), is thus proposed to measure the crash risk. This index reflects the accommodability of freeway traffic state to a traffic disturbance. We further apply this measure to evaluate the crash risks in a freeway section of Pacific Motorway, Australia. The results show that the proposed indicator outperforms the three traditional crash surrogate measures (i.e., Time to Collision, Proportion of Stopping Distance, and Crash Potential Index) in representing rear-end crash risks. The applications of this measure are also discussed. PMID:25710638

  15. Circulating mRNA Profiling in Esophageal Squamous Cell Carcinoma Identifies FAM84B As A Biomarker In Predicting Pathological Response to Neoadjuvant Chemoradiation

    PubMed Central

    Hsu, Feng-Ming; Chia-Hsien Cheng, Jason; Chang, Yih-Leong; Lee, Jang-Ming; Koong, Albert C.; Chuang, Eric Y.

    2015-01-01

    Esophageal cancer patients with pathological complete response (pCR) to neoadjuvant chemoradiation (CRT) have favorable outcomes. Currently, there was no reliable biomarker predicting the response to CRT. Perioperative circulating mRNA may be associated with prognosis, but its application for predicting treatment response is unclear. We prospectively assessed the value of circulating messenger RNA (mRNA) profiling in predicting pCR for esophageal squamous cell carcinoma (ESCC). Patients with ESCC completing CRT followed by surgery were enrolled for analysis. Venous peripheral blood was obtained before and after CRT, and total RNA was extracted for hybridization-based whole genome expression analysis and quantitative RT-PCR. We found circulating expression profiling was significantly altered after CRT. Altered FAM84B expression was significantly predictive of pCR. The decrease of serum FAM84B protein level after CRT was also associated with pCR. Immunohistochemistry and western blot confirmed that FAM84B protein was overexpressed in the majority of patients and ESCC cell lines. Furthermore, knockdown of FAM84B delayed tumor growth in ectopic xenografts. We demonstrated the decreased of circulating FAM84B mRNA and protein after neoadjuvant CRT may predict pCR, and FAM84B protein is overexpressed in ESCC. The potential of FAM84B as a novel predictive biomarker, and its biological functions deserve further investigation. PMID:25980316

  16. The social context for surrogates' motivations and satisfaction.

    PubMed

    Berend, Zsuzsa

    2014-10-01

    This Commentary takes up two of the main findings by Imrie and Jadva's study, namely surrogates' satisfaction with the post-surrogacy contact with intended parents and their motivation for surrogacy. It argues that the findings are in keeping with other qualitative research on surrogacy and that this similarity is not the result of the similarity of surrogates' psychological makeup. The Commentary highlights the centrality of social meanings and definitions, and following Howard Becker, insists on taking into account the collective doings that inform and shape individual feelings and behaviour. PMID:25129693

  17. Is (d,p{gamma}) a surrogate for neutron capture?

    SciTech Connect

    Hatarik, R.; Cizewski, J. A.; O'Malley, P. D.; Bernstein, L. A.; Burke, J. T.; Lesher, S. R.; Gibelin, J. D.; Phair, L. W.; Swan, T.

    2008-04-17

    To benchmark the validity of using the (d,p{gamma}) reaction as a surrogate for (n,{gamma}), the {sup 171,173}Yb(d,p{gamma}) reactions were measured and compared with the neutron capture cross sections measured by Wisshak et al. The (d,p{gamma}) ratios were measured using an 18.5 MeV deuteron beam from the 88-Inch Cyclotron at LBNL. Preliminary results comparing the surrogate ratios with the known (n,{gamma}) cross sections are discussed.

  18. A jet fuel surrogate formulated by real fuel properties

    SciTech Connect

    Dooley, Stephen; Won, Sang Hee; Chaos, Marcos; Heyne, Joshua; Ju, Yiguang; Dryer, Frederick L.; Kumar, Kamal; Sung, Chih-Jen; Wang, Haowei; Oehlschlaeger, Matthew A.; Santoro, Robert J.; Litzinger, Thomas A.

    2010-12-15

    An implicit methodology based on chemical group theory to formulate a jet aviation fuel surrogate by the measurements of several combustion related fuel properties is tested. The empirical formula and derived cetane number of an actual aviation fuel, POSF 4658, have been determined. A three component surrogate fuel for POSF 4658 has been formulated by constraining a mixture of n-decane, iso-octane and toluene to reproduce the hydrogen/carbon ratio and derived cetane number of the target fuel. The validity of the proposed surrogate is evaluated by experimental measurement of select combustion properties of POSF 4658, and the POSF 4658 surrogate. (1)A variable pressure flow reactor has been used to chart the chemical reactivity of stoichiometric mixtures of POSF 4658/O{sub 2}/N{sub 2} and POSF 4658 surrogate/O{sub 2}/N{sub 2} at 12.5 atm and 500-1000 K, fixing the carbon content at 0.3% for both mixtures. (2)The high temperature chemical reactivity and chemical kinetic-molecular diffusion coupling of POSF 4658 and POSF 4658 surrogate have been evaluated by measurement of the strained extinction limit of diffusion flames. (3)The autoignition behavior of POSF 4658 and POSF 4658 surrogate has been measured with a shock tube at 674-1222 K and with a rapid compression machine at 645-714 K for stoichiometric mixtures of fuel in air at pressures close to 20 atm. The flow reactor study shows that the character and extent of chemical reactivity of both fuels at low temperature (500-675 K) and high temperature (900 K+) are extremely similar. Slight differences in the transition from the end of the negative temperature coefficient regime to hot ignition are observed. The diffusion flame strained extinction limits of the fuels are observed to be indistinguishable when compared on a molar basis. Ignition delay measurements also show that POSF 4658 exhibits NTC behavior. Moreover, the ignition delays of both fuels are also extremely similar over the temperature range studied in

  19. Detailed Chemical Kinetic Modeling of Surrogate Fuels for Gasoline and Application to an HCCI Engine

    SciTech Connect

    Naik, C V; Pitz, W J; Sj?berg, M; Dec, J E; Orme, J; Curran, H J; Simmie, J M; Westbrook, C K

    2005-01-07

    Gasoline consists of many different classes of hydrocarbons, such as paraffins, olefins, aromatics, and cycloalkanes. In this study, a surrogate gasoline reaction mechanism is developed, and it has one representative fuel constituent from each of these classes. These selected constituents are iso-octane, n-heptane, 1-pentene, toluene, and methyl-cyclohexane. The mechanism was developed in a step-wise fashion, adding submechanisms to treat each fuel component. Reactions important for low temperature oxidation (<1000K) and cross-reactions among different fuels are incorporated into the mechanism. The mechanism consists of 1214 species and 5401 reactions. A single-zone engine model is used to evaluate how well the mechanism captures autoignition behavior for conditions corresponding to homogeneous charge compression ignition (HCCI) engine operation. Experimental data are available for both how the combustion phasing changes with fueling at a constant intake temperature, and also how the intake temperature has to be changed with pressure in order to maintain combustion phasing for a fixed equivalence ratio. Three different surrogate fuel mixtures are used for the modeling. Predictions are in reasonably good agreement with the engine data. In addition, the heat release rate is calculated and compared to the data from experiments. The model predicts less low-temperature heat release than that measured. It is found that the low temperature heat-release rate depends strongly on engine speed, reactions of RO{sub 2}+HO{sub 2}, fuel composition, and pressure boost.

  20. The Impacts of Intrusive Advising on the Persistence of First-Year Science, Technology, and Mathematics Students Identified Using a Risk Prediction Instrument

    ERIC Educational Resources Information Center

    Campbell, Matthew A.

    2013-01-01

    Set in a large, urban, public university, this study explores the use of an institutionally specific risk instrument developed to identify students who had a high risk of attrition and the effectiveness of subsequent interventions deployed through advising. Though implemented throughout the institution, this study identified control and treatment…

  1. Sister-sister in vitro fertilization surrogate pregnancy with donor sperm: the case for surrogate gestational pregnancy.

    PubMed

    Leeton, J; King, C; Harman, J

    1988-10-01

    A case of surrogate pregnancy is described in the sister of a 40-year-old hysterectomized woman where two oocytes of the latter were fertilized in vitro with known donor sperm and transferred into the surrogate. A normal singleton pregnancy developed which was complicated after 24 weeks of gestation with recurrent antepartum hemorrhages due to grade 3 placenta praevia. A healthy female baby was delivered by elective cesarean section at 36 weeks of gestation. The legal, social, psychological, and ethical issues of surrogacy remain unsettled and are discussed in this case report. PMID:3230346

  2. Cheminformatics Analysis of EPA ToxCast Chemical Libraries to Identify Domains of Applicability for Predictive Toxicity Models and Prioritize Compounds for Toxicity Testing

    EPA Science Inventory

    An important goal of toxicology research is the development of robust methods that use in vitro and chemical structure information to predict in vivo toxicity endpoints. The US EPA ToxCast program is addressing this goal using ~600 in vitro assays to create bioactivity profiles o...

