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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. Assessing a surrogate predictive value: a causal inference approach.

    PubMed

    Alonso, Ariel; Van der Elst, Wim; Meyvisch, Paul

    2017-03-30

    Several methods have been developed for the evaluation of surrogate endpoints within the causal-inference and meta-analytic paradigms. In both paradigms, much effort has been made to assess the capacity of the surrogate to predict the causal treatment effect on the true endpoint. In the present work, the so-called surrogate predictive function (SPF) is introduced for that purpose, using potential outcomes. The relationship between the SPF and the individual causal association, a new metric of surrogacy recently proposed in the literature, is studied in detail. It is shown that the SPF, in conjunction with the individual causal association, can offer an appealing quantification of the surrogate predictive value. However, neither the distribution of the potential outcomes nor the SPF are identifiable from the data. These identifiability issues are tackled using a two-step procedure. In the first step, the region of the parametric space of the distribution of the potential outcomes, compatible with the data at hand, is geometrically characterized. Further, in a second step, a Monte Carlo approach is used to study the behavior of the SPF on the previous region. The method is illustrated using data from a clinical trial involving schizophrenic patients and a newly developed and user friendly R package Surrogate is provided to carry out the validation exercise. Copyright © 2016 John Wiley & Sons, Ltd.

  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. 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

  5. Surrogate models for identifying robust, high yield regions of parameter space for ICF implosion simulations

    NASA Astrophysics Data System (ADS)

    Humbird, Kelli; Peterson, J. Luc; Brandon, Scott; Field, John; Nora, Ryan; Spears, Brian

    2016-10-01

    Next-generation supercomputer architecture and in-transit data analysis have been used to create a large collection of 2-D ICF capsule implosion simulations. The database includes metrics for approximately 60,000 implosions, with x-ray images and detailed physics parameters available for over 20,000 simulations. To map and explore this large database, surrogate models for numerous quantities of interest are built using supervised machine learning algorithms. Response surfaces constructed using the predictive capabilities of the surrogates allow for continuous exploration of parameter space without requiring additional simulations. High performing regions of the input space are identified to guide the design of future experiments. In particular, a model for the yield built using a random forest regression algorithm has a cross validation score of 94.3% and is consistently conservative for high yield predictions. The model is used to search for robust volumes of parameter space where high yields are expected, even given variations in other input parameters. Surrogates for additional quantities of interest relevant to ignition are used to further characterize the high yield regions. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, Lawrence Livermore National Security, LLC. LLNL-ABS-697277.

  6. 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

  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. 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.

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

    NASA Astrophysics Data System (ADS)

    Yang, Feiling; Hu, Jinming; Wu, Ruidong

    2016-08-01

    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.

  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

    2016-08-19

    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.

  12. Surrogate measures and consistent surrogates.

    PubMed

    Vanderweele, Tyler J

    2013-09-01

    Surrogates which allow one to predict the effect of the treatment on the outcome of interest from the effect of the treatment on the surrogate are of importance when it is difficult or expensive to measure the primary outcome. Unfortunately, the use of such surrogates can give rise to paradoxical situations in which the effect of the treatment on the surrogate is positive, the surrogate and outcome are strongly positively correlated, but the effect of the treatment on the outcome is negative, a phenomenon sometimes referred to as the "surrogate paradox." New results are given for consistent surrogates that extend the existing literature on sufficient conditions that ensure the surrogate paradox is not manifest. Specifically, it is shown that for the surrogate paradox to be manifest it must be the case that either there is (i) a direct effect of treatment on the outcome not through the surrogate and in the opposite direction as that through the surrogate or (ii) confounding for the effect of the surrogate on the outcome, or (iii) a lack of transitivity so that treatment does not positively affect the surrogate for all the same individuals for whom the surrogate positively affects the outcome. The conditions for consistent surrogates and the results of the article are important because they allow investigators to predict the direction of the effect of the treatment on the outcome simply from the direction of the effect of the treatment on the surrogate. These results on consistent surrogates are then related to the four approaches to surrogate outcomes described by Joffe and Greene (2009, Biometrics 65, 530-538) to assess whether the standard criteria used by these approaches to assess whether a surrogate is "good" suffice to avoid the surrogate paradox.

  13. Development of Fluorescence Surrogates to Predict the Photochemical Transformation of Pharmaceuticals in Wastewater Effluents.

    PubMed

    Yan, Shuwen; Yao, Bo; Lian, Lushi; Lu, Xinchen; Snyder, Shane A; Li, Rui; Song, Weihua

    2017-03-07

    The photochemical transformation of pharmaceutical and personal care products (PPCPs) in wastewater effluents is an emerging concern for environmental scientists. In the current study, the photodegradation of 29 PPCPs was examined in effluents under simulated solar irradiation. Direct photodegradation, triplet state effluent organic matter ((3)EfOM*)-mediated and hydroxyl radical (HO(•))-mediated degradation are three major pathways in the removal process. With the photodegradation of trace levels of PPCPs, the excitation-emission matrix (EEM) fluorescence intensities of the effluents were also gradually reduced. Therefore, fluorescence peaks have been identified, for the first time, as appropriate surrogates to assess the photodegradation of PPCPs. The humic-like fluorescence peak is linked to direct photolysis-labile PPCPs, such as naproxen, ronidazole, diclofenac, ornidazole, tinidazole, chloramphenicol, flumequine, ciprofloxacin, methadone, and dimetridazole. The tyrosine-like EEM peak is associated with HO(•)/CO3(•-)-labile PPCPs, such as trimethoprim, ibuprofen, gemfibrozil, atenolol, carbamazepine, and cephalexin. The tryptophan-like peak is associated with (3)EfOM*-labile PPCPs, such as clenbuterol, metoprolol, venlafaxine, bisphenol A, propranolol, ractopamine, salbutamol, roxithromycin, clarithromycin, azithromycin, famotidine, terbutaline, and erythromycin. The reduction in EEM fluorescence correlates well with the removal of PPCPs, allowing a model to be constructed. The solar-driven removal of EEM fluorescence was applied to predict the attenuation of 11 PPCPs in five field samples. A close correlation between the predicted results and the experimental results suggests that fluorescence may be a suitable surrogate for monitoring the solar-driven photodegradation of PPCPs in effluents.

  14. 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.

  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. Ensemble of Surrogates-based Optimization for Identifying an Optimal Surfactant-enhanced Aquifer Remediation Strategy at Heterogeneous DNAPL-contaminated Sites

    NASA Astrophysics Data System (ADS)

    Lu, W., Sr.; Xin, X.; Luo, J.; Jiang, X.; Zhang, Y.; Zhao, Y.; Chen, M.; Hou, Z.; Ouyang, Q.

    2015-12-01

    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.

  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).

  18. 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

    2014-01-06

    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).

  19. 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.

  20. 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 ...

  1. 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

  2. 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.

  3. Surrogate molecular markers for IGHV mutational status in chronic lymphocytic leukemia for predicting time to first treatment.

    PubMed

    Morabito, Fortunato; Cutrona, Giovanna; Mosca, Laura; D'Anca, Marianna; Matis, Serena; Gentile, Massimo; Vigna, Ernesto; Colombo, Monica; Recchia, Anna Grazia; Bossio, Sabrina; De Stefano, Laura; Maura, Francesco; Manzoni, Martina; Ilariucci, Fiorella; Consoli, Ugo; Vincelli, Iolanda; Musolino, Caterina; Cortelezzi, Agostino; Molica, Stefano; Ferrarini, Manlio; Neri, Antonino

    2015-08-01

    ZAP-70 is a marker of clinical outcome in chronic lymphocytic leukemia (CLL), however its assessment suffers from a lack of standardization consensus. To identify novel markers able to surrogate IGHV mutational status, CD19(+)CD5(+)-B-lymphocytes from 216 patients enrolled in a prospective study (ClinicalTrial.gov Identifier:NCT00917540), underwent gene expression profiling. Samples were split into CLL-Training (n=102) and CLL-Validation (n=114) sets, and an independent supervised analysis for IGHV mutational status was performed considering all genes with gene expression equal or above that of ZAP-70. Thirty-one genes (23 up- and 8 down-regulated) and 23 genes (18 up- and 5 down-regulated) satisfied these criteria in the CLL-Training and CLL-Validation sets, respectively, and 20 common genes (15 up and 5 down) were found to be differentially regulated in both sets. Two (SNORA70F, NRIP1) of the down-regulated and 6 (SEPT10, ZNF667, TGFBR3, MBOAT1, LPL, CRY1) of the up-regulated genes were significantly associated with a reduced risk of disease progression in both sets. Forcing the afore-mentioned genes in a Cox multivariate model together with IGHV mutational status, only CRY1 (HR=2.3, 95% CI: 1.1-4.9, P=.027) and MBOAT1 (HR=2.1, 95% CI: 1.1-3.7, P=.018) retained their independent prognostic impact, supporting the hypothesis that these genes may potentially act as surrogates for predicting IGHV mutational status.

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

    PubMed Central

    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

  5. 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.

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

    PubMed

    Zhao, Ying; Lu, Wenxi; Xiao, Chuanning

    2016-01-01

    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.

  7. Design, development, and analysis of a surrogate for pulmonary injury prediction.

    PubMed

    Danelson, Kerry A; Gayzik, F Scott; Stern, Amber Rath; Hoth, J Jason; Stitzel, Joel D

    2011-10-01

    Current anthropomorphic test devices (ATDs) measure chest acceleration and deflection to assess risk of injury to the thorax. This study presents a lung surrogate prototype designed to expand the injury assessment capabilities of ATDs to include a risk measure for pulmonary contusion (PC). The surrogate augments these existing measures by providing pressure data specific to the lung and its lobes. The prototype was created from a rendering of a 50th percentile male lung inflated to normal inspiration, obtained from clinical CT data. Surrogate size, lobe volume, and airway cross sections were selected to match the morphology of the lung. Elastomeric urethane was molded via rapid prototyping to create a functional prototype. Pressure sensors in each of the five terminal airways independently monitored pressure traces in the lobes during impacts to the surrogate. Software was created to analyze the surrogate impact pressure data, determine the lobe with the greatest pressure rise for a particular impact, and estimate the initial speed of surface deformation. Calibration testing indicates an approximately linear relationship between peak lobe pressure and surface impact speed. No type I or II errors were demonstrated during lobe detection testing. During repeatability testing, the standard deviation was between 2 and 4% of the mean peak pressure. Ongoing research will focus on correlating surrogate data, pressure pulses, or surface deformation, to risk functions for PC.

  8. Individual Identifiability Predicts Population Identifiability in Forensic Microsatellite Markers.

    PubMed

    Algee-Hewitt, Bridget F B; Edge, Michael D; Kim, Jaehee; Li, Jun Z; Rosenberg, Noah A

    2016-04-04

    Highly polymorphic genetic markers with significant potential for distinguishing individual identity are used as a standard tool in forensic testing [1, 2]. At the same time, population-genetic studies have suggested that genetically diverse markers with high individual identifiability also confer information about genetic ancestry [3-6]. The dual influence of polymorphism levels on ancestry inference and forensic desirability suggests that forensically useful marker sets with high levels of individual identifiability might also possess substantial ancestry information. We study a standard forensic marker set-the 13 CODIS loci used in the United States and elsewhere [2, 7-9]-together with 779 additional microsatellites [10], using direct population structure inference to test whether markers with substantial individual identifiability also produce considerable information about ancestry. Despite having been selected for individual identification and not for ancestry inference [11], the CODIS markers generate nontrivial model-based clustering patterns similar to those of other sets of 13 tetranucleotide microsatellites. Although the CODIS markers have relatively low values of the F(ST) divergence statistic, their high heterozygosities produce greater ancestry inference potential than is possessed by less heterozygous marker sets. More generally, we observe that marker sets with greater individual identifiability also tend toward greater population identifiability. We conclude that population identifiability regularly follows as a byproduct of the use of highly polymorphic forensic markers. Our findings have implications for the design of new forensic marker sets and for evaluations of the extent to which individual characteristics beyond identification might be predicted from current and future forensic data.

  9. Identifying cryptic diversity with predictive phylogeography.

    PubMed

    Espíndola, Anahí; Ruffley, Megan; Smith, Megan L; Carstens, Bryan C; Tank, David C; Sullivan, Jack

    2016-10-26

    Identifying units of biological diversity is a major goal of organismal biology. An increasing literature has focused on the importance of cryptic diversity, defined as the presence of deeply diverged lineages within a single species. While most discoveries of cryptic lineages proceed on a taxon-by-taxon basis, rapid assessments of biodiversity are needed to inform conservation policy and decision-making. Here, we introduce a predictive framework for phylogeography that allows rapidly identifying cryptic diversity. Our approach proceeds by collecting environmental, taxonomic and genetic data from codistributed taxa with known phylogeographic histories. We define these taxa as a reference set, and categorize them as either harbouring or lacking cryptic diversity. We then build a random forest classifier that allows us to predict which other taxa endemic to the same biome are likely to contain cryptic diversity. We apply this framework to data from two sets of disjunct ecosystems known to harbour taxa with cryptic diversity: the mesic temperate forests of the Pacific Northwest of North America and the arid lands of Southwestern North America. The predictive approach presented here is accurate, with prediction accuracies placed between 65% and 98.79% depending of the ecosystem. This seems to indicate that our method can be successfully used to address ecosystem-level questions about cryptic diversity. Further, our application for the prediction of the cryptic/non-cryptic nature of unknown species is easily applicable and provides results that agree with recent discoveries from those systems. Our results demonstrate that the transition of phylogeography from a descriptive to a predictive discipline is possible and effective.

  10. Suitability of Organic Matter Surrogates to Predict Trihalomethane Formation in Drinking Water Sources.

    PubMed

    Pifer, Ashley D; Fairey, Julian L

    2014-03-01

    Broadly applicable disinfection by-product (DBP) precursor surrogate parameters could be leveraged at drinking water treatment plants (DWTPs) to curb formation of regulated DBPs, such as trihalomethanes (THMs). In this study, dissolved organic carbon (DOC), ultraviolet absorbance at 254 nm (UV254), fluorescence excitation/emission wavelength pairs (IEx/Em), and the maximum fluorescence intensities (FMAX) of components from parallel factor (PARAFAC) analysis were evaluated as total THM formation potential (TTHMFP) precursor surrogate parameters. A diverse set of source waters from eleven DWTPs located within watersheds underlain by six different soil orders were coagulated with alum at pH 6, 7, and 8, resulting in 44 sample waters. DOC, UV254, IEx/Em, and FMAX values were measured to characterize dissolved organic matter in raw and treated waters and THMs were quantified following formation potential tests with free chlorine. For the 44 sample waters, the linear TTHMFP correlation with UV254 was stronger (r(2)=0.89) than I240/562 (r(2)=0.81, the strongest surrogate parameter from excitation/emission matrix pair picking), FMAX from a humic/fulvic acid-like PARAFAC component (r(2)=0.78), and DOC (r(2)=0.75). Results indicate that UV254 was the most accurate TTHMFP precursor surrogate parameter assessed for a diverse group of raw and alum-coagulated waters.

  11. Suitability of Organic Matter Surrogates to Predict Trihalomethane Formation in Drinking Water Sources

    PubMed Central

    Pifer, Ashley D.; Fairey, Julian L.

    2014-01-01

    Abstract Broadly applicable disinfection by-product (DBP) precursor surrogate parameters could be leveraged at drinking water treatment plants (DWTPs) to curb formation of regulated DBPs, such as trihalomethanes (THMs). In this study, dissolved organic carbon (DOC), ultraviolet absorbance at 254 nm (UV254), fluorescence excitation/emission wavelength pairs (IEx/Em), and the maximum fluorescence intensities (FMAX) of components from parallel factor (PARAFAC) analysis were evaluated as total THM formation potential (TTHMFP) precursor surrogate parameters. A diverse set of source waters from eleven DWTPs located within watersheds underlain by six different soil orders were coagulated with alum at pH 6, 7, and 8, resulting in 44 sample waters. DOC, UV254, IEx/Em, and FMAX values were measured to characterize dissolved organic matter in raw and treated waters and THMs were quantified following formation potential tests with free chlorine. For the 44 sample waters, the linear TTHMFP correlation with UV254 was stronger (r2=0.89) than I240/562 (r2=0.81, the strongest surrogate parameter from excitation/emission matrix pair picking), FMAX from a humic/fulvic acid-like PARAFAC component (r2=0.78), and DOC (r2=0.75). Results indicate that UV254 was the most accurate TTHMFP precursor surrogate parameter assessed for a diverse group of raw and alum-coagulated waters. PMID:24669183

  12. 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.

  13. Identifying Predictive Markers for Personalized Treatment Selection

    PubMed Central

    Shen, Yuanyuan

    2017-01-01

    Summary It is now well recognized that the effectiveness and potential risk of a treatment often vary by patient subgroups. Although trial-and-error and one-size-fits-all approaches to treatment selection remains a common practice, much recent focus has been placed on individualized treatment selection based on patient information (La Thangue and Kerr, 2011; Ong et al., 2012). Genetic and molecular markers are becoming increasingly available to guide treatment selection for various diseases including HIV and breast cancer (Mallal et al., 2008; Zujewski and Kamin, 2008). In recent years, many statistical procedures for developing individualized treatment rules (ITRs) have been proposed. However, less focus has been given to efficient selection of predictive biomarkers for treatment selection. The standard Wald test for interactions between treatment and the set of markers of interest may not work well when the marker effects are non-linear. Furthermore, interaction based test is scale dependent and may fail to capture markers useful for predicting individualized treatment differences. In this paper, we propose to overcome these difficulties by developing a kernel machine (KM) score test that can efficiently identify markers predictive of treatment difference. Simulation studies show that our proposed KM based score test is more powerful than the Wald test when there is non-linear effect among the predictors and when the outcome is binary with non-linear link functions. Furthermore, when there is high-correlation among predictors and when the number of predictors is not small, our method also over-performs Wald test. The proposed method is illustrated with two randomized clinical trials. PMID:26999054

  14. 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.

  15. Using a Surrogate Test of Math Skills to Predict Performance of Non-Traditional Accounting Students.

    ERIC Educational Resources Information Center

    Schiff, Jonathan B.

    1989-01-01

    A study was designed to predict student performance in the introductory accounting course, specifically the performance of nontraditional students. A predictive instrument to measure mathematical abilities was employed; outcomes were compared to individuals' final course grade. Results indicate that a brief math skills test can predict performance…

  16. Development of a surrogate model based on patient weight, bone mass and geometry to predict femoral neck strains and fracture loads.

    PubMed

    Taylor, Mark; Perilli, Egon; Martelli, Saulo

    2017-04-11

    Osteoporosis and related bone fractures are an increasing global burden in our ageing society. Areal bone mineral density assessed through dual energy X-ray absorptiometry (DEXA), the clinically accepted and most used method, is not sufficient to assess fracture risk individually. Finite element (FE) modelling has shown improvements in prediction of fracture risk, better than aBMD from DEXA, but is not practical for widespread clinical use. The aim of this study was to develop an adaptive neural network (ANN)-based surrogate model to predict femoral neck strains and fracture loads obtained from a previously developed population-based FE model. The surrogate model performance was assessed in simulating two loading conditions: the stance phase of gait and a fall. The surrogate model successfully predicted strains estimated by FE (r(2)=0.90-0.98 for level gait load case, r(2)=0.92-0.96 for the fall load case). Moreover, an ANN model based on three measurements obtainable in clinics (femoral neck length (level gait) or maximum femoral neck diameter (fall), femoral neck bone mass, body weight) was able to give reasonable predictions (r(2)=0.84-0.94) for all of the strain metrics and the estimated femoral neck fracture load. Overall, the surrogate model has potential for clinical applications as they are based on simple measures of geometry and bone mass which can be derived from DEXA images, accurately predicting FE model outcomes, with advantages over FE models as they are quicker and easier to perform.

  17. Serum midkine as a surrogate biomarker for metastatic prediction in differentiated thyroid cancer patients with positive thyroglobulin antibody

    PubMed Central

    Jia, Qiang; Meng, Zhaowei; Xu, Ke; He, Xianghui; Tan, Jian; Zhang, Guizhi; Li, Xue; Liu, Na; Hu, Tianpeng; Zhou, Pingping; Wang, Sen; Upadhyaya, Arun; Liu, Xiaoxia; Wang, Huiying; Zhang, Chunmei

    2017-01-01

    Serum thyroglobulin (Tg) is the main post-operative tumor biomarker for patients with differentiated thyroid cancer (DTC). However, the presence of thyroglobulin antibodies (TgAb) can interfere with Tg level and invalidate the test. In this study, we aimed to investigate the predicative value of midkine (MK) as a cancer biomarker for DTC patients with positive TgAb before the first 131I therapy. MK levels were measured by enzyme-linked immunosorbent assay in 151 recruited DTC patients after exercising strict inclusion and exclusion criteria. There were 28 TgAb positive DTC patients with metastases and 123 DTC patients without metastases. The value of pre-131I-ablative MK to predict metastasis was assessed by receiver operating characteristic (ROC) curves in these two groups of patients. MK levels in the TgAb positive DTC patients were significantly higher than the DTC patients without metastases. ROC showed good predictability of MK, with an area under the curve of 0.856 (P < 0.001), and a diagnostic accuracy of 83% at the optimal cut-off value of 550 pg/ml. In conclusion, we show that MK can potentially be used as a surrogate biomarker for predicting DTC metastases when Tg is not suitable due to TgAb positivity. PMID:28240744

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

    PubMed Central

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

    2016-01-01

    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 US 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 ask 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/ESRL Global Greenhouse Gas Reference Network (GGGRN). The surrogates consist of measured enhancements of various anthropogenic trace gases, including CO, SF6, and halo- and hydrocarbons acquired in vertical airborne sampling profiles near Cape May, NJ and Portsmouth, NH from 2005 through 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 uncertainties and potentially

  19. 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

  20. Surrogate gas prediction model as a proxy for Δ(14)C-based measurements of fossil fuel-CO2.

    PubMed

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

    2016-06-27

    The measured (14)C:(12)C isotopic ratio of atmospheric CO2 (and its associated derived Δ(14)C 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 US fossil fuel-CO2 emissions should be possible. However, the number of Δ(14)C measurements is presently constrained by cost, available sample volume, and availability of mass spectrometer measurement facilities. Δ(14)C is therefore measured in just a small fraction of samples obtained by ask 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/ESRL Global Greenhouse Gas Reference Network (GGGRN). The surrogates consist of measured enhancements of various anthropogenic trace gases, including CO, SF6, and halo- and hydrocarbons acquired in vertical airborne sampling profiles near Cape May, NJ and Portsmouth, NH from 2005 through 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 Δ(14)C measurements in the NOAA GGGRN and building new PPR models at additional sites would improve our understanding of uncertainties and

  1. 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

  2. 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...

  3. A comparative analysis of the pedestrian injury risk predicted by mechanical impactors and post mortem human surrogates.

    PubMed

    Kerrigan, Jason R; Crandall, Jeff R; Deng, Bing

    2008-11-01

    The objective of this study is to compare the risk of injury to pedestrians involved in vehicle-pedestrian impacts as predicted by two different types of risk assessment tools: the pedestrian subsystem impactors recommended by the European Enhanced Vehicle-Safety Committee (EEVC) and post-mortem human surrogates (PMHS). Seven replicate full-scale vehicle-pedestrian impact tests were performed with PMHS and a mid-sized sedan travelling at 40 km/h. The PMHS were instrumented with six-degree-of-freedom sensor cubes and sensor data were transformed and translated to predict impact kinematics at the head center of gravity, proximal tibiae, and knee joints. Single EEVC WG 17/EuroNCAP adult headform, upper legform and lower legform impactor tests of the same vehicle were selected for comparison based on the proximity of their impact locations to that of the PMHS. The PMHS experienced higher HIC values (1830/2160) and lower impact velocities (8.5/7.5 m/s) than the impactor (1532 and 11.1 m/s) in impacts at the lower fourth of the windshield. The lower legform impactor (31 degrees) and PMHS (right: 25-40 degrees, and left: 24-39 degrees) predicted similar maximum knee bending angles. Some PMHS tibial accelerations (114-613 g) exceeded the proposed acceptance criteria (150-200 g) in both the absence and presence of distal tibial fracture, with the impactor predicting a similar result (335 g). The upper legform impactor test resulted in bending moments (361 Nm) and forces (6.3 kN) exceeding the acceptance criteria, while PMHS sustained pelvic injuries in 6 out of 7 tests.

  4. Handgrip dynamometry: a surrogate marker of malnutrition to predict the prognosis in alcoholic liver disease

    PubMed Central

    Gaikwad, Nitin Rangrao; Gupta, Sudhir Jagdishprasad; Samarth, Amol Rajendra; Sankalecha, Tushar Hiralal

    2016-01-01

    Background The aim of the study was to determine the utility of handgrip dynamometry (HGD) in predicting short term mortality and complications in alcoholic liver disease. Methods Patients with alcoholic liver disease were included and nutritional assessment was done using the Subjective Global Assessment (SGA), HGD and other conventional parameters. Mortality rates and complications were compared to nutritional status. Results 80 patients were included in the study. Mean age of patients was 43.06±10.03 years. 69 patients survived and 11 patients died within the 3 month study duration. Handgrip strength (HGS) was higher in SGA A (28.76±5.48 kg) than SGA B (22.43±4.95 kg) and SGA C (16.78±3.83 kg) (P=<0.001). Number of complications including spontaneous bacterial Peritonitis, gastrointestinal bleeding and encephalopathy in SGA C group were 66.66%, in SGA B 20.75% and SGA A 10%. Mean HGS was significantly higher in the survivors (24.23±5.86) compared to non-survivors (18.04±4.82) (P=0.0011). There was a strong negative correlation between the HGS and Child-Pugh score (P=<0.0012). Multivariate logistic regression analysis to assess the risk factors for death showed handgrip to be in the suggestive significance range (P=0.072). The sensitivity of HGS was 88.41% in predicting short term mortality. Conclusions HGS correlates with Child-Pugh score in predicting short term mortality. HGD is a simple, inexpensive and sensitive tool for assessing the nutritional status in alcoholic liver disease and can reliably predict its complications and survival. PMID:27708519

  5. Prediction of ignition implosion performance using measurements of Low-deuterium surrogates

    NASA Astrophysics Data System (ADS)

    Spears, B. K.; Brandon, S.; Clark, D.; Cerjan, C.; Edwards, J.; Landen, O.; Lindl, J.; Haan, S.; Hatchett, S.; Salmonson, J.; Springer, P.; Weber, S. V.; Wilson, D.

    2010-08-01

    The National Ignition Campaign (NIC) will use non-igniting "THD" capsules with cryogenic ice layers to study and optimize the hydrodynamic assembly of the fuel without burn. These capsules are characterized by the ratios of T:H:D. The species ratios are set with two goals in mind: (1) control T:D in order to adjust the nuclear energy production and (2) preserve the average atomic number of the fuel at 2.5 to maintain hydrodynamic similarity with the DT ignition capsule. We have developed an experimentally observable ignition threshold factor (ITFX) that uses measurements from THD experiments to predict the performance of DT ignition implosions. It was developed and tested on multiple large databases of 2D radhydro simulations. Each of the thousands of simulations includes twin DT and THD simulations with a variety of physical failure mechanisms - drive asymmetry, capsule roughness, continuum mixing, fabrication errors, among others. The results of our numerical database and the ITFX metric have allowed us to develop an experimental estimate of the probability of DT ignition based on THD experiments. The analysis accounts for both diagnostic precision and the effects of a finite number of shots. The NIC expects to field a combination of diagnostics and experimental attempts that result in a 15 to 20 percent uncertainty in the experimentally inferred probability of ignition. This work was completed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  6. 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,…

  7. 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

  8. 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.

  9. 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.

  10. SitesIdentify: a protein functional site prediction tool

    PubMed Central

    2009-01-01

    Background The rate of protein structures being deposited in the Protein Data Bank surpasses the capacity to experimentally characterise them and therefore computational methods to analyse these structures have become increasingly important. Identifying the region of the protein most likely to be involved in function is useful in order to gain information about its potential role. There are many available approaches to predict functional site, but many are not made available via a publicly-accessible application. Results Here we present a functional site prediction tool (SitesIdentify), based on combining sequence conservation information with geometry-based cleft identification, that is freely available via a web-server. We have shown that SitesIdentify compares favourably to other functional site prediction tools in a comparison of seven methods on a non-redundant set of 237 enzymes with annotated active sites. Conclusion SitesIdentify is able to produce comparable accuracy in predicting functional sites to its closest available counterpart, but in addition achieves improved accuracy for proteins with few characterised homologues. SitesIdentify is available via a webserver at http://www.manchester.ac.uk/bioinformatics/sitesidentify/ PMID:19922660

  11. Toward a Psychology of Surrogate Decision Making.

    PubMed

    Tunney, Richard J; Ziegler, Fenja V

    2015-11-01

    In everyday life, many of the decisions that we make are made on behalf of other people. A growing body of research suggests that we often, but not always, make different decisions on behalf of other people than the other person would choose. This is problematic in the practical case of legally designated surrogate decision makers, who may not meet the substituted judgment standard. Here, we review evidence from studies of surrogate decision making and examine the extent to which surrogate decision making accurately predicts the recipient's wishes, or if it is an incomplete or distorted application of the surrogate's own decision-making processes. We find no existing domain-general model of surrogate decision making. We propose a framework by which surrogate decision making can be assessed and a novel domain-general theory as a unifying explanatory concept for surrogate decisions.

  12. A predictive approach to identify genes differentially expressed

    NASA Astrophysics Data System (ADS)

    Saraiva, Erlandson F.; Louzada, Francisco; Milan, Luís A.; Meira, Silvana; Cobre, Juliana

    2012-10-01

    The main objective of gene expression data analysis is to identify genes that present significant changes in expression levels between a treatment and a control biological condition. In this paper, we propose a Bayesian approach to identify genes differentially expressed calculating credibility intervals from predictive densities which are constructed using sampled mean treatment effect from all genes in study excluding the treatment effect of genes previously identified with statistical evidence for difference. We compare our Bayesian approach with the standard ones based on the use of the t-test and modified t-tests via a simulation study, using small sample sizes which are common in gene expression data analysis. Results obtained indicate that the proposed approach performs better than standard ones, especially for cases with mean differences and increases in treatment variance in relation to control variance. We also apply the methodologies to a publicly available data set on Escherichia coli bacteria.

  13. 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

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

    PubMed

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

    2016-03-10

    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.

  15. 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

  16. A novel anti-Vpre-B antibody identifies immunoglobulin-surrogate receptors on the surface of human pro-B cells

    PubMed Central

    1996-01-01

    Vpre-B and lambda 5 genes, respectively, encode V-like and C-like domains of a surrogate immunoglobulin light chain (psi L). Such psi L complex is expressed in early progenitor B (pro-B) cells, before conventional immunoglobulin heavy (microH) and light (L) chains are produced. We raised a wide panel of monoclonal antibodies (mAbs) against soluble recombinant Vpre-B proteins to study early events in human B cell development. One of these antibodies, B-MAD688, labeled surrogate Ig-complexes on the surface of microH- pro-B cell lines and normal bone marrow cells in immunofluorescence assays. Immunoprecipitations using surface-labeled pro-B cells and B-MAD688 mAb indicated that human psi L is associated with high molecular weight components homologous to the surrogate heavy (psi H) chains described in mouse. Using B-MAD688 and SLC2 mAbs, we were able to distinguish between psi H psi L and microH psi L complexes on the surface of human pro-B and later precursor, pre-B, cells. The finding of psi H psi L complexes in mouse and man lead us to hypothesize a role for psi H- containing receptors in B cell development. PMID:8676092

  17. 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.

  18. Total lymphocyte count as a surrogate marker to predict CD4 count in human immunodeficiency virus-infected children: a retrospective evaluation.

    PubMed

    Wang, Yuming; Li, Yuqian; Wang, Chongjian; Liang, Shuying; Guo, Jinling; Li, Zizhao; Zhang, Meixi; Li, Wenjie

    2012-01-01

    A retrospective study was conducted, and 576 human immunodeficiency virus-infected children with total lymphocyte count (TLC) and CD4 count were recruited from China. Spearman rank order correlation and receiver-operating characteristic were used. An overall positive correlation was noted between TLC and CD4 count (prehighly active antiretroviral therapy [pre-HAART], r = 0.789, 6 months of HAART, r = 0.642, 12 months of HAART, r = 0.691, P = 0.001). TLC ≤ 2600 cells/mm(3) predicted a CD4 count of ≤ 350 cells/mm(3) with 82.9% sensitivity, 79.6% specificity pre-HAART. Meanwhile, the optimum prediction for CD4 count of ≤ 350 cells/mm(3) was a TLC of ≤ 2400 cells/mm at 6 months (73.6% sensitivity and 74.1% specificity) and 12 months (81.7% sensitivity and 76.5% specificity) of HAART. TLC can be used as a surrogate marker for predicting CD4 count of human immunodeficiency virus-infected children before and during HAART in resource-limited countries.

  19. 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.

  20. Surrogate endpoint analysis: an exercise in extrapolation.

    PubMed

    Baker, Stuart G; Kramer, Barnett S

    2013-03-06

    Surrogate endpoints offer the hope of smaller or shorter cancer trials. It is, however, important to realize they come at the cost of an unverifiable extrapolation that could lead to misleading conclusions. With cancer prevention, the focus is on hypothesis testing in small surrogate endpoint trials before deciding whether to proceed to a large prevention trial. However, it is not generally appreciated that a small surrogate endpoint trial is highly sensitive to a deviation from the key Prentice criterion needed for the hypothesis-testing extrapolation. With cancer treatment, the focus is on estimation using historical trials with both surrogate and true endpoints to predict treatment effect based on the surrogate endpoint in a new trial. Successively leaving out one historical trial and computing the predicted treatment effect in the left-out trial yields a standard error multiplier that summarizes the increased uncertainty in estimation extrapolation. If this increased uncertainty is acceptable, three additional extrapolation issues (biological mechanism, treatment following observation of the surrogate endpoint, and side effects following observation of the surrogate endpoint) need to be considered. In summary, when using surrogate endpoint analyses, an appreciation of the problems of extrapolation is crucial.