  3. Structural Determinants of Drug Partitioning in Surrogates of Phosphatidylcholine Bilayer Strata

    PubMed Central

    Lukacova, Viera; Natesan, Senthil; Peng, Ming; Tandlich, Roman; Wang, Zhanbin; Lynch, Sandra; Subramaniam, Rajesh; Balaz, Stefan

    2013-01-01

    The knowledge of drug concentrations in bilayer headgroups, core, and at the interface between them is a prerequisite for quantitative modeling of drug interactions with many membrane-bound transporters, metabolizing enzymes and receptors, which have the binding sites located in the bilayer. This knowledge also helps understand the rates of trans-bilayer transport because balanced interactions of drugs with the bilayer strata lead to high rates, while excessive affinities for any stratum cause a slowdown. Experimental determination of bilayer location is so tedious and costly that the data are only available for some fifty compounds. To extrapolate these valuable results to more compounds at a higher throughput, surrogate phases have been used to obtain correlates of the drug affinities for individual strata. We introduced a novel system, consisting of a diacetyl phosphatidylcholine (DAcPC) solution with the water content of the fluid bilayer as the headgroup surrogate and n-hexadecane (C16) representing the core. The C16/DAcPC partition coefficients were measured for 113 selected compounds, containing structural fragments that are frequently occurring in approved drugs. The data were deconvoluted into the ClogP-based fragment solvation characteristics and processed using a solvatochromic correlation. Increased H-bond donor ability and excess molar refractivity of compounds promote solvation in the DAcPC phase as compared to bulk water, contrary to H-bond acceptor ability, dipolarity/polarizability, and volume. The results show that aromates have more balanced distribution in bilayer strata, and thus faster trans-bilayer transport, than similar alkanes. This observation is in accordance with the frequent occurrence of aromatic rings in approved drugs and with the role of rigidity of drug molecules in promoting intestinal absorption. Bilayer locations, predicted using the C16/DAcPC system, are in excellent agreement with available experimental data, in contrast to

  4. Salmonella surrogate reduction using industrial peanut dry roasting parameters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies were conducted to evaluate the effectiveness of industrial peanut dry roasting parameters in Salmonella reduction using a Salmonella surrogate, Enterococcus faecium, which is slightly more heat tolerant than Salmonella. Runner-type peanuts were inoculated with E. faecium and roasted in a lab...

  5. GENERATING SOPHISTICATED SPATIAL SURROGATES USING THE MIMS SPATIAL ALLOCATOR

    EPA Science Inventory

    The Multimedia Integrated Modeling System (MIMS) Spatial Allocator is open-source software for generating spatial surrogates for emissions modeling, changing the map projection of Shapefiles, and performing other types of spatial allocation that does not require the use of a comm...

  6. Defending commercial surrogate motherhood against Van Niekerk and Van Zyl.

    PubMed Central

    McLachlan, H V

    1997-01-01

    The arguments of Van Niekerk and Van Zyl that, on the grounds that it involves an inappropriate commodification and alienation of women's labour, commercial surrogate motherhood (CSM) is morally suspect are discussed and considered to be defective. In addition, doubt is cast on the notion that CSM should be illegal. PMID:9451602

  7. Fluorescent polymeric aggregates for selective response to sarin surrogates.

    PubMed

    Rusu, Anca D; Moleavin, Ioana A; Hurduc, Nicolae; Hamel, Matthieu; Rocha, Licinio

    2014-09-01

    By combining the sensitivity of fluorescent units with the response of "smart" polymers to environmental changes, we propose a new approach for chemical detection applications. The system proved to be sensitive to 12 ppb of diethyl chlorophosphate (DCP), a Sarin surrogate, and to discriminate between the interfering molecules. PMID:25034965

  8. Bayesian Analysis of Multivariate Probit Models with Surrogate Outcome Data

    ERIC Educational Resources Information Center

    Poon, Wai-Yin; Wang, Hai-Bin

    2010-01-01

    A new class of parametric models that generalize the multivariate probit model and the errors-in-variables model is developed to model and analyze ordinal data. A general model structure is assumed to accommodate the information that is obtained via surrogate variables. A hybrid Gibbs sampler is developed to estimate the model parameters. To…

  9. Defining Useful Surrogates for User Participation in Online Medical Learning

    ERIC Educational Resources Information Center

    Beddy, Peter; Ridgway, Paul F.; Beddy, David; Clarke, Eric; Traynor, Oscar; Tierney, Sean

    2009-01-01

    "School for Surgeons" is a web-based distance learning program which provides online clinical-based tutorials to surgical trainees. Our aim was to determine surrogates of active participation and to assess the efficacy of methods to improve usage. Server logs of the 82 participants in the "School for Surgeons" were assessed for the two terms of…

  10. Is Suicide Ideation a Surrogate Endpoint for Geriatric Suicide?

    ERIC Educational Resources Information Center

    Links, Paul S.; Heisel, Marnin J.; Quastel, Adam

    2005-01-01

    The present study explored the validity of treating suicide ideation as a surrogate endpoint that can serve as a proxy for suicide in clinical intervention research with suicidal seniors. Two criteria; that suicide ideation is modulated by the proposed intervention and that modulation of suicide ideation leads to a quantitative reduction in…

  11. First simultaneous measurement of fission and gamma probabilities of 237U and 239Np via surrogate reactions

    NASA Astrophysics Data System (ADS)

    Marini, P.; Ducasse, Q.; Jurado, B.; Aiche, M.; Mathieu, L.; Barreau, G.; Czajkowski, S.; Tsekhanovich, I.; Moro, A.; Lei, J.; Giacoppo, F.; Gorgen, A.; Tornyi; Audouin, L.; Tassan-Got, L.; Wilson, J. N.; Gunsing, F.; Guttormsen, M.; Larsen, A. C.; Lebois, M.; Renstrom, T.; Rose, S.; Siem, S.; Tveten, G. M.; Wiedeking, M.; Serot, O.; Boutoux, G.; Méot, V.; Morillon, B.; Denis-Petit, D.; Roig, O.; Oberstedt, S.; Oberstedt, A.

    2016-06-01

    Fission and gamma decay probabilities of 237U and 239Np have been measured, for the first time simultaneously in dedicated experiments, via the surrogate reactions 238U(3He, 4He) and 238U(3He,d), respectively. While a good agreement between our data and neutron-induced data is found for fission probabilities, gamma decay probabilities are several times higher than the corresponding neutron-induced data for each studied nucleus. We study the role of the different spin distributions populated in the surrogate and neutron-induced reactions. The compound nucleus spin distribution populated in the surrogate reaction is extracted from the measured gamma-decay probabilities, and used as input parameter in the statistical model to predict fission probabilities to be compared to our data. A strong disagreement between our data and the prediction is obtained. Preliminary results from an additional dedicated experiment confirm the observed discrepancies, indicating the need of a better understanding of the formation and decay processes of the compound nucleus.

  12. Recent Progress in the Development of Diesel Surrogate Fuels

    SciTech Connect

    Pitz, W J; Mueller, C J

    2009-12-09

    There has been much recent progress in the area of surrogate fuels for diesel. In the last few years, experiments and modeling have been performed on higher molecular weight components of relevance to diesel fuel such as n-hexadecane (n-cetane) and 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). Chemical kinetic models have been developed for all the n-alkanes up to 16 carbon atoms. Also, there has been much experimental and modeling work on lower molecular weight surrogate components such as n-decane and n-dodecane that are most relevant to jet fuel surrogates, but are also relevant to diesel surrogates where simulation of the full boiling point range is desired. For two-ring compounds, experimental work on decalin and tetralin recently has been published. For multi-component surrogate fuel mixtures, recent work on modeling of these mixtures and comparisons to real diesel fuel is reviewed. Detailed chemical kinetic models for surrogate fuels are very large in size. Significant progress also has been made in improving the mechanism reduction tools that are needed to make these large models practicable in multi-dimensional reacting flow simulations of diesel combustion. Nevertheless, major research gaps remain. In the case of iso-alkanes, there are experiments and modeling work on only one of relevance to diesel: iso-cetane. Also, the iso-alkanes in diesel are lightly branched and no detailed chemical kinetic models or experimental investigations are available for such compounds. More components are needed to fill out the iso-alkane boiling point range. For the aromatic class of compounds, there has been no new work for compounds in the boiling point range of diesel. Most of the new work has been on alkyl aromatics that are of the range C7 to C8, below the C10 to C20 range that is needed. For the chemical class of cycloalkanes, experiments and modeling on higher molecular weight components are warranted. Finally for multi-component surrogates needed to treat real

  13. Recent Progress in the Development of Diesel Surrogate Fuels

    SciTech Connect

    Pitz, W J

    2009-09-04

    There has been much recent progress in the area of surrogate fuels for diesel. In the last few years, experiments and modeling have been performed on higher molecular weight components of relevance to diesel fuel such as n-hexadecane (n-cetane) and 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). Chemical kinetic models have been developed for all the n-alkanes up to 16 carbon atoms. Also, there has been much experimental and modeling work on lower molecular weight surrogate components such as n-decane and do-decane which are most relevant to jet fuel surrogates, but are also relevant to diesel surrogates where simulation of the full boiling point range is desired. For the cycloalkanes, experimental work on decalin and tetralin recently has been published. For multi-component surrogate fuel mixtures, recent work on modeling of these mixtures and comparisons to real diesel fuel is reviewed. Detailed chemical kinetic models for surrogate fuels are very large in size. Significant progress also has been made in improving the mechanism reduction tools that are needed to make these large models practicable in multidimensional reacting flow simulations of diesel combustion. Nevertheless, major research gaps remain. In the case of iso-alkanes, there are experiments and modeling work on only one of relevance to diesel: iso-cetane. Also, the iso-alkanes in diesel are lightly branched and no detailed chemical kinetic models or experimental investigations are available for such compounds. More components are needed to fill out the iso-alkane boiling point range. For the aromatic class of compounds, there has been no new work for compounds in the boiling point range of diesel. Most of the new work has been on alkyl aromatics that are of the range C7 to C8, below the C10 to C20 range that is needed. For the chemical class of cycloalkanes, experiments and modeling on higher molecular weight components are warranted. Finally for multi-component surrogates needed to treat real diesel

  14. Development of a Human Cranial Bone Surrogate for Impact Studies

    PubMed Central

    Roberts, Jack C.; Merkle, Andrew C.; Carneal, Catherine M.; Voo, Liming M.; Johannes, Matthew S.; Paulson, Jeff M.; Tankard, Sara; Uy, O. Manny

    2013-01-01

    In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the three-layer (inner table-diplöe-outer table) architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three-layer surrogate cranial bone samples for three-point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures in pendulum impacts of intact human skulls, previously reported in the literature. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5 MPa√ m and 53 ± 4.9 MPa, respectively, while the same properties of human compact bone were 3.1 ± 1.8 MPa√ m and 68 ± 18 MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68 ± 5.7 MPa, while that of cranial bone was 82 ± 26 MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests. PMID:25023222

  15. Kinetic Modeling of Toluene Oxidation for Surrogate Fuel Applications

    SciTech Connect

    Frassoldati, A; Mehl, M; Fietzek, R; Faravelli, T; Pitz, W J; Ranzi, E

    2009-04-21

    New environmental issues, like the effect of combustion-generated greenhouse gases, provide motivation to better characterize oxidation of hydrocarbons. Transportation, in particular, significantly contributes to energy consumption and CO{sub 2} emissions. Kinetic studies about the combustion of fuels under conditions typical of internal combustion engines provides important support to improve mechanism formulation and to eventually provide better computational tools that can be used to increase the engine performance. It is foreseeable that at least in the next 30 years the main transportation fuels will be either gasoline or diesel. Unfortunately, these fuels are very complex mixtures of many components. Moreover, their specifications and performance requirements significantly change the composition of these fuels: gasoline and diesel mixtures are different if coming from different refineries or they are different from winter to summer. At the same time a fuel with a well defined and reproducible composition is needed for both experimental and modeling work. In response to these issues, surrogate fuels are proposed. Surrogate fuels are defined as mixtures of a small number of hydrocarbons whose relative concentrations is adjusted in order to approximate the chemical and physical properties of a real fuel. Surrogate fuels are then very useful both for the design of reproducible experimental tests and also for the development of reliable kinetic models. The primary reference fuels (PRF) are a typical and old example of surrogate fuel: n-heptane and iso-octane mixtures are used to reproduce antiknock propensity of complex mixtures contained in a gasoline. PRFs are not able to surrogate gasoline in operating conditions different from standard ones and new surrogates have been recently proposed. Toluene is included in all of them as a species able to represent the behavior of aromatic compounds. On the other side, the toluene oxidation chemistry is not so well

  16. Postmarket safety of drugs approved by Health Canada on the basis of clinical and surrogate outcomes: a cohort study

    PubMed Central

    Ahmed, Tareq

    2015-01-01

    Background Health Canada approves drugs on the basis of evidence from clinical trials using clinical or surrogate outcomes. This study compares the postmarket safety of these 2 groups of drugs. Methods Information about whether clinical or surrogate outcomes were used and the date of market approval were obtained from Health Canada’s Summary Basis of Decision documents issued from Jan. 1, 2005, to Dec. 31, 2014. Safety warnings and the dates they were issued were identified through advisories on the MedEffect Canada website. Kaplan–Meier survival curves were calculated to determine the likelihood that drugs in the clinical and surrogate outcome groups would receive a serious safety warning. The time from market authorization to first serious safety warning was compared for the 2 groups of drugs. Results A total of 124 drugs were approved by Health Canada using clinical outcomes and 114 using surrogate outcomes. Kaplan–Meier curves did not differ between the 2 groups (p < 0.9). The median time from market authorization to first serious safety warning was 722 days in the clinical outcome group and 818 days in the surrogate outcome group (difference 96 days, 95% confidence interval –295 to 425). Interpretation We found no statistically significant difference in postmarket safety between drugs approved using clinical outcomes and those approved using surrogate outcomes. Because drugs in the surrogate outcome group are approved before their benefit:harm ratio is fully established, these drugs should be used with caution until their clinical benefits are better understood. PMID:26442227

  17. Absolute Lymphocyte Count as a Surrogate Marker of CD4 Count in Monitoring HIV Infected Individuals: A Prospective Study

    PubMed Central

    Rane, Sharda Raju; Jadhav, Meenal Vitthal

    2016-01-01

    Introduction CD4 cell count has been proposed to be substituted by Absolute lymphocyte count in monitoring HIV infected individuals as methods of CD4 cell count and plasma viral estimation require expensive, specialized equipments and highly trained personnel. Aim To assess the clinical utility of the Absolute Lymphocyte Count (ALC) to serve as a surrogate marker for predicting a CD4 count < 200 cells/μl in patients with HIV infection in resource poor countries. Materials and Methods A prospective study of 61 patients with HIV/AIDS was conducted. Sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) of various ALC cut-offs were computed for CD4 cell count < 200 cells/μl for age < 30 or age ≥ 30 years. Pearson correlation, Linear regression and Receiver Operating Characteristics (ROC), were used. Results For patients aged ≥ 30 years, sensitivity, specificity, positive and negative predictive value of ALC <1200 cells/μl to predict CD4 cell count < 200 cells/μl were 34.48%, 67.5%, 43.48%, 58.69% respectively. For subjects aged < 30 years, these values were 27.27%, 67.5%, 18.75%, 77.14%, respectively. A ALC < 1643 was found to have maximal sensitivity for predicting a CD4 cell count <200/ μl. Conclusion Our data revealed good correlation between ALC and CD4 cell counts but ALC cut-off of 1200 was not a surrogate marker for CD4 cell count < 200 cells/μl. As we increase the cut-off to <1643/ μl it could be the cost-effective surrogate marker for CD4 cell counts < 200 cells/μl in resource limited settings. PMID:27437225

  18. Predictive Value of Baseline Electronic Columbia–Suicide Severity Rating Scale (eC–SSRS) Assessments for Identifying Risk of Prospective Reports of Suicidal Behavior During Research Participation

    PubMed Central

    Mundt, James C.; Gwaltney, Chad J.; Jefferson, James W.; Posner, Kelly

    2014-01-01

    Objective: Examine the ability of baseline electronic Columbia–Suicide Severity Rating Scale lifetime suicidal ideation and behavior categories to predict prospective reports of suicidal behavior in psychiatric and non-psychiatric research participants. Design: Meta-analysis of 74,406 eC-SSRS assessments completed between September 2009 and December 2012. Setting: Thirty-three clinical research studies that used the electronic Columbia–Suicide Severity Rating Scale to assess suicidal ideation and behavior at baseline and prospectively during follow-up visits. Participants: Records from 6,760 patients with psychiatric disorders (opioid dependence, generalized anxiety, major depressive, and posttraumatic stress disorders) and 2,077 nonpsychiatric disorder patients (chronic obstructive pulmonary disease, epilepsy, fibromyalgia, human immunodeficiency virus, insomnia, multiple sclerosis, osteoarthritis, pain/back pain, Parkinson’s disease, restless leg syndrome) were analyzed. Measurements: Electronic Columbia–Suicide Severity Rating Scale assessment of lifetime suicidal ideation (5 severity levels) and suicidal behavior (4 types) at baseline and prospectively reported suicidal behavior during study participation. Results: Increasingly more severe lifetime suicidal ideation at baseline was associated with a progressively greater likelihood of prospectively reported suicidal behavior during study participation. Intent to act on suicidal ideation was most predictive of reports of suicidal behavior. Reports of lifetime suicidal behaviors at baseline also predicted subsequent suicidal behavior, and multiple lifetime behaviors monotonically increased prospective risk of suicidal behavior. Baseline suicidal ideation and behavior predicted future suicidal behavior in both psychiatric and non-psychiatric trials. Conclusions: Lifetime reports of suicidal ideation and/or behavior at baseline significantly increased risk of prospectively reporting suicidal behavior during

  19. A Bayesian hierarchical surrogate outcome model for multiple sclerosis.

    PubMed

    Pozzi, Luca; Schmidli, Heinz; Ohlssen, David I

    2016-07-01

    The development of novel therapies in multiple sclerosis (MS) is one area where a range of surrogate outcomes are used in various stages of clinical research. While the aim of treatments in MS is to prevent disability, a clinical trial for evaluating a drugs effect on disability progression would require a large sample of patients with many years of follow-up. The early stage of MS is characterized by relapses. To reduce study size and duration, clinical relapses are accepted as primary endpoints in phase III trials. For phase II studies, the primary outcomes are typically lesion counts based on magnetic resonance imaging (MRI), as these are considerably more sensitive than clinical measures for detecting MS activity. Recently, Sormani and colleagues in 'Surrogate endpoints for EDSS worsening in multiple sclerosis' provided a systematic review and used weighted regression analyses to examine the role of either MRI lesions or relapses as trial level surrogate outcomes for disability. We build on this work by developing a Bayesian three-level model, accommodating the two surrogates and the disability endpoint, and properly taking into account that treatment effects are estimated with errors. Specifically, a combination of treatment effects based on MRI lesion count outcomes and clinical relapse was used to develop a study-level surrogate outcome model for the corresponding treatment effects based on disability progression. While the primary aim for developing this model was to support decision-making in drug development, the proposed model may also be considered for future validation. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27061897

  20. Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints

    PubMed Central

    Renfro, Lindsay A.; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J.

    2014-01-01

    Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer. PMID:25061255

  1. Remote Sensing of Explosives Surrogates Using Ultrashort Laser Induced Breakdown Spectroscopy

    NASA Astrophysics Data System (ADS)

    Ahmido, Tariq

    2011-12-01

    Ultrashort Laser-Induced Breakdown Spectroscopy (LIBS) was used for the analysis of contaminants on surfaces. In this technique, emission radiation from the breakdown of surface contaminants was spectrally identified. The research focused on the detection of molecular fragments present in the plasma, which were generated when the laser broke down the surface. An ultra short laser pulse produced by a Ti: Sapphire chirped pulse amplification laser at a wavelength of 800 nm was used. The large bandwidth associated with this laser allowed it to be propagated and focused transversely and longitudinally at standoff distances to initiate the LIBS. The application of this research is to detect surface chemical compounds, such as pollutants and explosive molecules. In this Ph.D. dissertation project, ultrashort pulse LIBS detection of chemical explosive surrogates was studied with respect to laser pulse lengths, power, and intensities. Spectral signature around 410 nm observed for Potassium Nitrate and Sodium Nitrate was identified as fluorescence transitions of nitro (NO)-molecular structures. Extensive parameter studies of this signature indicated that even pico-second laser pulses might fall into the realm of long-pulse LIBS and thus had to be avoided. Careful control of laser parameters, such as pulse length and intensity, could lead to unambiguous detection of the nitro-group explosives and their surrogates on a surface at standoff distances.