  1. 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

  2. A surrogate for topical delivery in human skin: silicone membranes.

    PubMed

    Sloan, Kenneth B; Synovec, Jennifer; Ketha, Hemamalini

    2013-02-01

    We have identified, for any surrogate membrane and human skin in vitro, the maximum flux through the membrane (output) should be measured if a correlation between the two is to be obtained. We also identified from an analysis of the passive permeation process that molecular weight, lipid and aqueous solubilities (which are easily measured) constitute the physicochemical properties of the active (input), upon which prediction of flux through the surrogate membrane and through skin in vitro should be based. Besides providing the bases for predicting flux, changes in these physicochemical properties can be easily implemented by those wishing to optimize new cosmetics or topical products. Maximum flux values through silicone membrane (n = 70) and through human skin in vitro (n = 52) have been collected and a good correlation between the flux through human skin in vitro and flux through silicone membrane (for the same molecules) was found.

  3. 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.

  4. 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

  5. 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

    2015-09-08

    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.

  6. 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

  7. Evaluating surrogate marker information using censored data.

    PubMed

    Parast, Layla; Cai, Tianxi; Tian, Lu

    2017-01-15

    Given the long follow-up periods that are often required for treatment or intervention studies, the potential to use surrogate markers to decrease the required follow-up time is a very attractive goal. However, previous studies have shown that using inadequate markers or making inappropriate assumptions about the relationship between the primary outcome and surrogate marker can lead to inaccurate conclusions regarding the treatment effect. Currently available methods for identifying and validating surrogate markers tend to rely on restrictive model assumptions and/or focus on uncensored outcomes. The ability to use such methods in practice when the primary outcome of interest is a time-to-event outcome is difficult because of censoring and missing surrogate information among those who experience the primary outcome before surrogate marker measurement. In this paper, we propose a novel definition of the proportion of treatment effect explained by surrogate information collected up to a specified time in the setting of a time-to-event primary outcome. Our proposed approach accommodates a setting where individuals may experience the primary outcome before the surrogate marker is measured. We propose a robust non-parametric procedure to estimate the defined quantity using censored data and use a perturbation-resampling procedure for variance estimation. Simulation studies demonstrate that the proposed procedures perform well in finite samples. We illustrate the proposed procedures by investigating two potential surrogate markers for diabetes using data from the Diabetes Prevention Program. Copyright © 2017 John Wiley & Sons, Ltd.

  8. 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,…

  9. 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

  10. 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.

  11. Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition.

    PubMed

    Gilbert, Peter B; Gabriel, Erin E; Huang, Ying; Chan, Ivan S F

    2015-09-01

    A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect

  12. Non-invasive combined surrogates of remifentanil blood concentrations with relevance to analgesia.

    PubMed

    Lötsch, Jörn; Skarke, Carsten; Darimont, Jutta; Zimmermann, Michael; Bräutigam, Lutz; Geisslinger, Gerd; Ultsch, Alfred; Oertel, Bruno G

    2013-10-01

    Surrogates may provide easy and quick access to information about pharmacological parameters of interest that can be directly measured only with difficulty. Surrogates have been proposed for opioid blood concentrations to replace invasive sampling, serving as a basis for target-controlled infusion systems to optimize analgesia. We aimed at identifying surrogates of remifentanil steady-state blood concentrations with relevance for its clinical, in particular, analgesic, effects. A "single ascending dose" study design assessed concentration-dependent effects of remifentanil in a double-blind randomized fashion in 16 healthy volunteers. Remifentanil was administered by means of computerized infusion aimed at steady-state effect-site concentrations of 0, 1.2, 1.8, 2.4, 3, 3.6, 4.8, and 6 ng/ml (one concentration per subject, two subjects per concentration). Arterial remifentanil blood concentrations were measured during apparent steady state. Pharmacodynamic parameters were measured at baseline and during steady-state conditions. Potential surrogate parameters included the pupil diameter, the amplitude of pupil light reflex, and the performance in a visual tracking task. Clinical parameters were analgesia to experimental pain, nausea, tiredness, and visual acuity. Remifentanil blood concentrations were well predicted by its effects on the pupil light reflex amplitude, better than by its miotic effects. However, the best prediction for both remifentanil blood concentrations and analgesic effects was obtained using a combination of three surrogate parameters (pupil diameter, light reflex amplitude, and tracking performance). This combination of pharmacodynamic parameters provided even better predictions of analgesia than could be obtained using the measured opioid blood concentrations. Developing surrogates only for opioid blood concentrations is insufficient when opioid effects are the final goal. Combining pharmacodynamic surrogate parameters seems to provide a

  13. Jet Pump Design Optimization by Multi-Surrogate Modeling

    NASA Astrophysics Data System (ADS)

    Mohan, S.; Samad, A.

    2014-09-01

    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.

  14. 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.

  15. Use of fluconazole as a surrogate marker to predict susceptibility and resistance to voriconazole among 13,338 clinical isolates of Candida spp. Tested by clinical and laboratory standards institute-recommended broth microdilution methods.

    PubMed

    Pfaller, M A; Messer, S A; Boyken, L; Rice, C; Tendolkar, S; Hollis, R J; Diekema, D J

    2007-01-01

    Clinical laboratories frequently face the problem of delayed availability of commercially prepared approved reagents for performing susceptibility testing of new antimicrobials. Although this problem is encountered more often with antibacterial agents, it is also an issue with antifungal agents. A current example is voriconazole, a new triazole antifungal with an expanded spectrum and potency against Candida spp., Aspergillus spp., and other opportunistic fungal pathogens. The present study addresses the use of fluconazole as a surrogate marker to predict the susceptibility of Candida spp. to voriconazole. Reference broth microdilution MIC results for 13,338 strains of Candida spp. isolated from more than 200 medical centers worldwide were used. Voriconazole MICs and interpretive categories (susceptible, < or =1 microg/ml; susceptible dose dependent, 2 microg/ml; resistant, > or =4 microg/ml) were compared with those of fluconazole by regression statistics and error rate bounding analyses. For all 13,338 isolates, the absolute categorical agreement was 91.6% (false susceptible or very major error [VME], 0.0%). Since voriconazole is 16- to 32-fold more potent than fluconazole, the performance of fluconazole as a surrogate marker for voriconazole susceptibility was improved by designating those isolates with fluconazole MICs of < or =32 microg/ml as being susceptible to voriconazole, resulting in a categorical agreement of 97% with 0.1% VME. Clinical laboratories performing antifungal susceptibility testing of fluconazole against Candida spp. can reliably use these results as surrogate markers until commercial FDA-approved voriconazole susceptibility tests become available.

  16. TU-AB-303-02: A Novel Surrogate to Identify Anatomical Changes During Radiotherapy of Head and Neck Cancer Patients

    SciTech Connect

    Gros, S; Roeske, J; Surucu, M

    2015-06-15

    Purpose: To develop a novel method to monitor external anatomical changes in head and neck cancer patients in order to help guide adaptive radiotherapy decisions. Methods: The method, developed in MATLAB, reveals internal anatomical changes based on variations observed in external anatomy. Weekly kV-CBCT scans from 11 Head and neck patients were retrospectively analyzed. The pre-processing step first corrects each CBCT for artifacts and removes pixels from the immobilization mask to produce an accurate external contour of the patient’s skin. After registering the CBCTs to the initial planning CT, the external contours from each CBCT (CBCTn) are transferred to the first week — reference — CBCT{sub 1}. Contour radii, defined as the distances between an external contour and the central pixel of each CBCT slice, are calculated for each scan at angular increments of 1 degree. The changes in external anatomy are then quantified by the difference in radial distance between the external contours of CBCT1 and CBCTn. The radial difference is finally displayed on a 2D intensity map (angle vs radial distance difference) in order to highlight regions of interests with significant changes. Results: The 2D radial difference maps provided qualitative and quantitative information, such as the location and the magnitude of external contour divergences and the rate at which these deviations occur. With this method, anatomical changes due to tumor volume shrinkage and patient weight loss were clearly identified and could be correlated with the under-dosage of targets or over-dosage of OARs. Conclusion: This novel method provides an efficient tool to visualize 3D external anatomical modification on a single 2D map. It quickly pinpoints the location of differences in anatomy during the course of radiotherapy, which can help determine if a treatment plan needs to be adapted.

  17. Surrogate end points in secondary analyses of cardiovascular trials.

    PubMed

    Buhr, Kevin A

    2012-01-01

    A surrogate end point is one that is used as a substitute for a clinical end point of more direct interest, usually for reasons of practicality, and that is expected to predict clinical benefit. Surrogate end points play a critical role in the advancement of all medical research, and cardiovascular (CV) research in particular. However, the relationship between a surrogate end point and its clinical end point is usually complex, and there are many examples where results based on surrogates have proved to be misleading. Secondary analyses of existing clinical trial data are likely to involve surrogate end points, if only because clinical end points will have been extensively studied as part of the primary analysis of a trial large enough to collect useful clinical end point data. Validation of a surrogate end point is a laudable goal for a secondary analysis of a large clinical end point trial (or meta-analysis of multiple smaller trials), and the result may be an important new tool for further study of a class of compounds in a particular disease context. Secondary analyses using surrogate end points may also provide new insight into disease or treatment mechanism, but as with any surrogate end point analysis, the results can mislead, and the existing literature is heavy on application and light on methodology. Surrogate end points often substitute efficiency for clarity, and while many interesting and potentially informative secondary analyses of CV trials will involve surrogates, results are likely to be ambiguous and should be interpreted with care.

  18. Use of anidulafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 4,290 clinical isolates of Candida by using CLSI methods and interpretive criteria.

    PubMed

    Pfaller, Michael A; Diekema, Daniel J; Jones, Ronald N; Castanheira, Mariana

    2014-09-01

    This study addressed the application of anidulafungin as a surrogate marker to predict the susceptibility of Candida to caspofungin due to unacceptably high interlaboratory variation of caspofungin MIC values. CLSI reference broth microdilution methods and species-specific interpretive criteria were used to test 4,290 strains of Candida (eight species), including 71 strains with documented fks mutations. Caspofungin MIC values were compared with those of anidulafungin to determine the percentage of categorical agreement (CA) and very major (VME), major (ME), and minor error rates, as well as the ability to detect fks mutants. For all 4,290 isolates the CA was 97.1% (0.2% VME and ME, 2.5% minor errors) using anidulafungin as the surrogate. Among the 62 isolates of Candida albicans (4 isolates), C. tropicalis (5 isolates), C. krusei (4 isolates), C. kefyr (2 isolates), and C. glabrata (47 isolates) that were nonsusceptible (NS; either intermediate [I] or resistant [R]) to both caspofungin and anidulafungin, 52 (83.8%) contained a mutation in fks1 or fks2. Eight mutants of C. glabrata, two of C. albicans, and one each of C. tropicalis and C. krusei were classified as susceptible (S) to both antifungal agents. The remaining 7 mutants (2 C. albicans and 5 C. glabrata) were susceptible to one of the agents and either intermediate or resistant to the other. Using the epidemiological cutoff value (ECV) of 0.12 μg/ml for both caspofungin and anidulafungin to differentiate wild-type (WT) from non-WT strains of C. glabrata, 42 of the 55 (76.4%) C. glabrata mutants were non-WT and 8 of the 55 (14.5%) were WT for both agents (90.9% concordance). Anidulafungin can accurately serve as a surrogate marker to predict S and R of Candida to caspofungin.

  19. Use of micafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 3,764 clinical isolates of Candida by use of CLSI methods and interpretive criteria.

    PubMed

    Pfaller, Michael A; Messer, Shawn A; Diekema, Daniel J; Jones, Ronald N; Castanheira, Mariana

    2014-01-01

    Due to unacceptably high interlaboratory variation in caspofungin MIC values, we evaluated the use of micafungin as a surrogate marker to predict the susceptibility of Candida spp. to caspofungin using reference methods and species-specific interpretive criteria. The MIC results for 3,764 strains of Candida (eight species), including 73 strains with fks mutations, were used. Caspofungin MIC values and species-specific interpretive criteria were compared with those of micafungin to determine the percent categorical agreement (%CA) and very major error (VME), major error (ME), and minor error rates as well as their ability to detect fks mutant strains of Candida albicans (11 mutants), Candida tropicalis (4 mutants), Candida krusei (3 mutants), and Candida glabrata (55 mutants). Overall, the %CA was 98.8% (0.2% VMEs and MEs, 0.8% minor errors) using micafungin as the surrogate marker. Among the 60 isolates of C. albicans (9 isolates), C. tropicalis (5 isolates), C. krusei (2 isolates), and C. glabrata (44 isolates) that were nonsusceptible (either intermediate or resistant) to both caspofungin and micafungin, 54 (90.0%) contained a mutation in fks1 or fks2. An additional 10 C. glabrata mutants, two C. albicans mutants, and one mutant each of C. tropicalis and C. krusei were classified as susceptible to both antifungal agents. Using the epidemiological cutoff values (ECVs) of 0.12 μg/ml for caspofungin and 0.03 μg/ml for micafungin to differentiate wild-type (WT) from non-WT strains of C. glabrata, 80% of the C. glabrata mutants were non-WT for both agents (96% concordance). Micafungin may serve as an acceptable surrogate marker for the prediction of susceptibility and resistance of Candida to caspofungin.

  20. 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.

  1. 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.

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

    PubMed Central

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

    2015-01-01

    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

  3. The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

    PubMed

    Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

    2015-01-01

    Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

  4. [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.

  5. 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.

  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. 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...

  8. 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)

  9. Stochastic surrogate Hamiltonian

    SciTech Connect

    Katz, Gil; Kosloff, Ronnie; Gelman, David; Ratner, Mark A.

    2008-07-21

    The surrogate Hamiltonian is a general scheme to simulate the many body quantum dynamics composed of a primary system coupled to a bath. The method has been based on a representative bath Hamiltonian composed of two-level systems that is able to mimic the true system-bath dynamics up to a prespecified time. The original surrogate Hamiltonian method is limited to short time dynamics since the size of the Hilbert space required to obtain convergence grows exponentially with time. By randomly swapping bath modes with a secondary thermal reservoir, the method can simulate quantum dynamics of the primary system from short times to thermal equilibrium. By averaging a small number of realizations converged values of the system observables are obtained avoiding the exponential increase in resources. The method is demonstrated for the equilibration of a molecular oscillator with a thermal bath.

  10. Stochastic surrogate Hamiltonian

    NASA Astrophysics Data System (ADS)

    Katz, Gil; Gelman, David; Ratner, Mark A.; Kosloff, Ronnie

    2008-07-01

    The surrogate Hamiltonian is a general scheme to simulate the many body quantum dynamics composed of a primary system coupled to a bath. The method has been based on a representative bath Hamiltonian composed of two-level systems that is able to mimic the true system-bath dynamics up to a prespecified time. The original surrogate Hamiltonian method is limited to short time dynamics since the size of the Hilbert space required to obtain convergence grows exponentially with time. By randomly swapping bath modes with a secondary thermal reservoir, the method can simulate quantum dynamics of the primary system from short times to thermal equilibrium. By averaging a small number of realizations converged values of the system observables are obtained avoiding the exponential increase in resources. The method is demonstrated for the equilibration of a molecular oscillator with a thermal bath.

  11. 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...

  12. 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

  13. The physician-surrogate relationship.

    PubMed

    Torke, Alexia M; Alexander, G Caleb; Lantos, John; Siegler, Mark

    2007-06-11

    The physician-patient relationship is a cornerstone of the medical encounter and has been analyzed extensively. But in many cases, this relationship is altered because patients are unable to make decisions for themselves. In such cases, physicians rely on surrogates, who are often asked to "speak for the patient." This view overlooks the fundamental fact that the surrogate decision maker cannot be just a passive spokesperson for the patient but is also an active agent who develops a complex relationship with the physician. Although there has been much analysis of the ethical guidelines by which surrogates should make decisions, there has been little previous analysis of the special features of the physician-surrogate relationship. Such an analysis seems crucial as the population ages and life-sustaining technologies improve, which is likely to make surrogate decision making even more common. We outline key issues affecting the physician-surrogate relationship and provide guidance for physicians who are making decisions with surrogates.

  14. IFN-γ/TNF-α ratio in response to immuno proteomically identified human T-cell antigens of Mycobacterium tuberculosis - The most suitable surrogate biomarker for latent TB infection.

    PubMed

    Prabhavathi, Maddineni; Pathakumari, Balaji; Raja, Alamelu

    2015-08-01

    The enormous reservoir of latent TB infection (LTBI) poses a major hurdle for global TB control. The existing Tuberculin skin test (TST) and IFN-γ release assays (IGRAs) are found to be suboptimal for LTBI diagnosis. Previously we had taken an immunoproteomic approach and identified 10 protein fractions (contains 16 proteins), which are solely recognized by LTBI. In a cohort of 40 pulmonary TB patients (PTB) and 35 healthy household contacts (HHC), IFN-γ and TNF-α response were measured against 16 antigens by using 1:10 diluted whole blood assay. Among all the antigens, IFN-γ response to Rv2626c has shown positivity of 88.57% in HHC and 7.5% in PTB group. IFN-γ response to combination of Rv2626c + Rv3716c has demonstrated 100% positivity in HHC and 17.5% positivity in PTB respectively. Compared to individual cytokines (i.e. IFN-γ and TNF-α), ratio of IFN-γ/TNF-α has shown promising results for diagnosis of LTBI. IFN-γ/TNF-α ratio against Rv3716c and TrxC has exhibited a positivity of 94.29% in HHC and 5% in PTB group. Accession of Rv2626c and Rv3716c may improve the diagnostic performance of existing QFT-GIT. Independent of QFT-GIT assay, ratio of IFN-γ/TNF-α in response to either Rv3716c or TrxC may acts as suitable surrogate biomarker for LTBI.

  15. Robustness of surrogates of biodiversity in marine benthic communities.

    PubMed

    Magierowski, Regina H; Johnson, Craig R

    2006-12-01

    The usefulness of surrogates to estimate complex variables describing community structure, such as the various components of biodiversity, is long established. Most attention has been given to surrogates of species richness and species diversity and has focused on identifying a subset of taxa as a surrogate of total community richness or diversity. In adopting a surrogate measure, it is assumed that the relationship between the surrogate(s) and total richness or diversity is consistent in both space and time. These assumptions are rarely examined explicitly. We examined the robustness of potential surrogates of familial richness and multivariate community structure for macrofauna communities inhabiting artificial kelp holdfasts by comparing among communities of dissimilar ages and among communities established at different times of the year. This is important because most benthic "landscapes" will be a mosaic of patches reflecting different intensities, frequencies, and timing of disturbances. The total abundance of organisms and familial richness of crustaceans or polychaetes were all good predictors of total familial richness (R2 > 0.68). In contrast, while the familial richness of other groups, such as mollusks and echinoderms, were well correlated with total familial richness for communities at an early stage of development, the strength of these relationships declined with community age. For multivariate community structure, carefully selected subsets of approximately 10% of the total taxa yielded similar patterns to the total suite of taxa, irrespective of the age of the community. Thus, useful surrogates of both familial richness and multivariate community structure can be identified for this type of community. However, the choice of technique for selecting surrogate taxa largely depends on the nature of the pilot data available, and careful selection is required to ensure that surrogates perform consistently across different-aged communities. While the

  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. 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.

  18. 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.

  19. 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.

  20. Strategies to design clinical studies to identify predictive biomarkers in cancer research.

    PubMed

    Perez-Gracia, Jose Luis; Sanmamed, Miguel F; Bosch, Ana; Patiño-Garcia, Ana; Schalper, Kurt A; Segura, Victor; Bellmunt, Joaquim; Tabernero, Josep; Sweeney, Christopher J; Choueiri, Toni K; Martín, Miguel; Fusco, Juan Pablo; Rodriguez-Ruiz, Maria Esperanza; Calvo, Alfonso; Prior, Celia; Paz-Ares, Luis; Pio, Ruben; Gonzalez-Billalabeitia, Enrique; Gonzalez Hernandez, Alvaro; Páez, David; Piulats, Jose María; Gurpide, Alfonso; Andueza, Mapi; de Velasco, Guillermo; Pazo, Roberto; Grande, Enrique; Nicolas, Pilar; Abad-Santos, Francisco; Garcia-Donas, Jesus; Castellano, Daniel; Pajares, María J; Suarez, Cristina; Colomer, Ramon; Montuenga, Luis M; Melero, Ignacio

    2017-02-01

    The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework-the DESIGN guidelines-to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field.

  1. Biomarkers and surrogate endpoints in glaucoma clinical trials.

    PubMed

    Medeiros, Felipe A

    2015-05-01

    Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies.

  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. Identifying the singleplex and multiplex proteins based on transductive learning for protein subcellular localization prediction.

    PubMed

    Cao, Junzhe; Liu, Wenqi; He, Jianjun; Gu, Hong

    2013-07-01

    A new method is proposed to identify whether a query protein is singleplex or multiplex for improving the quality of protein subcellular localization prediction. Based on the transductive learning technique, this approach utilizes the information from the both query proteins and known proteins to estimate the subcellular location number of every query protein so that the singleplex and multiplex proteins can be recognized and distinguished. Each query protein is then dealt with by a targeted single-label or multi-label predictor to achieve a high-accuracy prediction result. We assess the performance of the proposed approach by applying it to three groups of protein sequences datasets. Simulation experiments show that the proposed approach can effectively identify the singleplex and multiplex proteins. Through a comparison, the reliably of this method for enhancing the power of predicting protein subcellular localization can also be verified.

  6. 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

  7. 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

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

    PubMed

    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.

  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

    2016-04-07

    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. 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…

  12. 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

  13. Temporal effects in trend prediction: identifying the most popular nodes in the future.

    PubMed

    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.

  14. Predicting urinary creatinine excretion and its usefulness to identify incomplete 24 h urine collections.

    PubMed

    De Keyzer, Willem; Huybrechts, Inge; Dekkers, Arnold L M; Geelen, Anouk; Crispim, Sandra; Hulshof, Paul J M; Andersen, Lene F; Řehůřková, Irena; Ruprich, Jiří; Volatier, Jean-Luc; Van Maele, Georges; Slimani, Nadia; van't Veer, Pieter; de Boer, Evelien; De Henauw, Stefaan

    2012-09-28

    Studies using 24 h urine collections need to incorporate ways to validate the completeness of the urine samples. Models to predict urinary creatinine excretion (UCE) have been developed for this purpose; however, information on their usefulness to identify incomplete urine collections is limited. We aimed to develop a model for predicting UCE and to assess the performance of a creatinine index using para-aminobenzoic acid (PABA) as a reference. Data were taken from the European Food Consumption Validation study comprising two non-consecutive 24 h urine collections from 600 subjects in five European countries. Data from one collection were used to build a multiple linear regression model to predict UCE, and data from the other collection were used for performance testing of a creatinine index-based strategy to identify incomplete collections. Multiple linear regression (n 458) of UCE showed a significant positive association for body weight (β = 0·07), the interaction term sex × weight (β = 0·09, reference women) and protein intake (β = 0·02). A significant negative association was found for age (β = -0·09) and sex (β = -3·14, reference women). An index of observed-to-predicted creatinine resulted in a sensitivity to identify incomplete collections of 0·06 (95 % CI 0·01, 0·20) and 0·11 (95 % CI 0·03, 0·22) in men and women, respectively. Specificity was 0·97 (95 % CI 0·97, 0·98) in men and 0·98 (95 % CI 0·98, 0·99) in women. The present study shows that UCE can be predicted from weight, age and sex. However, the results revealed that a creatinine index based on these predictions is not sufficiently sensitive to exclude incomplete 24 h urine collections.

  15. 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

  16. Using individualized predictive disease modeling to identify patients with the potential to benefit from a disease management program for diabetes mellitus.

    PubMed

    Weber, Christian; Neeser, Kurt

    2006-08-01

    Diabetes is an increasing health problem, but efforts to handle this pandemic by disease management programs (DMP) have shown conflicting results. Our hypothesis is that, in addition to a program's content and setting, the choice of the right patients is crucial to a program's efficacy and effectiveness. We used individualized predictive disease modeling (IPDM) on a cohort of 918 patients with type 2 diabetes to identify those patients with the greatest potential to benefit from inclusion in a DMP. A portion of the patients (4.7%) did not have even a theoretical potential for an increase in life expectancy and would therefore be unlikely to benefit from a DMP. Approximately 16.1% had an increase in life expectancy of less than half a year. Stratification of the entire cohort by surrogate parameters like preventable 10-year costs or gain in life expectancy was much more effective than stratification by classical clinical parameters such as high HbA1c level. Preventable costs increased up to 50.6% (or 1,010 per patient (1 = US dollars 1.28), p < 0.01) and life expectancy increased up to 54.8% (or 2.3 years, p < 0.01). IPDM is a valuable strategy to identify those patients with the greatest potential to avoid diabetes-related complications and thus can improve the overall effectiveness and efficacy of DMPs for diabetes mellitus.

  17. 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

  18. A Review of Surrogate Assisted Multiobjective Evolutionary Algorithms.

    PubMed

    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.

  19. On the importance of identifying, characterizing, and predicting fundamental phenomena towards microbial electrochemistry applications.

    PubMed

    Torres, César Iván

    2014-06-01

    The development of microbial electrochemistry research toward technological applications has increased significantly in the past years, leading to many process configurations. This short review focuses on the need to identify and characterize the fundamental phenomena that control the performance of microbial electrochemical cells (MXCs). Specifically, it discusses the importance of recent efforts to discover and characterize novel microorganisms for MXC applications, as well as recent developments to understand transport limitations in MXCs. As we increase our understanding of how MXCs operate, it is imperative to continue modeling efforts in order to effectively predict their performance, design efficient MXC technologies, and implement them commercially. Thus, the success of MXC technologies largely depends on the path of identifying, understanding, and predicting fundamental phenomena that determine MXC performance.

  20. 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.

  1. CAsubtype: An R Package to Identify Gene Sets Predictive of Cancer Subtypes and Clinical Outcomes.

    PubMed

    Kong, Hualei; Tong, Pan; Zhao, Xiaodong; Sun, Jielin; Li, Hua

    2017-01-21

    In the past decade, molecular classification of cancer has gained high popularity owing to its high predictive power on clinical outcomes as compared with traditional methods commonly used in clinical practice. In particular, using gene expression profiles, recent studies have successfully identified a number of gene sets for the delineation of cancer subtypes that are associated with distinct prognosis. However, identification of such gene sets remains a laborious task due to the lack of tools with flexibility, integration and ease of use. To reduce the burden, we have developed an R package, CAsubtype, to efficiently identify gene sets predictive of cancer subtypes and clinical outcomes. By integrating more than 13,000 annotated gene sets, CAsubtype provides a comprehensive repertoire of candidates for new cancer subtype identification. For easy data access, CAsubtype further includes the gene expression and clinical data of more than 2000 cancer patients from TCGA. CAsubtype first employs principal component analysis to identify gene sets (from user-provided or package-integrated ones) with robust principal components representing significantly large variation between cancer samples. Based on these principal components, CAsubtype visualizes the sample distribution in low-dimensional space for better understanding of the distinction between samples and classifies samples into subgroups with prevalent clustering algorithms. Finally, CAsubtype performs survival analysis to compare the clinical outcomes between the identified subgroups, assessing their clinical value as potentially novel cancer subtypes. In conclusion, CAsubtype is a flexible and well-integrated tool in the R environment to identify gene sets for cancer subtype identification and clinical outcome prediction. Its simple R commands and comprehensive data sets enable efficient examination of the clinical value of any given gene set, thus facilitating hypothesis generating and testing in biological and

  2. 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.

  3. 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…

  4. 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

  5. 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.

  6. 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

  7. Ago2 Immunoprecipitation Identifies Predicted MicroRNAs in Human Embryonic Stem Cells and Neural Precursors

    PubMed Central

    Swerdel, Mavis R.; Moore, Jennifer C.; Cohen, Rick I.; Wu, Hao; Sun, Yi E.; Hart, Ronald P.

    2009-01-01

    Background MicroRNAs are required for maintenance of pluripotency as well as differentiation, but since more microRNAs have been computationally predicted in genome than have been found, there are likely to be undiscovered microRNAs expressed early in stem cell differentiation. Methodology/Principal Findings SOLiD ultra-deep sequencing identified >107 unique small RNAs from human embryonic stem cells (hESC) and neural-restricted precursors that were fit to a model of microRNA biogenesis to computationally predict 818 new microRNA genes. These predicted genomic loci are associated with chromatin patterns of modified histones that are predictive of regulated gene expression. 146 of the predicted microRNAs were enriched in Ago2-containing complexes along with 609 known microRNAs, demonstrating association with a functional RISC complex. This Ago2 IP-selected subset was consistently expressed in four independent hESC lines and exhibited complex patterns of regulation over development similar to previously-known microRNAs, including pluripotency-specific expression in both hESC and iPS cells. More than 30% of the Ago2 IP-enriched predicted microRNAs are new members of existing families since they share seed sequences with known microRNAs. Conclusions/Significance Extending the classic definition of microRNAs, this large number of new microRNA genes, the majority of which are less conserved than their canonical counterparts, likely represent evolutionarily recent regulators of early differentiation. The enrichment in Ago2 containing complexes, the presence of chromatin marks indicative of regulated gene expression, and differential expression over development all support the identification of 146 new microRNAs active during early hESC differentiation. PMID:19784364

  8. Surrogate data a secure way to share corporate data

    NASA Astrophysics Data System (ADS)

    Tetko, Igor V.; Abagyan, Ruben; Oprea, Tudor I.

    2005-09-01

    The privacy of chemical structure is of paramount importance for the industrial sector, in particular for the pharmaceutical industry. At the same time, companies handle large amounts of physico-chemical and biological data that could be shared in order to improve our molecular understanding of pharmacokinetic and toxicological properties, which could lead to improved predictivity and shorten the development time for drugs, in particular in the early phases of drug discovery. The current study provides some theoretical limits on the information required to produce reverse engineering of molecules from generated descriptors and demonstrates that the information content of molecules can be as low as less than one bit per atom. Thus theoretically just one descriptor can be used to completely disclose the molecular structure. Instead of sharing descriptors, we propose to share surrogate data. The sharing of surrogate data is nothing else but sharing of reliably predicted molecules. The use of surrogate data can provide the same information as the original set. We consider the practical application of this idea to predict lipophilicity of chemical compounds and we demonstrate that surrogate and real (original) data provides similar prediction ability. Thus, our proposed strategy makes it possible not only to share descriptors, but also complete collections of surrogate molecules without the danger of disclosing the underlying molecular structures.

  9. MISO - Mixed Integer Surrogate Optimization

    SciTech Connect

    Mueller, Juliane

    2016-01-20

    MISO is an optimization framework for solving computationally expensive mixed-integer, black-box, global optimization problems. MISO uses surrogate models to approximate the computationally expensive objective function. Hence, derivative information, which is generally unavailable for black-box simulation objective functions, is not needed. MISO allows the user to choose the initial experimental design strategy, the type of surrogate model, and the sampling strategy.

  10. Surrogate end points save lives

    PubMed Central

    Vinden, Christopher

    2017-01-01

    Summary Patient-centric markers are important, and when they can be conveniently measured they should dominate research questions. However, when the research question pertains to serious or potentially fatal illnesses and it will take years or even decades to answer with patient-centric outcomes, then a pragmatic approach based on common sense and surrogate markers should be adopted. This commentary discusses the important role that surrogate markers can play in medical research. PMID:28338466

  11. Dynamical model of surrogate reactions

    SciTech Connect

    Aritomo, Y.; Chiba, S.; Nishio, K.

    2011-08-15

    A new dynamical model is developed to describe the whole process of surrogate reactions: Transfer of several nucleons at an initial stage, thermal equilibration of residues leading to washing out of shell effects, and decay of populated compound nuclei are treated in a unified framework. Multidimensional Langevin equations are employed to describe time evolution of collective coordinates with a time-dependent potential energy surface corresponding to different stages of surrogate reactions. The new model is capable of calculating spin distributions of the compound nuclei, one of the most important quantities in the surrogate technique. Furthermore, various observables of surrogate reactions can be calculated, for example, energy and angular distribution of ejectile and mass distributions of fission fragments. These features are important to assess validity of the proposed model itself, to understand mechanisms of the surrogate reactions, and to determine unknown parameters of the model. It is found that spin distributions of compound nuclei produced in {sup 18}O+{sup 238}U{yields}{sup 16}O+{sup 240}*U and {sup 18}O+{sup 236}U{yields}{sup 16}O+{sup 238}*U reactions are equivalent and much less than 10({h_bar}/2{pi}) and therefore satisfy conditions proposed by Chiba and Iwamoto [Phys. Rev. C 81, 044604 (2010)] if they are used as a pair in the surrogate ratio method.

  12. Surrogate model based iterative ensemble smoother for subsurface flow data assimilation

    NASA Astrophysics Data System (ADS)

    Chang, Haibin; Liao, Qinzhuo; Zhang, Dongxiao

    2017-02-01

    Subsurface geological formation properties often involve some degree of uncertainty. Thus, for most conditions, uncertainty quantification and data assimilation are necessary for predicting subsurface flow. The surrogate model based method is one common type of uncertainty quantification method, in which a surrogate model is constructed for approximating the relationship between model output and model input. Based on the prediction ability, the constructed surrogate model can be utilized for performing data assimilation. In this work, we develop an algorithm for implementing an iterative ensemble smoother (ES) using the surrogate model. We first derive an iterative ES scheme using a regular routine. In order to utilize surrogate models, we then borrow the idea of Chen and Oliver (2013) to modify the Hessian, and further develop an independent parameter based iterative ES formula. Finally, we establish the algorithm for the implementation of iterative ES using surrogate models. Two surrogate models, the PCE surrogate and the interpolation surrogate, are introduced for illustration. The performances of the proposed algorithm are tested by synthetic cases. The results show that satisfactory data assimilation results can be obtained by using surrogate models that have sufficient accuracy.

  13. 34 CFR 303.422 - Surrogate parents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false Surrogate parents. 303.422 Section 303.422 Education... DISABILITIES Procedural Safeguards Surrogate Parents § 303.422 Surrogate parents. (a) General. Each lead agency... under paragraph (a) of this section, includes the assignment of an individual to act as a surrogate...

  14. 34 CFR 303.422 - Surrogate parents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true Surrogate parents. 303.422 Section 303.422 Education... DISABILITIES Procedural Safeguards Surrogate Parents § 303.422 Surrogate parents. (a) General. Each lead agency... under paragraph (a) of this section, includes the assignment of an individual to act as a surrogate...

  15. 34 CFR 303.422 - Surrogate parents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false Surrogate parents. 303.422 Section 303.422 Education... DISABILITIES Procedural Safeguards Surrogate Parents § 303.422 Surrogate parents. (a) General. Each lead agency... under paragraph (a) of this section, includes the assignment of an individual to act as a surrogate...

  16. 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. PMID:27540511

  17. Financial Surrogate Decision Making: Lessons from Applied Experimental Philosophy.

    PubMed

    Feltz, Adam

    2016-09-20

    An estimated 1 in 4 elderly Americans need a surrogate to make decisions at least once in their lives. With an aging population, that number is almost certainly going to increase. This paper focuses on financial surrogate decision making. To illustrate some of the empirical and moral implications associated with financial surrogate decision making, two experiments suggest that default choice settings can predictably influence some surrogate financial decision making. Experiment 1 suggested that when making hypothetical financial decisions, surrogates tended to stay with default settings (OR = 4.37, 95% CI 1.52, 12.48). Experiment 2 replicated and extended this finding suggesting that in a different context (OR = 2.27, 95% CI 1.1, 4.65). Experiment 2 also suggested that those who were more numerate were less likely to be influenced by default settings than the less numerate, but only when the decision is whether to "opt in" (p = .05). These data highlight the importance of a recent debate about "nudging." Defaults are common methods to nudge people to make desirable choices while allowing the liberty to choose otherwise. Some of the ethics of using default settings to nudge surrogate decision makers are discussed.

  18. 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.

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

    PubMed

    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.

  20. 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

  1. Surrogate-assisted network analysis of nonlinear time series

    NASA Astrophysics Data System (ADS)

    Laut, Ingo; Räth, Christoph

    2016-10-01

    The performance of recurrence networks and symbolic networks to detect weak nonlinearities in time series is compared to the nonlinear prediction error. For the synthetic data of the Lorenz system, the network measures show a comparable performance. In the case of relatively short and noisy real-world data from active galactic nuclei, the nonlinear prediction error yields more robust results than the network measures. The tests are based on surrogate data sets. The correlations in the Fourier phases of data sets from some surrogate generating algorithms are also examined. The phase correlations are shown to have an impact on the performance of the tests for nonlinearity.

  2. 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.

  3. Scope and Outcomes of Surrogate Decision Making Among Hospitalized Older Adults

    PubMed Central

    Torke, Alexia M.; Sachs, Greg A.; Helft, Paul R.; Montz, Kianna; Hui, Siu L.; Slaven, James E.; Callahan, Christopher M.

    2014-01-01

    Importance Hospitalized older adults often lack decisional capacity, but outside of the intensive care unit (ICU) and end-of-life care settings, little is known about the frequency of decision making by family members or other surrogates or its implications for hospital care. Objective To describe the scope of surrogate decision making, the hospital course and outcomes for older adults. Design Prospective, observational study. Setting Medical and Medical ICU services of two hospitals in one Midwest city. Participants 1083 hospitalized older adults identified by their physicians as requiring major medical decisions. Measures Clinical characteristics, hospital outcomes, nature of major medical decisions and surrogate involvement. Results Based on physician reports at 48 hours of hospitalization, 47.4% (44.4%–50.4%) of older adults required at least some surrogate involvement including 23.0% (20.6% – 25.6%) with all decisions made by a surrogate. Among patients who required a surrogate for at least one decision within 48 hours, 57.2% required decisions about life sustaining care (mostly addressing code status), 48.6% about procedures and surgeries and 46.9% about discharge planning. Patients who required a surrogate experienced a more complex hospital course with greater use of ventilators (2.5% patients who made decisions, 13.2% patients who required any surrogate decisions, p<0.0001), artificial nutrition (1.7% patient, 14.4% surrogate, p<0.0001) and greater length of stay (median 6 days patient, 7 days surrogate, p<0.0001). They were more likely to be discharged to an extended care facility (21.2% patient, 40.9% surrogate, p<0.0001), and had higher hospital mortality (0.0% patient; 5.9% surrogate, p<0.0001). Most surrogates were daughters (58.9%), sons (25.0%) or spouses (20.6%). Overall, only 7.4% had a living will and 25.0% a health care representative document in the medical record. Conclusion Surrogate decision making occurs for nearly half of hospitalized

  4. 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

  5. High-risk carotid plaques identified by CT-angiogram can predict acute myocardial infarction.

    PubMed

    Mosleh, Wassim; Adib, Keenan; Natdanai, Punnanithinont; Carmona-Rubio, Andres; Karki, Roshan; Paily, Jacienta; Ahmed, Mohamed Abdel-Aal; Vakkalanka, Sujit; Madam, Narasa; Gudleski, Gregory D; Chung, Charles; Sharma, Umesh C

    2017-04-01

    Prior studies identified the incremental value of non-invasive imaging by CT-angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to their superficial locations, larger calibers and motion-free imaging, the carotid arteries provide the best anatomic access for the non-invasive characterization of atherosclerotic plaques. We aim to assess the ability of predicting obstructive coronary artery disease (CAD) or acute myocardial infarction (MI) based on high-risk carotid plaque features identified by CTA. We retrospectively examined carotid CTAs of 492 patients that presented with acute stroke to characterize the atherosclerotic plaques of the carotid arteries and examined development of acute MI and obstructive CAD within 12-months. Carotid lesions were defined in terms of calcifications (large or speckled), presence of low-attenuation plaques, positive remodeling, and presence of napkin ring sign. Adjusted relative risks were calculated for each plaque features. Patients with speckled (<3 mm) calcifications and/or larger calcifications on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year compared to patients without (adjusted RR of 7.51, 95%CI 1.26-73.42, P = 0.001). Patients with low-attenuation plaques on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year than patients without (adjusted RR of 2.73, 95%CI 1.19-8.50, P = 0.021). Presence of carotid calcifications and low-attenuation plaques also portended higher sensitivity (100 and 79.17%, respectively) for the development of acute MI. Presence of carotid calcifications and low-attenuation plaques can predict the risk of developing acute MI and/or obstructive CAD within 12-months. Given their high sensitivity, their absence can reliably exclude 12-month events.

  6. 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.

  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.

  8. 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.

  9. Acutely-bereaved Surrogates' Stories about the Decision to Limit Life Support in the ICU

    PubMed Central

    Nunez, Eduardo R.; Schenker, Yael; Joel, Ian D.; Reynolds, Charles F.; Dew, Mary Amanda; Arnold, Robert M.; Barnato, Amber E.

    2015-01-01

    Objective Participating in a decision to limit life support for a loved one in the intensive care unit (ICU) is associated with adverse mental health consequences for surrogate decision makers. We sought to describe acutely-bereaved surrogates' experiences surrounding this decision. Design and setting Secondary analysis of interviews with surrogates approximately 4 weeks after a patient's death in one of 6 ICUs at 4 hospitals in Pittsburgh, Pennsylvania. Subjects Adults who participated in decisions about life support in the ICU. Interventions n/a Measurements We collected participant demographics, prior advance care planning, and decision control preferences. We used qualitative content analysis of transcribed interviews to identify themes in surrogates' experiences. Main results The 23 participants included the spouse (n=7), child/step-child (7), sibling (5), parent (3), or other relation (1) of the deceased patient. Their mean age was 55, 61% were women, all were white, 74% had prior treatment preferences discussions with the patient and 43% of patients had written advance directives. 15/23 (65%) surrogates preferred an active decision-making role, 8/23 (35%) preferred to share responsibility with the physician and no surrogates preferred a passive role. Surrogates report that key stressors in the ICU are the uncertainty and witnessed or empathic suffering. These factors contributed to surrogates' sense of helplessness in the ICU. Involvement in the decision to limit life support allowed surrogates to regain a sense of agency by making a decision consistent with the patient's wishes and values, counteracting surrogates' helplessness and ending the uncertainty and suffering. Conclusions In this all-white sample of surrogates with non-passive decision control preferences from a single US region, participating in decision making allowed surrogates to regain control, counteract feelings of helplessness, and end their empathic suffering. While prior research

  10. 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.

  11. Surrogate Nuclear Reactions using STARS

    SciTech Connect

    Bernstein, L A; Burke, J T; Church, J A; Ahle, L; Cooper, J R; Hoffman, R D; Moody, K; Punyon, J; Schiller, A; Algin, E; Plettner, C; Ai, H; Beausang, C W; Casten, R F; Hughes, R; Ricard-McCutchan, E; Meyer, D; Ressler, J J; Caggiano, J A; Zamfir, N V; Amro, H; Heinz, A; Fallon, P; McMahan, M A; Macchiavelli, A O; Phair, L W

    2004-10-26

    The results from two surrogate reaction experiments using the STARS (Silicon Telescope Array for Reaction Studies) spectrometer are presented. The surrogate method involves measuring the particle and/or {gamma}-ray decay probabilities of excited nuclei populated via a direct reaction. These probabilities can then be used to deduce neutron-induced reaction cross sections that lead to the same compound nuclei. In the first experiment STARS coupled to the GAMMASPHERE {gamma}-ray spectrometer successfully reproduce surrogate (n,{gamma}), (n,n'{gamma}) and (n,2n{gamma}) cross sections on {sup 155,156}Gd using Gd {sup 3}He-induced reactions. In the second series of experiments an energetic deuteron beam from the ESTU tandem at the Wright Nuclear Structure Lab at Yale University was used to obtain the ratio of fission probabilities for {sup 238}U/ {sup 236}U and {sup 237}U/ {sup 239}U populated using the {sup 236,238}U(d,d'f) and {sup 236,238}U(d,pf) reactions. Results from these experiments are presented and the implications for the surrogate reaction technique are discussed.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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... DISABILITIES Procedural Safeguards General § 303.406 Surrogate parents. (a) General. Each lead agency shall... paragraph (a) of this section, includes the assignment of an individual to act as a surrogate for the...

  18. 34 CFR 300.519 - Surrogate parents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true Surrogate parents. 300.519 Section 300.519 Education... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents... paragraph (a) of this section include the assignment of an individual to act as a surrogate for the...

  19. 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... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents... paragraph (a) of this section include the assignment of an individual to act as a surrogate for the...

  20. 34 CFR 300.519 - Surrogate parents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false Surrogate parents. 300.519 Section 300.519 Education... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents... paragraph (a) of this section include the assignment of an individual to act as a surrogate for the...

  1. 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... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents... paragraph (a) of this section include the assignment of an individual to act as a surrogate for the...

  2. 34 CFR 300.519 - Surrogate parents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false Surrogate parents. 300.519 Section 300.519 Education... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents... paragraph (a) of this section include the assignment of an individual to act as a surrogate for the...

  3. 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... DISABILITIES Procedural Safeguards General § 303.406 Surrogate parents. (a) General. Each lead agency shall... paragraph (a) of this section, includes the assignment of an individual to act as a surrogate for the...

  4. 77 FR 34788 - Surrogate Foreign Corporations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ... Internal Revenue Service 26 CFR Part 1 RIN 1545-BF47 Surrogate Foreign Corporations AGENCY: Internal... regulations regarding whether a foreign corporation is treated as a surrogate foreign corporation. The final... corporation as a surrogate foreign corporation (2006 temporary regulations). A notice of proposed...

  5. 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.

  6. Surrogate Modeling of Deformable Joint Contact using Artificial Neural Networks

    PubMed Central

    Eskinazi, Ilan; Fregly, Benjamin J.

    2016-01-01

    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. 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.

  8. 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

  9. 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

  10. Biodegradation of naphthenic acid surrogates by axenic cultures.

    PubMed

    Yue, Siqing; Ramsay, Bruce A; Ramsay, Juliana A

    2015-07-01

    This is the first study to report that bacteria from the genera Ochrobactrum, Brevundimonas and Bacillus can be isolated by growth on naphthenic acids (NAs) extracted from oil sands process water (OSPW). These pure cultures were screened for their ability to use a range of aliphatic, cyclic and aromatic NA surrogates in 96-well microtiter plates using water-soluble tetrazolium redox dyes (Biolog Redox Dye H) as the indicator of metabolic activity. Of the three cultures, Ochrobactrum showed most metabolic activity on the widest range of NA surrogates. Brevundomonas and especially Ochrobactrum had higher metabolic activity on polycyclic aromatic compounds than other classes of NA surrogates. Bacillus also oxidized a wide range of NA surrogates but not as well as Ochrobactrum. Using this method to characterize NA utilisation, one can identify which NAs or NA classes in OSPW are more readily degraded. Since aromatic NAs have been shown to have an estrogenic effect and polycyclic monoaromatic compounds have been suggested to pose the greatest environmental threat among the NAs, these bacterial genera may play an important role in detoxification of OSPW. Furthermore, this study demonstrates that bacteria belonging to the genera Ochrobactrum and Bacillus can also degrade surrogates of tricyclic NAs.

  11. 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

  12. Evaluation of different approaches for identifying optimal sites to predict mean hillslope soil moisture content

    NASA Astrophysics Data System (ADS)

    Liao, Kaihua; Zhou, Zhiwen; Lai, Xiaoming; Zhu, Qing; Feng, Huihui

    2017-04-01

    The identification of representative soil moisture sampling sites is important for the validation of remotely sensed mean soil moisture in a certain area and ground-based soil moisture measurements in catchment or hillslope hydrological studies. Numerous approaches have been developed to identify optimal sites for predicting mean soil moisture. Each method has certain advantages and disadvantages, but they have rarely been evaluated and compared. In our study, surface (0-20 cm) soil moisture data from January 2013 to March 2016 (a total of 43 sampling days) were collected at 77 sampling sites on a mixed land-use (tea and bamboo) hillslope in the hilly area of Taihu Lake Basin, China. A total of 10 methods (temporal stability (TS) analyses based on 2 indices, K-means clustering based on 6 kinds of inputs and 2 random sampling strategies) were evaluated for determining optimal sampling sites for mean soil moisture estimation. They were TS analyses based on the smallest index of temporal stability (ITS, a combination of the mean relative difference and standard deviation of relative difference (SDRD)) and based on the smallest SDRD, K-means clustering based on soil properties and terrain indices (EFs), repeated soil moisture measurements (Theta), EFs plus one-time soil moisture data (EFsTheta), and the principal components derived from EFs (EFs-PCA), Theta (Theta-PCA), and EFsTheta (EFsTheta-PCA), and global and stratified random sampling strategies. Results showed that the TS based on the smallest ITS was better (RMSE = 0.023 m3 m-3) than that based on the smallest SDRD (RMSE = 0.034 m3 m-3). The K-means clustering based on EFsTheta (-PCA) was better (RMSE <0.020 m3 m-3) than these based on EFs (-PCA) and Theta (-PCA). The sampling design stratified by the land use was more efficient than the global random method. Forty and 60 sampling sites are needed for stratified sampling and global sampling respectively to make their performances comparable to the best K

  13. Evaluation of a surrogate marker: validity and efficiency.

    PubMed

    Qu, Yongming

    2013-05-30

    Statistical validation of a surrogate endpoint or surrogate marker has been studied for three decades. However, there is still no consensus on how to evaluate surrogate endpoints or surrogate markers. There is much confusion on which method should be used for the evaluation of a surrogate endpoint or surrogate marker. In this article, we clarify the statistical definitions of the surrogate endpoint and surrogate marker and introduce the concept of the validity and efficiency of a surrogate marker. We suggest the proportion of information gain can be used to evaluate the validity of a surrogate marker.

  14. Review of surrogate modeling in water resources

    NASA Astrophysics Data System (ADS)

    Razavi, Saman; Tolson, Bryan A.; Burn, Donald H.

    2012-07-01

    Surrogate modeling, also called metamodeling, has evolved and been extensively used over the past decades. A wide variety of methods and tools have been introduced for surrogate modeling aiming to develop and utilize computationally more efficient surrogates of high-fidelity models mostly in optimization frameworks. This paper reviews, analyzes, and categorizes research efforts on surrogate modeling and applications with an emphasis on the research accomplished in the water resources field. The review analyzes 48 references on surrogate modeling arising from water resources and also screens out more than 100 references from the broader research community. Two broad families of surrogates namely response surface surrogates, which are statistical or empirical data-driven models emulating the high-fidelity model responses, and lower-fidelity physically based surrogates, which are simplified models of the original system, are detailed in this paper. Taxonomies on surrogate modeling frameworks, practical details, advances, challenges, and limitations are outlined. Important observations and some guidance for surrogate modeling decisions are provided along with a list of important future research directions that would benefit the common sampling and search (optimization) analyses found in water resources.

  15. 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

  16. 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

  17. 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.

  18. Can Falls Risk Prediction Tools Correctly Identify Fall-Prone Elderly Rehabilitation Inpatients? A Systematic Review and Meta-Analysis

    PubMed Central

    da Costa, Bruno Roza; Rutjes, Anne Wilhelmina Saskia; Mendy, Angelico; Freund-Heritage, Rosalie; Vieira, Edgar Ramos

    2012-01-01

    Background Falls of elderly people may cause permanent disability or death. Particularly susceptible are elderly patients in rehabilitation hospitals. We systematically reviewed the literature to identify falls prediction tools available for assessing elderly inpatients in rehabilitation hospitals. Methods and Findings We searched six electronic databases using comprehensive search strategies developed for each database. Estimates of sensitivity and specificity were plotted in ROC space graphs and pooled across studies. Our search identified three studies which assessed the prediction properties of falls prediction tools in a total of 754 elderly inpatients in rehabilitation hospitals. Only the STRATIFY tool was assessed in all three studies; the other identified tools (PJC-FRAT and DOWNTON) were assessed by a single study. For a STRATIFY cut-score of two, pooled sensitivity was 73% (95%CI 63 to 81%) and pooled specificity was 42% (95%CI 34 to 51%). An indirect comparison of the tools across studies indicated that the DOWNTON tool has the highest sensitivity (92%), while the PJC-FRAT offers the best balance between sensitivity and specificity (73% and 75%, respectively). All studies presented major methodological limitations. Conclusions We did not identify any tool which had an optimal balance between sensitivity and specificity, or which were clearly better than a simple clinical judgment of risk of falling. The limited number of identified studies with major methodological limitations impairs sound conclusions on the usefulness of falls risk prediction tools in geriatric rehabilitation hospitals. PMID:22815914

  19. Predicting conduct problems: can high-risk children be identified in kindergarten and grade 1?

    PubMed

    Bennett, K J; Lipman, E L; Brown, S; Racine, Y; Boyle, M H; Offord, D R

    1999-08-01

    Externalizing behavior symptoms (EBS) in childhood are a strong predictor of future conduct problems. This study evaluated their predictive accuracy using logistic regression and receiver operating characteristic curve techniques. EBS, alone and in combination with other child and familial risk factors, were used to predict conduct problems 30 months later in a nonclinic population of kindergartners and Grade 1 children. The sensitivity (Sn) and positive predictive value (PPV) of EBS alone were below preset criteria of > or = 50% for each (prevalence < or = 15%). Sn and PPV increased when other child and familial factors were combined with symptoms but did not exceed the preset criteria. From a developmental perspective, substantial stability of EBS exists over time. However, from the perspective of prevention science, significant levels of misclassification will occur when EBS are used to designate high-risk status under the low-prevalence conditions of normal populations.

  20. Using Standardized Tests to Identify Prior Knowledge Necessary for Success in Algebra: A Predictive Analysis

    ERIC Educational Resources Information Center

    Jensen, Jennifer

    2014-01-01

    This study sought to determine if there is a relationship between students' scores on the eighth-grade Indiana State Test of Education Progress Plus (ISTEP+) exam and success on Indiana's Algebra End-of-Course Assessment (ECA). Additionally, it sought to determine if algebra success could be significantly predicted by the achievement in one or…

  1. Tractable Experiment Design via Mathematical Surrogates

    SciTech Connect

    Williams, Brian J.

    2016-02-29

    This presentation summarizes the development and implementation of quantitative design criteria motivated by targeted inference objectives for identifying new, potentially expensive computational or physical experiments. The first application is concerned with estimating features of quantities of interest arising from complex computational models, such as quantiles or failure probabilities. A sequential strategy is proposed for iterative refinement of the importance distributions used to efficiently sample the uncertain inputs to the computational model. In the second application, effective use of mathematical surrogates is investigated to help alleviate the analytical and numerical intractability often associated with Bayesian experiment design. This approach allows for the incorporation of prior information into the design process without the need for gross simplification of the design criterion. Illustrative examples of both design problems will be presented as an argument for the relevance of these research problems.

  2. 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.

  3. Use of Surrogate Outcomes in Nephrology Research.

    PubMed

    Samuels, Joshua

    2016-11-01

    Clinical trials are large and expensive and could require exceedingly long-term follow-up for subjects to reach clinically meaningful end points. To combat these methodologic issues, researchers sometimes use biomarkers as surrogate end points. A biomarker is an objectively measured characteristic that is indicative of some underlying phenomenon or process, while a surrogate is a biomarker that "takes the place" of a clinically meaningful outcome, usually earlier in the disease process. This paper reviews the history, strengths, and weaknesses of surrogate outcome use in clinical research and then discusses potential surrogate outcomes in nephrology research.

  4. Health information-seeking on behalf of others: characteristics of "surrogate seekers".

    PubMed

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

    2015-03-01

    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.

  5. 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…

  6. 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'…

  7. Identifying the Factors That Predict Degree Completion for Entirely Online Community College Students

    ERIC Educational Resources Information Center

    Brock, Kishia R.

    2014-01-01

    The purpose of this research study was to identify demographic characteristics, academic factors, and student behaviors that contributed to successful degree and certificate completion for entirely online, nontraditional undergraduate students at a large community college. A discrete-time event history analysis was used to model the retention of…

  8. 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"…

  9. Identifying predictive clinical characteristics of the treatment efficacy of mirtazapine monotherapy for major depressive disorder

    PubMed Central

    Tsutsumi, Takahiro; Sugawara, Hiroko; Ito, Ryoko; Asano, Mizuho; Shimizu, Satoru; Ishigooka, Jun; Nishimura, Katsuji

    2016-01-01

    Background Mirtazapine, which is classified as a noradrenergic and specific serotonergic antidepressant, is widely prescribed for the treatment of major depressive disorder. The potential predictive factors of the efficacy of mirtazapine and the tolerability based on the incidence of oversedation and jitteriness/anxiety syndrome were evaluated. Patients and methods Patients with major depressive disorder were retrospectively investigated. Study subjects comprised 68 patients with depression who received mirtazapine as an initial antidepressant at the Department of Psychiatry of the Tokyo Women’s Medical University Hospital from September 2009 to March 2013. The efficacy of mirtazapine monotherapy was evaluated based on the Clinical Global Impression Improvement score. Clinical characteristics were compared between remission and nonremission groups to determine the factors predicting the efficacy. Moreover, discontinuation rates due to adverse effects, including oversedation and jitteriness/anxiety syndrome, were examined, and the effects of confounding factors were evaluated. Results The remission rate of mirtazapine monotherapy was 36.8% among the 68 enrolled subjects. The mean final doses in the remission and nonremission groups were 27.6±13.5 mg and 26.0±14.1 mg, respectively, and there was no significant difference between them. Multiple logistic analyses revealed that the absence of guilt (odds ratio [OR] =0.15; 95% CI [1.66–37.24], P=0.006) and the presence of psychomotor retardation (OR =4.30; 95% CI [1.30–16.60], P=0.016) were significantly related to the efficacy of mirtazapine monotherapy. The discontinuation rates due to oversedation and jitteriness/anxiety syndrome were 13.2% and 11.8%, respectively. Age did not differ significantly between patients with or without oversedation or jitteriness/anxiety syndrome (P=0.078 and P=0.579, respectively). Conclusion The absence of guilt and the presence of psychomotor retardation may predict the efficacy

  10. 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

  11. 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.

  12. 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.

  13. 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)

  14. Computational methods using genome-wide association studies to predict radiotherapy complications and to identify correlative molecular processes

    PubMed Central

    Oh, Jung Hun; Kerns, Sarah; Ostrer, Harry; Powell, Simon N.; Rosenstein, Barry; Deasy, Joseph O.

    2017-01-01

    The biological cause of clinically observed variability of normal tissue damage following radiotherapy is poorly understood. We hypothesized that machine/statistical learning methods using single nucleotide polymorphism (SNP)-based genome-wide association studies (GWAS) would identify groups of patients of differing complication risk, and furthermore could be used to identify key biological sources of variability. We developed a novel learning algorithm, called pre-conditioned random forest regression (PRFR), to construct polygenic risk models using hundreds of SNPs, thereby capturing genomic features that confer small differential risk. Predictive models were trained and validated on a cohort of 368 prostate cancer patients for two post-radiotherapy clinical endpoints: late rectal bleeding and erectile dysfunction. The proposed method results in better predictive performance compared with existing computational methods. Gene ontology enrichment analysis and protein-protein interaction network analysis are used to identify key biological processes and proteins that were plausible based on other published studies. In conclusion, we confirm that novel machine learning methods can produce large predictive models (hundreds of SNPs), yielding clinically useful risk stratification models, as well as identifying important underlying biological processes in the radiation damage and tissue repair process. The methods are generally applicable to GWAS data and are not specific to radiotherapy endpoints. PMID:28233873

  15. Computational methods using genome-wide association studies to predict radiotherapy complications and to identify correlative molecular processes

    NASA Astrophysics Data System (ADS)

    Oh, Jung Hun; Kerns, Sarah; Ostrer, Harry; Powell, Simon N.; Rosenstein, Barry; Deasy, Joseph O.

    2017-02-01

    The biological cause of clinically observed variability of normal tissue damage following radiotherapy is poorly understood. We hypothesized that machine/statistical learning methods using single nucleotide polymorphism (SNP)-based genome-wide association studies (GWAS) would identify groups of patients of differing complication risk, and furthermore could be used to identify key biological sources of variability. We developed a novel learning algorithm, called pre-conditioned random forest regression (PRFR), to construct polygenic risk models using hundreds of SNPs, thereby capturing genomic features that confer small differential risk. Predictive models were trained and validated on a cohort of 368 prostate cancer patients for two post-radiotherapy clinical endpoints: late rectal bleeding and erectile dysfunction. The proposed method results in better predictive performance compared with existing computational methods. Gene ontology enrichment analysis and protein-protein interaction network analysis are used to identify key biological processes and proteins that were plausible based on other published studies. In conclusion, we confirm that novel machine learning methods can produce large predictive models (hundreds of SNPs), yielding clinically useful risk stratification models, as well as identifying important underlying biological processes in the radiation damage and tissue repair process. The methods are generally applicable to GWAS data and are not specific to radiotherapy endpoints.

  16. Research priorities in biomarkers and surrogate end-points.

    PubMed

    Aronson, Jeffrey K

    2012-06-01

    Ideal tests of the effects of therapeutic interventions measure the desired outcomes; however, the desired outcomes are not always easily measured or may be long-term objectives. Biomarkers and surrogate end-points are often cheaper and easier to measure and can be measured over a shorter time span. They can be used in screening, diagnosing, staging, and monitoring diseases, in monitoring responses to interventions, and in various aspects of drug discovery and development. They can be extrinsic to the body or intrinsic, and can relate to any point in the pharmacological chain, at the molecular, cellular, tissue, or organ level. Problems arise when the relation between the pathophysiology of the disease and the mechanism of action of the intervention is not properly understood; when adverse effects obviate therapeutic effects; when confounding factors, such as other drugs, alter the surrogate independently of the final end-point; when a biomarker persists after resolution of the disease; and when the concentration-effect curves for the effects of an intervention on the primary outcome and the surrogate are different. Use of biomarkers may also be hindered by poor reproducibility of measurement techniques. Challenges for clinical pharmacologists are to devise biomarker tests that are reliable, reproducible, sensitive, and specific, and surrogate end-points that are associated with the clinical outcomes of concern and useful. A robust taxonomy is needed of the relations that link the pathophysiology of disease, the mechanisms of action of interventions and their adverse effects, the desired clinical outcomes, and the surrogate end-points that predict them.

  17. 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…

  18. Conservative Surrogate Model Using Weighted Kriging Variance for Sampling-Based RBDO

    DTIC Science & Technology

    2011-06-01

    Prediction Intervals,” Scandinavian J Stat, Vol. 30, pp. 175-192, 2003. [7] F.A.C. Viana , V . Picheny, and R.T. Haftka, "Using cross validation to...problems. Viana et al. [7] used cross-validation to estimate the safety margin for the conservative surrogate model. While the cross-validation...Design Optimization,” accepted by AIAA Journal, 2011. [4] V . Picheny., “Improving Accuracy and Compensating for Uncertainty in Surrogate Modeling

  19. 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.

  20. The interactive surrogate travel system.

    PubMed

    Nakajima, I; Ichimura, A; Juzoji, H; Mugita, K

    1999-01-01

    The Interactive Surrogate Travel (IST) system is based on the super-miniaturized system of virtual technology, Cave Automatic Virtual Environment (CAVE). Using bilateral virtual reality (VR-to-VR) communications, IST enables the testing of subjects via interactive communications. It appears that IST will find practical applications in the near future. We examined the utility of IST in medical treatment and psychiatric tests. Psychiatric symptoms reflect human pathos, which in turn are greatly influenced by culture. If these culture-bound symptoms can be adequately communicated between providers and clients of different cultures, we can develop effective telepsychiatric services across different societies and cultures. IST requires high-speed transmission and gigabyte circuits. A pilot project tested the utility of IST (through the use of optical fiber communications on earth) as a basis for experiments via the Gigabit satellite, to be launched in the year 2002.

  1. Gene expression profiling identifies genes predictive of oral squamous cell carcinoma.

    PubMed

    Chen, Chu; Méndez, Eduardo; Houck, John; Fan, Wenhong; Lohavanichbutr, Pawadee; Doody, Dave; Yueh, Bevan; Futran, Neal D; Upton, Melissa; Farwell, D Gregory; Schwartz, Stephen M; Zhao, Lue Ping

    2008-08-01

    Oral squamous cell carcinoma (OSCC) is associated with substantial mortality and morbidity. To identify potential biomarkers for the early detection of invasive OSCC, we compared the gene expressions of incident primary OSCC, oral dysplasia, and clinically normal oral tissue from surgical patients without head and neck cancer or preneoplastic oral lesions (controls), using Affymetrix U133 2.0 Plus arrays. We identified 131 differentially expressed probe sets using a training set of 119 OSCC patients and 35 controls. Forward and stepwise logistic regression analyses identified 10 successive combinations of genes which expression differentiated OSCC from controls. The best model included LAMC2, encoding laminin-gamma2 chain, and COL4A1, encoding collagen, type IV alpha1 chain. Subsequent modeling without these two markers showed that COL1A1, encoding collagen, type I alpha1 chain, and PADI1, encoding peptidyl arginine deiminase, type 1, could also distinguish OSCC from controls. We validated these two models using an internal independent testing set of 48 invasive OSCC and 10 controls and an external testing set of 42 head and neck squamous cell carcinoma cases and 14 controls (GEO GSE6791), with sensitivity and specificity above 95%. These two models were also able to distinguish dysplasia (n = 17) from control (n = 35) tissue. Differential expression of these four genes was confirmed by quantitative reverse transcription-PCR. If confirmed in larger studies, the proposed models may hold promise for monitoring local recurrence at surgical margins and the development of second primary oral cancer in patients with OSCC.

  2. Mathematical and experimental approaches to identify and predict the effects of chemotherapy on neuroglial precursors

    PubMed Central

    Hyrien, Ollivier; Dietrich, Jörg; Noble, Mark

    2010-01-01

    The adverse effects of chemotherapy on normal cells of the body create substantial clinical problems for many cancer patients. Relatively little is known, however, about the effects, other than promotion of cell death, of such agents on the function of normal precursor cells critical in tissue homeostasis and repair. We have combined mathematical and experimental analyses to identify the effects of sublethal doses of chemotherapy on glial precursor cells of the central nervous system (CNS). We modeled the temporal development of a population of precursor and terminally differentiated cells exposed to sublethal doses of carmustine (BCNU), a classical alkylating chemotherapeutic agent used in treatment of gliomas and non-Hodgkin’s lymphomas, as a multi-type age-dependent branching process. We fitted our model to data from in vitro clonal experiments using the method of pseudo-likelihood. This approach identifies several novel drug effects, including modification of the cell cycle length, the time between division and differentiation, and alteration in the probability of undergoing self-renewal division in precursor cells. These changes of precursor cell function in the chemotherapy-exposed brain may have profound clinical implications. Major Findings We applied our computational approach to analyze the effects of BCNU on clonal cultures of oligodendrocyte progenitor cells – one of the best-characterized neural progenitor cells in the mammalian brain. Our analysis reveals that transient exposures to BCNU increased the cell cycle length of progenitor cells and decreased their time to differentiation, while also decreasing the likelihood that they will undergo self-renewing divisions. By investigating the behavior of our mathematical model we demonstrate that precursor cell populations should recover spontaneously from transient modifications of the timing of division and of differentiation, but such recovery will not happen after alteration of cell fate. These

  3. Metabolomics to identify biomarkers and as a predictive tool in inflammatory diseases.

    PubMed

    Jutley, Gurpreet Singh; Young, Stephen P

    2015-12-01

    There is an overwhelming need for a simple, reliable tool that aids clinicians in diagnosing, assessing disease activity and treating rheumatic conditions. Identification of biomarkers in partially understood inflammatory disorders has long been sought after as the Holy Grail of Rheumatology. Given the complex nature of inflammatory conditions, it has been difficult to earmark the potential biomarkers. Metabolomics, however, is promising in providing new insights into inflammatory conditions and also identifying such biomarkers. Metabolomic studies have generally revealed increased energy requirements for by-products of a hypoxic environment, leading to a characteristic metabolic fingerprint. Here, we discuss the significance of such studies and their potential as a biomarker.