  2. Deconstructing the surrogate species concept: a life history approach to the protection of ecosystem services

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of the surrogate species concept is widespread in environmental risk assessment and in particular the protection of species that provide ecosystem services, yet there are no standard protocols in place for the choice of surrogates. Surrogates are often chosen on the basis of convenience or ...

  3. Deconstructing the surrogate species concept:a life history approach to the protection of ecosystem services.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of the surrogate species concept is widespread in environmental risk assessment and in particular the protection of species that provide ecosystem services, yet there are no standard protocols in place for the choice of surrogates. Surrogates are often chosen on the basis of convenience or v...

  4. Estimation of k-e parameters using surrogate models and jet-in-crossflow data.

    SciTech Connect

    Lefantzi, Sophia; Ray, Jaideep; Arunajatesan, Srinivasan; Dechant, Lawrence

    2015-02-01

    We demonstrate a Bayesian method that can be used to calibrate computationally expensive 3D RANS (Reynolds Av- eraged Navier Stokes) models with complex response surfaces. Such calibrations, conditioned on experimental data, can yield turbulence model parameters as probability density functions (PDF), concisely capturing the uncertainty in the parameter estimates. Methods such as Markov chain Monte Carlo (MCMC) estimate the PDF by sampling, with each sample requiring a run of the RANS model. Consequently a quick-running surrogate is used instead to the RANS simulator. The surrogate can be very difficult to design if the model's response i.e., the dependence of the calibration variable (the observable) on the parameter being estimated is complex. We show how the training data used to construct the surrogate can be employed to isolate a promising and physically realistic part of the parameter space, within which the response is well-behaved and easily modeled. We design a classifier, based on treed linear models, to model the "well-behaved region". This classifier serves as a prior in a Bayesian calibration study aimed at estimating 3 k [?] e parameters ( C u , C e 2 , C e 1 ) from experimental data of a transonic jet-in-crossflow interaction. The robustness of the calibration is investigated by checking its predictions of variables not included in the cal- ibration data. We also check the limit of applicability of the calibration by testing at off-calibration flow regimes. We find that calibration yield turbulence model parameters which predict the flowfield far better than when the nomi- nal values of the parameters are used. Substantial improvements are still obtained when we use the calibrated RANS model to predict jet-in-crossflow at Mach numbers and jet strengths quite different from those used to generate the ex- perimental (calibration) data. Thus the primary reason for poor predictive skill of RANS, when using nominal values of the turbulence model

  5. [F-18]-Fluoromisonidazole Quantification of Hypoxia in Human Cancer Patients using Image-derived Blood Surrogate Tissue Reference Regions

    PubMed Central

    Muzi, Mark; Peterson, Lanell M.; O’Sullivan, Janet N.; Fink, James R.; Rajendran, Joseph G.; McLaughlin, Lena J.; Muzi, John P.; Mankoff, David A.; Krohn, Kenneth A.

    2015-01-01

    18F-FMISO is the most widely used PET agent for imaging hypoxia, a condition associated with resistance to tumor therapy. 18F-FMISO equilibrates in normoxic tissues, but is retained under hypoxic conditions because of reduction and binding to macromolecules. A simple tissue-to-blood ratio (TB) is suitable for quantifying hypoxia. A threshold of TB ≥ 1.2 is useful in discriminating the hypoxic volume (HV) of tissue; TBmax is the maximum intensity of the hypoxic region and does not invoke a threshold. Because elimination of blood sampling would simplify clinical use, we tested the validity of using imaging regions as a surrogate for blood sampling. Methods Patients underwent 20 min 18F-FMISO scans during the 90–140 min interval post-injection with venous blood sampling. 223 18F-FMISO patient studies had detectable surrogate blood regions in the field-of-view. Quantitative parameters of hypoxia (TBmax, HV) derived from blood samples were compared to values using surrogate blood regions derived from heart, aorta and/or cerebellum. In a subset of brain cancer patients, parameters from blood samples and from cerebellum were compared for their ability to independently predict outcome. Results Vascular regions of heart showed the highest correlation to measured blood activity (R2 = 0.84). For brain studies, cerebellar activity was similarly correlated to blood samples. In brain cancer patients, Kaplan-Meier analysis showed that image-derived reference regions had nearly identical predictive power as parameters derived from blood, thus obviating the need for venous sampling in these patients. Conclusions Simple static analysis of 18F-FMISO PET captures both the intensity (TBmax) and spatial extent (HV) of tumor hypoxia. An image-derived region to assess blood activity can be used as a surrogate for blood sampling in quantification of hypoxia. PMID:26112020

  6. Using an external surrogate for predictor model training in real-time motion management of lung tumors

    SciTech Connect

    Rottmann, Joerg; Berbeco, Ross

    2014-12-15

    Purpose: Precise prediction of respiratory motion is a prerequisite for real-time motion compensation techniques such as beam, dynamic couch, or dynamic multileaf collimator tracking. Collection of tumor motion data to train the prediction model is required for most algorithms. To avoid exposure of patients to additional dose from imaging during this procedure, the feasibility of training a linear respiratory motion prediction model with an external surrogate signal is investigated and its performance benchmarked against training the model with tumor positions directly. Methods: The authors implement a lung tumor motion prediction algorithm based on linear ridge regression that is suitable to overcome system latencies up to about 300 ms. Its performance is investigated on a data set of 91 patient breathing trajectories recorded from fiducial marker tracking during radiotherapy delivery to the lung of ten patients. The expected 3D geometric error is quantified as a function of predictor lookahead time, signal sampling frequency and history vector length. Additionally, adaptive model retraining is evaluated, i.e., repeatedly updating the prediction model after initial training. Training length for this is gradually increased with incoming (internal) data availability. To assess practical feasibility model calculation times as well as various minimum data lengths for retraining are evaluated. Relative performance of model training with external surrogate motion data versus tumor motion data is evaluated. However, an internal–external motion correlation model is not utilized, i.e., prediction is solely driven by internal motion in both cases. Results: Similar prediction performance was achieved for training the model with external surrogate data versus internal (tumor motion) data. Adaptive model retraining can substantially boost performance in the case of external surrogate training while it has little impact for training with internal motion data. A minimum

  7. HCCI experiments with gasoline surrogate fuels modeled by a semidetailed chemical kinetic model

    SciTech Connect

    Andrae, J.C.G.; Head, R.A.

    2009-04-15

    Experiments in a homogeneous charge compression ignition (HCCI) engine have been conducted with four gasoline surrogate fuel blends. The pure components in the surrogate fuels consisted of n-heptane, isooctane, toluene, ethanol and diisobutylene and fuel sensitivities (RON-MON) in the fuel blends ranged from two to nine. The operating conditions for the engine were p{sub in}=0.1 and 0.2 MPa, T{sub in}=80 and 250 C, {phi}=0.25 in air and engine speed 1200 rpm. A semidetailed chemical kinetic model (142 species and 672 reactions) for gasoline surrogate fuels, validated against ignition data from experiments conducted in shock tubes for gasoline surrogate fuel blends at 1.0{<=} p{<=}5.0MPa, 700{<=} T{<=}1200 K and {phi}=1.0, was successfully used to qualitatively predict the HCCI experiments using a single zone modeling approach. The fuel blends that had higher fuel sensitivity were more resistant to autoignition for low intake temperature and high intake pressure and less resistant to autoignition for high intake temperature and low intake pressure. A sensitivity analysis shows that at high intake temperature the chemistry of the fuels ethanol, toluene and diisobutylene helps to advance ignition. This is consistent with the trend that fuels with the least Negative Temperature Coefficient (NTC) behavior show the highest octane sensitivity, and become less resistant to autoignition at high intake temperatures. For high intake pressure the sensitivity analysis shows that fuels in the fuel blend with no NTC behavior consume OH radicals and acts as a radical scavenger for the fuels with NTC behavior. This is consistent with the observed trend of an increase in RON and fuel sensitivity. With data from shock tube experiments in the literature and HCCI modeling in this work, a correlation between the reciprocal pressure exponent on the ignition delay to the fuel sensitivity and volume percentage of single-stage ignition fuel in the fuel blend was found. Higher fuel

  8. Toward predicting drug-induced liver injury: parallel computational approaches to identify multidrug resistance protein 4 and bile salt export pump inhibitors.

    PubMed

    Welch, Matthew A; Köck, Kathleen; Urban, Thomas J; Brouwer, Kim L R; Swaan, Peter W

    2015-05-01

    Drug-induced liver injury (DILI) is an important cause of drug toxicity. Inhibition of multidrug resistance protein 4 (MRP4), in addition to bile salt export pump (BSEP), might be a risk factor for the development of cholestatic DILI. Recently, we demonstrated that inhibition of MRP4, in addition to BSEP, may be a risk factor for the development of cholestatic DILI. Here, we aimed to develop computational models to delineate molecular features underlying MRP4 and BSEP inhibition. Models were developed using 257 BSEP and 86 MRP4 inhibitors and noninhibitors in the training set. Models were externally validated and used to predict the affinity of compounds toward BSEP and MRP4 in the DrugBank database. Compounds with a score above the median fingerprint threshold were considered to have significant inhibitory effects on MRP4 and BSEP. Common feature pharmacophore models were developed for MRP4 and BSEP with LigandScout software using a training set of nine well characterized MRP4 inhibitors and nine potent BSEP inhibitors. Bayesian models for BSEP and MRP4 inhibition/noninhibition were developed with cross-validated receiver operator curve values greater than 0.8 for the test sets, indicating robust models with acceptable false positive and false negative prediction rates. Both MRP4 and BSEP inhibitor pharmacophore models were characterized by hydrophobic and hydrogen-bond acceptor features, albeit in distinct spatial arrangements. Similar molecular features between MRP4 and BSEP inhibitors may partially explain why various drugs have affinity for both transporters. The Bayesian (BSEP, MRP4) and pharmacophore (MRP4, BSEP) models demonstrated significant classification accuracy and predictability. PMID:25735837

  9. Toward Predicting Drug-Induced Liver Injury: Parallel Computational Approaches to Identify Multidrug Resistance Protein 4 and Bile Salt Export Pump Inhibitors

    PubMed Central

    Welch, Matthew A.; Köck, Kathleen; Urban, Thomas J.; Brouwer, Kim L. R.

    2015-01-01

    Drug-induced liver injury (DILI) is an important cause of drug toxicity. Inhibition of multidrug resistance protein 4 (MRP4), in addition to bile salt export pump (BSEP), might be a risk factor for the development of cholestatic DILI. Recently, we demonstrated that inhibition of MRP4, in addition to BSEP, may be a risk factor for the development of cholestatic DILI. Here, we aimed to develop computational models to delineate molecular features underlying MRP4 and BSEP inhibition. Models were developed using 257 BSEP and 86 MRP4 inhibitors and noninhibitors in the training set. Models were externally validated and used to predict the affinity of compounds toward BSEP and MRP4 in the DrugBank database. Compounds with a score above the median fingerprint threshold were considered to have significant inhibitory effects on MRP4 and BSEP. Common feature pharmacophore models were developed for MRP4 and BSEP with LigandScout software using a training set of nine well characterized MRP4 inhibitors and nine potent BSEP inhibitors. Bayesian models for BSEP and MRP4 inhibition/noninhibition were developed with cross-validated receiver operator curve values greater than 0.8 for the test sets, indicating robust models with acceptable false positive and false negative prediction rates. Both MRP4 and BSEP inhibitor pharmacophore models were characterized by hydrophobic and hydrogen-bond acceptor features, albeit in distinct spatial arrangements. Similar molecular features between MRP4 and BSEP inhibitors may partially explain why various drugs have affinity for both transporters. The Bayesian (BSEP, MRP4) and pharmacophore (MRP4, BSEP) models demonstrated significant classification accuracy and predictability. PMID:25735837

  10. Efficient prediction designs for random fields

    PubMed Central

    Müller, Werner G; Pronzato, Luc; Rendas, Joao; Waldl, Helmut

    2015-01-01

    For estimation and predictions of random fields, it is increasingly acknowledged that the kriging variance may be a poor representative of true uncertainty. Experimental designs based on more elaborate criteria that are appropriate for empirical kriging (EK) are then often non-space-filling and very costly to determine. In this paper, we investigate the possibility of using a compound criterion inspired by an equivalence theorem type relation to build designs quasi-optimal for the EK variance when space-filling designs become unsuitable. Two algorithms are proposed, one relying on stochastic optimization to explicitly identify the Pareto front, whereas the second uses the surrogate criteria as local heuristic to choose the points at which the (costly) true EK variance is effectively computed. We illustrate the performance of the algorithms presented on both a simple simulated example and a real oceanographic dataset. © 2014 The Authors. Applied Stochastic Models in Business and Industry published by John Wiley & Sons, Ltd. PMID:26300698

  11. Comprehensive Review on the Surrogate Endpoints of Efficacy Proposed or Hypothesized in the Scientific Community Today.

    PubMed

    von Minckwitz, Gunter; Fontanella, Caterina

    2015-05-01

    An intermediate endpoint is a surrogate marker of treatment efficacy assessed earlier than the true outcome of interest. A suitable intermediate endpoint in neoadjuvant trials of specific breast cancer subtypes is pathological complete response (pCR) rate, defined as no invasive (+/-noninvasive) residual cancer in breast and nodes at surgery. On the basis of available evidence, Food and Drug Administration the US allowed to use of pCR as a surrogate endpoint for accelerated approval process. However, surrogacy to long-term outcome remains an unresolved issue. Literature data provide indications that triple-negative, HER2-positive, and high-grade hormone receptor-positive breast cancer subtypes achieved the highest pCR rate; the prognostic impact of pCR on survival is established only for these aggressive subtypes. In the German experience, early response after two to four cycles of neoadjuvant treatment strongly correlated with both pCR rate and long-term outcome. Therefore, early response may be considered a predictive marker for pCR and used for driving clinical trial design. PMID:26063882

  12. Processing of Oak Ridge B&C pond sludge surrogate in the transportable vitrification system

    SciTech Connect

    Zamecnik, J.R.; Young, S.R.; Peeler, D.K.; Smith, M.E.

    1997-04-16

    The Transportable Vitrification System (TVS) developed at the Savannah River Site is designed to process low-level and mixed radioactive wastes into a stable glass product. The TVS consists of a feed preparation and delivery system, a joule-heated melter, and an offgas treatment system. Surrogate Oak Ridge Reservation (ORR) B&C pond sludge was treated in a demonstration of the TVS system at Clemson University and at ORR. After initial tests with soda-lime-silica (SLS) feed, three melter volumes of glass were produced from the surrogate feed. A forthcoming report will describe glass characterization; and melter feeding, operation, and glass pouring. Melter operations described will include slurry characterization and feeding, factors affecting feed melt rates, glass pouring and pour rate constraints, and melter operating temperatures. Residence time modeling of the melter will also be discussed. Characterization of glass; including composition, predicted liquidity and viscosity, Toxic Characteristic Leaching Procedure (TCLP), and devitrification will be covered. Devitrification was a concern in glass container tests and was found to be mostly dependent on the cooling rate. Crucible tests indicated that melter shutdown with glass containing Fe and Li was also a devitrification concern, so the melter was flushed with SLS glass before cooldown.

  13. The evaluation of new multi-material human soft tissue simulants for sports impact surrogates.

    PubMed

    Payne, Thomas; Mitchell, Séan; Bibb, Richard; Waters, Mark

    2015-01-01

    Previous sports impact reconstructions have highlighted the inadequacies in current measures to evaluate the effectiveness of personal protective equipment (PPE) and emphasised the need for improved impact surrogates that provide a more biofidelic representation of human impact response. The skin, muscle and subcutaneous adipose tissues were considered to constitute the structures primarily governing the mechanical behaviour of the human body segment. A preceding study by Payne et al. (in press) investigated the formulation and characterisation of muscle tissue simulants. The present study investigates the development of bespoke blends of additive cure polydimethysiloxane (PDMS) silicones to represent both skin and adipose tissues using the same processes previously reported. These simulants were characterised mechanically through a range of strain rates and a range of hyperelastic and viscoelastic constitutive models were evaluated to describe their behaviour. To explore the worth of the silicone simulants, finite element (FE) models were developed using anthropometric parameters representative of the human thigh segment, derived from the Visible Human Project. The multi-material silicone construction was validated experimentally and compared with both organic tissue data from literature and commonly used single material simulants: Dow Corning Silastic 3480 series silicones and ballistics gelatin when subject to a representative sports specific knee impact. Superior biofidelic performance is reported for the PDMS silicone formulations and surrogate predictions. PMID:25448686

  14. Evaluating Microbial Purification during Soil Treatment of Wastewater with Multicomponent Tracer and Surrogate Tests

    USGS Publications Warehouse

    Van Cuyk, S.; Siegrist, R.L.; Lowe, K.; Harvey, R.W.

    2004-01-01

    Soil treatment of wastewater has the potential to achieve high purification efficiency, yet the understanding and predictability of purification with respect to removal of viruses and other pathogens is limited. Research has been completed to quantify the removal of virus and bacteria through the use of microbial surrogates and conservative tracers during controlled experiments with three-dimensional pilot-scale soil treatment systems in the laboratory and during the testing of full-scale systems under field conditions. The surrogates and tracers employed included two viruses (MS-2 and PRID-1 bacteriophages), one bacterium (ice-nucleating active Pseudomonas), and one conservative tracer (bromide ion). Efforts have also been made to determine the relationship between viruses and fecal coliform bacteria in soil samples below the wastewater infiltrative surface, and the correlation between Escherichia coil concentrations measured in percolating soil solution as compared with those estimated from analyses of soil solids. The results suggest episodic breakthrough of virus and bacteria during soil treatment of wastewater and a 2 to 3 log (99-99.9%) removal of virus and near complete removal of fecal coliform bacteria during unsaturated flow through 60 to 90 cm of sandy medium. Results also suggest that the fate of fecal coliform bacteria may be indicative of that of viruses in soil media near the infiltrative surface receiving wastewater effluent. Concentrations of fecal coliform in percolating soil solution may be conservatively estimated from analysis of extracted soil solids.

  15. Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers

    PubMed Central

    Parise, Carol A.