  4. 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.

  5. Identifying the source of unknown microcystin genes and predicting microcystin variants by comparing genes within uncultured cyanobacterial cells.

    PubMed

    Allender, Christopher J; LeCleir, Gary R; Rinta-Kanto, Johanna M; Small, Randall L; Satchwell, Michael F; Boyer, Gregory L; Wilhelm, Steven W

    2009-06-01

    While multiple phylogenetic markers have been used in the culture-independent study of microcystin-producing cyanobacteria, in only a few instances have multiple markers been studied within individual cells, and in all cases these studies have been conducted with cultured isolates. Here, we isolate and evaluate large DNA fragments (>6 kb) encompassing two genes involved in microcystin biosynthesis (mcyA2 and mcyB1) and use them to identify the source of gene fragments found in water samples. Further investigation of these gene loci from individual cyanobacterial cells allowed for improved analysis of the genetic diversity within microcystin producers as well as a method to predict microcystin variants for individuals. These efforts have also identified the source of the novel mcyA genotype previously termed Microcystis-like that is pervasive in the Laurentian Great Lakes and they predict the microcystin variant(s) that it produces.

  6. Regression Trees Identify Relevant Interactions: Can This Improve the Predictive Performance of Risk Adjustment?

    PubMed

    Buchner, Florian; Wasem, Jürgen; Schillo, Sonja

    2017-01-01

    Risk equalization formulas have been refined since their introduction about two decades ago. Because of the complexity and the abundance of possible interactions between the variables used, hardly any interactions are considered. A regression tree is used to systematically search for interactions, a methodologically new approach in risk equalization. Analyses are based on a data set of nearly 2.9 million individuals from a major German social health insurer. A two-step approach is applied: In the first step a regression tree is built on the basis of the learning data set. Terminal nodes characterized by more than one morbidity-group-split represent interaction effects of different morbidity groups. In the second step the 'traditional' weighted least squares regression equation is expanded by adding interaction terms for all interactions detected by the tree, and regression coefficients are recalculated. The resulting risk adjustment formula shows an improvement in the adjusted R(2) from 25.43% to 25.81% on the evaluation data set. Predictive ratios are calculated for subgroups affected by the interactions. The R(2) improvement detected is only marginal. According to the sample level performance measures used, not involving a considerable number of morbidity interactions forms no relevant loss in accuracy. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints.

    PubMed

    Bujkiewicz, Sylwia; Thompson, John R; Spata, Enti; Abrams, Keith R

    2015-08-13

    We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta-analytical methods are implemented using illustrative examples in relapsing-remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions.

  8. Surrogate mobility and orientation affect the early neurobehavioral development of infant rhesus macaques (Macaca mulatta).

    PubMed

    Dettmer, Amanda M; Ruggiero, Angela M; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2008-05-01

    A biological mother's movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard stationary rocking surrogates (RS) and to 9-15 infants reared with their biological mothers (MR) for early developmental outcome. We predicted that MS infants would develop more similarly to MR infants than RS infants. In neonatal assessments conducted at Day 30, both MS and MR infants showed more highly developed motor activity than RS infants on measures of grasping (p = .009), coordination (p = .038), spontaneous crawl (p = .009), and balance (p = .003). At 2-3 months of age, both MS and MR infants displayed higher levels of exploration in the home cage than RS infants (p = .016). In a novel situation in which only MS and RS infants were tested, MS infants spent less time near their surrogates in the first five minutes of the test session than RS infants (p = .05), indicating a higher level of comfort. Collectively, these results suggest that when nursery-rearing of infant monkeys is necessary, a mobile hanging surrogate may encourage more normative development of gross motor skills and exploratory behavior and may serve as a useful alternative to stationary or rocking surrogates.

  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. 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.

  11. 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.

  12. 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

  13. 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.

    2014-12-01

    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

  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. An unbiased lipidomics approach identifies early second trimester lipids predictive of Maternal Glycemic Traits and Gestational Diabetes Mellitus

    PubMed Central

    Lu, Liangjian; Koulman, Albert; Petry, Clive J.; Jenkins, Benjamin; Matthews, Lee; Hughes, Ieuan A.; Acerini, Carlo L.; Ong, Ken K.; Dunger, David B.

    2016-01-01

    Objective To investigate the relationship between early second trimester serum lipidomic variation and maternal glycemic traits at 28 weeks, and to identify predictive lipid biomarkers for Gestational Diabetes (GDM). Research Design and Methods Prospective study of 817 pregnant women (Discovery cohort, n=200; Validation cohort, n=617) who provided an early second trimester serum sample, and underwent oral glucose tolerance testing (OGTT) at 28 weeks. In the discovery cohort, lipids were measured using direct infusion mass spectrometry, and correlated with OGTT results. Variable Importance in Projection (VIP) scores were used to identify candidate lipid biomarkers. Candidate biomarkers were measured in the validation cohort using Liquid Chromatography- Mass Spectrometry, and tested for associations with OGTT results and GDM status. Results Early second trimester lipidomic variation was associated with 1-hour post-load glucose levels, but not with fasting plasma glucose. Of the 13 lipid species identified by VIP scores, 10 had nominally significant associations with post-load glucose levels. In the validation cohort, 5 of these 10 lipids had significant associations with post-load glucose levels independent of maternal age and BMI, i.e. TG(51:1), TG(48:1), PC(32:1), PCae(40:3) and PCae(40:4). All except the last were also associated with maternal GDM status. Together, these 4 lipid biomarkers had moderate ability to predict GDM (Area under curve (AUC)= 0.71±0.04, p=4.85×10-7), and improved the prediction of GDM by age and BMI alone from AUC 0.69 to AUC 0.74. Conclusions Specific early second trimester lipid biomarkers can predict maternal GDM status independent of maternal age and BMI, potentially enhancing risk factor-based screening. PMID:27703025

  16. 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.

  17. Identifying Thoracic Malignancies Through Pleural Fluid Biomarkers: A Predictive Multivariate Model.

    PubMed

    Porcel, José M; Esquerda, Aureli; Martínez-Alonso, Montserrat; Bielsa, Silvia; Salud, Antonieta

    2016-03-01

    The diagnosis of malignant pleural effusions may be challenging when cytological examination of aspirated pleural fluid is equivocal or noncontributory. The purpose of this study was to identify protein candidate biomarkers differentially expressed in the pleural fluid of patients with mesothelioma, lung adenocarcinoma, lymphoma, and tuberculosis (TB).A multiplex protein biochip comprising 120 biomarkers was used to determine the pleural fluid protein profile of 29 mesotheliomas, 29 lung adenocarcinomas, 12 lymphomas, and 35 tuberculosis. The relative abundance of these predetermined biomarkers among groups served to establish the differential diagnosis of: malignant versus benign (TB) effusions, lung adenocarcinoma versus mesothelioma, and lymphoma versus TB. The selected putative markers were validated using widely available commercial techniques in an independent sample of 102 patients.Significant differences were found in the protein expressions of metalloproteinase-9 (MMP-9), cathepsin-B, C-reactive protein, and chondroitin sulfate between malignant and TB effusions. When integrated into a scoring model, these proteins yielded 85% sensitivity, 100% specificity, and an area under the curve (AUC) of 0.98 for labeling malignancy in the verification sample. For lung adenocarcinoma-mesothelioma discrimination, combining CA19-9, CA15-3, and kallikrein-12 had maximal discriminatory capacity (65% sensitivity, 100% specificity, AUC 0.94); figures which also refer to the validation set. Last, cathepsin-B in isolation was only moderately useful (sensitivity 89%, specificity 62%, AUC 0.75) in separating lymphomatous and TB effusions. However, this last differentiation improved significantly when cathepsin-B was used with respect to the patient's age (sensitivity 72%, specificity 100%, AUC 0.94).In conclusion, panels of 4 (i.e., MMP-9, cathepsin-B, C-reactive protein, chondroitin sulfate), or 3 (i.e., CA19-9, CA15-3, kallikrein-12) different protein biomarkers on pleural

  18. Verification of the surrogate ratio method

    SciTech Connect

    Chiba, Satoshi; Iwamoto, Osamu

    2010-04-15

    Effects of difference in the spin and parity distributions for the surrogate and neutron-induced reactions are investigated. Without assuming specific (schematic) spin-parity distributions, it was found that the surrogate ratio method can be employed to determine neutron fission and capture cross sections if (1) weak Weisskopf-Ewing condition (defined in this paper) is satisfied, (2) there exist two surrogate reactions whose spin-parity distributions of the decaying nuclei are almost equivalent, and (3) difference of the representative spin values between the neutron-induced and surrogate reactions is no much larger than 10(Planck constant/2pi). If these conditions are satisfied, we need not know the spin-parity distributions populated by the surrogate method. Instead, we should just select a pair of surrogate reactions which will populate the similar spin-parity distributions, using targets having similar structure and reactions having the similar reaction mechanisms. Achievable accuracy is estimated to be around 5% and 10% for fission and capture channels, respectively, for nuclei of the Uranium region. The surrogate absolute method may be applicable to determination of fission cross sections with a caution. However, there will be little hope to apply this method for capture cross section measurements unless the spin-parity distributions in the neutron-induced and surrogate reactions are fairly close to each other (which is implausible) or the difference can be corrected theoretically. The surrogate ratio method was shown also to be a robust method in the presence of breakup reactions without assuming specific breakup reaction mechanisms.

  19. Utility of percentage of births to teenagers as a surrogate for the teen birth rate.

    PubMed Central

    Gould, J; Blackwell, T; Heilig, C; Axley, M

    1998-01-01

    OBJECTIVES: The teen birth rate is commonly used in comparing regional variation in teen pregnancies, but local teen birth rates are not always available. In this study the percentage of all births that are to teens was evaluated for its utility as a surrogate for the teen birth rate. METHODS: Rank correlation and sensitivity and specificity analyses were used. RESULTS: The Spearman rank correlations between percentage of teen births (PTB) and teen birth rate (TBR) were .995, .906, and .841 for the 3 age groups suggesting that it may be reasonable to employ PTB to prioritize zip codes. Zip codes with upper quartile levels of percentages of teen births identified zip codes with upper quartile levels of TBR with a sensitivity of 83.8%, 68.8%, and 65%; a false-positive rate of 2.1%, 8.6%, and 10%; and a positive predictive value of 89.3%, 67.6%, and 67.5% for the age groups 10 through 14, 15 through 17, and 18 through 19 years. CONCLUSIONS: The percentage of births to teens is a useful surrogate for teen birth rate in California, especially among younger teenagers. PMID:9618618

  20. Improved Prediction of Cardiovascular Disease Based on a Panel of Single Nucleotide Polymorphisms Identified Through Genome-Wide Association Studies

    PubMed Central

    Davies, Robert W.; Dandona, Sonny; Stewart, Alexandre F.R.; Chen, Li; Ellis, Stephan G.; Tang, W.H. Wilson; Hazen, Stanley L.; Roberts, Robert; McPherson, Ruth; Wells, George A.

    2011-01-01

    Background Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) at multiple loci that are significantly associated with coronary artery disease (CAD) risk. In this study, we sought to determine and compare the predictive capabilities of 9p21.3 alone and a panel of SNPs identified and replicated through GWAS for CAD. Methods and Results We used the Ottawa Heart Genomics Study (OHGS) (3323 cases, 2319 control subjects) and the Wellcome Trust Case Control Consortium (WTCCC) (1926 cases, 2938 control subjects) data sets. We compared the ability of allele counting, logistic regression, and support vector machines. Two sets of SNPs, 9p21.3 alone and a set of 12 SNPs identified by GWAS and through a model-fitting procedure, were considered. Performance was assessed by measuring area under the curve (AUC) for OHGS using 10-fold cross-validation and WTCCC as a replication set. AUC for logistic regression using OHGS increased significantly from 0.555 to 0.608 (P=3.59×10–14) for 9p21.3 versus the 12 SNPs, respectively. This difference remained when traditional risk factors were considered in a subgroup of OHGS (1388 cases, 2038 control subjects), with AUC increasing from 0.804 to 0.809 (P=0.037). The added predictive value over and above the traditional risk factors was not significant for 9p21.3 (AUC 0.801 versus 0.804, P=0.097) but was for the 12 SNPs (AUC 0.801 versus 0.809, P=0.0073). Performance was similar between OHGS and WTCCC. Logistic regression outperformed both support vector machines and allele counting. Conclusions Using the collective of 12 SNPs confers significantly greater predictive capabilities for CAD than 9p21.3, whether traditional risks are or are not considered. More accurate models probably will evolve as additional CAD-associated SNPs are identified. PMID:20729558

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

    PubMed

    Zhao, Tingting; Ruan, Dan

    2016-09-07

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  3. 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%.

  4. 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.

  5. 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.

  6. Predictive value of dobutamine echocardiography and positron emission tomography in identifying hibernating myocardium in patients with postischaemic heart failure

    PubMed Central

    Pagano, D; Bonser, R; Townend, J; Ordoubadi, F; Lorenzoni, R; Camici, P

    1998-01-01

    Objective—To compare the predictive value of dobutamine echocardiography (DE) and positron emission tomography (PET) in identifying reversible chronic left ventricular (LV) dysfunction (hibernating myocardium) in patients with coronary artery disease (CAD) and overt heart failure.
Patients—30 patients (four women) with CAD and heart failure undergoing coronary artery bypass grafting (CABG).
Methods—Myocardial viability was assessed with DE (5 and 10 µg/kg/min) and PET with [18F] 2-fluoro-2-deoxy-D-glucose (FDG) under hyperinsulinaemic euglycaemic clamp. Regional (echo) and global LV function (MUGA) were assessed at baseline and six months after CABG.
Results—192 of the 336 (57%) dysfunctional LV segments improved function following CABG (hibernating) and the LV ejection fraction (EF) increased from 23(7) to 32(9)% (p < 0.0001) (in 17 patients > 5%). DE and PET had similar positive predictive values (68% and 66%) in the identification of hibernating myocardium, but DE had a significantly lower negative predictive value than PET (54% v 96%; p < 0.0001). A significant linear correlation was found between the number of PET viable segments and the changes in EF following CABG (r = 0.65; p = 0.0001). Stepwise logistic regression identified the number of PET viable segments as an independent predictor of improvement in EF > 5%, whereas the number of DE viable segments, the baseline LVEF, and wall motion were not.
Conclusions—DE has a higher false negative rate than PET in identifying recoverable LV dysfunction in patients with severe postischaemic heart failure. The amount of PET viable myocardium correlates with the functional outcome following CABG.

 Keywords: dobutamine echocardiography;  positron emission tomography;  coronary artery disease;  heart failure;  hibernating myocardium PMID:9602663

  7. 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.

  8. Summarizing the field of surrogate modeling research

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2012-10-01

    As computer simulations of complex physical interactions grow, so do the time and expense required to operate them. Mirroring the development of such full-scale models has been the related field of surrogate modeling or metamodeling. Surrogate models take a variety of forms, but their shared goal is to provide a numerical output similar to that of a fully complex physical model while minimizing the computational time and cost required to calculate the result. With an eye toward introducing those unfamiliar with the practices and pitfalls of surrogate modeling to the topic and with a focus on its applications to water resources research, Razavi et al. prepared a systematic review of the surrogate modeling literature.

  9. Genomic Models of Short-Term Exposure Accurately Predict Long-Term Chemical Carcinogenicity and Identify Putative Mechanisms of Action

    PubMed Central

    Gusenleitner, Daniel; Auerbach, Scott S.; Melia, Tisha; Gómez, Harold F.; Sherr, David H.; Monti, Stefano

    2014-01-01

    Background Despite an overall decrease in incidence of and mortality from cancer, about 40% of Americans will be diagnosed with the disease in their lifetime, and around 20% will die of it. Current approaches to test carcinogenic chemicals adopt the 2-year rodent bioassay, which is costly and time-consuming. As a result, fewer than 2% of the chemicals on the market have actually been tested. However, evidence accumulated to date suggests that gene expression profiles from model organisms exposed to chemical compounds reflect underlying mechanisms of action, and that these toxicogenomic models could be used in the prediction of chemical carcinogenicity. Results In this study, we used a rat-based microarray dataset from the NTP DrugMatrix Database to test the ability of toxicogenomics to model carcinogenicity. We analyzed 1,221 gene-expression profiles obtained from rats treated with 127 well-characterized compounds, including genotoxic and non-genotoxic carcinogens. We built a classifier that predicts a chemical's carcinogenic potential with an AUC of 0.78, and validated it on an independent dataset from the Japanese Toxicogenomics Project consisting of 2,065 profiles from 72 compounds. Finally, we identified differentially expressed genes associated with chemical carcinogenesis, and developed novel data-driven approaches for the molecular characterization of the response to chemical stressors. Conclusion Here, we validate a toxicogenomic approach to predict carcinogenicity and provide strong evidence that, with a larger set of compounds, we should be able to improve the sensitivity and specificity of the predictions. We found that the prediction of carcinogenicity is tissue-dependent and that the results also confirm and expand upon previous studies implicating DNA damage, the peroxisome proliferator-activated receptor, the aryl hydrocarbon receptor, and regenerative pathology in the response to carcinogen exposure. PMID:25058030

  10. Surrogate utility estimation by long-term partners and unfamiliar dyads.

    PubMed

    Tunney, Richard J; Ziegler, Fenja V

    2015-01-01

    To what extent are people able to make predictions about other people's preferences and values?We report two experiments that present a novel method assessing some of the basic processes in surrogate decision-making, namely surrogate-utility estimation. In each experiment participants formed dyads who were asked to assign utilities to health related items and commodity items, and to predict their partner's utility judgments for the same items. In experiment one we showed that older adults in long-term relationships were able to accurately predict their partner's wishes. In experiment two we showed that younger adults who were relatively unfamiliar with one another were also able to predict other people's wishes. Crucially we demonstrated that these judgments were accurate even after partialling out each participant's own preferences indicating that in order to make surrogate utility estimations people engage in perspective-taking rather than simple anchoring and adjustment, suggesting that utility estimation is not the cause of inaccuracy in surrogate decision-making. The data and implications are discussed with respect to theories of surrogate decision-making.

  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. 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

  13. 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

  14. Cell-line selectivity improves the predictive power of pharmacogenomic analyses and helps identify NADPH as biomarker for ferroptosis sensitivity

    PubMed Central

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

    2016-01-01

    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. 2,565 cell-line-selective lethal compounds were identified and grouped into 18 clusters based on their 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

  15. 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.

  16. Dimensions and Role-Specific Mediators of Surrogate Trust in the ICU

    PubMed Central

    Hutchison, Paul J.; McLaughlin, Katie; Corbridge, Tom; Michelson, Kelly N.; Emanuel, Linda; Sporn, Peter H. S.; Crowley-Matoka, Megan

    2016-01-01

    Objective In the ICU, discussions between clinicians and surrogate decision makers are often accompanied by conflict about a patient’s prognosis or care plan. Trust plays a role in limiting conflict, but little is known about the determinants of trust in the ICU. We sought to identify the dimensions of trust and clinician behaviors conducive to trust formation in the ICU. Design Prospective qualitative study. Setting Medical ICU of a major urban university hospital. Subjects Surrogate decision makers of intubated, mechanically ventilated patients in the medical ICU. Measurements and Main Results Semistructured interviews focused on surrogates’ general experiences in the ICU and on their trust in the clinicians caring for the patient. Interviews were audio-recorded, transcribed verbatim, and coded by two reviewers. Constant comparison was used to identify themes pertaining to trust. Thirty surrogate interviews revealed five dimensions of trust in ICU clinicians: technical competence, communication, honesty, benevolence, and interpersonal skills. Most surrogates emphasized the role of nurses in trust formation, frequently citing their technical competence. Trust in physicians was most commonly related to honesty and the quality of their communication with surrogates. Conclusions Interventions to improve trust in the ICU should be role-specific, since surrogate expectations are different for physicians and nurses with regard to behaviors relevant to trust. Further research is needed to confirm our findings and explore the impact of trust modification on clinician-family conflict. PMID:27513360

  17. Genome context as a predictive tool for identifying regulatory targets of the TetR family transcriptional regulators.

    PubMed

    Ahn, Sang Kyun; Cuthbertson, Leslie; Nodwell, Justin R

    2012-01-01

    TetR family transcriptional regulators (TFRs) are found in most bacteria and archea. Most of the family members that have been investigated to date are repressors of their target genes, and the majority of these, like the well-characterized protein TetR, regulate genes that encode transmembrane efflux pumps. In many cases repression by TFR proteins is reversed through the direct binding of a small-molecule ligand. The number of TFRs in the public database has grown rapidly as a result of genome sequencing and there are now thousands of family members; however virtually nothing is known about the biology and biochemistry they regulate. Generally applicable methods for predicting their regulatory targets would assist efforts to characterize the family. Here, we investigate chromosomal context of 372 TFRs from three Streptomyces species. We find that the majority (250 TFRs) are transcribed divergently from one neighboring gene, as is the case for TetR and its target tetA. We explore predicted target gene product identity and intergenic separation to see which either correlates with a direct regulatory relationship. While intergenic separation is a critical factor in regulatory prediction the identity of the putative target gene product is not. Our data suggest that those TFRs that are <200 bp from their divergently oriented neighbors are most likely to regulate them. These target genes include membrane proteins (26% of which 22% are probable membrane-associated pumps), enzymes (60%), other proteins such as transcriptional regulators (1%), and proteins having no predictive sequence motifs (13%). In addition to establishing a solid foundation for identifying targets for TFRs of unknown function, our analysis demonstrates a much greater diversity of TFR-regulated biochemical functions.

  18. Myocardial Gene Expression Profiling to Predict and Identify Cardiac Allograft Acute Cellular Rejection: The GET-Study

    PubMed Central

    Bodez, Diane; Hocini, Hakim; Tchitchek, Nicolas; Tisserand, Pascaline; Benhaiem, Nicole; Barau, Caroline; Kharoubi, Mounira; Guellich, Aziz; Guendouz, Soulef; Radu, Costin; Couetil, Jean-Paul; Ghaleh, Bijan; Dubois-Randé, Jean-Luc; Teiger, Emmanuel; Hittinger, Luc

    2016-01-01

    Aims Serial invasive endomyocardial biopsies (EMB) remain the gold standard for acute cellular rejection (ACR) diagnosis. However histological grading has several limitations. We aimed to explore the value of myocardial Gene Expression Profiling (GEP) for diagnosing and identifying predictive biomarkers of ACR. Methods A case-control study nested within a retrospective heart transplant patients cohort included 126 patients with median (IQR) age 50 (41–57) years and 111 (88%) males. Among 1157 EMB performed, 467 were eligible (i.e, corresponding to either ISHLT grade 0 or ≥3A), among which 36 were selected for GEP according to the grading: 0 (CISHLT, n = 13); rejection ≥3A (RISHLT, n = 13); 0 one month before ACR (BRISHLT, n = 10). Results We found 294 genes differentially expressed between CISHLT and RISHLT, mainly involved in immune activation, and inflammation. Hierarchical clustering showed a clear segregation of CISHLT and RISHLT groups and heterogeneity of GEP within RISHLT. All EMB presented immune activation, but some RISHLT EMB were strongly subject to inflammation, whereas others, closer to CISHLT, were characterized by structural modifications with lower inflammation level. We identified 15 probes significantly different between BRISHLT and CISHLT, including the gene of the muscular protein TTN. This result suggests that structural alterations precede inflammation in ACR. Linear Discriminant Analysis based on these 15 probes was able to identify the histological status of every 36 samples. Conclusion Myocardial GEP is a helpful method to accurately diagnose ACR, and predicts rejection one month before its histological occurrence. These results should be considered in cardiac allograft recipients’ care. PMID:27898719

  19. A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

    PubMed

    Siddharth, Jay; Holway, Nicholas; Parkinson, Scott J

    2013-01-01

    The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets) correlating with formula (vs breast) feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

  20. 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

  1. Conserved residues in RF-NH₂ receptor models identify predicted contact sites in ligand-receptor binding.

    PubMed

    Bass, C; Katanski, C; Maynard, B; Zurro, I; Mariane, E; Matta, M; Loi, M; Melis, V; Capponi, V; Muroni, P; Setzu, M; Nichols, R

    2014-03-01

    Peptides in the RF-NH2 family are grouped together based on an amidated dipeptide C terminus and signal through G-protein coupled receptors (GPCRs) to influence diverse physiological functions. By determining the mechanisms underlying RF-NH2 signaling targets can be identified to modulate physiological activity; yet, how RF-NH2 peptides interact with GPCRs is relatively unexplored. We predicted conserved residues played a role in Drosophila melanogaster RF-NH2 ligand-receptor interactions. In this study D. melanogaster rhodopsin-like family A peptide GPCRs alignments identified eight conserved residues unique to RF-NH2 receptors. Three of these residues were in extra-cellular loops of modeled RF-NH2 receptors and four in transmembrane helices oriented into a ligand binding pocket to allow contact with a peptide. The eighth residue was unavailable for interaction; yet its conservation suggested it played another role. A novel hydrophobic region representative of RF-NH2 receptors was also discovered. The presence of rhodopsin-like family A GPCR structural motifs including a toggle switch indicated RF-NH2s signal classically; however, some features of the DMS receptors were distinct from other RF-NH2 GPCRs. Additionally, differences in RF-NH2 receptor structures which bind the same peptide explained ligand specificity. Our novel results predicted conserved residues as RF-NH2 ligand-receptor contact sites and identified unique and classic structural features. These discoveries will aid antagonist design to modulate RF-NH2 signaling.

  2. De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. Methods The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers. Results More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients. Conclusions Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications. PMID:22400902

  3. Surrogate end points for overall survival in breast cancer trials: A review.

    PubMed

    Fiteni, Frédéric; Bonnetain, Franck

    2016-10-01

    Our aim was to review the studies which assessed potential surrogate endpoints for overall survival (OS) in breast cancer trials. A Literature search in PubMed database of studies which assessed potential surrogate endpoints for OS in breast cancer trials was conducted. The surrogacy was assessed with the German institute of Quality and efficiency in Health Care's (IWQiG) framework and the Fleming hierarchy. Thirteen studies were identified. At the neoadjuvant setting, two individual patient data (IPD) meta-analyses and one aggregate data meta-analysis assessing surrogacy of pathological complete response (PCR) were identified. Trial-level association was calculated in one study and the squared correlation was 0.24. Therefore PCR was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the adjuvant setting, one meta-analysis on aggregate data was identified. 2-year DFS was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the metastatic setting, six meta-analyses based on aggregate data, three IPD meta-analyses and one retrospective study were identified. Within the IPD meta-analyses, at the trial-level association the squared correlation between the potential surrogates and OS ranged from 0.10 to 0.57 and no endpoint was judged to be valid surrogate for OS at the metastatic setting. The level of evidence available supporting a relationship between OS and potential surrogate endpoints in breast cancer trials is low.

  4. Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors

    PubMed Central

    Schütte, Moritz; Risch, Thomas; Abdavi-Azar, Nilofar; Boehnke, Karsten; Schumacher, Dirk; Keil, Marlen; Yildiriman, Reha; Jandrasits, Christine; Borodina, Tatiana; Amstislavskiy, Vyacheslav; Worth, Catherine L.; Schweiger, Caroline; Liebs, Sandra; Lange, Martin; Warnatz, Hans- Jörg; Butcher, Lee M.; Barrett, James E.; Sultan, Marc; Wierling, Christoph; Golob-Schwarzl, Nicole; Lax, Sigurd; Uranitsch, Stefan; Becker, Michael; Welte, Yvonne; Regan, Joseph Lewis; Silvestrov, Maxine; Kehler, Inge; Fusi, Alberto; Kessler, Thomas; Herwig, Ralf; Landegren, Ulf; Wienke, Dirk; Nilsson, Mats; Velasco, Juan A.; Garin-Chesa, Pilar; Reinhard, Christoph; Beck, Stephan; Schäfer, Reinhold; Regenbrecht, Christian R. A.; Henderson, David; Lange, Bodo; Haybaeck, Johannes; Keilholz, Ulrich; Hoffmann, Jens; Lehrach, Hans; Yaspo, Marie-Laure

    2017-01-01

    Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I–IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab. PMID:28186126

  5. 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.

  6. 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.

  7. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    SciTech Connect

    Herbinet, Olivier; Pitz, William J.; Westbrook, Charles K.

    2008-08-15

    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 and co-workers 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. (author)

  8. Integration of Traditional and Metabolomics Biomarkers Identifies Prognostic Metabolites for Predicting Responsiveness to Nutritional Intervention against Oxidative Stress and Inflammation

    PubMed Central

    Kim, You Jin; Huh, Iksoo; Kim, Ji Yeon; Park, Saejong; Ryu, Sung Ha; Kim, Kyu-Bong; Kim, Suhkmann; Park, Taesung; Kwon, Oran

    2017-01-01

    Various statistical approaches can be applied to integrate traditional and omics biomarkers, allowing the discovery of prognostic markers to classify subjects into poor and good prognosis groups in terms of responses to nutritional interventions. Here, we performed a prototype study to identify metabolites that predict responses to an intervention against oxidative stress and inflammation, using a data set from a randomized controlled trial evaluating Korean black raspberry (KBR) in sedentary overweight/obese subjects. First, a linear mixed-effects model analysis with multiple testing correction showed that four-week consumption of KBR significantly changed oxidized glutathione (GSSG, q = 0.027) level, the ratio of reduced glutathione (GSH) to GSSG (q = 0.039) in erythrocytes, malondialdehyde (MDA, q = 0.006) and interleukin-6 (q = 0.006) levels in plasma, and seventeen NMR metabolites in urine compared with those in the placebo group. A subsequent generalized linear mixed model analysis showed linear correlations between baseline urinary glycine and N-phenylacetylglycine (PAG) and changes in the GSH:GSSG ratio (p = 0.008 and 0.004) as well as between baseline urinary adenine and changes in MDA (p = 0.018). Then, receiver operating characteristic analysis revealed that a two-metabolite set (glycine and PAG) had the strongest prognostic relevance for future interventions against oxidative stress (the area under the curve (AUC) = 0.778). Leave-one-out cross-validation confirmed the accuracy of prediction (AUC = 0.683). The current findings suggest that a higher level of this two-metabolite set at baseline is useful for predicting responders to dietary interventions in subjects with oxidative stress and inflammation, contributing to the emergence of personalized nutrition. PMID:28273855

  9. 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.

  10. 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

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

    PubMed

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

    2016-03-18

    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.

  12. 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.

  13. Development of Surrogate Spinal Cords for the Evaluation of Electrode Arrays Used in Intraspinal Implants

    PubMed Central

    Cheng, Cheng; Kmech, Jonn; Mushahwar, Vivian K.

    2013-01-01

    We report the development of a surrogate spinal cord for evaluating the mechanical suitability of electrode arrays for intraspinal implants. The mechanical and interfacial properties of candidate materials (including silicone elastomers and gelatin hydrogels) for the surrogate cord were tested. The elastic modulus was characterized using dynamic mechanical analysis, and compared with values of actual human spinal cords from the literature. Forces required to indent the surrogate cords to specified depths were measured to obtain values under static conditions. Importantly, to quantify surface properties in addition to mechanical properties normally considered, interfacial frictional forces were measured by pulling a needle out of each cord at a controlled rate. The measured forces were then compared to those obtained from rat spinal cords. Formaldehyde-crosslinked gelatin, 12 wt% in water, was identified as the most suitable material for the construction of surrogate spinal cords. To demonstrate the utility of surrogate spinal cords in evaluating the behavior of various electrode arrays, cords were implanted with two types of intraspinal electrode arrays (one made of individual microwires and another of microwires anchored with a solid base), and cord deformation under elongation was evaluated. The results demonstrate that the surrogate model simulates the mechanical and interfacial properties of the spinal cord, and enables in vitro screening of intraspinal implants. PMID:23358939

  14. 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.

  15. A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds

    PubMed Central

    Lucantoni, Leonardo; Silvestrini, Francesco; Signore, Michele; Siciliano, Giulia; Eldering, Maarten; Dechering, Koen J.; Avery, Vicky M.; Alano, Pietro

    2015-01-01

    Plasmodium falciparum gametocytes, specifically the mature stages, are the only malaria parasite stage in humans transmissible to the mosquito vector. Anti-malarial drugs capable of killing these forms are considered essential for the eradication of malaria and tools allowing the screening of large compound libraries with high predictive power are needed to identify new candidates. As gametocytes are not a replicative stage it is difficult to apply the same drug screening methods used for asexual stages. Here we propose an assay, based on high content imaging, combining “classic” gametocyte viability readout based on gametocyte counts with a functional viability readout, based on gametocyte activation and the discrimination of the typical gamete spherical morphology. This simple and rapid assay has been miniaturized to a 384-well format using acridine orange staining of wild type P. falciparum 3D7A sexual forms, and was validated by screening reference antimalarial drugs and the MMV Malaria Box. The assay demonstrated excellent robustness and ability to identify quality hits with high likelihood of confirmation of transmission reducing activity in subsequent mosquito membrane feeding assays. PMID:26553647

  16. 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

  17. Surrogates for herbicide removal in stormwater biofilters.

    PubMed

    Zhang, Kefeng; Deletic, Ana; Page, Declan; McCarthy, David T

    2015-09-15

    Real time monitoring of suitable surrogate parameters are critical to the validation of any water treatment processes, and is of particularly high importance for validation of natural stormwater treatment systems. In this study, potential surrogates for herbicide removal in stormwater biofilters (also known as stormwater bio-retention or rain-gardens) were assessed using field challenge tests and matched laboratory column experiments. Differential UV absorbance at 254mn (ΔUVA254), total phosphorus (ΔTP), dissolved phosphorus (ΔDP), total nitrogen (ΔTN), ammonia (ΔNH3), nitrate and nitrite (ΔNO3+NO2), dissolved organic carbon (ΔDOC) and total suspended solids (ΔTSS) were compared with glyphosate, atrazine, simazine and prometryn removal rates. The influence of different challenge conditions on the performance of each surrogate was studied. Differential TP was significantly and linearly related to glyphosate reduction (R(2) = 0.75-0.98, P < 0.01), while ΔTP and ΔUVA254 were linearly correlated (R(2) = 0.44-0.84, P < 0.05) to the reduction of triazines (atrazine, simazine and prometryn) in both field and laboratory tests. The performance of ΔTP and ΔUVA254 as surrogates for herbicides were reliable under normal and challenge dry conditions, but weaker correlations were observed under challenge wet conditions. Of those tested, ΔTP is the most promising surrogate for glyphosate removal and ΔUVA254 is a suitable surrogate for triazines removal in stormwater biofilters.