    2014-01-01

    Introduction. ER, PR, and HER2 are routinely available in breast cancer specimens. The purpose of this study is to contrast breast cancer-specific survival for the eight ER/PR/HER2 subtypes with survival of an immunohistochemical surrogate for the molecular subtype based on the ER/PR/HER2 subtypes and tumor grade. Methods. We identified 123,780 cases of stages 1–3 primary female invasive breast cancer from California Cancer Registry. The surrogate classification was derived using ER/PR/HER2 and tumor grade. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess differences in survival and risk of mortality for the ER/PR/HER2 subtypes and surrogate classification within each stage. Results. The luminal B/HER2− surrogate classification had a higher risk of mortality than the luminal B/HER2+ for all stages of disease. There was no difference in risk of mortality between the ER+/PR+/HER2− and ER+/PR+/HER2+ in stage 3. With one exception in stage 3, the ER-negative subtypes all had an increased risk of mortality when compared with the ER-positive subtypes. Conclusions. Assessment of survival using ER/PR/HER2 illustrates the heterogeneity of HER2+ subtypes. The surrogate classification provides clear separation in survival and adjusted mortality but underestimates the wide variability within the subtypes that make up the classification. PMID:24955090

  16. Drinking Alcohol Surrogates Among Clients of an Alcohol-Misuser Treatment Clinic in Novosibirsk, Russia

    PubMed Central

    BOBROVA, NATALIA; WEST, ROBERT; MALUTINA, DARYA; KOSHKINA, EVGENIA; TERKULOV, RAVIL; BOBAK, MARTIN

    2014-01-01

    A pilot study was conducted in the Russian city Novosibirsk during 2006–2007 with 40 participants sampled from clients admitted to health services for drinking-related problems to explore surrogates for alcoholic beverage drinking using semistructured interviews. Types of surrogates consumed and reasons for their consumption were investigated. Results revealed that the most prevalent reported surrogate used was industrial spirit. The main reasons for drinking surrogates were the high affordability and physical availability of surrogates combined with the need to relieve severe withdrawal symptoms. The study limitations are described, and suggestions for future research are made. PMID:20001282

  17. Identifying the simplest predictive model of annual runoff ratio for quantifying the hydrologic impact of climate change in a Great Lakes river basin

    NASA Astrophysics Data System (ADS)

    Meissner, R.; Shaw, S. B.

    2014-12-01

    A standard approach to predict hydrologic fluxes in a changing climate is to downscale climate model output and feed it into a process-based hydrologic model. However, it has been demonstrated that 1) uncertainty in climate model projections often overwhelms uncertainties in the structure and parameterization of hydrologic models and 2) multiple parameter sets and structures can be used to make a hydrologic model match historical discharge (implying actual processes are not always known). Thus, it makes sense to attempt to use the simplest hydrologic model possible, both to focus on better quantifying uncertainty in climate model input and to try to ensure that the described hydrologic processes can actually be confirmed with some confidence. In addition, the use of a simple model increases the transparency of the science and can be helpful in building public consensus in making decisions regarding climate adaptation. As a case study, the Genesee River watershed was examined. The Genesee River is a 6475 sq km watershed extending from Northern Pennsylvania to Lake Ontario, running south to north. We focused on an important but simple measure of hydrologic function: the annual runoff ratio (annual average streamflow/annual average precipitation). The annual runoff ratio varies between 0.3 and 0.8 from 1927 to 2013. The obvious explanation for higher runoff ratio years - high precipitation in seasons with little evapotranspiration - does not readily explain the variations. Three simple attempts to explain this variation were explored: a statistical regression model, the Budyko Curve, and a hydrologic "bucket" model. All models were compared based on ability to replicate annual variations in runoff ratios. Preliminary analyses suggest that although the "bucket" model most closely predicts the annual runoff ratio values, none of the simple models sufficiently explain the annual runoff ratio variability. This indicates that a more complicated hydrologic model may be

  18. Inactivation of the Tulane Virus, a Novel Surrogate for the Human Norovirus

    PubMed Central

    TIAN, PENG; YANG, DAVID; QUIGLEY, CHRISTINA; CHOU, MARISSA; JIANG, XI

    2014-01-01

    Human noroviruses (HuNoVs) are the major cause of nonbacterial gastroenteritis epidemics. The culturable feline calicivirus and murine norovirus have been used extensively as surrogates to study HuNoV biology, as HuNoV does not grow in vitro. Additional efforts to identify new surrogates are needed, because neither of these common surrogates are truly intestinal pathogens. The newly described Tulane virus (TV) is a typical calicivirus, it is isolated from macaque stools, is cultivable in vitro, and recognizes human histo-blood group antigens. Therefore, TV is a promising surrogate for HuNoVs. In this study, we evaluated the resistance or stability of TV under various physical and environmental conditions by measuring a 50% reduction of tissue culture infective dose (TCID50) by using a TV cell culture system. Due to the nature of this virus, it is hard to produce a high-titer stock through tissue culture. In our study, the maximal reduction in virus titers was 5 D (D = 1 log) in heat-denaturation and EtOH experiments, and 4 D in UV, chlorine, and pH-stability experiments. Therefore in this study, we defined the inactivation of TV as reaching a TCID50/ml of 0 (a 4- to 5-D reduction in TCID50, depending on the detection limit). TV was inactivated after incubation at 63°C for 5 min, incubation at 56°C for 30 min (5 D), exposure to 60 mJ/cm2 of UVC radiation (4 D), or incubation at 300 ppm of free chlorine for 10 min (4 D). TV was shown to be stable from pH 3.0 to 8.0, though an obvious reduction in virus titer was observed at pH 2.5 and 9.0, and was inactivated at pH 10.0 (4 D). TV was resistant to a low concentration of EtOH (40% or lower) but was fully inactivated (5 D) by 50 to 70% EtOH after a short exposure (20 s). In contrast, quantitative real-time PCR was unable to detect, or poorly detected, virus titer reductions between treated and untreated samples described in this study. PMID:23575140

  19. Occupancy as a surrogate for abundance estimation

    USGS Publications Warehouse

    MacKenzie, D.I.; Nichols, J.D.

    2004-01-01

    In many monitoring programmes it may be prohibitively expensive to estimate the actual abundance of a bird species in a defined area, particularly at large spatial scales, or where birds occur at very low densities. Often it may be appropriate to consider the proportion of area occupied by the species as an alternative state variable. However, as with abundance estimation, issues of detectability must be taken into account in order to make accurate inferences: the non?detection of the species does not imply the species is genuinely absent. Here we review some recent modelling developments that permit unbiased estimation of the proportion of area occupied, colonization and local extinction probabilities. These methods allow for unequal sampling effort and enable covariate information on sampling locations to be incorporated. We also describe how these models could be extended to incorporate information from marked individuals, which would enable finer questions of population dynamics (such as turnover rate of nest sites by specific breeding pairs) to be addressed. We believe these models may be applicable to a wide range of bird species and may be useful for investigating various questions of ecological interest. For example, with respect to habitat quality, we might predict that a species is more likely to have higher local extinction probabilities, or higher turnover rates of specific breeding pairs, in poor quality habitats.

  20. Surrogate Model Application to the Identification of Optimal Groundwater Exploitation Scheme Based on Regression Kriging Method-A Case Study of Western Jilin Province.

    PubMed

    An, Yongkai; Lu, Wenxi; Cheng, Weiguo

    2015-08-01

    This paper introduces a surrogate model to identify an optimal exploitation scheme, while the western Jilin province was selected as the study area. A numerical simulation model of groundwater flow was established first, and four exploitation wells were set in the Tongyu county and Qian Gorlos county respectively so as to supply water to Daan county. Second, the Latin Hypercube Sampling (LHS) method was used to collect data in the feasible region for input variables. A surrogate model of the numerical simulation model of groundwater flow was developed using the regression kriging method. An optimization model was established to search an optimal groundwater exploitation scheme using the minimum average drawdown of groundwater table and the minimum cost of groundwater exploitation as multi-objective functions. Finally, the surrogate model was invoked by the optimization model in the process of solving the optimization problem. Results show that the relative error and root mean square error of the groundwater table drawdown between the simulation model and the surrogate model for 10 validation samples are both lower than 5%, which is a high approximation accuracy. The contrast between the surrogate-based simulation optimization model and the conventional simulation optimization model for solving the same optimization problem, shows the former only needs 5.5 hours, and the latter needs 25 days. The above results indicate that the surrogate model developed in this study could not only considerably reduce the computational burden of the simulation optimization process, but also maintain high computational accuracy. This can thus provide an effective method for identifying an optimal groundwater exploitation scheme quickly and accurately. PMID:26264008

  1. Surrogate Model Application to the Identification of Optimal Groundwater Exploitation Scheme Based on Regression Kriging Method—A Case Study of Western Jilin Province

    PubMed Central

    An, Yongkai; Lu, Wenxi; Cheng, Weiguo

    2015-01-01

    This paper introduces a surrogate model to identify an optimal exploitation scheme, while the western Jilin province was selected as the study area. A numerical simulation model of groundwater flow was established first, and four exploitation wells were set in the Tongyu county and Qian Gorlos county respectively so as to supply water to Daan county. Second, the Latin Hypercube Sampling (LHS) method was used to collect data in the feasible region for input variables. A surrogate model of the numerical simulation model of groundwater flow was developed using the regression kriging method. An optimization model was established to search an optimal groundwater exploitation scheme using the minimum average drawdown of groundwater table and the minimum cost of groundwater exploitation as multi-objective functions. Finally, the surrogate model was invoked by the optimization model in the process of solving the optimization problem. Results show that the relative error and root mean square error of the groundwater table drawdown between the simulation model and the surrogate model for 10 validation samples are both lower than 5%, which is a high approximation accuracy. The contrast between the surrogate-based simulation optimization model and the conventional simulation optimization model for solving the same optimization problem, shows the former only needs 5.5 hours, and the latter needs 25 days. The above results indicate that the surrogate model developed in this study could not only considerably reduce the computational burden of the simulation optimization process, but also maintain high computational accuracy. This can thus provide an effective method for identifying an optimal groundwater exploitation scheme quickly and accurately. PMID:26264008

  2. Resident physician interactions with surrogate decision-makers: the resident experience.

    PubMed

    Reckrey, Jennifer M; McKee, M Diane; Sanders, Justin J; Lipman, Hannah I

    2011-12-01

    This study explored interactions between medical residents and patient surrogates in order to clarify resident understanding of roles and relationships, resident emotional experience, and resident learning processes. Qualitative analysis of in-depth interviews were used involving three family medicine residency programs serving culturally diverse, urban, underserved patient populations. Eighteen second- and third-year trainees described a memorable interaction with a surrogate and then were prompted to discuss their learning experience and their role in the interaction. Interviews were transcribed verbatim and analyzed through an iterative process. Residents experienced significant emotional burden during interactions yet continued to value their relationships with surrogates. Despite their reservations about giving recommendations, residents adopted a variety of roles with surrogates as they gave support, information, and advice. Although residents reported little formal education about surrogate decision-making, they relied on passive role modeling and their own previous experiences to help surrogates make decisions. Residents have complex and emotionally significant interactions with surrogates despite minimal formal education about surrogate decision-making. Educational efforts should seek to help residents understand their own emotions and the ethical beliefs that underlie the roles they adopt with surrogates. This will help residents to facilitate value-based conversations with surrogates and better support surrogates in the decision-making process. PMID:22092192

  3. Motion prediction in MRI-guided radiotherapy based on interleaved orthogonal cine-MRI

    NASA Astrophysics Data System (ADS)

    Seregni, M.; Paganelli, C.; Lee, D.; Greer, P. B.; Baroni, G.; Keall, P. J.; Riboldi, M.

    2016-01-01

    In-room cine-MRI guidance can provide non-invasive target localization during radiotherapy treatment. However, in order to cope with finite imaging frequency and system latencies between target localization and dose delivery, tumour motion prediction is required. This work proposes a framework for motion prediction dedicated to cine-MRI guidance, aiming at quantifying the geometric uncertainties introduced by this process for both tumour tracking and beam gating. The tumour position, identified through scale invariant features detected in cine-MRI slices, is estimated at high-frequency (25 Hz) using three independent predictors, one for each anatomical coordinate. Linear extrapolation, auto-regressive and support vector machine algorithms are compared against systems that use no prediction or surrogate-based motion estimation. Geometric uncertainties are reported as a function of image acquisition period and system latency. Average results show that the tracking error RMS can be decreased down to a [0.2; 1.2] mm range, for acquisition periods between 250 and 750 ms and system latencies between 50 and 300 ms. Except for the linear extrapolator, tracking and gating prediction errors were, on average, lower than those measured for surrogate-based motion estimation. This finding suggests that cine-MRI guidance, combined with appropriate prediction algorithms, could relevantly decrease geometric uncertainties in motion compensated treatments.

  4. A Radio-genomics Approach for Identifying High Risk Estrogen Receptor-positive Breast Cancers on DCE-MRI: Preliminary Results in Predicting OncotypeDX Risk Scores.

    PubMed

    Wan, Tao; Bloch, B Nicolas; Plecha, Donna; Thompson, CheryI L; Gilmore, Hannah; Jaffe, Carl; Harris, Lyndsay; Madabhushi, Anant

    2016-01-01

    To identify computer extracted imaging features for estrogen receptor (ER)-positive breast cancers on dynamic contrast enhanced (DCE)-MRI that are correlated with the low and high OncotypeDX risk categories. We collected 96 ER-positive breast lesions with low (< 18, N = 55) and high (> 30, N = 41) OncotypeDX recurrence scores. Each lesion was quantitatively characterize via 6 shape features, 3 pharmacokinetics, 4 enhancement kinetics, 4 intensity kinetics, 148 textural kinetics, 5 dynamic histogram of oriented gradient (DHoG), and 6 dynamic local binary pattern (DLBP) features. The extracted features were evaluated by a linear discriminant analysis (LDA) classifier in terms of their ability to distinguish low and high OncotypeDX risk categories. Classification performance was evaluated by area under the receiver operator characteristic curve (Az). The DHoG and DLBP achieved Az values of 0.84 and 0.80, respectively. The 6 top features identified via feature selection were subsequently combined with the LDA classifier to yield an Az of 0.87. The correlation analysis showed that DHoG (ρ = 0.85, P < 0.001) and DLBP (ρ = 0.83, P < 0.01) were significantly associated with the low and high risk classifications from the OncotypeDX assay. Our results indicated that computer extracted texture features of DCE-MRI were highly correlated with the high and low OncotypeDX risk categories for ER-positive cancers. PMID:26887643

  5. Ichthyophonus parasite phylogeny based on ITS rDNA structure prediction and alignment identifies six clades, with a single dominant marine type

    USGS Publications Warehouse

    Gregg, Jacob; Thompson, Rachel L.; Purcell, Maureen; Friedman, Carolyn S.; Hershberger, Paul

    2016-01-01

    Despite their widespread, global impact in both wild and cultured fishes, little is known of the diversity, transmission patterns, and phylogeography of parasites generally identified as Ichthyophonus. This study constructed a phylogeny based on the structural alignment of internal transcribed spacer (ITS) rDNA sequences to compare Ichthyophonus isolates from fish hosts in the Atlantic and Pacific oceans, and several rivers and aquaculture sites in North America, Europe, and Japan. Structure of the Ichthyophonus ITS1–5.8S–ITS2 transcript exhibited several homologies with other eukaryotes, and 6 distinct clades were identified within Ichthyophonus. A single clade contained a majority (71 of 98) of parasite isolations. This ubiquitous Ichthyophonus type occurred in 13 marine and anadromous hosts and was associated with epizootics in Atlantic herring, Chinook salmon, and American shad. A second clade contained all isolates from aquaculture, despite great geographic separation of the freshwater hosts. Each of the 4 remaining clades contained isolates from single host species. This study is the first to evaluate the genetic relationships among Ichthyophonus species across a significant portion of their host and geographic range. Additionally, parasite infection prevalence is reported in 16 fish species.

  6. Ichthyophonus parasite phylogeny based on ITS rDNA structure prediction and alignment identifies six clades, with a single dominant marine type.

    PubMed

    Gregg, Jacob L; Powers, Rachel L; Purcell, Maureen K; Friedman, Carolyn S; Hershberger, Paul K

    2016-07-01

    Despite their widespread, global impact in both wild and cultured fishes, little is known of the diversity, transmission patterns, and phylogeography of parasites generally identified as Ichthyophonus. This study constructed a phylogeny based on the structural alignment of internal transcribed spacer (ITS) rDNA sequences to compare Ichthyophonus isolates from fish hosts in the Atlantic and Pacific oceans, and several rivers and aquaculture sites in North America, Europe, and Japan. Structure of the Ichthyophonus ITS1-5.8S-ITS2 transcript exhibited several homologies with other eukaryotes, and 6 distinct clades were identified within Ichthyophonus. A single clade contained a majority (71 of 98) of parasite isolations. This ubiquitous Ichthyophonus type occurred in 13 marine and anadromous hosts and was associated with epizootics in Atlantic herring, Chinook salmon, and American shad. A second clade contained all isolates from aquaculture, despite great geographic separation of the freshwater hosts. Each of the 4 remaining clades contained isolates from single host species. This study is the first to evaluate the genetic relationships among Ichthyophonus species across a significant portion of their host and geographic range. Additionally, parasite infection prevalence is reported in 16 fish species. PMID:27409236

  7. Semiparametric inference for surrogate endpoints with bivariate censored data.

    PubMed

    Ghosh, Debashis

    2008-03-01

    Considerable attention has been recently paid to the use of surrogate endpoints in clinical research. We deal with the situation where the two endpoints are both right censored. While proportional hazards analyses are typically used for this setting, their use leads to several complications. In this article, we propose the use of the accelerated failure time model for analysis of surrogate endpoints. Based on the model, we then describe estimation and inference procedures for several measures of surrogacy. A complication is that potentially both the independent and dependent variable are subject to censoring. We adapt the Theil-Sen estimator to this problem, develop the associated asymptotic results, and propose a novel resampling-based technique for calculating the variances of the proposed estimators. The finite-sample properties of the estimation methodology are assessed using simulation studies, and the proposed procedures are applied to data from an acute myelogenous leukemia clinical trial. PMID:17651457

  8. Cervical cancer chemoprevention, vaccines, and surrogate endpoint biomarkers.

    PubMed

    Follen, Michele; Meyskens, Frank L; Alvarez, Ronald D; Walker, Joan L; Bell, Maria C; Storthz, Karen Adler; Sastry, Jagannadha; Roy, Krishnendu; Richards-Kortum, Rebecca; Cornelison, Terri L

    2003-11-01

    At the Second International Conference on Cervical Cancer, held April 11-14, 2002, experts in cervical cancer prevention, detection, and treatment reviewed the need for more research in chemoprevention, including prophylactic and therapeutic vaccines, immunomodulators, peptides, and surrogate endpoint biomarkers. Investigators and clinicians noted the need for more rigorous Phase I randomized clinical trials, more attention to the risk factors that can affect study results in this patient population, and validation of optical technologies that will provide valuable quantitative information in real time regarding disease regression and progression. They discussed the role of the human papillomavirus (HPV) in cervical cancer development and the importance of developing strategies to suppress HPV persistence and progression. Results in Phase I randomized clinical trials have been disappointing because few have demonstrated statistically significant regression attributable to the agent tested. Researchers recommended using a transgenic mouse model to test and validate new compounds, initiating vaccine and immunomodulator trials, and developing immunologic surrogate endpoint biomarkers. PMID:14603541

  9. Consumption of Alcohol Surrogates Among Alcohol-Dependent Women.

    PubMed

    Razvodovsky, Yury Evgeny

    2015-01-01

    This is the first in-depth study of alcohol and surrogate drinking patterns, types, reasons, and correlates among alcohol-dependent women in Belarus. The structured interviews were performed in 2013 with 103 alcohol-dependent women admitted to a narcological clinic in Grodno, Belarus. The results suggest that at least 30.3% of alcohol-dependent women regularly consume samogon (moonshine) and 10.8% of women use surrogates, the most popular among which are medications with a high percentage of ethanol and industrial spirits. The belief that samogon exceeds licensed vodka in quality is the main motive for its consumption. The results from the present study confirm that noncommercial alcohol use is common among alcohol-dependent women although its use may be underreported. These findings emphasize that the implementation of a comprehensive alcohol policy must take fully into account the consumption of alcohol from illicit sources. PMID:26549001