  18. Carbonylations of alkenes with CO surrogates.

    PubMed

    Wu, Lipeng; Liu, Qiang; Jackstell, Ralf; Beller, Matthias

    2014-06-16

    Alkene carbonylation reactions are important for the production of value-added bulk and fine chemicals. Nowadays, all industrial carbonylation processes make use of highly toxic and flammable carbon monoxide. In fact, these properties impede the wider use of carbonylation reactions in industry and academia. Hence, performing carbonylations without the use of CO is highly desired and will contribute to the further advancement of sustainable chemistry. Although the use of carbon monoxide surrogates in alkene carbonylation reactions has been reported intermittently in the last 30 years, only recently has this area attracted significant interest. This Minireview summarizes carbonylation reactions of alkenes using different carbon monoxide surrogates.

  19. Which one is a valuable surrogate for predicting survival between Tomita and Tokuhashi scores in patients with spinal metastases? A meta-analysis for diagnostic test accuracy and individual participant data analysis.

    PubMed

    Lee, Chang-Hyun; Chung, Chun Kee; Jahng, Tae-Ahn; Kim, Ki-jeong; Kim, Chi Heon; Hyun, Seung-Jae; Kim, Hyun-Jib; Jeon, Sang Ryong; Chang, Ung-Kyu; Lee, Sun-Ho; Moon, Seong-Hwan; Majeed, Haroon; Zhang, Dan; Gravis, Gwenaelle; Wibmer, Christine; Kumar, Naresh; Moon, Kyung Yun; Park, Jin Hoon; Tabouret, Emeline; Fuentes, Stephane

    2015-06-01

    This study is to estimate the diagnostic accuracy of Tokuhashi and Tomita scores that assures 6-month predicting survival regarded as a standard of surgical treatment. We searched PubMed, EMBASE, European PubMed central, and the Cochrane library for papers about the sensitivities and specificities of the Tokuhashi and/or Tomita scores to estimate predicting survival. Studies with cut-off values of ≥9 for Tokuhashi and ≤7 for Tomita scores based on prior studies were enrolled. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC), and the best cut-off value were calculated via meta-analysis and individual participant data analysis. Finally, 22 studies were enrolled in the meta-analysis, and 1095 patients from 8 studies were included in the individual data analysis. In the meta-analysis, the pooled sensitivity/specificity/DOR for 6-month survival were 57.7 %/76.6 %/4.70 for the Tokuhashi score and 81.8 %/47.8 %/4.93 for Tomita score. The AUC of summary receiver operating characteristic plots was 0.748 for the Tokuhashi score and 0.714 for the Tomita score. Although Tokuhashi score was more accurate than Tomita score slightly, both showed low accuracy to predict 6 months residual survival. Moreover, the best cut-off values of Tokuhashi and Tomita scores were 8 and 6, not 9 and 7, for predicting 6-month survival, respectively. Estimation of 6-month predicting survival to decide surgery in patients with spinal metastasis is quite limited by using Tokuhashi and Tomita scores alone. Tokuhashi and Tomita scores could be incorporated as part of a multidisciplinary approach or perhaps interpreted in the context of a multidisciplinary approach.

  20. Use of Neuroanatomical Pattern Classification to Identify Subjects in At-Risk Mental States of Psychosis and Predict Disease Transition

    PubMed Central

    Koutsouleris, Nikolaos; Meisenzahl, Eva M.; Davatzikos, Christos; Bottlender, Ronald; Frodl, Thomas; Scheuerecker, Johanna; Schmitt, Gisela; Zetzsche, Thomas; Decker, Petra; Reiser, Maximilian; Möller, Hans-Jürgen; Gaser, Christian

    2014-01-01

    Context Identification of individuals at high risk of developing psychosis has relied on prodromal symptomatology. Recently, machine learning algorithms have been successfully used for magnetic resonance imaging–based diagnostic classification of neuropsychiatric patient populations. Objective To determine whether multivariate neuroanatomical pattern classification facilitates identification of individuals in different at-risk mental states (ARMS) of psychosis and enables the prediction of disease transition at the individual level. Design Multivariate neuroanatomical pattern classification was performed on the structural magnetic resonance imaging data of individuals in early or late ARMS vs healthy controls (HCs). The predictive power of the method was then evaluated by categorizing the baseline imaging data of individuals with transition to psychosis vs those without transition vs HCs after 4 years of clinical follow-up. Classification generalizability was estimated by cross-validation and by categorizing an independent cohort of 45 new HCs. Setting Departments of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany. Participants The first classification analysis included 20 early and 25 late at-risk individuals and 25 matched HCs. The second analysis consisted of 15 individuals with transition, 18 without transition, and 17 matched HCs. Main Outcome Measures Specificity, sensitivity, and accuracy of classification. Results The 3-group, cross-validated classification accuracies of the first analysis were 86% (HCs vs the rest), 91% (early at-risk individuals vs the rest), and 86% (late at-risk individuals vs the rest). The accuracies in the second analysis were 90% (HCs vs the rest), 88% (individuals with transition vs the rest), and 86% (individuals without transition vs the rest). Independent HCs were correctly classified in 96% (first analysis) and 93% (second analysis) of cases. Conclusions Different ARMSs and their clinical outcomes

  1. 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.

  2. Experimental and kinetic modeling study of combustion of JP-8, its surrogates and components in laminar premixed flows

    NASA Astrophysics Data System (ADS)

    Seshadri, Kalyanasundaram; Frassoldati, Alessio; Cuoci, Alberto; Faravelli, Tiziano; Niemann, Ulrich; Weydert, Patrick; Ranzi, Eliseo

    2011-08-01

    Experimental and kinetic modeling studies are carried out to characterize premixed combustion of jet fuels, their surrogates, and reference components in laminar nonuniform flows. In previous studies, it was established that the Aachen surrogate made up of 80 % n-decane and 20 % trimethylbenzene by weight, and surrogate C made up of 57 % n-dodecane, 21 % methylcyclohexane and 22 % o-xylene by weight, reproduce key aspects of combustion of jet fuels in laminar nonpremixed flows. Here, these surrogates and a jet fuel are tested in premixed, nonuniform flows. The counterflow configuration is employed, and critical conditions of extinction are measured. In addition, the reference components tested are n-heptane, n-decane, n-dodecane, methylcyclohexane, trimethylbenzene, and o-xylene. Measured critical conditions of extinction of the Aachen surrogate and surrogate C are compared with those for the jet fuel. In general the alkanes n-heptane, n-decane, and n-dodecane, and methylcyclohexane are found to be more reactive than the aromatics o-xylene and trimethylbenzene. Flame structure and critical conditions of extinction are predicted for the reference components and the surrogates using a semi-detailed kinetic model. The predicted values are compared with experimental data. Sensitivity analysis shows that the lower reactivity of the aromatic species arises from the formation of resonantly stabilized radicals. These radicals are found to have a scavenging effect. The present study on premixed flows together with previous studies on nonpremixed flows show that the Aachen surrogate and surrogate C reproduce many aspects of premixed and nonpremixed combustion of jet fuels.

  3. GppFst: genomic posterior predictive simulations of FST and dXY for identifying outlier loci from population genomic data.

    PubMed

    Adams, Richard H; Schield, Drew R; Card, Daren C; Blackmon, Heath; Castoe, Todd A

    2016-12-23

    We introduce GppFst, an open source R package that generates posterior predictive distributions of FST and dx under a neutral coalescent model to identify putative targets of selection from genomic data.

  4. Predictors of Self and Surrogate Online Health Information Seeking in Family Caregivers to Cancer Survivors.

    PubMed

    Oh, Young Sam

    2015-01-01

    The purpose of this research is to investigate various factors predicting online health information seeking for themselves (self OHIS) and online health information seeking for others (surrogate OHIS) in family caregivers to cancer survivors. To address this purpose, this study applies the comprehensive model of information seeking as a theoretical framework for explaining the relationships between various predictors and two types of OHIS. The data used in this study were taken from the Health Information National Trends Survey 4. A total of 1,113 family caregivers were included in this study. Logistic regression analyses were conducted to examine the effects of predictors on Internet use for health information seeking. Caregivers' self and surrogate OHIS were commonly predicted by their self-rated health and attention to the Internet. However, age, race, and education were significantly associated with self OHIS only, while gender and marital status were significantly associated with surrogate OHIS only. These results suggest that family caregivers' self and surrogate OHIS are predicted by common factors, as well as predicted by different specific factors.

  5. 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.

  6. A Statistical Test for Identifying the Number of Creep Regimes When Using the Wilshire Equations for Creep Property Predictions

    NASA Astrophysics Data System (ADS)

    Evans, Mark

    2016-12-01

    A new parametric approach, termed the Wilshire equations, offers the realistic potential of being able to accurately lift materials operating at in-service conditions from accelerated test results lasting no more than 5000 hours. The success of this approach can be attributed to a well-defined linear relationship that appears to exist between various creep properties and a log transformation of the normalized stress. However, these linear trends are subject to discontinuities, the number of which appears to differ from material to material. These discontinuities have until now been (1) treated as abrupt in nature and (2) identified by eye from an inspection of simple graphical plots of the data. This article puts forward a statistical test for determining the correct number of discontinuities present within a creep data set and a method for allowing these discontinuities to occur more gradually, so that the methodology is more in line with the accepted view as to how creep mechanisms evolve with changing test conditions. These two developments are fully illustrated using creep data sets on two steel alloys. When these new procedures are applied to these steel alloys, not only do they produce more accurate and realistic looking long-term predictions of the minimum creep rate, but they also lead to different conclusions about the mechanisms determining the rates of creep from those originally put forward by Wilshire.

  7. 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…

  8. 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...

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Insights Into Atmospheric Aqueous Organic Chemistry Through Controlled Experiments with Cloud Water Surrogates

    NASA Astrophysics Data System (ADS)

    Turpin, B. J.; Ramos, A.; Kirkland, J. R.; Lim, Y. B.; Seitzinger, S.

    2011-12-01

    There is considerable laboratory and field-based evidence that chemical processing in clouds and wet aerosols alters organic composition and contributes to the formation of secondary organic aerosol (SOA). Single-compound laboratory experiments have played an important role in developing aqueous-phase chemical mechanisms that aid prediction of SOA formation through multiphase chemistry. In this work we conduct similar experiments with cloud/fog water surrogates, to 1) evaluate to what extent the previously studied chemistry is observed in these more realistic atmospheric waters, and 2) to identify additional atmospherically-relevant precursors and products that require further study. We used filtered Camden and Pinelands, NJ rainwater as a surrogate for cloud water. OH radical (~10-12 M) was formed by photolysis of hydrogen peroxide and samples were analyzed in real-time by electrospray ionization mass spectroscopy (ESI-MS). Discrete samples were also analyzed by ion chromatography (IC) and ESI-MS after IC separation. All experiments were performed in duplicate. Standards of glyoxal, methylglyoxal and glycolaldehyde and their major aqueous oxidation products were also analyzed, and control experiments performed. Decreases in the ion abundance of many positive mode compounds and increases in the ion abundance of many negative mode compounds (e.g., organic acids) suggest that precursors are predominantly aldehydes, organic peroxides and/or alcohols. Real-time ESI mass spectra were consistent with the expected loss of methylglyoxal and subsequent formation of pyruvate, glyoxylate, and oxalate. New insights regarding other potential precursors and products will be provided.

  14. 26 CFR 1.7874-2 - Surrogate foreign corporation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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 foreign... as a surrogate foreign corporation under section 7874(a)(2)(B). Paragraph (b) of this...

  15. 26 CFR 1.7874-2 - Surrogate foreign corporation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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 foreign... as a surrogate foreign corporation under section 7874(a)(2)(B). Paragraph (b) of this...

  16. 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.

  17. 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.

  18. 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.

  19. The effectiveness of surrogate taxa for the representation of biodiversity.

    PubMed

    Lewandowski, Adam S; Noss, Reed F; Parsons, David R

    2010-10-01

    Biodiversity is too complex to measure directly, so conservation planning must rely on surrogates to estimate the biodiversity of sites. The species richness of selected taxa is often used as a surrogate for the richness of other taxa. Surrogacy values of taxa have been evaluated in diverse contexts, yet broad trends in their effectiveness remain unclear. We reviewed published studies testing the ability of species richness of surrogate taxa to capture the richness of other (target) taxa. We stratified studies into two groups based on whether a complementarity approach (surrogates used to select a combination of sites that together maximize total species richness for the taxon) or a richness-hotspot approach (surrogates used to select sites containing the highest species richness for the taxon) was used. For each comparison of one surrogate taxon with one target, we used the following predictor variables: biome, spatial extent of study area, surrogate taxon, and target taxon. We developed a binary response variable based on whether the surrogate taxon provided better than random representation of the target taxon. For studies that used an evaluation approach that was not based on better than random representation of target taxa, we based the response variable on the interpretation of results in the original study. We performed a categorical regression to elucidate trends in the effectiveness of surrogate taxa with regard to each of the predictor variables. A surrogate was 25% more likely to be effective with a complementarity approach than with a hotspot approach. For hotspot-based approaches, biome, extent of study, surrogate taxon, and target taxon significantly influenced effectiveness of the surrogate. For complementarity-based approaches, biome, extent, and surrogate taxon significantly influenced effectiveness of the surrogate. For all surrogate evaluations, biome explained the greatest amount of variation in surrogate effectiveness. From most to least

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

    DOE PAGES

    Ratkiewicz, A.; Cizewski, J.A.; Pain, S.D.; ...

    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

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

    SciTech Connect

    Ratkiewicz, A.; Cizewski, J. A.; Pain, S.; Adekola, A. S.; Burke, J. T.; Casperson, R.J.; Fotiades, N.; McCleskey, M.; Burcher, S.; Shand, C. M.; Baugher, T.; Carpenter, M. P.; Devlin, M.; Escher, J. E.; Hardy, S.; Howard, M.; Hughes, R.; 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.

    2015-01-01

    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 rprocess 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,py) reaction at low energies was identified as a promising surrogate for the (n,y) reaction, as both reactions share many characteristics. We report on a program to validate (d,py) as a surrogate for (n,y) using 95Mo as a target. The experimental campaign includes direct measurements of the y-ray intensities from the decay of excited states populated in the 95Mo(n,y) and 95Mo(d,py) reactions.

  7. 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.

  8. Escherichia coli strain diversity: Selecting isolates for use as pathogen surrogates

    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...

  9. Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis

    PubMed Central

    Farrell, Damien; Jones, Gareth; Pirson, Christopher; Malone, Kerri; Rue-Albrecht, Kevin; Chubb, Anthony J.; Vordermeier, Martin

    2016-01-01

    The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4+ T cells requires prediction of peptide binding to MHC class-II, an obligatory prerequisite for T cell recognition. To comprehensively prioritise potential MHC-II-binding epitopes from Mycobacterium bovis, the agent of bTB and zoonotic TB in humans, we integrated three binding prediction methods with the M. bovisproteome using a subset of human HLA alleles to approximate the binding of epitope-containing peptides to the bovine MHC class II molecule BoLA-DRB3. Two parallel strategies were then applied to filter the resulting set of binders: identification of the top-scoring binders or clusters of binders. Our approach was tested experimentally by assessing the capacity of predicted promiscuous peptides to drive interferon-γ secretion from T cells of M. bovis infected cattle. Thus, 376 20-mer peptides, were synthesised (270 predicted epitopes, 94 random peptides with low predictive scores and 12 positive controls of known epitopes). The results of this validation demonstrated significant enrichment (>24 %) of promiscuously recognised peptides predicted in our selection strategies, compared with randomly selected peptides with low prediction scores. Our strategy offers a general approach to the identification of promiscuous epitopes tailored to target populations where there is limited knowledge of MHC allelic diversity. PMID:28348866

  10. Selecting focal species as surrogates for imperiled species using relative sensitivities derived from occupancy analysis

    USGS Publications Warehouse

    Silvano, Amy; Guyer, Craig; Steury, Todd; Grand, James B.

    2017-01-01

    Most imperiled species are rare or elusive and difficult to detect, which makes gathering data to estimate their response to habitat restoration a challenge. We used a repeatable, systematic method for selecting focal species using relative sensitivities derived from occupancy analysis. Our objective was to select suites of focal species that would be useful as surrogates when predicting effects of restoration of habitat characteristics preferred by imperiled species. We developed 27 habitat profiles that represent general habitat relationships for 118 imperiled species. We identified 23 regularly encountered species that were sensitive to important aspects of those profiles. We validated our approach by examining the correlation between estimated probabilities of occupancy for species of concern and focal species selected using our method. Occupancy rates of focal species were more related to occupancy rates of imperiled species when they were sensitive to more of the parameters appearing in profiles of imperiled species. We suggest that this approach can be an effective means of predicting responses by imperiled species to proposed management actions. However, adequate monitoring will be required to determine the effectiveness of using focal species to guide management actions.

  11. Estimation of Model's Marginal likelihood Using Adaptive Sparse Grid Surrogates in Bayesian Model Averaging

    NASA Astrophysics Data System (ADS)

    Zeng, X.

    2015-12-01

    A large number of model executions are required to obtain alternative conceptual models' predictions and their posterior probabilities in Bayesian model averaging (BMA). The posterior model probability is estimated through models' marginal likelihood and prior probability. The heavy computation burden hinders the implementation of BMA prediction, especially for the elaborated marginal likelihood estimator. For overcoming the computation burden of BMA, an adaptive sparse grid (SG) stochastic collocation method is used to build surrogates for alternative conceptual models through the numerical experiment of a synthetical groundwater model. BMA predictions depend on model posterior weights (or marginal likelihoods), and this study also evaluated four marginal likelihood estimators, including arithmetic mean estimator (AME), harmonic mean estimator (HME), stabilized harmonic mean estimator (SHME), and thermodynamic integration estimator (TIE). The results demonstrate that TIE is accurate in estimating conceptual models' marginal likelihoods. The BMA-TIE has better predictive performance than other BMA predictions. TIE has high stability for estimating conceptual model's marginal likelihood. The repeated estimated conceptual model's marginal likelihoods by TIE have significant less variability than that estimated by other estimators. In addition, the SG surrogates are efficient to facilitate BMA predictions, especially for BMA-TIE. The number of model executions needed for building surrogates is 4.13%, 6.89%, 3.44%, and 0.43% of the required model executions of BMA-AME, BMA-HME, BMA-SHME, and BMA-TIE, respectively.

  12. Surrogates for macrofungi and mosses in reservation planning.

    PubMed

    McMullan-Fisher, Sapphire J M; Kirkpatrick, Jamie B; May, Tom W; Pharo, Emma J

    2010-06-01

    Our knowledge of cryptogam taxonomy and species distributions is currently too poor to directly plan for their conservation. We used inventory data from four distinct vegetation types, near Hobart Tasmania, to address the proposition that vegetation type, vascular plant taxon composition, and environmental variables can act as surrogates for mosses and macrofungi in reservation planning. The four vegetation types proved distinct in their taxon composition for all macrofungi, mosses, and vascular plants. We tested the strength of the relationships between the composition of cryptogam taxonomic groups and vascular plant composition and between the environmental variables and canopy cover. Taxon composition of woody vascular plants and vascular plants was the best predictor of the taxon composition of mosses and macrofungi. Combinations of environmental variables and canopy cover were also strong predictors of the taxon composition of mosses and macrofungi. We used an optimization routine for vascular plant taxa and woody plant species and determined the representation of cryptogam taxa in these selections. We identified sites with approximately 10% and 30% of the greatest proportions of vascular plants and woody vascular plants and calculated representation of mosses and macrofungi at these sites. We compared the results of these site selections with random site selections and random selections stratified by vegetation type. Random selection of sites by vegetation type generally captured more cryptogams than site selection by vascular plants at the 10% level. Vascular plant and woody plant taxon composition, vegetation type, and environmental and structural characteristics, all showed promise as surrogates for capturing common cryptogams in reserve systems.

  13. 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.

  14. Identifying High-Risk Chronic Lymphocytic Leukemia: A Pathogenesis-Oriented Appraisal of Prognostic and Predictive Factors in Patients Treated with Chemotherapy with or without Immunotherapy

    PubMed Central

    Martinelli, Sara; Cuneo, Antonio; Formigaro, Luca; Cavallari, Maurizio; Lista, Enrico; Quaglia, Francesca Maria; Ciccone, Maria; Bardi, Antonella; Volta, Eleonora; Tammiso, Elisa; Saccenti, Elena; Sofritti, Olga; Daghia, Giulia; Negrini, Massimo; Dabusti, Melissa; Tomasi, Paolo; Moretti, Sabrina; Cavazzini, Francesco; Rigolin, Gian Matteo

    2016-01-01

    Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment are important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers. Each biomarker was analysed in terms of reproducibility across the different studies with respect to its impact on time to first treatment (TTFT), progression free survival (PFS), overall survival (OS) and response to treatment. We were able to identify the following biomarkers as the most reliable in guiding risk stratification in the daily clinical practice: 17p-/TP53 mutations, IGHV unmutated configuration, short telomeres and 11q-. However, the method for measuring telomere length was not validated yet and 11q- was predictive of inferior OS only in those patients who did not receive FCR-like combinations. Stage and lymphocytosis were predictive of shorter TTFT and age, high serum thymidine kinase levels and poor performance status were predictive of shorter OS. Using our criteria no parameter was found to independently predict for inferior response to treatment. PMID:27872727

  15. 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

  16. 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; Dettman, Heather D.; Franz, James A.; Huber, Marcia L.; Natarajan, Mani; Pitz, William J.; Ratcliff, Matthew A.; Wright, Ken

    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 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 well-characterized, 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

  17. Two-dimensional surrogate contact modeling for computationally efficient dynamic simulation of total knee replacements.

    PubMed

    Lin, Yi-Chung; Haftka, Raphael T; Queipo, Nestor V; Fregly, Benjamin J

    2009-04-01

    Computational speed is a major limiting factor for performing design sensitivity and optimization studies of total knee replacements. Much of this limitation arises from extensive geometry calculations required by contact analyses. This study presents a novel surrogate contact modeling approach to address this limitation. The approach involves fitting contact forces from a computationally expensive contact model (e.g., a finite element model) as a function of the relative pose between the contacting bodies. Because contact forces are much more sensitive to displacements in some directions than others, standard surrogate sampling and modeling techniques do not work well, necessitating the development of special techniques for contact problems. We present a computational evaluation and practical application of the approach using dynamic wear simulation of a total knee replacement constrained to planar motion in a Stanmore machine. The sample points needed for surrogate model fitting were generated by an elastic foundation (EF) contact model. For the computational evaluation, we performed nine different dynamic wear simulations with both the surrogate contact model and the EF contact model. In all cases, the surrogate contact model accurately reproduced the contact force, motion, and wear volume results from the EF model, with computation time being reduced from 13 min to 13 s. For the practical application, we performed a series of Monte Carlo analyses to determine the sensitivity of predicted wear volume to Stanmore machine setup issues. Wear volume was highly sensitive to small variations in motion and load inputs, especially femoral flexion angle, but not to small variations in component placements. Computational speed was reduced from an estimated 230 h to 4 h per analysis. Surrogate contact modeling can significantly improve the computational speed of dynamic contact and wear simulations of total knee replacements and is appropriate for use in design sensitivity

  18. Approximating nonequilibrium processes using a collection of surrogate diffusion models

    NASA Astrophysics Data System (ADS)

    Calderon, Christopher P.; Chelli, Riccardo

    2008-04-01

    The surrogate process approximation (SPA) is applied to model the nonequilibrium dynamics of a reaction coordinate (RC) associated with the unfolding and refolding processes of a deca-alanine peptide at 300K. The RC dynamics, which correspond to the evolution of the end-to-end distance of the polypeptide, are produced by steered molecular dynamics (SMD) simulations and approximated using overdamped diffusion models. We show that the collection of (estimated) SPA models contain structural information "orthogonal" to the RC monitored in this study. Functional data analysis ideas are used to correlate functions associated with the fitted SPA models with the work done on the system in SMD simulations. It is demonstrated that the shape of the nonequilibrium work distributions for the unfolding and refolding processes of deca-alanine can be predicted with functional data analysis ideas using a relatively small number of simulated SMD paths for calibrating the SPA diffusion models.

  19. Carotid Intima-Media Thickness as Surrogate for and Predictor of CVD.

    PubMed

    Polak, Joseph F; O'Leary, Daniel H

    2016-09-01

    Carotid artery intima-media thickness (IMT) is a noninvasive measurement of the artery wall thickness, inclusive of atherosclerotic plaque, obtained using ultrasound imaging. In the MESA (Multi-Ethnic Study of Atherosclerosis) study, IMT measurements are used as a surrogate for subclinical cardiovascular disease and as a variable predictive of cardiovascular events. IMT measurements of the common carotid artery are available in more than 99% of the MESA population and are predictive of cardiovascular events. More importantly, IMT and plaque thickness measurements made in the internal carotid artery and carotid bulb are also available in more than 98% of the population and are also strongly predictive of cardiovascular events. This article reviews the techniques used to obtain the MESA IMT values, compares them to those made in other epidemiological studies, and summarizes how they have been used in the MESA study as both surrogates for and predictors of cardiovascular disease.

  20. Voices of African American, Caucasian, and Hispanic Surrogates on the Burdens of End-of-Life Decision Making

    PubMed Central

    Beyth, Rebecca J.; Ford, Marvella E.; McCullough, Laurence B.

    2008-01-01

    Background End-of-life decisions are frequently made by patients’ surrogates. Race and ethnicity may affect such decision making. Few studies have described how different racial/ethnic groups experience end-of-life surrogate decision making. Objectives To describe the self-reported experience the self-reported experience of African-American, Caucasian, and Hispanic surrogate decision makers of seriously ill patients and to examine the relationship of race, ethnicity, and culture to that experience. Design Purposive sample to include racial/ethnic minorities in a qualitative study using focus group interviews. Participants The participants of the study were 44 experienced, mostly female, surrogate decision makers for older veterans. Approach Transcripts were qualitatively analyzed to identify major themes, with particular attention to themes that might be unique to each of the three groups. Results The experience of burden of end-of-life decision making was similar in all three groups. This burden in its medical, personal, and familial dimensions is compounded by uncertainty about prognosis and the patient’s preferences. Racial/ethnic variations of responses to this burden concerned the physician–family relationship, religion and faith, and past experiences with race/ethnicity concordant versus non-concordant physicians. Conclusions Regardless of race/ethnicity, surrogates for seriously ill patients appeared to experience increased significant, multidimensional burdens of decision making under conditions of uncertainty about a patient’s preferences. This aspect of the burden of surrogate decision making may not be fully appreciated by physicians. Physicians should identify and be especially attentive to strategies used by surrogates, which may vary by race/ethnicity, to reduce the uncertainty about a patient’s preferences and thus the burden of surrogate decision making to assist them in this difficult process. PMID:18172738

  1. Identifying a Physical Indicator of Suicide Risk: Non-Suicidal Self-Injury Scars Predict Suicidal Ideation and Suicide Attempts

    PubMed Central

    Burke, Taylor A.; Hamilton, Jessica L.; Cohen, Jonah N.; Stange, Jonathan P.; Alloy, Lauren B.

    2015-01-01

    Background Suicide risk is challenging to quantify due to reliance on self-report, which is limited by individuals’ lack of insight and the desire to conceal such intentions. Non-suicidal self-injury (NSSI) is one of the most robust predictors of suicidal ideation (SI) and suicide attempts (SA). Although NSSI often leads to permanent scarring, which can be assessed by objective physical examination, no research has examined whether scarring denotes tangible risk for SI and SA. The present study examined whether NSSI scar presence and number predict current SI and SA history. Further, we examined whether brooding would exacerbate the effects of NSSI scarring on SI or SA. Methods Young adults (N = 231; M = 21.24 years; 78% female) completed self-report questionnaires assessing SA history, frequency of NSSI, presence/number of NSSI scars, brooding, current depressive symptoms, and SI. Results NSSI scar presence and number predicted current SI and SA history after controlling for current depressive symptoms. Moreover, scar presence and number predicted current SI over and above the effects of SA history and NSSI frequency, method, and medical severity. Further, NSSI scar presence and number predicted SI more strongly among individuals with greater levels of brooding than among individuals with lower levels of brooding. Conclusions The presence and number of NSSI scars are objective physical indicators of risk for SI and SAs. Brooding may further heighten the risk of SI for individuals bearing NSSI scars. PMID:26773994

  2. 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

  3. Surrogate Markers of Abdominal Aortic Aneurysm Progression.

    PubMed

    Wanhainen, Anders; Mani, Kevin; Golledge, Jonathan

    2016-02-01

    The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Standardized reporting of reproducible methods of measuring AAA diameter is essential. Newer imaging assessments, such as volume measurements, biomechanical analyses, and functional and molecular imaging, as well as circulating biomarkers, have potential to add important information about AAA progression. Currently, however, there is insufficient evidence to recommend their routine use in clinical practice.

  4. Surrogate matrix: opportunities and challenges for tissue sample analysis.

    PubMed

    Ho, Stacy; Gao, Hong

    2015-09-23

    Often there is limited availability of matching tissue matrix and/or the analyte may occur endogenously in the target tissue. Surrogate matrix provides an option for quantitation of drug, metabolite(s) and biomarker(s) in these circumstances. However, the use of a surrogate matrix also presents challenges. This paper summarizes and discusses the challenges of selecting a proper surrogate, validating the suitability of the surrogate and establishing a surrogate tissue method using the fit-for-purpose approach. This paper also systematically reviews the current practices for evaluating key parameters of a surrogate tissue assay, including sensitivity, specificity, selectivity, interference, precision, accuracy, recovery, matrix effects and stability. Considerations and suggestions are provided for dealing with such challenges during method establishment and tissue sample analysis.

  5. Family matters: effects of birth order, culture, and family dynamics on surrogate decision-making.

    PubMed

    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 Affairs 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 ± 14, and 29% were African American, 26% were white, 26% were Asian or 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 three overarching categories: communication (unspoken expectations and discussion of death as taboo), emotion (emotional stress and feelings of loneliness), and conflict (family conflict and 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.

  6. Implementation of Predictive Data Mining Techniques for Identifying Risk Factors of Early AVF Failure in Hemodialysis Patients

    PubMed Central

    Rezapour, Mohammad; Khavanin Zadeh, Morteza; Sepehri, Mohammad Mehdi

    2013-01-01

    Arteriovenous fistula (AVF) is an important vascular access for hemodialysis (HD) treatment but has 20–60% rate of early failure. Detecting association between patient's parameters and early AVF failure is important for reducing its prevalence and relevant costs. Also predicting incidence of this complication in new patients is a beneficial controlling procedure. Patient safety and preservation of early AVF failure is the ultimate goal. Our research society is Hasheminejad Kidney Center (HKC) of Tehran, which is one of Iran's largest renal hospitals. We analyzed data of 193 HD patients using supervised techniques of data mining approach. There were 137 male (70.98%) and 56 female (29.02%) patients introduced into this study. The average of age for all the patients was 53.87 ± 17.47 years. Twenty eight patients had smoked and the number of diabetic patients and nondiabetics was 87 and 106, respectively. A significant relationship was found between “diabetes mellitus,” “smoking,” and “hypertension” with early AVF failure in this study. We have found that these mentioned risk factors have important roles in outcome of vascular surgery, versus other parameters such as “age.” Then we predicted this complication in future AVF surgeries and evaluated our designed prediction methods with accuracy rates of 61.66%–75.13%. PMID:23861725

  7. 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

  8. An interdisciplinary effort to identify source parameters for models that predict eruption cloud transport and dispersion for aviation safety

    NASA Astrophysics Data System (ADS)

    Mastin, L. G.; Guffanti, M.; Servranckx, R.

    2007-12-01

    During recent decades, dozens of commercial and military jets have inadvertently flown through volcanic ash clouds downwind from eruptions. These encounters have caused up to tens of millions of dollars (U.S.) in damage to each jet; a few nearly crashed when ceramitized deposits of ingested ash caused engines to fail. In order to avoid such encounters, the International Civil Aviation Organization (ICAO) has established Volcano Ash Advisory Centers (VAACs) throughout the world to detect eruptions using satellite imagery and to notify aircraft. VAACs also predict the paths of ash clouds using atmospheric transport models, using information on volcanic plume height, the mass rate of tephra entering the atmosphere, the vertical distribution of tephra, eruption duration, and grain size distribution as input parameters. In some cases, these "source parameters" must be estimated during an ongoing eruption with few or no observational constraints. In other cases, satellite or ground-based observations obtained during an eruption constrain plume height, umbrella cloud dimensions or growth rate, and other properties, allowing VAACs to refine source parameters, re-run models, and improve predictions. ICAOs International Airways Volcano Watch Operations Group has recommended improving methods of estimating eruption source parameters as a key step towards improving predictions of volcanic ash transport and dispersion. In the spring of 2007, members of the USGS; NOAA; the Universities of Michigan, Alaska, Pisa, and South Florida; the Air Force Weather Agency; the Australian Bureau of Meteorology; and the Canadian Meteorological Centre began an interagency effort to establish constraints on eruption source parameters. This effort has involved (1) assigning default parameters to volcanoes based on magma and eruption type; (2) improving characterization of total grain-size distribution and the size distribution in distal ash clouds; (3) refining empirical and model

  9. 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.

  10. Comments on Surrogates measures and consistent surrogates (by Tyler VanderWeele)

    DTIC Science & Technology

    2013-03-01

    indirect effect,” “ principled strata,” “proportion-mediated,” and perhaps others? My second question was: If we take the negation of the “surrogate paradox...Angeles, Computer Science Department, CA. Forthcoming, Econometric Theory, special issue on Haavelmo Centennial. Pearl, J. and Bareinboim, E. (2011

  11. 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.

  12. Surrogate models of gravitational waveforms from numerical relativity simulations of precessing binary black hole mergers

    NASA Astrophysics Data System (ADS)

    Blackman, Jonathan; Field, Scott; Galley, Chad; Hemberger, Daniel; Scheel, Mark; Schmidt, Patricia; Smith, Rory

    2017-01-01

    Extracting astrophysical parameters and testing general relativity from gravitational wave observations of binary black hole mergers requires high-fidelity signal predictions. The effective-one-body model and phenomenological waveform models have been shown to work well for a subset of the possible parameter space. They could be insufficiently accurate for estimating the parameters of a loud gravitational wave detection in other regions of the parameter space. Numerical relativity (NR) surrogate models attempt to rapidly and accurately interpolate the waveforms from a set of NR simulations over a subset of parameter space. Using the Spectral Einstein Code (SpEC), we have built NR surrogate models for precessing binaries with a restricted spin direction on the smaller black hole, and are actively working on extending this to the full 7d parameter space of non-eccentric binaries. The NR surrogate models typically perform an order of magnitude better than other waveform models when compared to NR waveforms which were not included in the surrogate training set, and can be used in gravitational wave parameter estimation.

  13. 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,…

  14. 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

  15. 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.

  16. Priority wetland invertebrates as conservation surrogates.

    PubMed

    Ormerod, S J; Durance, Isabelle; Terrier, Aurelie; Swanson, Alisa M

    2010-04-01

    Invertebrates are important functionally in most ecosystems, but seldom appraised as surrogate indicators of biological diversity. Priority species might be good candidates; thus, here we evaluated whether three freshwater invertebrates listed in the U.K. Biodiversity Action Plan indicated the richness, composition, and conservation importance of associated wetland organisms as defined respectively by their alpha diversity, beta diversity, and threat status. Sites occupied by each of the gastropods Segmentina nitida, Anisus vorticulus, and Valvata macrostoma had greater species richness of gastropods and greater conservation importance than other sites. Each also characterized species assemblages associated with significant variations between locations in alpha or beta diversity among other mollusks and aquatic macrophytes. Because of their distinct resource requirements, conserving the three priority species extended the range of wetland types under management for nature conservation by 18% and the associated gastropod niche-space by around 33%. Although nonpriority species indicated variations in richness, composition, and conservation importance among other organisms as effectively as priority species, none characterized such a wide range of high-quality wetland types. We conclude that priority invertebrates are no more effective than nonpriority species as indicators of alpha and beta diversity or conservation importance among associated organisms. Nevertheless, conserving priority species can extend the array of distinct environments that are protected for their specialized biodiversity and environmental quality. We suggest that this is a key role for priority species and conservation surrogates more generally, and, on our evidence, can best be delivered through multiple species with contrasting habitat requirements.

  17. 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.

  18. A sensitivity analysis of RNA folding nearest neighbor parameters identifies a subset of free energy parameters with the greatest impact on RNA secondary structure prediction.

    PubMed

    Zuber, Jeffrey; Sun, Hongying; Zhang, Xiaoju; McFadyen, Iain; Mathews, David H

    2017-03-15

    Nearest neighbor parameters for estimating the folding energy changes of RNA secondary structures are used in structure prediction and analysis. Despite their widespread application, a comprehensive analysis of the impact of each parameter on the precision of calculations had not been conducted. To identify the parameters with greatest impact, a sensitivity analysis was performed on the 291 parameters that compose the 2004 version of the free energy nearest neighbor rules. Perturbed parameter sets were generated by perturbing each parameter independently. Then the effect of each individual parameter change on predicted base-pair probabilities and secondary structures as compared to the standard parameter set was observed for a set of sequences including structured ncRNA, mRNA and randomized sequences. The results identify for the first time the parameters with the greatest impact on secondary structure prediction, and the subset which should be prioritized for further study in order to improve the precision of structure prediction. In particular, bulge loop initiation, multibranch loop initiation, AU/GU internal loop closure and AU/GU helix end parameters were particularly important. An analysis of parameter usage during folding free energy calculations of stochastic samples of secondary structures revealed a correlation between parameter usage and impact on structure prediction precision.

  19. 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

  20. 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.

  1. Predicting the Pathogenic Potential of BRCA1 and BRCA2 Gene Variants Identified in Clinical Genetic Testing

    PubMed Central

    Brookes, Clare; Lai, Stella; Doherty, Elaine; Love, Donald R.

    2015-01-01

    Objectives: Missense variants are very commonly detected when screening for mutations in the BRCA1 and BRCA2 genes. Pathogenic mutations in the BRCA1 and BRCA2 genes lead to an increased risk of developing breast, ovarian, prostate and/or pancreatic cancer. This study aimed to assess the predictive capability of in silico programmes and mutation databases in assisting diagnostic laboratories to determine the pathogenicity of sequence-detectable mutations. Methods: Between July 2011 and April 2013, an analysis was undertaken of 13 missense BRCA gene variants that had been detected in patients referred to the Genetic Health Services New Zealand (Northern Hub) for BRCA gene analysis. The analysis involved the use of 13 in silico protein prediction programmes, two in silico transcript analysis programmes and the examination of three BRCA gene databases. Results: In most of the variants, the analysis showed different in silico interpretations. This illustrates the interpretation challenges faced by diagnostic laboratories. Conclusion: Unfortunately, when using online mutation databases and carrying out in silico analyses, there is significant discordance in the classification of some missense variants in the BRCA genes. This discordance leads to complexities in interpreting and reporting these variants in a clinical context. The authors have developed a simple procedure for analysing variants; however, those of unknown significance largely remain unknown. As a consequence, the clinical value of some reports may be negligible. PMID:26052455

  2. Which Anthropometric Indicators Identify a Pregnant Woman as Acutely Malnourished and Predict Adverse Birth Outcomes in the Humanitarian Context?

    PubMed Central

    Ververs, Mija-tesse; Antierens, Annick; Sackl, Anita; Staderini, Nelly; Captier, Valerie

    2013-01-01

    Currently there is no consensus on how to identify pregnant women as acutely malnourished and when to enroll them in nutritional programmes. Médecins Sans Frontières Switzerland undertook a literature review with the purpose of determining values of anthropometric indicators for acute malnutrition that are associated with adverse birth outcomes (such as low birth weight (LBW)), pre-term birth and intra-uterine growth retardation (IUGR). A literature search in PUBMED was done covering 1 January 1995 to 12 September 2012 with the key terms maternal anthropometry and pregnancy. The review focused on the humanitarian context. Mid-upper-arm circumference (MUAC) was identified as the preferential indicator of choice because of its relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings) and it does not require prior knowledge of gestational age. The MUAC values below which most adverse effects were identified were <22 and <23 cm. A conservative cut-off of <23 cm is recommended to include most pregnant women at risk of LBW for their infants in the African and Asian contexts. PMID:23787989

  3. 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

  4. Validation of ground-and-formed beef jerky processes using commercial lactic acid bacteria starter cultures as pathogen surrogates.

    PubMed

    Borowski, Alena G; Ingham, Steven C; Ingham, Barbara H

    2009-06-01

    Beef jerky has been linked to multiple outbreaks of salmonellosis and Escherichia coli O157:H7 infection over the past 40 years. With increasing government scrutiny of jerky-making process lethality, a simple method by which processors can easily validate the lethality of their ground-and-formed beef jerky process against Salmonella' and E. coli O157:H7 is greatly needed. Previous research with whole-muscle beef jerky indicated that commercial lactic acid bacteria (LAB) may be more heat resistant than Salmonella and E. coli O157:H7, suggesting the potential use of LAB as pathogen surrogates. Of six commercial LAB-containing cultures evaluated for heat resistance in ground-and-formed beef jerky, Saga 200 (Pediococcus spp.) and Biosource (Pediococcus acidilactici) were identified as consistently more heat resistant than Salmonella and E. coli O157:H7. Six representative ground-and-formed beef jerky commercial processes, differing widely in lethality, were used to identify an appropriate level of LAB reduction that would consistently indicate a process sufficiently lethal (> or = 5.0-log reduction) for Salmonella and E. coli O157:H7. Both Saga 200 and Biosource consistently predicted adequate process lethality with a criterion of > or = 5.0-1og reduction of LAB. When either LAB decreased by > or = 5.0 log CFU, processes were sufficiently lethal against Salmonella and E. coli O157:H7 in 100% of samples (n=39 and 40, respectively). Use of LAB as pathogen surrogates for ground-and-formed beef jerky process validation was fieldtested by three small meat processors, who found this technique easy to use for process validation.

  5. 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

  6. 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.

  7. Exon-level expression analyses identify MYCN and NTRK1 as major determinants of alternative exon usage and robustly predict primary neuroblastoma outcome

    PubMed Central

    Schramm, A; Schowe, B; Fielitz, K; Heilmann, M; Martin, M; Marschall, T; Köster, J; Vandesompele, J; Vermeulen, J; de Preter, K; Koster, J; Versteeg, R; Noguera, R; Speleman, F; Rahmann, S; Eggert, A; Morik, K; Schulte, J H

    2012-01-01

    Background: Using mRNA expression-derived signatures as predictors of individual patient outcome has been a goal ever since the introduction of microarrays. Here, we addressed whether analyses of tumour mRNA at the exon level can improve on the predictive power and classification accuracy of gene-based expression profiles using neuroblastoma as a model. Methods: In a patient cohort comprising 113 primary neuroblastoma specimens expression profiling using exon-level analyses was performed to define predictive signatures using various machine-learning techniques. Alternative transcript use was calculated from relative exon expression. Validation of alternative transcripts was achieved using qPCR- and cell-based approaches. Results: Both predictors derived from the gene or the exon levels resulted in prediction accuracies >80% for both event-free and overall survival and proved as independent prognostic markers in multivariate analyses. Alternative transcript use was most prominently linked to the amplification status of the MYCN oncogene, expression of the TrkA/NTRK1 neurotrophin receptor and survival. Conclusion: As exon level-based prediction yields comparable, but not significantly better, prediction accuracy than gene expression-based predictors, gene-based assays seem to be sufficiently precise for predicting outcome of neuroblastoma patients. However, exon-level analyses provide added knowledge by identifying alternative transcript use, which should deepen the understanding of neuroblastoma biology. PMID:23047593

  8. 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.

  9. 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.

  10. Naphthenic acids and surrogate naphthenic acids in methanogenic microcosms.

    PubMed

    Holowenko, F M; Mackinnon, M D; Fedorak, P M

    2001-08-01

    Naphthenic acids (NAs) are a complex mixture of naturally occurring acyclic and cyclic aliphatic carboxylic acids in petroleum. In the Athabasca oil sands. NAs have been identified as the largest component of dissolved organic matter in the tailings waters from oils sands extraction processes. They are the major contributor to the acute toxicity of the fine tailings wastewaters at the oil sands extraction plants in northeastern Alberta, Canada. In this study, three sources of NAs were studied, including commercially available NAs, those extracted from oil sands process-affected waters, and individual naphthenic-like surrogate compounds. Analysis by gas chromatography-mass spectrometry demonstrated differences between the commercial and extracted NAs. The NAs derived from the process-affected waters showed a short-term inhibition of methanogenesis from H2 or acetate, but with time the populations resumed methane production. It has been postulated that microbial metabolism of the carboxylated side chains of NAs would lead to methane production. The two NA mixtures failed to stimulate methanogenesis in microcosms that contained either oil sands fine tailings or domestic sewage sludge. However, in microcosms with sewage sludge, methanogenesis was stimulated by some surrogate NAs including 3-cyclohexylpropanoic acid at 400-800 mg/L, 5-cyclohexylpentanoic acid at 200 mg/L or 6-phenylhexanoic acid at 200 and 400 mg/L. When added at 200 mg/L to methanogenic microcosms containing fine tailings, 3-cyclohexylpropanoic and 4-cyclohexylbutanoic acids produced methane yields that suggested mineralization of the side chain and the ring.

  11. Prediction of magnetic orientation in driver gas associated -Bz events. [in interplanetary medium observed at earth when solar source is identified

    NASA Technical Reports Server (NTRS)

    Hoeksema, J. T.; Zhao, Xuepu

    1992-01-01

    The source regions of five strong -Bz events detected at 1 AU for which solar sources were identified by Tang et al. (1989) and Tsurutani et al. (1992) are investigated in order to determine whether the magnetic orientation of driver gas in the interplanetary medium observed at the earth can be predicted when its solar source is identified. Three -Bz events were traced to flare-associated coronal mass ejections (CMEs), one to an eruptive prominence associated CME, and one to three possible solar sources. The computed magnetic orientations at the candidate 'release height' (the height where the front of a CME ceases to accelerate) above the flare sites associated with CMEs show the existence of the expected southward field component. It is concluded that the magnetic orientation in flare-associated CME generated driver gas may be predictable.

  12. Predictive abilities of the STOP-Bang and Epworth Sleepiness Scale in identifying sleep clinic patients at high risk for obstructive sleep apnea.

    PubMed

    Vana, Kimberly D; Silva, Graciela E; Goldberg, Rochelle

    2013-02-01

    This study compared the predictive abilities of the STOP-Bang and Epworth Sleepiness Scale (ESS) for screening sleep clinic patients for obstructive sleep apnea (OSA) and sleep-disordered breathing (SDB). Forty-seven new adult patients without previous diagnoses of OSA or SDB were administered the STOP-Bang and ESS and were assigned to OSA or SDB risk groups based on their scores. STOP-Bang responses were scored with two Body Mass Index cut points of 35 and 30 kg/m(2) (SB35 and SB30). The tools' predictive abilities were determined by comparing patients' predicted OSA and SDB risks to their polysomnographic results. The SB30 correctly identified more patients with OSA and SDB than the ESS alone. The ESS had the highest specificity for OSA and SDB.

  13. 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

  14. 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.

  15. 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…

  16. 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) ...

  17. 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...

  18. Incorporating approximation error in surrogate based Bayesian inversion

    NASA Astrophysics Data System (ADS)

    Zhang, J.; Zeng, L.; Li, W.; Wu, L.

    2015-12-01

    There are increasing interests in applying surrogates for inverse Bayesian modeling to reduce repetitive evaluations of original model. In this way, the computational cost is expected to be saved. However, the approximation error of surrogate model is usually overlooked. This is partly because that it is difficult to evaluate the approximation error for many surrogates. Previous studies have shown that, the direct combination of surrogates and Bayesian methods (e.g., Markov Chain Monte Carlo, MCMC) may lead to biased estimations when the surrogate cannot emulate the highly nonlinear original system. This problem can be alleviated by implementing MCMC in a two-stage manner. However, the computational cost is still high since a relatively large number of original model simulations are required. In this study, we illustrate the importance of incorporating approximation error in inverse Bayesian modeling. Gaussian process (GP) is chosen to construct the surrogate for its convenience in approximation error evaluation. Numerical cases of Bayesian experimental design and parameter estimation for contaminant source identification are used to illustrate this idea. It is shown that, once the surrogate approximation error is well incorporated into Bayesian framework, promising results can be obtained even when the surrogate is directly used, and no further original model simulations are required.

  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.

  20. Effect prediction of identified SNPs linked to fruit quality and chilling injury in peach [Prunus persica (L.) Batsch].

    PubMed

    Martínez-García, Pedro J; Fresnedo-Ramírez, Jonathan; Parfitt, Dan E; Gradziel, Thomas M; Crisosto, Carlos H

    2013-01-01

    Single nucleotide polymorphisms (SNPs) are a fundamental source of genomic variation. Large SNP panels have been developed for Prunus species. Fruit quality traits are essential peach breeding program objectives since they determine consumer acceptance, fruit consumption, industry trends and cultivar adoption. For many cultivars, these traits are negatively impacted by cold storage, used to extend fruit market life. The major symptoms of chilling injury are lack of flavor, off flavor, mealiness, flesh browning, and flesh bleeding. A set of 1,109 SNPs was mapped previously and 67 were linked with these complex traits. The prediction of the effects associated with these SNPs on downstream products from the 'peach v1.0' genome sequence was carried out. A total of 2,163 effects were detected, 282 effects (non-synonymous, synonymous or stop codon gained) were located in exonic regions (13.04 %) and 294 placed in intronic regions (13.59 %). An extended list of genes and proteins that could be related to these traits was developed. Two SNP markers that explain a high percentage of the observed phenotypic variance, UCD_SNP_1084 and UCD_SNP_46, are associated with zinc finger (C3HC4-type RING finger) family protein and AOX1A (alternative oxidase 1a) protein groups, respectively. In addition, phenotypic variation suggests that the observed polymorphism for SNP UCD_SNP_1084 [A/G] mutation could be a candidate quantitative trait nucleotide affecting quantitative trait loci for mealiness. The interaction and expression of affected proteins could explain the variation observed in each individual and facilitate understanding of gene regulatory networks for fruit quality traits in peach.

  1. Sheet metal forming optimization by using surrogate modeling techniques

    NASA Astrophysics Data System (ADS)

    Wang, Hu; Ye, Fan; Chen, Lei; Li, Enying

    2017-01-01

    Surrogate assisted optimization has been widely applied in sheet metal forming design due to its efficiency. Therefore, to improve the efficiency of design and reduce the product development cycle, it is important for scholars and engineers to have some insight into the performance of each surrogate assisted optimization method and make them more flexible practically. For this purpose, the state-of-the-art surrogate assisted optimizations are investigated. Furthermore, in view of the bottleneck and development of the surrogate assisted optimization and sheet metal forming design, some important issues on the surrogate assisted optimization in support of the sheet metal forming design are analyzed and discussed, involving the description of the sheet metal forming design, off-line and online sampling strategies, space mapping algorithm, high dimensional problems, robust design, some challenges and potential feasible methods. Generally, this paper provides insightful observations into the performance and potential development of these methods in sheet metal forming design.

  2. RICTOR amplification identifies a subgroup in small cell lung cancer and predicts response to drugs targeting mTOR

    PubMed Central

    Sakre, Nneha; Wildey, Gary; Behtaj, Mohadese; Kresak, Adam; Yang, Michael; Fu, Pingfu; Dowlati, Afshin

    2017-01-01

    Small cell lung cancer (SCLC) is an aggressive cancer that represents ~15% of all lung cancers. Currently there are no targeted therapies to treat SCLC. Our genomic analysis of a metastatic SCLC cohort identified recurrent RICTOR amplification. Here, we examine the translational potential of this observation. RICTOR was the most frequently amplified gene observed (~14% patients), and co-amplified with FGF10 and IL7R on chromosome 5p13. RICTOR copy number variation correlated with RICTOR protein expression in SCLC cells. In parallel, cells with RICTOR copy number (CN) gain showed increased sensitivity to three mTOR inhibitors, AZD8055, AZD2014 and INK128 in cell growth assays, with AZD2014 demonstrating the best inhibition of downstream signaling. SCLC cells with RICTOR CN gain also migrated more rapidly in chemotaxis and scratch wound assays and were again more sensitive to mTOR inhibitors. The overall survival in SCLC patients with RICTOR amplification was significantly decreased (p = 0.021). Taken together, our results suggest that SCLC patients with RICTOR amplification may constitute a clinically important subgroup because of their potential response to mTORC1/2 inhibitors. PMID:27863413

  3. Crack Identification of Cantilever Plates Based on a Kriging Surrogate Model.

    PubMed

    Gao, Haiyang; Guo, Xinglin; Ouyang, Huajiang; Han, Fang

    2013-10-01

    This work presents an effective method to identify the tip locations of an internal crack in cantilever plates based on a Kriging surrogate model. Samples of varying crack parameters (tip locations) and their corresponding root mean square (RMS) of random responses are used to construct the initial Kriging surrogate model. Moreover, the pseudo excitation method (PEM) is employed to speed up the spectral analysis. For identifying crack parameters based on the constructed Kriging model, a robust stochastic particle swarm optimization (SPSO) algorithm is adopted for enhancing the global searching ability. To improve the accuracy of the surrogate model without using extensive samples, a small number of samples are first used. Then an optimal point-adding process is carried out to reduce computational cost. Numerical studies of a cantilever plate with an internal crack are performed. The effectiveness and efficiency of this method are demonstrated by the identified results. The effect of initial sampling size on the precision of the identified results is also investigated.

  4. An improved surrogate method for detecting the presence of chaos in gait.

    PubMed

    Miller, David J; Stergiou, Nicholas; Kurz, Max J

    2006-01-01

    It has been suggested that the intercycle variability present in the time series of biomechanical gait data is of chaotic nature. However, the proper methodology for the correct determination of whether intercycle fluctuations in the data are deterministic chaos or random noise has not been identified. Our goal was to evaluate the pseudoperiodic surrogation (PPS) [Small et al., 2001. Surrogate test for pseudoperiodic time series data. Physical Review Letters 87(18), 188,101-188,104], and the surrogation algorithms of Theiler et al. [1992. Testing for nonlinearity in time series: the method of surrogate data. Physica D 58(1-4), 77-94] and of Theiler and Rapp [1996. Re-examination of the evidence for low-dimensional, nonlinear structure in the human electroencephalogram. Electroencephalography and Clinical Neurophysiology 98, 213-222], to determine which is the more robust procedure for the verification of the presence of chaos in gait time series. The knee angle kinematic time series from six healthy subjects, generated from a 2-min walk, were processed with both algorithms. The Lyapunov exponent (LyE) and the approximate entropy (ApEn) were calculated from the original data and both surrogates. Paired t-tests that compared the LyE and the ApEn values revealed significant differences between both surrogated time series and the original data, indicating the presence of deterministic chaos in the original data. However, the Theiler algorithm affected the intracycle dynamics of the gait time series by changing their overall shape. This resulted in significantly higher LyE and ApEn values for the Theiler-surrogated data when compared with both the original and the PPS-generated data. Thus, the discovery of significant differences was a false positive because it was not based on differences in the intercycle dynamics but rather on the fact that the time series was of a completely different shape. The PPS algorithm, on the other hand, preserved the intracycle dynamics of

  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. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  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.

  14. An In Vivo Method to Identify microRNA Targets Not Predicted by Computation Algorithms: p21 Targeting by miR-92a in Cancer.

    PubMed

    Su, Xiaoping; Wang, Huaming; Ge, Wei; Yang, Mingjin; Hou, Jin; Chen, Taoyong; Li, Nan; Cao, Xuetao

    2015-07-15

    microRNA (miRNA) dysregulation is involved in the development and progression of various human cancers, including hepatocellular carcinoma (HCC). However, how to identify the miRNAs targeting specific mRNA in cells is a significant challenge because of the interaction complexity and the limited knowledge of rules governing these processes. Some miRNAs are not predictable by current computer algorithms available. Here, using p21 mRNA as target, we established a new method, called miRNA in vivo precipitation (miRIP), to identify which kind of miRNAs can actually bind to the specific mRNA in cells. Several unpredictable miRNAs that bound p21 mRNA in HepG2 and PC-3 cells were identified by the miRIP method. Among these miRNAs identified by miRIP, miR-92a was found and confirmed to interact robustly with p21 mRNA, both in HepG2 and PC-3 cells. miR-92a was found to be remarkably increased in HCC tissues, and higher expression of miR-92a significantly correlated with lower expression of p21, which is related to poor survival of HCC patients. Moreover, inhibition of miR-92a could significantly suppress HCC growth in vitro and in vivo by upregulating p21. Together, miR-92a, which is identified by miRIP, is functionally shown to be associated with HCC growth as an oncogenic miRNA by inhibiting expression of targeting gene p21. In addition, several unpredictable miRNAs that target STAT3 mRNA were also identified by the miRIP method in HepG2 cells. Our results demonstrated that the miRIP approach can effectively identify the unpredictable but intracellular existing miRNAs that target specific mRNA in vivo.

  15. 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

  16. 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

  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. PLAN-TA9-2443(U), Rev. B Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure

    SciTech Connect

    Brown, Geoffrey Wayne

    2016-03-16

    This document identifies scope and some general procedural steps for performing Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing. This Test Plan describes the requirements, responsibilities, and process for preparing and testing a range of chemical surrogates intended to mimic the energetic response of waste created during processing of legacy nitrate salts. The surrogates developed are expected to bound1 the thermal and mechanical sensitivity of such waste, allowing for the development of process parameters required to minimize the risk to worker and public when processing this waste. Such parameters will be based on the worst-case kinetic parameters as derived from APTAC measurements as well as the development of controls to mitigate sensitivities that may exist due to friction, impact, and spark. This Test Plan will define the scope and technical approach for activities that implement Quality Assurance requirements relevant to formulation and testing.

  19. 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.

  20. 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.

  1. Composite Sampling of a Bacillus anthracis Surrogate with ...

    EPA Pesticide Factsheets

    Journal Article A series of experiments were conducted to explore the utility of composite-based collection of surface samples for the detection of a Bacillus anthracis surrogate using cellulose sponge samplers on a stainless steel surface.

  2. 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...

  3. Bioaccessibility of metals in alloys: evaluation of three surrogate biofluids.

    PubMed

    Hillwalker, Wendy E; Anderson, Kim A

    2014-02-01

    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.

  4. 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

  5. Predicting moisture dynamics of fine understory fuels in a moist tropical rainforest system: results of a pilot study undertaken to identify proxy variables useful for rating fire danger.

    PubMed

    Ray, David; Nepstad, Dan; Brando, Paulo

    2010-08-01

    *The use of fire as a land management tool in the moist tropics often has the unintended consequence of degrading adjacent forest, particularly during severe droughts. Reliable models of fire danger are needed to help mitigate these impacts. *Here, we studied the moisture dynamics of fine understory fuels in the east-central Brazilian Amazon during the 2003 dry season. Drying stations established under varying amounts of canopy cover (leaf area index (LAI) = 0 - 5.3) were subjected to a range of water inputs (5-15 mm) and models were developed to forecast litter moisture content (LMC). Predictions were then compared with independent field data. *A multiple linear regression relating litter moisture content to forest structure (LAI), ambient vapor pressure deficit (VPD(M)) and an index of elapsed time since a precipitation event (d(-1)) was identified as the best-fit model (adjusted R(2) = 0.89). Relative to the independent observations, model predictions were relatively unbiased when the LMC was predicting fire danger based on forest structure and meteorological variables is promising; however, additional information to the LAI, for example forest biomass, may be required to accurately capture the influence of forest structure on understory microclimate.

  6. Association between Immune Markers and Surrogate Markers of Cardiovascular Disease in HIV Positive Patients: A Systematic Review

    PubMed Central

    Vos, Alinda G.; Hulzebosch, Annelieke; Grobbee, Diederick E.; Barth, Roos E.; Klipstein-Grobusch, Kerstin

    2017-01-01

    Background HIV infection is associated with an increased risk of cardiovascular disease (CVD). Chronic low-grade immune activation is likely one of the driving mechanisms. This systematic review provides an overview of the evidence addressing the relation between immune markers and surrogate markers of CVD (except CIMT) in HIV infection. Methods A systematic search was performed in PubMed, Embase and Cochrane Library identifying all articles from 1996 to April 2015. It addressed the relation between immune markers and surrogate markers of CVD (except Carotid Intima-media Thickness) in HIV-positive adults. Two authors, using predefined criteria, independently conducted the selection of articles, critical appraisal and extraction of the data. Analysis focused on immune markers that were assessed most frequently. The review was conducted according to the PRISMA guideline and performed as part of an overarching review registered with PROSPERO (CRD42014010516). Findings Twenty-nine articles were selected, describing 34 immune markers and nine different CVD surrogate outcomes: coronary calcium score (13 times) and flow-mediated dilation (10 times) were used most frequently. Twenty-seven studies had a cross-sectional design. CRP, IL-6 and sVCAM-1 were assessed most frequently. None of the immune markers were clearly associated with any of the surrogate CVD outcomes. No effect estimate could be calculated due to marked heterogeneity in study populations, immune markers, outcomes and statistical approaches. Interpretation This review could not identify a clear association between any of the immune markers and surrogate CVD outcomes. This may reflect a true lack of association, or may be explained by heterogeneity across studies and lack of follow-up data. Future research should focus on longitudinal studies measuring a select set of immune markers and surrogate CVD outcomes awaiting the primary outcome of clinical cardiovascular events. PMID:28085961

  7. Human surrogate models of neuropathic pain: validity and limitations.

    PubMed

    Binder, Andreas

    2016-02-01

    Human surrogate models of neuropathic pain in healthy subjects are used to study symptoms, signs, and the hypothesized underlying mechanisms. Although different models are available, different spontaneous and evoked symptoms and signs are inducible; 2 key questions need to be answered: are human surrogate models conceptually valid, ie, do they share the sensory phenotype of neuropathic pain states, and are they sufficiently reliable to allow consistent translational research?

  8. Surrogate nutrition markers, malnutrition, and adequacy of nutrition support.

    PubMed

    Seres, David S

    2005-06-01

    Surrogate nutrition markers are used to assess adequacy of nourishment and to define malnutrition despite evidence that fails to link nourishment, surrogate markers, and outcomes. Markers such as serum levels of albumin, prealbumin, transferrin, and IGF-1 and delayed hypersensitivity and total lymphocyte count may be valid to help stratify risk. However, it is not appropriate to consider these as markers of adequacy of nourishment in the sick patient.

  9. 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.

  10. Construction of accuracy-preserving surrogate for the eigenvalue radiation diffusion and/or transport problem

    SciTech Connect

    Wang, C.; Abdel-Khalik, H. S.

    2012-07-01

    The construction of surrogate models for high fidelity models is now considered an important objective in support of all engineering activities which require repeated execution of the simulation, such as verification studies, validation exercises, and uncertainty quantification. The surrogate must be computationally inexpensive to allow its repeated execution, and must be computationally accurate in order for its predictions to be credible. This manuscript introduces a new surrogate construction approach that reduces the dimensionality of the state solution via a range-finding algorithm from linear algebra. It then employs a proper orthogonal decomposition-like approach to solve for the reduced state. The algorithm provides an upper bound on the error resulting from the reduction. Different from the state-of-the-art, the new approach allows the user to define the desired accuracy a priori which controls the maximum allowable reduction. We demonstrate the utility of this approach using an eigenvalue radiation diffusion model, where the accuracy is selected to match machine precision. Results indicate that significant reduction is possible for typical reactor assembly models, which are currently considered expensive given the need to employ very fine mesh many group calculations to ensure the highest possible fidelity for the downstream core calculations. Given the potential for significant reduction in the computational cost, we believe it is possible to rethink the manner in which homogenization theory is currently employed in reactor design calculations. (authors)

  11. Surrogate population models for large-scale neural simulations.

    PubMed

    Tripp, Bryan P

    2015-06-01

    Because different parts of the brain have rich interconnections, it is not possible to model small parts realistically in isolation. However, it is also impractical to simulate large neural systems in detail. This article outlines a new approach to multiscale modeling of neural systems that involves constructing efficient surrogate models of populations. Given a population of neuron models with correlated activity and with specific, nonrandom connections, a surrogate model is constructed in order to approximate the aggregate outputs of the population. The surrogate model requires less computation than the neural model, but it has a clear and specific relationship with the neural model. For example, approximate spike rasters for specific neurons can be derived from a simulation of the surrogate model. This article deals specifically with neural engineering framework (NEF) circuits of leaky-integrate-and-fire point neurons. Weighted sums of spikes are modeled by interpolating over latent variables in the population activity, and linear filters operate on gaussian random variables to approximate spike-related fluctuations. It is found that the surrogate models can often closely approximate network behavior with orders-of-magnitude reduction in computational demands, although there are certain systematic differences between the spiking and surrogate models. Since individual spikes are not modeled, some simulations can be performed with much longer steps sizes (e.g., 20 ms). Possible extensions to non-NEF networks and to more complex neuron models are discussed.

  12. 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

  13. 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

  14. A surrogate reaction technique benchmark: ^92Zr(α,α') surrogate for n+^91Zr

    NASA Astrophysics Data System (ADS)

    Church, J. A.; Ahle, L.; Bernstein, L. A.; Dietrich, F.; Escher, J.; Forssen, C.; Ai, H.; Amro, H. A.; Beausang, C.; Caggiano, J. A.; Casten, R. F.; Heinz, A.; McCutchan, E.; Meyer, D.; Plettner, C.; Ressler, J. J.; Zamfir, N. V.

    2004-10-01

    Neutron-induced reaction cross sections are sometimes difficult to measure due to target or beam limitations. For two-step reactions which proceed through a compound nucleus, an alternate, "surrogate reaction" technique (J.D. Cramer and H.C. Britt, Nucl. Sci. Eng., 41), 177 (1970). is applicable, and is undergoing investigation at LLNL. Measured decay probabilities for a compound nucleus formed in a light-ion reaction are combined with optical-model calculations for the formation of the same compound nucleus via the n-induced reaction. The result is an estimation for overall (n, γ/n/2n) cross sections. As a benchmark, the reaction ^92Zr(α,α'), surrogate for n+^91Zr, was studied at Yale (WNSL). Particles were detected in the silicon telescope STARS and γ-rays were measured with YRAST-ball Ge clover detectors. The measurement, benchmarking issues, and existing ^91Zr(n,γ) data (CSISRS) will be discussed. Work performed under the auspices of the U.S. DOE by the Univ. of CA, LLNL contract No. W-7405-Eng-4, and DOE grants DE-FG02-91ER-40609 and DE-FG03-03NA00081.

  15. 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.

  16. Thinking Forward: Future-oriented Thinking among Patients with Tobacco-associated Thoracic Diseases and Their Surrogates

    PubMed Central

    Pflug, Emily; Madden, Vanessa; Halpern, Scott D.