  10. Surrogates of protection in repeated low-dose challenge experiments.

    PubMed

    Long, Dustin M; Hudgens, Michael G; Wu, Chih-Da

    2015-05-10

    A critical step toward developing a successful vaccine to control the human immunodeficiency virus pandemic entails evaluation of vaccine candidates in non-human primates (NHPs). Historically, these studies have usually entailed challenges (i.e., exposures) with very high doses of a simian version of human immunodeficiency virus, resulting in infection of all NHPs in the experiment after a single challenge. More recently, researchers have begun to conduct repeated low-dose challenge (RLC) studies in NHPs that are believed to more closely mimic typical exposure in natural human transmission settings. One objective of RLC studies is to assess whether measured immune responses to vaccination can serve as surrogate endpoints for the primary endpoint of interest, namely infection. In this paper, different designs of RLC studies for assessing a binary surrogate of protection are considered. PMID:25628249

  11. Surrogates of Protection in Repeated Low-Dose Challenge Experiments

    PubMed Central

    Long, Dustin M.; Hudgens, Michael G.; Wu, Chih-Da

    2015-01-01

    A critical step toward developing a successful vaccine to control the human immunodeficiency virus (HIV) pandemic entails evaluation of vaccine candidates in non-human primates (NHPs). Historically, these studies have usually entailed challenges (i.e., exposures) with very high doses of a simian version of HIV, resulting in infection of all NHPs in the experiment after a single challenge. More recently, researchers have begun to conduct repeated low-dose challenge (RLC) studies in NHPs that are believed to more closely mimic typical exposure in natural human transmission settings. One objective of RLC studies is to assess whether measured immune responses to vaccination can serve as surrogate endpoints for the primary endpoint of interest, namely infection. In this paper, different designs of RLC studies for assessing a binary surrogate of protection are considered. PMID:25628249

  12. Surrogate-based Reliability Analysis Using Support Vector Machine

    NASA Astrophysics Data System (ADS)

    Li, Gang; Liu, Zhiqiang

    2010-05-01

    An approach of surrogate-based reliability analysis by support vector machine with Monte-Carlo simulation is proposed. The efficient sampling techniques, such as uniform design and Latin Hypercube sampling, are used, and the SVM is trained with the sample pairs of input and output data obtained by the finite element analysis. The trained SVM model, as a solver-surrogate model, is intended to approximate the real performance function. Considering the selection of parameters for SVM affects the learning performance of SVM strongly, the Genetic Algorithm (GA) is integrated to the construction of the SVM, by optimizing the relevant parameters. The influence of the parameters on SVM is discussed and a methodology is proposed for selecting the SVM model. Support Vector Classification (SVC) based and Support Vector Regression (SVR) based reliability analyses are studied. Some numerical examples demonstrate the efficiency and applicability of the proposed method.

  13. International cross-validation of a BOD5 surrogate.

    PubMed

    Muller, Mathieu; Bouguelia, Sihem; Goy, Romy-Alice; Yoris, Alison; Berlin, Jeanne; Meche, Perrine; Rocher, Vincent; Mertens, Sharon; Dudal, Yves

    2014-12-01

    BOD5 dates back to 1912 when the Royal Commission decided to use the mean residence time of water in the rivers of England, 5 days, as a standard to measure the biochemical oxygen demand. Initially designed to protect the quality of river waters from extensive sewage discharge, the use of BOD5 has been quickly extended to waste water treatment plants (WWTPs) to monitor their efficiency on a daily basis. The measurement has been automatized but remains a tedious, time- and resource-consuming analysis. We have cross-validated a surrogate BOD5 method on two sites in France and in the USA with a total of 109 samples. This method uses a fluorescent redox indicator on a 96-well microplate to measure microbial catabolic activity for a large number of samples simultaneously. Three statistical tests were used to compare surrogate and reference methods and showed robust equivalence. PMID:24946712

  14. An Ethical and Legal Framework for Physicians as Surrogate Decision-Makers for Their Patients.

    PubMed

    Rosoff, Philip M; Leong, Kelly M

    2015-01-01

    In Western industrialized countries, it is well established that legally competent individuals may choose a surrogate healthcare decision-maker to represent their interests should they lose the capacity to do so themselves. There are few limitations on who they may select to fulfill this function. However, many jurisdictions place restrictions on or prohibit the patient's attending physician or other provider involved with an individual's care to serve in this role. Several authors have previously suggested that respect for the autonomy of patients requires that there be few (if any) constraints on whomever they may appoint as a proxy. In this essay we revisit this topic by first providing a survey of current state laws governing this activity. We then analyze the clinical and ethical circumstances in which potential difficulties could arise. We take a more nuanced and circumspect view of prior suggestions that patients should have virtually unfettered liberty to choose their healthcare proxies. We suggest a strategy to balance the freedom of patients' right to choose their surrogates with fiduciary duty of the state as regulator of medical practice. We identify six domains of possible concern with such relationships and suggest straightforward methods of mitigating their potential negative effects that could be plausibly be incorporated into physician practice. PMID:26711423

  15. A surrogate-based metaheuristic global search method for beam angle selection in radiation treatment planning

    PubMed Central

    Zhang, H H; Gao, S; Chen, W; Shi, L; D’Souza, W D; Meyer, R R

    2013-01-01

    An important element of radiation treatment planning for cancer therapy is the selection of beam angles (out of all possible coplanar and non-coplanar angles in relation to the patient) in order to maximize the delivery of radiation to the tumor site and minimize radiation damage to nearby organs-at-risk. This category of combinatorial optimization problem is particularly difficult because direct evaluation of the quality of treatment corresponding to any proposed selection of beams requires the solution of a large-scale dose optimization problem involving many thousands of variables that represent doses delivered to volume elements (voxels) in the patient. However, if the quality of angle sets can be accurately estimated without expensive computation, a large number of angle sets can be considered, increasing the likelihood of identifying a very high quality set. Using a computationally efficient surrogate beam set evaluation procedure based on single-beam data extracted from plans employing equally-spaced beams (eplans), we have developed a global search metaheuristic process based on the Nested Partitions framework for this combinatorial optimization problem. The surrogate scoring mechanism allows us to assess thousands of beam set samples within a clinically acceptable time frame. Tests on difficult clinical cases demonstrate that the beam sets obtained via our method are superior quality. PMID:23459411

  16. A surrogate-based metaheuristic global search method for beam angle selection in radiation treatment planning

    NASA Astrophysics Data System (ADS)

    Zhang, H. H.; Gao, S.; Chen, W.; Shi, L.; D'Souza, W. D.; Meyer, R. R.

    2013-03-01

    An important element of radiation treatment planning for cancer therapy is the selection of beam angles (out of all possible coplanar and non-coplanar angles in relation to the patient) in order to maximize the delivery of radiation to the tumor site and minimize radiation damage to nearby organs-at-risk. This category of combinatorial optimization problem is particularly difficult because direct evaluation of the quality of treatment corresponding to any proposed selection of beams requires the solution of a large-scale dose optimization problem involving many thousands of variables that represent doses delivered to volume elements (voxels) in the patient. However, if the quality of angle sets can be accurately estimated without expensive computation, a large number of angle sets can be considered, increasing the likelihood of identifying a very high quality set. Using a computationally efficient surrogate beam set evaluation procedure based on single-beam data extracted from plans employing equally-spaced beams (eplans), we have developed a global search metaheuristic process based on the nested partitions framework for this combinatorial optimization problem. The surrogate scoring mechanism allows us to assess thousands of beam set samples within a clinically acceptable time frame. Tests on difficult clinical cases demonstrate that the beam sets obtained via our method are of superior quality.

  17. A FRAX Experience in Korea: Fracture Risk Probabilities with a Country-specific Versus a Surrogate Model

    PubMed Central

    Min, Yong-Ki; Lee, Dong-Yun; Park, Youn-Soo; Moon, Young-Wan; Lim, Seung-Jae; Lee, Young-Kyun; Choi, DooSeok

    2015-01-01

    Background Recently, a Korean fracture-risk assessment tool (FRAX) model has become available, but large prospective cohort studies, which are needed to validate the model, are still lacking, and there has been little effort to evaluate its usefulness. This study evaluated the clinical usefulness of the FRAX model, a FRAX developed by the World Health Organization, in Korea. Methods In 405 postmenopausal women and 139 men with a proximal femoral fracture, 10-year predicted fracture probabilities calculated by the Korean FRAX model (a country-specific model) were compared with the probabilities calculated with a FRAX model for Japan, which has a similar ethnic background (surrogate model). Results The 10-year probabilities of major osteoporotic and hip fractures calculated by the Korean model were significantly lower than those calculated by the Japanese model in women and men. The fracture probabilities calculated by each model increased significantly with age in both sexes. In patients aged 70 or older, however, there was a significant difference between the two models. In addition, the Korean model led to lower probabilities for major osteoporotic fracture and hip fracture in women when BMD was excluded from the model than when it was included. Conclusions The 10-year fracture probabilities calculated with FRAX models might differ between country-specific and surrogate models, and caution is needed when applying a surrogate model to a new population. A large prospective study is warranted to validate the country-specific Korean model in the general population. PMID:26389086

  18. Current issues on a standard for surrogate pregnancy procedures

    PubMed Central

    2012-01-01

    While Korea does not have any legal statement on surrogacy, treatments are carried out in practice. As a result, every Institutional Review Board (IRB) of each fertility clinic faces an ethical predicament in reviewing each case. There is a need to arrange the institutions' own standards of surrogate pregnancy procedures before the establishment of national or professional regulation. This article examines the legal, social, and medical issues of surrogacy to help IRBs to