    2016-01-01

    Rationale: The goal of shared decision making is to match patient preferences, including evaluation of potential future outcomes, with available management options. Yet, it is unknown how patients with smoking-related thoracic diseases or their surrogates display future-oriented thinking. Objectives: To document prevalent themes in patients’ and potential surrogate decision makers’ future-oriented thinking when facing preference-sensitive choices. Methods: We conducted 44 scenario-based semistructured interviews among a diverse group of outpatients with smoking-associated thoracic diseases and potential surrogates for whom one of three preference-sensitive decisions would be medically relevant. Using content analysis, we documented prevalent themes to understand how these individuals display future-oriented thinking. Measurements and Main Results: Patients and potential surrogates generally expressed expectations for future outcomes but also acknowledged their limitations in doing so. When thinking about potential outcomes, decision makers relied on past experiences, including those only loosely related; perceived familiarity with treatment options; and spirituality. The content of these expectations included effects on family, emotional predictions, and prognostication. For surrogates, a tension existed between hope-based and fact-based expectations. Conclusions: Patients and surrogates may struggle to generate expectations, and these future-oriented thoughts may be based on loosely related past experiences or unrealistic optimism. These tendencies may lead to errors, preventing selection of treatments that promote true preferences. Clinicians should explore how decision makers engage in future-oriented thinking and what their expectations are as a component of the shared decision-making process. Future research should evaluate whether targeted guidance in future-oriented thinking may improve outcomes important to patients. PMID:26436758

  17. 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.

  18. Project ATHENA Creates Surrogate Human Organ Systems

    ScienceCinema

    MacQueen, Luke; Knospel, Fanny; Sherrod, Stacy; Iyer, Rashi

    2016-07-12

    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.

  19. 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

    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.

  20. 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

  1. 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

  2. Beyond multi-fractals: surrogate time series and fields

    NASA Astrophysics Data System (ADS)

    Venema, V.; Simmer, C.

    2007-12-01

    Most natural complex are characterised by variability on a large range of temporal and spatial scales. The two main methodologies to generate such structures are Fourier/FARIMA based algorithms and multifractal methods. The former is restricted to Gaussian data, whereas the latter requires the structure to be self-similar. This work will present so-called surrogate data as an alternative that works with any (empirical) distribution and power spectrum. The best-known surrogate algorithm is the iterative amplitude adjusted Fourier transform (IAAFT) algorithm. We have studied six different geophysical time series (two clouds, runoff of a small and a large river, temperature and rain) and their surrogates. The power spectra and consequently the 2nd order structure functions were replicated accurately. Even the fourth order structure function was more accurately reproduced by the surrogates as would be possible by a fractal method, because the measured structure deviated too strong from fractal scaling. Only in case of the daily rain sums a fractal method could have been more accurate. Just as Fourier and multifractal methods, the current surrogates are not able to model the asymmetric increment distributions observed for runoff, i.e., they cannot reproduce nonlinear dynamical processes that are asymmetric in time. Furthermore, we have found differences for the structure functions on small scales. Surrogate methods are especially valuable for empirical studies, because the time series and fields that are generated are able to mimic measured variables accurately. Our main application is radiative transfer through structured clouds. Like many geophysical fields, clouds can only be sampled sparsely, e.g. with in-situ airborne instruments. However, for radiative transfer calculations we need full 3-dimensional cloud fields. A first study relating the measured properties of the cloud droplets and the radiative properties of the cloud field by generating surrogate cloud

  3. 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.

  4. Synthetic aperture acoustic measurements of stationary suspended cinderblock and surrogate substitutes

    NASA Astrophysics Data System (ADS)

    Bishop, Steven; Woods, Teresa; Vignola, Joe; Judge, John; Soumekh, Mehrdad

    2009-05-01

    A synthetic aperture acoustic approach is used as a standoff method to assess material properties of a typical cinder block, referred to as a concrete masonry unit (CMU), and a variety of CMU surrogates. The objective is to identify anomalies in CMU wall surfaces. The acoustic specular return and phase change across the blocks are the fundamental measurements of interest. The CMU surrogates are created from commercially available closed cell expanding foam. Results from three test articles are presented that show potentially exploitable differences in terms of acoustic magnitude and acoustic phase response between the surrogates and typical CMUs. The test articles are; a typical CMU, a foam block, and a foam block with an embedded steel object. All test articles are similar in size and shape, and both foam blocks are covered in grout so that surface appearance closely matches that of a CMU. The results show that each of the test articles has characteristics that may be used for discrimination and anomaly detection.

  5. 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.

  6. 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.

  7. TU-CD-BRA-05: Atlas Selection for Multi-Atlas-Based Image Segmentation Using Surrogate Modeling

    SciTech Connect

    Zhao, T; Ruan, D

    2015-06-15

    Purpose: The growing size and heterogeneity in training atlas necessitates sophisticated schemes to identify only the most relevant atlases for the specific multi-atlas-based image segmentation problem. This study aims to develop a model to infer the inaccessible oracle geometric relevance metric from surrogate image similarity metrics, and based on such model, provide guidance to atlas selection in multi-atlas-based image segmentation. Methods: We relate the oracle geometric relevance metric in label space to the surrogate metric in image space, by a monotonically non-decreasing function with additive random perturbations. Subsequently, a surrogate’s ability to prognosticate the oracle order for atlas subset selection is quantified probabilistically. Finally, important insights and guidance are provided for the design of fusion set size, balancing the competing demands to include the most relevant atlases and to exclude the most irrelevant ones. A systematic solution is derived based on an optimization framework. Model verification and performance assessment is performed based on clinical prostate MR images. Results: The proposed surrogate model was exemplified by a linear map with normally distributed perturbation, and verified with several commonly-used surrogates, including MSD, NCC and (N)MI. The derived behaviors of different surrogates in atlas selection and their corresponding performance in ultimate label estimate were validated. The performance of NCC and (N)MI was similarly superior to MSD, with a 10% higher atlas selection probability and a segmentation performance increase in DSC by 0.10 with the first and third quartiles of (0.83, 0.89), compared to (0.81, 0.89). The derived optimal fusion set size, valued at 7/8/8/7 for MSD/NCC/MI/NMI, agreed well with the appropriate range [4, 9] from empirical observation. Conclusion: This work has developed an efficacious probabilistic model to characterize the image-based surrogate metric on atlas selection

  8. Return to Work: A Cut-Off of FIM Gain with Montebello Rehabilitation Factor Score in Order to Identify Predictive Factors in Subjects with Acquired Brain Injury

    PubMed Central

    2016-01-01

    Return to work (RTW) for people with acquired brain injury (ABI) represents a main objective of rehabilitation: this work presents a strong correlation between personal well-being and quality of life. The aim of this study is to investigate the prognostic factors that can predict RTW after ABI (traumatic or non- traumatic aetiology) in patients without disorders of consciousness (e.g. coma, vegetative or minimally conscious state) at the beginning of their admission to rehabilitation. At the end of a 6-month follow-up after discharge, data were successfully collected in 69 patients. The rehabilitation effectiveness (functional Recovery) between admission and discharge was assessed by Functional Independent Measure (FIM) gain, through the Montebello Rehabilitation Factor Score (MRFS), which was obtained as follows: (discharge FIM—admission FIM)/(Maximum possible FIM—Admission FIM) x 100. The cut-off value (criterion) deriving from MRFS, which helped identify RTW patients, resulted in .659 (sn 88.9%; sp 52.4%). Considering the Mini Mental State Examination (MMSE) and the MRFS data, the multivariable binary logistic regression analysis presented 62.96% of correct RTW classification cases, 80.95% of non-RTW leading to an overall satisfactory predictability of 73.91%. The results of the present study suggest that occupational therapy intervention could modify cut-off in patients with an MFRS close to target at the end of an in-hospital rehabilitative program thus developing their capabilities and consequently surpassing cut-off itself. PMID:27780215

  9. Return to Work: A Cut-Off of FIM Gain with Montebello Rehabilitation Factor Score in Order to Identify Predictive Factors in Subjects with Acquired Brain Injury.

    PubMed

    Franceschini, Marco; Massimiani, Maria Pia; Paravati, Stefano; Agosti, Maurizio

    2016-01-01

    Return to work (RTW) for people with acquired brain injury (ABI) represents a main objective of rehabilitation: this work presents a strong correlation between personal well-being and quality of life. The aim of this study is to investigate the prognostic factors that can predict RTW after ABI (traumatic or non- traumatic aetiology) in patients without disorders of consciousness (e.g. coma, vegetative or minimally conscious state) at the beginning of their admission to rehabilitation. At the end of a 6-month follow-up after discharge, data were successfully collected in 69 patients. The rehabilitation effectiveness (functional Recovery) between admission and discharge was assessed by Functional Independent Measure (FIM) gain, through the Montebello Rehabilitation Factor Score (MRFS), which was obtained as follows: (discharge FIM-admission FIM)/(Maximum possible FIM-Admission FIM) x 100. The cut-off value (criterion) deriving from MRFS, which helped identify RTW patients, resulted in .659 (sn 88.9%; sp 52.4%). Considering the Mini Mental State Examination (MMSE) and the MRFS data, the multivariable binary logistic regression analysis presented 62.96% of correct RTW classification cases, 80.95% of non-RTW leading to an overall satisfactory predictability of 73.91%. The results of the present study suggest that occupational therapy intervention could modify cut-off in patients with an MFRS close to target at the end of an in-hospital rehabilitative program thus developing their capabilities and consequently surpassing cut-off itself.

  10. Development of a Drug-Response Modeling Framework to Identify Cell Line Derived Translational Biomarkers That Can Predict Treatment Outcome to Erlotinib or Sorafenib.

    PubMed

    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.

  11. 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.

  12. miRNA expression profiling of inflammatory breast cancer identifies a 5-miRNA signature predictive of breast tumor aggressiveness.

    PubMed

    Lerebours, Florence; Cizeron-Clairac, Geraldine; Susini, Aurelie; Vacher, Sophie; Mouret-Fourme, Emmanuelle; Belichard, Catherine; Brain, Etienne; Alberini, Jean-Louis; Spyratos, Frédérique; Lidereau, Rosette; Bieche, Ivan

    2013-10-01

    IBC (inflammatory breast cancer) is a rare but very aggressive form of breast cancer with a particular phenotype. The molecular mechanisms responsible for IBC remain largely unknown. In particular, genetic and epigenetic alterations specific to IBC remain to be identified. MicroRNAs, a class of small noncoding RNAs able to regulate gene expression, are deregulated in breast cancer and may therefore serve as tools for diagnosis and prediction. This study was designed to determine miRNA expression profiling (microRNAome) in IBC. Quantitative RT-PCR was used to determine expression levels of 804 miRNAs in a screening series of 12 IBC compared to 31 non-stage-matched non-IBC and 8 normal breast samples. The differentially expressed miRNAs were then validated in a series of 65 IBC and 95 non-IBC. From a set of 18 miRNAs of interest selected from the screening series, 13 were differentially expressed with statistical significance in the validation series of IBC compared to non-IBC. Among these, a 5-miRNA signature comprising miR-421, miR-486, miR-503, miR-720 and miR-1303 was shown to be predictive for IBC phenotype with an overall accuracy of 89%. Moreover, multivariate analysis showed that this signature was an independent predictor of poor Metastasis-Free Survival in non-IBC patients.

  13. Improvements to surrogate data methods for nonstationary time series.

    PubMed

    Lucio, J H; Valdés, R; Rodríguez, L R

    2012-05-01

    The method of surrogate data has been extensively applied to hypothesis testing of system linearity, when only one realization of the system, a time series, is known. Normally, surrogate data should preserve the linear stochastic structure and the amplitude distribution of the original series. Classical surrogate data methods (such as random permutation, amplitude adjusted Fourier transform, or iterative amplitude adjusted Fourier transform) are successful at preserving one or both of these features in stationary cases. However, they always produce stationary surrogates, hence existing nonstationarity could be interpreted as dynamic nonlinearity. Certain modifications have been proposed that additionally preserve some nonstationarity, at the expense of reproducing a great deal of nonlinearity. However, even those methods generally fail to preserve the trend (i.e., global nonstationarity in the mean) of the original series. This is the case of time series with unit roots in their autoregressive structure. Additionally, those methods, based on Fourier transform, either need first and last values in the original series to match, or they need to select a piece of the original series with matching ends. These conditions are often inapplicable and the resulting surrogates are adversely affected by the well-known artefact problem. In this study, we propose a simple technique that, applied within existing Fourier-transform-based methods, generates surrogate data that jointly preserve the aforementioned characteristics of the original series, including (even strong) trends. Moreover, our technique avoids the negative effects of end mismatch. Several artificial and real, stationary and nonstationary, linear and nonlinear time series are examined, in order to demonstrate the advantages of the methods. Corresponding surrogate data are produced with the classical and with the proposed methods, and the results are compared.

  14. Direct Measurement of X-Ray Drive from Surrogate Targets in Nova Hohlraums

    NASA Astrophysics Data System (ADS)

    Amendt, P.; Glendinning, S. G.; Hammel, B. A.; Landen, O.; Suter, L. J.

    1996-10-01

    A new method for measuring x-ray drive in Nova hohlraums near target center using surrogate targets is proposed as an alternative to conventional wall-based techniques. A solid, low-density ( 0.3 g/cm3) SiO2 aerogel ball placed at the center of a Nova hohlraum is used to infer x-ray drive from the backlighter-imaged ablatively driven shock trajectory. A nearly 10% (40%) increase in peak radiation temperature (flux) near the hohlraum center in the presence of axial shields is predicted from radiation-hydrodynamics simulations and corroborated by experiment.

  15. Surrogate end points and postprogression survival in renal cell carcinoma: an analysis of first-line trials with targeted therapies.

    PubMed

    Petrelli, Fausto; Barni, Sandro

    2013-12-01

    Our end point was to determine the correlations between progression-free survival (PFS), postprogression survival (PPS), response rate (RR), and disease control rate (DCR) (RR + stable disease) and overall survival (OS) in first-line trials of renal cell carcinoma (RCC) treated with targeted therapies and to identify a potential surrogate for OS. Data were collected from first-line phase III randomized trials in RCC. Linear regression was undertaken to evaluate the correlations between end points and a potential surrogate end point for OS. Six randomized trials were identified containing a total of 7 treatment arms. The nonparametric Spearman rank correlation coefficients (r(s)) between PFS, PPS, and RR/DCR and OS are 0.869, and 1, 0.96/1 (all P < .0001), respectively. There is a strong relationship between differences (Δ) in DCR and ΔOS (r(s) = 1). The slope of the regression line is 0.3963 ± 0.0019, indicating that a novel drug producing a 10% increase for DCR will yield an estimated absolute 3.9% increase in OS. In first-line trials including novel targeted agents for RCC, PFS is a relatively flawed surrogate end point because of PPS influence. Improvement in DCR is strongly associated with improvement in median OS. In this population, DCR may be an appropriate surrogate for OS.

  16. Spatial prediction of habitat overlap of introduced and native thistles to identify potential areas of nontarget activity of biological control agents.

    PubMed

    Wiggins, G J; Grant, J F; Lambdin, P L; Ranney, Jack W; Wilkerson, J B; van Manen, F T

    2010-12-01

    Nontarget feeding of Rhinocyllus conicus Fröelich and Trichosirocalus horridus (Panzer) on native North American thistles in the genus Cirsium has been documented. Some species of these native thistles have shown greater infestation levels of R. conicus in populations that are in close proximity to the target plant species, Carduus nutans L. In 2005 a study was initiated to identify areas of potential nontarget feeding by R. conicus and T. horridus on thistle species by predicting habitats of two known introduced hosts [C. nutans and Cirsium vulgare (Savi) Tenore] and two native species [Cirsium carolinianum (Walter) Fernald and Schubert and C. discolor (Muhlenberg ex Willdenow) Sprengel] using Mahalanobis distance (D(2)). Cumulative frequency graphs showed that the D(2) models for all four plant species effectively identified site conditions that contribute to the presence of the respective species. Poisson regression showed an association between D(2) values and plant counts at field-test sites for C. nutans and C. carolinianum. However, negative binomial regression detected no association between D(2) values and plant counts for C. discolor or C. vulgare. Chi-square analysis indicated associations between both weevil species and sites where C. vulgare and Carduus nutans were found, but not between the weevil and native thistle species. Habitats of C. nutans and Cirsium carolinianum overlapped in ≈12% of the study area. Data-based habitat models may provide a powerful tool for land managers and scientists to monitor native plant populations for nontarget feeding by introduced biological control agents.

  17. Appraising bacterial strains for rapid BOD sensing--an empirical test to identify bacterial strains capable of reliably predicting real effluent BODs.

    PubMed

    Webber, Judith B; Noonan, Mike; Pasco, Neil F; Hay, Joanne M

    2011-01-01

    The measured response of rapid biochemical oxygen demand (BOD) biosensors is often not identical to those measured using the conventional 5-day BOD assay. This paper highlights the efficacy of using both glucose-glutamic acid (GGA) and Organisation for Economic Cooperation and Development (OECD) BOD standards as a rapid screen for microorganisms most likely to reliably predict real effluent BODs when used in rapid BOD devices. Using these two synthetic BOD standards, a microorganism was identified that produced comparable BOD response profiles for two assays, the MICREDOX® assay and the conventional 5-day BOD(5) test. A factorial experimental design systematically evaluated the impact of four factors (microbial strain, growth media composition, media strength, and microbial growth phase) on the BOD response profiles using GGA and OECD synthetic standard substrates. An outlier was identified that showed an improved correlation between the MICREDOX® BOD (BOD(sens)) and BOD(5) assays for both the synthetic standards and for real wastewater samples. Microbial strain was the dominant factor influencing BOD(sens) values, with Arthrobacter globiformis single cultures clearly demonstrating superior rapid BOD(sens) response profiles for both synthetic and real waste samples. It was the only microorganism to approach the BOD(5) response for the OECD substrate (171 mg O(2)L(-1)), and also reported BOD values for real waste samples that were comparable to those produced by the BOD(5) test, including discriminating between filtered and unfiltered samples.

  18. Surrogate Analysis and Index Developer (SAID) tool

    USGS Publications Warehouse

    Domanski, Marian M.; Straub, Timothy D.; Landers, Mark N.

    2015-10-01

    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.

  19. 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.

  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

    DOE PAGES

    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

  3. Surrogate-Based Optimization of Biogeochemical Transport Models

    NASA Astrophysics Data System (ADS)

    Prieß, Malte; Slawig, Thomas

    2010-09-01

    First approaches towards a surrogate-based optimization method for a one-dimensional marine biogeochemical model of NPZD type are presented. The model, developed by Oschlies and Garcon [1], simulates the distribution of nitrogen, phytoplankton, zooplankton and detritus in a water column and is driven by ocean circulation data. A key issue is to minimize the misfit between the model output and given observational data. Our aim is to reduce the overall optimization cost avoiding expensive function and derivative evaluations by using a surrogate model replacing the high-fidelity model in focus. This in particular becomes important for more complex three-dimensional models. We analyse a coarsening in the discretization of the model equations as one way to create such a surrogate. Here the numerical stability crucially depends upon the discrete stepsize in time and space and the biochemical terms. We show that for given model parameters the level of grid coarsening can be choosen accordingly yielding a stable and satisfactory surrogate. As one example of a surrogate-based optimization method we present results of the Aggressive Space Mapping technique (developed by John W. Bandler [2, 3]) applied to the optimization of this one-dimensional biogeochemical transport model.

  4. Surrogate modeling of ultrasonic simulations using data-driven methods

    NASA Astrophysics Data System (ADS)

    Du, Xiaosong; Grandin, Robert; Leifsson, Leifur

    2017-02-01

    Ultrasonic testing (UT) is used to detect internal flaws in materials and to characterize material properties. In many applications, computational simulations are an important part of the inspection-design and analysis processes. Having fast surrogate models for UT simulations is key for enabling efficient inverse analysis and model-assisted probability of detection (MAPOD). In many cases, it is impractical to perform the aforementioned tasks in a timely manner using current simulation models directly. Fast surrogate models can make these processes computationally tractable. This paper presents investigations of using surrogate modeling techniques to create fast approximate models of UT simulator responses. In particular, we propose to integrate data-driven methods (here, kriging interpolation with variable-fidelity models to construct an accurate and fast surrogate model. These techniques are investigated using test cases involving UT simulations of solid components immersed in a water bath during the inspection process. We will apply the full ultrasonic solver and the surrogate model to the detection and characterization of the flaw. The methods will be compared in terms of quality of the responses.

  5. 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.

  6. 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.

  7. 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

  8. Surrogate decision making: reconciling ethical theory and clinical practice.

    PubMed

    Berger, Jeffrey T; DeRenzo, Evan G; Schwartz, Jack

    2008-07-01

    The care of adult patients without decision-making abilities is a routine part of medical practice. Decisions for these patients are typically made by surrogates according to a process governed by a hierarchy of 3 distinct decision-making standards: patients' known wishes, substituted judgments, and best interests. Although this framework offers some guidance, it does not readily incorporate many important considerations of patients and families and does not account for the ways in which many patients and surrogates prefer to make decisions. In this article, the authors review the research on surrogate decision making, compare it with normative standards, and offer ways in which the 2 can be reconciled for the patient's benefit.

  9. Love as a regulative ideal in surrogate decision making.

    PubMed

    Stonestreet, Erica Lucast

    2014-10-01

    This discussion aims to give a normative theoretical basis for a "best judgment" model of surrogate decision making rooted in a regulative ideal of love. Currently, there are two basic models of surrogate decision making for incompetent patients: the "substituted judgment" model and the "best interests" model. The former draws on the value of autonomy and responds with respect; the latter draws on the value of welfare and responds with beneficence. It can be difficult to determine which of these two models is more appropriate for a given patient, and both approaches may seem inadequate for a surrogate who loves the patient. The proposed "best judgment" model effectively draws on the values incorporated in each of the traditional standards, but does so because these values are important to someone who loves a patient, since love responds to the patient as the specific person she is.

  10. The TeleStroke Mimic (TM)‐Score: A Prediction Rule for Identifying Stroke Mimics Evaluated in a Telestroke Network

    PubMed Central

    Ali, Syed F.; Viswanathan, Anand; Singhal, Aneesh B.; Rost, Natalia S.; Forducey, Pamela G.; Davis, Lawrence W.; Schindler, Joseph; Likosky, William; Schlegel, Sherene; Solenski, Nina; Schwamm, Lee H.

    2014-01-01

    Background Up to 30% of acute stroke evaluations are deemed stroke mimics (SM). As telestroke consultation expands across the world, increasing numbers of SM patients are likely being evaluated via Telestroke. We developed a model to prospectively identify ischemic SMs during Telestroke evaluation. Methods and Results We analyzed 829 consecutive patients from January 2004 to April 2013 in our internal New England–based Partners TeleStroke Network for a derivation cohort, and 332 cases for internal validation. External validation was performed on 226 cases from January 2008 to August 2012 in the Partners National TeleStroke Network. A predictive score was developed using stepwise logistic regression, and its performance was assessed using receiver‐operating characteristic (ROC) curve analysis. There were 23% SM in the derivation, 24% in the internal, and 22% in external validation cohorts based on final clinical diagnosis. Compared to those with ischemic cerebrovascular disease (iCVD), SM had lower mean age, fewer vascular risk factors, more frequent prior seizure, and a different profile of presenting symptoms. The TeleStroke Mimic Score (TM‐Score) was based on factors independently associated with SM status including age, medical history (atrial fibrillation, hypertension, seizures), facial weakness, and National Institutes of Health Stroke Scale >14. The TM‐Score performed well on ROC curve analysis (derivation cohort AUC=0.75, internal validation AUC=0.71, external validation AUC=0.77). Conclusions SMs differ substantially from their iCVD counterparts in their vascular risk profiles and other characteristics. Decision‐support tools based on predictive models, such as our TM Score, may help clinicians consider alternate diagnosis and potentially detect SMs during complex, time‐critical telestroke evaluations. PMID:24958778

  11. 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.

  12. In lumbosacral plexus injuries can we identify indicators that predict spontaneous recovery or the need for surgical treatment? Results from a clinical study on 72 patients

    PubMed Central

    2014-01-01

    Background Post-traumatic lumbosacral plexus injuries seem to be rare events, spontaneously recovering in high percentage: as surgery is often challenging and results in poor outcome, many Authors have advocated conservative treatment only. Nevertheless surgery should not be ruled out: in invalidating injuries, it can restore basic function in the lower extremities. Therefore, it might be necessary to establish guidelines for the management and the indication to surgery in such cases. This study aims to identify indicators predicting spontaneous recovery or the need for surgery. Method The clinical and radiological data of 72 patients with a post-traumatic lumbosacral plexus injury were reviewed. A follow up equal or superior to 3 years is available in 42 cases. Results Lumbosacral plexus injuries mostly occurred during road accidents. The incidence of associated lesions was relevant: bone injuries were found in 85% of patients, internal lesions in 30% and vascular injuries in 8%. Lumbosacral trunk and sacral plexus palsies were the most frequent injury patterns. Root avulsions were revealed in 23% of cases and only in sacral plexus and complete lumbosacral plexus injuries: L5 and S1 were the roots more prone to avulsions. About 70% of cases recovered spontaneously, mostly in 18 months. Spontaneous recovery was the rule in lumbar plexus and lumbosacral trunk injuries (where root avulsions never occurred) or in sacral and complete lumbosacral plexus palsies due to compression injuries. The causative mechanism correlated with the injury pattern, the associated bone injury being often predictive of the severity of the nerve injury. Lumbosacral plexus injuries occurred in car crashes were generally associated with fractures causing compression on the nerves, thus resulting in injuries often amenable of spontaneous recovery. Motorcycle accidents implied high kinetic energy traumas where traction played an important role, as the high percentage of sacroiliac joint

  13. Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

    PubMed Central

    Plewes, Katherine; Maude, Richard J.; Hanson, Josh; Herdman, M. Trent; Leopold, Stije J.; Ngernseng, Thatsanun; Charunwatthana, Prakaykaew; Phu, Nguyen Hoan; Ghose, Aniruddha; Hasan, M. Mahtab Uddin; Fanello, Caterina I.; Faiz, Md Abul; Hien, Tran Tinh; Day, Nicholas P. J.; White, Nicholas J.; Dondorp, Arjen M.

    2017-01-01

    Background Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. Methods Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African ‘AQUAMAT’ trial comparing artesunate and quinine (children), and the Vietnamese ‘AQ’ study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures. Results Improvements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the ‘AQUAMAT’ study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery. Conclusions The relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid

  14. 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.

  15. 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

  16. Quantitative analysis of the growth of Salmonella stanley during alfalfa sprouting and evaluation of Enterobacter aerogenes as its surrogate.

    PubMed

    Liu, Bin; Schaffner, Donald W

    2007-02-01

    Raw seed sprouts have been implicated in several food poisoning outbreaks in the last 10 years. Few studies have included investigations of factors influencing the effectiveness of testing spent irrigation water, and in no studies to date has a nonpathogenic surrogate been identified as suitable for large-scale irrigation water testing trials. Alfalfa seeds were inoculated with Salmonella Stanley or its presumptive surrogate (nalidixic acid-resistant Enterobacter aerogenes) at three concentrations (-3, -30, and -300 CFU/g) and were then transferred into either flasks or a bench top-scale sprouting chamber. Microbial concentrations were determined in seeds, sprouts, and irrigation water at various times during a 4-day sprouting process. Data were fit to logistic regression models, and growth rates and maximum concentrations were compared using the generalized linear model procedure of SAS. No significant differences in growth rates were observed among samples taken from flasks or the chamber. Microbial concentrations in irrigation water were not significantly different from concentrations in sprout samples obtaihed at the same time. E. aerogenes concentrations were similar to those of Salmonella Stanley at corresponding time points for all three inoculum concentrations. Growth rates were also constant regardless of inoculum concentration or strain, except that lower inoculum concentrations resulted in lower final concentrations proportional to their initial concentrations. This research demonstrated that a nonpathogenic easy-to-isolate surrogate (nalidixic acid-resistant E. aerogenes) provides results similar to those obtained with Salmonella Stanley, supporting the use of this surrogate in future large-scale experiments.

  17. Prediction of recurrence of non muscle-invasive bladder cancer by means of a protein signature identified by antibody microarray analyses.

    PubMed

    Srinivasan, Harish; Allory, Yves; Sill, Martin; Vordos, Dimitri; Alhamdani, Mohamed Saiel Saeed; Radvanyi, Francois; Hoheisel, Jörg D; Schröder, Christoph

    2014-06-01

    About 70% of newly diagnosed cases of bladder cancer are low-stage, low-grade, non muscle-invasive. Standard treatment is transurethral resection. About 60% of the tumors will recur, however, and in part progress to become invasive. Therefore, surveillance cystoscopy is performed after resection. However, in the USA and Europe alone, about 54 000 new patients per year undergo repeated cystoscopies over several years, who do not experience recurrence. Analysing in a pilot study resected tumors from patients with (n = 19) and without local recurrence (n = 6) after a period of 5 years by means of an antibody microarray that targeted 724 cancer-related proteins, we identified 255 proteins with significantly differential abundance. Most are involved in the regulation and execution of apoptosis and cell proliferation. A multivariate classifier was constructed based on 20 proteins. It facilitates the prediction of recurrence with a sensitivity of 80% and a specificity of 100%. As a measure of overall accuracy, the area under the curve value was found to be 91%. After validation in additional sample cohorts with a similarly long follow-up, such a signature could support decision making about the stringency of surveillance or even different treatment options.

  18. Immune reactivity against a novel HLA-A3-restricted influenza virus peptide identified by predictive algorithms and interferon-gamma quantitative PCR.

    PubMed

    Trojan, Andreas; Urosevic, Mirjana; Hummerjohann, Jörg; Giger, Robin; Schanz, Urs; Stahel, Rolf A

    2003-01-01

    The use of appropriate antigenic peptides for the most common human major histocompatibility complex (MHC) alleles is required for the amplification of the autologous cytotoxic compartment and the development of cytotoxic T cell-mediated immunity. The human A2 allele of the MHC plays an important role for the identification of peptide-specific cytotoxic T cells (CTL) against tumor and viral epitopes. Computer-based prediction algorithms, which are available on the Internet, have already proved to be applicable for the identification of novel CTL epitopes. Using the bioinformatics approach, the authors have identified the novel influenza matrix protein-derived and HLA-A3-restricted 9-mer peptide RLEDVFAGK capable of inducing peptide specific CTL reactivity. Peripheral blood mononuclear cells (PBMC) from healthy individuals and patients with lung cancer were pulsed with this peptide and with the well-characterized HLA-A2-restricted influenza A virus matrix peptide GILGFVFTL. Using quantitative PCR (TaqMan; Applied Biosystems, Foster City, CA, U.S.A), reactivity for both peptides was determined by measuring the change in type 1 cytokine (IFN-gamma) expression upon in vitro stimulation. Peptide-specific reactivity matched well with the subsequently determined MHC-class I alleles of the tested individuals. Results from this study indicate that the use of bioinformatics and the PCR-based screening system for the monitoring of T cell reactivity may allow for the identification of novel CTL epitopes.

  19. 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...

  20. Constrained Aeroacoustic Shape Optimization Using the Surrogate Management Framework

    DTIC Science & Technology

    2003-12-01

    412 A. L. Marsden, M. Wang & J. E. Dennis, Jr. rum for collaboration, as well as Charles Audet and Petros Koumoutsakos for valuable discussions...2003 Optimal aeroa- coustic shape design using the surrogate management framework. Submitted for review. MARSDEN, A. L., WANG, M. & KOUMOUTSAKOS , P

  1. A Study of Colonial Surrogates and Indigenous Others.

    ERIC Educational Resources Information Center

    Willard, William

    1993-01-01

    Carlos Montezuma, an Apache, was raised by whites, graduated from medical school, and worked as physician for the Indian Service and Carlisle Indian School. Montezuma's life as colonial surrogate advocating "civilization" of the Indians is compared to Kafka's story of the ape who studied to become a passable European because it was "a way out" of…

  2. Fluorescent polymeric aggregates for selective response to sarin surrogates.

    PubMed

    Rusu, Anca D; Moleavin, Ioana A; Hurduc, Nicolae; Hamel, Matthieu; Rocha, Licinio

    2014-09-07

    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.

  3. 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...

  4. 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…

  5. 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…

  6. 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…

  7. Surrogate based wind farm layout optimization using manifold mapping

    NASA Astrophysics Data System (ADS)

    Kaja Kamaludeen, Shaafi M.; van Zuijle, Alexander; Bijl, Hester

    2016-09-01

    High computational cost associated with the high fidelity wake models such as RANS or LES serves as a primary bottleneck to perform a direct high fidelity wind farm layout optimization (WFLO) using accurate CFD based wake models. Therefore, a surrogate based multi-fidelity WFLO methodology (SWFLO) is proposed. The surrogate model is built using an SBO method referred as manifold mapping (MM). As a verification, optimization of spacing between two staggered wind turbines was performed using the proposed surrogate based methodology and the performance was compared with that of direct optimization using high fidelity model. Significant reduction in computational cost was achieved using MM: a maximum computational cost reduction of 65%, while arriving at the same optima as that of direct high fidelity optimization. The similarity between the response of models, the number of mapping points and its position, highly influences the computational efficiency of the proposed method. As a proof of concept, realistic WFLO of a small 7-turbine wind farm is performed using the proposed surrogate based methodology. Two variants of Jensen wake model with different decay coefficients were used as the fine and coarse model. The proposed SWFLO method arrived at the same optima as that of the fine model with very less number of fine model simulations.

  8. Defending commercial surrogate motherhood against Van Niekerk and Van Zyl.

    PubMed

    McLachlan, H V

    1997-12-01

    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.

  9. Summary of Remediated Nitrate Salt Surrogate Formulation and Testing

    SciTech Connect

    Brown, Geoffrey Wayne; Leonard, Philip; Hartline, Ernest Leon; Tian, Hongzhao

    2016-05-05

    High Explosives Science and Technology (M-7) completed all required formulation and testing of Remediated Nitrate Salt (RNS) surrogates on April 27, 2016 as specified in PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure", released February 16, 2016. This report summarizes the results of the work and also includes additional documentation required in that test plan. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B. The work was carried out in three rounds, with the full matrix of samples formulated and tested in each round. Results from the first round of formulation and testing were documented in memorandum M7-J6-6042, " Results from First Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Results from the second round of formulation and testing were documented in M7-16-6053 , "Results from the Second Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Initial results from the third round were documented in M7-16-6057, "Initial Results from the Third Round of Remediated Nitrate Salt Formulation and Testing."

  10. Development of a Human Cranial Bone Surrogate for Impact Studies.

    PubMed

    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.

  11. 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

  12. 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

  13. 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

  14. 75 FR 20511 - Respecting the Rights of Hospital Patients to Receive Visitors and to Designate Surrogate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-20

    ... Hospital Patients to Receive Visitors and to Designate Surrogate Decision Makers for Medical Emergencies... unable to act as a legal surrogate if their partner is incapacitated. For all of these Americans,...

  15. 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

  16. 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.

  17. Deliberative Assessment of Surrogate Consent in Dementia Research

    PubMed Central

    Kim, Scott Y. H.; Uhlmann, Rebecca A.; Appelbaum, Paul S.; Knopman, David S.; Kim, H. Myra; Damschroder, Laura; Beattie, Elizabeth; Struble, Laura; De Vries, Raymond

    2009-01-01

    Background Research involving incapacitated persons with dementia involves complex scientific, legal, and ethical issues, making traditional surveys of layperson views regarding the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD)—involving balanced, detailed education and peer deliberation—on the views of those responsible for persons with dementia. Methods 178 community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family surrogate consent for dementia research (‘surrogate-based research’ or SBR) from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self perspectives), assessed at baseline, immediately post-DD session, and a month after DD date, for 4 research scenarios of varying risk-benefit profiles. Results At baseline, a majority in both DD and control groups supported a policy of family consent for dementia research for all research scenarios. The support for a policy of family consent for SBR increased for the DD group, but not for the control group; the change in the DD group was maintained one month later. In the DD group, there were transient changes in attitudes from surrogate or self perspectives; in the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective. Conclusions Intensive, balanced, and accurate education along with peer deliberation provided by democratic deliberation leads to a sustained increase in support for a societal policy of family consent for dementia research among those responsible for dementia patients. PMID:20188635

  18. 26 CFR 1.7874-2T - Surrogate foreign corporation (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Surrogate foreign corporation (temporary). 1... Surrogate foreign corporation (temporary). (a) Scope. This section provides rules for determining whether a foreign corporation shall be treated as a surrogate foreign corporation under section...

  19. 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...

  20. 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 ...

  1. Measures of Residual Risk with Connections to Regression, Risk Tracking, Surrogate Models, and Ambiguity

    DTIC Science & Technology

    2015-01-07

    Measures of Residual Risk with Connections to Regression, Risk Tracking, Surrogate Models, and Ambiguity1 R. Tyrrell Rockafellar Johannes O. Royset...insights and a new class of distributionally robust optimization models. Keywords: risk measures, residual risk, generalized regression, surrogate ...Measures of Residual Risk with Connections to Regression, Risk Tracking, Surrogate Models, and Ambiguity 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

  2. 26 CFR 1.7874-2T - Surrogate foreign corporation (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Surrogate foreign corporation (temporary). 1... Surrogate foreign corporation (temporary). (a) Scope. This section provides rules for determining whether a foreign corporation shall be treated as a surrogate foreign corporation under section...

  3. 26 CFR 1.7874-2T - Surrogate foreign corporation (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Surrogate foreign corporation (temporary). 1... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.7874-2T Surrogate foreign... shall be treated as a surrogate foreign corporation under section 7874(a)(2)(B). Paragraph (b) of...

  4. 3 CFR - Respecting the Rights of Hospital Patients To Receive Visitors and To Designate Surrogate...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Receive Visitors and To Designate Surrogate Decision Makers for Medical Emergencies Presidential Documents... Receive Visitors and To Designate Surrogate Decision Makers for Medical Emergencies Memorandum for the... legal surrogate if their partner is incapacitated. For all of these Americans, the failure to have...

  5. Estimation of k-ε parameters using surrogate models and jet-in-crossflow data

    SciTech Connect

    Lefantzi, Sophia; Ray, Jaideep; Arunajatesan, Srinivasan; Dechant, Lawrence

    2014-11-01

    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 - ε parameters ( C μ, C ε2 , C ε1 ) 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

  6. Ground Dwelling Ants as Surrogates for Establishing Conservation Priorities in the Australian Wet Tropics

    PubMed Central

    Yek, Sze Huei; Willliams, Stephen E; Burwell, Chris J.; Robson, Simon K.A.; Crozier, Ross H.

    2009-01-01

    This study aims to identify a set of areas with high biodiversity value over a small spatial scale within the Australian Wet Tropics. We identified sites of high biodiversity value across an altitudinal gradient of ground dwelling ant communities using three measures of biodiversity. The three measures considered were estimated species richness, complementarity between sites and evolutionary history. The latter measure was derived using the systematic nomenclature of the ants to infer a surrogate phylogeny. The goal of conservation assessments could then be achieved by choosing the most diverse site combinations. This approach was found to be valuable for identifying the most diverse site combinations across an altitudinal gradient that could ensure the preservation of terrestrial ground dwelling invertebrates in the Australian Wet Tropics. PMID:19613441

  7. Engineered Option Treatment of Remediated Nitrate Salts: Surrogate Batch-Blending Testing

    SciTech Connect

    Anast, Kurt Roy

    2016-03-11

    This report provides results from batch-blending test work for remediated nitrate salt (RNS) treatment. Batch blending was identified as a preferred option for blending RNS and unremediated nitrate salt (UNS) material with zeolite to effectively safe the salt/Swheat material identified as ignitable (U.S. Environmental Protection Agency code D001). Blending with zeolite was the preferred remediation option identified in the Options Assessment Report and was originally proposed as the best option for remediation by Clark and Funk in their report, Chemical Reactivity and Recommended Remediation Strategy for Los Alamos Remediated Nitrate Salt (RNS) Wastes, and also found to be a preferred option in the Engineering Options Assessment Report: Nitrate Salt Waste Stream Processing. This test work evaluated equipment and recipe alternatives to achieve effective blending of surrogate waste with zeolite.

  8. Aerosol and Surface Deposition Characteristics of Two Surrogates for Bacillus anthracis Spores.

    PubMed

    Bishop, Alistair H; Stapleton, Helen L

    2016-11-15

    Spores of an acrystalliferous derivative of Bacillus thuringiensis subsp. kurstaki, termed Btcry-, are morphologically, aerodynamically, and structurally indistinguishable from Bacillus anthracis spores. Btcry- spores were dispersed in a large, open-ended barn together with spores of Bacillus atrophaeus subsp. globigii, a historically used surrogate for Bacillus anthracis Spore suspensions (2 × 10(12) CFU each of B. atrophaeus subsp. globigii and Btcry-) were aerosolized in each of five spray events using a backpack misting device incorporating an air blower; a wind of 4.9 to 7.6 m s(-1) was also flowing through the barn in the same direction. Filter air samplers were situated throughout the barn to assess the aerosol density of the spores during each release. Trays filled with a surfactant in aqueous buffer were placed on the floor near the filter samplers to assess spore deposition. Spores were also recovered from arrays of solid surfaces (concrete, aluminum, and plywood) that had been laid on the floor and set up as a wall at the end of the barn. B. atrophaeus subsp. globigii spores were found to remain airborne for significantly longer periods, and to be deposited on horizontal surfaces at lower densities, than Btcry- spores, particularly near the spray source. There was a 6-fold-higher deposition of Btcry- spores than of B. atrophaeus subsp. globigii spores on vertical surfaces relative to the surrounding airborne density. This work is relevant for selecting the best B. anthracis surrogate for the prediction of human exposure, hazard assessment, and hazard management following a malicious release of B. anthracis IMPORTANCE: There is concern that pathogenic bacteria could be maliciously disseminated in the air to cause human infection and disruption of normal life. The threat from spore-forming organisms, such as the causative agent of anthrax, is particularly serious. In order to assess the extent of this risk, it is important to have a surrogate organism

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Compression moulding simulations of SMC using a multiobjective surrogate-based inverse modeling approach

    NASA Astrophysics Data System (ADS)

    Marjavaara, B. D.; Ebermark, S.; Lundström, T. S.

    2009-09-01

    A multiobjective surrogate-based inverse modeling technique to predict the spatial and temporal pressure distribution numerically during the fabrication of sheet moulding compounds (SMCs) is introduced. Specifically, an isotropic temperature-dependent Newtonian viscosity model of a SMC charge is fitted to experimental measurements via numerical simulations in order to mimic the temporal pressure distribution at two spatial locations simultaneously. The simulations are performed by using the commercial computational fluid dynamics (CFD) code ANSYS CFX-10.0, and the multiobjective surrogate-based fitting procedure proposed is carried out with a hybrid formulation of the NSGA-IIa evolutionary algorithm and the response surface methodology in Matlab. The outcome of the analysis shows the ability of the optimization framework to efficiently reduce the total computational load of the problem. Furthermore, the viscosity model assumed seems to be able to re solve the temporal pressure distribution and the advancing flow front accurately, which can not be said of the spatial pressure distribution. Hence, it is recommended to improve the CFD model proposed in order to better capture the true behaviour of the mould flow.

  15. Limitations of habitats as biodiversity surrogates for conservation planning in estuaries.

    PubMed

    Shokri, Mohammad Reza; Gladstone, William

    2013-04-01

    Increasing pressures on global biodiversity and lack of data on the number and abundance of species have motivated conservation planners and researchers to use more readily available information as proxies or surrogates for biodiversity. "Habitat" is one of the most frequently used surrogates but its assumed value in marine conservation planning is not often tested. The present study developed and tested three alternative habitat classification schemes of increasing complexity for a large estuary in south-east Australia and tested their effectiveness in predicting spatial variation in macroinvertebrate biodiversity and selecting estuarine protected areas to represent species. The three habitat classification schemes were: (1) broad-scale habitats (e.g., mangroves and seagrass), (2) subdivision of each broad-scale habitat by a suite of environmental variables that varied significantly throughout the estuary, and (3) subdivision of each broad-scale habitat by the subset of environmental variables that best explained spatial variation in macroinvertebrate biodiversity. Macroinvertebrate assemblages differed significantly among the habitats in each classification scheme. For each classification scheme, habitat richness was significantly correlated with species richness, total density of macroinvertebrates, assemblage dissimilarity, and summed irreplaceability. However, in a reserve selection process designed to represent examples of each habitat, no habitat classification scheme represented species significantly better than a random selection of sites. Habitat classification schemes may represent variation in estuarine biodiversity; however, the results of this study suggest they are inefficient in designing representative networks of estuarine protected areas.

  16. Imaging readouts as biomarkers or surrogate parameters for the assessment of therapeutic interventions.

    PubMed

    Rudin, Markus

    2007-10-01

    Surrogate markers and biomarkers based on imaging readouts providing predictive information on clinical outcome are of increasing importance in the preclinical and clinical evaluation of novel therapies. They are primarily used in studies designed to establish evidence that the therapeutic principle is valid in a representative patient population or in an individual. A critical step in the development of (imaging) surrogates is validation: correlation with established clinical endpoints must be demonstrated. Biomarkers must not fulfill such stringent validation criteria; however, they should provide insight into mechanistic aspects of the therapeutic intervention (proof-of-mechanism) or document therapy efficacy with prognostic quality with regard to the long-term clinical outcome (proof of concept). Currently used imaging biomarkers provide structural, physiological and metabolic information. Novel imaging approaches annotate structure with molecular signatures that are tightly linked to the pathophysiology or to the therapeutic principle. These cellular and molecular imaging methods yield information on drug biodistribution, receptor expression and occupancy, and/or intra- and intercellular signaling. The design of novel target-specific imaging probes is closely related to the development of the therapeutic agents and should be considered early in the discovery phase. Significant technical and regulatory hurdles have to be overcome to foster the use of imaging biomarkers for clinical drug evaluation.

  17. An integrated approach to identify distribution of Oncomelania hupensis, the intermediate host of Schistosoma japonicum, in a mountainous region in China.

    PubMed

    Yang, Kun; Wang, Xian-Hong; Yang, Guo-Jing; Wu, Xiao-Hua; Qi, Yun-Liang; Li, Hong-Jun; Zhou, Xiao-Nong

    2008-07-01

    The aim of this study is to better understand ecological variability related to the distribution of Oncomelania hupensis, the snail intermediate host of Schistosoma japonicum, and predict the spatial distribution of O. hupensis at the local scale in order to develop a more effective control strategy for schistosomiasis in the hilly and mountainous regions of China. A two-pronged approach was applied in this study consisting of a landscape pattern analysis complemented with Bayesian spatial modelling. The parasitological data were collected by cross-sectional surveys carried out in 11 villages in 2006 and mapped based on global positioning system (GPS) coordinates. Environmental surrogates and landscape metrics were derived from remotely-sensed images and land-cover/land-use classification data. Bayesian non-spatial and spatial models were applied to investigate the variation of snail density in relation to environmental surrogates and landscape metrics at the local scale. A Bayesian spatial model, validated by the deviance information criterion (DIC), was found to be the best-fitting model. The mean shape index (MSI) and Shannon's evenness indexes (SEI) were significantly associated with snail density. These findings suggest that decreasing the heterogeneity of the landscape can reduce snail density. A prediction maps were generated by the Bayesian model together with environmental surrogates and landscape metrics. In conclusion, the risk areas of snail distribution at the local scale can be identified using an integrated approach with landscape pattern analysis supported by remote sensing and GIS technologies, as well as Bayesian modelling.

  18. 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. ...

  19. 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

  20. Molecular Dynamics Simulations of Perylenediimide DNA Base Surrogates.

    PubMed

    Markegard, Cade B; Mazaheripour, Amir; Jocson, Jonah-Micah; Burke, Anthony M; Dickson, Mary N; Gorodetsky, Alon A; Nguyen, Hung D

    2015-09-03

    Perylene-3,4,9,10-tetracarboxylic diimides (PTCDIs) are a well-known class of organic materials. Recently, these molecules have been incorporated within DNA as base surrogates, finding ready applications as probes of DNA structure and function. However, the assembly dynamics and kinetics of PTCDI DNA base surrogates have received little attention to date. Herein, we employ constant temperature molecular dynamics simulations to gain an improved understanding of the assembly of PTCDI dimers and trimers. We also use replica-exchange molecular dynamics simulations to elucidate the energetic landscape dictating the formation of stacked PTCDI structures. Our studies provide insight into the equilibrium configurations of multimeric PTCDIs and hold implications for the construction of DNA-inspired systems from perylene-derived organic semiconductor building blocks.

  1. The Theory and Practice of Surrogate Decision-Making.

    PubMed

    Wendler, David

    2017-01-01

    When a patient lacks decision-making capacity and has not left a clear advance directive, there is now widespread agreement that patient-designated and next-of-kin surrogates should implement substituted judgment within a process of shared decision-making. Specifically, after discussing the "best scientific evidence available, as well as the patient's values, goals, and preferences" with the patient's clinicians, the patient-designated or next-of-kin surrogate should attempt to determine what decision the patient would have made in the circumstances. To the extent that this approach works, it seems to provide about as much respect for the autonomy of incapacitated patients as we could ask for. But, as articles in this issue of the Report by Jeffrey Berger and by Ellen Robinson and colleagues emphasize, reality presents challenges.

  2. Commercial agencies and surrogate motherhood: a transaction cost approach.

    PubMed

    Galbraith, Mhairi; McLachlan, Hugh V; Swales, J Kim

    2005-03-01

    In this paper we investigate the legal arrangements involved in UK surrogate motherhood from a transaction-cost perspective. We outline the specific forms the transaction costs take and critically comment on the way in which the UK institutional and organisational arrangements at present adversely influence transaction costs. We then focus specifically on the potential role of surrogacy agencies and look at UK and US evidence on commercial and voluntary agencies. Policy implications follow.

  3. New Meta Algorithms for Engineering Design Using Surrogate Functions

    DTIC Science & Technology

    2005-04-01

    Dennis, Jr., and Parviz Moin, Opti- mal aeroacoustic shape design using the surrogate management frame- work, Optimization and Engineering, 5(2):101...122, 2004. e Alison L. Marsden, Meng Wang, J. E. Dennis, Jr., and Parviz Moin), Suppression of vortex-shedding noise via derivative-free shape opti...solution. Contact: Dr. Dominique Orban (514)340-4711 ext 5967 "* Trailing edge design We have a collaboration with Parviz Moin’s tur- bulent flow group in

  4. 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 judge their cases. PMID:23346523

  5. Autoignition Chemistry of Surrogate Fuel Components in an Engine Environment

    DTIC Science & Technology

    2015-08-21

    establishing the impact on chemistry of recycle fraction in engines; and (3) development of the next generation of JP-8 surrogates and chemical models ...autoignition conditions; establish the impact of recycle fraction on chemistry, and aid in the development of chemical models . The program has made...Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 Hydrocarbon Oxidation in Engines; Hydrocarbon Autognition in Engines; Next

  6. ACOG committee opinion number 397, February 2008: surrogate motherhood.

    PubMed

    2008-02-01

    Ethical responsibilities are described for obstetrician-gynecologists who choose to participate in surrogacy arrangements by 1) advising couples who are considering surrogacy, 2) counseling potential surrogate mothers, 3) providing obstetric services for pregnant women participating in surrogacy, or 4) offering assisted reproductive technologies related to surrogacy. Although the obligations of physicians will vary depending on the type and level of their involvement, in all cases physicians should carefully examine all relevant issues related to surrogacy, including medical, ethical, legal, and psychologic aspects.

  7. The Confucian bioethics of surrogate decision making: its communitarian roots.

    PubMed

    Fan, Ruiping

    2011-10-01

    The family is the exemplar community of Chinese society. This essay explores how Chinese communitarian norms, expressed in thick commitments to the authority and autonomy of the family, are central to contemporary Chinese bioethics. In particular, it focuses on the issue of surrogate decision making to illustrate the Confucian family-grounded communitarian bioethics. The essay first describes the way in which the family, in Chinese bioethics, functions as a whole to provide consent for significant medical and surgical interventions when a patient has lost decision-making capacity. It is argued that the practice of not having an established order for surrogate decision makers (e.g., spouse, children, and then parents), as it is done in the United States, reflects the acknowledgment that the family as a social reality cannot be reduced to a stereotype of the appropriate order of default decision makers. This description of the family as being in authority to make surrogate decisions for an incompetent family member is enriched by an elaboration of the differences among the concepts of patient autonomy, family autonomy, and moral autonomy. The Chinese model, as well as the Confucian communitarian life of families, engages a family autonomy that is supported by a Confucian understanding of moral autonomy, rather than individual autonomy. Finally, the issue of possible conflicts between patient and family interests in relation to a patient's past wishes in the Chinese model is addressed in light of the role of the physician.

  8. Effects of data windows on the methods of surrogate data

    NASA Astrophysics Data System (ADS)

    Suzuki, Tomoya; Ikeguchi, Tohru; Suzuki, Masuo

    2005-05-01

    To generate surrogate data in nonlinear time series analysis, the Fourier transform is generally used. In the calculation of the Fourier transform, the time series is assumed to be periodic. Because such an assumption does not always hold true, the estimation accuracy of the Fourier transformed data and thus the power spectra is reduced. Due to such an estimation error, it is also possible that the surrogate test will lead to a false conclusion; for example, that a linear time series is nonlinear. In this paper, we experimentally evaluated the effects of data windows from the viewpoint of false rejections with several types of surrogate data. Our results indicate that if the data length becomes shorter, the false rejections by the data windows are reduced to a greater extent. However, if the data length is sufficient, the use of data windows is not a viable option. In the worst possible case wherein the linear memory of the original data is very long as in the nonstationary case, the critical length of the data for which the data windows were effective was approximately 1000.

  9. Development of novel synthetic muscle tissues for sports impact surrogates.

    PubMed

    Payne, Thomas; Mitchell, Séan; Bibb, Richard; Waters, Mark

    2015-01-01

    Impact injuries are commonplace in sport and often lead to performance detriment and debilitation. Personal Protective Equipment (PPE) is prescribed as a mandatory requirement in most sports where these impacts are likely to occur, though the methods of governance and evaluation criteria often do not accurately represent sports specific injury scenarios. One of the key shortcomings of such safety test standards is the human surrogate to which the PPE is affixed; this typically embodies unrepresentative geometries, masses, stiffness and levels of constraint when compared to humans. A key aspect of any human surrogate element is the simulant material used. Most previous sports specific surrogates tend to use off-the-shelf silicone blends to represent all the soft tissue structures within the human limb segment or organ; this approach potentially neglects important human response phenomena caused by the different tissue structures. This study presents an investigation into the use of bespoke additive cure Polydimethysiloxane (PDMS) silicone blends to match the reported mechanical properties of human relaxed and contracted skeletal muscle tissues. The silicone simulants have been tested in uniaxial compression through a range of strain rates and fit with a range of constitutive hyperelastic models (Mooney Rivlin, Ogden and Neo Hookean) and a viscoelastic Prony series.

  10. Efficient SRAM yield optimization with mixture surrogate modeling

    NASA Astrophysics Data System (ADS)

    Zhongjian, Jiang; Zuochang, Ye; Yan, Wang

    2016-12-01

    Largely repeated cells such as SRAM cells usually require extremely low failure-rate to ensure a moderate chi yield. Though fast Monte Carlo methods such as importance sampling and its variants can be used for yield estimation, they are still very expensive if one needs to perform optimization based on such estimations. Typically the process of yield calculation requires a lot of SPICE simulation. The circuit SPICE simulation analysis accounted for the largest proportion of time in the process yield calculation. In the paper, a new method is proposed to address this issue. The key idea is to establish an efficient mixture surrogate model. The surrogate model is based on the design variables and process variables. This model construction method is based on the SPICE simulation to get a certain amount of sample points, these points are trained for mixture surrogate model by the lasso algorithm. Experimental results show that the proposed model is able to calculate accurate yield successfully and it brings significant speed ups to the calculation of failure rate. Based on the model, we made a further accelerated algorithm to further enhance the speed of the yield calculation. It is suitable for high-dimensional process variables and multi-performance applications.

  11. An Artificial Turf-Based Surrogate Surface Collector for the ...

    EPA Pesticide Factsheets

    This paper describes the development of a new artificial turf surrogate surface (ATSS) sampler for use in the measurement of mercury (Hg) dry deposition. In contrast to many existing surrogate surface designs, the ATSS utilizes a three-dimensional deposition surface that may more closely mimic the physical structure of many natural surfaces than traditional flat surrogate surface designs (water, filter, greased Mylar film). The ATSS has been designed to overcome several complicating factors that can impact the integrity of samples with other direct measurement approaches by providing a passive system which can be deployed for both short and extended periods of time (days to weeks), and is not contaminated by precipitation and/or invalidated by strong winds. Performance characteristics including collocated precision, in-field procedural and laboratory blanks were evaluated. The results of these performance evaluations included a mean collocated precision of 9%, low blanks (0.8 ng), high extraction efficiency (97%–103%), and a quantitative matrix spike recovery (100%). In recent years, a growing number of intensive field campaigns and routine measurement networks have provided valuable information on the rates of total mercury (Hg) wet deposition in North America (Guentzel et al., 1995; Rea et al., 1996; Dvonch et al., 1999; Landis and Keeler, 2002; Dvonch et al., 2005; Hall et al., 2005; Keeler et al., 2005; Keeler et al., 2006; Butler et al., 2008; Prestbo an

  12. Identifying patterns of anxiety and depression in children with chromosome 22q11.2 deletion syndrome: Comorbidity predicts behavioural difficulties and impaired functional communications

    PubMed Central

    Stephenson, David D.; Beaton, Elliott A.; Weems, Carl F.; Angkustsiri, Kathleen; Simon, Tony J.

    2014-01-01

    Background Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex genetic disorder with a variable clinical presentation that can include cardiac, neural, immunological, and psychological issues. Previous studies have measured elevated anxiety and depression in children with 22q11.2DS. Comorbity of anxiety and depression is well established in the pediatric literature but the nature of comorbidity patterns has not been empirically established in children with 22q11.2DS. Comorbidity of anxiety and depression has important implications for treatment and prognosis, and may be a marker of risk in this population of children at high-risk for developing schizophrenia. Method Participants were 131 boys and girls ages 8 to 14 with (n = 76) and without (n = 55) 22q11.2DS and their mothers. Children and mothers independently completed self- and parent-report measures of anxiety and depression. Mothers also completed measures of behavioural functioning including the Behavioral Assessment for Children, 2nd ed. (BASC-2). Cluster analyses were conducted to test if theoretically based groupings of anxiety and depression could be identified. We hypothesized four psychological profiles based on child- and mother-reports: low/no anxiety and low/no depression, higher depression and low/no anxiety, higher anxiety and no/low depression, and a comorbid profile of higher anxiety and higher depression. BASC-2 subscale scores were then compared across subgroups of children to determine if a comorbid profile would predict greater behavioural difficulties. Results In the full sample of children both with and without 22q11.2DS, cluster analyses of self and maternal reported anxiety and depression revealed the expected subgroups: 1) a group of children with higher anxiety/lower depression (anxious); 2) a group with primary depression (lower anxiety/higher depression (depressed); 3) a comorbid group with higher anxiety/higher depression (comorbid); and, 4) a lowest anxiety

  13. Compound-nuclear reaction cross sections via the Surrogate method: considering the underlying assumptions

    NASA Astrophysics Data System (ADS)

    Escher, Jutta; Dietrich, Frank

    2006-10-01

    The Surrogate Nuclear Reactions approach makes it possible to determine compound-nuclear reaction cross sections indirectly. The method has been employed to determine (n,f) cross sections for various actinides, including unstable species [1-4]; other, primarily neutron- induced, reactions are being considered also [5,6]. The extraction of the sought-after cross sections typically relies on approximations to the full Surrogate formalism [7]. This presentation will identify and critically examine the most significant assumptions underlying the experimental work carried out so far. Calculations that test the validity of the approximations employed will be presented. [1] J.D. Cramer and H.C. Britt, Nucl. Sci. and Eng. 41, 177(1970); H.C. Britt and J.B. Wilhelmy, ibid. 72, 222(1979) [2] M. Petit et al, Nucl. Phys. A735, 345(2004) [3] C. Plettner et al, Phys. Rev. C 71, 051602(2005); J. Burke et al, Phys. Rev. C. 73, 054604(2006) [4] W. Younes and H.C. Britt, Phys. Rev. C 67, 024610(2003); 68, 034610(2003) [5] L.A. Bernstein et al, AIP Conf. Proc. 769, 890(2005) [6] J. Escher et al, Nucl. Phys. A758, 43c(2005) [7] J. Escher and F.S. Dietrich, submitted (2006)

  14. Validation of (d,p γ) as a Surrogate for (n, γ)

    NASA Astrophysics Data System (ADS)

    Ratkiewicz, A.; Cizewski, J. A.; Adekola, A.; Burcher, S.; Howard, M. E.; Manning, B.; Rice, S. L.; Shand, C.; Burke, J. T.; Casperson, R. J.; Scielzo, N.; Austin, R. A. E.; Fotiades, N.; Hughes, R. O.; Ross, T. J.; McCleskey, M.; Pain, S. D.; Peters, W. A.

    2013-10-01

    Although the importance of neutron capture on very exotic nuclei to nucleosynthesis is well known, direct measurements of these reactions are impossible. The (d,p γ) reaction at low energies was identified as a promising surrogate for (n, γ), as both reactions transfer relatively little angular momentum to the system. We report on a program to validate (d,p γ) as an (n, γ) surrogate reaction, using 95Mo as a target. The completed components of the experimental campaign include measurements of (d,p γ) in normal kinematics and of the intensities of transitions from excited states populated in (n, γ) as a function of neutron energies. Preliminary results from completed measurements and plans for an inverse kinematics measurement of 95Mo(d,p γ) will be presented. This work was supported in part by the NSF, the U.S. DOE (DE-FG52-08NA28552 (Rutgers, ORAU), DE-AC52-07NA27344 (LLNL), DE-FG02-05ER41379 and DE-FG52-06NA26206 (Richmond).

  15. 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

    2015-07-30

    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.

  16. 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

  17. 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…

  18. Identifying Essential Features of Juvenile Psychopathy in the Prediction of Later Antisocial Behavior: Is There an Additive, Synergistic, or Curvilinear Role for Fearless Dominance?

    PubMed

    Vize, Colin E; Lynam, Donald R; Lamkin, Joanna; Miller, Joshua D; Pardini, Dustin

    2016-05-01

    Despite years of research, and inclusion of psychopathy DSM-5, there remains debate over the fundamental components of psychopathy. Although there is agreement about traits related to Agreeableness and Conscientiousness, there is less agreement about traits related to Fearless Dominance (FD) or Boldness. The present paper uses proxies of FD and Self-centered Impulsivity (SCI) to examine the contribution of FD-related traits to the predictive utility of psychopathy in a large, longitudinal, sample of boys to test four possibilities: FD 1. assessed earlier is a risk factor, 2. interacts with other risk-related variables to predict later psychopathy, 3. interacts with SCI interact to predict outcomes, and 4. bears curvilinear relations to outcomes. SCI received excellent support as a measure of psychopathy in adolescence; however, FD was unrelated to criteria in all tests. It is suggested that FD be dropped from psychopathy and that future research focus on Agreeableness and Conscientiousness.

  19. Using exploratory data analysis to identify and predict patterns of human Lyme disease case clustering within a multistate region, 2010-2014.

    PubMed

    Hendricks, Brian; Mark-Carew, Miguella

    2017-02-01

    Lyme disease is the most commonly reported vectorborne disease in the United States. The objective of our study was to identify patterns of Lyme disease reporting after multistate inclusion to mitigate potential border effects. County-level human Lyme disease surveillance data were obtained from Kentucky, Maryland, Ohio, Pennsylvania, Virginia, and West Virginia state health departments. Rate smoothing and Local Moran's I was performed to identify clusters of reporting activity and identify spatial outliers. A logistic generalized estimating equation was performed to identify significant associations in disease clustering over time. Resulting analyses identified statistically significant (P=0.05) clusters of high reporting activity and trends over time. High reporting activity aggregated near border counties in high incidence states, while low reporting aggregated near shared county borders in non-high incidence states. Findings highlight the need for exploratory surveillance approaches to describe the extent to which state level reporting affects accurate estimation of Lyme disease progression.

  20. The Use of Surrogate Data in Demographic Population Viability Analysis: A Case Study of California Sea Lions

    PubMed Central

    2015-01-01

    Reliable data necessary to parameterize population models are seldom available for imperiled species. As an alternative, data from populations of the same species or from ecologically similar species have been used to construct models. In this study, we evaluated the use of demographic data collected at one California sea lion colony (Los Islotes) to predict the population dynamics of the same species from two other colonies (San Jorge and Granito) in the Gulf of California, Mexico, for which demographic data are lacking. To do so, we developed a stochastic demographic age-structured matrix model and conducted a population viability analysis for each colony. For the Los Islotes colony we used site-specific pup, juvenile, and adult survival probabilities, as well as birth rates for older females. For the other colonies, we used site-specific pup and juvenile survival probabilities, but used surrogate data from Los Islotes for adult survival probabilities and birth rates. We assessed these models by comparing simulated retrospective population trajectories to observed population trends based on count data. The projected population trajectories approximated the observed trends when surrogate data were used for one colony but failed to match for a second colony. Our results indicate that species-specific and even region-specific surrogate data may lead to erroneous conservation decisions. These results highlight the importance of using population-specific demographic data in assessing extinction risk. When vital rates are not available and immediate management actions must be taken, in particular for imperiled species, we recommend the use of surrogate data only when the populations appear to have similar population trends. PMID:26413746

  1. An Investigation of the Effects of a Diagnostic Prescriptive Kindergarten Program on the Predicted Reading Levels of Children Identified as Potential Reading Failures. Final Report.

    ERIC Educational Resources Information Center

    Stank, Peggy L.; Hayes, Robert B.

    An experimental design with experimental and control groups was used to evaluate the effect of a diagnostic structured kindergarten program upon the predicted reading levels of low income area children. The effect was compared with the effect of the traditional kindergarten program. The effects of the two curricula upon the total group of children…

  2. Analysis of baseline gene expression levels from toxicogenomics study control animals to identify sources of variation and predict responses to chemicals

    EPA Science Inventory

    The use of gene expression profiling to predict chemical mode of action would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control ...

  3. 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...

  4. On the application of an environmental radiological assessment system to an anthropomorphic surrogate.

    PubMed

    Brown, Justin E; Hosseini, Ali; Dowdall, Mark

    2014-01-01

    Recent developments have seen the expansion of the system of radiological protection for humans to one including protection of the environment against detrimental effects of radiation exposure, although a fully developed framework for integration of human and ecological risk assessment for radionuclides is only at an early stage. In the context of integration, significant differences exist between assessment methodologies for humans and the environment in terms of transfer, exposure, and dosimetry. The aim of this elaboration was to explore possible implications of the simplifications made within the system of environmental radiological protection in terms of the efficacy and robustness of dose-rate predictions. A comparison was conducted between human radiological assessment and environmental radiological assessment for an anthropomorphic surrogate, the results for which, produced by both the environmental and human-oriented risk assessment systems, were critically compared and contrasted. The adopted approach split the calculations into several parts, these being 1) physical transfer in an ecosystem, 2) transfer to humans, 3) internal doses to humans, and 4) external doses to humans. The calculations were carried out using both a human radiological assessment and ecological risk assessment system for the same surrogate. The results of this comparison provided indications as to where the 2 systems are amenable to possible integration and where such integration may prove difficult. Initial stage transport models seem to be an obvious component amenable for integration, although complete integration is arguably unattainable as the differences between endpoints mean that the relevant outputs from the models will not be the same. For the transfer and dosimetry components of 2 typical methodologies, it seems that the efficacy of the environmental system is radionuclide-dependent, the predictions given by the environmental system for (90) Sr and (60) Co bei